Comparative trial of short-course ofloxacin for uncomplicated typhoid fever in Vietnamese children

An open, randomised comparison of 2 or 3 days of oral ofloxacin (10 mg/kg/day) for uncomplicated typhoid fever was conducted in 235 Vietnamese children. Multi-drug-resistant Salmonella typhi was isolated from 182/202 (90%) children and 5/166 (3%) tested isolates were nalidixic acid-resistant (Na(R)). Eighty-nine of 116 children randomised to 2 days and 107/119 randomised to 3 days were blood culture-positive and eligible for analysis. There were 12 (13.5%) failures in the 2-day group (six clinical failures, four blood culture-positive post treatment, two relapses) compared with eight (7.5%) failures in the 3-day group (four clinical failures, one blood culture-positive post treatment, three relapses) (OR 1.9, 95% CI 0.7-5.5,p = 0.17). There were no significant differences in the mean (95% confidence interval) fever clearance times (h) [92 (82-102) vs 101 (93-110), p = 0.18] or duration of hospitalisation (d) [7.6 (7.2-8.1) vs 8.0 (7.6-8.4), p = 0.19] between the two groups. There was one failure in the four eligible children infected with an Na(R) isolate of S. typhi. No adverse events were attributable to the ofloxacin. These results extend previous observations on the efficacy of short courses of ofloxacin for children with uncomplicated multi-drug-resistant typhoid fever.     

Reduced hippocampal volume among adolescents with alcohol use disorders without psychiatric comorbidity

Studies have suggested that teens with alcohol use disorder (AUD) can demonstrate memory deficits, but the underlying neuroanatomical substrates are unclear. The hippocampus is crucial to intact memory functioning, and it actively develops during adolescence. The current study attempted to replicate and extend previous findings suggesting that adolescents with AUD show smaller hippocampal volumes than healthy adolescents. Manual tracings of bilateral hippocampi were performed on structural magnetic resonance images of 14 adolescents (ages 15 to 17 years) with AUD and 17 healthy comparison teens. Intracranial, white, and gray matter volumes, as well as memory abilities, were also measured. Results revealed that adolescents with AUD had significantly smaller left hippocampal volumes than healthy teens, even after removal of teens with comorbid conduct disorder from the analyses. In contrast the groups did not differ in right hippocampal, intracranial, gray or white matter volumes, or memory performance. Hippocampal volumes were not related to alcohol-consumption rates. These findings indicate that adolescents with AUD, but free from other psychiatric comorbidities, have reduced left hippocampal volume. Because hippocampal volume did not relate to alcohol use characteristics, it is possible that premorbid volumetric differences could account for some of the observed group differences in hippocampal volume.     

Adult hypophosphatasia and a low level of red blood cell thiamine pyrophosphate

OBJECTIVE: To report the first adult case of hypophosphatasia and absence of intestinal alkaline phosphatase (ALP) isoenzymes associated with a low level of red blood cell thiamine pyrophosphate. METHODS: We describe the clinical manifestation and laboratory findings in our patient and discuss underlying factors that potentially contribute to her condition. RESULTS: A 33-year-old Vietnamese-American female was referred for a long history of low levels of serum ALP and absence of intestinal ALP isoenzyme. She had a normal level of urinary phosphoethanolamine and a high level of plasma pyridoxal-5p-phosphate. She was found to have a low level of red blood cell thiamine pyrophosphate. CONCLUSION: Our adult case of hypophosphatasia presented with an absence of intestinal ALP isoenzyme that might result in decreasing the absorption of thiamine in the intestinal tract. Therefore, the thiamine level should be considered in hypophosphatasia with absence of intestinal ALP isoenzyme.     

