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Biomedical subjects

M Blair

Publications and source records attributed to M Blair.

At least 55 records · Page 3Linked to original sources
PubMed1994

[A six-month intravenous repeated dose toxicity study of tazobactam/piperacillin and tazobactam in dogs].

Tazobactam (TAZ) is a newly developed beta-lactamase inhibitor. Tazobactam/Piperacillin (TAZ/PIPC) is a formulation consisting of TAZ and PIPC in a ratio of 1:4. A six-month intravenous repeated dose toxicity study of TAZ/PIPC and TAZ including a one-month recovery period were carried out using male and female dogs. The doses were 200, 400 and 800 mg/kg/day for TAZ/PIPC, and 40, 80 and 160 mg/kg/day for TAZ. The results were as follows. 1. No test article-related deaths occurred during the study period. No effects on clinical findings, body weight and food consumption were evident. 2. No test article-related changes were noted in hematological, serum biochemical and urinalysis evaluations, and opthalmological and electrocardiographic examinations. 3. There were no test article-related changes in macroscopic findings or organ weight. 4. The histopathological examination revealed deposition of marked PAS-positive aggregates in liver cells of dogs given 400 mg/kg/day or more of TAZ/PIPC and 80 mg/kg/day or more of TAZ. Electron micrographs of hepatocytes revealed glycogen granules to be accumulated in the cytoplasm, and an increase of smooth endoplasmic reticulum. 5. After a one-month recovery period, the histopathological changes had generally disappeared, suggesting that they were reversible. 6. From the histopathological changes of liver, the no-toxic dose levels for TAZ/PIPC and TAZ were 200 mg/kg/day and 40 mg/kg/day, respectively.

Animals↗
PubMed1990

Neonatal cleft lip repair in Ayrshire; a contribution to the debate.

Neonatal cleft lip repair has been the normal practice in Ayrshire, Scotland, for the last 10 years. The surgical results are briefly presented. Anaesthetic and paediatric considerations are discussed. Assuming careful preoperative assessment is made, the procedure carries minimal morbidity, can give good results and is believed to offer distinct advantages to the parents and child.

Cleft Lip↗
PubMed1990

Calcium and phosphorus solubility in neonatal intravenous feeding solutions.

The limited solubility of calcium and phosphorus in standard parenteral nutrition formulations has restricted the ability to provide sufficient minerals to preterm infants to prevent substrate deficient metabolic bone disease. We determined the solubility limits of calcium and phosphorus in a total of 160 formulations under carefully controlled conditions. By increasing the concentrations of dextrose, amino acids, and by using Addiphos instead of 8.7% dipotassium hydrogen phosphate as the phosphorus source, higher concentrations of both calcium and phosphorus were held in solution. This should permit the delivery of increased concentrations of these minerals at rates which approximate fetal accretion.

Amino Acids↗
PubMed1990

Acid-base state of the preterm infant and the formulation of intravenous feeding solutions.

An acidic intravenous source of phosphorus (Addiphos) was compared with dipotassium hydrogen phosphate in 25 preterm infants to study acid-base state. Eight infants were given either Addiphos or dipotassium hydrogen phosphate alternately for 48 hour periods and similar amounts of calcium and phosphorus were delivered. There were no significant differences in calcium and phosphorus intake, calcium and phosphate plasma concentrations, or acid-base state between study periods on the two solutions. Seventeen infants were given the two solutions alternately for 72 hour periods; Addiphos was used to increase the amounts of calcium and phosphorus being delivered. Calcium and phosphorus intake was decreased on dipotassium hydrogen phosphate, but Addiphos significantly increased calcium and phosphorus intake and plasma calcium and phosphate concentrations. It also lowered the pH of the urine and raised the titratable acidity. Acid-base state, however, was not significantly different. It is therefore possible to increase intake of calcium and phosphorus in preterm infants without causing a significant metabolic acidosis.

Acid-Base Equilibrium↗
PubMed1989

Acute and subacute toxicity studies of ioversol in experimental animals.

