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Biomedical subjects

P Lamberton

Publications and source records attributed to P Lamberton.

12 recordsLinked to original sources

Establishment of a neovascular bed in a collagen-impregnated polyurethane sponge.

A technique for promoting vascularization of a polyurethane sponge is demonstrated in the present study. Collagen-impregnated polyurethane sponges (Hypol, 2002) Foamable Hydrophilic Prepolymer (FHP) were implanted in the femoral fossa of rats for 1 day to 6 weeks. The ligated femoral artery/vein was pulled through the sponges to facilitate more complete neovascularization. Light-microscopic evaluation of the implanted sponges revealed that significant vascularization had occurred by the seventh day of implantation, and was maximal by the fourth to sixth week. Sponges containing collagen had a more thorough vascularization process than sponges without collagen, perhaps due to a more uniform pore size as demonstrated by scanning EM. Time course studies suggested that the artery/vein pull-through enhanced the development of the neovascularization process in the center of the sponges. We conclude that significant vascular tissue in-growth can be developed in polyurethane sponges and that both collagen and centrally placed blood vessels help promote the vascularization process. Potential applications could extend to a variety of bioartificial systems including endocrine or hepatic transplantation, soft-tissue prosthetic materials, bone grafts, or drug delivery systems. Further studies would be useful in providing additional information on the factors promoting neovascularization, and on the potential applications of this methodology using the present or similar biomaterials.

Animals↗

Use of semipermeable polyurethane hollow fibers for pituitary organ culture.

A new model for organ culture of endocrine tissue is described. Rat anterior pituitary fragments were cultured for 4 wk within semipermeable polyurethane isocyanate hollow fibers. Growth hormone and prolactin, two of the anterior pituitary hormones, were released into the medium during the entire culture period. Electron microscopy of the pituitary fragments after 2 wk in culture showed a rim of viable tissue in all specimens examined. Individual cells, from this outer rim, exhibited excellent organelle preservation and numerous secretory granules. Experiments involving potassium depolarization and 10(-6) M dopamine provided evidence for the normal responsiveness of the cultured pituitary tissue to both stimulatory and inhibitory factors. These studies illustrate the potential utility of the described organ culture system for further investigations of endocrine physiology.

Animals↗

Prognostic factors in the diabetic hyperosmolar state.

To evaluate the current outcome of patients hospitalized with diabetic hyperosmolar state (DHS), we retrospectively studied 135 patients admitted to two general hospitals over an 11-year period. Mortality was 17%. Patients who died had a mean age of 77 years, compared to 68 years for the survivors (P = 0.008). They were also more likely to be nursing home residents (48 versus 23%, P = 0.01). Additionally, mean serum osmolality was significantly higher among those who died (383 versus 358 mosm/L, P less than 0.0001) as was blood urea nitrogen (81.3 versus 62.3 mg/dl, P = 0.006) and sodium (148 versus 137.4 mEq/L, P less than 0.001). However, mean glucose level and anion gap were similar among patients who died and patients who survived (1068 versus 1092 mg%; 23 versus 24 mEq/L, respectively). The presence of a chronic disease or an acute comorbid illness was not associated with mortality. Diminished physiologic reserve, attendant comorbidity, or functional disability may explain the effect of age and nursing home residence. High osmolality may indicate a greater water deficit and a more advanced stage of DHS at the time of diagnosis.

Age Factors↗

Predisposing factors for the diabetic hyperosmolar state.

To better understand risk factors for the development of diabetic hyperosmolar state (DHS), we studied 135 patients with DHS and 135 age-matched randomly selected diabetic controls admitted to two general hospitals during an 11-year period. To be eligible for the study, patients had to have a hospital admission glucose level of greater than 600 mg/dL (33.3 mmol/L) and an osmolality of greater than 325 mOsm/L (32.5 mmol/L). Patients were significantly more likely than controls to be female (71% vs 53%), to be nursing-home residents (28% vs 15%), to be newly diagnosed diabetics (36% vs 7%), to have a history of dementia (18% vs 8%), and to have an acute infection at the time of admission to the hospital (39% vs 19%). Multivariate analysis revealed three significant independent predictors of DHS: female gender, newly diagnosed diabetes, and acute infection; nursing-home residence and dementia had no independent effect. Other functionally debilitating diseases, acute illnesses, or medications that may impair glucose tolerance were not significantly associated with DHS.

