Fulminant recurrence of atypical hemolytic uremic syndrome during a calcineurin inhibitor-free immunosuppression regimen

Recurrence of hemolytic uremic syndrome (HUS) after kidney transplantation is frequent, occurring almost exclusively in patients with atypical HUS, which is not caused by Escherichia coli gastroenteritis and in which diarrhea is absent. Calcineurin inhibitors are associated with recurrence of HUS. In two children who underwent living donor kidney transplantation for atypical HUS, we pre-emptively employed sirolimus in a calcineurin inhibitor-free immunosuppression regimen. Both children had excellent early graft function, yet both developed severe recurrent disease and subsequently lost their grafts. Avoidance of calcineurin inhibitors did not prevent recurrence of severe HUS and graft loss. Transplantation for severe atypical HUS remains problematic.     

Pharmacodynamic effects of 3-day intravenous treatment with pantoprazole or ranitidine after 10 days of oral ranitidine

Tachyphylaxis (drug tolerance) is an undesirable condition in drug therapy with histamine-2-receptor antagonists (H2RAs). The concept of overcoming tachyphylaxsis via intravenous (i.v.) administration of proton-pump inhibitors (PPIs) or H2RAs is of significant interest to physicians. In the present study, 32 healthy Helicobacter pylori negative male volunteers were evaluated for the ability of i.v. pantoprazole or i.v. ranitidine to overcome oral ranitidine tachyphylaxis. After 10 days of oral treatment with enteric-coated 300-mg ranitidine tablets once daily in the evening, two groups of 16 volunteers each were randomized to receive either i.v. pantoprazole or i.v. ranitidine for up to 72 h. The primary variable was defined as the increase in 24-h gastric pH median after 1 day of i.v. treatment; the secondary variable was median percentage of time that 24-h gastric pH was <4, as calculated by Hodges-Lehman shift estimators. After 10 days of oral ranitidine treatment, tachyphylaxis was present in all volunteers. Within 1 day of continuous i.v. pantoprazole or i.v. ranitidine administration, 24-h median gastric pH increased from pH 1.45 to pH 3.50 (241%) and from pH 1.50 to pH 2.35 (157%), respectively. I.v. pantoprazole was found to be significantly more effective (p<0.05) than i.v. ranitidine in increasing the 24-h gastric pH after oral ranitidine tachyphylaxis.     

The multifocal ERG in diabetic patients without retinopathy during euglycemic clamping

PURPOSE: Prolonged multifocal electroretinogram (mfERG) implicit times have been observed in diabetes, although the acute response to hyperglycemia is an acceleration of the ERG. The hypothesis for the current investigation was that this discrepancy is caused by a protracted adaptational response of the retina to hyperglycemia. METHODS: Fourteen patients with type 1 diabetes without retinopathy were blood glucose clamped at 5 mM for 75 minutes before the recording of the mfERG. The results were compared with those found in 14 age-matched healthy subjects. RESULTS: During acute normoglycemia, patients with type 1 diabetes without retinopathy demonstrated an overall 1.36-ms delay of the P1 first-order implicit times (P = 0.0013) and a 0.72-ms delay of the second-order P1 (P = 0.0049) compared with healthy subjects at 4.9 +/- 0.28 mM blood glucose. During acute hyperglycemia, the P1 first-order delay was only 0.81 ms (P = 0.02), and the P1 second-order implicit time was comparable to that of healthy subjects (P > 0.05). The magnitude of the diabetes-associated implicit time delay, at both levels of glycemia, was proportional to the level of chronic hyperglycemia at study entry, as expressed by the patients' HbA1c. CONCLUSIONS: During acute normoglycemia, patients with type 1 diabetes without retinopathy demonstrated a delayed mfERG response compared with the healthy subjects. The delay was more pronounced during euglycemia than during hyperglycemia, and at both levels of glycemia, the delay was proportional to the patients' habitual hyperglycemia. The results show that chronic hyperglycemia induces an adaptational response that tends to normalize retinal implicit times at a higher level of habitual glycemia.     

Overnight thickness variation in diabetic macular edema

PURPOSE: To study the evening-to-morning variation in retinal thickness in patients with fovea-involving diabetic macular edema. METHODS: Twelve eyes in 12 patients aged 39 to 78 years (mean, 57) with fovea-involving diabetic macular edema and 14 eyes in 7 healthy volunteers aged 30 to 70 years (mean, 57) were examined by optical coherence tomography, in the evening and in the morning after > or =6 hours of sleep in the recumbent position in darkness followed by 0.5 hour wakefulness in the same position in room light with both eyes open. RESULTS: In patients with diabetic macular edema, macular thickness increased overnight, from 316 +/- 72 microm in the evening to 336 +/- 81 microm in the morning (P = 0.003). Visual acuity decreased from a mean of 41 ETDRS letters (Early Treatment of Diabetic Retinopathy Study; range, 4-61) in the evening, to a mean of 36 letters (range, 2-60) in the morning (P = 0.03). No overall change was found in mean arterial blood pressure (MABP; P = 0.48), blood glucose (P = 0.25), or corneal thickness (P = 0.26). The overnight change in macular thickness correlated directly with the change in MABP (r = 0.65, P = 0.03) but not with baseline MABP or blood glucose. The overnight increase in retinal thickness remained significant after statistical adjustment for the effect of arterial blood pressure (P = 0.002). Healthy subjects demonstrated no significant change in any parameter. CONCLUSIONS: In fovea-involving diabetic macular edema, a reduction in visual acuity accompanies overnight retinal thickening, the magnitude being related to the nocturnal change in blood pressure. The results indicate that deficient regulation of retinal capillary filling pressure promotes edema, but the bulk of the overnight increase in macular edema is caused by other mechanisms, of which postural variation in venous blood pressure and increased retinal metabolism in the dark merit further study.     

