Diazoxide no longer marketed.
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Diazoxide↗
Biomedical subjects
C Lowy
Publications and source records attributed to C Lowy.
Placental transfer and uptake of 2-deoxyglucose in control and diabetic rats.
Placental glucose transfer and sequestration were investigated in anesthetized control and streptozotocin-diabetic rats by perfusing the fetal side of one placenta in situ while infusing a mixture of [3H]D-glucose (to measure net transfer after metabolism) and [14C]2-deoxyglucose (to estimate tissue sequestration) into the maternal circulation. No difference was found between transfer ratios (perfusate/simultaneous maternal plasma ratio) of [3H]D-glucose (0.35 +/- 0.06, mean +/- SD) and [14C]2-deoxyglucose (0.36 +/- 0.06) in control rats. Ratios were reduced (P < .001) to the same extent in diabetic rats ([3H]D-glucose, 0.13 +/- 0.06; [14C]2-deoxyglucose, 0.15 +/- 0.07). Placental glucose utilization, estimated by the quantity of [14C]2-deoxyglucose-6-phosphate present, was increased from 66 nmol.min-1.g-1 in control to 595 nmol.min-1.g-1 (P < .001) in diabetic rats. Transfer to the perfusion fluid of unlabeled D-glucose was increased (P < .001) in diabetic rats (2.32 mumol/mL) compared with control rats (0.77 mumol/mL) due to elevated (P < .001) maternal plasma glucose levels. Upon phosphorylation, 2-deoxyglucose becomes trapped within the placenta, and therefore these results indicate that all the glucose destined for direct transfer to the fetus is protected from phosphorylation while traversing the placenta, and that diabetes appears to increase placental glucose utilization, but does not induce futile cycling of glucose in an attempt to protect the fetus from an excessive influx of glucose from the mother in the rat.
Animals↗
A comparison of CT and MRI in the assessment of the pituitary and parasellar region.
We have carried out a prospective study to compare high resolution thin slice, contrast-enhanced, axial computed tomography (CT) with unenhanced magnetic resonance imaging (MRI) at 1.5T in the assessment of the pituitary and parasellar region. Forty patients with suspected pituitary disease presenting to an endocrine unit were studied. MRI was superior to CT for the identification of the posterior pituitary and pituitary stalk and was better at showing the cystic nature of tumours. Visualization of the optic chiasm and assessment of displacement of the optic chiasm and the carotid arteries were also better with MRI. CT was equally good at showing cavernous sinus displacement or invasion, sphenoid sinus invasion and erosion of the floor of the sella turcica and was the only technique able to show calcification of the gland. More focal abnormalities were seen in the pituitary gland with CT than with unenhanced MRI, but there was a higher false positive rate for microadenoma detection with CT. All the scans were interpreted separately by three observers, two radiologists and one clinician. The percentage agreement between the observers for the identification of pituitary and parasellar structures was better for MRI than for CT and the clinician in particular found interpretation of the MR images easier. MRI thus not only gives more information overall than CT but it is a more reliable technique between different observers for the assessment of the pituitary and parasellar region.
Aged↗
Glucose metabolism in patients with Cushing's syndrome.
Glucose intolerance, sometimes severe enough to cause frank diabetes mellitus, is a frequent feature of Cushing's syndrome. The primary cause of the hyperglycaemia, whether due to glucose over-production or under-utilization, remains unresolved. We therefore measured glucose turnover using an intravenous bolus of 3-3H glucose in 14 normoglycaemic patients with Cushing's syndrome and 14 control subjects. Seven of the patients with Cushing's syndrome were also restudied post-operatively. Plasma glucose concentrations were similar in all three groups whereas glucose metabolic clearance rate (MCR) (1.80 +/- 0.06 ml/min/kg) and glucose turnover rate (9.09 +/- 0.36 mumol/min/kg) were significantly reduced in patients with Cushing's syndrome compared to normal subjects (2.21 +/- 0.1; P less than 0.001; 10.90 +/- 0.50; P less than 0.01) and rose post-operatively to normal values (2.35 +/- 0.14 ml/min/kg; 11.07 +/- 0.48 mumol/min/kg). We conclude from these results that the hyperglycaemia sometimes found in Cushing's syndrome may be primarily due to decreased utilization rather than increased glucose production.
