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Biomedical subjects

A S Breathnach

Publications and source records attributed to A S Breathnach.

At least 19 recordsLinked to original sources

Treatment of infections due to resistant organisms.

Antibiotic resistance remains rare in paediatric community-acquired pneumonia in the UK, but is more common in hospital-acquired pneumonia and in patients with chronic lung diseases. It should also be considered in children arriving from countries with a high prevalence of antibiotic resistance, children with previous heavy antibiotic exposure, those who are immunosuppressed, and those who are not responding to conventional therapy. The most frequent bacterial cause of paediatric pneumonia is Streptococcus pneumoniae and globally there are major concerns about the increasing resistance of this organism to penicillin. Intermediate resistance may be overcome with conventional doses of parenteral penicillin and there is as yet no convincing evidence that intermediate/high level resistance is associated with a worse clinical outcome. Continued vigilance and research is required. The recently introduced pneumococcal conjugate vaccines offer great promise as they are likely to prevent cases of disease due to penicillin-resistant serotypes.

Bacterial Vaccines↗

Documentation of positive blood culture results in a London teaching hospital.

OBJECTIVES: Our current practice is that initial (day 1) positive blood culture results are communicated to clinical teams; the task of recording those results in the notes is left to the clinical team. Microbiological information may be of crucial importance to an on-call doctor asked to review an unwell patient. We therefore sought to establish the extent to which day 1 positive blood culture information is available in patients' notes and its accuracy. METHODS: There were 51 positive blood cultures over a 14-day period. Patient notes of 39 of these were available for examination for evidence of the day 1 culture report, the accuracy of that report and evidence of clinical interpretation. RESULTS: The proportion of notes with a record was disappointingly low (54%), although the record was almost always accurate. Results reported at the weekend were as likely to be recorded in the notes as those given during the week. CONCLUSION: On-call doctors, not previously acquainted with a patient, will find that important information about day 1 positive blood culture results is not available to them in patient notes in around half of all cases. This adds weight to the view that medical microbiologists should give greater priority to ward visits and documentation of significant results, thus ensuring continuity of care from the laboratory bench to the bedside.

Bacteremia↗

Azelaic acid: potential as a general antitumoural agent.

Azelaic acid is a naturally occurring straight-chained 9-carbon atom dicarboxylic acid which is non-toxic, non-teratogenic, and non-mutagenic. Its antiproliferative and cytotoxic effect on a variety of tumoural cell lines in culture, due to inhibition of mitochondrial oxidoreductases of the respiratory chain and of enzymes concerned with DNA synthesis is well established; normal cells are unaffected at similar dosages and times of exposure. Human melanoma cells xenotransplanted onto athymic nude mice are significantly affected by administration of azelaic acid. Clinically, in humans, it has already been shown to cause regression of melanoma in situ and primary invasive malignant melanoma. These results rank azelaic acid as a potential general antitumoural agent. It can be administered topically, focally, orally, intravenously, intra-arterially, and intralymphatically, all without local or general ill-effects, and is metabolized without harmful side-products. Simultaneous administration by different routes can ensure delivery of high concentrations at lesional sites and for sustained periods. Courses can be repeated. In addition to melanoma, cutaneous and bronchial squamous cell carcinoma, bladder and breast cancers, and leukaemia would seem to be ideal candidates for further clinical investigation and trial of the anti-cancer potential of azelaic acid, as prime, adjuvant, and palliative therapy, and for disseminated disease.

Animals↗

An outbreak of multi-drug-resistant tuberculosis in a London teaching hospital.

We describe the epidemiology and control of a hospital outbreak of multi-drug-resistant tuberculosis (MDR-TB). A human immunodeficiency virus (HIV)-negative patient with drug-sensitive tuberculosis developed MDR-TB during a period of unsupervised therapy. She was admitted to an isolation room in a ward with HIV-positive patients, but the room, unbeknown to hospital staff, was at positive-pressure relative to the main ward. Seven HIV-positive contacts developed MDR-TB. The diagnosis in the second patient was delayed, partly because acid-fast bacilli in his sputum were assumed to be Mycobacterium avium-intracellulare. All the available Mycobacterium tuberculosis isolates were indistinguishable by molecular typing. Nearly 1400 staff and patient contacts were offered screening, but the screening programme detected only one of the cases. Despite therapy, the index patient and two of the contacts died. HIV-positive patients are more likely than others to develop tuberculosis after exposure, and the disease may progress more rapidly. In these patients the possibility that acid-fast bacilli may represent M. tuberculosis must always be considered. Patients with tuberculosis (suspected or proven) should not be nursed in the same wards as immunosuppressed patients, and should be isolated. MDR-TB cases must be isolated in negative-pressure rooms. Hospital side-rooms may be positive-pressure as a fire safety measure; infection control teams must be aware of the airflows in all isolation rooms, and must be consulted during the design of hospital buildings. Good communication between infection control teams and clinicians is important, and all medical and nursing staff must be aware of the principles of management of patients with proven or suspected tuberculosis and MDR-TB.

AIDS-Related Opportunistic Infections↗

Culture-negative endocarditis: contribution of bartonella infections.

