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Biomedical subjects

M C Robertson

Publications and source records attributed to M C Robertson.

At least 73 records · Page 4Linked to original sources

Simvastatin (MK 733): an effective treatment for hypercholesterolemia.

This study describes the efficacy of the drug simvastatin. It is likely to be the first HMG CoA reductase inhibitor in Australia and New Zealand available for the treatment of hyperlipidemia. Twenty-four patients, 12 men and 12 women with primary hypercholesterolemia were randomly allocated to treatment by cholestyramine (eight patients) or to simvastatin (16 patients) for a 12-week period. With simvastatin, total cholesterol levels decreased by 37.5% from a baseline mean of 10.33 mmol/L to 6.4 mmol/L after 12 weeks. Low density lipoprotein (LDL) cholesterol concentration decreased by 48.2% from 8.40 mmol/L to 4.39 mmol/L. These effects were better than observed for cholestyramine alone where cholesterol and LDL-cholesterol reductions were 24.9% and 33.1% respectively. Thirteen patients, however, did not achieve target LDL levels of 3.62 mmol/L, or below, and therefore were treated with a combination of cholestyramine and simvastatin, resulting in a decrease of total cholesterol and LDL-cholesterol by 45.5% and 53.5% of baseline values studied over an eight-week period. No major clinical side-effects were encountered. One patient appeared to have had a change in colour vision at the end of the study at 20 weeks, without loss of visual acuity.

Adult↗

Cleaved prolactin and its 16K fragment are generated by an acid protease.

A cleaved form of rat PRL (cldPRL), which resolves after reduction of the disulfide bonds into two fragments of 16K and 8K mol wt, has been reported in the pituitary gland. To further understand the genesis of this cleaved PRL and its related 16K fragment (cldPRL/16K), pituitary proteins were labeled with [35S]methionine and then dialyzed and lyophilized before sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Pulse-chase experiments did not show a precursor-product relationship between PRL and cldPRL. However, if proteins were concentrated by trichloroacetic acid instead of dialysis, no cldPRL/16K was observed. Other experiments demonstrated that during dialysis cldPRL/16K is generated in vitro at the expense of intact PRL in a time-dependent manner. Labeled proteins dialyzed against water previously adjusted to different pHs showed after electrophoresis that cldPRL/16K was generated only at acidic pH. In the presence of the protease inhibitors phenylmethylsulfonylfluoride, tosylamidelysyl chloromethylketone, or tosylphenylalanine chloromethylketone or when the incubation medium was heated at 65 C for 45 min, the acid pH was unable to generate cldPRL/16K. Trypsin inhibitors did not prevent cldPRL generation. In conclusion, an acid protease, possibly of lysosomal origin, cleaves PRL in vitro. cldPRL/16K form was not found in the pituitary or incubation medium under physiological conditions. This PRL variant is generated as a preparative artifact unless experimental conditions are controlled.

Animals↗

Physical training and plasma intermediate density lipoprotein cholesterol levels in men with hypertriglyceridemia.

Plasma lipoprotein lipid levels including IDL cholesterol concentration, physical fitness parameters, and anthropometric data were measured in 10 men with primary hypertriglyceridemia during a 12 week program of moderate physical training. Reduced pulse rate at submaximal workload and increased work performed on the treadmill indicated that the men had increased their physical fitness during the training period. Body weight (-4.9%) and total skinfold thickness (-15.6%) fell during the training program. A characteristic fall (-23%) in plasma triglyceride levels was seen over the first 8 weeks training. Plasma IDL cholesterol concentration fell (-18%) after 2 weeks training but then rose after 8 weeks to levels which tended to be higher than baseline values. Our data suggest that regular physical exercise is more likely to raise levels of the "proatherogenic" IDL than to lower them in hypertriglyceridemic patients.

Adult↗

Serum lipoprotein lipids and haematological variables in veteran runners, before and after a 2100 km relay run.

