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Biomedical subjects

J Barr

Publications and source records attributed to J Barr.

At least 19 recordsLinked to original sources
PubMed1992

Biguanide-associated lactic acidosis. Case report and review of the literature.

PURPOSE: The biguanides are a class of oral hypoglycemic agents that are commonly used in the treatment of diabetes mellitus. Such agents include metformin, phenformin, and buformin. The use of phenformin was discontinued in the United States in 1976 because of probable association with lactic acidosis. However, metformin is currently in common use in many parts of the world. In this report, we describe a patient with severe lactic acidosis secondary to metformin administration, and review the literature relevant to biguanide-associated lactic acidosis. PATIENT: We describe a diabetic man with end-stage renal failure and diabetes mellitus who was hospitalized with life-threatening lactic acidosis (lactate, 10.9 mmol/L). Unbeknownst to the hospital staff, he was being treated with metformin, which had been prescribed in Indonesia. RESULTS: Arterial blood gas analysis revealed a pH of 6.76 and a bicarbonate level of 1.6 mmol/L prior to treatment. Following therapy, which included oxygen, volume expansion, other supportive therapy, and hemodialysis, the patient completely recovered and was discharged from the hospital. CONCLUSIONS: Lactic acidosis can complicate biguanide therapy in diabetic patients with renal insufficiency. We review the literature relevant to the pathogenesis and therapy of biguanide-associated lactic acidosis. Physicians who have completed their training after 1976 may not be familiar with metformin and other biguanides, but with the increasing numbers of immigrants to the United States, physicians should be aware of the potential complications of these medications.

Acidosis, Lactic↗
PubMed1992

Septic shock: does adrenaline have a role as a first-line inotropic agent?

Fifteen adult patients, admitted to Baragwanath Hospital ICU with septic shock after adequate fluid loading and on no other inotropic agents, were given adrenaline in incremental doses. Oxygen transport and haemodynamic variables were monitored with each dose increment until a systolic blood pressure of 120 mmHg was obtained. This was reached on an average dose of adrenaline of 0.16 +/- 0.02 micrograms/kg/min. Mean arterial blood pressure increased by 22 +/- 2 mmHg mainly due to an increase in cardiac index (1 +/- 0.2 l/min/m2) and systemic vascular resistance index (130 +/- 41 dyn.s.cm.-5m-2) with a small increase in heart rate of 8 +/- 3 beats per minute. Oxygen delivery was increased with no significant increase in oxygen consumption and lactate levels increased. Adrenaline is therefore an effective initial inotropic agent. Patients may respond to lower doses than when used concurrently with other inotropic agents but there was still a significant dose variation in response. We cannot, however, exclude a deleterious effect on oxygen utilization.

Adult↗
PubMed1991

Autosomal recessive lethal infantile cytochrome C oxidase deficiency.

Three bedouin children with mitochondrial myopathy due to cytochrome c oxidase deficiency presented with progressive muscle weakness, failure to thrive, proximal renal tubular acidosis, and lactic acidemia leading to death. Two died by age 5 months and one by age 16 months. Cytochrome c oxidase was markedly reduced in skeletal muscle extracts of all three. Three other children of the same family with most probably the same metabolic aberration are also described. We suggest an autosomal recessive inheritance for this lethal mitochondrial myopathy.

Acidosis, Renal Tubular↗
PubMed1991

Improved algorithms for searching restriction maps.

We present algorithms for searching a DNA restriction enzyme map for a region that best matches a shorter 'probe' map. Our algorithms utilize a new model of map alignments, and extensive experiments prove our model superior to earlier approaches for certain applications. Let M be the number of map sites and P be the number of probe sites. Our first algorithm, which optimizes only over a restricted class of alignments, requires O(MP log P) worst-case time and O(M + P) space. Our second algorithm, which optimizes over all alignments, runs in O(MP3) time and O(M + P2) space, under reasonable assumptions about the distribution of restriction enzyme cleavage sites. Combining the algorithms gives a map-searching method that optimizes over all alignments in O(MP log P) time in practice. The algorithms' effectiveness is illustrated by searches involving a genomic restriction map of Escherichia coli.

