Search PubMed⌕ Search

Biomedical subjects

I Sanderson

Publications and source records attributed to I Sanderson.

16 recordsLinked to original sources
PubMed1995

Tryptophan-derived NK1 antagonists: conformationally constrained heterocyclic bioisosteres of the ester linkage.

The 3,5-bis(trifluoromethyl)benzyl ester of N-acetyl-L-tryptophan 1 (L-732,138) has been identified previously as a potent and selective substance P receptor antagonist. A series of analogs which introduced a 6-membered heterocyclic ring into the backbone of this structure were prepared for evaluation as bioisosteric replacements of the ester linkage of 1. The 2,5-dioxopiperazine 2 had very weak receptor affinity, but 2-oxopiperazine 5 exhibited modest activity. Examination of the conformations accessible to the substituents on these templates led to exploration of the corresponding 5-membered heterocyclic rings. This study culminated in the identification of oxazolidinedione 14 as a suitable ester mimic in terms of the retention of good NK1 binding affinity.

Animals↗
PubMed1995

Differential age effects of mean arterial pressure and rewarming on cognitive dysfunction after cardiac surgery.

Central nervous system dysfunction is a common consequence of otherwise uncomplicated cardiac surgery. Many mechanisms have been postulated for the cognitive dysfunction that is part of these neurologic sequelae. The purpose of our investigation was to evaluate the effects of mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) and the rate of rewarming on cognitive decline after cardiac surgery. Two hundred thirty-seven patients completed preoperative and predischarge neuropsychologic testing. MAP and temperature were recorded at 1-min intervals using an automated anesthesia record keeper. MAP area less than 50 mm Hg (time and degree of hypotension), as well as the maximal rewarming rate, were determined for each patient. Multivariable linear regression revealed that the rate of rewarming and MAP were unrelated to cognitive decline. However, interactions significantly associated with cognitive decline were found between age and MAP area less than 50 mm Hg on one measure, and between age and rewarming rate in another, identifying susceptibility of the elderly to these factors. Although MAP and rewarming were not the primary determinates of cognitive decline in this surgical population, hypotension and rapid rewarming contributed significantly to cognitive dysfunction in the elderly.

Aged↗
PubMed1977

Hepatic structure and function after modified jejunoileal bypass surgery for obesity.

The most serious adverse effect of standard intestinal bypass for obesity is the high incidence of hepatic dysfunction and death from hepatic failure. We therefore examined the long-term effects of a modified form of jejunoileal bypass (in which a greater continuous length of ileum is retained), on liver function in 120 patients. Substantial weight loss (119-0+/-SD 23-3 kg to 82-3+/-18-8 kg) occurred during the first nine months after surgery, accompanied by a significant rise in serum concentrations of bilirubin, alanine transferase, and alkaline phosphatase, and a significant reduction in albumin concentrations. Biochemical changes were unrelated to weight loss or halothane anaesthesia. After weight stabilisation liver function reverted to normal, and four years after bypass sulphobromophthalein retention and hepatic histology did not differ from those in obese controls. There were two postoperative deaths. Three other patients died during the period of rapid weight loss with severe hepatic steatosis. While transient mild impairment of liver function is common after modified jejunoileal bypass, clinically significant hepatic dysfunction is a rare and unexplained early complication.

Adult↗
PubMed1976

Metabolic studies in total parenteral nutrition with lipid in man. Comparison with glucose.

A study was undertaken of patients on a regimen of total parenteral nutrition comparing the nitrogen balance, energy substrates, blood amino acids, immunoreactive insulin, and immunoreactive glucagon levels during the sequential infusion of nonprotein calories as either glucose alone (glucose system) or 83% as Intralipid (Pharmacia Fine Chemicals, Montreal, Canada) and 17% glucose (lipid system). These nonprotein calories were administered with a constant background of amino acids (1 g/kg per day), vitamins, and minerals. Each system was infused for a week at a time and the order of infusion randomized. In some patients whole blood arteriovenous (A-V) levels of amino acids were measured across forearm muscle. During the glucose system there was a significantly higher level of pyruvate, lactate, alanine, and immunoreactive insulin, consistent with glucose being the principal source of energy. In contrast, during the lipid system there was a rise in free fatty acids and ketone bodies with a fall in insulin, suggesting that lipid was now the principal source of energy. Despite these two very diverse metabolic situations the nitrogen balance with both systems was positive to a comparable degree after the establishment of equilibrium. Correspondingly, A-V differences of whole blood amino acid nitrogen showed uptake by muscle to an equivalent degree with both systems. Clinical studies indicated that the lipid system as defined herein could be infused by peripheral vein for up to 43 days with resultant weight gain, elevation of serum proteins, and healing of fistulae. Our studies suggest that for both metabolic and clinical reasons exogenously infused lipid is a suitable source of nonprotein calories.

Adult↗
PubMed1975

Studies of sensory conductions. Comparison of latencies of orthodromic and antidromic sensory potentials.

Latencies of orthodromic and antidromic sensory potentials were compared in 16 normal median nerves. Peak latency was longer in the antidromic sensory response in every case. The peak latency of the antidromic sensory response depended on the distance between the recording electrodes; with shorter interelectrode distances it was similar to that of orthodromic sensory response.

Action Potentials↗
PubMedDate not supplied

The handling of glucose and insulin response before and after weight loss with jejuno-ileal bypass: a preliminary report.

Glucose and insulin response were studied in morbidly obese patients before and after jejuno-ileal bypass. Postbypass studies were performed after weight loss greater than 30% (9-48 mon). Six-hour oral glucose tolerance tests were performed on 33 patients before bypass and on 13 of these 33 patients after bypass. Thirteen patients had preoperative intravenous glucose tolerance tests performed, and 11 had postbypass intravenous glucose tolerance tests performed. Plasma insulins were drawn concomitantly. Before bypass, fasting blood sugars and insulins were elevated and both glucose intolerance and hyperinsulinemia were found on the tests. After bypass, oral glucose tolerance test curves were flat (malabsorption effect), while intravenous glucose tolerance tests revealed nonsignificant changes in the glucose curves but plasma insulin response returned toward normal (p greater than 0.05). The glucose intolerance and hyperinsulinemia found in these massively obese patients reverted toward normal after weight loss from jejuno-ileal bypass. Thus elevated plasma insulin does not appear to be a primary etiological factor in obesity.

Adult↗