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Biomedical subjects

K Mulholland

Publications and source records attributed to K Mulholland.

At least 19 recordsLinked to original sources
PubMed2005

Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: beginning of epidemic control.

As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The "tailor-made" outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4-6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2,519 microg participants and in 87% of 50 microg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 microg dosage.

Adolescent↗
PubMed2005

Bleeding gastric varices--a rare complication of ovarian cancer.

Splenic venous hypertension (or 'left-sided portal hypertension') is a rare underlying cause of gastro-oesophageal varices. Ovarian carcinoma recurring beyond 10 years, following primary treatment with no interval disease, is also a rare occurrence. We report an unusual case of bleeding gastric varices secondary to splenic venous obstruction as a result of metastatic ovarian carcinoma. This occurred 21 years following surgery and adjuvant chemotherapy for primary ovarian carcinoma. To our knowledge, until now, there have been no reported cases of splenic venous hypertension due to ovarian carcinoma. This case report illustrates the successful emergency management of this condition by splenectomy, with complete resolution of varices confirmed endoscopically at 6 weeks. It is followed by a brief discussion regarding varices due to splenic venous hypertension.

Aged↗
PubMed2002

Increased nm23 immunoreactivity is associated with selective inhibition of systemic tumour cell dissemination.

AIMS: In vitro transfection experiments show that the nm23 gene suppresses metastasis, although the evidence from clinical studies is contradictory. The purpose of this study was to investigate whether nm23 selectively influences systemic, pleural, and lymphatic metastasis in non-small cell lung cancer (NSCLC). METHODS: Forty two patients undergoing resection of NSCLC and lymph node sampling were enrolled prospectively. In each case, a bone marrow aspirate, pleural lavage, and lymph nodes were assessed using immunohistochemistry for epithelial antigens and morphology. The intensity of nm23-H1 immunoreactivity of the primary tumour was compared with the internal control of normal bronchial epithelium in 32 cases where available. The microvessel count (MVC) of each tumour was determined using immunohistochemistry for the endothelial cell marker CD34. RESULTS: Tumour cell dissemination was detected in the bone marrow in 18 patients, in the pleura in seven, and in the lymph nodes in 21. Increased immunoreactivity for nm23 was found in the primary tumour in six patients, with none having tumour cells in the bone marrow, compared with 12 of 26 patients who showed nm23 immunoreactivity equal to or less than the control (Fisher's exact test: p = 0.043). This effect was confirmed to be independent of the MVC on multivariate analysis. There was no significant difference in the incidence of pleural or lymphatic tumour cell dissemination between the two groups. CONCLUSION: nm23 appears to be a suppressor of systemic, but not lymphatic, metastasis in primary NSCLC.

Aged↗
PubMed2001

Multi-drug resistant Pseudomonas aeruginosa outbreak in a burns unit--an infection control study.

A newly introduced, multi-drug resistant (MDR) strain of Pseudomonas aeruginosa was isolated from four patients admitted to the Concord Hospital Burns Unit (BU) between December 1997 and March 1998. It was the cause of recurrent episodes of bacteraemia in two. This strain was resistant in vitro to gentamicin, piperacillin and ciprofloxacin. The isolates were confirmed as a clonal strain by pulse field gel electrophoresis (PFGE). Multiple environmental swabs were taken to search for an environmental reservoir, but no source was identified. Random cultures of staff members' hands failed to demonstrate ongoing carriage. In the absence of a demonstrable point source for the outbreak, direct cross-transmission patient to patient, via transient staff hand contamination, was the most likely route of infection. Following study commencement no new cases of infection with the MDR strain were detected. It would appear that the infection cycle has been interrupted, and the outbreak terminated following the discharge of the last infected patient from the BU. Contamination of a neutral detergent in the BU with Klebsiella oxytoca was detected incidentally during environmental surveillance. A potential hospital-wide outbreak was averted.

Australia↗
PubMed2000

Evaluation of vaccines to prevent childhood pneumonia: lessons relevant to planning tuberculosis vaccine trials.

Bacterial pneumonia in children is usually caused by one of the two leading pathogens, Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae, either type b (Hib) or nonencapsulated types. Hib conjugate vaccines suitable for use in infants have been available for about a decade, and experience with a trial of one of these vaccines in Africa showed that the vaccines can prevent Hib pneumonia, as well as other manifestations of Hib disease. It also showed that vaccine trials can provide useful estimates of the role of Hib in childhood pneumonia. Trials of pneumococcal conjugate vaccines that are currently under way have been designed to estimate disease burden and efficacy. A major risk of vaccine trials that use bacteriologic end points is that the vaccine may affect the diagnostic test itself, creating a misleading impression of efficacy. Trials of future tuberculosis vaccines are discussed in light of these experiences. It is important that the trials are designed to measure the effect on all clinical disease, as well as strict microbiological end points. The existence of bacille Calmette-Guérin (BCG) complicates future trials, and such trials should take into account possible nonspecific effects of BCG in addition to its effect on tuberculosis.

