Otosclerosis involving the vestibular aqueduct and Menière's disease

The coexistence of otosclerosis and endolymphatic hydrops in the temporal bone have been described; however, the mechanism for the development of endolymphatic hydrops in otosclerosis remains unknown. Among 128 temporal bones with otosclerosis, involvement of the vestibular aqueduct by otosclerosis was observed in four temporal bones from two patients. In all four, the vestibular aqueduct was filled with active otosclerotic foci; the lumen of the endolymphatic duct and sac was narrowed as a result of fibrosis, and endolymphatic hydrops, more severe in the pars inferior than the pars superior, was observed. Collapse of the ductus reuniens and dilated saccule was seen in three temporal bones. Our study indicates that otosclerotic obstruction of the vestibular aqueduct may create a disturbance of the outflow and/or absorption of endolymph, leading to the development of endolymphatic hydrops and Meniere's disease, thus supporting the theory of longitudinal flow of endolymph.     

Midazolam is metabolized by at least three different cytochrome P450 enzymes

Distribution volumes and metabolism determine the pharmacokineticsof midazolam. Cytochrome P450 3A4 has been considered a significantenzyme in its metabolism. Using heterologously expressed cytochromeP450 enzymes, we have confirmed the additional involvement ofcytochromes P450 3A3 and 3A5 in the hydroxylation of the midazolam.Whereas cytochrome P450 3A3 metabolized midazolam to the sameextent as cytochrome P450 3A4, cytochrome P450 3A5 increasedits metabolism by a factor of 2.7. The relationship of     

Novel species of Teschovirus B comprises at least three distinct evolutionary genotypes

Conventionally, Porcine teschovirus (PTV) consists of 13 genotypes (PTV 1–13, which belong to Teschovirus A); however, several novel members including PTV 14–22 have been discovered recently. PTV 21 was identified as a novel Teschovirus species named Teschovirus B. In this study, almost all 22 reported PTV genotypes except PTV 6, 7, 12 and 20 were identified in the pig populations of western Jiangxi, China, which reflects the high genotype diversity. Moreover, to the best of our knowledge, the nearly complete genome of PTV 22‐JiangX1 was first sequenced in the present study. The homology comparison of the polyprotein genes showed that PTV 22‐JiangX1 shared a relatively high nucleotide and deduced amino acid sequence identities ranging from 78.3% to 82.0% and 84.6% to 89.3%, respectively, with PTV 19 and 21. Additionally, the PTV strain of JiangX1 represents genotype 22 with the PTV 19, and 21 strains proved to be members of Teschovirus B based on the phylogenetic and evolutionary divergence analyses. Finally, we determined that the novel Teschovirus B species comprises at least three PTV genotypes.     

Alterations of uromodulin biology: a common denominator of the genetically heterogeneous FJHN/MCKD syndrome

Autosomal dominant hyperuricemia, gout, renal cysts, and progressive renal insufficiency are hallmarks of a disease complex comprising familial juvenile hyperuricemic nephropathy and medullary cystic kidney diseases type 1 and type 2. In some families the disease is associated with mutations of the gene coding for uromodulin, but the link between the genetic heterogeneity and mechanism(s) leading to the common phenotype symptoms is not clear. In 19 families, we investigated relevant biochemical parameters, performed linkage analysis to known disease loci, sequenced uromodulin gene, expressed and characterized mutant uromodulin proteins, and performed immunohistochemical and electronoptical investigation in kidney tissues. We proved genetic heterogeneity of the disease. Uromodulin mutations were identified in six families. Expressed, mutant proteins showed distinct glycosylation patterns, impaired intracellular trafficking, and decreased ability to be exposed on the plasma membrane, which corresponded with the observations in the patient's kidney tissue. We found a reduction in urinary uromodulin excretion as a common feature shared by almost all of the families. This was associated with case-specific differences in the uromodulin immunohistochemical staining patterns in kidney. Our results suggest that various genetic defects interfere with uromodulin biology, which could lead to the development of the common disease phenotype. 'Uromodulin-associated kidney diseases' may be thus a more appropriate term for this syndrome.     