The authors examined the acute and subacute toxicity of the low-osmolality nonionic radiographic contrast agent, ioversol. The median lethal dose (LD50) of ioversol administered intravenously to mice, rats, rabbits, and dogs was more than 12 g I/kg, which exceeds the maximal anticipated clinical dose by at least tenfold. When the acute intravenous toxicity of 35% I, wt/vol, ioversol was compared with 35% I, wt/vol, iohexol and 37% I, wt/vol, iopamidol in mice, no significant differences in LD50 values or general toxicity were found. Ioversol also was administered via intrathecal routes to rats, dogs, and monkeys. In a comparative study, acute intracisternal injections of 35% I, wt/vol, ioversol in rats demonstrated far less toxicity than 35% I, wt/vol, iohexol and 37% I, wt/vol, iopamidol, a result that may be due to the increased hydrophilic tendency of ioversol relative to iohexol and iopamidol. Acute intracisternal injections of 43% I, wt/vol, ioversol, 35% I, wt/vol, iohexol, and 37% I, wt/vol, iopamidol into dogs at 160 or 240 mg I/kg, demonstrated comparable, but only minimal, toxicity. Monkeys given lumbar intrathecal injections of ioversol tolerated 60 mg I/kg well with no resulting arachnoiditis. Subacute toxicity studies involving 4-week daily intravenous injections (0.2, 0.8, and 3.2 g I/kg/day) in rats and dogs showed ioversol to be well tolerated. The signs of toxicity included a reversible renal cytoplasmic tubular vacuolation in the rat at high doses and a reversible hepatocyte vacuolation in the dog at the same high dose. However, clinical chemistry tests showed no signs of renal or hepatic dysfunction, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Hypothyroidism and unusual rickets in a very preterm infant.

Two separate episodes of rickets developed in a female infant of 25 weeks gestation and birthweight 690 g, who had congenital hypothyroidism and required parenteral nutrition for more than 100 days. We speculate that there is a relationship between metabolic bone disease of prematurity and the preterm infant's thyroid status.

Congenital Hypothyroidism↗
PubMed1988

Evidence that insect embryogenesis is regulated by ecdysteroids released from yolk proteins.

That the yolk proteins (YPs), or vitellins, stored in the oocytes of insects are a nutritional store for subsequent embryogenesis has long been assumed. Exhaustive data base searching programs revealed highly significant sequence similarity between the three YPs of Drosophila melanogaster and part of the triacylglycerol lipase of the domestic pig. Based upon time of degradation of YPs during embryogenesis, existence of maternally stored ecdysteroid conjugates in embryos, location of these conjugates in locust embryos, and the fact that free active ecdysteroid hormones are released at a specific time in embryogenesis to trigger cuticle deposition, we postulate that the similarity reflects a common property of Drosophila YPs--the ability to bind the fatty acid ecdysteroid conjugates. Our finding of conjugated ecdysteroids tightly bound to purified Drosophila YP supports this prediction.

Amino Acid Sequence↗
PubMed1987

The use of an inhibitor of protein synthesis to investigate the roles of ecdysteroids and sex-determination genes on the expression of the genes encoding the Drosophila yolk proteins.

The three yolk-protein genes of Drosophila are normally expressed only in adult female fat bodies and ovaries. 20-hydroxyecdysone can affect the transcription of these genes in males and females, as can mutations in the sex-determining genes tra, tra-2, ix and dsx. We have asked a number of basic questions about how these genes are regulated, using an inhibitor of protein synthesis (cycloheximide), labelling RNA in vivo, a temperature-sensitive sex-determination mutant (tra-2ts1), and 20-hydroxyecdysone. We have found that the yolk-protein genes are continuously transcribed in the fat bodies of adult females and that maintenance of this transcription requires protein synthesis. Hormone induction in males is also inhibited by cycloheximide, suggesting that the products of other genes are essential both for 20-hydroxyecdysone to be able to switch on the genes, and for their continuous transcription in the female fat body. The products of the tra-2 gene are also required for continuous transcription of the yolk-protein genes, suggesting that the pathway inhibited by the cycloheximide is that of the sex-determination hierarchy. 20-hydroxyecdysone can override the sex-determination system and induce yolk protein synthesis in normal males and tra-2ts reared and maintained at the restrictive temperature.

Animals↗
PubMed1983

The regulation of yolk protein gene expression in Drosophila melanogaster.

The three genes, located in the X chromosome, which code for the three yolk polypeptides (YPs) of Drosophila melanogaster are expressed in the fat bodies and ovarian follicle cells of adult females. Both juvenile hormone and ecdysone are involved in regulating their expression. The yolk protein genes (YP genes), normally not transcribed in males, become expressed when males are injected with or fed 20-hydroxyecdysone. Superimposed on this hormonal regime is a sex determination mechanism which ensures that normally YP gene expression is female-specific. There are a series of autosomal genes in D. melanogaster which ensure that individual cells follow a male or female developmental pathway. When they are mutant, flies with two X chromosomes, which would normally be female, can become intersexual in phenotype or transformed into sterile males and flies with one X and one Y chromosome can become intersexual. It has been found that the YPs are part of the set of female characteristics controlled by these sex genes. The YP genes are expressed in female and intersexual flies, regardless of the X chromosome constitution, but not in males or pseudomales. Transcript levels of yolk proteins have been measured in female and intersexual flies by hybridization to cloned YP DNA sequences. It is suggested that transcription of the YP genes is under the cell-autonomous control of the sex genes and that the sex genes do not exert their effect by modulating the levels of steroid hormones in adults.

