PubMed Health⌕ Search

Biomedical subjects

R H Mortimer

Publications and source records attributed to R H Mortimer.

At least 37 records · Page 2Linked to original sources
PubMed1993

Blunted parathyroid response to correction of hypercalcemia in subjects with squamous cell carcinoma.

In malignancy-associated hypercalcemia (MAH) elevated plasma calcium levels are believed to inhibit parathyroid secretion independently of the underlying tumor. This predicts that correction of hypercalcemia should disinhibit circulating parathyroid hormone (PTH) levels, irrespective of the underlying disease. We have tested this hypothesis in subjects with multiple myeloma (MM) and squamous cell carcinoma (SCC) treated with pamidronate. In the MM group, PTH levels returned to normal as hypercalcemia was corrected. In contrast, PTH levels remained low in the SCC group despite a similar fall in plasma calcium. Calcitriol levels were significantly higher and magnesium levels slightly lower in the SCC group than those in the MM group. We conclude that the parathyroid response to the correction of hypercalcemia is blunted in subjects with SCC but not MM. In addition to hypercalcemia, other factors, perhaps related to tumor secretion of PTH-related protein, may therefore contribute to suppressing PTH secretion in MAH due to SCC.

Calcitriol↗
PubMed1992

Membrane transport of thyroid hormone in the human choriocarcinoma cell line, JAR.

We studied uptake of L-triiodothyronine (T3) by the human choriocarcinoma cell line, JAR. Uptake was time dependent with a half-time of 56.2 +/- 7.2 min (mean +/- SEM, n = 4). A non-saturable component accounted for about 24% of total uptake. We found a single saturable uptake mechanism with a calculated Michaelis constant (Km) of 586 +/- 206 nM (n = 9) and a corresponding maximum velocity of 17.0 +/- 5.7 pmol/min per mg protein (n = 9), values similar to those we have described recently in cultured normal human trophoblast cells. Uptake was dependent on temperature and intracellular energy, being reduced at lower temperatures and in the presence of potassium cyanide. It was independent of the Na+ gradient across the cell membrane and the presence of Na+ in the external medium, but was affected by the cell membrane potential.

Biological Transport↗
PubMed1992

Uptake of L-tri-iodothyronine by human cultured trophoblast cells.

We investigated the uptake of L-tri-iodothyronine (T3) by cultured human trophoblast cells. Uptake was time-dependent, initially linear and approaching equilibrium after 60 min with an approximate half-time of 13 +/- 4.5 min (mean +/- S.E.M., n = 4). It had a non-saturable component accounting for about 50% of total uptake. We demonstrated a single saturable T3 uptake mechanism with a calculated Michaelis constant (Km) of 755 +/- 145 nmol/l (n = 11-13) and a corresponding maximum velocity of 28.8 +/- 5.3 pmol/min per mg protein (n = 11-13). The Km value was similar to those reported in other tissues.

Cells, Cultured↗
PubMed1991

Selective liquid chromatographic assay for propylthiouracil in plasma.

A liquid chromatographic assay was developed to quantitate propylthiouracil in plasma using an internal standard, 5-propyl-2-thiouracil, of similar structure and physical properties. Caffeine, which coelutes with propylthiouracil, was removed by extraction from serum treated with base. No other compounds were found to interfere in the assay. The drug was extracted from plasma with chloroform with a recovery of 59.4% and the intra- and inter-assay coefficients of variation were 5.7 and 3.3%, respectively. The assay was linear to 3 micrograms/ml with a lower detection limit of 40 ng/ml for a sample volume of 1 ml.

Caffeine↗
PubMed1991

Liquid chromatographic analysis of prednisolone, prednisone and their 20-reduced metabolites in perfusion media.

A reversed-phase liquid chromatographic assay was developed to quantitate prednisolone, prednisone and the 20 alpha-dihydro and 20 beta-dihydro reduced metabolites of both parent compounds in tissue culture media from in vitro perfusions of the human placental lobule. Steroids were extracted from perfusate, using reversed-phase cartridges, with average recoveries of 95.2% or greater. The internal standard for the analyses was 6 alpha-methylprednisolone. In this assay cortisol coelutes with prednisolone, however, no other significant interferences were found. Assay of each steroid was linear in the range 0-1 microgram/ml. Intra-assay coefficients of variation were measured at 10 and 750 ng/ml with ranges of 3.4% (20 alpha-dihydroprednisone) to 8.8% (20 beta-dihydroprednisolone) and 4.1% (20 beta-dihydroprednisone) to 8.8% (prednisone). The corresponding inter-assay coefficients of variation were 3.3% (20 alpha-dihydroprednisone) to 9.1% (20 beta-dihydroprednisolone) and 1.9% (prednisolone) to 3.5% (prednisone). The analyses utilized two C18 columns which were linked together and maintained at 40 degrees C.

