Inhibition of neurally-evoked transmitter release by calcium channel antagonists in rat parasympathetic ganglia.

1. Excitatory postsynaptic potentials (e.p.s.ps) were recorded from the submandibular parasympathetic ganglia of newborn rats (10-20 days old), by intracellular microelectrode recording and a suction electrode to deliver stimulus trains to the lingual nerve (15 stimuli at 0.1, 0.3, 1, 3, and 10 Hz, 22 degrees C). Only evoked responses without voltage-dependent action potentials were analyzed (observed at membrane potentials negative to -70 mV), and e.p.s.p. amplitudes were determined for the plateau responses during each train (5-15th response). 2. Cadmium, an inorganic calcium channel antagonist, reduced e.p.s.p. amplitudes in a dose-dependent manner (Kd 74 microM, P less than 0.01). Nickel (1-300 microM) did not attenuate the amplitude of evoked responses. 3. Verapamil (0.1-30 microM), a phenylamine, had no significant effects upon e.p.s.p. amplitudes at any frequency examined. Higher concentrations of verapamil (100 microM) blocked neurally evoked responses in a manner consistent with the antagonism of voltage-sensitive sodium currents. 4. Diltiazem, a benzothiazepine, reduced e.p.s.p. amplitudes in a dose-dependent manner, the depression being accentuated at high stimulation frequencies (80% block at 30 microM and 10 Hz). The pure (-)-cis enantiomer of diltiazem (10-30 microM) was without effect. 5. Amlodipine, a 1,4-dihydropyridine, did not antagonize synaptic transmission at any stimulus frequency examined (10-30 microM, 0.1-10 Hz, n = 3). 6. Amiloride, a potassium-sparing diuretic, depressed the amplitudes of evoked responses in a dose-dependent manner (one-site Kd 31 microM, P less than 0.005), although the extent of the block was alleviated with high stimulus frequencies. The effects of 30 microM amiloride were unlikely to be of post-synaptic origin as both the amplitudes of miniature e.p.s.ps, and the iontophoretic potentials induced by exogenous acetylcholine, were not attenuated by treatment with this compound. The amiloride derivative, 3',4'-dichlorobenzamil was ineffective in reducing the amplitude of e.p.s.ps (30-100 microM). 7. omega-Conotoxin GVIA, a marine neurotoxin, which depressed whole cell calcium currents recorded from cultured rat parasympathetic cardiac neurones (up to 90% block at 10 nM), was ineffective at blocking synaptic transmission in submandibular ganglia (0.1-1 microM). 8. The differential effects of these calcium channel antagonists upon synaptic transmission in rat parasympathetic ganglia, suggest that either more than one type of calcium channel may be involved in transmitter release, or that the presynaptic calcium channels possess pharmacological sensitivities different from those of channel types described in ne     

Operative cholangiography

The value of operative cholangiography in the management of biliary tract disease has been questioned. To better define the role of cholangiography, we reviewed 579 consecutive cholecystectomies done by 1 group of surgeons in a small rural practice over 8 years. Cholangiography demonstrated unsuspected common bile duct disease in 5% of the procedures, while 12% of the patients were spared an unnecessary choledochotomy after a normal cholangiogram was obtained. There was no morbidity, mortality, or prolongation of the hospital stay attributed to the cholangiographic procedure. These findings bolster the argument for routine cholangiography as a safe, effective, and helpful screening examination for patients who are at risk for having common bile duct disease.     