Age Factors↗
PubMed1983

An open dose finding study of melperone in treatment of agitation and irritability associated with dementia.

Seventeen older patients with a diagnosis of Organic Brain Syndrome were placed on a four-week trial of melperone for treatment of behavioural disturbances associated with dementia. Efficacy evaluation of the drug revealed improved ratings of the patients in the areas of agitation/irritability, anxiety, unsociability, and mental alertness. Thirteen of the fourteen patients who completed the trial were rated generally as showing at least minimal improvement while on the drug. There were no serious side effects noted, with drowsiness the most frequent finding. These favourable results are suggestive of the usefulness of this drug, and point to the need for double-blind, comparative studies.

Aged↗
PubMed1983

Expression of the yolk-protein genes in the mutant doublesex dominant (dsxD) of Drosophila melanogaster.

Adult flies mutant for doublesex dominant (dsxD) are intermediate in phenotype between males and females. The dsxD mutation acts in the heterozygous state to transform only flies with two X chromosomes into intersexes, XY flies are unaffected by the mutation. Yolk-protein synthesis, which normally occurs in the ovaries and fat bodies of females, but not in males unless stimulated with 20-hydroxy-ecdysone, is reduced. The dsxD fat body synthesizes less yolk proteins throughout adult life, and the gonads rarely make yolk proteins. Using cloned yolk-protein genes as probes for measuring transcript levels we have shown that expression of these genes in dsxD is regulated both transcriptionally and post-transcriptionally. We suggest that the dsxD locus regulates the expression of the yolk-protein genes from within the fat body cells and does not operate by modulating ecdysteroid titres in the adults.

Animals↗
PubMed1983

20-hydroxyecdysone stimulates tissue-specific yolk-protein gene transcription in both male and female Drosophila.

The yolk polypeptides of Drosophila are normally synthesized in the fat body and ovarian follicle cells of adult females. In response to 20-hydroxyecdysone males synthesize yolk polypeptides. The actual level of yolk polypeptides synthesized in males is not always a direct reflection of the YP-transcripts present. Initially YP-transcripts are efficiently translated into polypeptides whereas later they are not and the YP-transcripts can have a half-life of less than 8 h in males. We suggest that the expression of the genes coding for the yolk polypeptides in males may be regulated at transcriptional and translational levels. Treatment of females with 20-hydroxyecdysone leads to a transient increase in YP-transcript accumulation, but the response is difficult to assess in whole flies due to the high variability in transcript levels during normal development. Analysing the response to 20-hydroxyecdysone at the level of specific tissues shows that transcript accumulation is dramatically increased in body walls (fat-body cells, epidermis and oenocytes) of both males and females. Gut, Malpighian tubules, testis and ovaries are not affected. Treatment of females with 20-hydroxyecdysone followed by measuring YP-transcript accumulation over the next 24 h in ovaries and body walls separately, confirms that only body walls respond to the hormone. There is an increase in yolk-polypeptide synthesis during the period of increased YP-transcript accumulation in females. We conclude that the response of the YP-genes to 20-hydroxyecdysone is tissue-, but not sex-specific.

Animals↗
PubMed1982

A clinical trial of norethisterone oenanthate (Norigest) injected every two months.

A clinical trial was carried out in which Norigest (200 mg norethisterone oenanthate) was administered by intramuscular injection every 56 days into 383 women studied for 5,521 woman-months of use. No pregnancies occurred. Continuation rates at the end of one, two and three years were 76.6%, 63.7% and 33.8%. Only minor side-effects were recorded. After one year of use, 20.1% women had gained more than 2 kg in weight and 14.8% had lost more than 2 kg. There was marked disruption of the menstrual pattern and irregular bleeding was the major cause of discontinuation. In 38% of the injection intervals analysed, women were amenorrhoeic. Norigest proved an effective and acceptable method of fertility control.

Amenorrhea↗
PubMed1982

Halothane hepatitis in a young child.

A 4-year-old girl developed severe hepatitis following the fourth administration of halothane in a period of 5 months. She was shown to have a circulating antibody which acted specifically against rabbit hepatocyte previously sensitized to halothane. The patient made a full recovery from the hepatitis, but 5 months later, developed diabetes mellitus.

Anesthesia, Inhalation↗