1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:46,760 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:46,760 --> 00:00:52,400 OUR SPEAKERS TODAY INCLUDE Dr. 12 00:00:52,400 --> 00:00:57,400 SEHER ANJUM FROM NIAID AND Dr. 13 00:00:57,400 --> 00:01:00,840 DINA HUMUT OF THE CLINICAL 14 00:01:00,840 --> 00:01:05,440 CENTER AND Dr. GARJAN CLINICAL 15 00:01:05,440 --> 00:01:08,480 FELLOW IN NCI AND PETER WILL 16 00:01:08,480 --> 00:01:10,040 JUMP SON, SENIOR INVESTIGATORS 17 00:01:10,040 --> 00:01:12,520 OF THE UNIT AND NIAID AND 18 00:01:12,520 --> 00:01:14,720 THEY'RE GOING TO PRESENT TWO 19 00:01:14,720 --> 00:01:16,920 SIDES OF THE A DEADLY CURVE, 20 00:01:16,920 --> 00:01:19,000 NEUROLOGICAL POST INFLAMMATORY 21 00:01:19,000 --> 00:01:20,440 DISEASE AND WITH THAT, I'LL LET 22 00:01:20,440 --> 00:01:22,080 Dr. ANJUM TAKE THE STAGE. 23 00:01:22,080 --> 00:01:27,760 >>I'M SEHER ANJUM 24 00:01:27,760 --> 00:01:31,480 WITH NIAID AND OUR TOPIC IS TWO 25 00:01:31,480 --> 00:01:32,840 SIDES OF A DEADLY CURVE 26 00:01:32,840 --> 00:01:34,840 REFERRING TO NEUROLOGICAL POST 27 00:01:34,840 --> 00:01:39,360 INFECTIOUS INFLAMMATORY DISEASE 28 00:01:39,360 --> 00:01:40,840 FOLLOWING INFECTION. 29 00:01:40,840 --> 00:01:43,040 YOU I WILL PRESENT THE CASE AND 30 00:01:43,040 --> 00:01:47,080 Dr. HAMMOUD WILL HAVE 31 00:01:47,080 --> 00:01:49,240 RADIOLOGY FINDINGS AND Dr. 32 00:01:49,240 --> 00:01:51,120 RAJAN WILL SHOW US PATHOLOGY AND 33 00:01:51,120 --> 00:01:55,040 Dr. WILLIAMSON WILL BE 34 00:01:55,040 --> 00:01:56,920 WRAPPING UP. 35 00:01:56,920 --> 00:01:58,680 WE, AS A GROUP, DO NOT HAVE ANY 36 00:01:58,680 --> 00:02:01,640 FINANCIAL DISCLOSURES AND THE 37 00:02:01,640 --> 00:02:03,440 LEARNING OBJECTIVES FOR TODAY'S 38 00:02:03,440 --> 00:02:06,120 TALK WILL BE TO GET TO KNOW THE 39 00:02:06,120 --> 00:02:08,560 CLINICAL FEATURE OF MENINGITIS 40 00:02:08,560 --> 00:02:12,480 AND HEALTHY ADULTS TO 41 00:02:12,480 --> 00:02:13,160 DISTINGUISH WE KNOW IMMUNE 42 00:02:13,160 --> 00:02:17,720 DAMAGE AND THE MANAGEMENT OF THE 43 00:02:17,720 --> 00:02:22,680 CRYPTO COCKAL MENINGITIS. 44 00:02:22,680 --> 00:02:33,120 SO START WITH THIS IS SHE 45 00:02:37,240 --> 00:02:38,920 STARTED HAVING A MEMORY LOSS, 46 00:02:38,920 --> 00:02:41,600 LIGHT SENSITIVITY, WORD FINDING 47 00:02:41,600 --> 00:02:42,800 DIFFICULTY AND DIZZINESS. 48 00:02:42,800 --> 00:02:44,760 HE WAS ADMIT TODAY AN OUTSIDE 49 00:02:44,760 --> 00:02:46,880 MEDICAL FACILITIES IN AUGUST OF 50 00:02:46,880 --> 00:02:49,560 2014 WITH ADDITIONAL SYMPTOMS OF 51 00:02:49,560 --> 00:02:51,880 VOMITING, RIGHT-UPPER EXTREMELY 52 00:02:51,880 --> 00:02:54,120 WEAKNESS, RIGHT-SIDED FACIAL 53 00:02:54,120 --> 00:02:56,760 DROOP AND FATIGUE. 54 00:02:56,760 --> 00:03:01,200 A BRAIN MRI SHOWED A LESION WITH 55 00:03:01,200 --> 00:03:03,920 MILD THE LEFT FRONTAL LOBE 56 00:03:03,920 --> 00:03:06,160 MEASURING 2.4 TO 2.3 CENTIMETERS 57 00:03:06,160 --> 00:03:11,320 AND IT WAS D1 HYPO WITH LESIONAL 58 00:03:11,320 --> 00:03:11,680 ADEMA. 59 00:03:11,680 --> 00:03:15,360 AND SINCE THERE WAS A SUSPICION 60 00:03:15,360 --> 00:03:19,000 FOR MALIGNANCY SHE WENT UNDER A 61 00:03:19,000 --> 00:03:21,000 WITH PATHOLOGY SHOWING REACTIVE 62 00:03:21,000 --> 00:03:22,800 CHANGES AND SHE WAS DISCHARGED 63 00:03:22,800 --> 00:03:24,920 FIVE DAYS LATER AND SHE WAS 64 00:03:24,920 --> 00:03:27,000 ORIENTED TIMES TWO AND STILL HAD 65 00:03:27,000 --> 00:03:30,600 DIFFICULTY AMBULATING. 66 00:03:30,600 --> 00:03:32,400 SO S. SHE WAS READMITTED JUST A 67 00:03:32,400 --> 00:03:34,600 DAY LATER FOR AGITATION AND 68 00:03:34,600 --> 00:03:36,080 DECREASED VERBAL RESPONSE THAT 69 00:03:36,080 --> 00:03:39,920 WAS ATTRIBUTED TO SODIUM OF 123 70 00:03:39,920 --> 00:03:43,640 AND HER HEAD CT SHOWED DILATED 71 00:03:43,640 --> 00:03:46,840 VENT RICKAL AND AN LP ON 6-16-14 72 00:03:46,840 --> 00:03:48,960 HAD AN OPENING PRESSURE OF 73 00:03:48,960 --> 00:03:52,320 WATER, GLUCOSE LESS THAN 20 AND 74 00:03:52,320 --> 00:03:55,800 A CYTO SIS AND HER PROTEIN WAS 75 00:03:55,800 --> 00:03:58,800 446. 76 00:03:58,800 --> 00:03:59,440 HER FUNGAL CULTURES AGREED AND 77 00:03:59,440 --> 00:04:01,360 SHE HAD A POSITIVE ANTIGEN WITH 78 00:04:01,360 --> 00:04:04,280 A TIGHTER OF 156. 79 00:04:04,280 --> 00:04:10,920 SHE WAS STARTED WITH -- SHE 80 00:04:10,920 --> 00:04:13,040 UNDERWENT A VP SHUNT PLACEMENT 81 00:04:13,040 --> 00:04:15,320 ON 9-4-14. 82 00:04:15,320 --> 00:04:19,320 MORE FOR POOR MENTAL STATUS. 83 00:04:19,320 --> 00:04:22,600 NOT FOR AN INCREASE INTRACRANIAL 84 00:04:22,600 --> 00:04:22,880 PRESSURE. 85 00:04:22,880 --> 00:04:25,480 AS PART OF HER IMMUNE WORKUP SHE 86 00:04:25,480 --> 00:04:27,280 HAD A HIV TEST WHICH WAS 87 00:04:27,280 --> 00:04:30,280 NEGATIVE AND A LOW COUNT OF 17. 88 00:04:30,280 --> 00:04:33,400 SHE WAS EVENTUALLY DISCHARGED ON 89 00:04:33,400 --> 00:04:36,480 9-12-14 TO REHAB TO COMPLETE A 90 00:04:36,480 --> 00:04:36,840 COURSE. 91 00:04:36,840 --> 00:04:40,560 AND THEN EVENTUALLY TRANSITIONED 92 00:04:40,560 --> 00:04:45,120 TO 9-27-14. 93 00:04:45,120 --> 00:04:46,080 UNFORTUNATELY, WITHIN THE NEXT 94 00:04:46,080 --> 00:04:48,320 FEW DAYS SHE STARTED TO BE MORE 95 00:04:48,320 --> 00:04:49,680 LETHARGIC AND SHE ALSO STARTED 96 00:04:49,680 --> 00:04:52,160 HAVING RIGHT-UPPER EXTREMELY 97 00:04:52,160 --> 00:04:55,360 JERKING MOVEMENTS AND SHE WAS 98 00:04:55,360 --> 00:04:58,320 TRANSFERRED FROM REHAB ON 99 00:04:58,320 --> 00:04:58,800 10-14-14. 100 00:04:58,800 --> 00:05:01,560 THIS TIME HER LP SHOWED 44 WIDE 101 00:05:01,560 --> 00:05:04,480 SHE HAD A DECREASE BUT HER 102 00:05:04,480 --> 00:05:06,560 PROTEIN WAS 500 AND GLUCOSE OF 103 00:05:06,560 --> 00:05:09,920 40 AND CFS ANTIGEN THAT WAS 104 00:05:09,920 --> 00:05:12,160 GREATER THAN 1 OUT OF 256. 105 00:05:12,160 --> 00:05:14,440 A REPEAT MRI SHOWED BOTH 106 00:05:14,440 --> 00:05:16,640 SURGICAL CHANGES OF THE LEFT 107 00:05:16,640 --> 00:05:19,720 FRONT AT MASS AND A SMALLER 108 00:05:19,720 --> 00:05:21,840 RESIDUAL RING ENHANCE LEASH AN 109 00:05:21,840 --> 00:05:23,840 AND THERE WERE CONCERNS FOR 110 00:05:23,840 --> 00:05:25,720 RECURRENCE OF CRYPTOCOCCAL 111 00:05:25,720 --> 00:05:31,520 INFECTION SO SHE WAS RETARDED ON 112 00:05:31,520 --> 00:05:32,160 MEDICINE. 113 00:05:32,160 --> 00:05:33,960 SO, FROM THEN ONWARDS, SHE 114 00:05:33,960 --> 00:05:36,080 REALLY HAD MULTIPLE RECURRENT 115 00:05:36,080 --> 00:05:36,920 HOSPITALIZATIONS AT THE NIH SO 116 00:05:36,920 --> 00:05:38,040 THE NEXT COUPLE OF SLIDES WILL 117 00:05:38,040 --> 00:05:41,320 ALL BE IN TIMELINE FORMAT. 118 00:05:41,320 --> 00:05:43,400 IN OCTOBER 2014, SHE WAS 119 00:05:43,400 --> 00:05:45,200 TRANSFERRED FROM THE OUTSIDE 120 00:05:45,200 --> 00:05:47,800 FACILITY AND ADMITTED TO THE NIH 121 00:05:47,800 --> 00:05:49,920 WITH LETHARGY. 122 00:05:49,920 --> 00:05:51,640 HER SPINAL FLUID THIS TIME 123 00:05:51,640 --> 00:05:54,880 SHOWED A WORSENING CYTO 124 00:05:54,880 --> 00:05:56,120 ADVERTISE AND HER PROTEIN WAS 125 00:05:56,120 --> 00:05:58,120 GREATER THAN 600 AND SHE HAD A 126 00:05:58,120 --> 00:06:08,360 GLUCOSE OF 21. 127 00:06:16,040 --> 00:06:18,840 SHE WAS WORSENING AND HER CSF 128 00:06:18,840 --> 00:06:20,640 WAS CONSISTENT WITH INFLAMMATORY 129 00:06:20,640 --> 00:06:21,680 MARKERS BEING UP. 130 00:06:21,680 --> 00:06:26,200 SHE STARTED ON ONE GRAM DAILY 131 00:06:26,200 --> 00:06:27,560 FOR SEVEN DAYS FOR POST 132 00:06:27,560 --> 00:06:29,880 INFECTIOUS INFLAMMATORY RESPONSE 133 00:06:29,880 --> 00:06:32,440 SYNDROME AND SHE WAS 134 00:06:32,440 --> 00:06:34,840 TRANSITIONED TO PRED NA ZONE 60 135 00:06:34,840 --> 00:06:39,360 AND DISCHARGED ON 11-21-14. 136 00:06:39,360 --> 00:06:41,640 SO THEN IN JANUARY OF 2015, SHE 137 00:06:41,640 --> 00:06:43,240 WAS READMITTED FOR FOLLOW-UP. 138 00:06:43,240 --> 00:06:45,320 THIS TIME SHE WAS DOING FINE. 139 00:06:45,320 --> 00:06:48,200 SHE ACTUALLY BEEN DECREASED PRED 140 00:06:48,200 --> 00:06:51,640 NA ZONE 40 MILL A GRAMS DAILY 141 00:06:51,640 --> 00:06:53,160 AND HER NEUROLOGICAL EXAM 142 00:06:53,160 --> 00:06:56,480 IMPROVED BUT IMAGING SHE HAD A 143 00:06:56,480 --> 00:06:57,920 NEW RIGHT BASAL GANGLIA LESION 144 00:06:57,920 --> 00:06:59,840 WHICH IS CONCERNING FOR HE IS 145 00:06:59,840 --> 00:07:00,080 KEEPIA. 146 00:07:00,080 --> 00:07:04,520 HER BRAIN MRA SHOWED 147 00:07:04,520 --> 00:07:07,040 STINZIANOOSIS OF HER RIGHT AND 148 00:07:07,040 --> 00:07:13,640 LEFT SUGGESTIVE OF AND AS PART 149 00:07:13,640 --> 00:07:24,200 OF A WORKUP SHE -- FOR WHICH SHE 150 00:07:27,720 --> 00:07:30,160 WAS ON ASPIRIN AND THERAPEUTIC 151 00:07:30,160 --> 00:07:33,440 INITIALLY AND THEN TRANSITIONED 152 00:07:33,440 --> 00:07:36,600 TO A DIRECT INHIBITOR. 153 00:07:36,600 --> 00:07:42,000 AND THEN SHE WAS DISCHARGED ON 154 00:07:42,000 --> 00:07:42,360 1-10-2015. 155 00:07:42,360 --> 00:07:44,760 SO THEN IN FEBRUARY OF 2015, SHE 156 00:07:44,760 --> 00:07:46,520 RETURNED FOR JUST TWO DAYS. 157 00:07:46,520 --> 00:07:49,880 SHE HAD DEVELOPED DOR SAL FOOT 158 00:07:49,880 --> 00:07:52,760 ULCERS THAT WERE NOT INFECTED. 159 00:07:52,760 --> 00:07:54,320 SHE WAS GIVEN SOME LACE I CANS 160 00:07:54,320 --> 00:07:58,040 THAT WAS PROBABLY AT TAUGHTED TO 161 00:07:58,040 --> 00:07:58,840 STEROID USE AND SHE WAS 162 00:07:58,840 --> 00:08:01,120 DISCHARGED AND DOING WELL. 163 00:08:01,120 --> 00:08:02,800 IN MARCH 2015, SHE RETURNED AND 164 00:08:02,800 --> 00:08:04,680 WAS INITIALLY ADMITTED TO THE 165 00:08:04,680 --> 00:08:06,640 OUTSIDE MEDICAL FACILITY WITH 166 00:08:06,640 --> 00:08:10,040 RIGHT LOWER EXTREMITY WEAKNESS. 167 00:08:10,040 --> 00:08:13,160 AND SHE ALSO HAD A FACIAL PULSE. 