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H O'Brien

Publications and source records attributed to H O'Brien.

At least 19 recordsLinked to original sources
PubMed2000

A comparison of molecular and enzyme-based assays for the detection of thiopurine methyltransferase mutations.

S-Methylation by thiopurine methyltransferase (TPMT) is an important route of metabolism for the thiopurine drugs. About one in 300 individuals are homozygous for a TPMT mutation associated with very low enzyme activity and severe myelosuppression if treated with standard doses of drug. To validate the use of molecular genetic techniques for the detection of TPMT deficiency, we have determined red blood cell TPMT activity in 240 adult blood donors and 55 normal children. Genotype was determined by restriction fragment length analysis of polymerase chain reaction products in a cohort of 79 of the blood donors and five cases of azathioprine-induced myelosupression, and this confirmed a close relationship between genotype and phenotype. In 17 of the 24 cases in which mutations were found, DNA was also available from remission bone marrow. In one of these cases, DNA from the remission marrow sample indicated the presence of a non-mutated allele that had not been seen in the blast DNA sample obtained at presentation. These results indicate that polymerase chain reaction-based assays give reliable and robust results for the detection of TPMT deficiency, but that caution should be exercised in relying exclusively on DNA obtained from lymphoblasts in childhood leukaemia.

Adolescent↗
PubMed2000

K-ras mutations, rectal crypt cells proliferation, and meat consumption in patients with left-sided colorectal carcinoma.

It has been suggested that N-nitroso compounds derived from meat may increase the risk of K-ras mutations in the human colon. We sought evidence of associations between red meat consumption, frequency and type of K-ras mutations in resected tumours, and the rate of crypt cell proliferation (CCP) in the normal mucosa of patients with left-sided colorectal carcinoma. Meat consumption was assessed by food frequency questionnaire, and CCP was determined in rectal biopsies obtained prior to surgery. K-ras mutations in the resected tumours were determined using a PCR-based oligonucleotide hybridization assay. Fifteen K-ras mutations were detected in tumours from 43 patients; 13/15 in codon 12, 3/15 in codon 13, and 1/15 in both codons 12 and 13. All mutations were G-->A or G-->T transitions. There was no statistically significant difference between intakes of red meat in patients with a K-ras mutation (92.4 +/- 9.7 g/day) and those without (82.3 +/- 7.7 g/day). Rectal CCP was significantly higher in patients than in healthy controls, but there was no correlation with meat consumption or K-ras mutation. These data do not support the hypothesis that meat consumption is a risk factor for acquisition of K-ras mutations during colorectal carcinogenesis.

Aged↗
PubMed1994

Nosocomial transmission of disease caused by nontypeable strains of Haemophilus influenzae.

PURPOSE: The authors evaluated a geographic and temporal cluster of lower respiratory tract infections due to unencapsulated (serologically nontypeable) Haemophilus influenzae to determine whether this event represented the transmission of a single clone. METHODS AND MATERIALS: H influenzae was recovered from eight patients at a nursing home and from three patients in an adjacent acute care hospital. Serotypes, biotypes, outer membrane protein profiles, and multilocus enzyme genotypes were determined to characterize bacterial isolates. Patient records were retrospectively examined to determine clinical and epidemiologic characteristics. RESULTS: During a 10-day period in September 1991, lower respiratory tract infections caused by H influenzae were diagnosed in four patients residing in a single nursing home unit. Oropharyngeal cultures from four of seven asymptomatic roommates of these patients also grew H influenzae. During the month before and after the nursing home cluster of cases, four other individuals in acute care areas of the hospital had positive sputum cultures for H influenzae. Three of these latter specimens were also available for analysis. All H influenzae isolates were unencapsulated and beta-lactamase-negative. Eight of the nine isolates from the nursing home patients (two morphologically distinct colony types of H influenzae were isolated from one case) had a single outer membrane protein profile arbitrarily designated as X and a single multilocus enzyme genotype arbitrarily designated as A. In contrast, none of the isolates from the acute care cases had this profile (P < or = 0.02; two-tailed Fisher's exact test). The isolates obtained from two of the patients in acute care areas had an outer membrane protein profile arbitrarily designated as Y and a single multilocus enzyme genotype designated as B. These two patients were contemporaneously hospitalized in adjacent intensive care unit cubicles. The remaining isolates displayed an outer membrane protein profile arbitrarily designated as W. All roommates of the four patients in the nursing home were administered oral rifampin 600 mg daily for 4 days. H influenzae was not recovered from follow-up oropharyngeal cultures obtained 1 week after the completion of therapy. No beta-lactamase-negative H influenzae were identified in this unit during the subsequent 9 months. CONCLUSION: This study furnishes strong evidence for the nosocomial transmission of a clone of unencapsulated H influenzae in a nursing home unit. Epidemiologic data showed temporal and geographic clustering of respiratory tract infections and colonization by H influenzae. Outer membrane protein profiles and multilocus enzyme genotype analysis indicated that seven of eight patients at the nursing home carried a single clone of unencapsulated H influenzae. Laboratory and epidemiologic data also demonstrated the presence, and possible nosocomial transmission, of a second clone of unencapsulated H influenzae in a physically separate area of the hospital. Finally, although a causal relationship is not proven, the outbreak ended following the administration of rifampin prophylaxis of asymptomatic carriers.

