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Biomedical subjects

B Shaw

Publications and source records attributed to B Shaw.

At least 55 records · Page 3Linked to original sources

Catecholamine-containing axon terminals in the hypoglossal nucleus of the rat: an immuno-electronmicroscopic study.

A correlative light and electron microscopic investigation was undertaken to determine the morphology and distribution of catecholamine (CA)-containing axon terminals in the hypoglossal nucleus (XII) of the rat. This was accomplished immunocytochemically with antibody to tyrosine hydroxylase (TH). The major findings in this study were the following: 1) Immunoreactive profiles were found throughout XII and included unmyelinated axons, varicosities, axon terminals and dendrites; 2) Nonsynaptic immunoreactive profiles (preterminal axons, varicosities) were more frequently observed (55.2%) than synaptic profiles (43.5%); 3) CA-containing axon terminals ending on dendrites were more numerous (71.8%) than those synapsing on somata (25.4%) or non-labeled axon terminals (2.7%); 4) The morphology of labeled axon terminals was variable. Axodendritic terminals typically contained numerous small, round agranular vesicles, a few large dense-core vesicles and were associated with either a symmetric or no synaptic specialization, axosomatic terminals were often associated with a presynaptic membrane thickening or a symmetric synaptic specialization and contained small, round and a few elliptical-shaped vesicles, while axoaxonic synapses formed asymmetric postsynaptic specializations; and 5) CA-positive dendritic processes were identified in XII. These findings confirm the CA innervation of XII, and suggest a complex, multifunctional role for CA in controlling oro-lingual motor behavior.

Animals↗

Effects of nitrous oxide on preimplantation mouse embryo cleavage and development.

Preimplantation mouse embryos were exposed to nitrous oxide for 30 min to determine its effects on subsequent development after short durations of exposure. Two-cell mouse embryos were exposed to 60% nitrous oxide/40% oxygen at 6-7 h, 3-4 h, or 0-1 h prior to the expected onset of their first cleavage in vitro, or at the 4-cell or morula stages. Effects of nitrous oxide were not observed except in 2-cell embryos treated within 4 h of the expected in vitro cleavage. At 3-4 h and 0-1 h prior to the onset of cleavage, exposure to 60% nitrous oxide/40% oxygen resulted in blastocyst development rates of 27.7% and 4.7%, respectively, while control rates ranged from 75% to 77%. The majority of affected embryos were halted at the 2-cell stage before completing cell division. Similar effects were obtained with 80% nitrous oxide/20% oxygen. Thus, we conclude that brief exposure of mouse preimplantation embryos to nitrous oxide may be deleterious to subsequent embryo cleavage, but this effect is highly dependent on the developmental stage at which exposure occurs.

Animals↗

One-stage posterolateral decompression and stabilization for primary and metastatic vertebral tumors in the thoracic and lumbar spine.

During the past decade, anterior approaches to the spine have been shown to be much more effective than laminectomy for the relief of pain and neurological deficits due to vertebral metastases. Laminectomy has failed because it does not allow adequate decompression of epidural lesions anterior to the thecal sac. In an effort to combine the advantages of the posterior approach with an adequate decompression, a one-stage posterolateral decompression-stabilization procedure was performed on nine patients with thoracolumbar spine tumors. The approach has been used for decompression and stabilization after thoracolumbar burst fractures. Marked lasting improvement was seen in all six patients with preoperative neurological deficits and in four patients with severe back pain and/or radiculopathy. Three nonambulators and two marginal ambulators could walk postoperatively without assistance. Of five patients who were working preoperatively, four returned full-time to their prior occupations. Three patients had serious complications, including one early postoperative death. No patient deteriorated neurologically due to the procedure. Although the series is small, it demonstrates that adequate one-stage decompression-stabilization of spinal epidural lesions is possible via the posterolateral approach and should be considered in certain cases as an alternative to the anterior approach.

Adult↗

Red blood cells mediate spontaneous aggregation of platelets in whole blood.