168 00:08:13,160 --> 00:08:16,120 HER MRI BRAIN WAS UNI MARKETABLE 169 00:08:16,120 --> 00:08:17,680 BUT THERE WERE CONCERNS FOR A 170 00:08:17,680 --> 00:08:18,880 RECURRENCE OF HER NEURO 171 00:08:18,880 --> 00:08:20,160 INFLAMMATION SO HER PREDNISONE 172 00:08:20,160 --> 00:08:22,720 WAS INCREASED TO 60 MILL A GRAMS 173 00:08:22,720 --> 00:08:23,520 DAILY. 174 00:08:23,520 --> 00:08:25,080 AND THEN, SHE WAS ADMITTED TO 175 00:08:25,080 --> 00:08:27,880 THE NIH A WEEK LATER WITH TWO 176 00:08:27,880 --> 00:08:32,120 NEW FARCS WITH SHE WAS PULSED 177 00:08:32,120 --> 00:08:37,760 AGAIN WITH SOL YOU MED RAL 178 00:08:37,760 --> 00:08:43,200 TRANSITIONED TO PREDNISONE 60 179 00:08:43,200 --> 00:08:43,480 DAILY. 180 00:08:43,480 --> 00:08:46,080 HER HOSPITAL COURSE WAS 181 00:08:46,080 --> 00:08:49,760 COMPLICATED AND SHE CONVERTED TO 182 00:08:49,760 --> 00:08:50,800 NORMAL RHYTHM SPONTANEOUSLY AND 183 00:08:50,800 --> 00:08:54,960 FOUND TO HAVE EXPANSION OF RIGHT 184 00:08:54,960 --> 00:09:00,160 DBT SO FEMALERRAL VEIN AND HER 185 00:09:00,160 --> 00:09:01,000 CHEST SHOT A CLOT IN HER 186 00:09:01,000 --> 00:09:02,840 ARTERIES AND SO IT WAS THOUGHT 187 00:09:02,840 --> 00:09:05,120 THAT THIS WOULD PROBABLY BE 188 00:09:05,120 --> 00:09:06,280 BECAUSE OF FAILURE SO SHE 189 00:09:06,280 --> 00:09:09,280 STARTED ON THERAPEUTIC LOVONOX 190 00:09:09,280 --> 00:09:14,480 AND TRANSITIONED TO WARFRIN. 191 00:09:14,480 --> 00:09:16,280 HER MENTAL STATUS IMPROVED BUT 192 00:09:16,280 --> 00:09:18,480 SINCE SHE WAS ON STEROIDS FOR SO 193 00:09:18,480 --> 00:09:23,040 LONG, IT WAS THOUGHT TO DO A 194 00:09:23,040 --> 00:09:23,840 STEROID SPARING TRIAL AND SHE 195 00:09:23,840 --> 00:09:28,120 WAS DISCHARGED ON 4-7-15 AND 196 00:09:28,120 --> 00:09:31,160 RETURNED MAY 20-15 WITH FOOD 197 00:09:31,160 --> 00:09:33,080 ULCER PAIN AND GIVEN LAY SIX AND 198 00:09:33,080 --> 00:09:35,800 WE ALSO HAD TO MAKE MEDICATION 199 00:09:35,800 --> 00:09:38,880 CHANGES SINCE HER LFTs WERE UP 200 00:09:38,880 --> 00:09:43,080 ALMOST FIVE TIMES AND SHE WAS 201 00:09:43,080 --> 00:09:45,880 TRANSITION FROM DRUGS AND HER 202 00:09:45,880 --> 00:09:47,920 DUMA DIN DOSE WAS TRANSITIONED 203 00:09:47,920 --> 00:09:51,720 FROM TWO TO FIVE ON HER INR AND 204 00:09:51,720 --> 00:09:53,640 SHE WAS FOLLOWING UP AT THE DUMA 205 00:09:53,640 --> 00:09:54,240 DIN CLINIC. 206 00:09:54,240 --> 00:09:56,160 AND THEN IN JUNE OF 2015, SHE 207 00:09:56,160 --> 00:09:57,760 WAS READMITTED AGAIN FOR 208 00:09:57,760 --> 00:10:08,160 WORSENING MEDICATION. 209 00:10:13,560 --> 00:10:17,120 RHEUMATOLOGY WAS CONSULTED AND 210 00:10:17,120 --> 00:10:18,800 THOUGHT IT WAS A POST AND THEY 211 00:10:18,800 --> 00:10:22,480 RECOMMENDED SIGH CO PHOSPHO 212 00:10:22,480 --> 00:10:26,320 MIGHT AND STEROIDS FOLLOWED BY 213 00:10:26,320 --> 00:10:27,320 PREDNISONE. 214 00:10:27,320 --> 00:10:30,760 ON 6-15-15 SHE WAS UNRESPONSIVE 215 00:10:30,760 --> 00:10:32,680 WITH A RAPID RESPONSE BEING 216 00:10:32,680 --> 00:10:32,920 CALLED. 217 00:10:32,920 --> 00:10:34,480 SHE WAS THEN EMERGENCY 218 00:10:34,480 --> 00:10:36,440 TRANSFERRED TO THE ICU AND 219 00:10:36,440 --> 00:10:38,000 INTUBATED AND HYPER VENTILATED 220 00:10:38,000 --> 00:10:41,720 TO A TARGET OF 20 AND GIVEN 221 00:10:41,720 --> 00:10:45,600 MANATOL FOR CEREBRAL ADEMA AND A 222 00:10:45,600 --> 00:10:49,400 HEAD CT SHOWED A MASSIVE LEFT 223 00:10:49,400 --> 00:10:52,000 HEM OR AGE AND HER INR WAS FOUND 224 00:10:52,000 --> 00:10:53,880 TO BE THREE AND QUICKLY 225 00:10:53,880 --> 00:10:55,440 NORMALIZED WITH FFB WITHIN FIVE 226 00:10:55,440 --> 00:10:58,360 HOURS OF THE RAPID RESPONSE 227 00:10:58,360 --> 00:11:00,280 BEING CALLED. 228 00:11:00,280 --> 00:11:05,720 AND THIS WAS A BRISK MASSIVE AR 229 00:11:05,720 --> 00:11:06,720 TERRAL BLEED SO THERE WAS LITTLE 230 00:11:06,720 --> 00:11:09,160 BENEFIT FROM INTERVENTION AND 231 00:11:09,160 --> 00:11:14,320 THE PATIENT EXPIRED ON 6-26 IN 232 00:11:14,320 --> 00:11:15,960 THE AFTERNOON WHICH AFTER AN 233 00:11:15,960 --> 00:11:16,960 AUTOPSY WAS PERFORMED. 234 00:11:16,960 --> 00:11:18,040 THAT'S HER HOSPITAL COURSE AND 235 00:11:18,040 --> 00:11:21,760 Dr. HAMM OUTAOUAIS D WILL BEMOU. 236 00:11:21,760 --> 00:11:22,480 SO MANY OWE LENS. 237 00:11:22,960 --> 00:11:25,400 >> SOME OF THE IMAGE FUNDINGS ON 238 00:11:25,400 --> 00:11:26,200 OUR PATIENT. 239 00:11:26,200 --> 00:11:28,040 THIS IS THE FIRST IMAGING STUDY 240 00:11:28,040 --> 00:11:32,880 WE HAVE ON HER ON FILE WHERE A 241 00:11:32,880 --> 00:11:35,840 PRE OPERATIVE PLANNING STUDY WAS 242 00:11:35,840 --> 00:11:37,640 PERFORMED WITH POST IMAGES ONLY 243 00:11:37,640 --> 00:11:39,680 AND AT WHICH POINT YOU CAN SEE 244 00:11:39,680 --> 00:11:44,920 THAT THERE'S A LEFT FRONTAL RIM 245 00:11:44,920 --> 00:11:45,960 ENHANCING MASS AND SURROUNDED 246 00:11:45,960 --> 00:11:48,880 WITH A BIT OF ADEMA AND 247 00:11:48,880 --> 00:11:50,120 ASSOCIATED WITH MID LINE SHIFT. 248 00:11:50,120 --> 00:11:52,560 WE CAN SEE THERE'S A LITTLE BIT 249 00:11:52,560 --> 00:11:55,840 OF CSF AND VENT RICK ALS AND IF 250 00:11:55,840 --> 00:11:58,920 YOU LOOK CAREFULLY AT THE 251 00:11:58,920 --> 00:12:00,800 RETRUCK YOU CAN SEE THAT THE 252 00:12:00,800 --> 00:12:05,840 ASPECT OF THAT LEASH AN IS 253 00:12:05,840 --> 00:12:06,760 CONTINUOUS WITH MENG ALLEN 254 00:12:06,760 --> 00:12:17,360 HANCEMENT ALONG THE CISTERN ANDE 255 00:12:20,600 --> 00:12:21,960 PATIENT WAS DIAGNOSED ALMOST A 256 00:12:21,960 --> 00:12:24,680 WEEK LATER AND STARTED ON 257 00:12:24,680 --> 00:12:25,720 ANTIFUNGALS AND THIS WAS THE 258 00:12:25,720 --> 00:12:27,840 FIRST POSTOPERATIVE MRI 259 00:12:27,840 --> 00:12:29,600 EXAMINATION AND I CAN NOTICE THE 260 00:12:29,600 --> 00:12:31,440 PATIENT HAD A LOT OF MOTION SO 261 00:12:31,440 --> 00:12:32,920 THIS IS NOT THE BEST EXAM, THIS 262 00:12:32,920 --> 00:12:37,120 IS PERFORMED ON OUTSIDE BASIS. 263 00:12:37,120 --> 00:12:38,240 THE LESION WHICH WE SAW IN THE 264 00:12:38,240 --> 00:12:40,280 LEFT FRONTAL LOBE DECREASED IN 265 00:12:40,280 --> 00:12:42,320 SIZE AND IT STILL SHOWS 266 00:12:42,320 --> 00:12:44,280 ENHANCEMENT OF THE RIM BUT THE 267 00:12:44,280 --> 00:12:47,160 COMPONENT IS SHOWING RESTRICTED 268 00:12:47,160 --> 00:12:49,080 DIFFUSION CONSISTENT WITH EXITED 269 00:12:49,080 --> 00:12:52,360 OR CONTENT AND WHICH WE COMMONLY 270 00:12:52,360 --> 00:12:58,760 SEE IN CRYPTO AND HER 271 00:12:58,760 --> 00:13:00,360 HYDROCEPHALUS HAD WORSENED 272 00:13:00,360 --> 00:13:02,440 SIGNIFICANTLY AND IT HAD BECOME 273 00:13:02,440 --> 00:13:08,880 MORE EVIDENCE AND AS WELL AS 274 00:13:08,880 --> 00:13:09,400 POSTOPERATIVE CHANGES. 275 00:13:09,400 --> 00:13:14,400 SHE WAS SHUNTED FOR 276 00:13:14,400 --> 00:13:15,440 HYDROCEPHALUS AND WHEN SHE 277 00:13:15,440 --> 00:13:17,800 PRESENTED HER FIRST TIME TO NIH, 278 00:13:17,800 --> 00:13:19,520 SHOULD WAS THE FIRST OUR 279 00:13:19,520 --> 00:13:20,840 EXAMINATION WE DID HERE. 280 00:13:20,840 --> 00:13:24,640 ON TOP HERE, YOU HAVE IMAGES AND 281 00:13:24,640 --> 00:13:28,200 THE SECOND ROW IS POST CONTRA 282 00:13:28,200 --> 00:13:30,320 IMAGES SO FLARE IMAGES ARE 283 00:13:30,320 --> 00:13:32,360 IMAGES WHERE WE SUPPRESS THE 284 00:13:32,360 --> 00:13:34,480 SIGNAL OF THE CSF SO IT'S EASIER 285 00:13:34,480 --> 00:13:36,600 TO SEE ABNORMAL SIGNAL 286 00:13:36,600 --> 00:13:39,200 ASSOCIATED WITH ADEMA OR WITH 287 00:13:39,200 --> 00:13:41,320 GLEOSIS LIKE YOU SEE HERE IN THE 288 00:13:41,320 --> 00:13:42,160 BRAIN STEM. 289 00:13:42,160 --> 00:13:45,600 HERE, AT NIH, WE PERFORMED THOSE 290 00:13:45,600 --> 00:13:47,160 STUDIES WITH POST CONTRAST. 291 00:13:47,160 --> 00:13:48,600 THIS IS NOT A STANDARD PROCEDURE 292 00:13:48,600 --> 00:13:52,240 ON THE OUTSIDE BUT WE HAVE FOUND 293 00:13:52,240 --> 00:13:53,720 IT TO BE SENSITIVE FOR DID HE 294 00:13:53,720 --> 00:13:55,480 TECHION OF SUDDEN ABNORMALITIES, 295 00:13:55,480 --> 00:13:59,520 WHEN YOU ARE WORRIED ABOUT MILD 296 00:13:59,520 --> 00:14:03,560 MENINGITIS OR MAYBE CARCINOMA 297 00:14:03,560 --> 00:14:10,600 MATOSIS. 298 00:14:10,600 --> 00:14:17,280 ENOUENOUGHTHE RIGHT HEMISPHERE O 299 00:14:17,280 --> 00:14:19,960 LEFT FRONTAL REGIONS THERE'S A 300 00:14:19,960 --> 00:14:22,520 LOT OF ENHANCEMENT ALONG THE 301 00:14:22,520 --> 00:14:24,080 BASE STEM STRUCTURES AND THE 302 00:14:24,080 --> 00:14:26,480 SISTERS AND ALSO ALONG THE 303 00:14:26,480 --> 00:14:29,480 CIRCLE OF ACAs AS WELL AS 304 00:14:29,480 --> 00:14:31,640 MCAs AND ENHANCEMENT IN THE 305 00:14:31,640 --> 00:14:35,160 INTERNAL AUDITORY CANALS AND THE 306 00:14:35,160 --> 00:14:36,600 POST CONTENT FLARES AS I SAID, 307 00:14:36,600 --> 00:14:39,440 SHOW THE ENHANCEMENT TO A LITTLE 308 00:14:39,440 --> 00:14:41,360 BIT MORE AND THEN YOU CAN 309 00:14:41,360 --> 00:14:43,800 IDENTIFY AREAS OF ADEMA IN THE 310 00:14:43,800 --> 00:14:47,640 ADJACENT STRUCTURES INCLUDING 311 00:14:47,640 --> 00:14:49,880 THE CORTICAL RIBBONS AND MID 312 00:14:49,880 --> 00:14:50,080 BRAIN. 313 00:14:50,080 --> 00:14:52,840 THERE WAS EVIDENCE OF A PENDULUM 314 00:14:52,840 --> 00:14:57,920 ENHANCEMENT WITH THIS. 315 00:14:57,920 --> 00:15:00,800 AN MRI WAS ALSO PERFORMED OF THE 316 00:15:00,800 --> 00:15:02,320 SPINE AND THESE ARE POST 317 00:15:02,320 --> 00:15:07,280 CONTRAST IMAGES AND YOU CAN SEE 318 00:15:07,280 --> 00:15:08,880 THAT THE NERVE ROOTS ARE THICK 319 00:15:08,880 --> 00:15:11,760 END AND ENHANCING AND THERE'S 320 00:15:11,760 --> 00:15:13,680 ENHANCEMENT AND ON THE ACTION I 321 00:15:13,680 --> 00:15:16,360 WILL IMAGES THEY'RE ALL MATTED 322 00:15:16,360 --> 00:15:19,200 AND STRONGLY ENHANCED CONSISTENT 323 00:15:19,200 --> 00:15:24,640 WITH THE SEVERE AND MENINGITIS. 