Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's disease)

Recent studies have demonstrated that α-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of α-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger’s Disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to α-SM actin. Our data showed that α-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy.     

A dosimetric approach to patient-specific radioiodine treatment of Graves' disease with incorporation of treatment-induced changes in thyroid mass

The traditional algorithms (Marinelli-Quimby and MIRD) used for the absorbed dose calculation in radionuclide therapy generally assume that the mass of the target organs does not change with time. In radioiodine therapy for Graves' disease this approximation may not be valid. In this paper a mathematical model of thyroid mass reduction during the clearance phase (30-35 days) after 131I administration to patients with Graves' disease is presented. A new algorithm for the absorbed dose calculation is derived, taking into account the reduction of the mass of the gland resulting from the 131I therapy. It is demonstrated that thyroid mass reduction has a considerable effect on the calculated radiation dose. Either the model of the thyroid mass reduction or the new equation for the absorbed dose calculation depend on a parameter k for each patient. This parameter can be calculated after the administration of a diagnostic amount of radioiodine activity (0.37-1.85 MBq). Thus, thyroid absorbed dose and thyroid mass reduction during the first month after therapy can be predicted before therapy administration. The absorbed dose values calculated by the new algorithm are compared to those calculated by the traditional Marinelli-Quimby and MIRD algorithms.     

Dynamic graciloplasty for urinary incontinence: the potential for sequential closed-loop stimulation

Muscle tissue transplantation applied to regain or dynamically assist contractile functions is known as 'dynamic myoplasty'. Success rates of clinical applications are unpredictable, because of lack of endurance, ischemic lesions, abundant scar formation and inadequate performance of tasks due to lack of refined control. Electrical stimulation is used to control dynamic myoplasties and should be improved to reduce some of these drawbacks. Sequential segmental neuromuscular stimulation improves the endurance and closed-loop control offers refinement in rate of contraction of the muscle, while function-controlling stimulator algorithms present the possibility of performing more complex tasks. An acute feasibility study was performed in anaesthetised dogs combining these techniques. Electrically stimulated gracilis-based neo-sphincters were compared to native sphincters with regard to their ability to maintain continence. Measurements were made during fast bladder pressure changes, static high bladder pressure and slow filling of the bladder, mimicking among others posture changes, lifting heavy objects and diuresis. In general, neo-sphincter and native sphincter performance showed no significant difference during these measurements. However, during high bladder pressures reaching 40 cm H(2)O the neo-sphincters maintained positive pressure gradients, whereas most native sphincters relaxed. During slow filling of the bladder the neo-sphincters maintained a controlled positive pressure gradient for a prolonged time without any form of training. Furthermore, the accuracy of these maintained pressure gradients proved to be within the limits set up by the native sphincters. Refinements using more complicated self-learning function-controlling algorithms proved to be effective also and are briefly discussed. In conclusion, a combination of sequential stimulation, closed-loop control and function-controlling algorithms proved feasible in this dynamic graciloplasty-model. Neo-sphincters were created, which would probably provide an acceptable performance, when the stimulation system could be implanted and further tested. Sizing this technique down to implantable proportions seems to be justified and will enable exploration of the possible benefits.     

Identification of the three-element windkessel model incorporating a pressure-dependent compliance

A new one-step computational procedure is presented for estimating the parameters of the nonlinear three-element windkessel model of the arterial system incorporating a pressure-dependent compliance. The data required are pulsatile aortic pressure and flow. The basic assumptions are a steadystate periodic regime and a purely elastic compliant element. By stating two conditions, zero mean flow and zero mean power in the compliant element, peripheral and characteristic resistances are determined through simple closed form formulas as functions of mean values of the square of aortic pressure, the square of aortic flow, and the product of aortic pressure with aortic flow. The pressure across as well as the flow through the compliant element can be then obtained so allowing the calculation of volume variation and compliance as functions of pressure. The feasibility of this method is studied by applying it to both simulated and experimental data relative to different circulatory conditions and comparing the results with those obtained by an iterative parameter optimization algorithm and with the actual values when available. The conclusion is that the proposed method appears to be effective in identifying the three-element windkessel even in the case of nonlinear compliance.     

Characterization of Mycobacterium montefiorense sp. nov., a novel pathogenic Mycobacterium from moray eels that is related to Mycobacterium triplex

The characterization of a novel Mycobacterium sp. isolated from granulomatous skin lesions of moray eels is reported. Analysis of the hsp65 gene, small-subunit rRNA gene, rRNA spacer region, and phenotypic characteristics demonstrate that this organism is distinct from its closest genetic match, Mycobacterium triplex, and it has been named M. montefiorense sp. nov.     

