Postmortem Diagnosis of Diabetic Ketoacidosis Presenting as the "Dead-in-Bed Syndrome".

OBJECTIVE: To report a case of a young male with type 1 diabetes mellitus found dead in his bed, initially assumed to have died from hypoglycemia (i.e., the "dead in bed" syndrome). However, his autopsy findings revealed that diabetic ketoacidosis (DKA) was the cause of death. METHODS: We present the laboratory and autopsy findings of the patient, highlighting the importance of laboratory analyses of the vitreous humor and microscopy of kidney tissue when investigating the cause of sudden death in patients with type 1 diabetes. RESULTS: A 25-year-old healthy male with type 1 diabetes on continuous subcutaneous insulin infusion therapy was found dead in his undisturbed bed. An autopsy included vitreous humor analyses. His results were as follows: glucose of 755 mg/dL (reference range 70-105 mg/dL), anion gap >36 mEq (reference range 4-12 mEq/L), elevated acetone at 66 mg/dL (reference range negative), which were consistent with DKA. Renal microscopy demonstrated subnuclear vacuoles in the proximal tubules, 1 of 2 lesions were described as an Armanni-Ebstein lesion, which is a postmortem finding in patients who die from diabetic coma. CONCLUSION: The most likely cause of death at home in young patients with type 1 diabetes is severe hypoglycemia. However, an autopsy of the present case confirmed DKA based on vitreous humor biochemistry and microscopic examination of the kidneys, which demonstrated the Armanni-Ebstein phenomenon. Analysis of the vitreous fluid and microscopic examination of the kidneys for the presence of Armanni-Ebstein lesion can be used to help determine the cause of death in patients with type 1 diabetes mellitus.

Evaluation of morphologically unclassified renal cell carcinoma with electron microscopy and novel renal markers: implications for tumor reclassification.

Despite progress in the classification of renal cell carcinomas (RCC), a subset of these carcinomas remains unclassified (RCC-U). Patients with RCC-U usually present at a late stage and have a poor prognosis. Several studies have attempted to extract new classifications of newly recognized renal carcinomas from the group of RCC-U. However, to date, no studies in the literature have attempted to characterize the RCC-U with unrecognizable cell types beyond the morphologic evaluation on H&E-stained sections. The purpose of this study was to evaluate this group of RCC-U using electron microscopy and novel renal markers. Ten cases of such RCC-U were identified for this study. At the ultrastructural level, they did not show typical morphology that resembled any of the well-studied, recognizable subtypes of RCC. However, they did reveal features of renal tubular epithelial differentiation. The histologic, ultrastructural, and immunophenotypic features indicated that these tumors are poorly differentiated renal epithelial tumors, possibly derived from the proximal nephron, with an immunohistochemical profile similar to high-grade clear cell RCC. It is, therefore, proposed that this group of renal carcinomas be renamed "poorly differentiated renal cell carcinoma, not otherwise specified." The current study showed that PAX-8 and carbonic anhydrase IX are reliable markers for this novel group of renal carcinoma, and that electron microscopy is an important adjunct in the evaluation of new and unusual renal entities.

HIV Screening and Awareness Survey for Pregnant Women in a Remote Area in Xinjiang Uyghur Autonomous Region of China.

OBJECTIVE: The number of people infected with human immunodeficiency virus (HIV) in China has increased in recent years. HIV screening for pregnant women was performed in a remote area in Xinjiang, as an effort to promote universal HIV screening in pregnant women and to help prevention of mother-to-child transmission. METHODS: Pregnant women in Burqin and Jeminay Counties in Xinjiang were offered free voluntary HIV screening. Local mid-level medical workers were trained to use Determine® HIV-1/2 kit for HIV screening. All the tested pregnant women signed a consent form, received HIV education material, and participated in an HIV knowledge survey. RESULTS: All the 890 pregnant women receiving HIV test had negative result. Among these women, 67.6% were Kazakh and 40.9% were farmers. Survey of HIV knowledge showed that these women's awareness about mother-to-child transmission was limited. The levels of HIV knowledge were related with ethnic background, age, education and profession of the pregnant women. CONCLUSION: The results suggested that HIV infection had not become a significant problem among the pregnant women in this remote area of Xinjiang, but continued efforts to improve the awareness of HIV, especially the knowledge about mother-to-child transmission of HIV, in pregnant women were needed.

Web-based nephropathology teaching modules and user satisfaction: the nephrology on-demand experience.

