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P J Molloy

Publications and source records attributed to P J Molloy.

At least 19 recordsLinked to original sources
PubMed2000

Detection of multiple reactive protein species by immunoblotting after recombinant outer surface protein A lyme disease vaccination.

Laboratory confirmation of the diagnosis of Lyme disease is based on the detection of an immune response to Borrelia burgdorferi. The serodiagnosis of B. burgdorferi infection is complex and may be further confounded by the immune response to the recombinant outer surface protein A (OspA) Lyme disease vaccine. To describe how the serological response to the recombinant OspA Lyme disease vaccine affects testing for antibody to B. burgdorferi, 240 specimens from 80 study subjects were obtained at defined intervals after recombinant OspA Lyme disease vaccination. Samples were tested by indirect enzyme-linked immunosorbent assay (ELISA), antibody capture enzyme immunoassay (EIA), and Western blotting (WB). After recombinant OspA Lyme disease vaccination, ELISA for 98% of the study subjects revealed reactivity. WB with use of OspA-containing B. burgdorferi strains as sources of antigens demonstrated multiple bands. Results of testing with a US Food and Drug Administration-approved WB kit showed homogeneous reactivity in the molecular weight region >30 kDa. Testing with OspA-free strains completely eliminated all vaccine-associated reactivity by both antibody capture EIA and WB.

Antibodies, Bacterial↗
PubMed1999

Association of antibiotic treatment-resistant Lyme arthritis with T cell responses to dominant epitopes of outer surface protein A of Borrelia burgdorferi.

OBJECTIVE: To explore further the association of antibiotic treatment-resistant Lyme arthritis and T cell reactivity with outer surface protein A (OspA) of Borrelia burgdorferi, including the identification of T cell epitopes associated with this treatment-resistant course. METHODS: The responses of peripheral blood and, if available, synovial fluid lymphocytes to B burgdorferi proteins, fragments, and synthetic peptides, as determined by proliferation assay and interferon-gamma production, were compared in 16 patients with treatment-responsive and 16 with treatment-resistant Lyme arthritis. RESULTS: The maximum severity of joint swelling correlated directly with the response to OspA. Moreover, the only significant difference between patients with treatment-resistant and treatment-responsive arthritis was in reactivity with N-terminal and C-terminal fragments of OspA, OspA1 (amino acids [aa] 16-106), and OspA3 (aa 168-273). Epitope mapping showed that 14 of the 16 patients with treatment-resistant arthritis had responses to OspA peptides (usually 4 or 5 epitopes), whereas only 5 of the 16 patients with treatment-responsive arthritis had reactivity with these peptides (usually 1 or 2 epitopes) (P = 0.003). Patients with HLA-DRB1 alleles associated with treatment-resistant arthritis were more likely to react with peptide 15 (aa 154-173) and, to a lesser degree, with peptide 21 (aa 214-233) than patients with other alleles, whereas the responses to other epitopes were similar in both groups. CONCLUSION: The maximum severity of joint swelling and the duration of Lyme arthritis after antibiotic treatment are associated with T cell responses to specific epitopes of OspA.

Adolescent↗
PubMed1998

A vaccine consisting of recombinant Borrelia burgdorferi outer-surface protein A to prevent Lyme disease. Recombinant Outer-Surface Protein A Lyme Disease Vaccine Study Consortium.

BACKGROUND: Lyme disease is a multisystem inflammatory disease caused by infection with the tick-borne spirochete Borrelia burgdorferi and is the most common vector-borne infection in the United States. We assessed the efficacy of a recombinant vaccine consisting of outer-surface protein A (OspA) without adjuvant in subjects at risk for Lyme disease. METHODS: For this double-blind trial, 10,305 subjects 18 years of age or older were recruited at 14 sites in areas of the United States where Lyme disease was endemic; the subjects were randomly assigned to receive either placebo (5149 subjects) or 30 microg of OspA vaccine (5156 subjects). The first two injections were administered 1 month apart, and 7515 subjects also received a booster dose at 12 months. The subjects were observed for two seasons during which the risk of transmission of Lyme disease was high. The primary end point was the number of new clinically and serologically confirmed cases of Lyme disease. RESULTS: The efficacy of the vaccine was 68 percent in the first year of the study in the entire population and 92 percent in the second year among the 3745 subjects who received the third injection. The vaccine was well tolerated. There was a higher incidence of mild, self-limited local and systemic reactions in the vaccine group, but only during the seven days after vaccination. There was no significant increase in the frequency of arthritis or neurologic events in vaccine recipients. CONCLUSIONS: In this study, OspA vaccine was safe and effective in the prevention of Lyme disease.