Bone marrow and peripheral blood globin chain synthesis in sickle cell beta zero thalassaemia.

A similar imbalance of globin chain synthesis, with low non-alpha/alpha ratios, was shown in peripheral blood and in bone marrow of compound heterozygotes for both the Hb S and beta zero thalassaemia genes (S/beta zero thalassaemia). Previous purification of whole cell globin obtained from the bone marrow did not change the non-alpha/alpha ratio. The mean non-alpha/alpha ratios were 0.57 +/- 0.13 (means +/- SD) for the peripheral blood of 12 patients, 0.52 +/- 0.10 for five patients using bone marrow globin purified on Sephadex G100, and 0.55 +/- 0.16 for the unfiltered bone marrow globin of five patients. The data show that patients with S/beta zero thalassaemia have a similar beta chain deficiency in reticulocytes and in bone marrow cells, provided whole cell globin is used which avoids the removal of the free alpha chains. The non-alpha/alpha ratios in the peripheral blood of an S/beta zero thalassaemia patient and a beta thalassaemia heterozygote from the same family were compared in seven families and no significant difference was found.     

Treatment of metastatic malignant melanoma with dacarbazine plus tamoxifen.

BACKGROUND. Endocrine factors may affect the clinical course of malignant melanoma and the response to the treatment of this disease. The presence of estrogen receptors in melanomas has been suggested, and occasional responses to antiestrogen therapy have been reported. METHODS AND RESULTS. We randomly assigned 117 patients with metastatic malignant melanoma to treatment with dacarbazine alone or dacarbazine in combination with tamoxifen. The overall rate of response, measured objectively, was higher (28 percent vs. 12 percent, P = 0.03) and survival was longer (median, 48 vs. 29 weeks, P = 0.02) among the patients who received dacarbazine plus tamoxifen than among those who received dacarbazine alone. Among women, both the response rate (38 percent vs. 10 percent, P = 0.04) and the median survival (69 vs. 30 weeks, P = 0.008) were better with dacarbazine plus tamoxifen than with dacarbazine alone, whereas among men the differences were smaller and not statistically significant. Among the patients given dacarbazine alone, there were no significant differences between women and men in response rate (10 percent vs. 13 percent) or survival (30 vs. 27 weeks), whereas among those given dacarbazine plus tamoxifen, women had better outcomes, as indicated by both response rate (38 percent vs. 19 percent, P = 0.15) and survival (69 vs. 31 weeks, P = 0.02). When we analyzed the Quetelet body-mass index (the weight in kilograms divided by the square of the height in meters) as an indirect indicator of the levels of endogenous estrogens in postmenopausal women and in men, survival was not affected by the body-mass index in the group given dacarbazine alone, whereas in the group given dacarbazine plus tamoxifen, survival was longer among patients whose Quetelet index was above the median value than among those with a Quetelet index lower than the median value (60 vs. 26 weeks, P less than 0.001). CONCLUSIONS. In the treatment of metastatic malignant melanoma, dacarbazine plus tamoxifen is more effective than dacarbazine alone, as indicated by both the response rate and the median survival; the difference in efficacy is among women.     

Physiological response and childhood anxiety: association with symptoms of anxiety disorders and cognitive bias.

This study examined the physiological response (skin conductance and heart rate [HR]) of youth exposed to a mildly phobic stimulus (video of a large dog) and its relation to child- and parent-reported anxiety symptoms and cognitive bias in a community-recruited sample of youth (n = 49). The results of this study indicated that HR and skin-conductance response were associated with youth report but not parent report of their child's symptoms of anxiety disorders and that HR response was more strongly associated with anxiety symptoms than skin-conductance response. Physiological response was uniquely associated with youth-reported symptoms of anxiety rather than youth-reported depression. Finally, HR response interacted with cognitive bias in predicting childhood anxiety disorder symptoms in a manner consistent with theories of the etiology of anxiety disorders.     

Ultrasound-guided in utero injections allow studies of the development and function of the eye

Ultrasound-guided in utero injections into the brain of murine embryos has been shown to facilitate gene delivery. We investigated whether these methods would allow gene transfer into ocular structures. Gene transfer using retroviral vectors or electroporation was found to be quite effective. We determined the window of time, as well as compared several strains of mice, that yield a high degree of survival and successful gene transfer. Several retroviral constructs were tested for expression and coexpresssion of two genes in retinal cell types. In addition, a retroviral vector was engineered to give cone photoreceptor-enriched expression, and a retroviral vector was demonstrated to provide RNAi-mediated loss-of-function. These methods enable access to early ocular structures and provide a more rapid method of assessment of gene and promoter function than possible using genetically engineered mice.