Strontium ranelate promotes osteoblastic cell replication through at least two different mechanisms

The cellular and molecular mechanisms involved in osteoblastic cell replication induced by strontium ranelate are presently under investigation. The calcium-sensing receptor is a suggested target but other potential mechanisms have not been investigated. Signaling pathways involved in strontium ranelate-induced replication were investigated in preosteoblastic MC3T3-E1 and pluripotent mesenchymal C3H10T1/2 cells. Strontium ranelate effects were compared with those of calcium chloride as Ca(2+). In MC3T3-E1 cells, strontium ranelate but not CaCl(2) dose-dependently increased cell number whereas similar effects were observed for both cations in C3H10T1/2 cells. Immunoblot analysis indicated that activation of ERK, PKC and PKD by strontium ranelate in MC3T3-E1 cells was delayed compared with CaCl(2). Indeed, onset of signaling by strontium ranelate was detected after one or several hours whereas CaCl(2) had a maximal effect already after 5 min exposure. In C3H10T1/2 cells, strontium ranelate induced two types of signaling, a rapid effect and a delayed response. In addition to activation of ERK, PKC and PKD, strontium ranelate and CaCl(2) also transiently activated p38 in C3H10T1/2 cells. Functional analysis with specific inhibitors indicated that cell replication induced by strontium ranelate involves a PKC/PKD pathway in MC3T3-E1 cells and p38 in C3H10T1/2 cells. In both cell types, inhibition of the ERK pathway decreased basal cell replication but not the strontium ranelate response. In conclusion, strontium ranelate increases the replication of cells of the osteoblastic lineage by two distinct cellular mechanisms. Strontium ranelate may directly interact with the CaSR and trigger mitogenic signals such as p38 in C3H10T1/2 cells. The delayed activation of several signaling pathways in both cell lines, however, suggests the release of an autocrine growth factor by strontium ranelate that represents another potential mechanism for inducing osteoblastic cell replication.     

Preoxygenation: a comparison of three different breathing systems

An end-tidal expiratory oxygen concentration (FE'_O2) greaterthan 0.90 is considered to be adequate for preoxygenation. Thisis generally achieved using a face mask, but this can be unsatisfactoryin some patients. We compared preoxygenation in 30 healthy volunteersusing a face mask, the NasOral system, which is a novel preoxygenationdevice, and a mouthpiece with a nose-clip. We measured the maximalFE'_O2, the FE'_O2 after 2 min and the time to reach maximalFE'_O2 and recorded the subjective judgement of the volunteers.The maximal FE'_O2 with face mask and mouthpiece was significantlygreater than with the modified NasOral system (P<0.05 andP<0.01). With the former devices, a FE'_O2 of 0.90 was achievedin 73% of the volunteers vs 46% with the modified NasOral system.Using the mouthpiece, the FE'_O2 after 2 min was significantlyhigher than using the face mask (P<0.01) or the modifiedNasOral system (P<0.01). The time to maximal FE'_O2 was significantlyshorter using the modified NasOral system than with the facemask or mouthpiece (P<0.001 and P=0.0001). The volunteersgave more positive ratings to the face mask and mouthpiece thanto the modified NasOral system (P<0.001 and P<0.01). Weconclude that the use of a mouthpiece can improve preoxygenationin some patients. The results obtained with the modified NasOralsystem do not justify its introduction into clinical practice. Br J Anaesth 2001; 87: 928–31     

Extranodal Rosai-Dorfman disease involving the bone marrow: a case report

Sinus histiocytosis with massive lymphadenopathy (SHML), also known as Rosai-Dorfman disease, is a very rare disorder of unknown etiology. Although classical SHML usually presents as massive, painless, bilateral neck lymph node enlargement, approximately 25% to 40% of SHML cases described to date present in extranodal organs or tissues, such as skin, upper respiratory tract, and bone etc. However, bone marrow as a site of initial presentation by SHML has not been described since the disease was initially recognized in 1969. Here, we report the first case of bone marrow involvement by extranodal SHML, which occured in a 73 year-old man with a history of refractory idiopathic thrombocytopenia purpura. The bone marrow biopsy demonstrates the distinctive and characteristic morphologic and immunophenotypic features of extranodal SHML.     