Algorithms↗
PubMed1991

Sequence of the major nucleocapsid protein gene of pneumonia virus of mice: sequence comparisons suggest structural homology between nucleocapsid proteins of pneumoviruses, paramyxoviruses, rhabdoviruses and filoviruses.

The complete nucleotide sequence of gene 3 of pneumonia virus of mice has been determined, and the 5' end of the mRNA mapped using a modification of the polymerase chain reaction technique. The gene contains a single open reading frame, beginning with a 5'-proximal AUG initiation codon, encoding a polypeptide with a predicted Mr of 43141. Expression of the gene 3 protein in Escherichia coli and in vitro showed that it reacted with virus-specific antiserum and comigrated with the major nucleocapsid (N) polypeptide. The predicted amino acid sequence has extensive identity with that of the N protein of human respiratory syncytial virus. Comparisons with the amino acid sequences of N proteins of other paramyxoviruses, vesicular stomatitis virus and Ebola virus suggest that these proteins may have retained much of the same structure. These regions of conserved structure would most likely have the common functions of RNA binding and protein/protein interactions in the virus nucleocapsid.

Amino Acid Sequence↗
PubMed1991

In-vitro hepatotoxicity of three dichlorobenzene isomers in human liver slices.

1 The cytotoxicity of dichlorobenzenes in cultured rat liver slices has previously been shown to be strain specific and biotransformation related. 2 In order to extrapolate animal models to humans, the dichlorobenzenes were incubated with human liver slices to try to clarify their hepatotoxic potential in man. 3 The degree of hepatotoxicity observed with the dichlorobenzenes depended on whether Waymouth's or Krebs-Henseleit was used as the incubation medium. 4 All three dichlorobenzenes (1 mM) produced no significant differences from control when incubated in Waymouth's medium. However, in the Krebs-Henseleit buffer there was a substantial increase in cytotoxicity. 5 In both incubation mediums the dichlorobenzene isomers exhibited the following rank order 1,3-DCB greater than 1,2-DCB greater than 1,4-DCB. 6 1,2-dichlorobenzene hepatotoxicity was blocked by metyrapone, 1,3-dichlorobenzene toxicity was blocked by SKF 525-A and neither one of these inhibitors could block the 1,4-dichlorobenzene cytotoxicity. 7 The use of human liver tissues to evaluate potential toxicants merits consideration since the hepatotoxicity of xenobiotics and drugs in man is the ultimate question.

Adolescent↗
PubMed1991

Liver slices in dynamic organ culture. I. An alternative in vitro technique for the study of rat hepatic drug metabolism.

1. Precision-cut liver slices in dynamic organ culture, a novel in vitro technique, is described and applied to the study of hepatic drug metabolism in the rat. 2. These slices catalysed the oxidative O-deethylation of the substrate, 7-ethoxycoumarin, over 6 h incubation. In addition, the direct conjugation of 7-hydroxycoumarin with either sulphate or glucuronic acid was maintained over 6 h. 3. The formation of 7-hydroxycoumarin and the presence of the sulphate and glucuronide conjugates in slices exposed to 7-ethoxycoumarin demonstrated integrated phase I and phase II drug metabolizing activities in this system. 4. Minor modifications of the incubation system allowed for the metabolism of four volatile chlorinated benzenes: monochlorobenzene 1,2-, 1,3-, and 1,4-dichlorobenzenes to aqueous soluble metabolites. 5. The use of liver slices in dynamic organ culture as an alternative preparation for the study of xenobiotic metabolism is discussed.

Animals↗
PubMed1991

Liver slices in dynamic organ culture. II. An in vitro cellular technique for the study of integrated drug metabolism using human tissue.

