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Biomedical subjects

J G Ratcliffe

Publications and source records attributed to J G Ratcliffe.

At least 109 records · Page 6Linked to original sources

Avoidance of anencephalic and spina bifida births by maternal serum-alphafetoprotein screening.

Screening of 11 585 pregnant women between 16 and 20 completed weeks' gestation for raised serum-alphafetoprotein (A.F.P.) levels showed that the birth of 81.4% of babies with open neural-tube defects could be avoided. The screening test was sensitive enough to detect 93% of those affected and serum-A.F.P. levels above the point at which intervention shouldbe considered were found in 1.7% of pregnancies. After 75.2% of false-positives had been excluded by ultrasonography or by a repeat of the serum test, only 0.63% of pregnancies proceeded to amniocentesis, 46.6% of amniocenteses showed raised amniotic A.F.P. levels due to fetal abnormality. Fetal loss by abortion or perinatal death after amniocentesis occurred in 0.034% of pregnancies screeded, 75% being associated with threatened abortion before amniocentesis. There were no terminations of normal pregnancies due to false-positive amniotic A.F.P. results. It is concluded that voluntary maternal serum-A.F.P. screening has a valuable role in antenatal care.

Amniocentesis↗

Thyroid function in lung cancer.

Thyroid function was assessed at the time of initial diagnosis in 204 patients with lung cancer and compared with that of age and sex-matched patients with non-malignant lung disease. Abnormalities in thyroid function were found in 67 patients (33%). The most prevalent abnormality was a low T3 concentration; this was not associated with other clinical or biochemical evidence of hypothyroidism, but the short-term prognosis of these patients was worse than that of matched patients with lung cancer having normal T3 concentrations. Primary hypothyroidism occurred in three patients, low T4 concentrations and free thyroxine index (FTI) with normal thyrotrophin (TSH) concentrations in four patients, and moderately raised TSH with normal thyroid hormone concentrations in six patients; nine patients had a raised FTI with or without raised T4 concentration as the sole abnormality.Overall, the pattern of thyroid hormone metabolism in lung cancer was a tendency towards reduced T3 concentrations with significantly increased T4/T3 ratios and modestly increased 3,3',5'-triiodothyronine (rT3) concentrations. The altered T4/T3 ratio was particularly noticeable in patients with anaplastic tumours of small ("oat cell") and large cell types, but was not apparently related to detectable extrathoracic metastases.These data suggest that thyroid hormone metabolism is altered in patients with lung cancer by decreased 5'-monodeiodination of T4. The resulting low T3 concentrations and altered T4/T3 ratio may be partly responsible for the reduced ratio of androsterone to aetiocholanolone observed in lung cancer, which is known to be a poor prognostic sign.

Adrenal Cortex Hormones↗

Serum-myelin-basic-protein assay in diagnosis and prognosis of patients with head injury.

Serum levels of myelin basic protein (M.B.P.), a nervous-system-specific protein, were measured in 157 patients after head injury and related both to the type of brain damage and to the clinical outcome assessed three months after injury. Mean concentrations of M.B.P. in patients with severe intracerebral damage, with or without associated extracerebral haematoma, were significantly raised at the time of admission and remained high for two weeks after injury. In patients with extracerebral haematoma not associated with severe intracerebral damage mean M.B.P. values rose four to six days after injury and were significantly raised only in patients with poor eventual outcome. Mean serum-M.B.P. concentrations in patients with a good outcome after injury were similar to those in controls. In patients with a poor outcome the mean M.B.P. levels between two and six days after injury were significantly higher than in those with a good outcome. The assay of serum-M.B.P. may be valuable in assessment of severity of brain damage in patients after head injury and in prediction of outcome.

Blood-Brain Barrier↗

Serum biochemical markers in lung cancer.

