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Biomedical subjects

M Hartog

Publications and source records attributed to M Hartog.

At least 19 recordsLinked to original sources

The human fumarylacetoacetase gene: characterisation of restriction fragment length polymorphisms and identification of haplotypes in tyrosinemia type 1 and pseudodeficiency.

Deficiency of human fumarylacetoacetase (FAH) activity results in hereditary tyrosinemia type I. Using the restriction enzymes BglII, KpnI and StuI and a 1.3-kb cDNA probe for the FAH gene, we have found 6 restriction fragment length polymorphisms (RFLPs). These RFLPs were utilised in 3 tyrosinemia families in which one or both parents are carriers of both a tyrosinemia and a pseudodeficiency gene for FAH. Full information was obtained in two of these families. The polymorphisms identified 6 haplotypes. The haplotype distribution was significantly different in 32 unrelated tyrosinemia patients compared with a reference population of 100 individuals. The combined polymorphism information content was 0.77.

Alleles

Staphylococcal septicaemia complicating intracavernosal autoinjection therapy for impotence in a man with diabetes.

Intracavernosal injection of vasoactive drugs is a safe, effective, and commonly used treatment for impotence in diabetic men. In prospective studies infection has rarely occurred. We report a case of life-threatening Staphylococcal septicaemia complicating this treatment in a 61-year-old man with Type 2 diabetes, probably due to a combination of an unsterile technique and drug-induced priapism. Infection is a potential risk in diabetic men using intracavernosal injection therapy and those offered it should be informed of the importance of a scrupulous sterile technique and the need to seek urgent medical help for decompression if an erection persists for more than 4-6 h.

Bacteremia

Management of diabetes in surgery: a survey of current practice by anaesthetists.

A questionnaire survey of anaesthetists, based at the three main hospitals in Bristol, was undertaken to determine what methods are currently being used by anaesthetists to manage diabetes in patients for surgery. Replies were received from 56 of the 90 anaesthetists (62%). Surgical procedures were defined as minor, moderate, and major. Two areas were identified where considerable differences in management between anaesthetists occurred, namely insulin-treated patients requiring minor surgery, and non-insulin-treated patients requiring moderate surgery. In addition, no consensus view was apparent for the preferred intra-operative blood glucose range or for the threshold blood glucose level at which to postpone an operation. It was apparent that anaesthetists preferred to administer intravenous insulin by a syringe pump rather than by a drip bag containing insulin, potassium, and glucose, particularly if more severe metabolic upset was anticipated. No difference in management was apparent between different hospital grades or between the three hospitals.

Anesthesiology

Impedance plethysmography and thrombo-embolic disease.

This study compares the results of impedance plethysmography with lower limb venography in 68 patients referred for investigation of clinical deep vein thrombosis, and with the results of ventilation/perfusion isotope scans in 125 patients with suspected pulmonary embolism. Impedance plethysmography had a sensitivity of 100% and a specificity of 61% for the detection of thromboses involving popliteal or more proximal veins (30 patients), but a sensitivity of 90% and a specificity of 68% in the detection of thrombosis at any level, because of a low sensitivity in the detection of isolated calf vein thrombosis (60% in 10 patients). It is a non-invasive, portable and low-cost technique and, in centres where anticoagulation is only given to patients with popliteal or more proximal thrombosis, venography may only be necessary if impedance plethysmography is positive. It may also be of value in the assessment of patients with suspected pulmonary embolic disease and an indeterminate ventilation/perfusion lung scan.

Humans

The effect of combined estrogen/progestogen treatment in women with hyperprolactinemic amenorrhea.

Eleven women with hyperprolactinemic amenorrhea were treated with a combined estrogen/progestogen preparation (Loestrin 30) for 3 months as hormone replacement therapy because of estrogen deficiency, with a view to protection against osteoporosis. Serum prolactin levels rose during the 1st month of treatment (p < 0.05) but did not rise significantly further during the 2nd and 3rd months. The levels rose in proportion to pretreatment levels by 28% (median), and fell significantly but not completely during the 1-week treatment-free intervals. After the study period, prolactin values appeared to remain stable in those women who continued longer on treatment, and returned to around pretreatment values in those who stopped. In one woman there was radiological evidence of pituitary tumor growth during treatment. This study shows that estrogen/progestogen treatment in standard contraceptive dosage usually leads to only moderate and non-progressive stimulation of pituitary activity in women with hyperprolactinemic amenorrhea, but occasional excessive growth of a prolactinoma can occur and treatment needs to be monitored. Women with relatively high prolactin levels seem to be at particular risk. Safer variations of estrogen therapy such as lower dosage or combination with a protective low dose of a dopamine agonist should also be considered.

Adolescent

Maternal postprandial blood glucose levels influence infant birth weight in diabetic pregnancy.