Aged↗

Role of a long-acting somatostatin analogue (SMS 201-995) in the treatment of acromegaly.

The beneficial effect of the long-acting analogue of somatostatin SMS 201-995 in the treatment of acromegaly is described in three cases, and current published experience is reviewed. A total of 64 patients from 10 series have received the drug from one to 25 months, usually in doses of 50-150 micrograms every eight hours by subcutaneous injection. Clinical and chemical improvement was observed in the majority of subjects but normal 24-hour serum growth hormone levels were achieved in no more than 35 percent of this group and possibly less. We have found that higher doses, up to 1,500 micrograms per day, which have generally been free of side effects, are sometimes required to normalize growth hormone secretion. A reduction of up to 33 percent in pituitary tumor size has been reported in more than half of the 27 cases studied from four groups. Clinically important side effects are infrequent, but diarrhea, usually transient, occurred in about 13 percent, with frank steatorrhea in 2 to 6 percent of cases. Alteration in carbohydrate metabolism, such as transient glucose intolerance at the start of therapy in non-diabetic acromegalic patients, and increased sensitivity to insulin or oral hypoglycemic agents in diabetic acromegalic patients, is common. Overall, SMS 201-995 appears to be a valuable new agent for the treatment of acromegaly, but long-term safety needs to be established.

Acromegaly↗

Treatment of resistant acromegaly with a long-acting somatostatin analogue (SMS 201-995).

Six patients with resistant acromegaly were given a long-acting somatostatin analogue (SMS 201-995) for 5 to 12 months. The clinical response was dramatic; relief of headache occurred within minutes of the injection. The mean 24-hour growth hormone levels fell acutely after the administration of 50 or 100 micrograms every 12 hours, especially in four patients with small tumors (p less than 0.001). Dosages of up to 1500 micrograms/d were necessary to produce maximum lowering of growth hormone secretion in some patients. On long-term treatment, plasma somatomedin-C levels fell in all patients and became normal in four. Plasma immunoreactive levels of SMS 201-995 related inversely to growth hormone concentration: A reproducible threshold for growth hormone inhibition in five of the patients, ranging from 70 to 1200 pg/mL, was maintained for 6 to 8 hours after the injections. This somatostatin analogue is effective in the treatment of acromegaly, has no major side effects, and causes only transient changes in carbohydrate metabolism.

Acromegaly↗

Thyrotropin-releasing hormone release from rat pancreas is stimulated by serotonin but inhibited by carbachol.

Immunoreactive TRH (IR-TRH) has been found in the mammalian pancreas, with several studies documenting high concentrations in the late fetal/early neonatal period. As the factors regulating pancreatic TRH synthesis and release have not been fully explored, we developed a monolayer culture system of dissociated fetal/neonatal rat pancreatic cells to study the release of TRH from the mammalian pancreas. IR-TRH was detected in the culture medium and the IR material appeared authentic based on parallelism with synthetic TRH in RIA and retention time on HPLC. Potassium-induced depolarization (60 mM KCl) resulted in a 170% increase in TRH release compared to that by the Krebs-Ringer bicarbonate control (P less than 0.05). Serotonin stimulated TRH release, with the maximal effect seen with 10(-6) M (130% increase compared to control; P less than 0.05). Carbachol resulted in a dose-dependent inhibition of TRH release (57% inhibition of release at 10(-8) M; P less than 0.01 compared to control). There was no effect on release with norepinephrine, epinephrine, dopamine, gamma-aminobutyric acid, or histamine. We conclude the following. 1) Authentic TRH is secreted by fetal/neonatal rat pancreatic cells in culture. 2) The secretion of TRH is stimulated by potassium-induced depolarization in a calcium-dependent manner, suggesting a classic neurosecretory process of release. 3) The secretion of pancreatic TRH may be under specific neurotransmitter control, with serotonin stimulating and acetylcholine inhibiting release of the tripeptide.

Animals↗