Adrenalectomy↗
Comparison of the real-time use of glycosylated haemoglobin and plasma fructosamine in the diabetic clinic.
The within-clinic use of glycosylated haemoglobin (HbA1) and plasma fructosamine results in assessing blood glucose control and clinical management was compared in 1030 diabetic patients. The physician initially reviewed the patient with one randomly allocated measure (HbA1 or fructosamine) and completed a questionnaire concerning perception of blood glucose control, alteration to diet, alteration to medication, referral for diabetes education, and follow-up interval. The patient was then re-assessed using the second measure and the questionnaire repeated. Discordance rates for the study end-points, judged as binary outcomes, were: blood glucose control 15%; alteration to diet 7%; alteration to medication 9%; referral for education 3%; follow-up interval 4%. A significantly greater number of patients were rated as poorly controlled with HbA1 than with fructosamine (p less than 0.001) and were, in consequence, more frequently recommended alteration to diet and medication, referral for education and shorter follow-up interval; the rate of discordance for at least one of the management decisions was 16%. Multifactorial analysis showed that discordant management was dependent on the reviewing physician (p less than 0.001) and a history of cardiovascular disease (p less than 0.01); but neither type of diabetes, nor presence of nephropathy or variant haemoglobins, nor plasma glucose concentration, significantly influenced the likelihood of a discordance. Replacing HbA1 with fructosamine in the diabetic clinic may result in significant differences in the physician's perception of blood glucose control and in the management of patients.
Adult↗
Growth hormone therapy in adults with growth hormone deficiency.
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Adolescent↗
The problem of autonomic neuropathy in diabetic pregnancy.
The hazards of pregnancy for both the mother and the fetus in diabetic women with severe retinopathy and nephropathy are well reported. We wish to highlight a poorly recognized problem in the obstetric management of the diabetic mother, that of pregnancy in a patient with autonomic neuropathy. Two such cases are reported where the presence of autonomic neuropathy severely jeopardized the health of the mother, with the loss of the fetus in one, due to occurrence of severe and intractable vomiting. The presence of moderate to severe symptomatic diabetic autonomic neuropathy, particularly with evidence of gastroparesis, may be a relative contraindication to pregnancy.
Adult↗
Effect of long-term inhibition of gonadotrophin secretion by the gonadotrophin-releasing hormone agonist, buserelin, on sex steroid secretion and ovarian morphology in polycystic ovary syndrome.
In order to investigate the effect of long-term suppression of the gonadotrophin axis in polycystic ovary syndrome, eight affected subjects were given s.c. infusions of gonadotrophin-releasing hormone (GnRH) agonist buserelin for 12 weeks. Hormone measurement and ultrasound studies were carried out weekly, from 6 weeks before to 12 weeks after administration of buserelin. An overnight dexamethasone-suppression test was carried out before and after treatment. Maximal suppression of LH to below the lower limit of that in normal subjects occurred after 6 weeks of treatment with buserelin. Plasma testosterone and androstenedione fell to normal levels during the infusion but reached pretreatment levels during the follow-up period. There was no effect of buserelin on plasma dehydroepiandrosterone sulphate or sex hormone-binding globulin. Ovarian size decreased significantly during the infusion with the disappearance of cysts in six subjects. After cessation of buserelin therapy, there was rapid and spontaneous ovulation which occurred within 3 weeks in all subjects. The results suggest that treatment with this GnRH agonist facilitates ovulation in this condition.
Adult↗
The use of two in-situ simultaneously-perfused placentas to investigate the effect of carrier proteins on linoleic and palmitic acid transfer in the guinea pig.