Intravascular malignant lymphomatosis involving the kidney: three case reports

We report three autopsy cases of patients with renal symptoms related to intravascular malignant lymphomatosis (IML) exclusively involving both kidneys. The patients were one woman and two men, aged 64, 65, and 82 years, respectively. Their presenting symptoms included fever, anemia, thrombocytopenia, icterus, dyspnea, weight loss, and enlarged adrenal glands. All patients presented with acute renal dysfunction, with creatinine ranging from 2.0 to 6.5 mg/dl, or with modest proteinuria. One patient had an underlying bilateral disease, chronic pyelonephritis. Another patient also had an autoimmune disease. None of the three patients were aggressively treated. All died of progressive disease 2 weeks to 2 months after the onset of their renal symptoms. The diagnosis of the lymphomas was confirmed by morphological and immunohistochemical studies of the postmortem material. The lymphomas were subclassified as large-cell, characterized by angiotropism. Immunophenotyping revealed that all were B-lineage neoplasms. Renal involvement by IML was characterized histologically by a unique pattern of multifocal neoplastic disseminations within the glomerular and peritubular capillaries, with relative sparing of the interstitum. In one patient, glomerular mesangiolysis in association with embolic proliferations of lymphoma cells was a striking feature. All patients had bilateral renal involvement by IML which occurred in a setting of widespread disease. Our studies indicate that IML is an unusual subset of secondary renal lymphomas with bilateral diseases, and, rarely, may produce renal symptomatology early in the course. Received: June 10, 1998 / Accepted; December 24, 1998     

Challenges in Crohn's disease: Crohn's disease involving the duodenum

Duodenal Crohn's disease (CD) is an uncommon condition, and the treatment options include medications, endoscopic dilation or surgical intervention. The most common indication for surgery is presence of progressive obstructive symptoms despite medical therapy or endoscopic dilatation. Surgical options for duodenal CD include bypass, resection or strictureplasty. However, as yet an optimal surgical strategy for duodenal CD has not been established. Fistula involving the duodenum in patients with CD is rare. Duodenal fistula almost always originates from the adjacent CD in the transverse colon or from an ileocolic anastomosis. In fact, an ideal surgical strategy for duodenal fistula remains to be defined. In this review, optimal therapeutic strategies, particularly appropriate to surgical approaches, for both duodenal CD and duodenal fistula are discussed.     

Quantitative trait loci that modulate femoral mechanical properties in a genetically heterogeneous mouse population.

The goal of this study was to investigate genetic effects on mechanical properties of the mouse femur. We found evidence for QTL on eight chromosomes that affect mechanical traits. Some of these QTL may have primary effects on body weight or femoral geometry, and others seem to affect bone quality directly. INTRODUCTION: Previous studies have shown a dependence of fragility-related fracture risk on genetic background. Although many of these studies investigated the effect of genetics on BMD, basic measures of bone geometry and mechanical integrity may provide a more comprehensive characterization of the genetic effects on bone fragility. The purpose of this study was to identify quantitative trait loci (QTL) that affect mechanical and material properties of cortical bone in a genetically heterogeneous mouse population. MATERIALS AND METHODS: A total of 486 female UM-HET3 mice was used for this study. UM-HET3 mice are produced as the offspring of (BALB/cJ x C57BL/6J) F(1) females and (C3H/HeJ x DBA/2J) F(1) males. Femurs from 18-month-old mice were tested to failure in four-point bending to assess mechanical properties of cortical bone; these properties were compared with genotype data from 185 biallelic loci. A permutation-based test was used to detect significant associations between genetic markers and mechanical traits. This test generates p values that account for the effect of testing multiple hypotheses. Throughout the experiment, p < or = 0.05 was considered statistically significant. Analysis of covariance was used to examine possible effects of body weight and femoral geometry. RESULTS: We found evidence for genes on maternal chromosomes 11 and 13 and paternal chromosomes 2, 4, 7, 10, 11, and 17 that affect mechanical and material properties of femoral bone. The total variance explained by genetic effects on each mechanical trait ranges from 2.9% to 15.4%. Most of the identified polymorphisms influence mechanical traits even after adjustment for body weight. Adjustment for femoral geometry reduces the effects of some of the QTL, but those on chromosomes 2 and 10 do not seem to be influenced by femoral geometry. CONCLUSIONS: Many genes and chromosomes are involved in the genetic control over mechanical integrity of cortical bone. QTL on paternal chromosomes 4 and 11 may mediate mechanical properties, at least in part, by modulation of femoral geometry. Other QTL identified here may directly affect bone tissue quality.     

Quantitative trait loci for femoral size and shape in a genetically heterogeneous mouse population.