The flow cytometric crossmatch and early renal transplant loss

Data from this retrospective study indicate that a positive two-color T and/or B cell flow cytometric crossmatch (FCXM) is predictive of early renal allograft loss (less than 2 months) in cadaveric kidney donor recipients who had a negative crossmatch by the antihuman globulin complement-dependent cytotoxicity technique. Among 90 cadaveric kidney donor recipients (67 primary, 23 regrafts), 14 (8 primary, 6 regrafts) lost their renal allografts within 2 months, and 10 of the 14 were FCXM positive and HLA sensitized. The remaining 76 allografts survived beyond 2 months, 12 of which were FCXM-positive. Thus, the FCXM sensitivity rate for detecting early graft loss was 71%, and the specificity rate was 84%. Cadaveric graft-loss rates at 2 months were 33% for primary and 60% for FCXM-positive regrafts in contrast to 7% for primary and 0% for FCXM-negative regrafts. The difference in early graft loss between FCXM-positive and FCXM-negative recipients was statistically significant (P less than 0.0001). Subset analyses of FCXM-positive graft recipients indicate: (1) previous early graft loss contraindicates transplantation of an FXCM-positive regraft (P = 0.03); and (2) panel reactive antibody (PRA) less than or equal to 10% at crossmatch is not associated with early graft loss (P = 0.04). There was no significant difference in 1-year graft survival between primary and regrafts in either FCXM-negative recipients (85% vs. 77%, respectively) or FCXM-positive recipients (67% vs. 40%). All 12 of the FCXM-positive primary and regrafts that survived 2 months continued to function at 2 years. Stepwise logistic regression analysis of 5 independent predictor variables (FCXM status, gender, primary vs. regraft status, PRA level, and HLA mismatched antigens) indicated that the FCXM test was the best predictor of early graft loss. When FCXM results of the 90 cadaveric graft recipients were ranked in three groups, an FCXM channel shift of 29 or greater (third tertile) on a 1024 channel log scale was associated with a 7.0-fold (95% confidence interval 1.9-25.5) increased risk of early graft failure when compared to the first two tertiles. These data indicate that the FCXM offers an additional approach for identifying sensitized patients at risk of early renal allograft loss.     

Cyclosporine A inhibition of microcystin toxins

Cyclosporine A (CyA) given i.v. at a dose of 1.25 mg/mouse blocks a subsequent i.v. lethal dose (1.7-1.8 x LD50) of microcystin-LR for 24 hr, and is about 50% protective at 48 hr. Conversely, the fraction of mice that can be rescued by CyA (0.2 mg/mouse) after a lethal dose of microcystin-LR decreases rapidly with a pharmacodynamic half-time of only about 100 sec. The prophylactic action of CyA was tested against lethal doses of four microcystins. The acute lethality of 1.7-1.8 x LD50 dose of microcystin-LR, -RR, -LY, or -LA given 1 hr after administration of 0.2 mg of CyA is 0%, 0%, 58%, or 100%, respectively. Even a 0.6 mg/mouse dose of CyA is ineffective prophylaxis against a lethal dose of microcystin-LA. The inhibitory potency of CyA on microcystin toxicity can be completely reversed by the single L-amino acid substitution of alanine for arginine in the microcystin.     

Schultz metacarpophalangeal arthroplasty: a long-term follow-up study

We describe a prospective, long-term evaluation of the Schultz metacarpophalangeal joint implant. The prosthesis is a semiconstrained, cemented implant with a ball-in-socket articulation. Thirty-six implants were followed for an average of 10.9 years. There was a progressive decrease in range of motion and strength and a recurrence of ulnar deviation. The neck of the proximal phalangeal component fractured in 39% of the joints. Periarticular heterotopic bone formed in all joints, but was extensive in only 22%. Although some lucency of the bone-cement interface was seen in 80% of the joints, no prosthetic loosening occurred in this series. Our results indicate that long-term, intramedullary cement fixation of relatively long-stemmed components can be satisfactory. However, the articulated portion of this implant does not consistently withstand the stresses transmitted across the joint and does not provide long-term joint stability.     

Use of sterile gloves in the management of sutured hand wounds in the A&E department

In a single-blind, controlled, prospective trial of 242 sutured wounds of the hand in the A&E department there was increased late purulent infection in those treated without gloves. This difference is statistically significant. We recommend wearing of sterile gloves to suture all wounds in A&E departments.