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J McNamara

Publications and source records attributed to J McNamara.

At least 37 records · Page 2Linked to original sources
PubMed1999

Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus. ACTG 179 Study Team. AIDS Clinical Trials Group.

BACKGROUND: Dapsone is an alternative drug for Pneumocystis carinii pneumonia (PCP) prophylaxis in individuals intolerant to trimethoprim-sulfamethoxazole (T/S). There are, however, few data on the pharmacokinetics, toxicity or efficacy of dapsone in children. Design. Randomized, multicenter trial comparing daily (1 or 2 mg/kg) with weekly (4 mg/kg) dapsone regimens in 94 HIV-infected children intolerant to T/S. METHODS: Hematologic and hepatic toxicity was monitored, as well as the occurrence of skin rash, PCP or death. RESULTS: Initial pharmacokinetic data indicated that adequate serum dapsone concentrations were not achieved with the daily 1-mg/kg regimen; the daily dose was then increased to 2 mg/kg. Both short and long term hematologic toxicities were marginally greater in children receiving the daily 2 mg/kg compared with the weekly regimen. Allergic skin rashes were similar in children receiving the daily and weekly regimens (17% in both) and were not associated with prior history of rash with T/S. PCP occurred most frequently with the daily 1-mg/kg regimen (22.0 cases/100 patient years), least frequently with the daily 2-mg/kg regimen (0 case/100 patient years) and at intermediate frequency with the weekly regimen (9.5 cases/100 patient years). More deaths were observed in patients receiving the daily than the weekly regimen (8 vs. 2, respectively), although the deaths were not directly attributable to dapsone treatment. CONCLUSION: Although a weekly dapsone regimen of 4 mg/kg produced less hematologic toxicity than a daily regimen of 2 mg/kg, this advantage was offset by a trend toward higher breakthrough rates of PCP.

AIDS-Related Opportunistic Infections↗
PubMed1999

Pharmacokinetics of dapsone administered daily and weekly in human immunodeficiency virus-infected children.

Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0. 3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age.

Adolescent↗
PubMed1998

Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group.

OBJECTIVE: To determine the ability of live attenuated canarypox virus expressing HIV antigens to induce CD8+ cytotoxic T-cell responses and to prime for neutralizing antibody responses to boosting with purified recombinant gp120 subunit vaccine. DESIGN: A prospective, double-blind, randomized, immunogenicity and safety study was conducted in healthy adults at low risk for acquiring HIV infection and who were seronegative for HIV. METHODS: CD8+ cytotoxic T-cells directed against Env or Gag expressing target cells were measured after live recombinant canarypox-HIV-1 vaccine priming (vaccine given at days 0, 7, 14 and 21). Neutralizing antibodies were measured after subunit boosting (vaccine given at days 28 and 84). RESULTS: CD8+ CTL were induced in 64% of volunteers by the live recombinant canarypox-HIV-1 vaccine. All volunteers who received two doses of subunit vaccine after live recombinant canarypox priming developed neutralizing antibodies directed against laboratory strains of HIV-1 and seven out of eight volunteers tested developed neutralizing antibodies to the primary isolate, BZ167, but to none of eight other primary isolates. Unprimed controls had low or absent neutralizing antibodies after two doses of subunit vaccine. CONCLUSIONS: The live canarypox vector was safe, stimulated cytotoxic T-cells and primed for a vigorous neutralizing antibody response upon boosting with subunit gp120 vaccine. This vaccine combination should be evaluated further for inducing protection against HIV infection.

AIDS Vaccines↗
PubMed1998

Safety and immunogenicity of HIV recombinant envelope vaccines in HIV-infected infants and children. National Institutes of Health-sponsored Pediatric AIDS Clinical Trials Group (ACTG-218).

Study objectives were to evaluate the safety and immunogenicity of three HIV recombinant glycoproteins in HIV-infected infants and children between 1 month and 18 years of age with asymptomatic (P-1) infection. Using Chiron rgp 120 (SF-2) 15 or 50 microg; MicroGeneSys rgp 160 (IIIB) 40 or 320 microg; Genentech rgp120 (MN) 75 or 300 microg; or adjuvant control (Alum or MF-59), children were randomized to a double-blind, placebo-controlled, dose-escalating study of vaccine administered intramuscularly at entry and 1, 2, 3, 4, and 6 months later. No adverse events were attributed to study vaccines. Between 30% and 56% of volunteers exhibited a lymphoproliferative response as defined in terms of stimulation index (SI) to vaccine antigens; 65% of vaccinees but none of placebo recipients exhibited moderate or strong responses after enzyme immunoassay to HIV specific antigens. CD4 cell counts and quantitative HIV culture did not differ significantly among vaccine and control groups, nor were differences found among groups in HIV disease progression. The rgp160 and gp120 subunit vaccines were safe and immunogenic in this population.