Chromatography, Liquid↗
PubMed1991

Metabolism of prednisolone by the isolated perfused human placental lobule.

Previous studies of the metabolism of 11 beta-hydroxy corticosteroids by placental tissue have indicated that the only product is the C11-oxidized metabolite. In the present study we have re-examined the metabolism of prednisolone in the isolated, perfused, dual recirculating human placental lobule, using a perfusate based on tissue culture medium 199. Four metabolites were identified in both the maternal and fetal compartments in 6 h perfusions by comparison of relative retention times measured by HPLC and capillary gas chromatography (GC) and of mass spectra recorded by capillary gas chromatography-mass spectrometry (GC-MS) with those of authentic reference standards. The steroids were derivatized as the MO-TMS ethers for mass spectral measurements. Analysis of samples from five perfusion experiments resulted in the following percentage conversions after 6 h perfusion (mean +/- SD, maternal and fetal perfusate, respectively): prednisone (49.1 +/- 7.8, 49.1 +/- 6.6), 20 alpha-dihydroprednisone (0.84 +/- 0.29, 0.81 +/- 0.35), 20 beta-dihydroprednisone (39.1 +/- 6.7, 39.2 +/- 5.9), 20 beta-dihydroprednisolone (6.8 +/- 2.7, 6.3 +/- 1.6) and unmetabolized prednisolone (4.1 +/- 1.8, 4.6 +/- 2.1). No evidence was found for metabolites formed by 6 beta-hydroxylation or cleavage of the C17-C20 bond.

Chromatography, Gas↗
PubMed1991

Ketoconazole and plasma and urine steroid levels in Cushing's disease.

1. Plasma and urine steroid and plasma ACTH levels were measured for 2 weeks in eight subjects (six female, two male) with Cushing's disease with each given 200 mg ketoconazole orally four times daily. 2. Treatment was associated with major falls in excretion of free cortisol and the cortisol metabolites tetrahydrocortisol, 5 alpha-tetrahydrocortisol and tetrahydrocortisone. 3. Plasma cortisol and ACTH levels did not change significantly. 4. Excretion of the androgen metabolites, androsterone, 11 beta-hydroxyandrosterone and aetiocholanolone was also reduced but there was no significant fall in plasma testosterone. Plasma levels of progesterone, 17 alpha-hydroxyprogesterone and 11 beta-deoxycortisol and excretion of pregnanediol, pregnanetriol and tetrahydrodeoxycortisol rose with treatment. 5. Analysis of steroid precursor/product ratios indicated that ketoconazole significantly inhibited 11 beta-hydroxylase and 17,20-lyase but not 17 alpha-hydroxylase in these patients with Cushing's disease.

Administration, Oral↗
PubMed1991

Single-dose intravenous pamidronate is effective alternative therapy for Paget's disease refractory to calcitonin.

We have conducted an open, prospective study to investigate the efficacy of a single 60 mg infusion of pamidronate as alternative therapy in 15 subjects with severe Paget's bone disease refractory to calcitonin. Disease activity was assessed with a visual-analogue score of symptom severity, plasma alkaline phosphatase and quantitative estimation of 99mTc-methylene biphosphonate uptake on bone scan. All indices of disease activity fell after pamidronate, reaching a nadir at 3 months. Although disease activity increased thereafter, only 3 subjects required retreatment within 12 months. Plasma calcium fell after 3 days and remained below baseline levels for 6 months associated with evidence of secondary hyperparathyroidism. Pamidronate was well tolerated; femoral neck fractures occurred in 2 subjects with severe local Paget's disease but were unlikely to be due to the drug. We conclude that pamidronate is an effective and promising alternative for treatment of patients with severe Paget's disease no longer adequately controlled by calcitonin. Calcium supplementation may be prudent to prevent secondary hyperparathyroidism associated with the use of this agent.