324 00:15:24,640 --> 00:15:26,200 SO, THE PATIENT WAS STARTED ON 325 00:15:26,200 --> 00:15:28,840 TREATMENT AND THE FOLLOW-UP 326 00:15:28,840 --> 00:15:30,600 EXAMINATION WAS IN JANUARY OF 327 00:15:30,600 --> 00:15:33,200 2015 AT WHICH POINT YOU CAN SEE 328 00:15:33,200 --> 00:15:36,400 IMAGES THAT THERE WAS COMPLETE 329 00:15:36,400 --> 00:15:38,000 RESOLUTION OF THE ENHANCEMENT ON 330 00:15:38,000 --> 00:15:41,000 FLARE HOWEVER YOU CAN STILL SEE 331 00:15:41,000 --> 00:15:42,520 RESIDUAL MENG ALLEN HANCEMENT 332 00:15:42,520 --> 00:15:45,320 AND THE FISHERS ON THE SOUTH 333 00:15:45,320 --> 00:15:48,160 SIDE AND THE ENHANCEMENT IS 334 00:15:48,160 --> 00:15:48,400 DIFFERENT. 335 00:15:48,400 --> 00:15:52,080 THIS IS BECAUSE OF SHUNTING BUT 336 00:15:52,080 --> 00:15:56,880 THE MEN GEE ALLEN HANCEMENT WAS 337 00:15:56,880 --> 00:16:07,440 THERE AND WE OBTAIN TO WHICH IS 338 00:16:12,680 --> 00:16:14,120 THE HE IS KEEPIA AND ALSO IN 339 00:16:14,120 --> 00:16:16,320 OTHER SITUATIONS YOU CAN SEE 340 00:16:16,320 --> 00:16:21,560 THAT THIS LEASH AN HAD INFUSION 341 00:16:21,560 --> 00:16:23,640 CONSISTENT WITH EARLY SUBACUTE 342 00:16:23,640 --> 00:16:28,240 AND THERE WERE A FIE OTHER 343 00:16:28,240 --> 00:16:30,840 DIFFUSION IN THE AS WELL AS IN 344 00:16:30,840 --> 00:16:32,080 THE PAWNS WHICH SEEM TO BE 345 00:16:32,080 --> 00:16:34,040 SLIGHTLY OLDER. 346 00:16:34,040 --> 00:16:38,160 ALL OF THESE WERE CONSISTENT 347 00:16:38,160 --> 00:16:40,360 WITH THE DISTRIBUTION OF THE 348 00:16:40,360 --> 00:16:41,960 ARTERIES AND THE PER FER 349 00:16:41,960 --> 00:16:44,520 EIGHTING BRANCHES. 350 00:16:44,520 --> 00:16:47,040 AND MRA WAS PERFORMED TWO DAYS 351 00:16:47,040 --> 00:16:49,680 LATER AND AS CAN SEE, THE LEFT 352 00:16:49,680 --> 00:16:52,160 MCA IS MARK HE HADLY ABNORMAL 353 00:16:52,160 --> 00:16:55,200 AND THERE'S MARKED IRREGULAR LAR 354 00:16:55,200 --> 00:17:01,280 TEE AND FOCAL AREA OF STENO SIS 355 00:17:01,280 --> 00:17:04,400 AND A SLIGHTLY LESS APPRECIATION 356 00:17:04,400 --> 00:17:06,640 OF THE BRANCHES AND ON THE RIGHT 357 00:17:06,640 --> 00:17:11,360 SIDE IT SHOWED IRREGULARITIES 358 00:17:11,360 --> 00:17:20,880 AND NOTHING SIMILAR TO THE LEFT 359 00:17:20,880 --> 00:17:22,720 MCA. 360 00:17:22,720 --> 00:17:23,960 I'M SHOWING THE FUSION WEIGHTED 361 00:17:23,960 --> 00:17:25,200 IMAGES FROM MULTIPLE STUDIES, 362 00:17:25,200 --> 00:17:28,600 THIS ONE WE FIRST SAW AND AS 363 00:17:28,600 --> 00:17:32,040 EXPECTED OVER TIME, THESE AREAS 364 00:17:32,040 --> 00:17:34,840 INCREASED SIGNAL WOULD DISAPPEAR 365 00:17:34,840 --> 00:17:36,920 AND ON THIS EXAMINATION YOU 366 00:17:36,920 --> 00:17:38,160 DON'T SEE THEM ANYMORE BUT THEN 367 00:17:38,160 --> 00:17:43,520 IN MAY, SHE PRESENTED WITH 368 00:17:43,520 --> 00:17:46,000 SYMPTOM TOLL GEE WITH BRAIN STEM 369 00:17:46,000 --> 00:17:48,360 INVOLVEMENT AND WE IDENTIFIED 370 00:17:48,360 --> 00:17:49,480 RESTRICTED DIFFUSION IN THE 371 00:17:49,480 --> 00:17:50,240 BRAIN STEM. 372 00:17:50,240 --> 00:17:54,520 AND THE MID BRAIN. 373 00:17:54,520 --> 00:17:57,320 FOLLOWING THAT, SHE PRESENTED IN 374 00:17:57,320 --> 00:17:58,400 JANUARY THERE WAS ALMOST 10 DAYS 375 00:17:58,400 --> 00:17:59,960 BEFORE SHE PASSED AWAY AND THAT 376 00:17:59,960 --> 00:18:02,360 WAS HER LAST MRI EXAMINATION AND 377 00:18:02,360 --> 00:18:04,040 AT THAT POINT THERE WERE NO 378 00:18:04,040 --> 00:18:10,640 SIGNS RESTRICTED DIFFUSION. 379 00:18:10,640 --> 00:18:13,360 YOU CAN SEE THAT THE LAST MRA 380 00:18:13,360 --> 00:18:14,560 SHOWED IMPROVEMENT. 381 00:18:14,560 --> 00:18:17,480 YOU CAN SEE NOW BETTER 382 00:18:17,480 --> 00:18:21,360 ENHANCEMENT AND THERE'S STILL 383 00:18:21,360 --> 00:18:23,400 IRREGULARITY AND STINZIANOOSIS 384 00:18:23,400 --> 00:18:31,640 AND INVOLVEMENT OF THE LEFT MCA 385 00:18:31,640 --> 00:18:33,960 AND 386 00:18:33,960 --> 00:18:35,520 AND THE ARTERY AND THESE ARE 387 00:18:35,520 --> 00:18:37,920 OTHER SEQUENCES ON HER LAST MRI 388 00:18:37,920 --> 00:18:48,440 AND THIS IS THE -- YOU CAN SEE A 389 00:18:51,960 --> 00:18:53,920 MUCH BETTER EXTENT AND YOU CAN 390 00:18:53,920 --> 00:19:01,080 SEE IT ALONG THE FOLIA ALONG THE 391 00:19:01,080 --> 00:19:03,280 FRONTAL CELL SIDE AND THE LEFT 392 00:19:03,280 --> 00:19:04,960 FRONTAL REGION AND YOU CAN STILL 393 00:19:04,960 --> 00:19:10,240 SEE IT ALONG THE LEFT MCA TRACKS 394 00:19:10,240 --> 00:19:12,160 THIS IS MAGNIFIED VIEW COMPARED 395 00:19:12,160 --> 00:19:14,160 TO OF A NORMAL PATIENT WITH THE 396 00:19:14,160 --> 00:19:16,200 SAME EXACT PARAMETERS AND THE 397 00:19:16,200 --> 00:19:17,160 SAME TIME PERIOD. 398 00:19:17,160 --> 00:19:20,600 THIS ENHANCEMENT IS MENGAL AND 399 00:19:20,600 --> 00:19:22,800 IT'S DIFFICULT TO TELL WHETHER 400 00:19:22,800 --> 00:19:23,840 THERE'S INVOLVEMENT OF THE 401 00:19:23,840 --> 00:19:25,080 VESSEL WALL AND THERE'S 402 00:19:25,080 --> 00:19:35,560 ENHANCEMENT ON THE RIGHT SIDE. 403 00:19:38,200 --> 00:19:40,280 IT'S A MASSIVE BLEED. 404 00:19:40,280 --> 00:19:42,880 THE ADEMA SURROUNDING IT IS 405 00:19:42,880 --> 00:19:44,720 CONFORMING TO THE FORM OF THE 406 00:19:44,720 --> 00:19:49,320 SHAPE OF THE HEMATOMA SUGGESTING 407 00:19:49,320 --> 00:19:53,680 IT'S AN ACTUAL THERE WAS A LOT 408 00:19:53,680 --> 00:19:57,640 OF MASS EFFECT, MID LINE SHIFT, 409 00:19:57,640 --> 00:20:00,200 COMPRESSION OF THE VENTRICLES 410 00:20:00,200 --> 00:20:01,960 AND THE BASIL SYSTEMS AND 411 00:20:01,960 --> 00:20:03,840 COMPASSION OF THE FORCED 412 00:20:03,840 --> 00:20:05,920 VENTRICLES SUGGESTING THERE'S 413 00:20:05,920 --> 00:20:13,000 EARLY HERNIATION. 414 00:20:13,000 --> 00:20:15,160 THE PATIENT PASSED AWAY ONE DAY 415 00:20:15,160 --> 00:20:15,360 LATER. 416 00:20:15,360 --> 00:20:19,960 WE DESCRIBED IN PATIENTS WITH 417 00:20:19,960 --> 00:20:20,240 MENINGITIS. 418 00:20:20,240 --> 00:20:24,440 WE HAVE REALLY IDENTIFIED WHAT 419 00:20:24,440 --> 00:20:28,600 WE REFER TO AS CRYPTOCOCCAL 420 00:20:28,600 --> 00:20:30,880 MENINGITIS AND LESIONS, AND THE 421 00:20:30,880 --> 00:20:33,600 LEASHANCE SEEN IN THE BASIL 422 00:20:33,600 --> 00:20:34,840 GANGLIA WITH OR WITHOUT 423 00:20:34,840 --> 00:20:36,040 ENHANCEMENT AND WE SEE THEM 424 00:20:36,040 --> 00:20:38,080 QUITE A BIT IN THE CORTICAL 425 00:20:38,080 --> 00:20:41,600 REGIONS IN CLOSE TO MENINGEAL 426 00:20:41,600 --> 00:20:42,120 ENHANCEMENT. 427 00:20:42,120 --> 00:20:43,760 IF YOU HAVE SICK MENINGEAL 428 00:20:43,760 --> 00:20:45,520 ENHANCEMENT YOU SEE IT VERY 429 00:20:45,520 --> 00:20:46,800 NICELY ON THE IMAGES BUT 430 00:20:46,800 --> 00:20:48,960 SOMETIMES WE ONLY SEE IT OR SEE 431 00:20:48,960 --> 00:20:51,200 IT ON MUCH BETTER EXTENT ON THE 432 00:20:51,200 --> 00:20:54,760 FLARE IMAGES AS YOU CAN SEE HERE 433 00:20:54,760 --> 00:21:00,880 AND TWO SPECIFIC FINDINGS FOR 434 00:21:00,880 --> 00:21:07,840 CRYPCRYPTOCOCCAL MENINGITIS WHIH 435 00:21:07,840 --> 00:21:10,560 EVERY NOW AND THEN IS ASSOCIATED 436 00:21:10,560 --> 00:21:13,400 WITH ADHESIONS AND ENTRAPMENT OF 437 00:21:13,400 --> 00:21:17,120 PORTIONS OF THE VENTRICLES. 438 00:21:17,120 --> 00:21:18,240 THE VAAS LIEU LAR INVOLVEMENT IS 439 00:21:18,240 --> 00:21:21,120 LESS WELL DESCRIBED AND THERE 440 00:21:21,120 --> 00:21:22,760 ARE REPORTS OF PRESENTATIONS 441 00:21:22,760 --> 00:21:25,000 SIMILAR TO OUR PATIENT WHERE 442 00:21:25,000 --> 00:21:30,400 THEY HAVE BEEN DESCRIBED IN THE 443 00:21:30,400 --> 00:21:33,200 BASE SAL GANGLIA AND THOSE ARE 444 00:21:33,200 --> 00:21:35,520 SUPPOSED TO BE DUE TO 445 00:21:35,520 --> 00:21:38,200 INFLAMMATORY CHANGES INVOLVING 446 00:21:38,200 --> 00:21:44,160 ARTERIES AND LIKE THE TRY EIGHT 447 00:21:44,160 --> 00:21:54,680 FOR EXAMPLE AND BECAUSE OF THE 448 00:21:55,120 --> 00:21:56,760 IT'S LESS COMMONLY REPORT AND WE 449 00:21:56,760 --> 00:21:58,840 HAVE TWO CASES AT LEAST NOW AND 450 00:21:58,840 --> 00:22:02,680 WITH THE PRESENTATION AND 451 00:22:02,680 --> 00:22:04,440 HOWEVER IT'S RARE. 452 00:22:04,440 --> 00:22:08,440 WITH THAT I'D LIKE TO CONCLUDE. 453 00:22:08,440 --> 00:22:12,720 THANK YOU AND Dr. RAJAN WILL 454 00:22:12,720 --> 00:22:15,480 SHOW THE PATHOLOGY FINDINGS. 455 00:22:15,480 --> 00:22:18,280 >> THANK YOU Dr. HAMMOUD. 456 00:22:18,280 --> 00:22:21,000 SO WE WILL NOW GO OVER THE NEURO 457 00:22:21,000 --> 00:22:28,240 PATHOLOGICAL FINDINGS FOR THIS 458 00:22:28,240 --> 00:22:30,680 PATIENT. 459 00:22:30,680 --> 00:22:34,480 THE FIRST IS THE LEFT SIDE OF 460 00:22:34,480 --> 00:22:36,760 THE SO THE SCALP HAS BEEN 461 00:22:36,760 --> 00:22:39,880 REFLECTED AND IT'S BEEN OPEN 462 00:22:39,880 --> 00:22:43,000 TRANSVERSANCE AND THE LARGE CLOT 463 00:22:43,000 --> 00:22:45,360 WAS IDENTIFIED OVER THE LEFT 464 00:22:45,360 --> 00:22:50,200 HEMISPHERE AND THIS WAS A LARGE 465 00:22:50,200 --> 00:22:50,600 PRESSURIZED CLOT. 466 00:22:50,600 --> 00:22:53,920 THE BRAIN WAS EXTRACTED AND IT 467 00:22:53,920 --> 00:23:04,440 WEIGHED 1,120 GRAMS FRESH AND 468 00:23:05,960 --> 00:23:08,880 AND IN CROSS EXAM, CONGESTION OF 469 00:23:08,880 --> 00:23:14,240 THE LIP TOE MINUTE VESSELS WERE 470 00:23:14,240 --> 00:23:16,280 AND A LARGE LESION WAS 471 00:23:16,280 --> 00:23:22,360 IDENTIFIED WITH DISTORTION OF 472 00:23:22,360 --> 00:23:24,680 THE A MOVING OVER TO THE VESSELS 473 00:23:24,680 --> 00:23:26,560 OF THE CIRCLE AND HERE WE CAN 474 00:23:26,560 --> 00:23:32,320 IDENTIFY THE BASIL ARTERY AND NO 475 00:23:32,320 --> 00:23:36,880 FINDINGS OF SCLEROSIS WAS NOTED. 476 00:23:36,880 --> 00:23:39,000 HERE ON THE LEFT SIDE WE HAVE A 477 00:23:39,000 --> 00:23:40,360 TRANSVERSE SECTION OF THE SERRE 478 00:23:40,360 --> 00:23:42,520 BELL UM AND THIS IS A FRESH 479 00:23:42,520 --> 00:23:46,600 SECTION AND ON THE RIGHT SIDE 480 00:23:46,600 --> 00:23:57,240 HERE, WE HAVE THESE CAN BE SEENN 481 00:24:04,800 --> 00:24:06,520 THERE'S DOWNWARD MISPLACEMENT 482 00:24:06,520 --> 00:24:09,520 CAUSING TRACTION OF THE 483 00:24:09,520 --> 00:24:11,200 PENETRATING VESSELS RESULTING IN 484 00:24:11,200 --> 00:24:12,160 HEMORRHAGE AND AREAS OF NECK ROW 485 00:24:12,160 --> 00:24:19,480 SIS AND THESE ARE CALLED TO 486 00:24:19,480 --> 00:24:22,400 RIDGES. 