AIDS Vaccines↗
PubMed1998

A randomized study of combined zidovudine-lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection. The Pediatric AIDS Clinical Trials Group Protocol 300 Study Team.

OBJECTIVE: The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 300 assessed the clinical efficacy and safety of combination zidovudine/lamivudine (ZDV/3TC) compared with either didanosine (ddI) alone or combination ZDV/ddI. STUDY DESIGN: Children with symptomatic human immunodeficiency virus (HIV) infection, 6 weeks through 15 years of age, were stratified according to age and randomly assigned to receive ddI, ZDV/3TC, or ZDV/ddI. The primary endpoint was time to first progression of HIV disease or death. Enrollment in the ZDV/ddI arm stopped after 11 months on the basis of results of PACTG Protocol 152, but blinded follow-up continued. RESULTS: For the 471 children who could be evaluated, the median age was 2.7 years, median CD4 cell count was 699 cells/mm3, and median log10 HIV RNA was 5.1/mL. Median follow-up was 9.4 months. Patients receiving ZDV/3TC had a lower risk of HIV disease progression or death than those receiving ddI alone (15 vs 38 failures, P = .0006) and a lower risk of death (3 vs 15 deaths, P = .0039). Weight and height growth rates, CD4+ cell counts, and RNA concentrations showed results favoring ZDV/3TC. For patients concurrently randomized to all 3 treatment arms, both ZDV/3TC and ZDV/ddI recipients had lower risk of HIV disease progression than those who received ddI alone (P = .0026 and P = .0045). CONCLUSIONS: Combination therapy with either ZDV/3TC or ZDV/ddI was superior, as determined by clinical and laboratory measures, to monotherapy with ddI.

Adolescent↗
PubMed1998

Phase I safety and pharmacokinetics study of micronized atovaquone in human immunodeficiency virus-infected infants and children. Pediatric AIDS Clinical Trials Group.

A phase I dose-escalating safety and pharmacokinetic study evaluated an oral suspension of micronized atovaquone (m-atovaquone) in infants and children stratified into age groups from 1 month to 12 years of age. Dosages of 10, 30, and 45 mg/kg of body weight/day were evaluated as single daily doses over a period of 12 days. Steady-state concentrations in plasma were determined on day 12, and single postdose concentrations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24. Prior studies with adults suggest that the average plasma atovaquone concentration of 15 micrograms/ml is associated with therapeutic success in more than 95% of patients with Pneumocystis carinii pneumonitis. The results showed m-atovaquone to be safe and well tolerated. Dosages of 30 mg/kg/day were adequate to achieve an average steady-state concentration of greater than 15 micrograms/ml in children ages 1 to 3 months and 2 to 12 years, but a dosage of 45 mg/kg/day was needed to reach this concentration in infants 3 to 24 months of age. The oral suspension of atovaquone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may require a dosage of 45 mg/kg/day.

AIDS-Related Opportunistic Infections↗
PubMed1996

Consequences of hypogammaglobulinemia and steroid therapy in severe bronchopulmonary dysplasia.

We retrospectively studied the relation between corticasteroid therapy, hypogammaglobulinemia (HG), and recurrent infections in 37 infants with moderate to severe bronchopulmonary dysplasia (BPD). Nineteen of the 37 patients had tracheostomies because of chronic respiratory failure. We hypothesized that recurrent infections were most prevalent in infants whose IgG levels remained low at one year of age (persistent HG) and in infants receiving high doses of corticosteroids during the first year of life. We further hypothesized that the duration of HG was strongly correlated with the cumulative first year steroid dose. We also studied the response to intravenous gammaglobulin (IVIG) replacement therapy in this population of BPD infants. Our results showed an association between first year corticosteroid dose, duration of HG (r = 0.49, p < 0.003), and frequency of infections (r = 0.51, p < 0.001). We noted a relatively strong correlation between frequency of infections and duration of HG (r = 0.84, p < 0.0001). Twenty-four of 37 (65%) infants showed persistent HG and 49% had evidence of abnormal specific antibody production. Sixty-four percent of infants studied had reduced lymphocyte responsiveness to mitogen stimulation. Nineteen of 37 (51%) infants required IVIG for an average duration of 17.9 months due to recurrent infections. The average number of infections per year decreased from 10.6 to 2.8 (t = 12.32, p < 0.0001). There were no complications associated with IVIG therapy, but one infant died of bronchiolitis obliterans following heart-lung transplantation. Eight of 37 (22%) infants have persistent immunologic dysfunction requiring ongoing IVIG at four years or more of follow-up. We conclude that a substantial number of ill infants with BPD will have immune dysfunction characterized by persistently low IgG levels and reduced specific antibody responsiveness to protein antigens. We speculate that these findings are related to the cumulative dose of corticosteroids received in the first year of life and to the severity of underlying disease.