Two cases of bartonella endocarditis are described: one in a 55 year old homeless alcoholic man, caused by Bartonella quintana; the other in a 41 year old male with a history of exposure to cat fleas, caused by B henselae. Serological testing and polymerase chain reaction of the excised valves were used to identify the organisms. False positive serology for chlamydia was detected in one case.

Adult↗

Streptococcus pyogenes bacteraemia: a 27-year study in a London teaching hospital.

The clinical and epidemiological features of 120 episodes of Streptococcus pyogenes bacteraemia in St. Thomas' Hospital between 1970 and 1997 were analysed. One-third of episodes were nosocomial. M1 was the most common serotype, and 29% of strains were non-typable. There was a variety of presenting features, but nearly half of the patients had cellulitis, 15% were shocked, and 6% had necrotic infections. There was no focus of infection in 13%. 54% of patients had an underlying disease, and 23% of infections were associated with a medical procedure or device. The mortality rate was 19%, and was associated with shock, coma, no focus of infection, and underlying disease. Since 1989, the annual incidence has more than doubled, and M1 strains and necrotic infections have increased, but the mortality rate and the proportion of patients presenting with shock have decreased, and the increase in cases involved many different M-types.

Bacteremia↗

Abnormal phagocytic function in children under one year of age.

The action of white blood cells (WBC) against Proteus mirabilis was assayed in 22 children following meningitis or septicaemia and compared with that in control groups of: (1) adult volunteers, (2) children undergoing minor surgical procedures for non-infective conditions, and (3) children being investigated for suspected renal disease. WBC bacterial killing tests were normal in all 55 adult volunteers. Abnormal results were obtained in 11 of 22 (50%) children with meningitis or septicaemia, 10 of 21 (47.6%) children undergoing surgery and six of 13 (46%) children with suspected renal disease, thereby indicating that there were no significant differences in phagocytic function among these three groups. Of children aged 1 year or less, 75% had abnormal phagocytic function. The significance of this finding is discussed.

Adult↗

A mixed outbreak of cryptosporidium and campylobacter infection associated with a private water supply.

In an outbreak of gastroenteritis affecting 43 people, cryptosporidium and campylobacter were isolated from stool specimens and in two cases dual infection was found. All the cases had drunk unboiled water from a private untreated water supply. Investigations revealed the carcasses of three lambs in a collection chamber connected with the water supply, and these, or run-off of slurry from surrounding fields, were the presumed source of contamination. Issues relating to the maintenance and monitoring of private water supplies are discussed. Problems with such supplies include old piping, proximity of livestock, inadequate knowledge of the layout and limited resources for monitoring and maintenance.

Adult↗

Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies.

Clinical studies of patients with melasma have shown that topical 20 percent azelaic acid is superior to 2 percent hydroquinone and as effective as 4 percent hydroquinone, without the latter's undesirable side effects. Tretinoin appears to enhance this effect of azelaic acid. Azelaic acid with tretinoin caused more skin lightening after three months than azelaic acid alone, and a higher proportion of excellent responders at the end of treatment. The effect of azelaic acid can be attributed to its ability to inhibit the energy production and/or DNA synthesis of hyperactive melanocytes, and partially to its antityrosinase activity. This may also account for the beneficial effect on postinflammatory hyperpigmentation. Destruction of malignant melanocytes by a combination of the same activities, enhanced by the greater permeability of tumoral cells to azelaic acid, may account for the clinical effects of azelaic acid observed in lentigo maligna and individual lesions of primary melanoma.

Administration, Topical↗

Effect of azelaic acid on melanoma cells in culture.

Using a clonogenic assay in vitro, it has been shown that exposure to azelaic acid (1-100 mM) for 24 hours has a dose-dependent effect on the survival of the colony-forming ability of murine (B16) and human (HMB2, and SK23) melanoma cells as compared with a non-melanotic non-tumoral Chinese hamster cell line (CHO). Both human cell lines were more sensitive to the diacid than the murine cells, and the HMB2 cells were more sensitive than the SK23 cells. These differences may be partly correlated with differences in pigmentation and doubling times between the three melanoma cell lines. The two human lines were more pigmented than the B16, and the SK23 more than the HMB2; the human lines had a longer doubling time than the others.

Animals↗

Penile lentiginosis. An ultrastructural study.

This study on five patients has revealed more extensive alterations to melanocytes than previously reported, and emphasizes the fact that depigmentation is an essential element of the condition. In hyperpigmented areas, melanocytes were increased in number along the basal layer of the epithelium, were hyperactive, and in some cases contained bizarre melanosomes. In two cases there was suggestion of a defect in melanosome transfer to keratinocytes. Lymphocytes were closely apposed to melanocytes, and, in hypopigmented areas, were clearly involved in their disintegration. In depigmented areas, there was complete absence of melanocytes and of melanosomes in keratinocytes, and lymphocytes were present in the basal layer. In general, the appearances did not resemble melanoma in situ with spontaneous regression, although a second biopsy of one patient after one year did reveal features of melanocytes suggestive of an early stage of this condition. The study has provided no clear information as to the initial cause of the condition, but the manner of destruction of melanocytes suggests an immune reaction. Neither has it been of assistance in suggesting a more precise name for it.

Adult↗