487 00:24:22,400 --> 00:24:24,960 THIS IS THE SPINAL CORD. 488 00:24:24,960 --> 00:24:26,600 HEMORRHAGE WAS SEEN AND BOTH AT 489 00:24:26,600 --> 00:24:30,320 THE CERVICAL AS WELL AS THORACIC 490 00:24:30,320 --> 00:24:30,640 LEVELS. 491 00:24:30,640 --> 00:24:34,200 AND NEXT WE MOVE ONTO THE IMAGES 492 00:24:34,200 --> 00:24:35,480 THAT THE FIRST SECTION THAT WE 493 00:24:35,480 --> 00:24:37,160 HAVE IS THAT OF THE LEFT 494 00:24:37,160 --> 00:24:43,320 KAWARTHA TECORTEX ANDTHIS IS THE 495 00:24:43,320 --> 00:24:44,560 MATTER AND THE RIGHT SIDE THIS 496 00:24:44,560 --> 00:24:48,560 IS A LARGE AREA OF INTRA CRANIAL 497 00:24:48,560 --> 00:24:48,840 HEMORRHAGE. 498 00:24:48,840 --> 00:24:50,160 THIS IS ANOTHER SECTION OF THE 499 00:24:50,160 --> 00:24:55,240 LEFT CORTEX AND VASCULAR 500 00:24:55,240 --> 00:24:56,600 CONGESTION AS WELL AS HEMORRHAGE 501 00:24:56,600 --> 00:24:59,560 IS BEING HIGHLIGHTED HERE. 502 00:24:59,560 --> 00:25:03,840 THIS IS A SECTION OF THE THIN 503 00:25:03,840 --> 00:25:06,520 WALL VESSEL WITH SER UNDERRING 504 00:25:06,520 --> 00:25:12,320 AREAS OF NECROSIS WITHIN THE 505 00:25:12,320 --> 00:25:12,680 POINTS. 506 00:25:12,680 --> 00:25:15,880 ON THE LEFT SIDE HERE, WE HAVE A 507 00:25:15,880 --> 00:25:17,240 CROSS SECTION OF THE ARTERY AND 508 00:25:17,240 --> 00:25:20,000 ON THE RIGHT WE HAVE THE VESSELS 509 00:25:20,000 --> 00:25:23,760 AND IF WE FOCUS CLOSELY ON THE 510 00:25:23,760 --> 00:25:27,440 BASSLAR ARTERY WE CAN SEE THE 511 00:25:27,440 --> 00:25:31,840 INTERNAL ELASTIC SO IT'S THE 512 00:25:31,840 --> 00:25:33,520 MEDICINE YAN AND THE 513 00:25:33,520 --> 00:25:35,240 ADVANTAGEOUS AND THE ARTERY 514 00:25:35,240 --> 00:25:36,720 APPEARS THICK END AND EVEN ON 515 00:25:36,720 --> 00:25:40,360 LOW POWER WE CAN SEE 516 00:25:40,360 --> 00:25:42,360 INFLAMMATORY CELLS SURROUNDING 517 00:25:42,360 --> 00:25:44,080 BOTH THE BASILAR ARTERY AS WELL 518 00:25:44,080 --> 00:25:51,600 AS THE HELP TOE VESSEL SO WE 519 00:25:51,600 --> 00:25:55,400 HAVE INFLAMMATORY CELL 520 00:25:55,400 --> 00:26:00,520 SURROUNDING IT AND THEY ARE 521 00:26:00,520 --> 00:26:03,840 HIGHLIGHTED WITH THE CD68 AND B 522 00:26:03,840 --> 00:26:07,040 AND T CELLS HIGHLIGHTED ON CD20 523 00:26:07,040 --> 00:26:11,320 AND CD3 IMMUNO SO IT'S A MIXED 524 00:26:11,320 --> 00:26:13,080 INFLAMMATORY THAT WAS IDENTIFIED 525 00:26:13,080 --> 00:26:17,080 SURROUNDING THE VESSELS. 526 00:26:17,080 --> 00:26:21,160 HERE WE HAVE AN H AND E SECTION 527 00:26:21,160 --> 00:26:23,400 OF THE THESE ARE BUDDING FORMS 528 00:26:23,400 --> 00:26:26,240 OF VARIOUSES CRISIS WITH THICK 529 00:26:26,240 --> 00:26:31,600 CAPSULE AND THIS IS CRYPTOCOCCAL 530 00:26:31,600 --> 00:26:33,800 ORGANISMS AND THEY WERE SEEN 531 00:26:33,800 --> 00:26:35,600 SURROUNDING THE VESSELS. 532 00:26:35,600 --> 00:26:40,720 THIS IS A SECTION OF THE AGAIN 533 00:26:40,720 --> 00:26:42,640 WE CAN SEE SEVERAL CRYPTICAL 534 00:26:42,640 --> 00:26:45,480 ORGANISMS AND FOCAL AREAS OF THE 535 00:26:45,480 --> 00:26:49,120 NECROSIS AND THIS IS WITHIN THE 536 00:26:49,120 --> 00:26:51,320 PROSECUTE' AND THIS IS A RGMS 537 00:26:51,320 --> 00:26:52,480 AND AGAIN THIS IS A CROSS 538 00:26:52,480 --> 00:26:56,360 SECTION OF THE VESSEL AND IT 539 00:26:56,360 --> 00:26:58,600 HIGH LIGHTS THE BUDDING YEAST 540 00:26:58,600 --> 00:27:02,880 FORMS IN THESE DARK BROWNISH 541 00:27:02,880 --> 00:27:09,520 BLACK COLOR AND AS WELL AS THE 542 00:27:09,520 --> 00:27:10,600 VESSEL WALL THIS IS A HIGHER 543 00:27:10,600 --> 00:27:12,200 POWER IMAGE AGAIN HIGHLIGHTING 544 00:27:12,200 --> 00:27:22,480 THE ORGANISMS ON SILVER STAIN 545 00:27:22,480 --> 00:27:32,960 AND AND OWN HISTOLOGY AS WELL 546 00:27:36,360 --> 00:27:39,840 THESE ARE THE PLOTS WITH AN AREA 547 00:27:39,840 --> 00:27:44,880 OF HEMORRHAGE AND UPON DOING A 548 00:27:44,880 --> 00:27:46,520 STAIN, CRYPTOCOCCAL ORGANISMS 549 00:27:46,520 --> 00:27:47,880 WERE IDENTIFIED WITHIN THE BLOCK 550 00:27:47,880 --> 00:27:49,280 AS WELL SO MOVING FORWARD TO THE 551 00:27:49,280 --> 00:27:52,320 SUMMARY OF THE FINDINGS, THIS 552 00:27:52,320 --> 00:27:59,520 PATIENT HAD A INFRACTION AND AND 553 00:27:59,520 --> 00:28:05,560 HEMORRHAGE AND HEMORRHAGE IN THE 554 00:28:05,560 --> 00:28:08,360 BONDS AND AND THANK YOU VERY 555 00:28:08,360 --> 00:28:09,720 MUCH AND Dr. WILLIAMSON WILL 556 00:28:09,720 --> 00:28:13,080 TAKE OVER FROM NOW. 557 00:28:13,080 --> 00:28:15,080 >>ALL RIGHT, THANK YOU, VERY 558 00:28:15,080 --> 00:28:15,280 MUCH. 559 00:28:15,280 --> 00:28:17,240 THOSE ARE TERRIFIC 560 00:28:17,240 --> 00:28:17,600 PRESENTATIONS. 561 00:28:17,600 --> 00:28:19,320 IT'S VERY COMPLICATED CASE, LET 562 00:28:19,320 --> 00:28:22,680 ME SEE IF I COULD PROVIDE OF A 563 00:28:22,680 --> 00:28:24,560 CONTEXT AND SUMMARY OF THE WORK 564 00:28:24,560 --> 00:28:27,240 THAT'S BEEN DONE ON THIS DISEASE 565 00:28:27,240 --> 00:28:29,040 AT NIH. 566 00:28:29,040 --> 00:28:30,840 SO, THIS IS SUMMARIZED QUICKLY, 567 00:28:30,840 --> 00:28:33,560 THIS IS A 64-YEAR-OLD PREVIOUSLY 568 00:28:33,560 --> 00:28:39,040 HEALTHY FEMALE DEVELOPS 569 00:28:39,040 --> 00:28:40,120 CRYPTOCOCCAL MENINGITIS AND THEN 570 00:28:40,120 --> 00:28:42,080 WITH CLINICAL WORSENING THE 571 00:28:42,080 --> 00:28:44,360 TERMINAL EVENT OF A HEMORRHAGE, 572 00:28:44,360 --> 00:28:48,720 SO THE NUMBER OF COM REFLECTING 573 00:28:48,720 --> 00:28:52,480 COMPLICATING FACTORS HERE AND 574 00:28:52,480 --> 00:29:00,080 THIS WAS SEVEN OR EIGHT YEARS 575 00:29:00,080 --> 00:29:02,560 AGO AND SOME OF THE CASES THAT 576 00:29:02,560 --> 00:29:05,560 COMPLICATE THIS IS WE HAVE 577 00:29:05,560 --> 00:29:07,040 INFECTIOUS ORGANISMS, AND WE 578 00:29:07,040 --> 00:29:09,200 HAVE A POST INFECTIOUS 579 00:29:09,200 --> 00:29:10,200 INFLAMMATORY RESPONSE SYNDROME 580 00:29:10,200 --> 00:29:12,000 AND THIS IS THE DEADLY CURVE 581 00:29:12,000 --> 00:29:13,360 THAT OUR TITLE CAME FROM. 582 00:29:13,360 --> 00:29:16,440 AND BASICALLY I'M GOING TO TALK 583 00:29:16,440 --> 00:29:18,080 ABOUT THIS A LITTLE BIT MORE IN 584 00:29:18,080 --> 00:29:18,480 DETAIL. 585 00:29:18,480 --> 00:29:20,200 WHEN YOU HAVE AN INFECTION, A 586 00:29:20,200 --> 00:29:22,000 NEUROLOGICAL INFECTION, EARLY 587 00:29:22,000 --> 00:29:24,600 ON, YOU HAVE INCREASED FUNGAL 588 00:29:24,600 --> 00:29:25,680 CULTURES AND YOU HAVE A LOT OF 589 00:29:25,680 --> 00:29:28,000 DAMAGE FROM THE ORGANISMS ITSELF 590 00:29:28,000 --> 00:29:30,280 PRODUCING PRODUCTS, DIGESTING 591 00:29:30,280 --> 00:29:33,560 AND THEN AS YOU KILL THE FUNGUS, 592 00:29:33,560 --> 00:29:35,760 IN CRYPTOCOCCAL, YOU HAVE 593 00:29:35,760 --> 00:29:37,160 RELEASE OF ALL THESE FUNG ALAN 594 00:29:37,160 --> 00:29:38,920 TEE AGAINS THAT CULTURES ARE 595 00:29:38,920 --> 00:29:40,600 NEGATIVE BUT YOU HAVE AN 596 00:29:40,600 --> 00:29:41,400 INFLAMMATORY RESPONSE THAT COMES 597 00:29:41,400 --> 00:29:43,840 IN INTO THE BRAIN AND CAUSES 598 00:29:43,840 --> 00:29:45,040 IMMUNE DAMAGE FROM THAT AND THE 599 00:29:45,040 --> 00:29:46,840 QUESTION IS, AT ANY GIVEN TIME, 600 00:29:46,840 --> 00:29:49,040 IS WHERE ARE YOU ON THIS CURVE. 601 00:29:49,040 --> 00:29:52,040 WE ALSO HAVE AN ADDITIONAL 602 00:29:52,040 --> 00:29:57,080 EFFECT OF THE VAAS CUE ON AGENT' 603 00:29:57,080 --> 00:29:59,320 AND COULD DEAL WITH BOTH AND YOU 604 00:29:59,320 --> 00:30:01,480 HAVE NEURO VASCULAR DISEASE AND 605 00:30:01,480 --> 00:30:03,600 WE HAVE COMPLICATIONS OF THOM 606 00:30:03,600 --> 00:30:06,480 BOW SIS AND ANTI COAGULATION. 607 00:30:06,480 --> 00:30:08,280 IF YOU THINK ON THAT AUTOPSY, I 608 00:30:08,280 --> 00:30:10,160 SEE ALL THOSE ORGANISMS AND IT 609 00:30:10,160 --> 00:30:11,400 MUST HAVE BEEN THE FUNGUS WAS 610 00:30:11,400 --> 00:30:13,680 GROWING AND IT WASN'T BEING 611 00:30:13,680 --> 00:30:15,840 CONTROLLED AND THE FUNGUS IS NOT 612 00:30:15,840 --> 00:30:18,800 LIKE A BACTERIA THAT JUST 613 00:30:18,800 --> 00:30:22,840 DISAPPEARS OR PROTOZONE WHEN IT 614 00:30:22,840 --> 00:30:24,880 SKILLS IT DISAPPEARS, THE FUNGAL 615 00:30:24,880 --> 00:30:26,080 FORMS STAY IN THE BRAIN FOR A 616 00:30:26,080 --> 00:30:26,760 LONG TIME. 617 00:30:26,760 --> 00:30:28,080 JUST TO ILLUSTRATE THAT FACT, 618 00:30:28,080 --> 00:30:30,080 HERE IS ANOTHER PATIENT WHO DIED 619 00:30:30,080 --> 00:30:32,520 10 YEARS AFTER THEIR 620 00:30:32,520 --> 00:30:34,600 CRYPTOCOCCAL INFECTION OF 621 00:30:34,600 --> 00:30:37,480 UNRELATED CAUSES AFTER ANTI FUNG 622 00:30:37,480 --> 00:30:40,920 ALS AND STABLE BUT YOU CAN SEE 623 00:30:40,920 --> 00:30:47,760 THESE ALONG THE CHANNEL IN THE 624 00:30:47,760 --> 00:30:48,680 BRAIN. 625 00:30:48,680 --> 00:30:50,440 IT LOOKS LIKE AN ACTIVE 626 00:30:50,440 --> 00:30:50,960 INFECTION THAT WAS JUST 627 00:30:50,960 --> 00:30:51,640 HAPPENING YESTERDAY. 628 00:30:51,640 --> 00:30:52,800 IT CAN BE DIFFICULT. 629 00:30:52,800 --> 00:30:54,480 AND THE CREATION OF BIOMARKERS 630 00:30:54,480 --> 00:30:56,440 IS REALLY CRITICAL. 631 00:30:56,440 --> 00:30:57,680 SO LET'S PULL BACK A LITTLE BIT 632 00:30:57,680 --> 00:31:01,440 AND JUST A LITTLE REVIEW OF WHAT 633 00:31:01,440 --> 00:31:02,720 CRYPTOCOCCAL IS. 634 00:31:02,720 --> 00:31:05,000 IT'S SOIL OF BIRDS WE ACQUIRE 635 00:31:05,000 --> 00:31:07,120 THIS WHEN WE WERE FIVE-YEARS-OLD 636 00:31:07,120 --> 00:31:07,920 DRAWING AROUND ON THE DIRT AND 637 00:31:07,920 --> 00:31:09,920 IT'S A REACTIVATION DISEASE IN 638 00:31:09,920 --> 00:31:12,280 MANY OF THESE CASES, PROBABLY 639 00:31:12,280 --> 00:31:14,560 10% OF US HAVE A LIVE FUNGUS IN 640 00:31:14,560 --> 00:31:15,160 OUR LUNG. 641 00:31:15,160 --> 00:31:16,520 IT'S THAT COMMON. 