Adrenal Cortex Hormones↗
PubMed1996

An economic evaluation of propofol/fentanyl compared with midazolam/fentanyl on recovery in the ICU following cardiac surgery.

A comparison was made of the drug costs and nursing dependency of patients undergoing elective cardiac surgery and routine postoperative recovery for two anaesthetic techniques using either propofol with low dose fentanyl or midazolam with high dose fentanyl. Estimates of resource use were based on a randomised clinical trial undertaken at the Northern General Hospital, Sheffield. Times from entry to the intensive care unit until extubation and discharge were recorded for 70 patients and were transformed to nursing shifts. Nursing dependency was calculated on the basis of one nurse per ventilated patient and 0.5 nurse from the start of the shift after extubation. Nursing costs were allocated on the basis of the patient's status at the beginning of each shift in line with the hospital's staffing policy. All drugs used from the morning of the operation until discharge were recorded. Costs of nursing and drugs were calculated. The total cost of patients in the propofol group was 13.3% less than midazolam patients (p = 0.043, for geometric means Cl 0.4% to 27.8%). The clinical study was not designed for economic endpoints; however, it demonstrated achievable savings in propofol-treated patients.

Adult↗
PubMed1995

Pictorial adaptation of Stroop measures of body-related concerns in eating disorders.

Patients with eating disorders were asked to color-name pictures of a variety of body shapes. The time taken to color-name these stimuli was compared with the time taken to color-name a series of neutral visual stimuli. There was a significant delay in naming body shapes in comparison to neutral stimuli, and this delay was greater in anorexic and bulimic patients than in controls. Previous Stroop adaptations have used verbal stimuli to assess the intensity of weight and shape-related concerns. The possible advantages of pictorial stimuli are discussed.

Body Image↗
PubMed1994

HIV vaccine development and clinical trials.

The magnitude of HIV pandemic has made the development of HIV vaccines an urgent biomedical research priority. Although the biologic problems in designing a vaccine for a chronic viral infection like HIV are formidable, there has been encouraging progress. More than a dozen first generation prophylactic HIV vaccine candidates have completed phase I human trials that have established the safety and immunogenicity of these products in adults. A phase II trial of two HIV subunit envelope vaccines in adults at high risk of HIV infection is underway in the United States, and preparations for phase III efficacy trials have begun. Preliminary studies are under way to evaluate the potential application of active and passive immunization for preventing vertical transmission of HIV. Because of the higher rate of HIV transmission and a more abbreviated time course to disease, it may be more efficient to evaluate the efficacy of HIV vaccines in HIV infected pregnant women and their offspring than in adults who are exposed sexually to HIV.

AIDS Vaccines↗
PubMed1993

Pulmonary follow-up 2.5 years after a randomized, controlled, multiple dose bovine surfactant study of preterm newborn infants.

Forty-seven preterm infants, who were previously enrolled in a prospective, randomized, blinded study at birth to assess the effects of multiple doses of exogenous bovine surfactant to prevent respiratory distress syndrome, underwent lung function evaluation and review of their medical histories at 2 1/2 years of age. During their initial hospitalization there were no differences between the 17 control infants and the 30 surfactant-treated infants in the duration of ventilator or oxygen therapy and the incidence of bronchopulmonary dysplasia. At the follow-up both groups were similar in chronological and corrected ages, weights, lengths, and sex ratios and there were no differences in the occurrence of allergy, asthma, bronchiolitis, eczema, pneumonia, and wheezing. In addition, there was no significant difference regarding the incidence of chest illnesses lasting either 3 or 7 days and in the total number of required rehospitalizations. Functional residual capacity (FRC), tidal volume (VT/kg), compliance (Crs/kg), resistance (Rrs), and time constant of the respiratory system were not significantly different between the two groups at 2 1/2 years of age. We conclude that bovine surfactant, when given during the neonatal period, has little long-term effect on lung function. Neonatal bovine surfactant therapy neither improves nor produces any adverse effects on the developing respiratory system.

