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Biomedical subjects

D Griffiths

Publications and source records attributed to D Griffiths.

At least 19 recordsLinked to original sources

Inappropriate circumcision referrals by GPs.

One hundred and twenty boys were referred by GPs over a 12-month period to a paediatric urologist for circumcision. The reasons for referral were: ballooning in 36, non-retraction in 28, balanoposthitis in 36 or a combination in 15. On examination 53% had a retractile, 21% a partially retractile and 21% a non-retractile foreskin. Six patients had obvious balanitis xerotica obliterans. Only one quarter of the patients required a circumcision. The penis was not examined by the referring doctor in 15 patients. The implications of this survey are that a large proportion of general practitioners have difficulty in discriminating between a true phimosis and a developmentally non-retractile foreskin. This diagnostic inaccuracy was greatest when the referring doctor did not examine the patient.

Adolescent

Nitrous oxide sedation causes post-hyperventilation apnoea.

We have studied, in six normal subjects, the effect of nitrous oxide sedation on the ventilatory pattern and oxygen saturation using pulse oximetry (SpO2) after hyperventilation to an end-tidal carbon dioxide partial pressure (PE'CO2) of 3 kPa. This value of PE'CO2 was shown to be less than the apnoeic threshold of all these subjects when their ventilation vs PE'CO2 response curves were plotted. All subjects became apnoeic when told to relax following hyperventilation while breathing 75% nitrous oxide for 90 s. Apnoea was defined as cessation of breathing for 20 s or more. The mean duration of apnoea was 78 s (range 29-130 s). All subjects demonstrated arterial desaturation (mean SpO2 75%, range 44-87%). In contrast, following hyperventilation with air, no apnoea was seen in any subject, although there was some evidence of desaturation (mean SpO2 92.5%, range 88-98%). It was concluded that subjects who are sedated with nitrous oxide behave similarly to those who are anaesthetized rather than to those who were fully conscious, in that they become apnoeic below the apnoeic threshold point. The reduction in SpO2 after hyperventilation was explained almost entirely by apnoea and may explain abnormalities of respiratory control and hypoxaemia in patients recovering from general anaesthesia or sedation accompanied by hypocapnia. This mechanism may be of importance in obstetric patients after breathing Entonox, when apnoea and hypoxaemia may reduce oxygen delivery to the fetus.

Adult

The complement-inhibiting protein, protectin (CD59 antigen), is present and functionally active on glomerular epithelial cells.

Protectin (CD59 antigen) is a 20-kD phosphatidyl-inositol-linked membrane protein that inhibits formation of the membrane attack complex (MAC) of complement on homologous cells. Although the antigen has been identified in a number of human tissues, until recently a functional role had been demonstrated only in circulating cells. Using immunofluorescence techniques we have shown the presence of protectin on human glomerular epithelial cells (GEC) in culture and on GEC, tubular epithelial cells and endothelial cells in frozen sections of normal human renal cortex. In addition, we present evidence that this protein functions in protection of GEC from homologous complement: cultured cells incubated with the Fab2 fragment of a monoclonal anti-protein antibody were markedly more susceptible to killing by homologous serum than were cells in the absence of Fab2 anti-protectin. These findings suggest that this protein may be important in the maintenance of glomerular integrity in vivo, and may be of relevance in certain renal diseases.

Animals

Asymptomatic hypothyroidism and hypercholesterolaemia.

Hypothyroidism is a cause of secondary hyperlipidaemia. This study investigates the frequency of biochemically diagnosed hypothyroidism and its relationship with plasma cholesterol concentration in apparently healthy people. Thyroid function tests (total T4, TSH, and free T4) were performed on 272 apparently healthy men and women (179 vegetarians, 93 meat eaters) with a plasma cholesterol concentration above 7 mmol/l and on 90 individuals with a plasma cholesterol below 4.1 mmol/l who were matched for age, sex and dietary habits. Six per cent of those with a plasma cholesterol above 7 mmol/l had biochemical evidence of hypothyroidism as defined by a TSH greater than 10 mIU/l (reference range 1-6) and a low free T4 below 10 pmol/l (reference range 10.1-25). Eighty per cent of these people had a high titre of thyroid anti-microsomal antibodies. Of the 90 individuals with a plasma cholesterol level below 4.1 and the 25 randomly selected participants none had biochemical evidence of hypothyroidism. Hypothyroidism is relatively common in apparently healthy people with a raised plasma cholesterol. It appears no commoner in vegetarians than in meat eaters.

Adult

Nitrendipine once or twice daily in hypertensive non-insulin-dependent diabetes mellitus.

Twenty (12 male, 8 female) hypertensive patients were recruited into the study; their mean (+/- SD) sitting blood pressure (BP) was 166 +/- 13/101 +/- 4 mm Hg, age 59.6 +/- 5.8 years, weight 83.4 +/- 14.2 kg, and glycosylated hemoglobin (HbA1) 9.9 +/- 2.6%. After a run-in period of 4 weeks, patients were randomized to receive nitrendipine once or twice daily, with 15 patients completing the 12-week study period. Prior to treatment with nitrendipine, the patients subsequently treated on a twice-daily regimen had a higher sitting systolic BP (SBP) of 173 +/- 15 mm Hg compared to the once-daily patient group at 159 +/- 7 mm Hg (p less than 0.05). There were no differences between the two treatment groups in weight or diabetes control. Once-daily nitrendipine effectively reduced the sitting SBP and diastolic BP (DBP), i.e., SBP fell from 159 +/- 7 to 147 +/- 12 mm Hg (p less than 0.05) and DBP fell from 100 +/- 4 to 86.3 +/- 8 mm Hg (p less than 0.001). Nonsignificant reductions in weight from 81.5 +/- 11.3 to 80.9 +/- 11.2 kg and HbA1 from 9.8 +/- 3.3 to 8.4 +/- 1.3% were also seen. Similarly, with twice-daily nitrendipine, a significant (p less than 0.01) fall in sitting systolic BP from 173 +/- 15 to 148 +/- 9 mm Hg and DBP 103 +/- 4 to 85 +/- 8 mm Hg was also achieved. Little or no change was observed in weight or glycemic control in this patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

1,2,4-Triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity. 1. Synthesis and biological properties of alkyl alcohol and statine derivatives.

