Differential effects of monoclonal antibodies to tumor necrosis factor alpha and gamma interferon on induction of hepatic nitric oxide synthase in experimental gram-negative sepsis.

To investigate the stimuli required for the induction of nitric oxide synthase (NOS) in sepsis, we have analyzed the levels of this enzyme in the livers of mice infected with a 90% lethal dose of Escherichia coli in a model of gram-negative sepsis. Hepatic NOS levels are markedly induced in this model, with peak values occurring 12 to 22 h following infection. Treatment with TN3-19.12, a neutralizing monoclonal antibody to tumor necrosis factor alpha (TNF-alpha), resulted in complete protection from death in this model of sepsis but had no significant effect on the level of induction of hepatic NOS. Treatment with H22, a monoclonal antibody to gamma interferon (IFN-gamma), also gave significant protection against death and, in addition, did lead to a decrease in the level of induction of the hepatic NOS. Treatment of mice with pure TNF-alpha (0.2 microgram), IFN-gamma (2,000 U), or a combination of the two did not induce the hepatic NOS, but treatment with the combination led to significant mortality (probability of survival at 22 h, 0.32). Thus, the level of induction of NOS within the liver either in sepsis or by the coadministration of TNF-alpha and IFN-gamma does not correlate with death.     

How negative are we to the idea of suicide prevention?

Assessment of attitudes amongst health care professionals to suicide prevention reveals a considerable degree of doubt with regards to its feasibility and appropriateness. The various professional groups may vary considerably in the degree of negative attitudes which they exhibit. Such findings suggest that there is an urgent need to ensure that health care professionals are fully informed about the key facts concerning suicide and preventive strategies. Key elements of clinical practice and service organization with regards to suicide prevention are discussed.     

Biliary infusion therapy in the inspissated bile syndrome of cystic fibrosis

A 3.5-month-old white boy was born with meconium ileus, peritonitis, and jejunal atresia from cystic fibrosis. He subsequently developed unrelenting and severe extrahepatic biliary obstruction as demonstrated by liver biopsy showing periportal inflammation, cholestasis, and fibrosis. Surgical exploration confirmed the diagnosis of extrahepatic biliary obstruction by severely inspissated bile. A cholecystostomy tube was left in place. The cholestasis remained unresponsive to conservative medical therapy. The obstruction was relieved by hydrostatic infusion of 2% N-acetylcysteine into the biliary tree over a 6-day period. The child also received concurrently four i.v. injections of synthetic cholecystokinin. This therapeutic modality was thought to be both safe and effective.     

The zygomatico-temporal approach to the skull base: a critical review of 11 patients.

The zygomatico-temporal approach to the base of the skull is a relatively new but established surgical technique. The approach involves the removal of the zygomatic bone to provide access to the skull base, middle cranial fossa, parasellar region and interpeduncular cistern with minimal brain retraction. An excellent view of the bifurcation of the basilar artery and suprasellar region is provided. The outcome of 11 patients undergoing this procedure is reported with particular reference to the post-operative morbidity and the cosmetic result.     

Examination of pre- and posttreatment MHPG during cognitive therapy.

Sixteen unipolar depressed patients were treated with cognitive therapy for 12 weeks. Pretreatment 24-hour urinary MHPG levels were unable to predict treatment response. There was a nonsignificant trend for cognitive therapy responders to show a decrease in MHPG during treatment when compared to nonresponders.     

In vitro study of the transfer of cytokine-inducing substances across selected high-flux hemodialysis membranes.

The in vitro transfer of cytokine-inducing substances (CIS) across cellulose triacetate and polyacrylonitrile hollow-fiber high-flux hemodialyzers was studied using culture filtrates of gram-negative bacteria isolated from hemodialysis center environments. With Enterobacter cloacae, no transfer of CIS was seen despite the potent cytokine inducibility and endotoxin content of the challenge solution. In contrast, interleukins 1 and 6 and tumor necrosis factor inducing substances did penetrate both dialyzer types challenged with Pseudomonas aeruginosa culture filtrates containing a high endotoxin content. Transfer was not seen, however, upon dilution of the challenge solution to lower, yet clinically very high levels of endotoxin. These results show that, in vitro, the transfer of CIS across high-flux membranes is critically dependent upon the quality and the quantity of the challenge material employed.     

Adenosine as a vasodilator in primary pulmonary hypertension

BACKGROUND. The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS. The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS. Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension.