Mycobacterium ulcerans infection in Ashanti region, Ghana

We describe a series of 96 cases of Mycobacterium ulcerans infection (Buruli ulcer) from a new endemic focus in the Afram valley, north of Agogo, in Ghana. 63 cases were children under 13 years old. Active treatment by excision and skin grafting necessitates long stays in hospital and repeated procedures. Scarring and contracture are frequent. Eyes and other vital organs may be destroyed. In its endemic foci Buruli ulcer is a serious health burden on rural populations. Research is urgently needed, especially in prevention and non-surgical management.     

Acinar redistribution and heterogeneity in transport of the organic cation rhodamine B in rat liver

We studied a possible acinar heterogeneity in the transport of organic cations, using rhodamine B as model compound. Employing perfusions of isolated rat livers in the ante- and retrograde mode and quantitative fluorescence microscopy, Zones 1 and 3 were shown to be equally efficient in taking up rhodamine B. Ten minutes after injection in an antegrade perfusion, 95% of the dose was localized in the portal half of the acinus. Fifty minutes later, however, the amount of rhodamine B in Zone 1 had been reduced to 23%; 30 and 31% were in Zones 2 and 3, respectively, and the medium concentration was doubled. Thus, unchanged rhodamine B appeared to be transported downstream within the liver, either via the medium or directly from cell to cell, finally resulting in a relatively higher rhodamine B concentration in Zone 3. To obtain additional data, we designed a perfusion setup in which the zones could be studied separately. In both zones, the amount excreted into the medium was about 30 times the amount excreted into bile. Intracellular sequestration of rhodamine B and the rate constant for sinusoidal secretion were higher in Zone 3, while the sinusoidal uptake rates were equal; biliary excretion was higher in Zone 1. Acinar distribution changed with time because rhodamine B, primarily accumulated in Zone 1, was secreted into the sinusoids and taken up again by downstream cells. The finally higher rhodamine B concentration in Zone 3 was caused by a zonal heterogeneity in intracellular sequestration and sinusoidal secretion of rhodamine B.     

The importance of self-examination in the earliest diagnosis of multiple primary cutaneous melanomas: a report of 47 cases

BACKGROUND: Development of more than one primary melanoma in a patient is a relatively uncommon but well-recognized phenomenon. Its frequency has ranged from 1.2% to 8.2% in several series. This subgroup of patients with multiple primary lesions has not been characterized sufficiently. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. METHOD: Study subjects were drawn from 1240 patients with histologically confirmed melanoma, including melanoma in situ. From this group, multiple melanomas developed in 47 patients (3.79%). Every one of our patients has been taught to perform self-examination of the skin to detect suspicious pigmented lesions. RESULTS: Of the 47 patients described in this study, 38 had two primary melanomas, 7 had three melanomas and 2 had 5 and 10 melanomas, respectively. Mean age at first diagnosis was 46.2 years. The majority of subsequent melanomas (74.5%) were removed within 5 years of the initial operation. Synchronous lesions were found in 10 patients. In male patients, the lesion appeared most frequently on the trunk; in female patients, melanoma appeared mostly on the lower extremities. The second primary melanomas developed in the same anatomic region from the first in 53.2% of our patients. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Regarding invasive melanomas, the mean thickness of the first melanomas was 1.31 mm compared with 0.66 mm for the second ones. Dividing patients into two groups, of more and less than 50, it is highlighted that in older patients synchronous lesions appear more frequently (36.4% vs. 8.0%); the median time interval between sequential melanomas is longer (84 vs. 63.7 months); and the ratio between the primary and secondary melanoma mean thickness is lower (1.21 : 1.08 vs. 1.43 : 0.63 mm). CONCLUSIONS: The study confirms that second primary melanoma is usually thinner than the first lesion, and it is more common in the same region of the body as the initial melanoma. The highest risk for a second melanoma is during the first 5 years, but a much longer time interval of 28 years is possible. Continued medical follow-up with complete skin examinations seems prudent, but it is very important to promote self-skin evaluation in patients to detect not only metastases but also subsequent primary melanomas in their earliest phases.     