Nephropathology is an integral component of nephrology education. Online teaching sites provide valuable educational materials to learners, but learner satisfaction has not been measured. We developed a nephropathology website and measured learners' satisfaction. The Nephrology On-Demand Histopathology website (http://blog.ecu.edu/sites/nephrologyondemand/?page_id=4502) provided nephropathologic specimens with explanations. Users were asked to complete a Likert-based survey (1-strongly agree . . . 5-strongly disagree) regarding four key areas of content quality: accuracy, currency, objectivity, and usefulness. Learners of all training levels perceived the content quality favorably. The mean (±SD) for accuracy was 1.70 (0.89), currency 1.62 (0.90), objectivity 1.80 (1.01), and usefulness 1.72 (0.95). Nephrology On-Demand Histopathology is a well-received teaching tool to learners of all training levels. Educators may consider using it, as well as other online nephropathology sites, as adjunctive teaching tools.

Notch-1 signaling is lost in prostate adenocarcinoma and promotes PTEN gene expression.

Prostate tumorigenesis is associated with loss of PTEN gene expression. We and others have recently reported that PTEN is regulated by Notch-1 signaling. Herein, we tested the hypothesis that alterations of the Notch-1 signaling pathway are present in human prostate adenocarcinoma and that Notch-1 signaling regulates PTEN gene expression in prostate cells. Prostate adenocarcinoma cases were examined by immunohistochemistry for ligand cleaved (activated) Notch-1 protein. Tumor foci exhibited little cleaved Notch-1 protein, but expression was observed in benign tissue. Both tumor and benign tissue expressed total (uncleaved) Notch-1. Reduced Hey-1 expression was seen in tumor foci but not in benign tissue, confirming loss of Notch-1 signaling in prostate adenocarcinoma. Retroviral expression of constitutively active Notch-1 in human prostate tumor cell lines resulted in increased PTEN gene expression. Incubation of prostate cell lines with the Notch-1 ligand, Delta, resulted in increased PTEN expression indicating that endogenous Notch-1 regulates PTEN gene expression. Chromatin immunoprecipitation demonstrated that CBF-1 was bound to the PTEN promoter. These data collectively indicate that defects in Notch-1 signaling may play a role in human prostate tumor formation in part via a mechanism that involves regulation of the PTEN tumor suppressor gene.

Fibromuscular dysplasia in association with intrauterine cocaine exposure.

BACKGROUND: Fibromuscular dysplasia (FMD) is an idiopathic disease of small- and medium-sized arteries, involving one or more vascular beds. Patients may present with a range of symptoms, which may not readily lead to a diagnosis of FMD. While maternal cocaine abuse during pregnancy has previously been associated with vascular alterations in the fetus, an association specifically with FMD has not previously been described. METHODS/RESULTS: In this case report, a 21-month-old male presented with a 3-week history of daily vomiting, with temporary improvement of symptoms, then relapse followed by loss of consciousness. His medical history was significant only for maternal cocaine use. Clinical evaluation revealed dilated cardiomyopathy, and a presumptive diagnosis of myocarditis was rendered. Respiratory arrest and death occurred 2 days after admission. Postmortem examination demonstrated intimal-type multivessel FMD, which was determined to be the cause of the clinical presentation. CONCLUSION: Without a postmortem examination, it is unlikely that a diagnosis of intimal fibroplasia, a rare variant of FMD (5% of cases), would have been made. This case thus illustrates the continuing utility of the classic postmortem examination. More intriguingly, the case suggests a possible relationship between in utero cocaine exposure and the development of fibromuscular dysplasia in the child.

Desmosomes and microvilli mean a lot: diagnosis of neoplasms of unknown origin using electron microscopy.

Neoplasms of unknown origin present a difficult diagnostic dilemma, particularly if they are very poorly differentiated. Adenocarcinomas, squamous cell carcinomas, melanomas, lymphomas, and sarcomas can all be very difficult to diagnose if the light microscopic cytomorphology is sufficiently undifferentiated. Electron microscopy (EM) can either demonstrate differentiation or narrow the range of differential diagnoses. The authors report the case of a 64-year-old male who has been HIV positive for several years and was found to have expansile lytic lesions in several ribs and a thumb fracture associated with a soft tissue mass which was biopsied. The tumor was composed of very pleomorphic malignant cells without specific differentiation. The malignant cells stained positive for pancytokeratin (AE 1/3), EMA, CEA, CK20, and CK7. Rare cells had mucicarmine-positive intracytoplasmic droplets. They were negative for S-100, calretinin, CD45, MART-1, and vimentin. EM revealed intracytoplasmic lumina with long microvilli and many well-formed desmosomal junctions. The diagnosis was initially very broad. Immunohistochemistry narrowed the diagnosis to carcinoma, but EM alone was able to narrow the diagnosis to poorly differentiated adenocarcinoma. In a neoplasm of unknown origin, EM can either narrow the differential significantly or, in the case of limited material, provide information that otherwise may not be attainable.