Plasma lipids and lipoprotein lipids, body characteristics, serum insulin concentration, distance run during training and haematological variables were determined in nine men aged between 62 and 72 years and who were regular runners. Multiple regression analysis showed that much of the variation in HDL cholesterol levels was explained by plasma triglycerides, and, to a lesser extent, by the distance run during training; although these variables contributed about equally to the variation in plasma HDL2 cholesterol levels. The effects on measured variables of a 2100 km relay, run over a 17-day period, were also studied. During the relay the men were running an average 20% further, per week, than during their training before the relay. Plasma LDL cholesterol concentration, red blood cell volume, red cell count and haemoglobin levels fell significantly during the relay, and in three men raised serum insulin levels were reduced to within the normal range. Reticulocyte counts were not raised after the relay which suggests that the anaemia, seen in these men, was not due to erythrocyte destruction. The results indicate that in elderly runner, plasma triglycerides are an important predictor of plasma HDL cholesterol levels.

Aged↗

Clinical features of ischaemic heart disease correlated with high density lipoprotein cholesterol levels in men with hyperbetalipoproteinaemia.

Thirty males with familial hypercholesterolaemia were divided on the basis of levels of high-density lipoprotein cholesterol into tertiles of high, middle and low values. Symptoms and signs were scored on an arbitrary system by three methods which either included or excluded angiographic findings. Symptomatic severity and clinical manifestations of hyperlipidaemia were related to high-density lipoprotein cholesterol levels irrespective of the effect of age, level of the blood pressure, or levels of other lipoproteins. The association was not improved by adding weightings drawn from coronary angiographic findings.

Adolescent↗

Ovarian factors inhibit and fetal factors stimulate the secretion of rat placental lactogen.

Removal of fetuses at day 14 of gestation (Ftx14) in the pregnant rat leads to a marked suppression of serum levels of rat placental lactogen (rPL-II). One might attribute this to compromised placental growth in the absence of a fetus. However, if ovariectomy and fetectomy (Ftx14 Ovx14) are carried out at the same time, a great increase in serum rPL-II levels is seen. This occurs despite a significant decrease in placental weight. When Ftx14 was performed on day 14 and Ovx was delayed 1, 2, or 3 days, the expected large increase in serum rPL-II was progressively attenuated compared to that seen when Ftx and Ovx were carried out simultaneously. Daily administration of 17 beta-estradiol (4 micrograms/rat X day) to Ftx14 Ovx14 pregnant rats resulted in a significant suppression of rPL-II and elevation of rPRL levels, a reversal of what is seen for these hormones in untreated Ftx14 Ovx14 animals. To test whether 17 beta-estradiol was acting through rat PRL (rPRL), serum levels of rPRL were elevated in Ftx13 Ovx13 animals with pimozide (0.6 mg/kg), a dopamine receptor blocker. There was no effect of this treatment on rPL-II levels. In late pregnancy (day 17) serum rPL-II levels remained high after removal of half the fetuses (1/2 Ftx), compared to the rapid fall in pregnant rats in which all fetuses were removed (Ftx17). Serum levels were also elevated in 1/2 Ftx animals compared to those in which half of the fetuses and placentas were removed by hemi-hysterectomy, suggesting that the increase in rPL-II levels in 1/2 Ftx animals was due to a stimulatory effect of the remaining fetuses on all of the placentas. These results indicate that the presence of the fetus is necessary for the normally observed increase in rPL-II levels in late pregnancy. In conclusion, fetal stimulators and ovarian inhibitors influence rPL-II secretion.

Animals↗

Ovariectomy leads to a rapid increase in rat placental lactogen secretion.

Serum placental lactogen (rPL) levels were measured by RIA in late pregnant rats subjected to a number of endocrine ablations. Adrenalectomy or unilateral ovariectomy had no significant effect on serum rPL levels. Hypophysectomy of the dam at midpregnancy resulted in a significant increase in serum rPL at late pregnancy. Bilateral ovariectomy of day-14 or -16 pregnant rats led to a rapid increase in serum rPL levels for 2 days followed by a gradual decrease as fetuses were reabsorbed or aborted. Adrenalectomy combined with ovariectomy led to sustained, elevated levels of serum rPL which were greater than those seen with bilateral ovariectomy alone. When progesterone (4 mg/rat X day) and estrone (500 ng/rat X day) or 17 beta-estradiol (100 or 200 ng/rat X day) were administered to ovariectomized pregnant rats, serum rPL remained elevated and the conceptuses were retained. In conclusion our studies have shown that ovarian and adrenal factors influence rPL secretion.