Cyclic vertical deviation after ocular myositis and treatment by recession of the inferior rectus muscle

Background Cyclic strabismus is a rare disorder in which strabismus and orthotropia regularly alternate over a period of mostly 48 h. It may occur spontaneously, upon squint surgery, or in association with lesions of the central nervous system. In most cases the deviations are convergent. Methods Clinical case report. Results A 34-year-old woman with bilateral recurrent ocular myositis for 2 years had developed cyclic vertical deviation 6 months after clinical remission. A hypotropia of the left eye alternated with an orthotropia, following a 48-h rhythm. Three months after recession of the inferior rectus muscle the alternating squint had disappeared. Discussion The aetiology of cyclic eye deviations, most of them occurring in a constant rhythm, is not known. The association with lesions of the central nervous system indicates a primary central dysregulation of a “biological clock”. Their well-known occurrence, however, after squint surgery and, as in the present case, after orbital myositis, suggests that alteration of peripheral structures may contribute to a central dysregulation. Squint surgery seems to be the treatment of choice, even in rare cases with vertical deviations. Presented at the DOG, Berlin, 2003     

Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings

BACKGROUND: Celiac disease (CD) is increasingly recognized in North America and is associated with a peripheral neuropathy. OBJECTIVE: To report the clinical characteristics and skin biopsy results in patients with CD and small-fiber neuropathy symptoms. DESIGN: Case series. SETTING: Academic peripheral neuropathy clinic. PATIENTS: Eight patients with CD and neuropathy symptoms.Intervention Three-millimeter punch biopsy using the panaxonal marker protein gene product 9.5 to assess epidermal nerve fiber (ENF) density and a gluten-free diet. MAIN OUTCOME MEASURE: Clinical data and ENF density. RESULTS: All patients had asymmetric numbness and paresthesias. Three had more prominent involvement of hands than feet, and 3 had facial numbness. Celiac disease was diagnosed in 5 after their neuropathy began. The following serum antibody levels were elevated: tissue transglutaminase (n = 6), IgA gliadin (n = 4), and IgG gliadin (n = 7). Results of nerve conduction studies were normal in 7 patients. One patient had mildly reduced sural amplitudes. The ENF density was reduced in 5 patients. The ENF density was at the low limit of the normal range in 3 additional patients, 2 of whom had morphologic changes in axons. Three patients had decreased ENF density at the thigh or forearm, which was more severe than at the distal leg, compatible with a non-length-dependent process. Four reported improvement with a gluten-free diet. One had no improvement after 4 months. Symptoms developed in 2 while receiving a gluten-free diet. CONCLUSIONS: Patients with CD may have a neuropathy involving small fibers, demonstrated by results of skin biopsy. The pattern of symptoms, with frequent facial involvement and a non-length-dependent pattern on skin biopsy findings, suggests a sensory ganglionopathy or an immune-mediated neuropathy. Improvement of symptoms in some patients after initiating a gluten-free diet warrants further study.     

Predictors and impact of aneurysm rebleeding after subarachnoid hemorrhage

BACKGROUND: Aneurysm rebleeding has historically been an important cause of mortality after subarachnoid hemorrhage (SAH). OBJECTIVE: To describe the frequency and impact of rebleeding in the modern era of aneurysm care, which emphasizes early surgical or endovascular treatment. DESIGN: Inception cohort. SETTING: Tertiary care medical center. PATIENTS: A total of 574 patients enrolled in the Columbia University SAH Outcomes Project between August 1996 and June 2002. Early aneurysm repair was performed whenever feasible. MAIN OUTCOME MEASURES: Rebleeding was defined by prespecified clinical and radiographic criteria, excluding prehospital, intraprocedural, and postrepair events. Functional outcome was assessed at 3 months with the modified Rankin Scale. Multiple logistic regression was used to identify predictors of rebleeding, poor functional outcome, and mortality. RESULTS: Rebleeding occurred in 40 (6.9%) of the 574 patients; most cases (73%) occurred within 3 days of ictus. Hunt-Hess grade on admission (odds ratio [OR], 1.92 per grade; 95% confidence interval [CI], 1.33-2.75; P<.001) and maximal aneurysm diameter (OR, 1.07/mm; 95% CI, 1.01-1.13; P = .005) were independent predictors of rebleeding. After controlling for Hunt-Hess grade and aneurysm size, rebleeding was associated with a markedly reduced chance of survival with functional independence (modified Rankin Scale score, 相似文献   

Sex differences in knee joint laxity change across the female menstrual cycle

AIM: To elucidate the hormonal influences on sex differences in knee joint behavior, normal-menstruating females were compared to males on serum hormone levels and anterior knee joint laxity (displacement at 46N, 89N and 133N) and stiffness (Linear slope of deltaForce/deltaDisplacement for 46-89N and 89-133N) across the female menstrual cycle. METHODS: Twenty-two females were tested daily across one complete menstrual cycle, and 20 males were tested once per week for 4 weeks. Five days each representing the hormonal milieu for menses, the initial estrogen rise near ovulation, and the early and late luteal phases (total of 20 days) were compared to the average value obtained from males across their 4 test days. RESULTS: Sex differences in knee laxity were menstrual cycle dependent, coinciding with significant elevations in estradiol levels. Females had greater laxity than males on day 5 of menses, days 3-5 near ovulation, days 1-4 of the early luteal phase and days 1, 2, 4 and 5 of the late luteal phases. Within females, knee laxity was greater on day 5 near ovulation compared to day 3 of menses, and days 1-3 of the early luteal phase compared to all days of menses and day 1 near ovulation. On average, differences observed between sexes were greater than those within females across their cycle. There were no differences in anterior knee stiffness between sexes or within females across days of the menstrual cycle.