Villonodular synovitis (PVNS) of the spine

Objective To describe the imaging features of spinal pigmented villonodular synovitis (PVNS).Design and patients We retrospectively reviewed 15 cases of pathologically proven spinal PVNS. Patient demographics and clinical presentation were reviewed. Radiologic studies were evaluated by consensus of two musculoskeletal radiologists for spinal location, spinal segments affected, lesion center, detection of facet origin and intrinsic characteristics on radiography (n =11), myelography (n =7), CT (n =6) and MR imaging (n =6).Results Women (64%) were more commonly affected than men (36%) with an average age of 28 years. Clinical symptoms were pain (45%), neurologic (9%) or both (36%). Lesions most frequently affected the cervical spine (53%) followed by the thoracic (27%) and lumbar regions (20%). The majority of lesions (93%) were centered in the posterior elements with frequent involvement of the pedicle (67%), neural foramina (73%), lamina (67%) and facets (93%). No lesions showed calcification. Determination of a facet origin by imaging was dependent on imaging modality and lesion size. A facet origin could be determined in 45% of cases by radiography vs 67% of patients by CT (n=6) and MR (n=6). Large lesions (greater than 3 cm in at least one dimension) obscured the facet origin in all cases with CT and/or MR imaging (44%,n=4). Small lesions (less than 3 cm in any dimension) demonstrated an obvious facet origin in all cases by CT and/or MR imaging (56%,n=5). Low-to-intermediate signal intensity was seen in all cases on T2-weighted MR images resulting from hemosiderin deposition with blooming effect in one case with gradient echo MR images.Conclusions PVNS of the spine is rare. Large lesions obscure the facet origin and simulate an aggressive intraosseous neoplasm. Patient age, a solitary noncystic lesion centered in the posterior elements, lack of mineralization and low-to-intermediate signal intensity on all MR pulse sequences may suggest the diagnosis in these cases. Small lesions demonstrate a facet origin on CT or MR imaging. This limits differential considerations to synovial-based lesions and additional features of a solitary focus, lack of underlying disease or systemic arthropathy, no calcification as well as low-to-intermediate signal intensity on all MR images should allow spinal PVNS to be suggested as the likely diagnosis.The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Departments of the Air Force, Army, Navy or Defense.     

Cellular prion protein/laminin receptor: distribution in adult central nervous system and characterization of an isoform associated with a subtype of cortical neurons

The 67-kDa LR protein was originally discovered as a non-integrin laminin receptor. Several more recent in vitro studies demonstrated the function of 67-kDa LR and its related 'precursor' form 37-kDa LRP as receptors of cellular prion protein and their implication in abnormal prion protein propagation in vitro. In addition, expression of both proteins was shown to increase considerably in the brain of scrapie-infected mice and hamsters. While LRP/LR are thus likely to play important roles in neuronal cell adhesion, survival and homeostasis and during pathological disorders, little is known so far about their fine cellular distribution in adult central nervous system. Using immunocytochemistry and western blotting, we show here that the 67-kDa LR is the major receptor form in adult rat brain and spinal cord, expressed within the cytoplasm and at the plasma membrane of most neurons and in a subset of glial cells. The overall distribution of LR correlates well with that reported for laminin-1 but also with brain regions classically associated with prion-related neurodegeneration. In contrast to LR, the 37-kDa LRP form is much less abundant in adult than in postnatal central nervous system. Characterization of a novel antibody allowed us to study the distribution across tissues of cell membrane-associated LRP. Interestingly, this form is almost exclusively found on a subclass of parvalbumin-immunoreactive cortical interneurons known to degenerate during the early stages of Creutzfeldt-Jakob disease. Our demonstration of local differences in the expression of particular LRP/LR isoforms may be a first step towards unraveling their specific molecular interactions.     