Bacterial Outer Membrane Proteins↗
PubMed1993

Characterization of the alpha 1-adrenoceptors of the rat prostate gland.

The alpha 1-adrenoceptor-mediated responses of the rat prostate to phenylephrine have been examined in-vitro. Phenylephrine induced concentration-dependent contractions of the isolated prostate gland which were antagonized by WB4101 (1-30 nM). Schild plot analysis of the antagonism yielded a straight line with a slope not significantly different from unity. The pKB value of 9.2 was similar to that obtained for WB4101 on the rat vas deferens (9.4) but was greater than that obtained on the rat spleen (8.4). Chloroethylclonidine depressed responses to phenylephrine of the rat spleen but not the prostate or the vas deferens. These results indicate that the rat prostate gland possesses a typical alpha 1A-adrenoceptor similar to that found in the vas deferens.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1993

Effects of alfentanil on the hemodynamic and catecholamine response to tracheal intubation.

A randomized, placebo-controlled study was conducted in 60 ASA Class I, II, and III patients to determine the dose response of alfentanil in moderating the cardiovascular and catecholamine response to tracheal intubation (INT). Patients were randomly allocated into one of four groups to receive either 15 micrograms/kg alfentanil (A15), 30 micrograms/kg alfentanil (A30), 45 micrograms/kg alfentanil (A45), or normal saline (control), given intravenously (i.v.) before induction of anesthesia. One minute after administration of 4.0 mg/kg thiopental and 1.5 mg/kg succinylcholine i.v., tracheal intubation was performed using direct laryngoscopy. In response to INT, increases in heart rate, systolic blood pressure, and systemic vascular resistance occurred in the control group. These changes were significantly more than corresponding changes of heart rate, systolic blood pressure, and systemic vascular resistance in all three alfentanil groups (P < 0.05). In contrast, cardiac index and ejection fraction decreased moderately in every group during the study period, but there were no differences among groups with respect to either cardiac index or ejection fraction at corresponding times following INT. In the control group, epinephrine and norepinephrine serum concentrations increased by 152 +/- 52% and 58 +/- 62%, respectively, following INT (different from A30 and A45, P < 0.05). However, up to a dose of 30 micrograms/kg (A30), a dose-dependent decrease in the maximum percent changes of both epinephrine and norepinephrine occurred in response to INT. A larger dose of alfentanil was no more efficacious as the catecholamine response to tracheal intubation was not significantly different when comparing the A45 and A30 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Management and epidemiologic analyses of an outbreak due to methicillin-resistant Staphylococcus aureus.

PURPOSE: Following implementation of special measures to control a nosocomial outbreak of methicillin-resistant Staphylococcus aureus (MRSA), we used immunoblot typing in conjunction with antimicrobial susceptibility testing to investigate the epidemiology of this event and to determine whether this outbreak represented the failure of infection control measures to limit the spread of previously endemic MRSA strains or the introduction of a new strain of MRSA. MATERIALS AND METHODS: Isolates of MRSA recovered from hospitalized patients were initially categorized on the basis of antimicrobial susceptibility results. Organisms susceptible to ciprofloxacin and/or trimethoprim/sulfamethoxazole were recovered from patients at a relatively constant rate prior to December 1988 and were categorized as endemic isolates. Subsequently, there was an outbreak due to organisms resistant to both of these antibiotics; these were therefore categorized as outbreak isolates. Isolates were later characterized by immunoblot typing. Prior to this analysis, isolates were given code numbers so that clinical and epidemiologic data as well as resistance patterns were not known until this testing was complete. RESULTS: Between January 1986 and November 1988, an average of 3.9 patients per month acquired nosocomial MRSA in the Sepulveda Veterans Administration Medical Center. In contrast, from December 1988 to October 1989, 369 MRSA isolates were collected from 125 patients (an average of 11.4 patients per month). Prior to December 1988, all tested nosocomial isolates of MRSA were susceptible to ciprofloxacin and/or to trimethoprim/sulfamethoxazole. In contrast, the outbreak was due to spread of MRSA isolates resistant to these antibiotics. Immunoblot typing of 204 isolates from 98 individuals identified five distinct immunoblot types of which types B and C were by far the most common. Type B was highly associated with outbreak isolates, whereas type C was associated with endemic isolates (p less than 0.001). All sequential isolates from single patients that belonged to different susceptibility categories demonstrated discordant immunoblot types. In contrast, concordant immunoblot types were observed for 25 of 27 sequential isolates that displayed minor variations in antimicrobial resistance. The institution of more stringent infection control measures was followed by the return of nosocomial MRSA acquisition rates to pre-outbreak levels. Although novobiocin and trimethoprim/sulfamethoxazole were extensively used to treat patients harboring outbreak and endemic isolates, respectively, in no instance was the initial MRSA isolate from any patient resistant to novobiocin and only 6% of initial endemic isolates displayed trimethoprim/sulfamethoxazole resistance. A modest, significant increase in the resistance of endemic isolates to various other antimicrobial agents was noted however. CONCLUSION: Immunoblot analyses provided strong, corroborative evidence that at least two separate strains of MRSA were present during the outbreak and that a newly introduced strain with a distinctive antimicrobial resistance pattern was primarily responsible for the rapid spread of MRSA during the outbreak. The observation that previously effective infection control measures failed to prevent the nosocomial spread of a newly introduced community-acquired MRSA strain suggests that a single set of control measures may not be equally efficacious against all strains of MRSA. In this regard, previously reported variations in resistance to topical antimicrobials and/or antiseptics, and differences in virulence factors such as colonization potential, invasiveness, and survival on fomites, may warrant further study. Control of the outbreak strain of MRSA in our institution did occur after the implementation of more strenuous isolation procedures.(ABSTRACT TRUNCATED)

