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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 181 records · Page 10Linked to original sources
PubMed1994

Sequencing of irradiation and chemotherapy for early-stage breast cancer.

The optimal sequencing and timing of radiation and chemotherapy for patients with early-stage breast cancer are unknown, both with regard to each other and to surgery. Although intuitively it seems prudent to start both radiotherapy and combination chemotherapy as soon as possible following surgery, there is little information to suggest that reasonably short delays (up to a few months, perhaps) are deleterious. Study results do not suggest that concurrent chemoradiotherapy produces any substantial advantage in local control rates, compared with sequential treatment. However, the available data are very limited, and no randomized studies have been performed. Because of its theoretical advantages, concurrent chemoradiotherapy remains an approach worthy of further investigation, but the potential toxicity of such regimens makes careful study design imperative. At present, the effectiveness of chemotherapy does not appear to be impaired significantly by a 2- to 3-month break in therapy imposed by split-course combined-modality regimens.

Breast Neoplasms↗
PubMed1994

Synthesis of disulfide-bridged fragments of omega-conotoxins GVIA and MVIIA. Use of Npys as a protecting/activating group for cysteine in Fmoc syntheses.

The 3-nitro-2-pyridinesulphenyl (Npys) moiety is finding increasing utility as a protecting-activating group for cysteine, particularly in the synthesis of cyclic and unsymmetrical disulfides using the Boc strategy. This chemistry has been extended to peptides assembled by the Fmoc strategy. N-Terminal Cys(Npys) is introduced via Boc-Cys(Npys)-OPfp. Non-N-terminal Cys(Npys) is incorporated by reacting a resin-bound, fully protected Cys(Acm) peptide with NpysCl. This approach has been applied to the synthesis of four disulfide-bridged fragments of omega-conotoxins GVIA and MVIIA.

Amino Acid Sequence↗
PubMed1993

Structural features of the 26 S proteasome complex.

Proteasomes play a key role in the degradation of abnormal proteins, of short-lived regulatory proteins and in antigen processing. Evidence is accumulating that the 20 S proteasome represents the proteolytic core of the 26 S protease complex (26 S proteasome) which contains several additional subunits implicated in regulation and substrate recognition. Using electron microscopy and digital image analysis we obtained first insights into the structure of this complex which has an estimated molecular weight of approximately 2000 kDa. Two highly asymmetric masses which presumably contain the regulatory subunits of the 26 S complex are attached to both ends of the dimeric 20 S proteasome clearly reflecting its C2 symmetry. The structural uniformity of the complex, i.e. the absence of significant inter-image variations, has important implications for the structure of the latter: It indicates that, in spite of their sequence similarities, the various alpha-type and beta-type subunits of the 20 S proteasome are not promiscuous but occupy precisely defined positions.

Animals↗
PubMed1993

Prostitution and risk of HIV: female prostitutes in London.

OBJECTIVE: To measure the prevalence of HIV and to describe established risk factors in female prostitutes. DESIGN: A cross sectional survey. SETTING: A genitourinary medicine clinic, streets, and magistrates' courts in London. SUBJECTS: 280 female prostitutes recruited between April 1989 and August 1991. MAIN OUTCOME MEASURES: Infection with HIV-1, reported risk behaviours, and prevalence of sexually transmitted infections. RESULTS: 228 of the women had HIV tests, and two (0.9% (95% confidence interval 0% to 2.1%)) were infected with HIV-1. Reported use of condoms was high for commercial clients and low for non-paying partners: 98% (251/255) of women used condoms with all clients and 12% (25/207) with non-paying partners for vaginal intercourse. Twenty two women were current or past injecting drug users. Of the 193 women examined for sexually transmitted infections, 27 had an acute infection (gonorrhoea, chlamydia, trichomonas, or primary genital herpes) at the time of interview. Infection was associated with younger age and increasing numbers of non-paying sexual partners, but not with duration of prostitution, numbers of clients, or reports of condom failures. When age and numbers of non-paying partners were analysed by logistic regression they remained significantly associated with sexually transmitted infections. CONCLUSIONS: A large and diverse sample of prostitutes had a low prevalence of infection with HIV and high levels of use of condoms in commercial sex. There was a significant risk of other sexually transmitted infections associated with prostitutes' non-commercial sexual relationships, in which unprotected sex is common. Interventions to reduce the risk of sexually transmitted infections in prostitutes should address both commercial and non-commercial sexual partnerships.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Chest wall recurrence of ductal carcinoma in situ of the breast after mastectomy.