The aim of this study was to examine the genetic effects on cortical bone geometry. Genotypes from 487 mice were compared with geometric traits obtained from microCT. We found 14 genetic markers that associate with geometric traits, showing the complexity of genetic control over bone geometry. INTRODUCTION: Previous studies have shown that genetic background affects bone characteristics, particularly bone mineral density, in both mouse and human populations. Much less is known, however, about the effects of polymorphic genes on bone size, shape, and mechanical integrity. In this study, we investigated the genetic determinants of geometric properties of cortical bone in mice. MATERIALS AND METHODS: This study used a genetically heterogeneous mouse population, which is denoted UM-HET3 stock and is derived as the progeny of (BALB/cJ X C57BL/6J) F1 females and (C3H/HeJ X DBA/2J) F1 males. The experimental group consisted of 487 female UM-HET3 mice. Genotypic data from 99 polymorphic genetic loci was obtained from the mice at 4 weeks of age. At 18 months of age, the mice were humanely killed, and the right femurs were scanned with microcomputed tomography to assess geometric properties of cortical bone. A permutation-based test was used to detect significant associations between genetic markers and geometric traits. This test generates experiment-wise p values, which account for the effect of testing multiple hypotheses. An experiment-wise p < or = 0.05 was considered statistically significant. RESULTS: Fourteen genetic markers were found to significantly associate with one or more geometric traits. Two markers (D3Mit62 and D4Mit155) were associated with traits describing bone size; 2 (D12Mit167 and D14Mit170) were linked with traits describing bone shape; and 10 (D1Nds2, D5Mit95, D6Mit216, D7Mit91, D8Mit51, D9Mit110, D11Mit83, D15Mit100, D15Mit171, and D17Mit46) were associated with both size and shape. CONCLUSIONS: Our results indicate that the genetic control of cortical bone geometry is complex and that femoral size and shape may be influenced by different, although overlapping, groups of polymorphic loci.     

Rural trauma recidivism: a different disease

HYPOTHESIS: Unlike the well-characterized urban trauma recidivist (RC), factors associated with the rural RC remain undefined. In an attempt to devise preventative strategies, we theorized that the rural RC profile would be similar to that of urban counterparts. DESIGN: Retrospective review. SETTING: Rural, university-affiliated, level I trauma center. PATIENTS: All trauma patients admitted between January 1, 1994, and December 30, 2002. INTERVENTIONS: Identification and characterization of rural trauma RCs. MAIN OUTCOME MEASURES: Trauma recidivism incidence, risk factors, and cost. RESULTS: Of 15 370 consecutive admissions, 528 (3.4%) were RCs. Demographic comparisons to a non-RC cohort demonstrated rural RCs to be significantly older (mean +/- SD age, 55.9 +/- 24.8 vs 39.7 +/- 24.1 years), disproportionately white (65.2% [344/528] vs 56.5% [8386/14 842]), and more likely female (49.1% [259/528] vs 37.3% [5537/14 842]) (P<.001 for all). Clinical comparisons revealed significant associations between recidivism and substance abuse. The percentage of positive blood ethanol screen results (58.7% [310/528] vs 39.9% [5923/14 842]) and the mean +/- SD blood ethanol content (132.1 +/- 139.9 mg/dL [28.7 +/- 30.4 mmol/L] vs 69.5 +/- 114.4 mg/dL [15.1 +/- 24.8 mmol/L]) were higher for RCs (P<.001 for both). In addition, cocaine use was significantly higher in the RC cohort (6.4% [34/528] vs 4.1% [607/14 842]; P=.02). The total cost for all RC admissions exceeded $7 million. CONCLUSIONS: The rural RC profile is strikingly different from urban counterparts. The common feature seems to be substance abuse. Correspondingly, prevention strategies for recidivism must be considerably different among rural and urban populations.     

Artefactual breast disease: a report of three cases

Three cases of suspected artefactual conditions of the breast are presented, one case each of recurrent bleeding, recurrent infection and atypical eczema. Involvement of the breast is rare, but may go undiagnosed in many cases. Patients are usually married and in the second half of their reproductive life. An unusual pattern of disease appearance and behavior, lack of response to treatment, inappropriate affect and a request for mastectomy are helpful in suggesting the diagnosis. A disturbance in personal relationships can often be elucidated by psychiatric assessment. Treatment is difficult and may be limited to suspecting the diagnosis, excluding organic disease and avoiding unnecessary and repetitive surgery.     

