Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial

CONTEXT: Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. OBJECTIVE: To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Eleven community-based clinical research centers. SUBJECTS: Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). INTERVENTION: All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. MAIN OUTCOME MEASURES: Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. RESULTS: Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. CONCLUSIONS: In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.     

Whipple's syndrome (uveitis, B27-negative spondylarthropathy, meningitis, and lymphadenopathy) associated with Arthrobacter sp. infection

OBJECTIVE: To report an unusual case of Whipple's disease, including uveitis, seronegative spondylarthropathy, meningitis, and lymphadenopathy, associated with an Arthrobacter sp. infection. DESIGN: Interventional case report. PATIENT AND INTERVENTION: A 60-year-old white man presenting with severe chronic uveitis and systemic inflammatory manifestations was treated efficiently for Whipple's disease after histopathologic analysis of vitreous and inguinal adenopathy biopsy specimens. The authors performed a retrospective, laboratory-based evaluation of stored tissue specimens. MEASUREMENTS: Molecular analysis based on 16S ribosomal RNA gene amplification was applied to pretreatment biopsy specimens of inguinal lymph node to identify a causative bacterial agent. RESULTS: Tropheryma whippelii genome was not detected in these specimens. However, an amplification product was obtained after the first polymerase chain reaction run and subsequently was sequenced. It corresponded to an Arthrobacter sp., a gram-positive agent presenting diagnostic patterns and therapeutic management similar to those of Whipple's disease caused by T. whippelii. CONCLUSION: The absence of T. whippelii identification by molecular amplification during a clinically and histologically oriented Whipple's syndrome should not rule out the diagnosis. Arthrobacter infection may represent a new bacterial etiology of systemic inflammatory disorders involving the eye and associated with periodic acid-Schiff-positive inclusions.     

Extrarenal rhabdoid tumors of soft tissue: a clinicopathologic and immunohistochemical study of 18 cases

Rhabdoid tumor is a well-accepted clincopathologic entity among childhood renal neoplasms; similar tumors have been described in extrarenal locations. We present the clinicopathologic profile and the immunohistochemical features of a series of soft tissue rhabdoid tumors. Twenty-eight cases coded as extrarenal rhabdoid tumor (ERRT), RT, possible ERRT, and "large cell sarcoma" were retrieved from the Armed Forces Institute of Pathology soft tissue registry. The tumors were reclassified according to strict criteria by light microscopy, clinical information, immunohistochemistry, and, in some cases, electron microscopy. Soft tissue rhabdoid tumor (STRT) was defined as (1) a tumor composed of noncohesive single cells, clusters, or sheets of large tumor cells with abundant glassy eosinophilic cytoplasm, an eccentric vesicular nucleus, and an extremely large nucleolus; (2) positivity for vimentin and/or cytokeratin or other epithelial markers by immunostaining; and (3) exclusion of other tumor types with rhabdoid inclusions (melanoma, other sarcomas, carcinoma). Eighteen cases met our criteria for soft tissue rhabdoid tumors. The median patient age was 13 years (range, 6 months to 56 years). Ninety-four percent of STRT cases were positive for vimentin and 59% for pan-cytokeratin. Sixty-three percent and 60% were positive for CAM 5.2 and EMA, respectively. Seventy-nine percent stained for at least one epithelial marker; 76% stained for both vimentin and epithelial markers simultaneously. Forty-two percent stained for MSA, and 14% for CEA and SMA. CD99, synaptophysin, CD57 (Leu-7), NSE, and focal S100 protein were identified in 75%, 66%, 56%, 54%, and 31% of the STRT cases, respectively. All STRT cases examined were negative for HMB-45, chromogranin, BER-EP4, desmin, myoglobin, CD34, and GFAP. Follow-up examination in 61% of the STRT patients revealed that 64% of patients died of disease within a median follow-up interval of 19 months (range, 4 months to 5 years); 82% had metastases to lung, lymph nodes, or liver; 22% had local recurrences before metastasis; and 18% were alive without known disease status (median, 5.5 years). Soft tissue rhabdoid tumor is a highly aggressive sarcoma, predominantly of childhood. Besides having nearly consistent coexpression of vimentin and epithelial markers, STRTs show positivity for multiple neural/neuroectodermal markers that overlap with those of primitive neuroectodermal tumor.     

Elimination protocols in atopic dermatitis

Both dacryocystography and dacryoscintigraphy are well established in the evaluation of stenoses of the lacrimal drainage system. They provide limited information about the ductal anatomy itself and about periductal structures. MR imaging was evaluated for its capability to directly visualize the lacrimal drainage system in detail and simultaneously provide functional characterization of dacryostenosis. SUBJECTS AND METHODS: Twenty-seven lacrimal drainage systems of 23 patients suffering from epiphora were examined in an MR unit before and after conjunctival and intravenous application of Gd-DTPA using a surface coil. RESULTS: Dacryostenosis was found in 23 of 27 lacrimal systems. Stenoses were localized to the canalicular (n = 3), saccular (n = 8), and ductal (n = 12) level, and were classified as stenosis or occlusion. CONCLUSION: MR imaging with conjunctival contrast application allows within one examination both detailed morphological and functional assessment of the lacrimal drainage system with depiction of surrounding structures. Limitations arise mainly from demands on technical and patient-related preconditions.     

