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Biomedical subjects

T V Murphy

Publications and source records attributed to T V Murphy.

At least 55 records · Page 3Linked to original sources
PubMed1989

Modulation of noradrenaline release in slices of rat kidney cortex through alpha 1- and alpha 2-adrenoceptors.

Slices of rat kidney cortex were incubated in [3H]noradrenaline, then placed in a flow cell and subjected to electrical field stimulation. At a stimulation frequency of 5 Hz, both the alpha 2-adrenoceptor antagonist idazoxan (0.1 microM) and the alpha 1-adrenoceptor antagonist prazosin (0.1 microM) significantly enhanced the stimulation-induced (S-I) outflow of radioactivity from the slice. However, neither clonidine (0.1 microM) nor methoxamine (10 microM), alpha 2- and alpha 1-agonists respectively, affected the S-I outflow of radioactivity at this stimulation frequency. At a lower stimulation frequency (1 Hz), the S-I outflow of radioactivity was not affected by idazoxan or prazosin, but was inhibited by both clonidine and methoxamine. The effect of clonidine was prevented by idazoxan (0.1 microM), but not by prazosin (0.1 microM). The effect of methoxamine was abolished by prazosin (0.1 microM), but not by idazoxan (0.1 microM). The inhibitory effect of methoxamine was not prevented by the prostaglandin synthesis inhibitor indomethacin (10 microM) or the adenosine receptor antagonist 8-phenyltheophylline (1 microM) and thus was not mediated by either prostaglandins or adenosine. The results suggest that both prejunctional alpha 1- and alpha 2-adrenoceptors are directly involved in modulation of noradrenaline release from the renal sympathetic nerves of the rat.

Animals↗
PubMed1989

Host and bacterial factors associated with Haemophilus influenzae type b disease in Minnesota children vaccinated with type b polysaccharide vaccine.

Host and bacterial factors were evaluated among 86 Minnesota children with Haemophilus influenzae type b disease detected by active surveillance after introduction of type b polysaccharide vaccine in the state. Children were 2-6 y of age. Thirty-three (38%) had been vaccinated. There was no significant difference between the frequency of low serum concentrations of IgM, IgA, IgG, or IgG2 in the vaccinated and nonvaccinated subjects (13% vs. 8%, P = .5). The presence of the Gm immunoglobulin allotype phenotype (1,3,17;23;5,13,21), previously associated with a lower relative risk of vaccine failure in children from other states, was associated with a fourfold decrease in the relative risk of vaccine failure in Minnesota (P less than .07). Haemophilus isolates from 58 of the children were available for clonal characterization by multilocus electrophoresis and outer membrane protein subtyping. There were no significant differences between the clone distribution of the strains causing disease in vaccinated and nonvaccinated patients, and nearly all disease-producing clones in Minnesota also are known to cause disease in other areas of the country. Thus, vaccine failure in Minnesota is infrequently associated with hypogammaglobulinemia or with infection by unusual clones of a H. influenzae type b. Also, the Gm phenotype associated with protection against vaccine failure in other areas of the USA appears to be protective in Minnesota.

Antibodies, Bacterial↗
PubMed1989

Beta-adrenoceptor blockade and sympathetic neurotransmission in the pithed rat.

The effects of the beta 1-adrenoceptor blocking drug atenolol and the beta 2-adrenoceptor blocking drug ICI 118551 (ICI, Melbourne, Australia) on noradrenaline release and blood pressure were investigated using the pithed rat, which was subjected to continuous electrical stimulation of the spinal sympathetic outflow (pulses at 3 Hz). This stimulation increased blood pressure but not heart rate. The noradrenaline release rate was calculated by infusing [3H] noradrenaline and measuring the steady-state concentrations of both endogenous and infused noradrenaline. Atenolol (0.2 mg/kg bolus plus 0.1 mg/kg per h, intra-arterially) had no effect on the noradrenaline release rate or heart rate, but significantly decreased blood pressure. On the other hand, ICI 118551 (0.2 mg/kg bolus plus 0.1 mg/kg per h. intra-arterially) had no significant effect on blood pressure or heart rate, but did inhibit the noradrenaline release rate. The sympathoinhibitory effect of ICI 118551 was not observed in animals which had been adrenal medullectomized, suggesting that its effect on noradrenaline release was due to blockade of activation of facilitatory prejunctional beta 2-adrenoceptors by adrenaline. The reduced noradrenaline release in the presence of ICI 118551 was not accompanied by a reduction in blood pressure. This may be because ICI 118551 also blocked vasodilatory beta 2-adrenoceptors on vascular smooth muscle. Indeed, in unstimulated pithed rats, infusions of adrenaline which were non-pressor were found to be pressor after ICI 118551 was administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗
PubMed1989

Excretion of Haemophilus influenzae type b polysaccharide antigen in urine of healthy nasopharyngeal carriers.