642 00:31:16,520 --> 00:31:18,760 AND IT SITS THERE AND IT'S LIKE 643 00:31:18,760 --> 00:31:22,320 TB BUT NOT AS VIRULENT AND WE 644 00:31:22,320 --> 00:31:24,360 GET SUPPRESSED FOR WHATEVER 645 00:31:24,360 --> 00:31:27,240 REASON, GENETICALLY, WITH AGE OR 646 00:31:27,240 --> 00:31:29,520 WITH HIV, OR WITH STEROIDS, THEN 647 00:31:29,520 --> 00:31:31,760 YOU CAN REACTIVATE. 648 00:31:31,760 --> 00:31:33,680 IF THE PULMONARY PRESENTATION 649 00:31:33,680 --> 00:31:38,720 CAN COMPOSE OF INFRILL TRAITS 650 00:31:38,720 --> 00:31:40,560 THE NODULES AND INSEV LIGHT US 651 00:31:40,560 --> 00:31:43,320 IS A BAD THING AND THE NEURO 652 00:31:43,320 --> 00:31:45,360 TROPPISM OF THIS ORGANISM IS 653 00:31:45,360 --> 00:31:46,760 REALLY IMPRESSIVE AND IT'S 654 00:31:46,760 --> 00:31:48,360 RELATED TO A NUMBER OF THINGS 655 00:31:48,360 --> 00:31:50,360 INCLUDING THE ABILITY TO INVADE 656 00:31:50,360 --> 00:31:52,320 THE NEURO VASCULAR AND HERE IS 657 00:31:52,320 --> 00:31:54,400 WORK FROM Dr. FUNG CHUNG'S LAB 658 00:31:54,400 --> 00:31:57,560 IN LCIM WHERE SHE CHOSE THE 659 00:31:57,560 --> 00:31:59,240 FUNGUS BEING TAKEN OUT AND OVER 660 00:31:59,240 --> 00:32:02,160 HERE ON THE RIGHT WE HAVE A 661 00:32:02,160 --> 00:32:03,840 FRESH SAMPLE OF BRAIN AND YOU 662 00:32:03,840 --> 00:32:06,280 CAN SEE THIS HAZINESS IS NOT 663 00:32:06,280 --> 00:32:08,480 BECAUSE OF FIXATION OR BECAUSE 664 00:32:08,480 --> 00:32:10,520 OF ANY ARTIFACTS, BUT THIS IS 665 00:32:10,520 --> 00:32:12,880 THE ORGANISM AND THE 666 00:32:12,880 --> 00:32:14,600 INFLAMMATION THAT CAN OBSTRUCT 667 00:32:14,600 --> 00:32:19,560 IN THE SEVERE ASPECT OF THE A 668 00:32:19,560 --> 00:32:26,600 RACK NODE VILLY SO THIS IS 669 00:32:26,600 --> 00:32:37,080 REALLY -- NOW, YOU THINK THIS 670 00:32:52,360 --> 00:32:56,040 CRYPTOCOCCAL IS SO RARE BUT NOW 671 00:32:56,040 --> 00:32:58,440 BECAUSE OF THE CRYPTO COCK US 672 00:32:58,440 --> 00:33:02,200 BECAUSE OF THE VACCINES OF THE 673 00:33:02,200 --> 00:33:12,680 PATHOGENS, CRYPTOCOCCUS AS 674 00:33:13,040 --> 00:33:14,520 STAYED THE GAME AND IT'S THE 675 00:33:14,520 --> 00:33:16,440 MOST COMMON NON VIRAL MENINGITIS 676 00:33:16,440 --> 00:33:18,760 IN THE UNITED STATES. 677 00:33:18,760 --> 00:33:20,520 SO LET'S COME BACK TO THIS 678 00:33:20,520 --> 00:33:21,440 DEADLY CURVE A LITTLE BIT. 679 00:33:21,440 --> 00:33:22,720 WHAT WE'VE BEEN ABLE TO DO 680 00:33:22,720 --> 00:33:24,440 BECAUSE OF THE REALLY THE 681 00:33:24,440 --> 00:33:26,800 SPECIALIST OF THE NIH CLINICAL 682 00:33:26,800 --> 00:33:28,320 CENTER, IS WE'RE ABLE TO SEE 683 00:33:28,320 --> 00:33:31,120 PATIENTS AT THE BEDSIDE AND 684 00:33:31,120 --> 00:33:33,800 WE'RE ABLE TO DO PRETTY 685 00:33:33,800 --> 00:33:36,400 EXTENSIVE IMMUNO PHENOTYPING OF 686 00:33:36,400 --> 00:33:38,920 THE PATIENT WITHIN AN HOUR AND 687 00:33:38,920 --> 00:33:40,240 CSF DOES NOT LAST VERY LONG SO 688 00:33:40,240 --> 00:33:41,720 IT'S REALLY IMPORTANT. 689 00:33:41,720 --> 00:33:45,840 WE DID THIS IN COLLABORATION 690 00:33:45,840 --> 00:33:47,480 WITH OUR LARGER LABORATORY AND 691 00:33:47,480 --> 00:33:51,360 DEVELOPED A LOT OF THESE 692 00:33:51,360 --> 00:33:51,840 PROTOCOLS FOR MULTIPLE 693 00:33:51,840 --> 00:33:52,120 SCLEROSIS. 694 00:33:52,120 --> 00:33:52,920 WE WERE ABLE TO FIND A NEW 695 00:33:52,920 --> 00:33:55,200 SYNDROME OF POST INFECTIOUS 696 00:33:55,200 --> 00:33:56,440 INFLAMMATORY RESPONSE SYNDROME 697 00:33:56,440 --> 00:33:58,120 AND WE DEFINED AS FOUR WEEKS IN 698 00:33:58,120 --> 00:34:01,240 THE EFFECTIVE ANTI FUNGALS AND 699 00:34:01,240 --> 00:34:03,160 CSF FUNGAL CULTURES NEGATIVE, 700 00:34:03,160 --> 00:34:07,160 DECLINING MENTAL STATUS AND WE 701 00:34:07,160 --> 00:34:11,880 USED A MOCA SCORE MONTREAL 702 00:34:11,880 --> 00:34:13,400 COGNITIVE AND I WOULDN'T SUGGEST 703 00:34:13,400 --> 00:34:15,240 IT FOR PRESIDENTS BUT YOU DRAW 704 00:34:15,240 --> 00:34:17,000 CLOCKS AND YOU HAVE TO MEMORIZE 705 00:34:17,000 --> 00:34:18,200 THINGS AND DO SERIAL AND IT 706 00:34:18,200 --> 00:34:20,080 GIVES YOU A NICE NUMEROUS I 707 00:34:20,080 --> 00:34:22,560 CANAL ASSESSMENT OF HOW 708 00:34:22,560 --> 00:34:24,920 COGNITIVE AWARE YOU ARE. 709 00:34:24,920 --> 00:34:28,320 ALSO, IN ADDITION TO DECLINING 710 00:34:28,320 --> 00:34:29,680 MENTAL STAGE AND PROGRESSIVE 711 00:34:29,680 --> 00:34:31,200 HEARING DEFICITS, AFTER THESE 712 00:34:31,200 --> 00:34:32,440 CULTURES ARE BECOMING NEGATIVE 713 00:34:32,440 --> 00:34:35,240 AND THE REASON WHY THE MO CA22 714 00:34:35,240 --> 00:34:37,160 IS SO IMPORTANT IS IN A 715 00:34:37,160 --> 00:34:39,200 COLLECTION OF 25 CENTERS WE DID 716 00:34:39,200 --> 00:34:40,920 WITH KAREN AND JOHN HOPKINS THE 717 00:34:40,920 --> 00:34:44,000 LOW MOCA SCORE OF 22 YOU CAN SEE 718 00:34:44,000 --> 00:34:45,880 MANY OF THEM DO NOT ACHIEVE A 719 00:34:45,880 --> 00:34:48,840 NORMAL MOCA SCORE AT END 720 00:34:48,840 --> 00:34:50,560 WHEREAS, PEOPLE ABOVE 22 DO 721 00:34:50,560 --> 00:34:52,080 FINE. 722 00:34:52,080 --> 00:34:53,680 IT'S A NICE MARKATOR OF THE 723 00:34:53,680 --> 00:34:54,040 DISEASE. 724 00:34:54,040 --> 00:34:56,600 AND OF COURSE, WE WERE ABLE TO 725 00:34:56,600 --> 00:34:58,760 CHARACTERIZE THE IMMUNE SYSTEM 726 00:34:58,760 --> 00:35:00,800 BY CLOSE CYTOMETRY AND I REALLY 727 00:35:00,800 --> 00:35:01,880 IMPORTANT BECAUSE OUR FIRST 728 00:35:01,880 --> 00:35:04,600 PATIENT WHO REALLY DID BADLY WE 729 00:35:04,600 --> 00:35:06,000 GAVE HIM STEROIDS AND HE 730 00:35:06,000 --> 00:35:09,240 IMPROVED AND WE DID ALL SORTS OF 731 00:35:09,240 --> 00:35:11,600 CRAZY THINGS AND THE IMPORTANCE 732 00:35:11,600 --> 00:35:13,600 OF BEING ABLE TOLL DO 733 00:35:13,600 --> 00:35:15,680 PHENOTYPING IS IT ALLOWED US TO 734 00:35:15,680 --> 00:35:17,800 BE PERSISTENT AND PUSH THE 735 00:35:17,800 --> 00:35:20,480 AMOUNT OF IMMUNO SUPPRESSION AND 736 00:35:20,480 --> 00:35:21,000 STEROID TREATMENT. 737 00:35:21,000 --> 00:35:23,040 THIS PARTICULAR PATIENT WAS 738 00:35:23,040 --> 00:35:25,240 DIFFICULT BECAUSE WE HAD AN WE 739 00:35:25,240 --> 00:35:28,040 COULDN'T ACCESS THE LB AND WE 740 00:35:28,040 --> 00:35:29,920 HAD TO USE MRI THAT WE'RE STILL 741 00:35:29,920 --> 00:35:31,440 LEARNING HOW TO USE. 742 00:35:31,440 --> 00:35:35,120 TO DESCRIBE THIS CASE, WE 743 00:35:35,120 --> 00:35:37,520 HAVE -- WE COMPARED IT TO THE 744 00:35:37,520 --> 00:35:39,360 HIV RELATED IRIS AND IN THIS 745 00:35:39,360 --> 00:35:42,320 CASE THE CRYPTOCOCCUS KILLED 746 00:35:42,320 --> 00:35:43,360 WHEN YOU GET WE HAVE A 747 00:35:43,360 --> 00:35:44,680 RECONSTITUTION OF THE IMMUNE 748 00:35:44,680 --> 00:35:46,760 SYSTEM IT COMES BACK AND OVER 749 00:35:46,760 --> 00:35:47,960 ANYWHERE FROM THREE TO SIX 750 00:35:47,960 --> 00:35:51,000 MONTHS LATER, ALL THE ANTIGENS 751 00:35:51,000 --> 00:35:53,800 FROM THE CRYPTOCOCCUS STIMULATE 752 00:35:53,800 --> 00:35:57,640 THE CELLS AND ACTIVATE T CELLS 753 00:35:57,640 --> 00:36:03,680 AND YOU HAVE ACTIVATION. 754 00:36:03,680 --> 00:36:04,720 THEY'RE HEALTHY PREVIOUSLY AND 755 00:36:04,720 --> 00:36:06,800 WE DON'T GIVE THEM ANYTHING TO 756 00:36:06,800 --> 00:36:08,520 RECONSTITUTE THEM. 757 00:36:08,520 --> 00:36:10,640 WHEN YOU LICE THOSE 758 00:36:10,640 --> 00:36:11,600 CRYPTOCOCCUS, IT'S COVERED BY 759 00:36:11,600 --> 00:36:13,160 THIS CAPSULE THAT IS SORT OF 760 00:36:13,160 --> 00:36:15,000 INSULATING IT FROM THE IMMUNE 761 00:36:15,000 --> 00:36:16,400 SYSTEM BUT WHEN YOU BREAK IT 762 00:36:16,400 --> 00:36:18,720 OPEN AND RELEASE IT'S LIKE 763 00:36:18,720 --> 00:36:20,000 INJECTING PROTEIN INTO YOU AND 764 00:36:20,000 --> 00:36:23,400 YOU HAVE A IMMUNE RESPONSE AND 765 00:36:23,400 --> 00:36:25,240 FOLLOWED BY T-CELL ACTIVATION. 766 00:36:25,240 --> 00:36:26,640 ONE THING TO NOTE HERE, THIS IS 767 00:36:26,640 --> 00:36:30,320 ONE OF THE SOL YOU BULL MARKERS 768 00:36:30,320 --> 00:36:32,520 AND YOU NOTICE IN THE CNC 769 00:36:32,520 --> 00:36:36,560 PATIENTS HAZEL RATE ISED, 10 TO 770 00:36:36,560 --> 00:36:36,880 100 FOLD. 771 00:36:36,880 --> 00:36:37,920 IT'S IMPORTANT BECAUSE THE 772 00:36:37,920 --> 00:36:40,080 CURRENT IBSA RECOMMENDATIONS ARE 773 00:36:40,080 --> 00:36:42,280 IN THESE PATIENTS IS THAT ARE 774 00:36:42,280 --> 00:36:45,360 REFLECTORRING THE DISEASE AND 775 00:36:45,360 --> 00:36:47,440 NON IS TO GIVE THEM AND KNOWING 776 00:36:47,440 --> 00:36:48,960 THE PATHOGENESIS OF THE DISEASE, 777 00:36:48,960 --> 00:36:50,520 THIS IS LIKE PUTTING GASOLINE ON 778 00:36:50,520 --> 00:36:51,080 THE FIRE. 779 00:36:51,080 --> 00:36:54,920 YOU CAN SEE WHY IT MAY NOT BE A 780 00:36:54,920 --> 00:36:56,920 GOOD IDEA AND WE GIVE IT TO A 781 00:36:56,920 --> 00:36:58,880 FIRST PATIENT AND THEY 782 00:36:58,880 --> 00:36:59,960 DETERIORATED AND THEY FLIPPED 783 00:36:59,960 --> 00:37:01,320 OVER AND GAVE THEM STEROIDS AND 784 00:37:01,320 --> 00:37:02,240 THEY IMPROVED. 