Complications and functional evaluation of 17 saddle prostheses for resection of periacetabular tumors

Seventeen saddle prostheses were inserted between 1988 and 1997 after resection of periacetabular tumors. The tumors involved the zones II and III of Enneking classification in 13 patients, the zones I and II in 2 patients, and the zone II in 2 patients. The tumors included 11 chondrosarcomas, 3 Ewing sarcomas, 2 giant cells tumors, and 1 metastasis of renal carcinoma. The tumoral resection was wide "en bloc" in 14 cases, marginal in 2 cases, and intratumoral in 1 case. The mean follow-up period of the patients is 42 months ranging from 8 to 84 months. Local recurrences occurred in five cases and metastases in four cases. Five patients died of tumoral disease and one of intercurrent disease. Complications were observed in 11 cases (65%) including nerve damages (3 cases), deep infections (3 cases), upward migrations of the saddle (4 cases), saddle dislocations (3 cases), sacroiliac subluxations (2 cases), and mechanical failures (2 cases). The modified Musculoskeletal Tumor Society Score (MSTS) and the Toronto Extremity Salvage Score (TESS) were used for functional analysis. Functional results were available for only nine patients of the series with a mean MSTS of 17 points ranging from 11 to 23 points and a mean TESS of 58 points ranging from 39 to 95 points. The saddle prosthesis provided in all cases of this series an early painfree weight-bearing reconstruction with minimal limb shortening, but the functional results remained fair in most patients due to a limited range of motion and a poor abductor strength.     

Long-term follow-up after quinacrine sterilization in Vietnam. Part II: interim safety analysis

Objective: To determine the long-term safety of nonsurgical sterilization with quinacrine.

Design: Observational cohort study.

Setting: Rural provinces in northern Vietnam.

Patient(s): Two thousand eight hundred forty women who had had quinacrine insertions and an age-matched comparison group of 1,658 women who had an intrauterine device (IUD) insertion between 1989 and 1993.

Method(s): Interviews in 1994, 1995, and 1996 and review of available medical records. This is a planned interim analysis.

Main Outcome Measure(s): Ectopic pregnancies and the occurrence of other adverse health events.

Result(s): Over 90% of women were interviewed at least once. Despite matching on age, the groups differed on baseline parity. The ectopic pregnancy rates were similar after either one or two insertions and were similar to the rate of ectopic pregnancies after surgical sterilization in the United States. The quinacrine group reported more gynecologic health problems than the IUD group. However, after correcting for information bias, there was no dose–response effect between the one- and two-insertion quinacrine groups, suggesting the possibility of recall bias or differing baseline health status.

Conclusion(s): Ectopic pregnancies do not appear to be increased compared with U.S. surgical sterilization rates. The data on other adverse events are more difficult to interpret.     

An aberrant prostate antigen–specific immune response causes prostatitis in mice and is associated with chronic prostatitis in humans

Chronic prostatitis is a common disease of unclear etiology and has no specific treatment. Mice deficient in the expression of the autoimmune regulator (Aire) gene, which are defective in thymic expression of self antigens and central tolerance, develop spontaneous prostatitis. In this study, we found that Aire-deficient mice developed spontaneous B and T cell immune responses to a prostate autoantigen, seminal vesicle secretory protein 2 (SVS2), which we believe to be novel. We show that thymic expression of this self antigen was Aire dependent. Moreover, prostatitis was induced in WT mice through immunization with SVS2, demonstrating that immunity to SVS2 was sufficient to induce prostatitis. The clinical relevance of this antigen was highlighted by our observation that patients with chronic prostatitis possessed specific autoantibodies against the human SVS2-like seminal vesicle protein semenogelin. These results provide direct evidence that spontaneous chronic prostatitis is an autoimmune disease and is regulated by both central and peripheral tolerance. Moreover, SVS2 and semenogelin are among the relevant autoantigens in mice and humans, respectively.     

A new geranyl flavanone from Macaranga triloba

A new geranyl flavanone, 2′-hydroxy-macarangaflavnone A (1), and a known 4′,7-dihydroxy-8-methylflavan were isolated from the leaves of Macaranga triloba (Euphorbiceae). The structure of 1 was elucidated based on spectroscopic methods, including 1D and 2D NMR analysis.