By perfusing two placentas concurrently in five animals we have found that linoleic acid is transferred across the guinea-pig placenta more readily than palmitic acid. In the in-situ perfusion this transfer is modulated by the type of albumin used in the perfusate. Removing the associated lipid from the perfusate albumin reduced the amount of non-esterified fatty acid (NEFA) transfer rather than enhanced it. Many researchers use fat free albumin as a protein carrier in in vivo and in-vitro systems, our results indicate that this may not be the most appropriate substance to use.
Animals↗
The effects of maternal diabetes on placental transfer of essential and non-essential fatty acids in the rat.
Studies were performed on the transfer of essential and non-essential non-esterified fatty acids across the in-situ perfused placenta in normal and diabetic rats in late gestation. Results indicated that increasing maternal glycaemia is associated with a decrease in the unidirectional transfer of both essential and non-essential fatty acids. This reduced transfer is dependent upon the uteroplacental blood flow, which is compromised in the diabetic animals. The transfer of essential fatty acid was always twofold that of non-essential fatty acids regardless of the total amount of lipid transferred, indicating a selective mechanism for the transfer of these moieties.
Animals↗
Cardiac failure responding to growth hormone.
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Cardiac Output↗
Maternal and cord blood plasma. Comparative analyses by 1H NMR spectroscopy.
Normal and 'Hahn' spin-echo 500 MHz 1H NMR spectra of 21 pairs of plasma from mother and cord taken at the time of delivery are reported. The concentrations of 'NMR-visible' lactate, alanine, and valine in the cord plasma significantly exceed those in the maternal plasma. In both maternal and cord plasma, measured lactate levels appear to increase with the length of the second stage of labour. Ethanol was unexpectedly detected in five samples of cord plasma. Lipoprotein--CH3 and--(CH2)n--resonances are more intense in the spectra of maternal plasma compared to cord plasma, and are unusual in composition. The intensities of N-acetyl signals from 'acute-phase' plasma glycoproteins are greater in spin-echo spectra of maternal plasma compared to those of cord plasma (mean ratio 2.1 (SD 0.8]. These results suggest that high resolution NMR spectroscopy may provide a useful new insight into the comparative biochemistry of maternal and cord plasma.
Acute-Phase Proteins↗
Treatment of acromegaly by external irradiation.
Despite the place of hypophysectomy as the primary treatment in acromegaly, external radiotherapy maintains a role as a relatively slow but effective therapy for inadequately treated patients or those unsuitable for operation. Over the last 25 years our radiotherapy regimen has differed from the published series in that we give a larger dose per fraction, with fewer treatments. We have analysed the efficacy and side-effects of this regimen in 27 subjects with acromegaly. Growth hormone levels have fallen by, on average, 27% per year in the first five years, 83% of subjects achieving a basal growth hormone of less than 10 mU/l. The acute and chronic side-effects of irradiation are discussed, including the relevance of estimates of biological potency, for example the Time Dose Fraction (TDF). One patient suffered visual loss that was most likely to be secondary to the radiotherapy. We also report the histological appearances of the pituitary fossa in five subjects previously treated with radiotherapy.
Acromegaly↗
The effect of alloxan induced diabetes in the rabbit on placental transfer of glucose and non-esterified fatty acids.
In situ perfusion of the fetal side of the placenta of five normal and eight diabetic anaesthetized rabbits was performed. The does were infused with a mixture of 14C palmitic acid and 3H glucose whilst simultaneous maternal blood and placental perfusate samples were taken for 90 min. Radiolabelled palmitate and glucose levels in the perfusate closely followed levels in the maternal plasma in both normal and diabetic animals. Total placental non-esterified fatty acid transfer was 0.96 mumol/min in the diabetic animals, although due to the considerable variation within the groups this was not statistically significantly more than the 0.58 mumol/min transferred in the normal rabbits. This transfer was significantly affected by maternal uteroplacental blood flow. Total placental glucose transfer was significantly raised in the diabetic (5.0 mumols/min) compared with the normal (1.8 mumols/min) animals, reflecting maternal hyperglycaemia in the diabetic rabbits. Placental glucose transfer was also significantly correlated with maternal uteroplacental blood flow. Maternal diabetes thus increases the placental flux of nutrients to the fetus in the rabbit.
