Histoplasma endocarditis: clinical and mycologic features and outcomes

OBJECTIVES: To define the salient clinical and microbiologic characteristics and outcome of infective endocarditis caused by Histoplasma capsulatum. METHODS: Case report and review of 43 literature cases. RESULTS: Infection involved both native (36 cases) and prosthetic (7) heart valves, had a high rate of systemic embolization (58%), and a more delayed diagnosis than bacterial endocarditis. Cardiac involvement generally occurred on mitral and/or aortic valves, and almost always in the setting of disseminated disease. Antemortem diagnosis was best made by serology (serum antibody titers or urinary antigen) or culture of blood (positive in <20% of cases), bone marrow, excised valves, and other non-blood specimens. Other diagnostic methods included histopathology and immunofluorescent staining of tissue samples. Untreated infection was uniformly fatal. Prolonged antifungal therapy with amphotericin B, without surgical intervention, appeared more effective than for Candida endocarditis. CONCLUSIONS: Histoplasma endocarditis is an infrequent but important cause of left-sided, blood culture-negative endocarditis. Its true prevalence may be underestimated because of the relative difficulty in making a precise microbiologic diagnosis. Amphotericin B therapy appears more effective than for Candida endocarditis, while the role for azole treatment and secondary prophylaxis remains uncertain. Indications for surgical valve replacement are similar to those for bacterial endocarditis.     

Three staged approach to the surgical management of renal cell carcinoma extending into the right atrium. Case report

Left renal cell carcinoma extending into the right atrium was treated by angioinfarction, removal of right atrial tumour using cardiopulmonary bypass and ten days later abdominal radical nephrectomy and inferior vena cava thrombectomy. Twenty four months later the patient remains well with no evidence of tumour recurrence.     

Experimental complete ureteric occlusion in sheep: radionuclide renography and histopathologic findings

Complete ureteric occlusion produces various pathophysiological changes that can be monitored externally by technetium 99m diethylenetriamine penta-acetic acid (^99mTc-DTPA) diuretic renography (RDR). Being a dynamic imaging study, it reflects the function of the kidneys and the urodynamics of the urinary tract. The aim of this study was to correlate the changes in parameters of RDR with the histological changes before and after the release of complete ureteric occlusion. In 9 sheep, RDR studies were performed serially after various periods of complete ureteric occlusion (up to 7 weeks) and after release of the occlusion (up to 5 weeks). The histological changes were correlated with changes in RDR. The progressive decrease in renal flow seen on renal images and flow time-activity curves (TACs) was explained by the development of endarteritis and thrombosis of small renal arteries. The progressive decrease in the renal uptake as indicated by the percentage renal uptake and the extraction slope of TAC is related to the progressive damage to the renal parenchyma, initially affecting the collecting ducts and tubules, with increasing interstitial fibrosis in the later stages. Obstruction for 3 weeks or less was associated with moderate damage to the parenchyma from which recovery was possible. Obstruction for 7 weeks was associated with marked damage without chance of recovery. The RDR is a non-invasive technique that can be used to monitor kidney damage after various periods of complete ureteric occlusion and to predict the outcome of surgery before the release of occlusion.This project was supported by grant no. MN013 from the Research Council, Kuwait University     

Mast cells and histamine responses of the ureter,ultrastructural features of cell-to-cell associations and functional implications

Summary In this study of normal adult human and ovine ureters, a characteristic distribution of a large population of typical mast cells was described by light and electron microscopy. Pharmacological studies were used to ascribe a functional role for these cells in normal and pathological states. In the structural investigations typical mast cells with their cytoplasm packed with characteristic electron dense granules were found in close vincinity to smooth muscle cells. A close association between mast cells and a fibroblast like La-cell and non myelinated nerve fibers was noted. The prevalence of mast cells was higher in human ureters. Human and sheep ureteral ring preparations exhibited spontaneous rhythmical contractions in vitro. Addition of histamine (10^-6–10^-5 M) induced an increase in the frequency of contractions and enhanced the basal tone particularly in human samples. It is likely that histamine under pathological conditions such as renal colic and inflammatory reactions is released from mast cells within the ureter and induces a state of forceful contractions and pain fibre stimulation.Supported by grant No. MA 015, Kuwait University     

Genetic unraveling of colorectal cancer

Colorectal cancer is a common disease in both men and women (being the third most common cancer in men and the second most common among women) and thus represents an important and serious public health issue, especially in the western world. Although it is a well-established fact that cancers of the large intestine produce symptoms relatively earlier at a stage that can be easily cured by resection, a large number of people lose their lives to this deadly disease each year. Recent times have seen an important change in the incidence of colorectal cancer in different parts of the world. The etiology of colorectal cancer is multifactorial and is likely to involve the actions of genes at multiple levels along the multistage carcinogenesis process. Exhaustive efforts have been made out in the direction of unraveling the role of various environmental factors, gene mutations, and polymorphisms worldwide (as well as in Kashmir—“a valley of gastrointestinal cancers”) that have got a role to play in the development of this disease so that antitumor drugs could be developed against this cancer, first, and, finally, the responsiveness or resistance to these agents could be understood for combating this global issue.     

Analysis of IDH mutation, 1p/19q deletion,and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas

Background

Grades II and III gliomas have unpredictable rates of progression, making management decisions difficult. Currently, several clinical and radiological characteristics are utilized to predict progression and survival but collectively are suboptimal.

Methods

In this study, we analyzed a set of 108 nonenhancing hemispheric grade II–III gliomas. Demographic variables, including patient age, tumor diameter, extent of resection, and performance status, were combined with molecular data (IDH mutation status [mIDH], 1p/19q codeletion, PTEN deletion, and EGFR amplification). A complete dataset for all variables was compiled for 70 of the 108 patients. Both univariable and multivariable analyses were performed to determine whether the molecular data singly or in combination offer advantages over tumor type and grade for prediction of overall survival (OS) and/or progression-free rate (PFR).

Results

Patient age, clinical variables (tumor diameter, extent of resection, performance status), and pathology (tumor type and grade) were not predictive of OS or PFR. IDH mutation status alone was predictive of longer OS and PFR for the entire group of tumors; 1p/19q deletion alone was predictive of OS but not PFR. In the multivariable analysis, none of the clinical or demographic factors were predictive of OS or PFR. IDH mutation status, 1p/19q codeletion, and PTEN deletion were predictive of OS (P = .003, P = .005, P = .02, respectively). Both mIDH (P < .001) and the interaction term of 1p/19q and PTEN (P < .001) were found to be predictive of PFR.

Conclusions

We conclude that the combination of mIDH, 1p/19q codeletion, and PTEN deletion may be particularly effective in discriminating good prognosis from poor prognosis hemispheric gliomas. We propose that such a scheme merits testing on larger prospective cohorts. Should our findings be confirmed, routine clinical analysis of hemispheric gliomas for mIDH, 1p/19q codeletion, and PTEN deletion would be justified.