Potential errors due to aliasing in digital video analysis of quantitative autoradiography

Digital image analysis of quantitative autoradiographic (QAR) films is widely used in neuroscience applications. Unless proper precautions are taken when autoradiographic images are converted to digital form they can be inadvertently modified by improper application of the sampling process. This type of modification is termed aliasing error and can cause nonexistent structures to appear in the reconstructed digital image, changing the apparent optical density values of the data. The theoretical basis of aliasing error is presented, along with examples of aliasing from optical resolution test patterns and 2-deoxy[14C]glucose (2-DG) experimental QAR images. We show that aliasing can change the apparent shape of structures, as well as the derived values obtained from QAR experiments. In an example with experimental 2-DG images, aliasing in the cerebellar cortex consistently underestimates tissue radioactivity levels in gray matter (P less than 0.001) and overestimates levels in adjacent white matter (P less than 0.001). Additional data transformations, such as the equations used for blood flow or glucose utilization, can, somewhat unpredictably, accentuate the errors introduced by aliasing. We present a discussion of the autoradiographic image features and electronic design that play a role in introducing aliasing errors and means by which aliasing can be recognized and minimized.     

Gliotoxin non-selectively induces apoptosis in fibrotic and normal livers.

BACKGROUND: Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis. Several lines of evidence indicate that inducing apoptosis of hepatic stellate cells (HSC) may lead to regression of liver fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC. However, the clinical use of GTX may be limited because of the lack of cell and tissue specificity, causing a high risk of potentially severe adverse effects. The aim of this study, therefore, was to study the effect of GTX on different cells of the liver. METHODS: We used normal and fibrotic precision-cut rat liver slices to study the effect of GTX on the various resident liver cell types. In these slices, the complex cell-cell interactions are preserved, which closely mimics the in vivo situation. RESULTS: GTX exhibited a potent apoptosis-inducing activity in these slices. Both immunohistochemical stainings and real-time mRNA techniques showed that this apoptosis-inducing effect was seen in HSC. However, Kupffer cells and liver endothelial cells were also affected by GTX, whereas hepatocytes were only mildly affected. CONCLUSIONS: This study indicates that the apoptosis-inducing strategy to treat liver fibrosis has high potential, but it will be necessary to develop an HSC-specific therapy to prevent adverse effects.     

Buthionine sulfoximine-mediated depletion of glutathione in intracranial human glioma-derived xenografts

D-54 MG, a human glioma-derived continuous cell line growing as subcutaneous or intracranial xenografts in athymic mice, was found to be sensitive to the effects of D,L-buthionine-(SR)-sulfoximine, a selective inhibitor of gamma-glutamylcysteine synthetase. Intraperitoneal administration of one dose of buthionine sulfoximine (BSO, 5 mmol/kg) resulted in depletion of total intracellular glutathione to 57 and 47% of control 12 hr, and 73 and 23% of control 24 hr, after BSO in subcutaneous and intracranial xenografts respectively. Concurrent measurement of total glutathione in the contralateral (non-tumor-containing) cerebral hemisphere in mice bearing intracranial D-54 xenografts demonstrated insignificant depletion of glutathione. Multiple doses of BSO, at 12-hr intervals, resulted in further depletion to 27% (s.c.) and 16.5% (i.c.) of control 12 hr following the final dose of BSO. Quantitative analysis of BSO delivery to xenograft and contralateral brain tissue revealed transfer constants, K1, of 15.8-24.1 x 10(-3) and 2.4 x 10(-3) ml.g-1.min-1 for xenograft and "normal" brain respectively. This highly selective depletion of glutathione in neoplastic tissue versus surrounding non-neoplastic host tissue may have therapeutic implications for the rational use of chemotherapeutic and radiotherapeutic intervention.     

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.