Corticosteroids for the management of severe intracranial hypertension in meningoencephalitis caused by Cryptococcus gattii: A case report and review.

Immune reconstitution inflammatory syndrome in meningitis caused by Cryptococcus gattii in immunocompetent patients after initiation of antifungal therapy appears to be the result of paradoxical antifungal treatment-induced clinical deterioration due to improved local immune responses to cryptococcal organisms. Recent anecdotal reports have suggested a favorable clinical response to corticosteroids in select patients with C. gattii central nervous system (CNS) infections. In this report, we describe a 65-year-old patient with meningoencephalitis caused by C. gattii who developed persistent intracranial hypertension and was successfully managed with antifungal therapy, repeated lumbar puncture and corticosteroids. Our observations suggest a possible benefit of dexamethasone in the management of select cases of C. gattii CNS infection with intracranial hypertension. Further studies are necessary to evaluate the long-term use of steroids in select patients with C. gattii with intracranial hypertension.

Genetic ablation of the p66Shc adaptor protein reverses cognitive deficits and improves mitochondrial function in an APP transgenic mouse model of Alzheimer's disease.

The mammalian ShcA adaptor protein p66Shc is a key regulator of mitochondrial reactive oxygen species (ROS) production and has previously been shown to mediate amyloid ß (Aß)-peptide-induced cytotoxicity in vitro. Moreover, p66Shc is involved in mammalian longevity and lifespan determination as revealed in the p66Shc knockout mice, which are characterized by a 30% prolonged lifespan, lower ROS levels and protection from age-related impairment of physical and cognitive performance. In this study, we hypothesized a role for p66Shc in Aß-induced toxicity in vivo and investigated the effects of genetic p66Shc deletion in the PSAPP transgenic mice, an established Alzheimer's disease mouse model of ß-amyloidosis. p66Shc-ablated PSAPP mice were characterized by an improved survival and a complete rescue of Aß-induced cognitive deficits at the age of 15 months. Importantly, these beneficial effects on survival and cognitive performance were independent of Aß levels and amyloid plaque deposition, but were associated with improved brain mitochondrial respiration, a reversal of mitochondrial complex I dysfunction, restored adenosine triphosphate production and reduced ROS levels. The results of this study support a role for p66Shc in Aß-related mitochondrial dysfunction and oxidative damage in vivo, and suggest that p66Shc ablation may be a promising novel therapeutic strategy against Aß-induced toxicity and cognitive impairment.

Early accumulation of intracellular fibrillar oligomers and late congophilic amyloid angiopathy in mice expressing the Osaka intra-Aß APP mutation.

Pathogenic amyloid-ß peptide precursor (APP) mutations clustered around position 693 of APP-position 22 of the Aß sequence--are commonly associated with congophilic amyloid angiopathy (CAA) and intracerebral hemorrhages. In contrast, the Osaka (E693Δ) intra-Aß APP mutation shows a recessive pattern of inheritance that leads to AD-like dementia despite low brain amyloid on in vivo positron emission tomography imaging. Here, we investigated the effects of the Osaka APP mutation on Aß accumulation and deposition in vivo using a newly generated APP transgenic mouse model (E22ΔAß) expressing the Osaka mutation together with the Swedish (K670N/M671L) double mutation. E22ΔAß mice exhibited reduced α-processing of APP and early accumulation of intraneuronal fibrillar Aß oligomers associated with cognitive deficits. In line with our in vitro findings that recombinant E22Δ-mutated Aß peptides form amyloid fibrils, aged E22ΔAß mice showed extracellular CAA deposits in leptomeningeal cerebellar and cortical vessels. In vitro results from thioflavin T aggregation assays with recombinant Aß peptides revealed a yet unknown antiamyloidogenic property of the E693Δ mutation in the heterozygous state and an inhibitory effect of E22Δ Aß42 on E22Δ Aß40 fibrillogenesis. Moreover, E22Δ Aß42 showed a unique aggregation kinetics lacking exponential fibril growth and poor seeding effects on wild-type Aß aggregation. These results provide a possible explanation for the recessive trait of inheritance of the Osaka APP mutation and the apparent lack of amyloid deposition in E693Δ mutation carriers.