785 00:37:02,240 --> 00:37:05,480 THE INTERESTING THING IS MANY 786 00:37:05,480 --> 00:37:07,120 CASES THEY ARE REALLY WHERE THE 787 00:37:07,120 --> 00:37:10,560 DEFECT IS RATHER THAN T CELLS 788 00:37:10,560 --> 00:37:11,720 AND ON AUTOPSY AND BRAIN BIOPSY, 789 00:37:11,720 --> 00:37:14,640 THIS IS A BRAIN BIOPSY SPECIMEN, 790 00:37:14,640 --> 00:37:16,320 MARKERS SUCH AS INOS WHICH MARK 791 00:37:16,320 --> 00:37:19,960 AN ACTIVATED N1 POLARIZED TISSUE 792 00:37:19,960 --> 00:37:25,080 AND YOU CAN TAKE UP CYTO SIS AND 793 00:37:25,080 --> 00:37:27,800 KILL IT IT'S NOT PRESENT AND TWO 794 00:37:27,800 --> 00:37:29,040 MARKERS ARE ACTIVATED SUGGESTING 795 00:37:29,040 --> 00:37:31,520 AN ALTERNATIVELY ACTIVATED MACRO 796 00:37:31,520 --> 00:37:35,040 PAGE WHICH DOESN'T DO A GO AHEAB 797 00:37:35,040 --> 00:37:37,040 IN CLEARING THE FUNGUS SO IT'S 798 00:37:37,040 --> 00:37:38,840 NOT ENOUGH TO DESCRIBE A 799 00:37:38,840 --> 00:37:40,480 SYNDROME, YOU KNOW, IT'S NICE IF 800 00:37:40,480 --> 00:37:42,000 YOU HAVE A THERAPY FOR IT, MUCH 801 00:37:42,000 --> 00:37:46,160 BETTER FOR PATIENTS AND SO, OVER 802 00:37:46,160 --> 00:37:47,200 A PERIOD OF TIME WE DEVELOPED 803 00:37:47,200 --> 00:37:49,560 THIS IDEA OF DOING THIS PULSE 804 00:37:49,560 --> 00:37:51,960 TAPER THERAPY, AND THEN WHEN WE 805 00:37:51,960 --> 00:37:53,520 HAD ALL THE SORT OF END POINTS 806 00:37:53,520 --> 00:37:56,120 WE WANTED DO WE DID A 807 00:37:56,120 --> 00:37:57,280 PERSPECTIVE FOLLOWING OF THESE 808 00:37:57,280 --> 00:37:59,400 USING A UNIFORM TREATMENT AND 809 00:37:59,400 --> 00:38:01,640 FOLLOW-UP AND THIS IS REPORT OF 810 00:38:01,640 --> 00:38:03,280 15 PREVIOUSLY HEALTHY PATIENTS 811 00:38:03,280 --> 00:38:04,880 ADMITTED OVER A FIVE-YEAR PERIOD 812 00:38:04,880 --> 00:38:08,440 ALL TREATED UNIFORMLY AND 813 00:38:08,440 --> 00:38:13,000 RETROSPECTIVE LEANNE ALLIES AND 814 00:38:13,000 --> 00:38:18,520 THEY ALL GOT 5FC FOR WOULD YOU 815 00:38:18,520 --> 00:38:19,800 WEEKS AND CULT TURES NEGATIVE. 816 00:38:19,800 --> 00:38:21,120 THEY HAD A PULSE FOR SEVEN DAYS 817 00:38:21,120 --> 00:38:23,880 AND REALLY IS NEEDED AND THEN WE 818 00:38:23,880 --> 00:38:26,960 FOLLOW IT WITH A MILL A GRAM OR 819 00:38:26,960 --> 00:38:28,560 KILOGRAM OF PREDNISONE AND IT 820 00:38:28,560 --> 00:38:30,320 TAKES ABOUT A YEAR TO GET 821 00:38:30,320 --> 00:38:32,520 PATIENTS OFF IT AND OF COURSE WE 822 00:38:32,520 --> 00:38:35,720 DO PROPHYLACTIC BACK DROWN AND 823 00:38:35,720 --> 00:38:37,400 VIRUSES AT THIS POINT AND WE 824 00:38:37,400 --> 00:38:38,800 TAPER THEM OVER SLOWLY WATCHING 825 00:38:38,800 --> 00:38:40,640 THEM CLINICALLY AND GETTING A 826 00:38:40,640 --> 00:38:44,400 LOT OF MRI, WHICH CAN BE USEFUL. 827 00:38:44,400 --> 00:38:45,080 SO, WHAT ARE THE RESULTS ON 828 00:38:45,080 --> 00:38:45,560 THIS? 829 00:38:45,560 --> 00:38:46,960 THEY HAD A TREMENDOUS RESPONSE, 830 00:38:46,960 --> 00:38:48,320 IT'S LIKE SOMETHING OUT OF A 831 00:38:48,320 --> 00:38:49,920 MOVIE ACTUALLY. 832 00:38:49,920 --> 00:38:58,480 THEY ALL RESPONDED SEM PRESS I 833 00:38:58,480 --> 00:38:58,720 HAVELY. 834 00:38:58,720 --> 00:39:00,680 THERE'S ANOTHER MEASURE OF 835 00:39:00,680 --> 00:39:04,160 NEUROLOGICAL PERFORMANCE ALL 836 00:39:04,160 --> 00:39:05,440 IMPROVED AND THE PRESSURE CAME 837 00:39:05,440 --> 00:39:06,920 DOWN AND WE WERE ABLE TO AVOID 838 00:39:06,920 --> 00:39:10,240 SHUNTING IN HALF THE PATIENTS. 839 00:39:10,240 --> 00:39:12,240 VISUAL FEELS ARE A MEASURE BY 840 00:39:12,240 --> 00:39:14,040 DIS A BELL AND THEY DO IT WITH 841 00:39:14,040 --> 00:39:15,240 HEARING AND ALSO WITH VISION. 842 00:39:15,240 --> 00:39:17,440 YOU CAN SEE ON THE BOTTOM A 843 00:39:17,440 --> 00:39:20,480 CARTOON, ZERO DECIBELS IS A 844 00:39:20,480 --> 00:39:21,600 NORMAL FIELDS WHEN YOU COME DOWN 845 00:39:21,600 --> 00:39:23,120 AND LOSE YOUR VISUAL FIELDS HERE 846 00:39:23,120 --> 00:39:24,840 IS AN EXAMPLE OF -20. 847 00:39:24,840 --> 00:39:27,120 YOU CAN SEE THEY ALL IMPROVE AS 848 00:39:27,120 --> 00:39:28,880 WELL SO EVERYBODY IMPROVES WITH 849 00:39:28,880 --> 00:39:29,800 THIS THERAPY. 850 00:39:29,800 --> 00:39:33,120 LOOKING AT THE CSF PARAMETERS, 851 00:39:33,120 --> 00:39:36,520 THE CSF GLUCOSE RISES TOWARDS 852 00:39:36,520 --> 00:39:37,960 NORMAL AND THIS IS AFTER JUST 853 00:39:37,960 --> 00:39:41,920 SEVEN DA OF A FULLS AND IT IMPRS 854 00:39:41,920 --> 00:39:43,360 LATER ON THE THE CELL COUNTS 855 00:39:43,360 --> 00:39:45,080 COME DOWN AND ELEVATED PROTEINS 856 00:39:45,080 --> 00:39:47,720 COME DOWN, AND HERE WE GO WITH 857 00:39:47,720 --> 00:39:49,640 SOME OF O'ER FLOW CYTOMETRY AND 858 00:39:49,640 --> 00:39:52,640 THE MARKER OF T-CELL ACTIVATION 859 00:39:52,640 --> 00:39:54,680 AND T CELLS CAN PRESENT ANTIGENS 860 00:39:54,680 --> 00:39:55,760 IT'S NOT THE QUESTION. 861 00:39:55,760 --> 00:39:57,120 IT'S BEEN USED AS A T-CELL 862 00:39:57,120 --> 00:39:59,120 MARKER AND YOU CAN SEE HERE THE 863 00:39:59,120 --> 00:40:00,720 CD4, THE PURPLE CELLS HERE, ARE 864 00:40:00,720 --> 00:40:04,120 THE ACTIVATED CELLS AND WITH 865 00:40:04,120 --> 00:40:08,560 SEVEN DAYS OF PULSE, THEY COME. 866 00:40:08,560 --> 00:40:09,760 ABOUT 10-FOLD FOR EACH PATIENT 867 00:40:09,760 --> 00:40:11,600 AND THE INFLAMMATORY MONEY 868 00:40:11,600 --> 00:40:20,720 SIMONOCYTESARE AND TH CYTOKINESD 869 00:40:20,720 --> 00:40:22,800 CD25 THE IL2 RECEPTORS WHICH IS 870 00:40:22,800 --> 00:40:25,880 ALSO A MARKER IN OTHER 871 00:40:25,880 --> 00:40:29,600 ACTIVATION SYNDROMES LIKE HLH 872 00:40:29,600 --> 00:40:31,280 AND MACRO FAGE ACTIVATION COMES 873 00:40:31,280 --> 00:40:31,720 DOWN 10 FOLD. 874 00:40:31,720 --> 00:40:33,040 AFTER ABOUT THREE DAYS THE 875 00:40:33,040 --> 00:40:35,000 PATIENT BEGINS TO WAKE UP AND 876 00:40:35,000 --> 00:40:36,720 PROGRESSES FROM THERE AND SO 877 00:40:36,720 --> 00:40:47,800 Dr. HAMM OUTAOUAIS OUD AND AND D 878 00:40:48,200 --> 00:40:51,000 IMPROVEMENT IN EVERYTHING 879 00:40:51,000 --> 00:40:51,200 PATIENT. 880 00:40:51,200 --> 00:40:53,600 IN ADDITION MARKER A LITTLE 881 00:40:53,600 --> 00:40:58,920 DAMAGE AND YOU CREDIT SEE IN THE 882 00:40:58,920 --> 00:41:01,560 CSF AND SHOWED BY YOU CAN SEE IT 883 00:41:01,560 --> 00:41:03,280 OVER TIME THERE'S NOT A REBOUND 884 00:41:03,280 --> 00:41:05,040 BUT THERE'S A PROGRESSIVE 885 00:41:05,040 --> 00:41:07,680 DECREASE AS YOU REDUCE DAMAGE TO 886 00:41:07,680 --> 00:41:09,640 THE NEUROLOGICAL TISSUE AND THEY 887 00:41:09,640 --> 00:41:10,920 IMPROVE ALL THE WAY OUT TO A 888 00:41:10,920 --> 00:41:13,040 YEAR VERY SLOWLY. 889 00:41:13,040 --> 00:41:15,000 SO, LET ME GIVE YOU SOME 890 00:41:15,000 --> 00:41:15,880 ANECDOTES BECAUSE YOU SEE 891 00:41:15,880 --> 00:41:17,200 NUMBERS AND YOU ARE LIKE A 892 00:41:17,200 --> 00:41:18,600 COUPLE NUMBERS HERE. 893 00:41:18,600 --> 00:41:21,000 THIS IS ACTUALLY A VERY TYPICAL 894 00:41:21,000 --> 00:41:26,360 RESPONSE THAT WE SEE. 895 00:41:26,360 --> 00:41:28,920 WHIFF 15 PATIENTS THAT HAVE 896 00:41:28,920 --> 00:41:29,800 TAPERED DOWN. 897 00:41:29,800 --> 00:41:31,880 IT TOOK A AVERAGE OF 1 POINT A 898 00:41:31,880 --> 00:41:35,080 YEARS TO GET THEM OFF ST STEROI. 899 00:41:35,080 --> 00:41:36,560 WE HAD ONE DEATH FROM A 900 00:41:36,560 --> 00:41:40,720 PULMONARY AM BOLISM. 901 00:41:40,720 --> 00:41:42,360 THE COMPLICATIONS WE DIDN'T SEE 902 00:41:42,360 --> 00:41:45,040 ANY INFECTIONS AND WE GET THEM 903 00:41:45,040 --> 00:41:46,760 OFF STEROIDS FAIRLY QUICKLY AND 904 00:41:46,760 --> 00:41:48,440 THEY TAPER DOWN FREQUENTLY SO 905 00:41:48,440 --> 00:41:50,360 COMPARED TO OTHER DISEASES WHERE 906 00:41:50,360 --> 00:41:52,000 THEY'RE ON LIFELONG STEROIDS AND 907 00:41:52,000 --> 00:41:54,280 WE DID HAVE TO USE THIS 908 00:41:54,280 --> 00:41:55,640 PHOSPHATES AND WE DID SEE SOME 909 00:41:55,640 --> 00:41:56,840 CAT A RACKS AND MOST OF THESE 910 00:41:56,840 --> 00:42:07,360 PATIENTS ARE OLDER AND NOT TOO 911 00:42:13,960 --> 00:42:14,920 BAD CONSIDERING THE DOWNSIDE OF 912 00:42:14,920 --> 00:42:15,720 THE DISEASE. 913 00:42:15,720 --> 00:42:19,040 HERE ARE SOME TYPICAL ANECDOTE 914 00:42:19,040 --> 00:42:19,280 STORIES. 915 00:42:19,280 --> 00:42:20,680 YOU SEE THE NUMBERS BUT YOU WANT 916 00:42:20,680 --> 00:42:23,920 TO SEE AN AVERAGE PATIENT. 917 00:42:23,920 --> 00:42:25,800 SO THIS IS WITHIN TWO MONTHS OF 918 00:42:25,800 --> 00:42:27,600 DIAGNOSIS, THEY GO TOO FAR THE 919 00:42:27,600 --> 00:42:29,000 DAMAGE IS ALREADY BEEN DONE AND 920 00:42:29,000 --> 00:42:31,400 YOU CAN SEE IN THIS PATIENT HOW 921 00:42:31,400 --> 00:42:35,400 THAT CHRONIC CRYPTO AND CHRONIC 922 00:42:35,400 --> 00:42:36,600 INFLAMMATION CAN CAUSE A LOT OF 923 00:42:36,600 --> 00:42:36,840 DAMAGE. 924 00:42:36,840 --> 00:42:38,960 THIS IS A PATIENT, A 59-YEAR-OLD 925 00:42:38,960 --> 00:42:40,680 PREVIOUSLY HEALTHY PATIENT SHE 926 00:42:40,680 --> 00:42:42,960 WAS CULTURE NEGATIVE IN TWO 927 00:42:42,960 --> 00:42:44,920 WEEKS AND DETERIORATING MENTAL 928 00:42:44,920 --> 00:42:46,000 STATUS AND DISCUSSION TO 929 00:42:46,000 --> 00:42:46,920 REFERRAL OF THE HOSPITAL AND 930 00:42:46,920 --> 00:42:48,720 THEY PUT HIM ON A JET AND FLEW 931 00:42:48,720 --> 00:42:50,120 HIM HERE AND THIS IS WHERE THE 932 00:42:50,120 --> 00:42:52,200 NIGHT HE ARRIVED HERE AND THIS 933 00:42:52,200 --> 00:42:53,440 IS HIS WIFE TRYING TO GET HIM TO 934 00:42:53,440 --> 00:42:58,200 RESPOND A LITTLE BIT. 935 00:42:58,200 --> 00:42:59,200 >> CAN YOU TALK TO ME? 936 00:42:59,200 --> 00:43:02,760 >> CAN YOU TALK TO ME? 937 00:43:02,760 --> 00:43:05,640 >> YOU CAN SEE NOT TERRIBLY 938 00:43:05,640 --> 00:43:08,000 RESPONSIVE AND AFTER 10 DAYS OF 939 00:43:08,000 --> 00:43:10,960 THERAPY, HERE HE IS STANDING UP 940 00:43:10,960 --> 00:43:13,040 AND HE IS FACIAL DROOP BUT HE IS 941 00:43:13,040 --> 00:43:13,680 OR' ENTERTAINMENTED TIMES THREE 942 00:43:13,680 --> 00:43:15,280 AT THIS POINT AND WALKING AROUND 943 00:43:15,280 --> 00:43:16,880 THE HALL WITH A WALKER. 944 00:43:16,880 --> 00:43:19,520 IN THREE MONTHS ACTUALLY HE WON 945 00:43:19,520 --> 00:43:20,520 THE BASS FISHING CONTEST. 946 00:43:20,520 --> 00:43:22,160 HE WAS A BASS FISHER AND HE HAD 947 00:43:22,160 --> 00:43:23,760 BEEN FISHING IN A YEAR AND HE 948 00:43:23,760 --> 00:43:26,200 WENT OUT AND WON THE CONTEST. 949 00:43:26,200 --> 00:43:27,680 THE HAT ON HIS HEAD IS BECAUSE 950 00:43:27,680 --> 00:43:31,760 OF THE SUN AND HE WAS VERY HAPPY 951 00:43:31,760 --> 00:43:35,400 AT THAT POINT AND THEN A PATIENT 952 00:43:35,400 --> 00:43:36,120 CAN RESPOND. 