The prevalence of elevated serum levels of 5 potential tumour-associated antigens was determined in patients with lung cancer sampled at the time of initial presentation, using age- and sex-matched patients with benign lung disease as controls. Elevated levels (greater than upper 95th centile of controls) were found as follows: carcinoembryonic antigen (CEA), 17%; pregnancy-associated alpha-macroglobulin (PAM), 16%; casein 14%; human chorionic gonadotrophin (HCG) 6%; alpha-foetoprotein (AFP), 1.5%. The prevalence of elevated CEA levels (but not other markers) was higher in patients with evidence of extra-thoracic tumour spread (23%) mainly due to anaplastic tumours and adenocarcinomas. A degree of concordance of elevated marker levels occurred with CEA, HCG, casein and AFP, but there was a striking discordance of elevated CEA and PAM levels. Simultaneous assays of CEA and PAM will detect the majority of patients with elevations of any of the markers studied, and are likely to be the most useful biochemical markers in following the response of lung tumours to therapy.

Adult↗

Mechanism of impaired glucose tolerance in patients with neoplasia.

The disappearance rate (k) of i.v. glucose was measured in cachectic and non-cachectic cancer patients and tumour-free controls. The respective k values were found to be 1.06 +/- 0.27 (mean +/- s.d.), 1.64 +/- 0.34 and 1.63 +/- 0.23. Of the other parameters measured, only plasma albumin level was found to vary significantly amongst the 3 categories, the mean level being the lowest in cachectic cancer patients. The means of total plasma protein, fasting blood glucose and plasma liver enzyme concentrations were similar in the 3 groups. Glucagon, a potent insulin secretogogue, failed to augment the fasting insulin level in cachectic but did so in non-cachectic cancer patients. Taken together, the findings suggest that the reduced glucose tolerance in patients with neoplasia is due to impairment of insulin release exhibited predominantly by ill-nourished advanced cancer patients having a moderate to sever degree of hypoalbuminemia.

Adult↗

Solute, amino acid, and hormone changes with coated charcoal hemoperfusion in uremia.

This investigation assesses the effect of two-hour activated charcoal hemoperfusion using a column containing 300 g of acrylic hydrogel-coated activated charcoal either alone or combined with hemodialysis on small and "middle molecule" removal in uremic patients. Comparison was made with standard five-hour hemodialysis. Two patients with dialysis encephalopathy were treated with four-hour combined hemoperfusion/hemodialysis without beneficial clinical effects. Hemoperfusion increased the clearance rates of creatinine and urate when combined with dialysis. Hemoperfusion alone removed 1.3 +/- 0.6 g (mean +/- SD) of creatinine and 0.6 +/- 0.2 g of urate, while combined hemoperfusion/hemodialysis removed 1.7 +/- 0.6 g of creatinine and 1.0 +/- 0.5 g of urate in a two-hour period. Both treatment schedules removed less solute than standard five-hour hemodialysis but were associated with comparable "middle molecule" removal. Hemoperfusion accounted for additional amino acid removal when combined with hemodialysis, while hemoperfusion alone produced significant reduction only in the amino acid cystine. Changes in the hormones thyroxine, triiodothyronine, human growth hormone, and insulin were noted during the procedures. Acceptable falls in platelet counts and fibrinogen occurred with hemoperfusion. Coated charcoal hemoperfusion may prove to have a role in the management of uremic patients, although the acrylic hydrogel-coated charcoal hemoperfusion device requires combination with techniques allowing fluid and electrolyte removal.

Amino Acids↗

Thyroid function in acute intermittent porphyria: a neurogenic cause of hyperthyroidism?

Thyroid function was investigated in 17 patients with acute intermittent porphyria (AIP). In 13 patients in remission and latent for the disease, thyroid function was normal. In contrast, transient hyperthyoridism with elevated total T4, T3 free T4 and T3, and FTI levels occurred in one pregnant patient with severe attacks of AIP, and similar, though less pronounced, alterations in thyroid function were found in three other symptomatic female patients. It is suggested that increased thyroidal sympathetic neural stimulation is responsible for these changes in thyroid function.

Adult↗

Evidence for thyroidal secretion of 3,3',5'-triiodothyronine in man and its control by TSH.