Functional deficits and morphological changes in the neurogenic bladder match the severity of spinal cord compression.

UNLABELLED: Following spinal cord injury (SCI), loss of spinal and supraspinal control results in desynchronisation of detrusor vesicae (parasympathicus) and external urethral sphincter (sympathicus) activity. Despite recovery of lower urinary tract function being a high priority in patients with SCI, effective treatment options are unavailable largely because mechanisms are poorly understood. PURPOSE AND METHODS: We used a clinically relevant model of thoracic SCI compression injury in adult female Wistar rats and confirmed that lesion volumes following severe injuries were significantly greater compared to moderate injuries (p < 0.05). Between 1-9 weeks, we assessed recovery of bladder function as well as return of locomotor function using the Basso, Beattie and Bresnahan (BBB) score. Bladder morphometrics and overall intramural innervation patterns, as assessed with ß-III tubulin immunohistochemistry, were also examined. RESULTS: Despite variability, bladder function was significantly worse following severe compared to moderate compression injury (p < 0.05); furthermore, the degree of bladder and locomotor dysfunction were significantly correlated (r = 0.59; p < 0.05). In addition, at 9 weeks after SCI we saw significantly greater increases in bladder dry weight (p < 0.05) and wall thickness following severe compared to moderate injury as well as increases in intramural axon density (moderate: 3× normal values; severe 5×; both p < 0.05) that also correlated with injury severity (r = 0.89). CONCLUSION: The moderate and severe compression models show consistent and correlated deficits in bladder and locomotor function, as well as in gross anatomical and histopathological changes. Increased intramural innervation may contribute to neurogenic detrusor overactivity and suggests the use of therapeutic agents which block visceromotoric efferents.

Cervical discectomy. A prospective analysis of three operative techniques.

BACKGROUND: Cervical disc herniation causing neurological compromise is a common affliction. Sophisticated surgical treatments have been developed throughout the twentieth century and are largely successful. Although each procedure has its supporters, it is still unclear if one surgical technique is superior. METHODS: A prospective trial was designed to evaluate the efficacy of three surgical procedures for the treatment of cervical radiculopathy caused by a unilateral acute herniated cervical disc. Patients were randomized to posterior cervical foraminotomy (FOR), and anterior cervical discectomy with (ACDF), and without (ACD) fusion. Perioperative data, office follow-up and long-term follow-up were used to compare the procedures. RESULTS: All of the procedures yielded excellent relief of symptoms and signs postoperatively and during follow-up. Operative time and hospital stay were slightly shorter for ACD compared with ACDF and FOR. Reoperations occurred in all groups but there was a trend for higher recurrence at the same level with FOR and recurrence at other levels with ACDF. CONCLUSION: All three of the procedures were successful for treatment of cervical radiculopathy caused by a herniated cervical disc. Although the numbers in this study were small, none of the procedures could be considered superior to the others. This study suggests that the selection of surgical procedure may reasonably be based on the preference of the surgeon and tailored to the individual patient.

Anterior cervical discectomy: is fusion necessary?

OBJECT: A prospective, randomized trial was performed to compare the efficacy of anterior cervical discectomy (ACD) with ACD and fusion (ACDF) for the treatment of cervical spondylosis in patients with neurological compromise. METHODS: Forty-four patients underwent ACD and 40 underwent ACDF. Operative time and length of hospital stay were shorter and there was less need for analgesia in the ACD group. It was found that whereas the incidence of fusion was greater in the ACDF group compared to the ACD group (97 compared with 70%, respectively; p<0.01), patient satisfaction and a return to preoperative activity level was similar between groups. CONCLUSIONS: Analysis of the results suggests that the addition of a fusion procedure may be unnecessary.

Disseminated cutaneous protothecosis in an immunocompromised host: a case report and literature review.