Relationships between maternal glycaemia and neonatal birth weight were studied prospectively in 14 tightly controlled pregnant women with pre-existing type 1 diabetes mellitus. Maternal glycaemia throughout pregnancy was determined from daily self blood glucose (BG) monitoring with memory meters and fortnightly fructosamine (Fr) and glycated haemoglobin (HbA1) measurements. Mean non-fasting BG and mean HbA1 throughout pregnancy correlated strongly (Spearman rank) with birth weight (0.64 and 0.73 respectively), as did mean second trimester non fasting BG (0.54), HbA1 (0.7) and Fr (0.64) and mean third trimester HbA1 (0.65), whereas mean fasting BG showed no significant correlations with birth weight at any age of pregnancy. The disparity between the strong correlation of non fasting BG with birth weight and the poor correlation of fasting BG suggests that postprandial as opposed to basal glycaemia significantly influences foetal growth and neonatal size.

Adult

Laboratory investigation in the diagnosis of pulmonary thromboembolism.

Laboratory findings were compared with lung scans in a prospective study of 260 patients undergoing ventilation-perfusion (V/Q) lung scanning for suspected pulmonary thromboembolism. The best discrimination between different lung scan results was obtained from the level of plasma cross-linked fibrin degradation products, every patient with a scan indicating a high probability of thromboembolism having detectable levels. An acute phase response was demonstrated in patients with pulmonary thromboembolism by a raised neutrophil count and elevated levels of plasma fibrinogen and serum C-reactive protein. A normal level of serum C-reactive protein and/or plasma cross-linked fibrin degradation productions in blood taken within 4 days of onset of symptoms virtually excluded the diagnosis of pulmonary thromboembolism. Detection of free plasma DNA was not helpful in discriminating between groups with different lung scan results. Discriminant analysis was used to assess the variables examined and to derive diagnostic models. An accuracy of 78 per cent was obtained with one model for classifying test patients according to the three lung scan classes of low, intermediate and high probability. A second model, for distinguishing patients with a low and a high probability of pulmonary thromboembolism on the basis of lung scans, and a third for predicting those with a low probability on lung scan, were accurate in 94.6 per cent and 83.5 per cent of patients respectively. Discriminant models could be used in the diagnosis of pulmonary thromboembolism, especially when diagnostic imaging is not available.

C-Reactive Protein

Identification of three human pseudogenes for subunit VIb of cytochrome c oxidase: a molecular record of gene evolution.

Three pseudogenes for the nuclear-encoded subunit VIb of cytochrome c oxidase (COX) were isolated by screening a human genomic library with cloned human cDNA coding for COX subunit VIb. The nucleotide sequences of the pseudogenes, designated psi COX6b-1, psi COX6b-2 and psi COX6b-3, were determined. Pseudogene psi COX6b-1 bears all the hallmarks of a processed pseudogene and diverged from the parental gene after the divergence of man and cow. Alu repetitive elements were integrated into the structural sequences of the other two pseudogenes. Comparison with the human and bovine cDNA sequences encoding COX subunit VIb suggests that psi COX6b-2 and psi COX6b-3 were formed earlier in evolution than psi COX6b-1. Genomic Southern analysis indicated that a few more pseudogenes for COX subunit VIb are likely to be present in the human genome. Identical nt differences with respect to the human cDNA sequence in the pseudogenes provide some clues on the evolution of the ancestral gene coding for COX subunit VIb.

Amino Acid Sequence

Survey on the use of pulmonary scintigraphy and angiography for suspected pulmonary thromboembolism in the UK.

A survey of UK radiologists in 360 acute hospitals was undertaken to assess the current use of pulmonary angiography and radionuclide lung scanning in the investigation of suspected pulmonary thromboembolism (PTE). Replies were received from 340 (94%) hospitals, of which 48 (out of 50) were teaching hospitals or centres which perform cardiothoracic surgery. Lung scintigraphy was provided by 200 (59%) hospitals and angiography by 120 (35%), with 99 (29%) providing both. Twenty-two hospitals which could undertake angiography had not performed more than one angiogram for suspected PTE in the preceding 3 years. Average numbers of lung scans performed in each hospital were 21.8 per month, in contrast with an average of 4.1 angiograms (including digital subtraction angiography) per year performed for suspected PTE over the previous 3 years. The total number of V/Q lung scans performed for the diagnosis of PTE per year was approximately 47,000 compared with 490 pulmonary angiograms.

Analysis of Variance

Transfer from animal insulins to semisynthetic human insulin: a study in four centres.