BACKGROUND: Optimal management of ductal carcinoma in situ (DCIS) of the breast is a problem that is occurring with greater frequency, mostly because of the increasing use of mammographic screening. The traditional role of mastectomy for DCIS has been challenged by breast-conserving procedures. Regardless of the method of treatment used, local control with complete tumor eradication is the major goal in the management of DCIS. METHODS AND RESULTS: A patient is reported in whom DCIS recurred in residual breast tissue in the chest wall several years after mastectomy. CONCLUSIONS: Chest wall recurrence of DCIS within residual breast tissue probably is caused by failure of tumor excision, new primary tumor, or both. This observation underscores that (1) mastectomy may not result in complete removal of breast tissue, and (2) this residual breast tissue may be the substrate for "chest wall recurrences" in some patients with breast cancer.

Adult↗
PubMed1993

Long-term results of post-operative radiation therapy following mastectomy with or without chemotherapy in stage I-III breast cancer.

PURPOSE: To determine the risk of local-regional failure following post-mastectomy radiotherapy and the incidence of complications associated with such treatment. METHODS AND MATERIALS: We retrospectively analyzed the results in 309 patients with Stage I-III invasive breast cancer treated with post-mastectomy radiation therapy between 1975 and 1985. The median radiotherapy dose was 45 Gy in 1.8 to 2.25 Gy fractions. One hundred forty-seven (48%) of the patients received adjuvant systemic chemotherapy with 115 (78%) of these receiving a CMF-based or doxorubicin-containing regimen. The median follow-up time of surviving patients was 130 months (range, 28 to 191 months) after mastectomy. RESULTS: Seventeen patients (6%) developed a local-regional failure at an interval of 4 to 87 months after radiotherapy. Moderate or severe complications related to radiotherapy and requiring treatment were uncommon. Symptomatic radiation pneumonitis occurred in four patients (1.3%), arm edema in 18 (5.8%), and brachial plexopathy in 2 (0.6%). CONCLUSION: We conclude that post-operative radiotherapy is a safe and effective means of reducing local-regional failure following mastectomy. The efficacy of post-mastectomy radiotherapy in improving survival should be addressed in new large randomized controlled studies.

Adult↗
PubMed1993

Two-dimensional crystals of the molecular chaperone GroEL reveal structural plasticity.

For two-dimensional (2-D) crystallization we have purified the molecular chaperone GroEL from Escherichia coli to homogeneity. The final and important step for crystallization in the purification procedure was an ATP-agarose column, on which the spacer between ATP and agarose was attached to C8 of adenine. Using the mica spreading "negative staining-carbon film" procedure and polyethylene glycol as a precipitant, we obtained four different 2-D periodic arrays. Two of them turned out to be true crystals. One crystal has P2 symmetry and lattice constants of a = 24.3 nm and b = 16.9 nm, the other has essentially P4 symmetry and shows smoothly varying local changes in the lattice parameters (a = b = 23 (+/- 1.3) nm). Very striking in the P4 crystal is the departure within each individual GroEL particle from the GroEL-typical seven-fold symmetry, which seems to be required for GroEL to accommodate to a crystal symmetry.

Bacterial Proteins↗
PubMed1993

Socioeconomic status and physical health, how are they related? An empirical study based on twins reared apart and twins reared together.

This investigation used the powerful combined twin and adoption design to assess the validity of three different hypotheses--social causation, childhood experiences, and health selection--on the origin of the association between socioeconomic status (SES) and health. The sample contains 99 pairs of monozygotic twins reared apart, 166 pairs of monozygotic twins reared together, 238 pairs of dizygotic twins reared apart, and 221 pairs of dizygotic twins reared together, who completed questionnaire items concerning their SES and health status. Genetic effects, environmental effects unique to the individual, as well as environmental effects shared by twins were involved in mediating the associations between SES and health. However, the relative importance of these effects varied for the different associations depending on the measures of health and SES respectively. The results indicate that social causation, childhood experiences, and health selection may all be important for the association between SES and health. It is argued that these hypotheses are not contradictory, rather the relationship between the complex dimensions SES and health may be explained by several different causes.