BCG Vaccine↗
PubMed2000

Effect of fever on the serum antibody response of Gambian children to Haemophilus influenzae type b conjugate vaccine.

BACKGROUND: Acute malaria is a major pediatric problem in developing countries and it is known to be immunosuppressive. METHODS: The serum antibody response to Haemophilus influenzae type b (Hib) conjugate vaccine was investigated in children ages 12 to 30 months with fever associated with malaria, fever associated with other causes or no fever. Groups of 57 children with malaria, 57 children with fever without malaria and 60 healthy children were bled and vaccinated with a single dose of H. influenzae type b capsular polysaccharide-tetanus protein conjugate vaccine. Of these 137 were bled again 1 to 2 months after vaccination. RESULTS: The median antibody titers at baseline were low and similar in the three groups; 77, 65 and 57% of children in the malaria, febrile and healthy groups, respectively, had prevaccination titers of anti-polyribosylribitol phosphate antibodies below 0.15 microg/ml. The median antibody titers after vaccination were 6.3, 7.5 and 23 microg/ml in the malaria, febrile and healthy groups, respectively (P < 0.001, healthy group vs. the two febrile groups). All the healthy children had protective titers (>0.15 microg/ml) after vaccination, but 11% of the children with malaria and 4% of the other febrile children did not have protective titers. CONCLUSIONS: Anti-polyribosylribitol phosphate titers after Hib vaccination were lower in children with malaria or other febrile illnesses at the time of vaccination than in controls. Fever associated with malaria or other acute illnesses is associated with a diminished response to Hib conjugate vaccine. These findings raise questions about the vaccination of febrile children and indicate the need for further studies in this area.

Antibodies, Bacterial↗
PubMed2000

Older workers' progression from private disability benefits to Social Security disability benefits.

People with medical conditions that limit their ability to work tend to receive short-term disability benefits initially and may then move to long-term and eventually to permanent disability benefits. The progression of older workers (those aged 55 to 64) along that continuum of benefits is documented here with data from a large disability insurance company. The data show that older workers who receive short-term medical disability benefits are three times as likely as younger workers to progress to receipt of Social Security Disability Insurance (SSDI) benefits, although a slight reversal of that trend occurs as workers pass age 62. Musculoskeletal conditions are the most frequent basis of short-term disability claims among older workers, with circulatory conditions running a close second. Furthermore, although all medical conditions are more likely to lead to SSDI benefits among older workers, circulatory conditions do so most frequently. This article discusses industry standards for the management of disability claims at each level of severity. It also addresses common and emerging disability management practices that may reduce the likelihood of impaired workers developing long-term or permanent financial dependence on disability benefits programs.

Adolescent↗
PubMed1999

Strategies for the control of pneumococcal diseases.

Streptococcus pneumoniae (pneumococcus) is a Gram-positive, encapsulated bacteria that is a major cause of human disease in people of all ages. It is the most important cause of bacterial pneumonia in infancy, childhood and adult life, and the most important cause of meningitis in all age groups except children of 3 months to 2 years in whom Haemophilus influenzae type b (Hib) predominates (in the absence of Hib vaccination). Antibodies to the pneumococcal polysaccharide capsule are protective, and at present 90 capsular serotypes are recognized. The global burden of pneumococcal disease is poorly understood. It is believed to be responsible for 1-2 million deaths among children under 5 years of age every year and probably a similar number among adults. Thus, the global burden of pneumonia in adults is probably significantly underestimated at present. Strategies for the control of pneumococcal disease include control of risk factors, treatment of established cases and vaccination. In children, improved nutrition, better housing and reduced indoor air pollution are difficult to address, but should eventually reduce pneumonia rates. In adults, the risk factors are even more difficult to address, although control of alcohol and tobacco consumption and reduced transmission of HIV should all affect pneumococcal disease rates. Penicillin-resistant pneumococci are now widespread throughout the world. Where penicillin resistance occurs, penicillin should not be used to treat pneumococcal meningitis; however, penicillin, at higher doses if necessary, remains the drug of choice for the treatment of pneumococcal pneumonia, even where penicillin resistance is prevalent. There are three approaches to pneumococcal vaccination: polysaccharide vaccines (covering 23 serotypes), polysaccharide-protein conjugate vaccines (covering 9-11 serotypes) and common protein vaccines (which are not serotype-specific). Only polysaccharide vaccines are available now, but conjugate vaccines will be available soon. Polysaccharide vaccines probably have a role in protecting the elderly from pneumococcal disease, especially those at high risk. The potential role of conjugate vaccines in infants is unclear.