A series of 1,2,4-triazolo[4,3-a]pyrazine derivatives with human renin inhibitory activity, which incorporate (1S,2S)-2-amino-1,3-dicyclohexyl-1-hydroxypropane, statine (Sta), and (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy-pentanoic acid (ACHPA) transition-state mimetics, have been prepared. Structure-activity relationships for renin inhibitory activity in the series are consistent with the 2-[8-isobutyl-6-phenyl-1,2,4-triazolo[4,3-a]pyrazin-3-yl]-3-(3 pyridyl)propionic acid moiety 10b acting as a non-peptidic replacement for the P4-P2 (Pro-Phe-His) residues of the natural substrate angiotensinogen. Compounds 12m, 12o and 12q were potent inhibitors of partially purified human renin (IC50 values 1.7, 6.8, and 3.7 nM, respectively), and also effectively lowered blood pressure in anesthetized, sodium depleted marmosets following intravenous administration. On oral administration however, no blood pressure lowering activity could be detected, and absorption studies in bile duct cannulated rats indicate that this may be due primarily to poor oral absorption, rather than rapid biliary excretion. The reason for the observed poor oral activity is not clear, but it seems unlikely that poor aqueous solubility or metabolic instability to gut enzymes are rate-determining, and other factors such as high molecular weight may also be very important.

Administration, Oral

Lateral release for recurrent dislocation of the patella.

We reviewed 41 knees after arthroscopic lateral release for recurrent dislocation of the patella at a mean follow-up of four years, and graded the results according to the criteria of Crosby and Insall (1976). There were no dislocations after operation in 28 knees (68%); the less satisfactory results were in patients with subluxation of the patella on extension of the knee and those with generalised ligamentous laxity. There were no complications. A characteristic and previously unreported lesion of the patellar surface was seen in eight of the 41 knees. The results of lateral release are better than those reported for other techniques. This treatment, by either open or arthroscopic methods, is recommended.

Adult

Study of DTH and resistance in Mycobacterium lepraemurium infection using a T-cell line isolated from mice infected with Mycobacterium bovis (BCG).

A T-cell line of mixed phenotype (60% L3T4+, 40% Lyt-2+) was isolated from mice infected with Mycobacterium bovis (BCG). This line responded to M. lepraemurium and BCG but not to M. leprae and produced TCGF spontaneously. It also produced factors which stimulated macrophages to secrete hydrogen peroxide and superoxide anion. In vivo studies showed that only L3T4+ cells were required to transfer DTH responses and that Lyt-2+ cells suppressed this response. Both L3T4+ and Lyt-2+ cells were required to inhibit M. lepraemurium multiplication in vivo.

Animals

Melatonin reduces the production and secretion of prolactin and growth hormone from rat pituitary cells in culture.

A culture of clonal tumour cells from rat pituitary gland that secrete both prolactin and growth hormone were used to investigate whether the pineal hormone melatonin can act directly on the pituitary gland to control prolactin production. Melatonin inhibition of prolactin and growth hormone production was significant but mild. Concentrations of between 10(-8) M and 10(-6) M reduced both prolactin and growth hormone production and prolactin secretion by 10-50%. 17 beta-oestradiol (OE) and thyrotrophin-releasing hormone (TRH) stimulated prolactin production but had no significant effect on growth hormone production. Melatonin reduced the effects of both of these compounds. Both TRH and vasoactive intestinal peptide (VIP) stimulated secretion of prolactin, and TRH also of growth hormone. Melatonin reduced these effects significantly. TRH and VIP increased cAMP production two- and 12-fold, respectively. Melatonin had no effect on basal or stimulated cAMP production. The melatonin-induced changes in prolactin and growth hormone production and secretion seen here do not approach the magnitude of the fluctuations seen in plasma in vivo. It is concluded that while melatonin does have a direct effect on the lactotroph in the regulation of prolactin production, its main physiological target must be elsewhere.

Animals

Anatomical and physiological observations on supraspinal control of bladder and urethral sphincter muscles in the cat.

In 15 cats injections of 3H-leucine were made in the pontine tegmentum. Injections in the medial part of the dorsolateral pontine tegmentum (M-region) resulted in specific projections to the sacral intermediomedial and intermediolateral cell groups. The intermediolateral cell group contains preganglionic parasympathetic neurons that form the motor supply of the detrusor muscle of the bladder. Injections in the lateral part of the pontine tegmental field (L-region) produced labeled fibers in the nucleus of Onuf, which contains motoneurons innervating the pelvic floor including the anal and urethral sphincters. L-region projections to the sacral preganglionic parasympathetic neurons and M-region projections to the nucleus of Onuf were very limited or absent. In 12 cats physiological experiments were performed. Electrical stimulation in the L-region elicited a prompt increase in the pelvic floor EMG and urethral pressure but had little influence on the intravesical pressure. Stimulation in the M-region elicited a prompt decrease in the pelvic floor EMG and urethral pressure followed, after a delay of 2 seconds, by an increase in the intravesical pressure, so simulating normal micturition.

Animals