Inhibition of nitric oxide synthesis extends cerebrovascular autoregulation during hypertension

In anesthetized intact rats, cerebral blood flow is autoregulated until mean arterial blood pressure (MAP) exceeds 150 mmHg. At higher pressures cerebral blood flow breaks through autoregulation and rapidly increases. However, interruption of the arterial baroreceptor reflex eliminates breakthrough of autoregulation. Thus, breakthrough may reflect active rather than passive vasodilatation. We, therefore, sought to determine if breakthrough depends upon synthesis of the vasodilator nitric oxide. Thirty-eight anesthetized adult male Sprague-Dawley rats were studied. In all, MAP was raised by slow i.v. infusion of phenylephrine. In rats pretreated with the nitric oxide synthase inhibitor L-nitroarginine (L-NA; 22 mg/kg i.v.) or with a combination of L-NA plus D-arginine (D-Arg; 240 mg/kg i.v.), breakthrough did not occur even when MAP exceeded 185 mmHg (L-NA) and 165 mmHg (D-Arg). In contrast, breakthrough occurred in rats treated with L-NA plus L-arginine (L-Arg; 240 mg/kg i.v.) and in rats whose basal vascular tone had been increased by pretreatment with arginine vasopressin prior to infusion of phenylephrine. Removal of sympathetic innervation to cerebral vessels attenuated, but did not eliminate, effects of L-NA on breakthrough. Thus, vasodilatation seen with breakthrough of autoregulation depends upon release of nitric oxide or a nitric oxide donor.     

Mechanism for the Peritectic Reaction and Growth of Aligned Grains in YBa2Cu3O6+x

It is experimentally observed that the peritectic reaction, 211 + liquid → 123, can be driven essentially to completion in 1 h at an undercooling of only ∽30°C. The kinetic data, together with the observed microstructures, are inconsistent with the normal mechanism of the peritectic reaction. It is proposed that the mechanism of the reaction involves dissolution of 211 particles into the liquid and precipitation of solid 123. The aligned grain structure is explained through sympathetic nucleation of new 123 grains on existing grains.     

The effect of random vaccine response on the vaccination coverage required to prevent epidemics

The response people have to vaccination varies because their immune systems differ and vaccine failures occur. Here we consider the effect that a random response, independent for each vaccinee, has on the vaccination coverage required to prevent epidemics in a large community. For a community of uniformly mixing individuals an explicit expression is found for the critical vaccination coverage (CVC) and the effect of the vaccine response is determined entirely by the mean E(AB), where A and B, respectively, reflect the infectivity and susceptibility of a vaccinated individual. This result shows that the usual concept of vaccine efficacy, which focuses on the amount of protection the vaccine provides the vaccinee against infection, is not adequate to describe the requirements for preventing epidemics when vaccination affect infectivity. The estimation of E(AB) poses a problem because A and B refer to the vaccine response of the same individual. Similar results are found when there are different types of individual, but now the mean E(AB) may differ between types. However, for a community made up of households it is shown that the CVC also depends on other characteristics of the vaccine response distribution. In practice this means that estimating a single measure of vaccine effectiveness is generally not enough to determine the CVC. For a specific community of households it is found that the vaccination coverage required to prevent epidemics decreases as the variation in the vaccine response increases.     

Risk stratification using the Society of Thoracic Surgeons Program

In an era of progressive cost containment and public scrutiny, the wisdom of aggressive surgical therapy for high-risk candidates has been questioned. At our center in the previous 24 months, 728 patients with coronary artery disease were entered into The Society of Thoracic Surgeons national database, and the hospital outcomes plus length of stay were analyzed. Patients were separated according to the predicted mortality based on the groupings in The Society of Thoracic Surgeons database: 0 to 5% (453 patients); 5% to 10% (126 patients); 10% to 20% (96 patients); 20% to 30% (17 patients); and 30% and greater (36 patients). There was a close correlation with the predicted rates of mortality. Importantly, the preoperative risk stratification demonstrated a strong correlation with the significant morbidity and excessive length of stay in the highest-risk groups (predicted risk of 20% to > or = 30%). The incidences of the most common complications in the group with the highest predicted risk (> or = 30%) were 28%, renal failure; 33%, ventilator dependence; and 17%, cardiac arrest. In addition, at short-term follow-up (6 to 8 months), a 24.3% mortality was identified in patients with a predicted mortality that exceeded 20%. These data quantify the risks and morbidities associated with the care of seriously ill patients with coronary artery disease and demonstrate the need for professional and public discussions focusing on the association of a high preoperative risk status and the consumption of resources.     

Histomorphometric, physical, and mechanical effects of spaceflight and insulin-like growth factor-I on rat long bones

Pituitary adenylate cyclase activating peptide and vasoactive intestinal peptide belong to the same neuropeptide family. Both peptides are present in nerve fibers in the gastric wall and are thought to be involved in the regulation of inflammatory processes. Experimental ulcers were induced in the rat gastric mucosa by local application of acetic acid. During the healing process we examined the PACAP and VIP innervation by means of immunohistochemistry and in situ hybridization. The ulcer area was examined from day 1 to day 15 after ulcer induction. There was a marked depletion of PACAP in nerve fibers at the ulcer margin from day 1 and onwards. On day 10 and day 15, PACAP-immunoreactive nerve fibers could again be visualized at the ulcer margin. In contrast, VIP immunoreactive nerve fibers were present at the ulcer margin at all time points studied. From day 10 following ulcer induction PACAP- and VIP- immunoreactive nerve fibers were increased in frequency in the smooth muscle beneath the ulcer. An upregulation of VIP and PACAP mRNA was also demonstrated in the myenteric ganglia adjacent to ulcer. The present results indicate that neuronal PACAP and VIP react differently to the inflammation at the ulcer margin but similarly in the smooth muscle during the ulcer healing.     

Learning curve for oesophageal cancer surgery

BACKGROUND: Surgical training and experience are frequently claimed to influence early and late outcome measures. The aim of this study was to examine any improvement in an individual surgeon's performance in one operation over a period of 7 years from initial appointment to date. METHODS: Patients undergoing Ivor Lewis subtotal oesophagectomy performed by a single surgeon between April 1990 and December 1996 were identified from a prospectively compiled oesophageal cancer database. Operating time (abdominal, thoracic and 'one-lung time'), blood loss, transfusion requirements (intraoperative and total), extent of lymphadenectomy (number of lymph nodes sampled), intensive treatment unit (ITU) stay, hospital stay, postoperative morbidity and mortality, pathological stage, grade and survival were recorded. RESULTS: The records of 150 patients were identified for analysis. The cohort was split into five groups, each of 30 patients operated on consecutively. Each of the groups was comparable for age, sex, smoking history, preoperative haemoglobin and creatinine levels, weight loss, American Society of Anesthesiologists' grade, and histological stage and grade of disease. Analysis of the variables pertaining to operation revealed a significant improvement with time including reduced single-lung operating time (P=0.01), reduced blood loss (P=0.03), reduced transfusion requirement (P < 0.0001), reduced ITU stay (P< 0.0001), reduced inpatient stay (P< 0.0001) and an increased yield of lymph nodes (P < 0.0001). CONCLUSION: This study showed a continuing improvement in a surgeon's performance over a 7-year period. With the current trend to shorter training periods there is a case for continuing supervision of the 'fully trained' surgeon within highly specialist units.