Thyroidal secretion of 3,3',5'-triiodothyronine (reverse T3, rT3) and its control by TSH was assessed by measuring (1) arterio-venous hormone gradients in patients undergoing surgery, (2) changes of hormone concentrations after induction of anaesthesia, and (3) changes induced by TRH administration. In ten patients in whom thyroid activity was under TSH control (parathyroidectomy and non-toxic goitre) increased thyroid vein/carotid artery ratios (TV/CA) for rT3 (mean TV/CA ratio 2.53) were found when compared to six patients with non-toxic goitre on suppressive doses of T4 (mean TV/CA ratio, 1.27) (P less than 0.05). The mean calculated operative secretion rate of rT3 was 12.5 microgram/day but only 2.4 microgram/day in patients receiving T4. In thirteen patients undergoing elective surgery induction of anaesthesia significantly increased rT3 levels. In nine euthyroid adults intravenous TRH (200 microgram) increased peripheral venous rT3 levels between 3 h (P less than 0.005) and 8 h (P less than 0.05) after the injection. It is concluded that significant amounts of rT3 are secreted by the thyroid gland at operation and this is, in part, under TSH control.

Adult↗

Hyperprolactinaemia in renal disease.

Basal prolactin concentrations in 357 patients with renal disease of defined pathology have been compared with those in 210 control subjects. Elevated prolactin concentrations were found in 113 renal patients (32%) including 53 patients in whom elevated concentrations were possibly attributable to drug therapy. In the remaining 60 patients who had hyperprolactinaemia not attributable to drugs, elevated concentrations (P less than 0.005) were found exclusively in patients with impaired renal function. A significant correlation was observed between prolactin and creatinine concentrations in these patients (r = 0.45 P less than 0.005) and prolactin reverted towards normal after successful renal transplantation. A significant arteriovenous prolactin concentration difference across the kidney (mean 16% range 8-29% P less than 0.02) was found in seven patients with non-renal non-endocrine disease. It is concluded that the hyperprolactinaemia found commonly in patients with impaired renal function is only partly attributable to drug therapy. The positive correlation between prolactin and creatinine reversion of prolactin towards normal after successful transplantation and arteriovenous hormone concentration differences across the normal kidney suggests that the kidney has a important role in prolactin metabolism. Abnormal regulation of prolactin secretion in renal failure may also be involved.

Adolescent↗

Pituitary function in Down's syndrome.

Pituitary function studies have been carried out in eight male and eight female patients with Down's syndrome who were suspected of having hypothyroidism secondary to pituitary deficiency. In all cases, the response of Human Growth Hormone to hypoglycaemia was adequate and the response of Lutenising Hormone and Follicle Stimulating Hormone to the injection of Lutenising Hormone and Follicle Stimulating Hormone was not signfiicantly greater than that in age and sex-matched institutionalised controls. Therefore there is no evidence that the relative hypothyroidism in these patients is due to pituitary hypofunction, nor do the results provide evidence of pituitary deficiency in Down's syndrome generally.

Adult↗

A critical comparison of the value of pregnancy-associated alpha2-glycoprotein and carcinoembryonic antigen assays in patients with colorectal cancer.

Absolute serum concentrations of pregnancy-associated alpha2-glycoprotein (alpha2-PAG) and carcinoembryonic antigen (CEA) were compared in 54 patients before and after surgery for colorectal cancer. Preoperatively, elevated levels of alpha2-PAG were found in 32 (59%) and of CEA in 35 (65%). Postoperatively, elevated alpha2-PAG levels were found in 10 of 18 patients (56%) without clinical evidence of recurrence whereas elevated CEA levels were present in three (16%). In patients who developed clinical evidence of tumour recurrence, alpha2-PAG levels were elevated in 8 of 13 (62%) while CEA levels were uniformly abnormal. It is concluded that, in this cross-sectional study, measurement of alpha2-PAG concentrations is less reliable than CEA in the detection of tumour recurrence after apparently curative surgery for colorectal cancer.

Adult↗

A study of thyroid function in psychiatric in-patients.

The prevalence of abnormal serum total thyroxine (T4) and triiodothyronine (T3) concentrations were determined in 1,206 in-patients in two associated psychiatric hospitals. The biochemical pattern of primary hypothyroidism occurred in five females and one male (prevalence 0.5 per cent), but in only one patient was the diagnosis clinically obvious. Eight patients (all female) were clinically hyperthyroid (prevalence 0.7 per cent), of whom six were previously undiagnosed. There was no evidence that phenothiazines or benzodiazepine therapy had any significant effect on thyroid hormone levels. The small differences in thyroid hormone levels between psychiatric diagnostic groups could be explained by differences in age distribution.

Adolescent↗