Treatment of edematous disorders with diuretics

Generalized edema results from alterations in renal sodium homeostasis that ultimately result in an expansion of extracellular fluid volume and accumulation of interstitial fluid. The common edematous disorders include congestive heart failure, cirrhosis, nephrotic syndrome, and renal insufficiency. The abnormalities of sodium homeostasis contributing to edema formation in each condition are discussed. Management of volume homeostasis, with an emphasis on the role of diuretic therapy, is reviewed.     

Dissociable dopaminergic control of saccadic target selection and its implications for reward modulation

To investigate mechanisms by which reward modulates target selection, we studied the behavioral effects of perturbing dopaminergic activity within the frontal eye field (FEF) of monkeys performing a saccadic choice task and simulated the effects using a plausible cortical network. We found that manipulation of FEF activity either by blocking D1 receptors (D1Rs) or by stimulating D2 receptors (D2Rs) increased the tendency to choose targets in the response field of the affected site. However, the D1R manipulation decreased the tendency to repeat choices on subsequent trials, whereas the D2R manipulation increased that tendency. Moreover, the amount of shift in target selection resulting from the two manipulations correlated in opposite ways with the baseline stochasticity of choice behavior. Our network simulation results suggest that D1Rs influence target selection mainly through their effects on the strength of inputs to the FEF and on recurrent connectivity, whereas D2Rs influence the excitability of FEF output neurons. Altogether, these results reveal dissociable dopaminergic mechanisms influencing target selection and suggest how reward can influence adaptive choice behavior via prefrontal dopamine.     

Sequence variability of a prolonged tetranucleotide repeat

A tetranucleotide repeat located in intron 20 of the RB geneconsists of 16–26 CTTT(±T) repeats in 99% of thealleles. In the remaining 1% of alleles the segment is extendedto a length of >60 repeats. Sequence analysis revealed thatthe prolonged alleles either consisted of perfect CTTT(±T)repeats or irregular repeat sequences with variable combinationsof C and T. The data provide clues to the mechanisms causingunstable expansions of repeat     

Effect of N-acetylcysteine(NAC) treatment on HIV-1 infection: a double-blind placebo-controlled trial

Objective: In a double-blind placebo-controlled trial, human immunodeficiency virus (HIV)-seropositive patients with a CD4 lymphocyte cell count of more than 200 × 10⁶⋅l⁻¹ were randomised to receive either 800 mg N-acetylcysteine (NAC) or placebo for 4 months. Before treatment low plasma cysteine levels, high free radical activity in neutrophils in the presence of autologous plasma – measured by the nitroblue tetrazolium (NBT) test – and increased tumor necrosis factor (TNF)-α levels were found in the HIV positive patients. Results: After treatment the low plasma cysteine level in the NAC group increased to normal, and the decline of the CD4+ lymphocyte count before the study start, was less steep in the NAC group than in the placebo group after treatment. There was also a reduction in TNF-α level. However, NAC had no effect on the radical production by neutrophils, and although it did not increase the CD4+ cell count, it may have decreased the decline in CD4+ cells. Conclusion: Further controlled trials with NAC are needed to devermine whether it has a beneficial effect in the treatment of asymptomatic HIV-infected individuals. Received: 25 October 1995/Accepted in revised form: 15 February 1996     

Reduced threshold to suction-induced blister formation in insulin-dependent diabetics

Diabetics may have an increased susceptibility to cutaneous blister formation clinically manifest as the bullous eruption of diabetes. We evaluated the mechanical force necessary to induce suction blisters in fifteen insulin-dependent diabetics and twenty age-matched normal controls. The mean suction blister threshold for the diabetics was 31.9 minutes versus 68.0 minutes for the controls, a highly significant difference (p less than 0.01). Histologic appearance of suction blisters was similar in diabetic and normal skin, under both light and electron microscopic examination, with a noninflammatory subepidermal separation in the lamina lucida between the cell membrane and the basal lamina. These results demonstrate that insulin-dependent diabetics have a marked reduction in suction blister threshold as compared to age-matched controls.     

Large acquired nevocytic nevi induced by the Koebner phenomenon

A patient with characteristic clinical, histopathological, ullrastruclural and family history of cpidermolysis bullosa simplex (EBS) developed large acquired nevocytic at the sites of some healing blisters. An isomorphic reaction may have initiated the development of these ncvi. Such large acquired nevi should be considered in the differential diagnosis of large and giant congenital nevi which have the potential to evolve into malignant melanoma.     

Further studies on the mechanism of suppression of human lymphocyte transformation by human alpha fetoprotein

We investigated the possibility that noncovalent binding of negatively charged molecules such as prostaglandins (PGs) might be partly responsible for human alpha fetoprotein (HAFP) heterogeneity with respect to charge and the suppression of human lymphocyte responses, since PGs are potent suppressors of lymphocyte transformation. Indomethacin, an inhibitor of PG synthesis, had no effect upon the transformation of adherent-cell-depleted human lymphocytes, nor did it interfere with the capacity of HAFP to inhibit lymphocyte transformation. When a partially suppressive dose of HAFP was added to mitogen-stimulated lymphocytes together with varying doses of prostaglandin E₁ or E₂ (PGE₁ or PGE₂), no evidence of inhibitory synergy was demonstrable; their combined suppressive action was either less than or approximately equal to the sum of their respective inhibitory effects. Addition of PGE₂ to a nonsuppressive dose of an impotent HAFP preparation resulted in no greater lymphocyte suppression than that achieved by PGE₂ alone. Analysis of the kinetics of suppression of lymphocyte transformation by PG and HAFP yielded unequivocal evidence for their disparate mechanisms of action. Suppression of lymphocyte transformation by PGE₂ is evident by 24 to 40 hr of culture, persists throughout the entire culture period (including peak deoxyribonucleic acid [DNA] synthesis at 72 to 88 hr and beyond), and does not vary in profundity at any time. By contrast, HAFP-induced suppression of lymphocyte DNA synthesis is lacking at 24 to 40 hr, reaches a peak at 72 to 88 hr, and is waning by 96 to 112 hr. Cultures containing HAFP synthesize more DNA than control cultures during the 120 to 136 hr culture period. These observations, together with our earlier demonstration of a subpopulation of human lymphocytes resistant to HAFP inhibition, suggest that, after the first 24 to 40 hr of culture, HAFP may enhance the proliferation of a suppressor population which gradually dampens the proliferative response. HAFP is capable of suppressing the proliferative response of periodate-treated lymphocytes; this confirms that it does not act via competition with the cell membrane for a mitogen-binding site. Immunofluorescence studies indicate that human peripheral blood lymphocytes lack membrane-associated HAFP or HAFP receptors of high affinity. Our results indicate that PG, either present as a putative contaminant in HAFP isolates or endogenously synthesized by lymphocytes (or monocytes), plays no role in lymphocyte suppression by HAFP.     

Distinctive acral erythema occurring during therapy for severe myelogenous leukemia

A distinctive acral erythema developed in four patients with myelogenous leukemia, subsequent to blood transfusions and intensive chemotherapy with cytarabine. The clinical and histopathologic features of the eruption were suggestive of a drug-induced toxic eruption. To our knowledge, only one previous similar case has been reported in the literature. For patients in whom this self-limited condition develops, reassurance should serve as the mainstay of therapy.