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Biomedical subjects

C Smith

Publications and source records attributed to C Smith.

At least 829 records · Page 46Linked to original sources
PubMed1987

Antitumor imidazotetrazines. 14. Synthesis and antitumor activity of 6- and 8-substituted imidazo[5,1-d]-1,2,3,5-tetrazinones and 8-substituted pyrazolo[5,1-d]-1,2,3,5-tetrazinones.

The systematic variation of the potent antitumor agent mitozolomide (1) is extended to cover alteration of substituents at positions 6 and 8 and to change the imidazo[5,1-d]-1,2,3,5-tetrazinone (1) skeleton to the isomeric pyrazolo-[5,1-d]-1,2,3,5-tetrazinone (17) skeleton. The series of eight 6-alkyl and 6-aralkyl derivatives of 1 showed optimal antitumor activity when the group was small or linear, but activity diminished as size and branching of this substituent increased. This may reflect altered transport characteristics, or failure of the enlarged derivatives to fit a binding site, or possibly a reduced tendency for the derivatives having bulky groups at position 6 to hydrolytically generate the putatively active triazenes (21). Testing of 14 derivatives of 1 differently substituted at position 8 revealed a complex structure-activity relationship, with good antitumor activity obtained for carbamoyl and sulfamoyl groups bearing small substituents. The 8-methylsulfonyl compound had noteworthy activity, but the 8-cyano, 8-nitro, and 8-phenyl derivatives were devoid of useful antitumor activity in these tests. From the limited number of pyrazolotetrazinones (17) reported here, it is suggested that the same conclusions as regards activity also hold true for this ring system.

Animals↗
PubMed1987

Increased arachidonic acid levels in phospholipids of human colonic mucosa in inflammatory bowel disease.

1. Colonic mucosa from 19 patients with ulcerative colitis, eight with Crohn's disease and 14 controls were analysed for arachidonic acid (C20:4), linoleic acid (C18:2), oleic acid (C18:1), stearic acid (C18:0) and palmitic acid (C16:0). 2. Gas-liquid chromatography of lipid extracts showed that arachidonic acid was significantly higher in ulcerative colitis (19 +/- 4) and Crohn's disease (20 +/- 3) than in controls (13 +/- 5 micrograms/mg of protein) (means +/- SD). Neither the degree of inflammation nor treatment with sulphasalazine or prednisolone appeared to influence the fatty acid concentrations. 3. Seventy-five to ninety-five per cent of the arachidonic acid was found in the phospholipid fraction after separation by thin-layer chromatography. There were no significant changes in the concentrations of the other fatty acids measured, although oleic acid was lower in inflammatory bowel disease. The ratios of oleic acid to stearic acid and to palmitic acid were lower in inflammatory bowel disease. 4. The alteration in the fatty acid profile may partly explain the increased synthesis of eicosanoids in colonic mucosa in inflammatory bowel disease.

Adolescent↗
PubMed1987

Interleukin 4 (B-cell stimulatory factor 1) can enhance or antagonize the factor-dependent growth of hemopoietic progenitor cells.

Our studies show that although interleukin 4 (IL-4) fails to stimulate significant colony formation by bone marrow progenitor cells, it enhances erythroid, granulocyte, macrophage, and mast-cell colony formation when used as a costimulant with erythropoietin, granulocyte colony-stimulating factor, macrophage colony-stimulating factor, and interleukin 3 (IL-3), respectively. In contrast, IL-4 suppresses IL-3-dependent colony formation by granulocyte and macrophage progenitor cells and by multipotential progenitor cells. Furthermore, it appears to inhibit the in vitro generation of colony-forming progenitor cells from immature IL-3-dependent stem cells. We also found that IL-4 inhibits stromal cell-dependent growth of bone marrow-derived pre-B cells. The ability of IL-4 to directly or indirectly regulate both positive and negative aspects of progenitor cell growth is discussed.

Animals↗
PubMed1987

Elderly immigrants--a disadvantaged group?

Asian, Caribbean and British born Nottingham hospital discharge rates of people of pensionable age for a variety of diagnoses and elective surgery were compared. No evidence of under-utilization of services by immigrants was found, but marked excess discharges were observed for tuberculosis, diabetes, asthma, gastrointestinal bleeding and cataract surgery. Increased hospital use for most diagnoses probably reflects true differences in disease risk between immigrants and the indigenous population.

Aged↗
PubMed1987

Internal countershock produces myocardial damage and lactate production without myocardial ischemia in anesthetized dogs.

The global myocardial extraction of lactate was measured in 13 halothane anesthetized dogs to assess the effect of electric countershock applied directly to the heart. Seven animals received two countershocks of 30 delivered joules each, while six animals were not shocked but were atrially paced to a rate of 190-200, both with and without occlusion of the vena cava to produce a mean arterial pressure of 40-50 mmHg. All animals had substantially positive lactate extraction in the baseline state (36 +/- 10% for countershock group vs. 41 +/- 3% for pacing group). Myocardial lactate extraction reached a markedly negative nadir 2.5 min after countershock (-19 +/- 15%), but returned toward normal by 6 min (10 +/- 6%). Lactate extraction was not significantly changed from baseline in the pacing group. The relationship between changes in regional myocardial blood flow (radiolabeled microspheres) and post-countershock myocardial damage (technetium pyrophosphate uptake) was assessed in six dogs shocked as above. Mean myocardial blood flow was increased minimally immediately after countershock (0.78 +/- 0.08 ml X min-1 X g-1 vs. 1.16 +/- 0.3), but there was no difference in blood flow between damaged and undamaged tissue at either time point. The epicardial-to-endocardial ratio of blood flow was unchanged after countershock (0.97 +/- 0.05 vs. 0.99 +/- 0.08). There was no relationship between myocardial damage and either the absolute amount of blood flow after countershock (r = -0.03) or the change in blood flow compared with the pre-shock period (r = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Deaths from urologic injury due to external trauma.