Animals↗
PubMed1991

The clinical course of residual carotid arterial disease.

Over a 5-year period 642 patients underwent 686 carotid endarterectomies with patch closure and intraoperative surveillance with continuous-wave Doppler. The perioperative stroke rate was 1.5%. Patients were screened with duplex scans immediately after operation for the presence of residual carotid lesions, and followed every 3 to 6 months for either the development of a true recurrent lesion or a change in a residual one. Five hundred thirty-nine arteries (84%) had no postoperative abnormalities. The incidence of recurrent carotid lesions in this groups was 1.5%, 3.4%, and 5.2% at 1, 2, and 3 years, respectively. The incidence of symptoms in this group was 0.2%, 0.7%, and 1.4% at 1, 2, and 3 years, respectively. The earliest recurrence or symptom occurred 8 months from operation. One hundred forty-seven arteries had residual lesions that were more common when either a temporary shunt was used or the operation was carried out above the hypoglossal nerve or below the omohyoid muscle. Sixty-one patients who had plaque proximal to the arteriotomy without a significant stenosis were followed an average of 21 months. There were no changes in plaque morphology and no proven symptoms related to the residual lesion. Fifty-six patients with both plaque and significant hemodynamic abnormalities in the carotid bulb were followed an average of 18 months. Seven of these patients (12.5%) had either a significant deterioration of the lesion or a symptom from it. Each event occurred within 6 months of operation. Thirty patients had significant flow abnormalities but no visible plaque. None of these lesions deteriorated. Although common, residual carotid lesions are benign unless the lesion is characterized by both plaque within the artery and a hemodynamically significant stenosis. These lesions should be further investigated and treated when discovered.

Arteriosclerosis↗
PubMed1991

Long-term follow-up after thoracic outlet decompression: an analysis of factors determining outcome.

We reviewed our 12-year experience with transaxillary first rib resection in 136 patients screened by neurologists and thought to have neurologic thoracic outlet syndrome to determine what factors affected outcome. These patients represented 85% of the operative experience in a referral area of 1.2 million people. Patients were recalled every 2 years for surveillance. The mean follow-up was 60 +/- 7 months. There were no brachial plexus or vascular injuries. Secondary operations in the neck were required in 20 patients. The quality of the operative result was determined by whether the patient was able to return to preillness activities and whether the patient would undergo operation again if the same result would be obtained. The most important determinant of result was a history of trauma precipitating the neurologic symptoms, particularly in women. Only 25 of the 53 patients (47%) with a history of trauma returned to preillness activities compared to 65 of the 83 patients (78%) without such a history. Overall patient satisfaction was not affected by trauma. Thirty-eight of the 53 patients with trauma (72%) and 69 of the 83 patients (83%) without trauma were satisfied. When the men and women were analyzed separately men were found to have better results after trauma than did women. Other factors with a negative impact on operative results were the need to return to an activity that required repetitive arm movements, coverage under a worker's compensation insurance policy, and fixed joint abnormalities or neurologic findings in the upper extremity. The presence of an anatomic abnormality had no effect on operative results.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1991

Comparison of Trypanosoma grayi-like isolates from west and east Africa.

Three flagellates recently isolated from the hindguts of tsetse flies in West Africa were compared with a previously described T. grayi-like trypanosome isolated in East Africa. In media with Microtus agrestis feeder layer cells, the flagellates developed into bloodstream-like trypomastigotes, which resembled the description of T. grayi from the blood of crocodiles. The results of isoenzyme electrophoresis suggest that the isolates are T. grayi-like trypanosomes, and that some variation exists between the West and East African stocks of these reptile trypanosomes.

Africa, Western↗
PubMed1990

BE-2 antigen: appearance in activation and long-term growth of T cells.

The BE-2 lymphocyte surface protein is frequently expressed by the malignant cells of cutaneous T-cell lymphoma (CTCL) but is not detectable on the surface of normal resting peripheral blood lymphocytes. The expression of BE-2 by normal T cells can be induced by lectin stimulation. Membrane expression of BE-2 surpasses that of the membrane receptor for IL-2, another T-cell activation marker, at day 5. The peak expression of BE-2 appears at day 6-8. The appearance of BE-2 could also be demonstrated after anti-CD3 and allogeneic stimulation. Long-term T-cell clones derived from normal donors and maintained in culture with periodic stimulation were also found to express BE-2 continuously. Thus, BE-2 is a late activation marker not expressed on normal peripheral blood lymphocytes and pathologically expressed on circulating malignant cells in the disease CTCL.

Antigens, Differentiation, T-Lymphocyte↗