We measured concentrations of Haemophilus influenzae type b (Hib) polysaccharide antigen by ELISA in urine samples from 81 healthy North American children with positive or negative throat cultures for Hib, to investigate the possibility that asymptomatic carriers may have antigenuria. For comparison, we determined the concentrations of Hib polysaccharide antigen in urine samples from 56 patients with proven Haemophilus disease, including 13 children with lower respiratory infections who resided in developing countries. Among the healthy children, antigen was detected in the urine of seven of 19 (37%) carriers of Hib compared with one of 62 (2%) children with negative throat cultures (p less than 0.001). Among the patients with invasive Haemophilus infections, 93% had antigen detected. Although there was overlap in the concentrations of antigen in the positive urines from the asymptomatic carriers and those of the ill patients, the concentrations of the ill patients were higher than those of the carriers. The respective geometric means of the positive patients were: American patients with meningitis, 42.5 ng/mL (range 1.7-9800 ng/mL); American patients with infections not involving the CNS, 5.8 ng/mL (range: 1.0-96 ng/mL); patients from developing countries with lower respiratory infections, 29.6 ng/mL (range: 0.9-5290), and American asymptomatic carriers, 1.9 ng/mL (range: 0.6-16.7 ng/mL). Thus, antigenuria is present in a high proportion of healthy children with positive throat cultures for Hib, and the antigen concentrations of the carriers overlap those of ill patients. These results suggest that either mucosal colonization itself is sufficient to produce antigen-uria, or asymptomatic carriers may be experiencing asymptomatic invasive Hib infection.

Antigens, Bacterial↗
PubMed1989

Haemophilus influenzae type b in respiratory secretions.

Oral and respiratory secretions of 31 children who were healthy or had mild upper respiratory infection, and who had a positive throat culture for Haemophilus influenzae type b, were cultured to determine which secretions contain this organism and how long it can be recovered from fomites. Rhinorrhea was present in 11 of 31 (34%) children and nasal mucus was positive for H. influenzae type b in 10 (91%). In 5 of these children the concentration of H. influenzae type b in nasal mucus was 10(4) to 10(7) colony-forming units/ml3. H. influenzae type b in nasal mucus applied to fomites were recovered for 12 hours. Cultures of saliva and cough secretions compared with nasal mucus were less often positive (3 of 31, P less than 0.001; 3 of 25, P less than 0.001, respectively) and contained fewer H. influenzae type b (5 and 15 colony-forming units, respectively). H. influenzae type b was recovered from the hand of 2 of 27 (7%) children; both children had positive cultures of saliva. These data indicate that H. influenzae type b can be found in oral and respiratory secretions of pharyngeal carriers and can contaminate children's hands. Nasal mucus was the most consistently positive secretion and contained the largest number of bacteria. Careful management of nasal mucus secretions is warranted in settings where transmission could occur to susceptible children.

Child↗
PubMed1988

The protective efficacy of Haemophilus b polysaccharide vaccine.

To assess the protective efficacy of the Haemophilus b polysaccharide vaccine, a case-control study was conducted in Connecticut, Dallas County, and greater Pittsburgh. Seventy-six children 24 to 72 months of age who had H influenzae type b isolated from normally sterile sites from August 1985 through July 1987 were enrolled. For each case two controls, matched by age and place of residence, were randomly selected from the records of all live births in the area. Antecedent receipt of the Haemophilus b polysaccharide vaccine was ascertained from the records of all physicians and clinics at which the subjects received medical care. Overall, 12% of the cases and 39% of the controls had received the vaccine. The estimate of the protective efficacy of the vaccine was 88% overall (95% confidence interval, 74% to 96%) and 91% (95% confidence interval, 71% to 99%), 92% (95% confidence interval, 76% to 99%), and 81% (95% confidence interval, 45% to 96%) in Connecticut, Dallas County, and greater Pittsburgh, respectively. The estimates were not substantially affected by adjusting with logistic regression for differences between the cases and controls in race and the attendance of group day care. We conclude that the Haemophilus b polysaccharide vaccine is highly effective in these areas among children who receive the vaccine when they are 24 months of age or older.