Aged↗
PubMed1990

Acromegaly first diagnosed in pregnancy: the role of bromocriptine therapy.

We report a case of acromegaly diagnosed in the second trimester of pregnancy. Bromocriptine (7.5 mg per day) corrected visual field defects and suppressed prolactin secretion but did not reduce fasting growth hormone levels. We propose that suppression of physiologic lactotroph hyperplasia by bromocriptine may permit noninvasive management of pituitary adenomas during pregnancy.

Acromegaly↗
PubMed1990

Psychological stress and blood glucose regulation in type I diabetic patients.

Fifteen Type I diabetic patients self-monitored daily mean blood glucose levels (BGL), psychological stress, diet, exercise, and insulin injections for a period of 8 weeks. Separate multiple-regression analyses were conducted for each subject to assess the predictability of BGL from stress reports, independent of the effects of diet, exercise, and insulin self-administration. Considerable individual variability in findings was evident, with stress predicting BGL in a statistically significant manner in 7 of the 15 subjects. Stress had a significant effect on BGL independent of diet, exercise, and insulin administration for each of these 7 subjects. Discussion focused on the problems of measuring the key self-management behaviors influencing BGL and on the possibility that a subgroup of diabetic patients may be BGL stress responders.

Adolescent↗
PubMed1990

Graves' disease in pregnancy: TSH receptor binding inhibiting immunoglobulins and maternal and neonatal thyroid function.

We studied interrelationships between maternal and neonatal thyroid function, TSH receptor binding inhibiting immunoglobulins (TBII), and dose of thionamide antithyroid drugs in 44 women with active Graves' disease presenting during 46 pregnancies, and their 48 infants. The women were treated with propylthiouracil (PTU) or carbimazole (CBZ). In 30 pregnancies (30 infants) treatment was withdrawn from 3 to 18 weeks before delivery (Group A). Drug treatment (PTU, n = 10, dose 50-400 mg/day or CBZ, n = 6, dose 5-45 mg/day) was continued throughout pregnancy and delivery in 16 pregnancies producing 18 infants (Group B). The maternal TBII at delivery was well correlated with maternal free thyroxine index (FTI) averaged over the third trimester (r = 0.603, P less than 0.001) and umbilical venous serum TBII (r = 0.940, P less than 0.001). Neonatal FTI was independently related to umbilical vein TBII (t = 2.29, P = 0.03) and maternal dose of antithyroid drug (t = -2.21, P = 0.03). Neonatal thyrotoxicosis was seen in all four infants (8% of births) of women whose TBII levels at delivery exceeded 70%. No child was born with a subnormal FTI but 7/18 infants in group B had raised TSH at birth. This was more likely to occur (P = 0.05) if maternal TBII was less than 30% (6/10) than if maternal TBII was greater than 30% (1/8). Four Group B women with FTI in the lower half of the reference range delivered infants with raised TSH compared with 3/14 (21%) women whose FTI was in the upper half of the reference range or above (P = 0.05). In pregnant women with active Graves' disease TBII levels reflect stimulatory TSH receptor antibody activity. TBII measurements are of use in the prediction of neonatal thyrotoxicosis and impaired neonatal thyroid function in infants of women treated with antithyroid drugs.

Autoantibodies↗
PubMed1989

Lupus anticoagulant.

Explore the source record for details and available documents.

Adrenal Gland Diseases↗
PubMed1989

Role of 131I-metaiodobenzylguanidine in the localization of suspected phaeochromocytomas.

Iodine-131-metaiodobenzylguanidine is a recently-developed radiopharmaceutical agent for adrenal medullary scintigraphy. Twenty-one scans with 131I-metaiodobenzylguanidine were performed in 20 adults with suspected phaeochromocytomas over a four-year period. All patients previously had undergone computed tomographic scans of the abdomen and pelvis. The computed-tomographic scans were abnormal in 14 patients (16 tumours), eight (nine tumours) of whose 131I-metaiodobenzylguanidine scans gave positive results. Both types of scan gave negative results in the remaining six patients. Among 12 patients who underwent surgery or postmortem examination, the 131I-metaiodobenzylguanidine scan correctly showed eight phaeochromocytomas; six tumours that were found on computed-tomographic scans but not on 131I-metaiodobenzylguanidine scans proved not to be phaeochromocytoma. The 131I-metaiodobenzylguanidine scan probably gave a true-positive result in an additional case (surgical confirmation was not available). None of the remaining seven patients in whom the 131I-metaiodobenzylguanidine scan gave negative results has been shown to harbour a phaeochromocytoma on extended follow-up (2.5 to four years). Iodine-131-metaiodobenzylguanidine is a highly sensitive and specific agent for the localization of phaeochromocytomas. In patients with suspected phaeochromocytomas and abnormal computed-tomographic findings, 131I-metaiodobenzylguanidine permits a non-invasive, functional evaluation of the morphological abnormalities to be made. The importance of making a biochemical diagnosis of a phaeochromocytoma before attempting localization studies is emphasized.