Adult↗
PubMed1993

Pneumothorax in patients with AIDS.

Eighty-seven inpatients were treated for 93 episodes of Pneumocystis carinii at St Mary's Hospital between January 1989 and December 1990. During this period, 298 patients with the acquired immunodeficiency syndrome (AIDS) were treated at this hospital. Sixteen episodes of pneumothorax occurred and 12 of these, occurring in ten patients, were unrelated to procedure. In six of 12 (50%), the pneumothoraces occurred concurrently with Pneumocystis carinii pneumonia (PCP) and in ten (83%) cases there was a past history of PCP. Bilateral pneumothorax occurred in five cases (42%). In seven (58%) of the cases, patients had been using aerosolized pentamidine as prophylaxis for PCP. This retrospective study confirms the association of pneumothorax with current PCP and also shows an association with previous infection. The use of aerosolized pentamidine was not associated with pneumothorax development. It is important to suspect pneumothorax in a patient with PCP who deteriorates acutely. The high incidence of bilateral pneumothorax means that pleurodesis should be considered early.

AIDS-Related Opportunistic Infections↗
PubMed1993

The effect of cigarette smoking on the development of AIDS in HIV-1-seropositive individuals.

OBJECTIVE: To determine whether HIV-1-seropositive cigarette smokers progress more rapidly to AIDS than HIV-1-seropositive non-smokers. SETTING: The genitourinary medicine outpatient department of St Mary's Hospital, London, which is a London University teaching hospital (tertiary care centre). SUBJECTS AND DESIGN: Case series of 84 individuals with AIDS who provided accurate details of their smoking habits before their AIDS-defining diagnosis. MAIN OUTCOME MEASURE: Progression time to AIDS in relation to smoking habit. RESULTS: Progression time to AIDS (all diagnoses) was significantly reduced in HIV-1-seropositive smokers: median time to AIDS was 8.17 months for smokers (n = 43) and 14.50 months for non-smokers (n = 41) (P = 0.003). Smokers developed Pneumocystis carinii pneumonia (PCP) more rapidly than non-smokers, with a median time to PCP of 9.0 months, compared with 16.0 months for non-smokers (P = 0.002). Smoking had no significant effect on progression time to AIDS when not due to PCP. CONCLUSION: Cigarette smoking by HIV-1-seropositive individuals is associated with a more rapid development of AIDS and should be discouraged.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Treatment of cryptococcosis with liposomal amphotericin B (AmBisome) in 23 patients with AIDS.

OBJECTIVE: To determine the safety and efficacy of liposomal amphotericin B (AmBisome) in the primary treatment of AIDS-associated cryptococcosis. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of AmBisome in 23 patients (26 enrolments) with cryptococcosis. Dose requirements, mycological response and toxicity were documented. SETTING: Hospital-based HIV units. PATIENTS: Twenty-three HIV-1-seropositive patients. RESULTS: Drug toxicity, assessed in 25 enrolments, was well-tolerated with little renal, hepatic or haematological toxicity. Eighteen out of 23 (78%) enrolments responded clinically. Nineteen enrolments had cryptococcal meningitis: sterilization of spinal fluid was achieved in 12 out of the 18 (67%) who were mycologically evaluable. Fourteen out of the 19 (74%) responded clinically. CONCLUSION: AmBisome is well-tolerated and may be an effective formulation in the treatment of cryptococcosis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Is HIV infection associated with an increase in the prevalence of cervical neoplasia?