The role of Alx-4 in the establishment of anteroposterior polarity during vertebrate limb development

We have determined that Strong's Luxoid (lstJ) [corrected] mice have a 16 bp deletion in the homeobox region of the Alx-4 gene. This deletion, which leads to a frame shift and a truncation of the Alx-4 protein, could cause the polydactyly phenotype observed in lstJ [corrected] mice. We have cloned the chick homologue of Alx-4 and investigated its expression during limb outgrowth. Chick Alx-4 displays an expression pattern complementary to that of shh, a mediator of polarizing activity in the limb bud. Local application of Sonic hedgehog (Shh) and Fibroblast Growth Factor (FGF), in addition to ectodermal apical ridge removal experiments suggest the existence of a negative feedback loop between Alx-4 and Shh during limb outgrowth. Analysis of polydactylous mutants indicate that the interaction between Alx-4 and Shh is independent of Gli3, a negative regulator of Shh in the limb. Our data suggest the existence of a negative feedback loop between Alx-4 and Shh during vertebrate limb outgrowth.     

Decreased expression and functionality of NMDA receptor complexes persist in the CA1, but not in the dentate gyrus after transient cerebral ischemia

The authors investigated the gene expression of the NR2A and NR2B subunits of N-methyl-D-aspartate (NMDA) receptor and the functional electrophysiologic activity of NMDA receptor complexes in the vulnerable CA1 and less vulnerable dentate gyrus subfields of the rat hippocampus at different times after transient cerebral ischemia. Decreased expression for both subtypes was observed in both the CA1 subfield and dentate granule cell layer at early times after challenge; however, the decreased expression in the dentate granule cell layer was reversible because mRNA levels for both the NR2A and NR2B subtypes recovered to, or surpassed, sham-operated mRNA levels by 3 days postchallenge. No recovery of expression for either subtype was observed in the CA1 subfield. The functional activity of NMDA receptor complexes, as assessed by slow field excitatory postsynaptic potentiations (slow f-EPSP) in CA1 pyramidal neurons, was maintained at 6 hours postchallenge; however, this activity was diminished greatly by 24 hours postchallenge, and absent at 7 days postchallenge. A similar pattern was observed for the non-NMDA receptor-mediated fast f-EPSP. In dentate granule neurons, however, no significant change in NMDA receptor-mediated slow f-EPSP from sham control was observed at any time after insult. The non-NMDA receptor-generated fast f-EPSPs also were maintained at all times postinsult in the dentate gyrus. These results illustrate that the activity of NMDA receptors remains functional in dentate granule neurons, but not in the pyramidal neurons of the CA1 subfield, at early and intermediate times after transient cerebral ischemia, and suggest that there is a differential effect of ischemia on the glutamatergic transmission systems in these two hippocampal subfields.     

Disinfection and sterilization of reusable devices]

Official of quality assurance requirements for the disinfection and sterilization of reusable medical devices in health care facilities has been reminded recently. These requirements concern good manufacturing practices, essential to avoid adverse events. Identification of non critical and invasive devices, protocols for pre-disinfection, cleaning, high level disinfection and sterilization for thermosensitive materials must be evaluated. Monitoring and process control of these operations are defined by French regulations and European standards, and every health professional has to become aware of these limits.     

Success of surgery for primary aldosteronism judged by residual autonomous aldosterone production

Since February 1996 we have prospectively assessed residual adrenal autonomy by the fludrocortisone suppression test (FST) in 23 patients 3 months after unilateral adrenalectomy for Conn syndrome and in 45 patients after a longer interval. In regard to blood pressure, 36 (53%) patients were cured of hypertension and the remaining 32 (47%) patients had improved hypertension control at the time of their latest postoperative clinical assessment. In regard to the outcome of surgery, patients who achieved normal suppressibility of aldosterone were regarded as cured, and those who had greater suppressibility after surgery were considered improved. Time since surgery for the whole group averaged 26 months. By these biochemical criteria, 42 patients (62%) were cured by surgery, and the rest improved; 16 (76%) of 21 women were cured, and 26 (55%) of 47 men. The women (mean +/- SD age 47 +/- 11 years) were significantly (p < 0.05) younger than the men (52 +/- 9 years). Preoperative aldosterone levels before and after FST were similar in the cured and improved groups and fell significantly (p < 0.01) in both groups following surgery. After surgical reduction of autonomous aldosterone production, mean plasma renin activity levels increased sixfold in the cured group and threefold in the improved group. Surgical mortality in this group of 68 patients with Conn syndrome was zero.     

Human herpesvirus 8--the first human Rhadinovirus

Kaposi's sarcoma (KS)-associated herpesvirus, also known as human herpesvirus 8 (HHV-8), is the first known human member of the genus Rhadinovirus. It is regularly found by polymerase chain reaction in all forms of KS, in certain types of Castleman's disease, and in body cavity-based B-cell lymphoma. Other members of this virus group occur in nonhuman primates, ungulates, rabbits, and mice and cause in part fulminant lymphomas and other neoplastic disorders of the hematopoietic system. Rhadinoviruses share a typical genome structure; most characteristically, they contain numerous sequences that appear to be sequestered from cellular DNA. We cloned and sequenced almost the complete genome of HHV-8 from a single KS biopsy specimen. Although this procedure revealed collinear organization and extensive homologies with the open reading frames of herpesvirus saimiri, genes with homology to the known oncoproteins (Stp, Tip) were not identified in the HHV-8 genome. However, HHV-8 reading frame K1, the positional analogue of Stp/Tip, was found to be significantly variable between different strains. We found, in addition, the reading frames for homologues of cellular interleukin 6, macrophage inflammatory proteins alpha and beta (MIP1 alpha and MIP1 beta, respectively), an interferon-responsive factor, and two inhibitors of apoptosis. Several of these cell-homologous genes of HHV-8 have already been shown to code for functional proteins.