The effects of transfer from animal insulin to semisynthetic human insulin on glycaemic control, insulin dose and anti-insulin antibodies were investigated in a total of 108 patients at four centres in a double-blind controlled study of eight months duration. Six months after transfer from porcine to human insulin there was a mean (+/- SE) increase in pre-breakfast blood glucose of 1.1 +/- 0.6 mmol l-1 (vs a reduction of 1.6 +/- 0.7 mmol l-1 in controls) (p less than 0.01), and a mean increase of pre-lunch blood glucose of 0.9 +/- 0.7 mmol l-1 (vs a reduction of 1.14 +/- 0.7 mmol l-1 in controls) (p less than 0.05). Six months after transfer from bovine to human insulin, there were no significant changes in blood glucose. Glycated haemoglobin showed no significant change six months after transfer from either bovine or porcine to human insulin. Hypoglycaemic symptoms, the total daily insulin dose, and the ratio of short- to intermediate-acting insulin did not change significantly after transfer from either bovine or porcine to human insulin. Transfer from bovine to human insulin resulted in a significant decline in anti-human insulin antibodies (mean (range): 50.5(14.8-125)% of initial levels), vs controls (113(43.4-234)% of initial levels; p = 0.034), and a non-significant decline in anti-bovine insulin antibodies (52.2(25.8-111)% vs 81.7(42.5-128)%; p = 0.082).

Adult

Duplication of the tRNA(MMet) and tRNA(Cys) genes and of fragments of a gene encoding a subunit of the NADH dehydrogenase complex in Neurospora grassa mitochondrial DNA.

Neurospora crassa mitochondrial DNA (mtDNA) contains duplications of the tRNA(MMet) gene upstream of a gene (ND2) encoding a subunit of the NADH dehydrogenase complex and of the tRNA(Cys) gene which is found downstream of the apocytochrome b gene. Both duplicated genes are located upstream of the small rRNA gene. The duplications are extended to flanking sequences. In the case of the tRNA(MMet) duplication, two fragments of the ND2 gene are also duplicated. These two fragments, which are not contiguous in the ND2 gene, are connected to each other by a palindromic sequence of 37 bp and together they constitute an open reading frame. The possible involvement of this palindromic sequence in the processes of gene duplication and transfer is discussed. Two overlapping reading frames are present between the tRNA(MMet) and tRNA(Cys) copies. All information of the ND2 duplication and the two overlapping reading frames are present on a polycistronic transcript.

Amino Acid Sequence

Plasma and lipoprotein lipids and apolipoproteins AI, AII and B in patients with chronic airflow limitation.

Plasma and lipoprotein cholesterol and triglycerides, and plasma apolipoproteins AI, AII and B were compared in patients with chronic airflow limitation, and normal controls matched for body mass index. The controls were non-smokers, and free from respiratory disease. High-density lipoprotein (HDL) cholesterol concentration was significantly elevated in the patients, due mainly to a raised HDL2 cholesterol level. HDL triglyceride was significantly lower in the patients. All other lipids were not different from normal. Apolipoprotein AI levels were significantly raised in the patients but other apolipoproteins were unchanged. The changes found may account in part for the fact that patients with chronic airflow limitation have a lower incidence of atherosclerotic heart disease.

Adult

Carbohydrate-containing materials in urine from normal and diabetic subjects.

1. Abnormalities in glycoprotein metabolism are believed to play a role in diabetic microangiopathy. We have therefore measured the urinary excretion of carbohydrate-containing materials in normal and diabetic subjects. 2. Diabetic subjects were found to excrete excessive quantities of such material, which may parallel the increases observed in plasma and structural glycoproteins found in previous studies. 3. Systemic administration of a synthetic derivative of vasicine, which is known to affect mucus glycoprotein, was shown to restore these elevated urinary concentrations seen in diabetic subjects to values close to normal, but his drug had no significant effect on urinary concentrations of such materials in normal subjects.

Carbohydrates

Immunological features of juvenile onset diabetic patients correlated to HLA type.

Ninety-six juvenile onset type diabetics showed an increase in the frequency of HLA B8 and B15 and a decrease in frequency of HLA B7 antigens. Sixty-four maturity onset diabetics showed no disturbance in the frequency of these antigens. Fifty-four of the juvenile onset type diabetics, with an average duration of disease of 3.2 years were tested for the presence of islet cell antibodies (ICAs). Thirty-two per cent were positive, the incidence decreasing from 70% in those patients tested within 1 year of diagnosis to zero in those patients tested within 1 year of diagnosis to zero in those patients tested more than 5 years after diagnosis. No correlation was found between the incidence of ICAs and either cell-mediated immune reactions or HLA type. B15 positive patients were associated with cell-mediated immune reactions to pancreatic antigens and with the presence of other tissue autoantibodies. HLA phenotypes were not associated with environmental data. Diabetic siblings had identical HLA A-B haplotypes more often than could be expected to occur by chance.

Adolescent