Adrenalectomy↗

A register of individuals with inborn errors of lipoprotein metabolism and their families.

One hundred and fifty-five hyperlipidaemic families resident in the Christchurch and Dunedin areas were included on a computerised register with built in confidentiality safeguards. Investigation of the relatives of the 155 probands identified 519 with normal lipids and a further 381 with hyperlipidaemia. The presence of 536 hyperlipidaemic individuals in the population of the two areas indicates a frequency of at least 0.12% which extrapolates to approximately 3800 cases of familial hyperlipidaemia nationwide. Our findings suggest that less than half of these are likely to have been detected. The most common condition was the mendelian dominant disorder familial hypercholesterolaemia found in 108 families. The register has been used to facilitate detection of further cases of familial hyperlipidaemias and appropriate counseling as well as for detecting and reassuring normal relatives. It also facilitates the long term study of the treatment of the affected individuals.

Humans↗

The prevalence of dental fear and avoidance: a recent survey study.

This study evaluates the current incidence of dental fear and avoidance in the general population. A telephone survey, using a random dialing procedure, was used as a means of data collection. Results indicated that 11.7% of the respondents reported high dental fear, and another 17.5% reported moderate dental fear. Results also disclosed that 36.5% of those surveyed had not been to the dentist in over a year. Approximately 15.5% of the respondents surveyed had some degree of dental fear and were dental avoiders (using the criterion of no dental visitation for at least one year). These findings highlight the fact that additional attention and research efforts still need to be dedicated to dealing with the highly fearful and avoidant dental patient.

Adult↗

Temporal concentrations of rat placental lactogen in the peripheral circulation.

Placental lactogen (PL) is an abundant placental protein identified in several species, but to date little is known of mode or control of PL secretion. In the present study we sought to define the minute-to-minute variation in rat PL (rPL) secretion in late pregnancy by repeated blood sampling over a 3-h period. The results indicate that rPL may be secreted in an episodic pulsatile manner similar to the pulsatile secretion of pituitary prolactin (Prl) and growth hormone (GH). This evidence suggests a highly regulated dynamic control of secretion of a placental hormone.

Animals↗

Two forms of rat placental lactogen revealed by radioimmunoassay.

A radioimmunoassay (RIA) has been developed to the species of lactogenic hormone (rPL) present in late pregnant rat placenta. Partially purified rPL calibrated against oPRL in the rat liver receptor assay (RRA) was used as standard. None of the PL's, PRL's, and GH's from other species cross-reacted in the RIA when tested at 1000 ng/ml. Rat serum PL levels remained stable in samples stored at -70C but not at -20C. In previous studies, using RRA, two peaks of rPL were found in rat serum, one at Day 11-13 and one at Day 20. By RIA, however, only the 20,000 dalton species of rPL present in late pregnant serum was immunoreactive. The RIA did not detect the larger, 40-50,000 dalton molecular species of rPL predominant in mild-pregnant serum, thus revealing the presence of two possibly unrelated forms of rPL. Serum rPL concentrations at Day 21 of pregnancy increased exponentially as the number of fetuses increased until a maximum of nine fetus.

Animals↗

Secretion of placental lactogen, growth hormone, and prolactin in late pregnant rats.

The secretory patterns of placental lactogen (PL), GH, and PRL were determined in conscious unrestrained late pregnant rats by measurement of the plasma concentrations of each hormone by RIA. Blood samples were collected over a 4-h period at 15-min intervals on days 18 and 19 of gestation. From days 18-19, GH levels increased 2-fold, no change was observed in PRL levels, while PL concentrations increased slightly. There was an ultradian rhythm present in GH and PRL secretion, with a frequency of two to three secretory spikes per 4-h collection period. The variable concentrations of PL in the peripheral circulation were suggestive of an episodic or ultradian secretory pattern. PL levels increased 100% or more within 30 min (i.e. from 485 to 1132 ng/ml) or decreased as much as 65% within 60 min (i.e. from 792 to 247 ng/ml). The relative magnitude of these changes were similar to, but not coincident or correlated with, those for GH.

Animals↗