Protothecosis is an infection caused by achloric algae of the genus Prototheca. These organisms have been isolated from water, sewage, soil, and the slime flux of trees, and are a known cause of disease in other mammals. Infection in humans occurs after traumatic inoculation, producing localized olecranon bursal or, rarely, systemic disease. Only two previous cases of disseminated cutaneous disease have been reported in patients with defective neutrophil function. We describe a rare case of widespread cutaneous dissemination occurring after an arthropod bite in an immunocompromised patient.

Diagnosis and treatment of cutaneous vascular lesions.

Cutaneous vascular lesions are the most common pediatric birthmarks. Flat vascular malformations tend to persist, but raised vascular lesions, known as hemangiomas, generally involute. Although not always necessary, treatment of flat lesions, if desired, is best accomplished with flash-lamp pumped pulsed dye laser. Therapy of hemangiomas varies depending on the presence of associated symptoms or syndromes. Specifically, hemangiomas that are likely to lead to loss of function or life ( e.g. lesions of internal organs, lesions associated with coagulopathy) should be treated promptly. Treatment may also be required for hemangiomas that are likely to lead to scarring when the lesion involutes, such as hemangiomas of the nose and lip. The natural history of hemangiomas includes proliferative, stationary and involutional phases. Many superficial hemangiomas resolve with minimal sequelae.

Lymphomatoid contact dermatitis caused by nickel.

Lymphomatoid contact dermatitis is a rarely reported entity consisting of allergic contact dermatitis that resembles mycosis fungoides pathologically. Although the histopathology has been previously described, there have been no attempts to reproduce the dermatitis for pathologic evaluation. A 68-year-old woman presented with a papular rash on her neck after exposure to a nickel-containing necklace. A biopsy specimen was suspicious for mycosis fungoides. However, the dermatitis responded quickly to topical steroids and avoidance of the necklace. A patch test to nickel was positive, and a biopsy specimen from the patch test site had no findings of mycosis fungoides. Although we were able to reproduce the contact dermatitis at a distant site, the disease was dissimilar. Lymphomatoid contact dermatitis has an excellent prognosis and resolves completely simply by avoiding the offending agent.

Cutaneous mucormycosis with subsequent visceral dissemination in a child with neutropenia: a case report and review of the pediatric literature.

Primary cutaneous mucormycosis is a rare opportunistic fungal infection that is usually limited to the skin. We describe a primary cutaneous Rhizopus infection occurring at a site occluded by a sterile adhesive dressing in which the disease was viscerally disseminated at the time fo diagnosis. Mucormycosis should be considered in all ecthyma-like lesions in immunocompromised patients. It may be rapidly diagnosed by examination of hematoxylin-eosin and PAS-stained sections of the eschar base and a culture of a leading edge tissue aspirate. We review 21 cases of primary cutaneous mucormycosis in children and compare them with the present case.

Evaluation of an elastomeric holographic index-matching medium.

A transparent silicone elastomer is evaluated for suitability as an index-matching material for holography. Transparency, index of refraction, adhesion, dimensional stability, and optical activity are determined. Trials conducted in a student laboratory yield positive results.

Rupture of previously documented small asymptomatic saccular intracranial aneurysms. Report of three cases.

In a recent study from the Mayo Clinic on the natural history of intact saccular intracranial aneurysms, none of the aneurysms smaller than 10 mm in diameter ruptured. It was concluded that these aneurysms carry a negligible risk for future hemorrhage and that surgery for their repair could not be recommended. These findings and recommendations have been the subject of much controversy. The authors report three patients with previously documented asymptomatic intact saccular intracranial aneurysms smaller than 5 mm in diameter that subsequently ruptured. In Case 1, a 70-year-old man bled from a 4-mm middle cerebral artery aneurysm that had been discovered incidentally 2 1/2 years previously during evaluation of cerebral ischemic symptoms. A 10-mm internal carotid artery aneurysm and a contralateral 4-mm middle cerebral artery aneurysm had not ruptured. Case 2 was that of a 66-year-old woman who bled from a 4-mm pericallosal aneurysm that had been present 9 1/2 years previously when she suffered subarachnoid hemorrhage (SAH) from a 7 x 9-mm posterior inferior cerebellar artery aneurysm. Although the pericallosal aneurysm had not enlarged in the intervening years, a daughter aneurysm had developed. The third patient was a 45-year-old woman who bled from a 4- to 5-mm posterior inferior cerebellar artery aneurysm that had measured approximately 2 mm on an angiogram obtained 4 years previously; at that time she had suffered SAH due to rupture of a 5 x 12-mm posterior communicating artery aneurysm. These cases show that small asymptomatic intact saccular intracranial aneurysms are not innocuous and that careful consideration must be given to their surgical repair and long-term follow-up study.