The influence of red blood cells on spontaneous platelet aggregation (SPA) has been studied ex vivo. Platelet aggregation was quantified by measuring the fall in single platelet count using a new whole blood platelet counter. When aliquots of whole blood and autologous platelet rich plasma (PRP) were roller-mixed at 37 degrees C, a marked fall in platelet count occurred in whole blood due to SPA but platelet count remained almost unchanged in PRP. When blood from healthy young controls, aged 20-35 years, was compared with healthy old controls, aged 48-80 years, and patients with thrombotic complications, the extent of SPA was in the order: thrombotic patients greater than old controls greater than young controls. Prostacyclin and the new stable prostacyclin analogue Iloprost, at 8 nM effectively inhibited SPA. 2-Chloroadenosine (10 microM) which is an inhibitor of ADP-induced platelet aggregation was also an effective inhibitor of SPA. Acetylsalicylic acid (56 microM) and the thromboxane A2 receptor blocker BM13.177 (0.5 microM) only partially inhibited SPA. ADP from red blood cells is suspected to mediate red cell-induced SPA. However, the possibility that the red cells have an important physical role in SPA cannot be ruled out.

2-Chloroadenosine↗

Sequential calcium and phosphorus balance studies in preterm infants.

Forty-six infant boys less than 1500 g at birth and less than 32 weeks gestation were fed enterally from birth until day 47. Cohorts were given milk formula varying in calcium and phosphorus content: group A, calcium 45 mg/dL, phosphorus 33 mg/dL; group B, calcium 85 mg/dL, phosphorus 33 mg/dL; group C, calcium 125 mg/dL, phosphorus 33 mg/dL; group D, calcium 125 mg/dL, phosphorus 50 mg/dL; and group E, calcium 125 mg/dL, phosphorus 64 mg/dL. Three-day balance studies were begun at days 10, 20, 30, and 40. Calcium net absorption and retention were influenced by postnatal age and calcium intake. Calcium retention best approached intrauterine accretion rates in group C. Phosphorus was well absorbed irrespective of the calcium content of the milk. Phosphorus retention increased with increments in the calcium content of the milk. Increasing the phosphorus content of the milk (groups D and E) resulted in no overall change in calcium absorption and retention but some increments in phosphorus retention.

Birth Weight↗

A critical investigation into the existence of circulating platelet aggregates.

By a method of counting single platelets in diluted whole blood, platelet aggregates were quantified ex-vivo. Four groups: 20 thrombotic patients, 10 non-thrombotic patients, 10 healthy old controls and 10 healthy young controls were included in the study. Using a 19 gauge needle, with and without tubing, venous blood was taken into buffered EDTA, as a disaggregating agent and buffered EDTA-formalin, as the fixative. The amount of platelet aggregates quantified was affected by the quality of venepuncture or the rate of blood flow through the needle, but was unaffected by the presence of the tubing. There was no statistically significant difference between the four groups, in terms of the platelet aggregates quantified, but scanning electron microscopy revealed the presence of irreversible aggregates, composed of platelet red and white blood cells, in the blood of a greater number of thrombotic patients than non-thrombotic or healthy controls. Platelet aggregates were also quantified in aliquots of platelet rich plasma, and were found to be significantly greater than the corresponding values in whole blood. The difference appeared to be due to increased viscosity of the plasma, induced by the fixative which reduces platelet mobility during centrifugation. It is concluded that the platelet aggregates which disaggregate in buffered EDTA may represent an artifact of blood collection; the irreversible aggregates are suspected to represent the in vivo circulating aggregates.

Adult↗

Cardiovascular depression secondary to ionic hypocalcemia during hepatic transplantation in humans.

Cardiovascular function, serum ionized calcium (Ca+2), and serum citrate were measured intraoperatively in patients (n = 9) undergoing orthotopic hepatic homotransplantation. Serum citrate increased 20-fold (P less than 0.0006) following transfusion of citrated blood products in the absence of a functional liver. Serum ionized calcium decreased (P less than 0.003) with concomitant decreases in cardiac index (P less than 0.005), stroke index (P less than 0.004), and left ventricular stroke work index (P less than 0.001). Hemodynamic depression and ionic hypocalcemia were reversed following the administration of CaCl2. In contrast to patients with normal hepatic function, who may tolerate large amounts of citrated blood, patients with end-stage liver disease demonstrate acute ionic hypocalcemia with concomitant hemodynamic depression when receiving citrated blood products during the course of hepatic transplantation.

Calcium Chloride↗

Cyclosporine metabolism and pharmacokinetics following intravenous and oral administration in the dog.