Adolescent↗
PubMed1997

A preliminary experience with GM-CSF plus interferon in patients with HBV and HCV resistant to interferon therapy.

An open label trial of GM-CSF plus high-dose interferon (IFN) alpha 2b was performed in eight patients with chronic hepatitis B infection and 16 patients with chronic hepatitis C, who either failed to clear virus with 6 months of daily high-dose IFN (5 MU daily) therapy (n = 22) or were considered untreatable because of advanced disease and leukopenia (n = 2). The dose of GM-CSF used was 500 micrograms subcutaneously twice weekly. The dose of IFN used was 5 MU daily. Both agents were administered for 4 months. Five of the eight hepatitis B patients and five of the 16 hepatitis C virus patients responded to combined therapy having previously failed IFN therapy alone. The hepatitis B virus responders had low entry ALT, AST, and gamma GPT levels as compared to the non-responders. No such differences for responders and non-responders were seen with the hepatitis C virus patients. These data suggest that the combination of GM-CSF and IFN may be more effective at achieving viral clearance than IFN alone.

Adult↗
PubMed1996

New approach to HCV treatment. Recognition of disease process as systemic viral infection rather than as liver disease.

Chronic viral hepatitis C is a problem of immense proportions. The only therapy that currently exists and is FDA approved is interferon (IFN). Much controversy exists regarding the dose and duration as well as the effectiveness of IFN therapy. This study was performed to determine whether a new endpoint of successful treatment, HCV-RNA negativity in plasma and liver, would produce a greater number of long-term responders than is achievable with the currently recommended six months of therapy. The 45 patients enrolled in this study were randomized 2 to 1 in a treatment paradigm consisting of 5 MU IFN three times a week for six months or the same dose of IFN daily until HCV-RNA was undetectable in plasma X 3 over 3 consecutive monthly determinations followed by demonstrated HCV-RNA negativity in liver biopsy tissue. No differences in age, initial WBC count, platelet count, or hepatic injury measures were evident between the two treatment groups. At the end of therapy, 43% of those in group 1 vs 100% in group 2 responded to the IFN therapy as defined by the serum ALT level. More importantly, all of those in group 1, but only half of those in group 2, relapsed and became HCV-RNA positive with discontinuation of the IFN therapy. These data suggest that: (1) IFN therapy is more effective when given for a longer rather than a shorter period; (2) virologic response definitions are now possible and are preferred; (3) using longer therapy and a virologic endpoint, the responses achieved are more durable.

Adult↗
PubMed1996

Treatment of chronic hepatitis B and hepatitis C with interferon alfa-2b.

Chronic viral hepatitis B and C are problems of immense proportions. Interferon alfa-2b is the only agent currently approved by the U.S. Food and Drug Administration for the treatment of chronic hepatitis B and C. Initial enthusiasm for this therapy has waned with the realization that response rates are low and relapses are common. Recent studies, however, provide evidence of improved response rates with higher doses of interferon alfa-2b and the use of this agent in combination with iron reduction therapy consisting of repeated phlebotomies. Predictors of an increased likelihood of response to interferon alfa-2b therapy have also been identified, and their use may improve the cost-benefit ratio for this treatment.

Algorithms↗
PubMed1995

Chronic hepatitis C in patients with normal or near normal alanine aminotransferase levels: the role of interferon alpha 2b therapy.

