Comparative plasma catecholamine and hemodynamic responses to handgrip, cold pressor and supine bicycle exercise testing in normal subjects

Serial hemodynamic and plasma catecholamine responses were compared among 10 healthy men (27 +/- 3 years) (+/- 1 standard deviation) during symptom-limited handgrip (33% maximal voluntary contraction for 4.4 +/- 1.8 minutes), cold pressor testing (6 minutes) and symptom-limited supine bicycle exercise (22 +/- 5 minutes). Plasma catecholamine concentrations were measured by radioenzymatic assays: ejection fraction and changes in cardiac volumes were assessed by equilibrium radionuclide angiography. During maximal supine exercise, plasma norepinephrine and epinephrine concentrations increased three to six times more than during either symptom-limited handgrip or cold pressor testing. Additionally, increases in heart rate, systolic blood pressure, rate-pressure product, stroke volume, ejection fraction and cardiac output were significantly greater during bicycle exercise than during the other two tests. A decrease in ejection fraction of 0.05 units or more was common in young normal subjects during the first 2 minutes of cold pressor testing (6 of 10 subjects) or at symptom-limited handgrip (3 of 10), but never occurred during maximal supine bicycle exercise. The magnitude of hemodynamic changes with maximal supine bicycle exercise was greater, more consistent and associated with much higher sympathetic nervous system activation, making this a potentially more useful diagnostic stress than either handgrip exercise or cold pressor testing.     

Secretin snuff: evaluation of the action on pentagastrin-stimulated gastric acid secretion and on pancreatic bicarbonate production.

In an informative qualitative study 75 U (near the range of 1 U/kg) secretin given as a snuff resulted in a weak but significant stimulation of pancreatic bicarbonate output in 8 volunteers studied. The result further indicated that this dose would slightly inhibit pentagastrin-stimulated gastric acid secretion. This was confirmed in a quantitative study at the dose of 150 U (similar to 2 U/kg), and the mean amount of inhibition of MAO was 30% in the 10 subjects studied. A supramaximal dose of 1 mg (approximatively 54 U/kg) of synthetic secretin given to one volunteer resulted in a transient block of near maximally pentagastrin-stimulated gastric acid secretion. The amount of acid inhibition as compared to a control experiment was 45% in the first and 52% in the two post-secretin hours. These results indicate that secretin given as a snuff at dose levels that would induce maximal pancreatic secretion when given as an i.v. injection results only in a weak inhibition of stimulated gastric acid secretion and evokes only a little stimulation of pancreatic bicarbonate secretion. Supramaximal secretin snuff doses have, however, a potent effect on both gastric and pancreatic secretion that is of similar order to that achieved by intravenous secretin. Owing to the obviously incomplete absorption of secretin through the nasal mucosa, secretin snuff is unlikely to solve the therapeutic problem of duodenal ulcer disease. If, however, an active fragment of the peptide could be synthetized at a reasonable price, the greater convenience of pernasal application might compensate for the partial loss of action.     

Acute effects of adrenergic-mediated ischemia on nerve conduction in subjects with type 2 diabetes

Several lines of evidence support peripheral nerve ischemia as a contributing factor in the etiology of human diabetic neuropathy. We questioned whether diabetic subjects with relatively normal nerve function in the baseline state would be more likely than healthy control subjects to show either improvement of ulnar nerve function with acute intraarterial infusion of nitroprusside (vasodilation) or be more sensitive than control subjects to worsening of nerve function with acute intraarterial infusion of norepinephrine (vasoconstriction). We measured forearm blood flow (FABF) using venous occlusion plethysmography and assessed ulnar nerve function at baseline and during two intrabrachial artery infusions. Six nondiabetic control subjects (mean age, 56 years) and 11 subjects with type 2 diabetes (mean age, 58 years) in good general health participated. Only three type 2 diabetic subjects had peripheral sensory neuropathy, which was mild. Among control subjects, there was no significant change in sensory distal latency, motor distal latency, motor proximal latency, or sensory or motor conduction velocity during norepinephrine infusion. In contrast, among type 2 diabetic subjects, there was a significant increase in sensory (baseline vnorepinephrine, 2.73+/-0.10 v 2.94+/-0.10 milliseconds [MS], P< or =.01) and motor distal latencies (baseline v norepinephrine, 2.90+/-0.06 v 3.18+/-0.1 ms, P< or =.001) and motor proximal latency (baseline v norepinephrine, 7.15+/-0.18 v 7.60+/-0.23 ms, P<.01) and a decrease in sensory conduction velocity (baseline v norepinephrine, 52.1+/-2.0 v 47.7+/-1.6 m/s, P<.01) during norepinephrine infusion. There were no consistent changes in nerve function during nitroprusside infusion in either group. In summary, we found that subjects with type 2 diabetes, but not control subjects, demonstrate a decrement in nerve function with vasoconstriction during intraarterial infusion of norepinephrine, but no consistent change during nitroprusside-induced vasodilation. These findings suggest there may be enhanced sensitivity of nerve function to ischemia in type 2 diabetic subjects with mild or absent clinical neuropathy.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Healing of experimental gastric ulcers

Grant support: Swiss National Science Foundation (grant 32-26478.89).     

The Waterlow score for risk assessment in surgical patients

Introduction

Perioperative scoring systems aim to predict outcome following surgery and are used in preoperative counselling to guide management and to facilitate internal or external audit. The Waterlow score is used prospectively in many UK hospitals to stratify the risk of decubitus ulcer development. The primary aim of this study was to assess the potential value of this existing scoring system in the prediction of mortality and morbidity in a general surgical and vascular cohort.

Methods

A total of 101 consecutive moderate to high risk emergency and elective surgical patients were identified through a single institution database. The preoperative Waterlow score and outcome data pertaining to that admission were collected. The discriminatory power of the Waterlow score was compared against that of the American Society of Anesthesiologists (ASA) grade and the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM).

Results

The inpatient mortality rate was 17% and the 30-day morbidity rate was 29%. A statistically significant association was demonstrated between the preoperative Waterlow score and inpatient mortality (p<0.0001) and 30-day morbidity (p=0.0002). Using a threshold Waterlow score of 20 to dichotomise risk, accuracies of 0.84 and 0.76 for prediction of mortality and morbidity were demonstrated. In comparison with P-POSSUM, the preoperative Waterlow score performed well on receiver operating characteristic analysis. With respect to mortality, the area under the curve was 0.81 (0.80–0.85) and for morbidity it was 0.72 (0.69–0.76). The ASA grade achieved a similar level of discrimination.

Conclusions

The Waterlow score is collected routinely by nursing staff in many hospitals and might therefore be an attractive means of predicting postoperative morbidity and mortality. It might also function to stratify perioperative risk for comparison of surgical outcome data. A prospective study comparing these risk prediction scores is required to support these findings.