The influence of assay method on single dose cyclosporine (CsA) pharmacokinetics was studied in nine dogs receiving either i.v. or oral CsA. Samples were drawn from hepatic, portal, and systemic veins at various times after the dose and CsA levels were determined by radioimmunoassay (RIA) and high-performance liquid chromatography (HPLC). Blood concentration-time data were analyzed by nonlinear least-squares regression, using two-compartment models. RIA/HPLC ratios for all samples were greater than one, and did not change significantly over time. The mean RIA/HPLC ratios for samples drawn from all three veins were higher after oral than i.v. doses of the drug (P less than 0.05). Area under the concentration-time curve (AUC) was higher and systemic clearance (CIs) lower than calculated on the basis of RIA results, regardless of the route of administration. AUC calculated for CsA metabolites (RIA-HPLC) was highest in the portal vein after an oral dose of CsA. Bioavailability was 20.4% and 27.0% when estimated using HPLC and RIA data, respectively. The mean CsA metabolite index (CMI), when calculated for hepatic, portal, or systemic vein, was greater when the drug was administered orally. The mean hepatic extraction ratio (HER) of the parent drug and for CsA metabolites was approximately 23% in i.v. and p.o. studies. These results suggest that the gastrointestinal tract may play a role in the metabolism of CsA when the drug is administered orally. In addition, if CsA metabolites not measured by HPLC have either toxic or immunosuppressive properties, the RIA assay may be more useful for monitoring patients.

Administration, Oral↗

Syndrome of galactorrhea, amenorrhea, and obesity as possible indicators of prolactinoma: a case study approach.

Four female patients were found to have microadenomas and high prolactin levels, but the symptoms of the syndrome varied among the patients. Three of four patients had overt galactorrhea, obesity, and amenorrhea. One patient was postmenopausal, and another showed menstrual irregularities. Two patients sought medical attention for headaches, and one for visual disturbances. Two patients previously had used psychotropic drugs, and two patients used birth control pills. When tested, all patients had high serum prolactin levels, abnormal sellar tomograms, and the presence of microadenoma of the pituitary was confirmed by computerized tomography.Because of the high incidence of pituitary tumor among these four patients, this study suggests that a complete workup should be done for patients having galactorrhea, amenorrhea, and obesity as a syndrome or as separate entities.

Adenoma↗

Evening primrose oil (Efamol) in the treatment of Raynaud's phenomenon: a double blind study.

Prostaglandin E1 (PGE1) and prostacyclin have been used in Raynaud's phenomenon (RP) but are unstable and require intravenous administration. An alternative approach is to stimulate the body's own PGE1 production via administration of the precursor essential fatty acid. We studied the effect of 12 capsules/day of evening primrose oil (EPO) on the manifestations of RP. 21 patients received a two week course of placebo, thereafter 11 received EPO for 8 weeks and 10 patients received placebo. As the weather worsened the placebo group experienced significantly more attacks than the EPO group. Visual analogue scales assessing the severity of attacks and coldness of hands improved in the EPO group. No changes were seen in either group in hand temperatures and cold challenge plethysmography. Blood tests showed some antiplatelet effects of the drug. In conclusion patients receiving EPO benefited symptomatically. This was not matched however by any change in objective assessment of blood flow, although changes in platelet behaviour and blood prostanoids were observed.

Cold Temperature↗

Double-blind trial of CL115,347, a transdermally absorbed prostaglandin E2 analogue, in treatment of Raynaud's phenomenon.

CL115,347 (Cyanamid International) is a stable transdermally absorbed prostaglandin E2 analogue said to have an antiplatelet vasodilatory effect. In a trial of this drug in Raynaud's phenomenon 15 patients were given 1 mg CL115,347/day transdermally for 6 weeks and 14 were given a placebo. The treated group had fewer and shorter spasm attacks and better healing of ulcers as assessed on a visual analogue scale. Blood supply as measured by cold challenge plethysmography ('Medimatic SP2') was also improved by CL115,347, as were hand temperatures. The treated group also had a significant rise in platelet count, but initial decreases in platelet aggregation were not maintained up to the end of the study.

Administration, Topical↗

Evidence against prostaglandin-mediation of somatostatin-inhibition of gastric secretions.

The inhibitory activities of somatostatin and PGE2 against pentagastrin-stimulated gastric acid and pepsin secretions were investigated, with and without pretreatment with the cyclooxygenase inhibitor indomethacin, in conscious cats prepared with gastric fistulae. Somatostatin was a potent inhibitor of acid secretion in both vagus intact and vagotomized animals, and its effect was not diminished by indomethacin pretreatment. Somatostatin inhibition of pepsin secretion was diminished after indomethacin, but a similar effect was noted with exogenous PGE2, suggesting a mechanism unrelated to inhibition of prostaglandin synthesis. It is concluded that there is no evidence to implicate endogenous prostaglandins in somatostatin inhibition of feline gastric exocrine secretions.