3-Iodobenzylguanidine↗
PubMed1989

Virilizing adrenal adenoma in an adult with the Beckwith-Wiedemann syndrome: paradoxical response to dexamethasone.

An adult woman with Beckwith-Wiedemann syndrome, hemihypertrophy and an androgen-secreting adrenal adenoma is described. She presented with a 7-year history of progressive virilization and was found to have high plasma levels of testosterone and dehydroepiandrosterone (DHEA) sulphate and elevated levels of urinary metabolites of testosterone and its precursors. Administration of dexamethasone was associated with progressive rises in plasma 17 alpha OH progesterone, 11 beta-desoxycortisol, DHEA sulphate, androstenedione and testosterone, together with increased urinary excretion of androsterone, 11 beta OH androsterone, etiocholanolone, DHEA, and 16 alpha OH DHEA. Hormone levels fell to normal following removal of the tumour.

17-alpha-Hydroxyprogesterone↗
PubMed1988

Generation of homozygosity at the c-Ha-ras-1 locus on chromosome 11p in an adrenal adenoma from an adult with Wiedemann-Beckwith syndrome.

Generation of homozygosity for the human c-Ha-ras-1 locus on the short arm of chromosome #11 (11p) has been demonstrated for an adrenal adenoma from an adult with Wiedemann-Beckwith syndrome (WBS). This is the first demonstration of loss of somatic heterozygosity for a locus on 11p in an adrenal neoplasm and is the first instance where a tumor of any type, from a patient with WBS, shows loss of heterozygosity in this region of the genome. Generation of homozygosity in an adenoma, rather than a carcinoma, demonstrates that this mechanism is an early event in tumorigenesis rather than a late event associated with tumor progression.

Adenoma↗
PubMed1988

Markers of physical integrity and metabolic viability of the perfused human placental lobule.

1. Peripheral lobules of term placentae obtained from healthy females at Caesarian section were perfused using separate maternal and fetal circulations for 6 h periods under either oxygenated or anoxic conditions. 2. Markers of physical integrity during setting-up and initial perfusion were establishment of dual perfusion within 25 min of placental delivery, pressure in the fetal capillary network less than 40 mmHg, leakage of perfusate from fetal to maternal compartments less than or equal to 2 ml/h, and overlap of maternal with fetal perfusion as indicated visually by appropriate blanching and verified by a fetal artery to vein oxygen gradient of greater than or equal to 90 mmHg. 3. Post-perfusion markers of metabolic viability were most reliably indicated by glucose consumption (oxygenated 7.8 +/- 1.5, anoxic 17.7 +/- 1.2 mmol/kg per h), lactate production (oxygenated 8.5 +/- 1.4, anoxic 33.9 +/- 2.5 mmol/kg per h) and human placental lactogen production (oxygenated 41.2 +/- 9.8, anoxic 12.2 +/- 3.4 mg/kg per h).

Female↗
PubMed1987

Morphometric analysis of thyroid cell aspirates.

One hundred and nineteen patients with thyroid nodules underwent fine needle aspiration cytology. Fifty eight were subsequently shown to have multinodular goitre: 36 had a follicular adenoma; 12 follicular carcinoma; and 13 papillary carcinoma on paraffin section. Morphometry performed on the aspirated cells stained by Papanicolaou and Giemsa methods showed significant differences in mean nuclear area and nuclear perimeter between groups of patients with benign thyroid nodules and those with malignant nodules. The wide variation in the mean nuclear areas and perimeters, however, severely limits the diagnostic use of morphometry in individual aspirates.

Adenocarcinoma↗