BACKGROUND/AIMS: Interferon is the only approved therapy for chronic hepatitis occurring as a consequence of an infection with the hepatitis C virus. Because interferon is expensive, has a large number of untoward effects and its efficacy is not guaranteed, many physicians limit their use of this therapy to those with histologically advanced but not end-stage cirrhotic disease. Moreover, most cases are biopsied only after 6 months or more of abnormal alanine aminotransferase levels have been documented. The rationale for this approach to patients with hepatitis C virus infection has not been demonstrated. METHODS: In the present study, a total of 37 patients with alanine aminotransferase levels < 1.5 upper limits of normal (59 IU/l or less) who were HCV-RNA positive by reverse transcriptase polymerase chain reaction, were selected for interferon treatment, having been identified as having hepatitis C virus disease as the result of a screening Ab-HCV test confirmed with a positive radio immune blotting assay. Once identified, each subject underwent a percutaneous liver biopsy and was tested for the presence of HBsAg, Ab-HBs and HBV-DNA. All liver biopsies were read and graded according to the criteria of Knodell et al. Each subject was treated with interferon a2b at a dose of 5 MU administered daily until a response was achieved (a minimum period of 6 months) or until a full year had elapsed. A response was defined as HCV-RNA negativity in serum on three consecutive monthly determinations. The study population consisted of 21 males and 16 females ranging in age from 17 to 72 years (mean 46.7 +/- 2.2 years). Their mean serum alanine aminotransferase level at the initiation of therapy was 37.5 +/- 2.1 IU/l with a range of 10-59 (normal values being 40 IU/l or less). 54% of the subjects were presumed to have acquired their hepatitis C virus infection as a result of a blood transfusion; 32% as a result of prior intravenous drug abuse; and 13% had no identifiable risk factor for hepatitis C virus. Despite having normal or near normal serum alanine aminotransferase levels, 9 subjects had chronic persistent hepatitis, 13 had chronic active hepatitis and 15 had chronic active hepatitis + cirrhosis documented by histopathologic assessment of their liver biopsies. RESULTS: An interferon response was achieved in 5/9 with chronic persistent hepatitis, 11/13 with chronic active hepatitis and 8/15 with chronic active hepatitis + cirrhosis for an overall response rate of 65%. CONCLUSIONS: This study has demonstrated that individuals who: 1) are hepatitis C virus positive with serum alanine aminotransferase levels < 1.5 x upper limits of normal can have histologically advanced liver disease; 2) can respond to interferon therapy defined as clearance of detectable HCV-RNA in serum; and, 3) should be considered for interferon treatment.

Adult↗
PubMed1995

Treatment of hepatitis C virus in elderly persons with interferon alpha.

BACKGROUND: Hepatitis C virus (HCV) is a health problem that is common in adults. Because screening of blood and blood products for HCV has only been possible recently, older adults are more likely than younger adults to have HCV. Despite the higher prevalence of HCV in older adults, few are treated. This failure to treat is a result of the concern that the untoward effects of Interferon alpha (IFN) may not be tolerable in older individuals. METHODS: Twenty-five subjects age > 65 years who were Ab-HCV positive and desired IFN therapy were treated with 5 MU Interferon administered TIW for 6 months. Twenty-five adults (mean age 44 +/- 1 years) matched for gender and histologic disease were utilized as a control population. Responses were classified as full if the ALT level was normal, and partial if the ALT fell by > 50% but was still abnormal after 6 months of therapy. All other responses were defined as failures. RESULTS: At the end of treatment, no biochemical difference between the elderly and younger adults was evident for any parameter. Moreover, the response rates (48% and 41%, respectively) were nearly identical. None of the elderly discontinued IFN therapy during the treatment period. The rate of untoward events reported by the elderly was similar to that reported by the younger controls. CONCLUSIONS: These data demonstrate that: (a) the elderly with HCV infections can be treated with IFN; (b) the response rate is similar in elderly and younger adults; and, (c) the rate and type of untoward IFN effects experienced by the elderly do not differ from that reported by younger adults.

Adult↗
PubMed1995

Interferon-alpha can be used successfully in patients with hepatitis C virus-positive chronic hepatitis who have a psychiatric illness.