Animals↗

Fungal infections in liver transplant recipients.

Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection. Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P less than 0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P less than 0.05) and antibiotics (P less than 0.05), longer transplant operative time (P less than 0.02), longer posttransplant operative time (P less than 0.01), duration of antibiotic use after transplant surgery (P less than 0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P less than 0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P less than 0.05). A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.

Adult↗

Comparison of the gastric exocrine inhibitory activities and plasma kinetics of somatostatin-28 and somatostatin-14 in cats.

The gastric exocrine inhibitory activities of somatostatin-28 (SS-28) and somatostatin-14 (SS-14) were determined in conscious cats prepared with gastric fistulae. Gastric acid and pepsin secretions were stimulated with pentagastrin. Expressed in terms of exogenous doses, SS-14 (ID50: 1.49 nmol . kg-1 . h-1) was 3.4 times more potent than SS-28 (ID50: 5.12 nmol . kg-1 . h-1) as an inhibitor of gastric acid secretion. Similarly SS-14 (ID50: 0.25 nmol . kg-1 . h-1) was 3.8 times more potent than SS-28 (ID50: 0.96 nmol . kg-1 . h-1) as an inhibitor of pepsin secretion. Expressed in terms of circulating plasma concentration measured by radioimmunoassay, SS-14 (ID50: H+, 232 and pepsin 73 pM) was 8-9 times more potent than SS-28 (ID50: H+, 2112 and pepsin, 611 pM) as an inhibitor of gastric exocrine secretions. The plasma immunoreactive half-life of SS-28 (6.1 min) was double that for SS-14 (2.4 min) possibly due to a slower theoretical metabolic clearance rate of the larger peptide (30 and 87 ml . kg-1 . min-1, respectively). Both peptides had similar apparent distribution volumes (SS-14, 306 and SS-28, 263 ml . kg-1). As judged by gel chromatography of plasma samples, there was no evidence for the conversion of SS-28 to SS-14 in vivo. The reduced activity of SS-28, compared with SS-14, against gastric exocrine secretions contrasts with its more potent effects in the pituitary and pancreas.

Animals↗

Neurotensin inhibition of gastric exocrine secretions in the cat.

The gastric exocrine inhibitory activities of neurotensin were characterized in conscious cats prepared with gastric fistulae. Neurotensin was a potent inhibitor of pentagastrin-stimulated pepsin secretion (ID50, approx. 0.3 mumol . kg-1 . h-1) but was approximately 60 times less potent against acid secretion. Neurotensin did not significantly reduce submaximal histamine-stimulated acid or pepsin secretions. the total 2 h acid and pepsin outputs in response to insulin-hypoglycaemia were not reduced by neurotensin, although the peak 15-min outputs were reduced. The reduction in peak secretion was possibly related to neurotensin antagonism of the ability of insulin to lower blood glucose concentrations. Neurotensin alone was not hyperglycaemic when given as an intravenous infusion. Two C-terminal fragments of neurotensin, the dodecapeptide and nonapeptide, inhibited pentagastrin-stimulated pepsin secretion, but were less potent than neurotensin. The observations with the C-terminal fragments indicate that the major determinants of gastric exocrine inhibitory activity of neurotensin reside in its C-terminal; this agrees with observations on other biological activities of neurotensin. The reduced potency of the dodecapeptide indicates the importance of the N-terminal pyroglutamyl residue for full gastric exocrine inhibitory activity.

Animals↗

Immune responses of sheep to louping-ill virus vaccine.

The immune responses of sheep to single and double doses of commercially available louping-ill virus vaccine were examined. The susceptibility to challenge of sheep which had been vaccinated but showed a poor response was also investigated. Two injections of vaccine were required to provoke an adequate antibody response and maximum titres were obtained when there was an interval of two to eight weeks between injections. After challenge, viraemia could not be detected in animals with an antibody titre of 20 although increase in the concentration of humoral antibodies indicated that infection had occurred. Vaccinated but seronegative sheep and vaccinated animals with an antibody titre of 10 were also clinically resistant to the challenge, although circulation of virus was demonstrated. That vaccination had sensitised those animals to viral antigen was evident from the reduced viraemias, the early rise in humoral antibody titres and subsequent protection afforded compared to unvaccinated control animals. Thus, animals with minimal antibody titres after vaccination are protected, but it is recommended that vaccines eliciting the highest possible antibody responses will be the most useful under field conditions.

Animals↗