Mechanism of gastric emptying of a nondisintegrating radiotelemetry capsule in man.

We studied the mechanism of gastric emptying of a pH-sensitive radiotelemetry capsule with respect to phases of the interdigestive migrating motor complex (IMMC) in fasting normal volunteers and the effect of the Heidelberg capsule (HC) on the duration or timing of the IMMC phases. A manometric catheter with eight mounted solid-state strain gauges was passed transnasally and positioned fluoroscopically in the duodenum and jejunum in four normal, fasted male volunteers, in their right lateral position. The HC was administered orally following the establishment of one complete IMMC cycle (defined by the recording time between the end of two subsequent phase III activity fronts) and during the beginning of Phase I of the next cycle. The gastric residence time (GRT) of the HC was measured as the time of a gastric pH rise of greater than or equal to 3.0 units. In three subjects, GRT of the HC lasted to within 5 min of the onset of the next duodenal phase III of the IMMC, while in the fourth subject, the HC passed during the second phase III activity front. There were no significant differences in the duration of each phase of duodenal IMMC in the presence or absence of the HC (Phase I, 54 +/- 9.3 vs 31.6 +/- 10.1; Phase II, 22 +/- 8.1 vs 58.9 +/- 32; Phase III, 5.3 +/- 0.7 vs 4.2 +/- 0.7 min; mean +/- SE; P greater than 0.1 in all phases). In addition, the HC had no effect on motility index or patterns of contractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of lactose on mineral absorption in preterm infants.

To determine whether a reduction of dietary lactose affects mineral absorption in preterm infants, a controlled, randomized, 72-hour balance study was conducted with very low birth weight infants (birth weights less than 1400 gm) fed Similac Special Care formula with a 50:50 carbohydrate blend of glucose polymers and lactose (n = 8) or a nearly identical formula with 100% carbohydrate as lactose (n = 10). The studies were conducted after at least 3 consecutive days of full oral feeds at a mean age of approximately 23 days. There was no difference between groups in percentage of apparent absorption of calcium, phosphorus, magnesium, zinc, copper, or manganese. Retention of these nutrients was similar to or greater than that which occurs in utero. Calcium absorption was 75% of intake. These results indicate that reducing the lactose content of premature-infant formulas to 50% of the carbohydrate does not impair mineral absorption.

Congenital malformations and psychosocial development in children conceived by in vitro fertilization.

To determine whether in vitro fertilization (IVF) as a method of conception is associated with an increased risk for congenital malformations or developmental dysfunction, we performed a general physical examination for malformations, neurologic examination, developmental examination (Bayley Scales), echocardiography, electrocardiography, abdominal ultrasound study, and, when possible, cranial ultrasound examination on a cohort of 83 IVF children and 93 matched non-IVF children. Major malformations were found in two IVF and one non-IVF subject; the rates were not significantly different. The mean Mental Development Index scores for IVF subjects and the comparison group were 115 +/- 13 and 111 +/- 13, respectively (p = 0.12). The mean Psychomotor Development Index scores were 114 +/- 14 and 108 +/- 15 (p = 0.04). Based on these small numbers but extensive evaluation, we found no association between conception by IVF and an increased risk for congenital malformations. Likewise, children conceived by IVF showed no evidence of developmental delay. Their high average achievement on the Bayley tests probably resulted from the exceptional motivation of their parents ("wantedness") and their generally high socioeconomic status.