Animals↗
Warning on serum testosterone measurement.
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Adult↗
The interrelationships between circulating maternal esterified and non-esterified fatty acids in pregnant guinea pigs and their relative contributions to the fetal circulation.
The relative contributions of esterified and non-esterified fatty acids to placental lipid transfer were estimated in 7 pregnant guinea-pigs. The fetal side of the placenta was perfused in situ whilst a constant infusion of a mixture of [3H]triacylglycerol emulsion (Intralipid) and [14C]non-esterified fatty acid was given i.v. to the anaesthetised mother. Considerable interconversion of the lipid moieties circulating in the mother was observed. Metabolic turnover rates of triacylglycerol and non-esterified fatty acid were found to be 14.6 mmol/day and 55 mmol/day respectively. No intact triacylglycerol was found to cross the placenta from the mother. Relatively more [3H]non-esterified fatty acid than [14C]non-esterified fatty acid was found in the perfusion fluid when compared with simultaneous circulating maternal levels of these non-esterified fatty acids indicating hydrolysis and direct transfer of [3H]triacylglycerol within the placental tissue. This hydrolysis resulted in the transfer of approximately 0.2 mmol non-esterified fatty acid/day across each placenta at this gestational age (53 days). This is in contrast to the transfer of circulating maternal non-esterified fatty acids, these can be calculated to give a mother to fetus unidirectional transport value of 3.62 mmol/day/placenta, but the total maternal to fetal flux taking into account back transfer to the mother is 1.26 mmol/day/placenta. Results from simultaneous carotid artery and uterine vein samples showed that approximately 40% of the maternal arterial triacylglycerol is removed during a pass through the uterine bed, but the majority of the triacylglycerol re-emerges in the uterine vein as non-esterified fatty acids, and masks the uterine vein uptake of circulating maternal non-esterified fatty acid. The uterine vein non-esterified fatty acid concentration is highly dependent upon levels of circulating maternal triacylglycerols and apparent uterine bed production of non-esterified fatty acid occurs when maternal triacylglycerols are high relative to non-esterified fatty acids.
Animals↗
The UK diabetic pregnancy survey.
A prospective, national survey of the UK which examined the management and outcome of pregnancy complicated by maternal diabetes is described. The perinatal mortality rate was 3.7 and 1.5 times greater than the overall UK rate and the malformation rate 6.4% and 1.9% in pregnancies where the mother had insulin-dependent and gestational diabetes respectively. In 57% of cases no blood glucose measurement was recorded in the first trimester of pregnancy. Significantly fewer malformed infants resulted from pregnancies where a first trimester blood glucose was recorded, irrespective of the value. Second and third trimester blood glucose values did not predict malformation but correlated inversely with gestational age at delivery and this was the major factor predicting the outcome of pregnancy.
Congenital Abnormalities↗
Lipid chain length alterations during placental transfer in the guinea pig.
Using an in situ perfusion of the fetal side of the guinea-pig placenta the modification of a non-esterified fatty acid during transfer across the placenta was investigated. Simultaneous constant infusions of [9,10(3)H] palmitic acid and [1-14C] palmitic acid (3 animals) or [9,10(3)H] and [6-14C] palmitic acids (3 animals) or [9,10(3)H] and universal [14C] palmitic acids (3 animals) were given to the mothers and blood samples and perfusion fluid collected over 90 min in each experiment. When expressed as a ratio of perfusion fluid/maternal plasma radioactive counts, no difference between [3H] isotopes results were found for the 3 triplets of experiments. However significant differences were found between the [14C] isotope ratios. More radioactive lipid was found in the perfusion fluid when the label was positioned away from the C1 terminal of the fatty acid chain, i.e. the ratios were [1-14C] less than [6-14C] less than [9,10(3)H] less than universal [14C] palmitic acid. It was concluded that this indicates release of partially oxidised fatty acid products from the fetal side of the placenta, and it was speculated that this partial oxidation takes place in placental peroxisomes.
Animals↗