1. Precision cut human liver slices in dynamic organ culture have been used to study the integrated metabolism of 7-ethoxycoumarin and the conjugation of 7-hydroxycoumarin. 2. The metabolism of 7-ethoxycoumarin and 7-hydroxycoumarin was monitored for 6 h. For both substrates there was a time-dependent increase in metabolites present in the incubation medium. The low levels of free 7-hydroxycoumarin found in the medium when 7-ethoxycoumarin was the substrate suggests good coupling of phase I and phase II metabolism. 3. With suitable incubation conditions, i.e. change of medium containing new substrate every 2 h, the metabolism of both 7-ethoxycoumarin and 7-hydroxycoumarin by human liver slices was found to proceed at similar rates for up to 24 h. This was demonstrated using five separate human liver preparations. 4. Human liver slices also metabolized mono-chlorobenzene and o-, m- and p-dichlorobenzene to aqueous soluble metabolites. There was a time-dependent increase in the appearance of aqueous soluble metabolites present in the incubation medium. Metabolites were not retained by the liver slices. 5. A cold-storage transit buffer has been described and used to maintain the levels of drug metabolism in both rat and human tissue for periods of up to 6 h. 6. The use of human liver slices in dynamic organ culture as a suitable method for the direct assessment of integrated hepatic drug metabolism is proposed.

Adolescent↗
PubMed1990

Long-term trial with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1). I. Iron chelation and metabolic studies.

A long-term clinical trial of 1-15 months has been carried out with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in 13 transfusion-dependent iron-loaded patients. Urinary iron excretion was greatest in patients with thalassaemia major and was related to the number of previous transfusions but not to the serum ferritin level. Substantial increases of urinary iron were observed in all the patients when the frequency of the daily dose was doubled and in response to 2 x 3 g L1 daily 11 of 12 patients tested excreted greater than 25 mg iron daily, the mean daily intake of iron from transfusion. Serum ferritin levels have fluctuated but overall have remained unchanged. Pharmacological studies in five patients have indicated rapid absorption probably from the stomach and variable plasma half life of 77 +/- 35 min (X +/- SD). Glucuronation was identified as a major route of L1 metabolism. Short-term intensive chelation studies using repeated administration of L1 resulted in further increases of urinary iron excretion by comparison to a single dose. In one case 325 mg of iron were excreted in the urine following the administration of 16 g (5 x 2 g + 2 x 3 g) within 24 h. Iron excretion studies were carried out in six transfusional iron-loaded patients who were maintained on a low iron diet before and during chelation. No significant increases of faecal iron excretion were observed with L1 using daily doses of up to 3 x 3 g and 4 x 2 g. The high level of compliance during treatment with L1 and the levels of urine iron excretion that can be achieved increase the prospects for oral chelation in transfusional iron-loaded patients.

Anemia↗
PubMed1990

Molecular cloning of pneumonia virus of mice.

cDNA clones representing nine genes of pneumonia virus of mice (PVM) have been generated. The sizes of the corresponding mRNAs and a provisional transcriptional map of the virus genome have been determined. The apparent gene order is very similar to that of respiratory syncytial virus. The sequences adjacent to the 3' termini of the PVM genes were determined and are very similar to those of respiratory syncytial virus. Several PVM gene polypeptide products have been assigned.

Animals↗
PubMed1988

Acute rheumatic fever in the young: changing prevalence and pattern.

Acute rheumatic fever (ARF) is rare in young people. A group of 28 patients is described who were hospitalized during the years 1960-1984. Patients were divided into two groups: children who were admitted between 1960 and 1966 and those admitted between 1966 and 1984. The annual incidence of ARF declined from 1.17 to 0.44 cases per 10,000 population at risk. The incidence of arthritis declined in parallel to the decrease in number of children presenting with ARF, whereas the incidence of carditis remained the same.