California↗
PubMed1991

Intravenous gammaglobulin therapy in the thrombocytopenia of haemorrhagic varicella.

We report the case of a teenage boy with thrombocytopenia complicating varicella infection, which responded promptly to treatment with intravenous immunoglobulin therapy. Such treatment is well recognized in the management of immune thrombocytopenia, particularly where steroids are contra-indicated, but we have not found any previous case reports of the use of immunoglobulin in this condition.

Adolescent↗
PubMed1987

Stomatocytosis, abnormal platelets and pseudo-homozygous hypercholesterolaemia.

A 13-yr-old girl with congenital haemolytic anaemia associated with pseudo-homozygous hypercholesterolaemia is described. The erythrocyte morphology showed 50-80% stomatocytes, but no abnormality of membrane lipid or protein composition or of cation transport was detected. The platelets were reduced in number, abnormally large and showed reduced adhesion. Successful treatment of the hypercholesterolaemia did not influence the stomatocytosis.

Adolescent↗
PubMed1982

Recurrent thrombocytopenia, erythroid hypoplasia and sideroblastic anaemia associated with hypothermia.

A distinct and previously undescribed haematological picture was noted in three patients with hypothermia. During hypothermia there was anaemia with reduced normoblastic erythropoiesis, marked sideroblastic change and thrombocytopenia in the presence of a normal number of megakaryocytes. In two patients as the body temperature returned to normal these changes were slowly reversed. Evidence both from observations in patients and from animal experiments is given why the haematological changes are due to the hypothermia.

Adult↗
PubMed1980

Autoimmune thrombocytopenia in pregnancy.

The laboratory diagnosis of autoimmune thrombocytopenia has only recently become more satisfactory. In this study a fluorescein-labelled antiglobulin technique was used to investigate the immunochemical properties of the platelet antibody detected in a pregnant woman with severe thrombocytopenia. The antibody was autoimmune and appeared to have specificity for platelet antigens. It had both IgG and IgM components and did not fix complement. Steroids had a beneficial effect indicated by a return to normal of the platelet count, a falling antibody titre and the disappearance of detectable antibody on the patient's own platelets. Studies on the baby showed that the antibody had not crossed the placenta in detectable amounts.

Adult↗
PubMed1980

Hydrolysis of pyridoxal-5'-phosphate in plasma in conditions with raised alkaline phosphate.

Hydrolysis of pyridoxal phosphate in plasma was demonstrated in patients with liver disease and other conditions with raised alkaline phosphatase, and this usually closely paralleled the alkaline phosphatase level, whether of liver or bone origin. The endogenous plasma pyridoxal phosphate was inversely related to the alkaline phosphatase, and plasma hydrolysis of pyridoxal phosphate may at least in part be responsible. Very large doses of vitamin B6 may be necessary to compensate for this hydrolysis.

Alkaline Phosphatase↗
PubMed1979

Photochemotherapy in psoriasis: the first six months in Australia.

The results of the first six months of treatment of psoriasis with photochemotherapy in the Skin and Cancer Foundation's clinic resulted in 30 out of 53 patients being completely clear of psoriasis lesions, 14 showing progressive improvement (and subsequently clearing), four failures, and five withdrawals. The treatment is not a cure, and requires maintenance therapy. It involves the use of large expensive machines to deliver ultraviolet light, and demands careful supervision and control dosimetry.

Australia↗