Age Factors↗
PubMed1987

Risk of subsequent disease among day-care contacts of patients with systemic Hemophilus influenzae type B disease.

There is controversy about whether to provide rifampin prophylaxis routinely to contacts in day-care facilities of a patient with a primary case of Hemophilus influenzae type b disease. We prospectively investigated primary cases of H. influenzae type b disease in day-care facilities in Dallas County, Texas, to determine the rate of subsequent disease among contacts. Ninety-one children with primary cases of H. influenzae type b disease who were attending day-care facilities were enrolled from October 1982 to October 1984. A total of 587 classroom contacts of these children under four years of age were not given rifampin. During 60 days of follow-up, there was one subsequent case in a classroom contact. Untreated children under two years of age who were directly exposed to a patient with a primary case were considered to be at highest risk of disease, but there were no subsequent cases in this group of 361 children. However, there were two cases in new enrollees who started attending day-care facilities during the 60-day follow-up period but who were not exposed to a patient with a primary case. At day-care centers in which there was a second case during the follow-up period, there was a high prevalence of colonization with H. influenzae type b in both patient and nonpatient groups of preschool children. These data indicate that the rate of subsequent disease in classroom contacts of patients in day-care facilities is lower than that reported in households (1 of 587 vs. 20 of 829, P = 0.001) and that this rate may be similar to the base rate of primary disease in day-care facilities. We conclude that rifampin prophylaxis may not be appropriate after the occurrence of a primary case of H. influenzae type b disease in a day-care facility in Dallas County.

Child Day Care Centers↗
PubMed1987

Second episodes of Haemophilus influenzae type b disease following rifampin prophylaxis of the index patients.

Patients treated for Haemophilus influenzae type b disease frequently remain nasopharyngeal carriers of that organism and fail to develop protective concentrations of serum antibody. It has been suggested that rifampin prophylaxis of the index patient may prevent recurrence of disease by eliminating type b Haemophilus carriage. We report nine children who developed second episodes of disease 1 week or more after receiving rifampin prophylaxis. The median interval between the last dose of rifampin and admission to the hospital for the second episode was 70 days (range, 9 to 138). Analysis of biotypes and outer membrane protein polyacrylamide gel electrophoresis patterns of paired isolates from eight cases revealed that the second episodes in two of the children were caused by acquisition of new type b Haemophilus strains, whereas the second episodes in the remaining six children were caused by isolates which were indistinguishable from the respective isolates from the first episodes. Rifampin prophylaxis of the index patient may prevent some episodes of recurrent disease. However, in some patients who have received prophylaxis, second episodes can occur, probably as a result of reacquisition of the organism from contacts who did not receive rifampin or from acquisition of new type b strains.

Bacterial Outer Membrane Proteins↗
PubMed1987

Prospective surveillance of Haemophilus influenzae type b disease in Dallas County, Texas, and in Minnesota.

Among children less than 12 years of age residing in Dallas County, Texas, and in the state of Minnesota we conducted prospective, active surveillance of invasive Haemophilus influenzae disease. During 18 months, 616 cases were identified, of which 600 were caused by type b organisms. The annual incidence of disease was significantly greater in Dallas than in Minnesota (109 v 68/100,000 children younger than 5 years of age, P less than .001) and was greater in Dallas, even when rates for white children in the two regions were compared (P less than .001). Other regional differences were observed. In Dallas, a larger proportion of cases were in children attending day-care centers (27% compared with 12% in Minnesota, P less than .001) and more patients attended day care for greater than 40 h/wk (56% compared with 30% in Minnesota, P less than .001). Outer membrane protein subtyping of isolates revealed that in Dallas 6U isolates were associated significantly with cases in black children who attended day care. In Minnesota, but not in Dallas, isolates with subtype 1H were associated significantly with cases in children in day care. These data indicate that there are regional differences in the epidemiology of type b Haemophilus disease that may relate to differences in strains, day-care practices, or other unknown cultural or environmental factors. Finally, because only 15% of systemic Haemophilus disease in these regions occurred in children in the age groups recommended for vaccination (24 to 59 months), the new Haemophilus type b polysaccharide vaccine is expected to have a limited impact on the overall incidence of disease.