Acute Disease↗
PubMed1987

Effective chelation of iron in beta thalassaemia with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one.

The main iron chelator used for transfusional iron overload is desferrioxamine, which is expensive, has toxic side effects, and has to be given subcutaneously. An orally active iron chelator is therefore required. The effects of oral 1,2-dimethyl-3-hydroxypyrid-4-one on urinary iron excretion were studied in eight patients who had received multiple transfusions: four had myelodysplasia and four beta thalassaemia major. Different daily doses of the drug up to 100 mg/kg/day, alone or in combination with ascorbic acid, were used. In three patients with thalassaemia the effect of the drug was compared with that of subcutaneous desferrioxamine at the same daily dose. In all eight patients a single dose of oral 1,2-dimethyl-3-hydroxypyrid-4-one resulted in substantial urinary iron excretion, mainly in the first 12 hours. Urinary iron excretion increased with the dose and with the degree of iron loading of the patient. Giving two or three divided doses over 24 hours resulted in higher urinary iron excretion than a single dose of the same amount over the same time. In most patients coadministration of oral ascorbic acid further increased urinary iron excretion. 1,2-Dimethyl-3-hydroxypyrid-4-one caused similar iron excretion to that achieved with subcutaneous desferrioxamine at a comparable dose. In some cases the iron excretion was sufficiently high (maximum 99 mg/day) to suggest that a negative iron balance could be easily achieved with these protocols in patients receiving regular transfusions. No evidence of toxicity was observed on thorough clinical examination or haematological and biochemical testing in any of the patients. None of the patients had any symptoms that could be ascribed to the drug. These results suggest that the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one is as effective as subcutaneous desferrioxamine in increasing urinary iron excretion in patients loaded with iron. Its cheap synthesis, oral activity, and lack of obvious toxicity at effective doses suggest that it should be developed quickly and thoroughly tested for the management of transfusional iron overload.

Administration, Oral↗
PubMed1986

A bovine respiratory virus vaccination trial.

A respiratory virus vaccination trial was carried out in a commercial calf-rearing unit with a history of virus pneumonia. The effects of vaccination on the incidence of virus respiratory disease and growth rate were assessed. Forty-four bought-in calves were allocated to groups and treated as follows: A, unvaccinated controls; B, intranasal temperature-sensitive infectious bovine rhinotracheitis (IBR) vaccine at three and 10 weeks; C, intranasal temperature-sensitive combined IBR and parainfluenza-3 (PI3) vaccine at three and 10 weeks; D, intranasal temperature-sensitive combined IBR and PI3 vaccine at three and 10 weeks plus live attenuated bovine respiratory syncytial (BRS) virus vaccine intramuscularly at seven, 10 and 16 weeks. Two outbreaks of virus pneumonia occurred, one at three to four months of age associated with BRS virus and the other at four to five months of age with PI3 virus. During these outbreaks the incidence of pneumonia was lower and the number of days of elevated temperature and the number of treatments were significantly less in groups vaccinated against the associated virus. Despite these findings there were no significant differences between the growth rates of the groups either during the outbreaks of virus pneumonia or during the 10 month period to slaughter.

Animals↗
PubMed1986

A randomized clinical trial of oral ursodeoxycholic acid in obstructive jaundice.

Forty patients with obstructive jaundice (bilirubin greater than 100 mumol/l) were entered into a randomized trial of oral ursodeoxycholic acid for 48 h before surgery versus no additional therapy. Pre-operative venous and operative portal total bile salt concentrations were higher in the bile salt treated patients (P less than 0.001). Portal endotoxaemia during operation was reduced in ursodeoxycholic acid treated patients (P less than 0.05). There was no significant difference in systemic venous endotoxaemia, renal function or postoperative morbidity or mortality. This study suggests pre-operative oral bile salt therapy may be of no clinical benefit in patients with obstructive jaundice.

Administration, Oral↗