Nephrotic proteinuria as a result of essential hypertension.

BACKGROUND: The presence of nephrotic-range proteinuria in a nondiabetic hypertensive patient is generally indicative of an underlying glomerular disease. A few published reports have noted nephrotic proteinuria in some patients with hypertensive nephrosclerosis. The frequency of this association is unknown. METHODS: We retrospectively reviewed renal biopsy reports on all cases of nephrotic syndrome over an 8-year period (1993-2000). We excluded all cases of diabetes mellitus, lupus, hepatitis, human immunodeficiency virus, and chronic use of nonsteroidal anti-inflammatory drugs. Biopsy specimens showing glomerular eosinophilic hyalinosis lesions, positive immunofluorescence staining, or dense deposits on electron microscopy were also excluded. Thirteen of the remaining 237 (5.5%) biopsy specimens satisfied the standard histological criteria for hypertensive nephrosclerosis. RESULTS: All patients were African-Americans with a mean age of 47.5 +/- 13 years and an average mean arterial blood pressure of 122 +/- 19 mm Hg. The mean values for urinary protein excretion, serum creatinine, albumin, and cholesterol were 8.9 g/day, 3.3 mg/dl, 3.1 g/dl, and 245 mg/dl, respectively. Optimal blood pressure control required at least three antihypertensive agents. Progression to end-stage renal disease occurred over a mean duration of 8.3 +/- 6.5 months. Multivariate regression showed a strong but nonsignificant association between the level of proteinuria at the time of biopsy, duration of hypertension, and number of blood pressure medications (R(2) = 0.56, p = 0.38). CONCLUSIONS: Nephrotic syndrome may be more common in poorly controlled essential hypertension than previously realized. In African-American patients, the differential diagnosis of nephrotic syndrome should include hypertensive nephrosclerosis, but abrogation of renal biopsy is not implied.

Chronic plasma cell pneumonia in a patient with long-standing HIV infection.

Chronic bibasilar alveolar infiltrates existed for more than 2 years in a 25-year-old woman infected with HIV for more than a decade. Bronchoscopically, there were copious, purulent secretions that grew methicillin-resistant Staphylococcus aureus (MRSA). Transbronchial biopsy specimens demonstrated plasma cell interstitial pneumonia (PCIP). Focal, transient radiographic improvement occurred after antistaphylococcal antimicrobial therapy. With recurrent and progressive symptoms, sustained clinical and radiographic improvement did not occur until corticosteroid therapy was instituted with tuberculosis chemoprophylaxis. Persistent antigenic stimulation in immunosuppressed patients causes PCIP. In this instance, the stimulus is MRSA. The previous model and support for this theory is Pneumocystis carinii. There is good experimental reason for a plasma cell response in persons infected with HIV. To our knowledge, this is the first case of chronic plasma cell interstitial pneumonia caused by indolent MRSA infection.

"Black swan in the kidney": renal involvement in the antiphospholipid antibody syndrome.

The antiphosphospholipid antibody syndrome (APS) describes a clinical entity with recurrent thrombosis, fetal loss, thrombocytopenia in the presence of lupus anticoagulant and/or antibodies to cardiolipin. These antibodies may be associated with connective tissue diseases such as systemic lupus erythematosus (secondary APS) or be found in isolation (primary APS). Renal syndromes increasingly being reported in association with these antibodies include thrombotic microangiopathy, renal vein thrombosis, renal infarction, renal artery stenosis and/or malignant hypertension, increased allograft vascular thrombosis, and reduced survival of renal allografts. Although much has been understood concerning the biology of these antibodies and the pathogenesis of thrombosis, the optimal therapy remains to be elucidated. This article presents a historical review of the renal involvement in the antiphospholipid syndrome and discusses therapeutic options. Further research is needed.

Celecoxib-induced acute interstitial nephritis.

Data about the nephrotoxicity of selective cyclooxygenase-2 inhibitors are still evolving. Acute interstitial nephritis is a well-described complication of therapy with nonselective nonsteroidal anti-inflammatory drugs. We report a case of biopsy-proven acute interstitial nephritis in a 73-year-old diabetic woman, who had taken celecoxib for more than 1 year before presentation. She presented with clinical findings of subnephrotic proteinuria and acute renal failure that required dialysis. She recovered renal function with cessation of celecoxib therapy after 2 weeks. Other medications were reintroduced safely, without recurrence of renal failure. A kidney biopsy specimen showed acute interstitial nephritis with a prominent eosinophilic infiltrate in the interstitium. This case documents the occurrence of acute interstitial nephritis with celecoxib and emphasizes the need for continued vigilance and care in use of cyclooxygenase-2 inhibitors in high-risk patients.