Bacterial Outer Membrane Proteins↗
PubMed1986

Hemophilus influenzae type B disease in children vaccinated with type B polysaccharide vaccine.

We studied 55 cases of invasive Hemophilus influenzae type b disease occurring in children at least three weeks after vaccination with type b polysaccharide vaccine. Their mean age at the time of immunization was 27.8 months (range, 18 to 47). Meningitis developed in 39 patients, of whom 3 died and 6 had neurologic sequelae. We investigated certain host factors that may have contributed to the failure of the vaccine. The geometric mean concentration of antibody to type b polysaccharide in convalescent-phase serum from 31 of the vaccinated patients who had hemophilus disease was significantly lower than that in serum from 25 patients of similar age with the disease who had never been vaccinated (0.59 vs. 3.46 micrograms per milliliter, P less than 0.001). However, only 3 of 46 patients in whom the vaccine failed and who were tested for hypogammaglobulinemia had this finding, and none of 33 children tested for IgG2 had low serum concentrations of this immunoglobulin subclass, which is thought to be important in the immune response to polysaccharide antigens. In addition, all but 1 of the 46 patients in whom the vaccine failed and who were tested for IgG antibody to tetanus toxoid protein, a thymic-dependent antigen, had normal values, and 19 of 20 tested for hemolytic complement activity had normal levels. In white children, the presence of the Gm immunoglobulin phenotype (1,2,3, 17; ;5,13,21) was associated with a sevenfold increase in the relative risk of vaccine failure (P less than 0.003). We conclude that vaccine failure may be related in part to genetic factors, and that most vaccinated children in whom Hemophilus influenzae disease develops have deficient antibody responses to the type b polysaccharide despite normal serum concentrations of immunoglobulin and normal antibody responses to tetanus toxoid.

Antibodies, Bacterial↗
PubMed1986

Use of rapidly generated results in patient management.

The usefulness of a rapid diagnostic test in patient management depends on the sensitivity of the test, the clinical consequences of false-negative or false-positive results, the ease and cost of performance, and the timely availability of results. A test that is sensitive, specific, inexpensive, and rapid is presumed to be useful clinically. However, there has been surprisingly little effort to measure the actual impact of the results on patient care. Since antigen detection for Haemophilus influenzae type b disease has been available for more than a decade, it will be used as a model to illustrate several factors that help determine the benefits, limitations, and pitfalls of antigen detection in the management of patients with serious bacterial infections. Herein we will compare the use of antigen detection in meningitis with that in other Haemophilus influenzae type b diseases. We also will review our experience with the impact of rapid diagnosis on the treatment of bacterial meningitis. Finally, other factors that influence the usefulness of antigen detection on patient care will be explored by comparing the potential consequences of laboratory error on the management of patients with Haemophilus influenzae type b infections with that of management of other kinds of infections, such as streptococcal pharyngitis, sexually transmitted diseases, and viral respiratory infections.

Antigens, Bacterial↗
PubMed1985

Pharyngeal colonization with Haemophilus influenzae type b in children in a day care center without invasive disease.

During an 18-month period, monthly pharyngeal cultures for Haemophilus influenzae type b (Hib) were obtained from 66 children and their caretakers in a day care center in which no systemic disease caused by Hib occurred. The average colonization rate for Hib was 10%, and ranged from 0% to 23% for a single month. Infants housed in a separate building with a cohorted staff were not colonized by Hib. However, 71% of the toddler group and 48% of the preschool group became colonized by Hib at some time during the 18-month-study. Of 89 Hib isolates, 93% were biotype 1 (Kilian), and 90% of these had a similar outer membrane protein profile, designated subtype 1L. This strain was recovered from children at the center for 15 of 18 months. No invasive disease occurred. Thus, Hib may be widespread among preschool children in a day care center and persist for longer than a year without resulting in systemic disease.

Child↗