The priority for treatment of a urologic injury in multiple injured patients from external trauma should be determined by the frequency of death from the urologic injury. The medical records of 2,058 patients with urologic injury from external trauma including 214 deaths were reviewed. Four deaths were attributed mainly to the urologic injury; one early in the postinjury period from continued severe hemorrhage from a ruptured kidney managed conservatively and three 6 to 8 weeks after injury from sepsis with a pelvic abscess from a ruptured urethra or bladder. The remaining 210 deaths were attributed to the associated injuries and occurred in the more severely injured older patients compared to the survivors. Death in multiple injured patients was rarely due to the urologic injury.

Adult↗
PubMed1987

Long-term cultivation of canine keratinocytes.

The growth characteristics and morphology of canine keratinocytes grown in vitro were studied. Keratinocytes from canine oral mucosa, ear skin, and ventral abdominal skin were grown in culture either as explants or as dispase/trypsin-derived suspensions in the absence of a feeder cell layer. Cholera toxin and epidermal growth factor were essential to the successful long-term growth and propagation of the cells during multiple passages. Keratinocytes from all tissue sources, either as primary cultures or subcultivated for up to 10 passages, had growth characteristic and morphology similar to that reported in other species. The use of cultured canine keratinocytes should provide a suitable model for comparative in vitro studies of the pathogenesis of dermatologic diseases.

Abdomen↗
PubMed1987

Cardiovascular and hormonal responses to thyrotrophin releasing hormone in acromegalics.

The effect of TRH (200 micrograms) on blood pressure, pulse rate, TSH and GH release was investigated in 10 acromegalics, four patients with non-GH secreting pituitary tumours, and seven normal controls. TRH produced a rapid-onset, short-lived pressor response in the acromegalic group (delta mean blood pressure 33 mmHg) compared to the two control groups (P less than 0.001). There was no response to the same volume of saline. The pressor response in the acromegalic group was not different in those who did or did not release GH. The pressor response to TRH was linearly related over the range 50-200 micrograms. Measurement of plasma noradrenaline and plasma renin activity during TRH testing in six acromegalics indicated that the pressor effect was neither mediated by adrenergic mechanisms, nor the renin-angiotensin system. Echocardiographic monitoring in five of these six patients showed that there was a significant increase in directly measured end systolic, end diastolic dimensions and heart rate (all P less than 0.02), and calculated stroke volume (P less than 0.001) and cardiac output (P less than 0.01) without changes in systemic vascular resistance. These data suggest that increase in preload, probably via venoconstriction, is the most likely factor producing the pressor response to TRH in acromegalics.

Acromegaly↗
PubMed1987

Long-term results of conservative and surgical management of blunt renal lacerations.

In the management of renal lacerations most attention has centered on surgical or non-surgical treatment and little attention has been given to the long-term results. We have evaluated the medical records and radiographs of 70 patients with blunt renal lacerations; 30 had initial non-surgical management and 40 had initial surgical management. Patients with initial non-surgical management were followed up for an average of 40.4 months. Normal blood pressure and/or radiological evaluation of the kidney were noted in 22% of those who had non-surgical management (hypertension in 55%) and in 75% of those who had delayed renal surgery (hypertension in 29%). Patients with immediate surgical management were followed up for an average of 49.6 months and normal blood pressure and/or radiological evaluation of the kidney were present in 83% (no hypertension). On long-term follow-up, patients with non-surgical management had a much higher rate of hypertension and/or abnormal radiological evaluation of the kidney than those with immediate surgical management.

Adolescent↗
PubMed1987

Changes of blood flow in oestrogen-induced hyperplastic anterior pituitary lobe following bromocriptine administration.

Anterior pituitary hyperplasia and histologically verified adenomas were induced by diethylstilboestrol (DES) containing implants in a total of 104 female F344 rats. Thirty rats were used as controls. Blood flow in the anterior pituitary (PBF) was measured using the hydrogen clearance method. PBF was progressively reduced to 25% by DES in 13 weeks but the total adenohypophysial blood flow (flow as measured per unit weight multiplied by weight of the gland) was raised by 75%. Bromocriptine (BC, 1 mg/kg intravenously) reduced PBF by a maximum of 27% in tumour-bearing rats. When bromocriptine (1 mg/kg/day subcutaneously) was given for 7 days before the measurements the hyperplastic effect of DES on the pituitary gland and the total blood flow through the pituitary were both reduced by 23%. Reduction of blood supply may be one of the reasons that bromocriptine is clinically useful.

Adenoma↗
PubMed1987

Bacterial protease-induced reduction of chorioamniotic membrane strength and elasticity.

We demonstrated that in vitro exposure to bacterial collagenase and collagenase-producing microorganisms significantly reduces measures of strength (bursting load), elasticity, and work to rupture of human amniochorion in a dose-dependent fashion. An attenuated noncollagenase-producing stain did not alter these measures. These findings support previous suggestions that infection within the lower uterine segment adjacent to the cervix may mediate some instances of premature rupture of membranes.

Amnion↗