953 00:43:36,120 --> 00:43:37,800 HERE IS ANOTHER 25-YEAR-OLD WITH 954 00:43:37,800 --> 00:43:41,240 HEADACHES FOR TWO MONTHS 955 00:43:41,240 --> 00:43:43,080 TESTICULAR PAIN, BLURRY VISION 956 00:43:43,080 --> 00:43:44,720 AND PRETTY SUPER US AT THAT 957 00:43:44,720 --> 00:43:46,960 POINT AND WE GAVE HIM AND AFTER 958 00:43:46,960 --> 00:43:49,120 TWO DAYS, HE WAS OFF ALL HIS 959 00:43:49,120 --> 00:43:50,480 NARCOTICS AND HE SAID CAN THEY 960 00:43:50,480 --> 00:44:00,720 GO TO THE GYM? 961 00:44:07,160 --> 00:44:10,600 AND THEN WITH THE PULSE DECLINED 962 00:44:10,600 --> 00:44:13,600 AND NORMALIZED GOING FORWARD 963 00:44:13,600 --> 00:44:15,480 FROM THAT SO THE RESULTS ARE 964 00:44:15,480 --> 00:44:19,240 PRETTY MUCH LIKE THIS AND THIS 965 00:44:19,240 --> 00:44:21,000 IS THE EXPERIENCE WITH PATIENTS 966 00:44:21,000 --> 00:44:22,560 WITH A NEUROLOGICAL SCORED 967 00:44:22,560 --> 00:44:24,520 LOOKING AT THE LOWER MOTOR 968 00:44:24,520 --> 00:44:26,560 NEURON FUNCTION AND THAT WILL 969 00:44:26,560 --> 00:44:28,480 IMPROVE WITH TIME. 970 00:44:28,480 --> 00:44:31,360 DESPITE REALLY SMALL AND IT'S 971 00:44:31,360 --> 00:44:34,600 BECAUSE OF THE EFFECT SIZE AND 972 00:44:34,600 --> 00:44:35,160 SO LARGE. 973 00:44:35,160 --> 00:44:38,480 WE HAVE AN OUTRAGEOUS GOAL, WE 974 00:44:38,480 --> 00:44:44,520 MAKE NON HIV THIS IS A HISTORY 975 00:44:44,520 --> 00:44:47,160 OF OUTCOME AND SO IN THE 50s, 976 00:44:47,160 --> 00:44:50,720 BEFORE THE ADVENT, WE HAD 100% 977 00:44:50,720 --> 00:44:51,560 MORTALITY AND WE WERE ABLE TO 978 00:44:51,560 --> 00:44:54,000 GET IT DOWN TO 30% AND STAYED 979 00:44:54,000 --> 00:44:55,440 THE SAME FOR 30 YEARS. 980 00:44:55,440 --> 00:44:58,280 AND THIS IS KIND OF A 60 YEARS 981 00:44:58,280 --> 00:44:59,640 SO IT'S EMBARRASSING BECAUSE 982 00:44:59,640 --> 00:45:02,040 I'VE BEEN WORKING ON 983 00:45:02,040 --> 00:45:03,760 CRYPTOCOCCUS AND TRYING TO KILL 984 00:45:03,760 --> 00:45:05,680 THE FUNGUS AND IT WAS 985 00:45:05,680 --> 00:45:06,560 INFLAMMATORY RESPONSE KILLING 986 00:45:06,560 --> 00:45:07,720 ABOUT A THIRD OF THESE PATIENTS 987 00:45:07,720 --> 00:45:09,680 AND WHEN HE TREATED THEM WITH 988 00:45:09,680 --> 00:45:11,120 STEROIDS WE GOT THE MORTALITY 989 00:45:11,120 --> 00:45:17,520 DOWN TO 1% TO 2%ER AEVERYTHINGS 990 00:45:17,520 --> 00:45:18,800 WELL AND GO BACK AND FUNCTION. 991 00:45:18,800 --> 00:45:20,240 THE HARDEST QUESTION WAS BY THE 992 00:45:20,240 --> 00:45:26,600 FORMER CLINICAL DIRECTOR JOHN 993 00:45:26,600 --> 00:45:28,240 GOUGHEN SAID WHY DID IT TAKE YOU 994 00:45:28,240 --> 00:45:29,560 60 YEARS TO FIGURE THIS OUT. 995 00:45:29,560 --> 00:45:31,080 WITH THE KNOWLEDGE OF 996 00:45:31,080 --> 00:45:31,960 PATHOGENESIS WE WERE ABLE TO 997 00:45:31,960 --> 00:45:33,400 GAIN WITH THE INTIMATE 998 00:45:33,400 --> 00:45:34,920 ASSOCIATION OF OUR LABORATORY 999 00:45:34,920 --> 00:45:36,320 FACILITIES AND GOING TO THE 1000 00:45:36,320 --> 00:45:37,400 BEDSIDE AND BACK AND FOURTH AND 1001 00:45:37,400 --> 00:45:39,920 BACK AND FOURTH AND NO NEW 1002 00:45:39,920 --> 00:45:41,440 THERAPY JUST UNDERSTANDING THE 1003 00:45:41,440 --> 00:45:43,040 PATH OF PHYSIOLOGY OF THIS 1004 00:45:43,040 --> 00:45:45,080 DISEASE SO SOME OF OUR FUTURE 1005 00:45:45,080 --> 00:45:47,800 STUDIES WE'RE LOOKING AT 1006 00:45:47,800 --> 00:45:49,560 STEROIDS SPARING AGENTS AND WAYS 1007 00:45:49,560 --> 00:45:52,000 WE TRY BUT IT WASN'T IMPRESSIVE 1008 00:45:52,000 --> 00:45:55,320 AND WE FOUND THAT REXOLINDEN 1009 00:45:55,320 --> 00:45:56,840 SEEMS TO BE MORE IMPRESSIVE AND 1010 00:45:56,840 --> 00:45:58,800 IT'S PROXIMAL AND YOU CAN SEE 1011 00:45:58,800 --> 00:46:01,200 THIS MULTIFACETED AND IMMUNE 1012 00:46:01,200 --> 00:46:03,080 RESPONSE WITH T-CELL ACTIVATION 1013 00:46:03,080 --> 00:46:05,600 AND RECRUITMENT AND REALLY TAKES 1014 00:46:05,600 --> 00:46:07,920 A SLEDGEHAMMER TO DO THAT AND IN 1015 00:46:07,920 --> 00:46:09,400 HUMANS WE'VE HAD A COUPLE 1016 00:46:09,400 --> 00:46:10,920 PATIENTS, FOUR COURSES WHERE WE 1017 00:46:10,920 --> 00:46:21,640 KEEP PREDNISONE THE SAME AND TH- 1018 00:46:21,640 --> 00:46:23,040 WE GO TO A MOUSE MODEL WHERE WE 1019 00:46:23,040 --> 00:46:25,640 HAD TO DEVELOP A NEW MODEL 1020 00:46:25,640 --> 00:46:27,080 BECAUSE WE DIDN'T HAVE ONE AND 1021 00:46:27,080 --> 00:46:30,480 THAT ALLOWS US 20 LOOK AT IT 1022 00:46:30,480 --> 00:46:31,440 ALLOW WITHOUT STEROIDS SO IT'S 1023 00:46:31,440 --> 00:46:34,560 NOT SURPRISING WE CAN REDUCE CD4 1024 00:46:34,560 --> 00:46:36,400 CELLS IN THE BRAIN OR REDUCE 1025 00:46:36,400 --> 00:46:38,960 ACTIVATED T CELLS IN THE BRAIN 1026 00:46:38,960 --> 00:46:40,360 OR MYELOID OR MONOCYTES IN THE 1027 00:46:40,360 --> 00:46:44,400 BRAIN THE IMPORTANT THING IS WE 1028 00:46:44,400 --> 00:46:46,480 CAN REDUCE BRAIN EDEMA. 1029 00:46:46,480 --> 00:46:47,960 WE WERE GIVING STEROIDS AND IT 1030 00:46:47,960 --> 00:46:49,760 HAD NOTHING TO DO WITH THE 1031 00:46:49,760 --> 00:46:51,040 INFLAMMATION BUT TREATING THE 1032 00:46:51,040 --> 00:46:52,640 INFLAMMATION ALONE CAN HAVE SOME 1033 00:46:52,640 --> 00:46:54,000 IMPACT AND WE MIGHT USE THIS 1034 00:46:54,000 --> 00:46:57,000 GOING FORWARD AND NOW THIS AS 1035 00:46:57,000 --> 00:46:58,560 ANNAN SIL ARY TREATMENT WE'LL 1036 00:46:58,560 --> 00:47:02,120 HAVE TO DO A RANDOMIZED TRIAL 1037 00:47:02,120 --> 00:47:04,200 BECAUSE WE HAVE SIGNIFICANT 1038 00:47:04,200 --> 00:47:11,920 POSSIBILITY FOR TOXICITY FROM 1039 00:47:11,920 --> 00:47:20,040 THIS. 1040 00:47:20,040 --> 00:47:21,640 THE FIRST STUDY WAS DONE BECAUSE 1041 00:47:21,640 --> 00:47:23,240 THEY DIDN'T KNOW THESE RESPONDED 1042 00:47:23,240 --> 00:47:24,480 NORMALLY WITHOUT THERAPY AND SO 1043 00:47:24,480 --> 00:47:26,000 THEY KNEW THEY HAD TO HAVE A 1044 00:47:26,000 --> 00:47:28,800 RANDOMIZED STUDY BUT THE 1045 00:47:28,800 --> 00:47:32,000 PRECEDING THAT WAS TB MENINGITIS 1046 00:47:32,000 --> 00:47:34,040 WHERE THEY ALL DIE SO IF YOU 1047 00:47:34,040 --> 00:47:35,240 TREAT ANYBODY AND THEY GET 1048 00:47:35,240 --> 00:47:36,440 BETTER THEY'RE HAPPY AND THEY 1049 00:47:36,440 --> 00:47:38,880 DIDN'T FEEL LIKE THEY NEEDED A 1050 00:47:38,880 --> 00:47:44,800 RANDOM SIZED STUDY. 1051 00:47:44,800 --> 00:47:46,520 SO EVERYBODY ALWAYS ASKS ME, WHY 1052 00:47:46,520 --> 00:47:48,640 DO THESE PREVIOUSLY HEALTHY 1053 00:47:48,640 --> 00:47:51,320 PATIENTS GET CRYPTO CAUCUS? 1054 00:47:51,320 --> 00:47:53,600 WE'VE SEQUENCES THIS STUDY 86 1055 00:47:53,600 --> 00:47:55,800 PATIENTS AND WE TOOK THE STOP 1056 00:47:55,800 --> 00:48:00,400 700 GENES THAT SHOWED MUTANT 1057 00:48:00,400 --> 00:48:02,440 ALLELES AND WE USED THE MUTANT 1058 00:48:02,440 --> 00:48:03,400 FREQUENCY AND VERY RARE BECAUSE 1059 00:48:03,400 --> 00:48:05,840 THE DISEASE IS RARE AND WE USED 1060 00:48:05,840 --> 00:48:08,920 A CAD SCORE OF 25 WHICH IS A 1061 00:48:08,920 --> 00:48:10,240 MEASURE OF PROBABLE DYSFUNCTION 1062 00:48:10,240 --> 00:48:11,640 OF THE INDIVIDUAL MUTATION AND 1063 00:48:11,640 --> 00:48:14,360 WE USED PATHWAY ANALYSIS FOR THE 1064 00:48:14,360 --> 00:48:15,600 INGENUITY AND PATHWAY TOOL. 1065 00:48:15,600 --> 00:48:18,240 WE DO THAT AND WE FIND ONE A 1066 00:48:18,240 --> 00:48:21,920 PREDOMINANT PATHWAY INVOLVED IS 1067 00:48:21,920 --> 00:48:24,480 KINASE AKT TOUR PATHWAY AND WE 1068 00:48:24,480 --> 00:48:26,040 HAVE PATIENTS THAT WE'RE 1069 00:48:26,040 --> 00:48:27,760 EXAMINING NOW LOOKING AT 1070 00:48:27,760 --> 00:48:29,160 MUTATIONS, RARE MUTATIONS IN 1071 00:48:29,160 --> 00:48:30,360 THESE. 1072 00:48:30,360 --> 00:48:31,080 INCLUDING RAPTOR AND WE HAVE 1073 00:48:31,080 --> 00:48:34,920 FOUR PATIENTS WITH M.T.O. R 1074 00:48:34,920 --> 00:48:35,200 MUTATIONS. 1075 00:48:35,200 --> 00:48:39,280 IF YOU KNOW ANYTHING ABOUT 1076 00:48:39,280 --> 00:48:42,440 M.T.O. R IT'S A KINASE AND IT IS 1077 00:48:42,440 --> 00:48:45,280 INVOLVED IN METABOLISM AND IN 1078 00:48:45,280 --> 00:48:46,200 T-CELL ACTIVATION AS WELL AND 1079 00:48:46,200 --> 00:48:49,400 YOU CAN MEASURE IT BY S6 FOSS 1080 00:48:49,400 --> 00:48:51,320 FILLATION SO MOST OF THESE CASES 1081 00:48:51,320 --> 00:48:53,080 ACTUALLY HAVE BEEN REPORTED SO 1082 00:48:53,080 --> 00:48:54,600 FAR AND THEY HAVE BEEN GAIN OF 1083 00:48:54,600 --> 00:48:56,920 FUNCTION AND THE CLASSIC ONE IS 1084 00:48:56,920 --> 00:49:01,720 THE SMITH KINGS MORE SYNDROME 1085 00:49:01,720 --> 00:49:04,040 AND GAIN OF FUNCTION AND MUTANT 1086 00:49:04,040 --> 00:49:07,080 PATIENTS AND IT'S EXHIBITING THE 1087 00:49:07,080 --> 00:49:08,200 MOW SAY CIVIL AS YOU CAN IMAGINE 1088 00:49:08,200 --> 00:49:10,000 IT'S NOT IN BLOOD BUT ONLY IN 1089 00:49:10,000 --> 00:49:14,360 BRAIN AND THEN FOCAL CORTICAL 1090 00:49:14,360 --> 00:49:16,720 DYSPLASIA TYPE TWO AND INTENSE 1091 00:49:16,720 --> 00:49:19,800 ACTIVATION OF THIS S6K AND AS A 1092 00:49:19,800 --> 00:49:22,520 LOW FRACTION IN BRAIN, AND IT'S 1093 00:49:22,520 --> 00:49:23,360 NOT IN BLOOD. 