Previous studies have demonstrated significant discrepancy rates between clinical and autopsy diagnoses. However, infectious diseases have not received emphasis in these studies. We conducted a study to determine whether the clinical and autopsy diagnoses of infectious diseases are concordant or discrepant and to determine discrepancy rates. Retrospective reviews of the records of 276 patients (adults, 182; fetuses and neonates, 94) who underwent autopsy during the years 1996 through 2001 were performed. Comparison of clinical and autopsy diagnoses was performed using the Goldman classification scheme. Of 182 adult patients, 137 (75.3%) had an infectious disease at autopsy. In 59 (43.1%) of 137 patients, the infectious disease diagnoses were unknown clinically. Of 94 fetuses and neonates, 45 (48%) had an infectious disease at autopsy. In 26 (58%) of 45 patients, the infectious disease diagnoses were unknown before death. There are substantial discrepancies between clinical and autopsy diagnoses of infectious diseases. In adults, acute bronchopneumonia is the infectious disease most often missed clinically; in fetuses and neonates, it is acute chorioamnionitis.
B5 fixation achieves superior morphologic detail. However, environmental concerns have led to labor-intensive and costly requirements for disposal of mercury-containing fixatives. We performed a blinded prospective study to find a safe, mercury-free alternative to B5. Morphology was evaluated with 6 fixatives, including B5, in a blinded fashion. Acetic acid-zinc-formalin (AZF) was selected for further evaluation of immunohistochemistry, in situ hybridization, and molecular analysis. AZF fixation resulted in overall staining and morphologic detail comparable to B5 and achieved equivalent or superior antigen preservation for immunohistochemical studies. Strong signal intensity was achieved with in situ hybridization, and DNA amplification could be successfully performed. AZF allows greater flexibility in fixation times, decreases decalcification time, and eliminates labor-intensive steps required for B5 processing.
Context.—Cdc6 has been extensively studied as a marker for cellular proliferation that is expressed during the normal cell cycle. Recent studies indicate that Cdc6 may be a marker for cervical intraepithelial neoplasia (CIN) and carcinoma; however, the histologic distribution of Cdc6 has not been explicitly defined. Expression of Cdc6 in the endocervical mucosa also remains unexplored. Objective.—The goal of the current study was to evaluate the distribution of Cdc6 protein, MIB-1 protein, and human papillomavirus (HPV) DNA in a broad range of cervical tissues, including normal, potentially premalignant, and malignant lesions of the ectocervical and endocervical mucosa. Methods.—We used an indirect immunoperoxidase method to stain formalin-fixed, paraffin-embedded tissues and frozen tissues, including biopsy and hysterectomy specimens, for Cdc6 and MIB-1 proteins, and we used in situ hybridization to detect HPV DNA in a subset of cases. Results.—Cdc6 staining was exclusively nuclear and was present in both squamous and glandular epithelial cells of histologic sections. Cdc6 staining was rarely present in specimens of normal cervical squamous mucosa (2/84, 2.4%) or in specimens with squamous metaplasia (3/59, 5.1%) and was not detected in normal endocervical glands (0/84). Staining was present in most cases of CIN I (31/48, 65%). Staining was present in the majority of cases of CIN II (25/28, 89%) and in all cases of CIN III (36/36) and squamous cell carcinomas (34/34). The proportion of cells staining for Cdc6 increased with the grade of dysplasia, and the proportion of stained cells in squamous cell carcinomas was similar to that in lesions of high-grade dysplasia. Cdc6 staining was present in the majority of cases in glandular lesions including adenocarcinoma in situ (11/14, 79%) and adenocarcinoma (8/10, 80%). The histologic distribution of Cdc6-immunoreactive cells was similar to that of cells with a strong signal for HPV DNA, but Cdc6 protein and HPV DNA did not colocalize at the level of individual cells. Conclusion.—Cdc6 expression is a marker for high-grade cervical squamous and glandular dysplasia and carcinoma and is associated with HPV infection. The mechanistic basis of the association between HPV infection and Cdc6 immunopositivity remains to be determined but may represent either up-regulation of Cdc6 expression or stabilization of the Cdc6 protein.
To our knowledge we report the first case of meningitis from Coccidioides immitis associated with massive dural and cerebral venous thrombosis and with mycelial forms of the organism in brain tissue. The patient was a 43-year-old man with late-stage acquired immunodeficiency syndrome (AIDS) whose premortem and postmortem cultures confirmed C immitis as the only central nervous system pathogenic organism. Death was attributable to multiple hemorrhagic venous infarctions with cerebral edema and herniation. Although phlebitis has been noted parenthetically to occur in C immitis meningitis in the past, it has been overshadowed by the arteritic complications of the disease. This patient's severe C immitis ventriculitis with adjacent venulitis appeared to be the cause of the widespread venous thrombosis. AIDS-related coagulation defects may have contributed to his thrombotic tendency.
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