Short-term results under three different immunosuppressive regimens at one center

We examined short-term outcomes and posttransplant medical complications under three different immunosuppressive regimens at a single center. The study design was a randomized, prospective, open-label trial comparing a calcineurin inhibitor-free (CNI) protocol to standard triple therapy with tacrolimus, prednisone, and mycophenolate mofetil. They were also compared to a concurrent but nonrandomized third cohort treated with a prednisone-free protocol. All three groups had excellent early outcomes with no significant difference in patient or graft survival or biopsy-proven acute rejection. Serum creatinine was significantly lower in the CNI-free recipients. Lipid panels and posttransplant diabetes mellitus were significantly lower in the prednisone-free patients. Prednisone-free kidney transplant recipients have improved early glucose metabolism and hyperlipidemia compared to CNI-free or standard triple therapy recipients with comparable rejection and graft survival rates.     

Sclerosing epithelioid fibrosarcomas involving the neuraxis: report of three cases

OBJECTIVE AND IMPORTANCE: Sclerosing epithelioid fibrosarcoma (SEF) is a rare mesenchymal neoplasm composed of rounded, vimentin-immunoreactive tumor cells disposed in nests and cords within a hyalinized collagenous matrix. Most examples arise in the deep skeletal muscles of adults. The cases recorded to date have been characterized by protracted clinical evolutions with a tendency for stubborn local recurrence, followed by late metastasis. Accordingly, SEF has been regarded as a low-grade sarcoma. A single instance of brain and vertebral metastasis has been described. We report three examples of SEF distinguished by primary involvement of the neuraxis at initial presentation. CLINICAL PRESENTATION: Two tumors had intracranial, calvarial and extracalvarial, soft-tissue components, whereas the third tumor manifested as a paraspinal mass with extension into the T12-L1 neural foramen and invasion of the T12 nerve root. INTERVENTION: All three affected patients experienced local recurrence and distant metastasis after resection of the primary site. These complications appeared early in the disease course in two cases. In no case was there a response to adjuvant chemotherapy or radiotherapy. CONCLUSION: Our experience indicates that SEFs arising along the neuraxis may demonstrate unexpectedly aggressive clinical behavior, compared with those arising in the more typical location of deep skeletal muscles.     

Adhesion after erbium, chromium:yttrium-scandium-gallium-garnet laser application at three different irradiation conditions

The aim of this study was to investigate whether distinct cooling of low fluence erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser irradiation would influence adhesion. Main factors tested were: substrates (two), irradiation conditions (three), and adhesives (three). A 750 μm diameter tip was used, for 50 s, 1 mm from the surface, with a 0.25 W power output, 20 Hz, energy density of 2.8 J/cm² with energy per pulse of 12.5 mJ. When applied, water delivery rate was 11 ml/min. The analysis of variance (ANOVA) showed that laser conditioning significantly decreased the bond strength of all adhesive systems applied on enamel. On dentin, laser conditioning significantly reduced bond strength of etch-and-rinse and one-step self-etch systems; however, laser irradiation under water cooling did not alter bonding of two-step self-etching. It may be concluded that the irradiation with Er,Cr:YSGG laser at 2.8 J/cm² with water coolant was responsible for a better adhesion to dentin, while enamel irradiation reduced bond strength, irrespective of cooling conditions.     

Anti-cardiolipin antibody and renal disease: a report three cases

Anti-cardiolipin antibodies have been linked to recurrent arterial and venous thrombosis in multiple organs. We present a biopsy-documented report of thrombotic renal disease apparently attributable to circulating anti-cardiolipin antibodies. One patient had primary anti-cardiolipin syndrome, one had mild SLE, and the third had a mild lupus-like syndrome. All three patients had a clinical course dominated by repeated multi-organ system thrombosis. Renal biopsy disclosed thrombosis at the level of the glomerular capillaries, arterioles, and interlobular arteries--similar to that described in other thrombotic microangiopathies. Renal thrombosis was not associated with active endocapillary proliferative lupus nephritis, suggesting a mechanism independent of subendothelial immune deposit injury. Renal presentation was variable, ranging from asymptomatic mild proteinuria to nephrotic-range proteinuria, renal insufficiency, and hypertension.