1094 00:49:23,360 --> 00:49:33,080 BUT AS I SAID, YOU CAN SEE THAT 1095 00:49:33,080 --> 00:49:35,920 MTOR AND WE'RE FINDING IN THESE 1096 00:49:35,920 --> 00:49:37,840 PATIENTS, LOSS OF FUNCTION AND 1097 00:49:37,840 --> 00:49:39,560 IT WOULD GO ALONG WITH THE 1098 00:49:39,560 --> 00:49:41,200 T-CELL DEFECTS THAT YOU MIGHT 1099 00:49:41,200 --> 00:49:45,160 SEE IN EXPECTED IN ADAPTIVE 1100 00:49:45,160 --> 00:49:46,280 IMMUNITY ORGANISM HERE AND THE 1101 00:49:46,280 --> 00:49:48,000 SECOND ONE I'M GOING TO TALK 1102 00:49:48,000 --> 00:49:49,840 ABOUT, I THINK I'M GOING TO GET 1103 00:49:49,840 --> 00:49:52,080 TIME TO DO THIS IS A NEWLY 1104 00:49:52,080 --> 00:49:55,520 DEVELOPED MODEL OF POOR 1105 00:49:55,520 --> 00:49:57,320 DEPENDENT RNA DEGRADATION WHICH 1106 00:49:57,320 --> 00:49:59,560 IS DIFFERENT FROM RNA INDUCED 1107 00:49:59,560 --> 00:50:04,120 SILENCING AND WHAT THAT INVOLVES 1108 00:50:04,120 --> 00:50:06,040 IS POOR PHOSPHORYLATION OF THIS 1109 00:50:06,040 --> 00:50:07,680 MOLECULE AND WE GET RECRUITMENT 1110 00:50:07,680 --> 00:50:12,680 OF MRNA AND A MICRO MRNA AND 1111 00:50:12,680 --> 00:50:15,160 CAPPING AND WE'VE BEEN ABLE TO 1112 00:50:15,160 --> 00:50:16,280 DESCRIBE BOTH DEFECTS IN INNATE 1113 00:50:16,280 --> 00:50:20,640 AND ADAPT OF IMMUNITY AND MOST 1114 00:50:20,640 --> 00:50:23,320 RECENTLY I'M GOING TO TROY TO 1115 00:50:23,320 --> 00:50:26,280 WHIP THROUGH THIS IT WAS THE PI3 1116 00:50:26,280 --> 00:50:27,520 AND WE WERE ABLE TO SHOW THE 1117 00:50:27,520 --> 00:50:29,480 EFFECT ON INNATE IMMUNITY BUT 1118 00:50:29,480 --> 00:50:31,360 THE INTERESTING ONE 20 THIS TALK 1119 00:50:31,360 --> 00:50:32,720 IS A 2-YEAR-OLD THAT INVOLVED TO 1120 00:50:32,720 --> 00:50:35,120 VANCOUVER ISLAND WHICH IS FULL 1121 00:50:35,120 --> 00:50:37,800 OF CRYPTOCOCCUS HAD MULTIPLE 1122 00:50:37,800 --> 00:50:40,920 NODULES AND INTEGRATED 14 1123 00:50:40,920 --> 00:50:42,760 MUTATION NOVEL AND INTEGRATED 1124 00:50:42,760 --> 00:50:45,960 COMPLEX IS INVOLVED IN THE 1125 00:50:45,960 --> 00:50:49,480 PRODUCTION OF NON MICRO RNAs 1126 00:50:49,480 --> 00:50:54,440 AND MR12-46 THE CO FINDER AND 1127 00:50:54,440 --> 00:50:56,440 DEGRADED BY THIS PATHWAY AND SO 1128 00:50:56,440 --> 00:50:59,400 IN THIS PARTICULAR CASE, IN THIS 1129 00:50:59,400 --> 00:51:01,520 PATIENT, THE 12-46 IS REDUCED 1130 00:51:01,520 --> 00:51:03,040 WAS OF THE MUTATION RESULTING IN 1131 00:51:03,040 --> 00:51:06,640 A HUGE INCREASE IN FOX P3 WHICH 1132 00:51:06,640 --> 00:51:08,880 ALSO RESULTED IN AN INCREASE IN 1133 00:51:08,880 --> 00:51:11,120 P CELL SUPPRESSER CELLS AND 1134 00:51:11,120 --> 00:51:12,800 AGAIN IS OPPOSITE TO A DISEASE 1135 00:51:12,800 --> 00:51:14,560 ON THE LEFT WHERE YOU HAVE 1136 00:51:14,560 --> 00:51:18,560 ACTIVATION OF TOR AND HERE YOU 1137 00:51:18,560 --> 00:51:20,320 HAVE INSTEAD OF INFLAMMATORY YOU 1138 00:51:20,320 --> 00:51:23,640 HAVE IMMUNE SUPPRESSION AND 1139 00:51:23,640 --> 00:51:26,480 T-CELL POSSESSORS PREVENT THE T 1140 00:51:26,480 --> 00:51:29,800 CELLS FROM GETTING INTO THE LUNG 1141 00:51:29,800 --> 00:51:31,320 AND CONTROLLING IT. 1142 00:51:31,320 --> 00:51:33,360 WITH THAT, I'D LIKE TO THANK MY 1143 00:51:33,360 --> 00:51:34,880 COLLABORATORS AND A LOT OF THIS 1144 00:51:34,880 --> 00:51:39,480 WORK WAS DONE BY Dr. UNJUM AND 1145 00:51:39,480 --> 00:51:45,960 THE REST OF OUR LAB AND OUR 1146 00:51:45,960 --> 00:51:47,040 NEUROLOGICAL CONSULT AND A 1147 00:51:47,040 --> 00:51:49,600 NUMBER OF OUTSIDE INVESTIGATORS 1148 00:51:49,600 --> 00:51:51,560 AND AS WELL SO THANK YOU VERY 1149 00:51:51,560 --> 00:51:55,600 MUCH AND IF THERE ARE ANY 1150 00:51:55,600 --> 00:51:56,800 QUESTIONS? 1151 00:51:56,800 --> 00:51:58,560 >> THANK YOU, EVERYONE FOR THAT 1152 00:51:58,560 --> 00:51:59,640 FANTASTIC PRESENTATION. 1153 00:51:59,640 --> 00:52:00,960 I'LL REMIND THE AUDIENCE IF YOU 1154 00:52:00,960 --> 00:52:02,360 HAVE QUESTIONS, YOU CAN SUBMIT 1155 00:52:02,360 --> 00:52:05,880 THEM BY USING THE LIVE FEEDBACK 1156 00:52:05,880 --> 00:52:06,720 BUTTON ON YOUR SCREENS. 1157 00:52:06,720 --> 00:52:08,520 IN THE MEANTIME, Dr. 1158 00:52:08,520 --> 00:52:09,840 WILLIAMSON, I DO HAVE A QUESTION 1159 00:52:09,840 --> 00:52:12,160 FOR YOU. 1160 00:52:12,160 --> 00:52:15,360 SO, I MAY HAVE MISSED THIS BUT 1161 00:52:15,360 --> 00:52:19,480 DOES EVERY PERSON WHO GET 1162 00:52:19,480 --> 00:52:20,360 CRYPTOCOCCAL MENINGITIS DEVELOP 1163 00:52:20,360 --> 00:52:21,640 THIS INFLAMMATORY RESPONSE 1164 00:52:21,640 --> 00:52:25,200 SYNDROME AND IF NOT, ARE THERE 1165 00:52:25,200 --> 00:52:27,200 BIOMARKERS TO PREDICT WHO MIGHT 1166 00:52:27,200 --> 00:52:30,000 DEVELOP IT SO YOU CAN THEN FLAG 1167 00:52:30,000 --> 00:52:31,760 THEM FOR TREATMENT WITH STEROIDS 1168 00:52:31,760 --> 00:52:34,000 OR OTHER IMMUNOSUPPRESS ANTS? 1169 00:52:34,000 --> 00:52:36,440 >> THE PATIENTS WE HAVE A 1170 00:52:36,440 --> 00:52:38,120 REFERRAL SO WE HAVE TO GO AND 1171 00:52:38,120 --> 00:52:39,840 DIG INTO OUR MULTI CENTER 1172 00:52:39,840 --> 00:52:41,120 TRAVELS TO DO THAT AND WHEN WE 1173 00:52:41,120 --> 00:52:47,160 FIND THAT WE FIND THAT SOME OF E 1174 00:52:47,160 --> 00:52:48,720 MARKERS WILL BE ELEVATED IN THE 1175 00:52:48,720 --> 00:52:50,120 PATIENTS WHO GET THE DISEASE AND 1176 00:52:50,120 --> 00:52:52,760 WHEN YOU COMPARE, IL6 IS HERE 1177 00:52:52,760 --> 00:52:55,080 AND I L6 IS LIKE HERE IN THE 1178 00:52:55,080 --> 00:52:56,800 ONES THAT DON'T SO THE CLINICAL 1179 00:52:56,800 --> 00:52:58,440 MARKER IS STILL THE BEST THING 1180 00:52:58,440 --> 00:53:00,080 AND IT'S LIKE NEW ASSISTANCE WHO 1181 00:53:00,080 --> 00:53:01,640 IS GOING TO GET THE DISEASE AND 1182 00:53:01,640 --> 00:53:08,400 REQUIRE A STEROIDS THERE? 1183 00:53:08,400 --> 00:53:09,640 THEY GIVE YOU P VALUES AND 1184 00:53:09,640 --> 00:53:12,040 GRANTS IF YOU ARE EXTRAMURAL BUT 1185 00:53:12,040 --> 00:53:13,800 FOR THE CLINICIAN THEY'RE NOT 1186 00:53:13,800 --> 00:53:15,280 POWERFUL ENOUGH MARKERS TO 1187 00:53:15,280 --> 00:53:15,880 PREDICT THINGS. 1188 00:53:15,880 --> 00:53:18,840 I THINK WHAT IS MORE USEFUL IS, 1189 00:53:18,840 --> 00:53:20,560 YOU ARE CONFRONTED WITH A 1190 00:53:20,560 --> 00:53:22,480 PATIENT WHO IS DOING BADLY, WHY 1191 00:53:22,480 --> 00:53:24,240 IS THAT AND WHAT CAN YOU DO? 1192 00:53:24,240 --> 00:53:26,000 AND THAT IS WHERE WE REALLY PUT 1193 00:53:26,000 --> 00:53:27,040 OUR ENERGY IN. 1194 00:53:27,040 --> 00:53:27,960 THAT'S VERY STRONG. 1195 00:53:27,960 --> 00:53:29,280 SO WHAT WE HAVE FOUND IS THAT 1196 00:53:29,280 --> 00:53:32,440 SOME OF THESE BIOMARKERS, LIKE 1197 00:53:32,440 --> 00:53:37,240 IL6, LIKE THE 25, THE ACTIVATED 1198 00:53:37,240 --> 00:53:40,200 T CELLS, THEY HAVE THRESHOLDS SO 1199 00:53:40,200 --> 00:53:42,280 IF WE GET A PATIENT THE 1200 00:53:42,280 --> 00:53:45,280 ACTIVATED T CELLS DOWN TO 200, 1201 00:53:45,280 --> 00:53:46,200 WE CAN TELL THEY'RE GOING TO 1202 00:53:46,200 --> 00:53:48,480 RESPOND AND WHEN THEY DON'T GET 1203 00:53:48,480 --> 00:53:49,360 BELOW 200 THEY DON'T SEEM TO 1204 00:53:49,360 --> 00:53:51,040 RESPOND AND WE HAVE THIS ONE 1205 00:53:51,040 --> 00:53:52,440 POOR GUY THAT'S GONE A YEAR AND 1206 00:53:52,440 --> 00:53:54,720 HE STILL HAS ACTIVATED T CELLS 1207 00:53:54,720 --> 00:53:57,280 WAY BEYOND THAT AND WE HAD THE 1208 00:53:57,280 --> 00:53:59,640 FIRST ONE TO USE AND WE GET THEM 1209 00:53:59,640 --> 00:54:01,960 BACK DOWN AND THEN THEY DO FINE, 1210 00:54:01,960 --> 00:54:03,720 OR WE HAVE SOMEONE THAT COMES IN 1211 00:54:03,720 --> 00:54:05,360 AND DOES A RESPOND TO THEIR 1212 00:54:05,360 --> 00:54:09,520 PULSE AND WE CAN MEASURE THEM 1213 00:54:09,520 --> 00:54:10,560 AND THEY HAVE A LOT OF 1214 00:54:10,560 --> 00:54:11,800 INFLAMMATION AND WE HIT THEM 1215 00:54:11,800 --> 00:54:12,840 WITH ANOTHER PULSE THEY COME 1216 00:54:12,840 --> 00:54:13,680 DOWN AND WAKE UP. 1217 00:54:13,680 --> 00:54:15,920 THE TREATMENT EFFECT IS 1218 00:54:15,920 --> 00:54:16,400 DIFFICULT. 1219 00:54:16,400 --> 00:54:17,880 USUALLY PROGNOSTIC MARKERS ARE 1220 00:54:17,880 --> 00:54:19,720 EASY TO FIND AND TREATMENT 1221 00:54:19,720 --> 00:54:20,720 MODIFIERS ARE DIFFICULT AND IN 1222 00:54:20,720 --> 00:54:22,000 THIS CASE THE TREATMENT 1223 00:54:22,000 --> 00:54:23,160 MODIFIERS HAVE BEEN EASIER TO 1224 00:54:23,160 --> 00:54:27,560 FIND AND THE PROGNOSTIC MARKERS 1225 00:54:27,560 --> 00:54:29,920 AREN'T QUITE AS STRONG. 1226 00:54:29,920 --> 00:54:31,080 >> GREAT. 1227 00:54:31,080 --> 00:54:34,240 THERE'S A QUESTION THROUGH THE 1228 00:54:34,240 --> 00:54:36,680 LIVE FEEDBACK BUTTON. 1229 00:54:36,680 --> 00:54:38,560 THIS IS FROM JUAN. 1230 00:54:38,560 --> 00:54:41,760 IS THE AN TO BE PATHWAY GAIN OF 1231 00:54:41,760 --> 00:54:43,440 FUNCTION MUTATION DOES THAT 1232 00:54:43,440 --> 00:54:46,640 SUGGEST THE PATHOGENESIS IS 1233 00:54:46,640 --> 00:54:48,680 SIMILAR TO PK DELTA SYNDROME. 1234 00:54:48,680 --> 00:54:50,280 >> WE SEE THE REVERSE. 1235 00:54:50,280 --> 00:54:51,840 WE SEE DEFECTS IN THAT WHICH 1236 00:54:51,840 --> 00:54:53,280 ACTUALLY HAVEN'T BEEN REPORTED 1237 00:54:53,280 --> 00:54:56,320 BUT WE THINK IT'S GOT TO BE A 1238 00:54:56,320 --> 00:54:58,480 MOW A SIS SYSTEM AS WELL BUT WE 1239 00:54:58,480 --> 00:55:00,600 SEE DEFECTS AND THAT'S MORE 1240 00:55:00,600 --> 00:55:01,440 EXPECTED. 1241 00:55:01,440 --> 00:55:03,440 SO WE HAVE THE YING AND THE YANG 1242 00:55:03,440 --> 00:55:05,480 HERE CONTINUALLY AND A LOT OF 1243 00:55:05,480 --> 00:55:08,960 OUR -- A NUMBER OF QUEEN'SING ON 1244 00:55:08,960 --> 00:55:10,560 WE HAVE DEFECTS AND YOU SEE 1245 00:55:10,560 --> 00:55:12,400 Dr. GOLD BACK WILL HAVE UP 1246 00:55:12,400 --> 00:55:14,120 REGULATED THE SAME QUEEN AND 1247 00:55:14,120 --> 00:55:18,280 SHE'LL HAVE INFLAM ON AGENT' AND 1248 00:55:18,280 --> 00:55:20,200 WHERE THEY GET ALL SORTS OF 1249 00:55:20,200 --> 00:55:21,800 INFLAMMATORY DISEASES SO IT JUST 1250 00:55:21,800 --> 00:55:23,640 DEPENDS ON WHICH DIRECTION YOU 1251 00:55:23,640 --> 00:55:27,640 ARE GOING AND OURS ARE LOSS OF 1252 00:55:27,640 --> 00:55:27,880 FUNCTION. 1253 00:55:27,880 --> 00:55:30,280 >> OK. 1254 00:55:30,280 --> 00:55:30,800 GREAT. 1255 00:55:30,800 --> 00:55:32,960 THANK YOU, AGAIN, TO ALL OUR 1256 00:55:32,960 --> 00:55:36,320 WONDERFUL PRESENTERS FOR REALLY 1257 00:55:36,320 --> 00:55:37,920 INTERESTING TALK TODAY. 1258 00:55:37,920 --> 00:55:40,000 IF ANYBODY HAS QUESTIONS, FEEL 1259 00:55:40,000 --> 00:55:42,480 FREE TO E-MAIL THEM TO OUR 1260 00:55:42,480 --> 00:55:44,640 PRESENTERS AFTER THE DISCUSSION. 1261 00:55:44,640 --> 00:55:46,240 I THINK WE'RE COMING CLOSE TO 1262 00:55:46,240 --> 00:55:50,520 TIME HERE AND I I DON'T SEE ANY 1263 00:55:50,520 --> 00:55:51,280 OTHER QUESTIONS COMING THROUGH 1264 00:55:51,280 --> 00:55:52,720 THE LIVE FEEDBACK. 1265 00:55:52,720 --> 00:55:54,360 I'LL SAY THANK YOU AGAIN AND 1266 00:55:54,360 --> 00:00:00,000 HAVE A GREAT REST OF THE DAY.