Effects of bile acids on ventricular muscle contraction and electrophysiological properties: studies in rat papillary muscle and isolated ventricular myocytes

Summary The effects of sodium salts of various bile acids on the contractile force and the electrophysiological properties of rat ventricular muscle were studied in vitro. Primary, conjugated, and secondary bile acids were studied in a concentration range of 10^–9–10^–6 mol/l, which corresponds to concentrations found in the plasm of patients with cholestatic jaundice. In general, the bile acid induced a negative inotropic effect which was manifested as a reduction in active tension, maximum rate of tension activation, and maximum rate of tension relaxation. Twitch duration and time to peak tension were unaffected by the bile acids. The negative inotropism was associated with a reduction in ventricular action potential duration. Resting potential, action potential amplitude, and maximum upstroke velocity of phase 0 depolarization were unaffected. Voltage clamp experiments in rat ventricular myocytes demonstrated that sodium taurocholate decreased the slow inward current and slightly increased the outward potassium current. Hence, these effects on the membrane currents are probably responsible for the negative inotropic effect. Send offprint requests to O. Binah at the above address     

Localized osteolysis in stable, non-septic total hip replacement

We are reporting four cases of extensive, localized bone resorption adjacent to a rigidly anchored, cemented total hip replacement. None of these hips showed evidence of infection on clinical, bacteriological, or pathological evaluation. The tissue from the regions of osteolysis showed sheets of macrophages and foreign-body giant cells invading the femoral cortices. Abundant methylmethacrylate particulate debris was present in the tissues, but polyethylene wear debris was absent. The histological appearance of this tissue resembled that reported about loosened total hip implants with the exception of the synovial-like layer at the cement surface. The cases reported here show that aggressive bone lysis may occur around stable cemented total hip arthroplasties without the presence of sepsis or malignant disease.     

Bactericidal/permeability-increasing protein in host defense and its efficacy in the treatment of bacterial sepsis

The 55-kD bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived polypeptide belonging to a family of lipid and endotoxin binding proteins. BPI is composed of two functionally distinct structural domains: a potently antibacterial and antiendotoxin ∼ 20-kD aminoterminal half, and an opsonic carboxy-terminal portion. In multiple animal models, a recombinant amino-terminal fragment of BPI (rBPI₂₁) is nontoxic and protects against gram-negative bacteria and endotoxin. In humans, rBPI₂₁ is also nontoxic and nonimmunogenic and has undergone phase II/III clinical trials with apparent therapeutic benefit.     

Adenocarcinoma arising in a chondroid syringoma of vulva.

Chondroid syringoma of the vulva is an extremely rare tumor. Of the previously reported cases, only one was clinically malignant. The authors describe a case of chondroid syringoma of the right labium majus from which arose a papillary adenocarcinoma. A right inguinal lymph node was replaced with metastatic adenocarcinoma.     

Focal glomerulosclerosis in the remnant kidney model--an inflammatory disease mediated by cytokines

BACKGROUND: The mechanism of progression of established renal disease remains unclear. While a low protein diet slows this progression, the role of cytokines in this process has been little investigated. METHODS: We investigated cytokine expression by Northern blot and immunohistochemistry in two groups of 5/6 nephrectomized rats (5/6 Nx) fed a normal (24%) or low (6%) protein diet and compared them with sham operated controls. RESULTS: The rats on 6% protein diet had significantly less focal glomerulosclerosis (FGS) (17.4 +/- 4.4 vs 27.4 +/- 8.8%, P < 0.05) and global sclerosis (GGS) after 7 weeks (0.4 +/- 0.8 vs 3.5 +/- 2.1% of glomeruli P < 0.05). Both experimental groups showed three times control levels of MCP-I expression after 2 weeks. However in the 5/6 Nx 6% protein group the expression decreased at 4 weeks (1.5 times controls) and reached control levels after 7 weeks. In contrast, the 5/6 Nx 24% protein group exhibited a further marked increase after 4 weeks (5.6 times controls) and was still two-fold higher after 7 weeks. TGF-beta expression was modestly but consistently increased at all time points (120-160% of controls), with no difference between the two study groups. Neither IL-1 beta or TNF-alpha was detectable at any time. Immunohistochemistry demonstrated TGF-beta intracellularly in distal tubular cells in both experimental and control animals, while MCP-1 protein was found in the area of FGS and in the apical pole of distal tubular cells in both experimental groups. Glomerular and interstitial ED1 positive cells were significantly increased after four weeks in the 5/6 Nx 24% protein group (P < 0.05). CONCLUSIONS: A 'mechanical' injury to the kidney clearly results in an inflammatory response associated with the upregulation of MCP-1. A low protein diet modulates the expression of MCP-1 and improves the morphological sequelae seen after renal ablation.      

Noninvasive measurement of systemic vascular resistance using Doppler echocardiography.

BACKGROUND: Systemic vascular resistance (SVR) is an integral therapeutic component of patients with heart failure and shock. We hypothesized that the ratio of the peak mitral regurgitant velocity (MRV) (m/s) to left ventricular outflow time-velocity integral (TVI(LVOT)) (cm) by Doppler would provide a noninvasive correlate of SVR. METHODS: SVR was correlated to MRV/TVI(LVOT) in 33 patients undergoing right heart catheterization. Receiver operating characteristic curves were generated to determine the best-balanced sensitivity and specificity to identify SVR > 14 Wood units (WU) and <10 WU. RESULTS: MRV/TVI(LVOT) correlated well with SVR (r = 0.842, 95% confidence interval 0.7-0.92, P <.001, Y = 0.459 + 49.397*X). By receiver operating characteristics, MRV/TVI(LVOT) > 0.27 had a 70% sensitivity and a 77% specificity to identify SVR > 14 WU. MRV/TVI(LVOT) < 0.2 had a 92% sensitivity and a 88% specificity to identify SVR < 10 WU. CONCLUSION: Doppler echocardiography provides a reliable noninvasive assessment of SVR.