OBJECTIVE: To determine whether individuals with concurrent active psychiatric disease and chronic hepatitis C virus (HCV) can be treated safely and effectively with interferon-alpha. DESIGN: Prospective, open label study. SETTING: Tertiary referral hospital. PATIENTS: Thirty-one consecutive patients with co-existent chronic HCV and a psychiatric illness. INTERVENTIONS: Interferon-alpha was administered at doses of either 5 MU three times per week for 6 months (n = 17) or 5 MU daily for 6 months (n = 14). METHODS: HCV-RNA in serum was measured using reverse transcriptase polymerase chain reaction. Serum alanine aminotransferase levels were assessed and liver biopsy was performed before and after 6 months of treatment and again after 6 months of follow-up. RESULTS: Twenty-nine of the 31 patients completed 6 months of therapy. Two patients discontinued therapy after 2 and 3 months of treatment. Serum alanine aminotransferase levels returned to normal in 22 (71%) patients. Fifteen (48%) of the 31 patients cleared HCV-RNA from their serum. Only four patients experienced a worsening of their psychiatric illness during treatment. Interferon therapy was discontinued in two of these patients. CONCLUSIONS: Patients with a co-existent psychiatric illness and chronic HCV can be treated successfully with interferon-alpha with the active participation of a psychiatrist and the maintenance of psychotropic drug therapy during interferon treatment.

Adult↗
PubMed1994

Treatment of Lyme arthritis.

OBJECTIVE: To test treatment regimens for Lyme arthritis. METHODS: Patients were randomly assigned to treatment with doxycycline or amoxicillin plus probenecid for 30 days. Patients who had persistent arthritis for at least 3 months after treatment with oral antibiotics or parenteral penicillin were given intravenous ceftriaxone for 2 weeks. RESULTS: Eighteen of the 20 patients treated with doxycycline and 16 of the 18 patients who completed the amoxicillin regimen had resolution of the arthritis within 1-3 months after study entry. However, neuroborreliosis later developed in 5 patients, 4 of whom had received the amoxicillin regimen. Of 16 patients (2 from the oral antibiotic study and 14 additional patients) who had persistent arthritis despite previous oral antibiotics or parenteral penicillin, none had resolution of the arthritis within 3 months after ceftriaxone therapy. The HLA-DR4 specificity and OspA reactivity were associated with a lack of response. CONCLUSION: Lyme arthritis can usually be treated successfully with oral antibiotics, but patients may still develop neuroborreliosis. Patients with certain genetic and immune markers may have persistent arthritis despite treatment with oral or intravenous antibiotics.

Adolescent↗
PubMed1991

Traumatic rupture of the thoracic aorta: ten-year experience with follow up.

In the past 10 years, 13 cases of acute traumatic rupture of the thoracic aorta were treated at the Dunedin Hospital. Ages ranged from 16 to 77 years, with a mean of 27 years. Twelve of the patients were involved in high speed motor vehicle accidents and one sustained a fall. The diagnosis was suspected in all 13 cases by a widened mediastinum on plain chest X-ray and confirmed by aortography in all cases. Associated injuries were common. The time interval from injury to surgery ranged from 5 h to 16 days, with a mean of 3 days. A Gott Shunt was used in five patients, seven had partial bypass and one had simple aortic cross-clamping. Mean aortic cross-clamp time was 62 min. Mortality was 15%, both deaths occurring in the bypass group. There were two cases of paraplegia, one occurring in the bypass group and the other in the patient having simple cross-clamping of the aorta. Follow up was possible in 8 of 13 patients and ranged from 3 months to 10 years, with a mean of 39 months. Delayed death due to heart failure occurred after discharge in a 77 year old man 40 days after operation. The long-term results were satisfactory in all survivors, apart from one poorly rehabilitated paraplegic.

Accidents, Traffic↗
PubMed1991

Resection for congenital tracheal stenosis.

A case of congenital tracheal stenosis is reported. The diagnosis was made on plain X-ray, tomography and computerized axial tomography of the trachea when the child was 8 years old. The operative approach was via a median sternotomy and anaesthesia maintained with dual simultaneous ventilation of the right upper lobe bronchus and distal trachea. Histology of the stenotic area revealed the cartilaginous rings to be completely encircling the trachea.

Child↗