Bacterial Vaccines↗
PubMed1999

Clinical predictors of hypoxaemia in Gambian children with acute lower respiratory tract infection: prospective cohort study.

OBJECTIVES: To determine clinical correlates and outcome of hypoxaemia in children admitted to hospital with an acute lower respiratory tract infection. DESIGN: Prospective cohort study. SETTING: Paediatric wards of the Royal Victoria Hospital and the hospital of the Medical Research Council's hospital in Banjul, the Gambia. SUBJECTS: 1072 of 42 848 children, aged 2 to 33 months, who were enrolled in a randomised trial of a Haemophilus influenzae type b vaccine in the western region of the Gambia, and who were admitted with an acute lower respiratory tract infection to two of three hospitals. MAIN OUTCOME MEASURES: Prevalence of hypoxaemia, defined as an arterial oxygen saturation <90% recorded by pulse oximetry, and the relation between hypoxaemia and aetiological agents. RESULTS: 1072 children aged 2-33 months were enrolled. Sixty three (5.9%) had an arterial oxygen saturation <90%. A logistic regression model showed that cyanosis, a rapid respiratory rate, grunting, head nodding, an absence of a history of fever, and no spontaneous movement during examination were the best independent predictors of hypoxaemia. The presence of an inability to cry, head nodding, or a respiratory rate >/= 90 breaths/min formed the best predictors of hypoxaemia (sensitivity 70%, specificity 79%). Hypoxaemic children were five times more likely to die than non-hypoxaemic children. The presence of malaria parasitaemia had no effect on the prevalence of hypoxaemia or on its association with respiratory rate. CONCLUSION: In children with an acute lower respiratory tract infection, simple physical signs that require minimal expertise to recognise can be used to determine oxygen therapy and to aid in screening for referral. The association between hypoxaemia and death highlights the need for early recognition of the condition and the potential benefit of treatment.

Acute Disease↗
PubMed1999

Respiratory illness after severe respiratory syncytial virus disease in infancy in The Gambia.

OBJECTIVE: To determine the frequency of later respiratory tract morbidity after respiratory syncytial virus (RSV) disease in infancy. DESIGN: Cohort study with passive, clinic-based surveillance. SETTING: Outpatient department in The Gambia. SUBJECTS: One hundred five children admitted to the hospital with severe RSV disease (case cohort), 105 control children matched for age not admitted to the hospital during the previous RSV season (control cohort 1), and 102 control children born after the RSV season (control cohort 2). MAIN OUTCOME MEASURES: Frequencies of pneumonia, wheezing, and hospital admission with acute lower respiratory tract infection. RESULTS: Pneumonia was more common in case children than in both control groups (adjusted incidence rate ratio [IRR, 95% CI]: 3.80 [2.73, 6. 10]), as was wheezing (IRR 7.33 [3.10,17.54]), pneumonia or wheezing (IRR 3.96 [2.60, 6.04]), and admission with pneumonia or wheezing (IRR 3.40 [1.87, 6.15]). The incidence rate per 100 child-years for pneumonia in the dry season for 12-month-old children was 27 for case patients, 8.1 for control cohort 1, and 6.51 for control cohort 2. By 3 years of age, the rates had fallen to low levels in all groups. CONCLUSIONS: Pneumonia and wheezing are significantly more common in children after RSV-associated lower respiratory tract disease than in control subjects, but the incidence declines rapidly with increasing age.

Acute Disease↗
PubMed1999

A randomised trial of a Haemophilus influenzae type b conjugate vaccine in a developing country for the prevention of pneumonia--ethical considerations.

In 1993 a placebo-controlled field trial of a Haemophilus influenzae type b (Hib) conjugate vaccine was started in The Gambia. At that time Hib conjugate vaccines had been shown to be efficacious in Europe and North America for the prevention of Hib meningitis. However doubts remained about their value in developing countries, where the epidemiology of Hib disease is quite different and the most important manifestation of Hib disease is pneumonia. The ethical issues facing the investigators before and during the trial are outlined in this paper, along with the views of the different groups involved in the trial. The trial demonstrated the efficacy of the vaccine in this setting and revealed the proportion of childhood pneumonia that is likely due to Hib, which was much higher than had previously been estimated. Since the completion of the trial Hib vaccines are now recommended for use in developing countries by the World Health Organization, largely based on the results of this trial. After a delay of 17 months following the completion of the trial, national Hib vaccination was started in The Gambia in 1997 using vaccine provided by a donation from industry.

Ethics, Medical↗