OBJECTIVE: To test the hypotheses: (1) that HIV infection predisposes to cervical intraepithelial neoplasia (CIN); (2) that this CIN is a result of HIV related immunosuppression; and (3) that this CIN is a result of immunosuppression causing increased expression of the potentially oncogenic viruses, human papilloma virus (HPV), Epstein Barr virus (EBV) and herpes simplex virus (HSV). DESIGN: A matched cross sectional study. SETTING: The Department of Gynaecological Oncology, The Samaritan Hospital, London; the Department of Genitourinary Medicine, St Mary's Hospital, London; and the Family Planning Clinic, Claremont Terrace, Glasgow. SUBJECTS: Fifty HIV seropositive women enrolled from the Genitourinary Medicine Department and the Drug Dependency Unit at St Mary's Hospital, London, and the Unit of Infectious Diseases at Ruchill Hospital, Glasgow. Forty-three HIV seronegative controls enrolled from the Department of Genitourinary Medicine at St Mary's Hospital, matched against 43 of the seropositive women for age, age at first intercourse, lifetime number of sexual partners, and smoking habit. MAIN OUTCOME MEASURES: Associations between CIN, as detected by cytology and histology, and HIV infection. Association was also sought between CIN and immunosuppression, as measured clinically by T4 cell number, beta-2-microglobulin and p24 antigen. Associations of these with: (1) HPV, as detected by Southern blot testing and the polymerase chain reaction; (2) EBV, as detected by Southern blot testing; and (3) HSV, as detected by tissue culture of endocervical swabs, was also studied. RESULTS: There was no significant difference in the prevalence of CIN or oncogenic viruses between HIV seropositive and seronegative women in the absence of immunosuppression. If the HIV infected women showed signs of immunosuppression, the prevalence of CIN was increased. No association was shown between detection of HPV, EBV and HSV and immunosuppression or CIN. CONCLUSION: HIV infection may only be associated with an increased risk of CIN when immunosuppression is present.

Adult↗
PubMed1993

Systemic Pneumocystis carinii pneumonia prophylaxis with dapsone and pyrimethamine fails to protect against extrapulmonary pneumocystosis.

Extrapulmonary pneumocystosis is a feature of severe immunosuppression which earlier reports have suggested is limited to patients receiving either no prophylaxis or aerosolised pentamidine. We report a case of disseminated pneumocystosis which developed in an HIV positive homosexual man despite systemic primary Pneumocystis carinii pneumonia prophylaxis.

AIDS-Related Opportunistic Infections↗
PubMed1993

Neisseria gonorrhoeae isolated at St. Mary's Hospital London, 1980-91.

OBJECTIVE: To describe and discuss the trends in the isolation of Neisseria gonorrhoeae from patients attending the Genitourinary Medicine Clinic at St. Mary's Hospital, Paddington, London between 1980 and 1991. DESIGN: A retrospective study of the total number of gonococci isolated over an eleven year period was performed. In addition, for the years 1988-1991 the number of isolates from homosexual men was analysed by age of the patient, site of infection and HIV antibody status of the patient. RESULTS: The total number of N. gonorrhoeae isolates identified declined markedly between 1980 and 1989 from 3670 to 750 isolates. Over the same time period the number of specimens screened for N. gonorrhoeae fell by 50%. In 1990 there was an increase in N. gonorrhoeae isolates but this was not maintained, and in 1991 the number of N. gonorrhoeae fell to its lowest level of 638 isolates. The decrease since 1980 occurred in both men and women although the number of rectal isolates from men showed a steeper decline reaching its lowest level of 24 isolates in 1988. The number of rectal isolates from homosexual men has since increased with a peak in 1990. Many of the infections among homosexual men occurred in older men and included insignificant number of patients who were HIV positive. CONCLUSION: Gonorrhoea among attenders at St. Mary's Hospital has declined dramatically since 1980 following trends reported from much of Europe. The increase in gonococcal isolates since 1989 and the peak in 1990 are unexplained but are coincident with a higher number of isolates from homosexual men.

Adult↗
PubMed1993

Outpatient follow-up in women with HIV infection in Parkside Health Authority (UK).

OBJECTIVE: To describe patterns of attendance for follow-up among HIV infected women in Parkside, UK and their correlates. DESIGN: Retrospective cohort study. SUBJECTS: 103 HIV infected women. MAIN OUTCOME MEASURES: Whether patients attended for follow-up between three and 18 months. RESULTS: 31% of women were married and 46% had children. Women born in sub-Saharan Africa were significantly less likely to attend for follow-up after three months (56%) than women born in other areas who had acquired HIV either heterosexually (82%) or through injecting drug use (81%). This pattern persisted on multivariate analysis controlling for whether women were symptomatic, had had a previous positive test, were married or had children. CONCLUSIONS: HIV positive sub-Saharan African women are less likely to reattend for follow-up than women with heterosexually acquired HIV from other areas or those who acquired infection through intravenous drug use. Further studies are needed to identify barriers to follow-up for women and to shape the development of more appropriate and accessible services for HIV infected women, especially those of sub-Saharan African origin.

Adult↗