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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 235 records · Page 13Linked to original sources
PubMed1991

Negative staining-carbon film technique: new cellular and molecular applications.

Two techniques are presented which extend the original negative staining-carbon film technique into new areas of cellular and molecular application. These relate (1) to the production of negatively stained specimens of single-layer plasma membrane split from intact cells during the overall procedure that are negatively stained from the cytoplasmic face and (2) to the production of negatively stained specimens directly from glycerol-containing protein solutions, membrane or viral suspensions. In both cases in vacuo drying onto mica from glycerol is performed, prior to deposition of a carbon film. (For the cellular technique, freshly cleaved mica is firstly rendered positively charged by immersion in Alcian blue.) This is followed by release of the carbon film plus adsorbed membrane or protein by floating onto water, with subsequent negative staining. Selected preliminary applications using human erythrocyte membrane and the high molecular weight (native) human erythrocyte tripeptidyl peptidase-II complex are given and considered speculation as to the future application of the techniques is provided.

Carbon↗
PubMed1991

Results of radical radiotherapy for inflammatory breast cancer.

We performed a retrospective review of 65 patients with nonmetastatic clinical inflammatory breast carcinoma treated with radical radiotherapy as the sole local treatment between 1968 and 1986. Chemotherapy was given to 47 patients (72%). The median total radiation dose to the target volume was 6,984 cGy. With a median follow-up in survivors of 41 months, the 5-year actuarial probability of relapse-free survival was 17% and the overall survival was 28%. Thirty patients experienced failure in the treated breast, skin, or draining lymph nodes, for a crude, uncensored local recurrence rate of 46%. Of the factors analyzed, only the response to initial chemotherapy was predictive of local recurrence. Local recurrence was noted in 0 of 3 patients with a complete response (CR) to initial chemotherapy, 5 of 17 patients with a partial response (PR), and 12 of 17 patients with less than a partial response (CR/PR versus less than PR, p = 0.009). We conclude that conventional radical radiotherapy in unselected patients is insufficient to manage the local tumor burden presented by inflammatory breast cancer, even when high doses are employed.

Actuarial Analysis↗
PubMed1991

Cytomegalovirus infection in AIDS. Patterns of disease, response to therapy and trends in survival.

Among 347 AIDS patients seen at St Mary's Hospital, London between 1983 and 1989, cytomegalovirus (CMV) disease was observed in 75 (22%). Of these, 58 (77%) had CMV retinitis, 26 (35%) CMV colitis, and 12 (16%) had CMV infection diagnosed at other sites. Relapse occurred in 71%. A favourable response to the use of ganciclovir as induction therapy for CMV retinitis was observed in 92%. Relapse of CMV retinitis occurred in 54% at a median time of 97 days. Neutropenia was the most frequent and serious side-effect of ganciclovir, 76% patients having neutrophil counts less than 1.0 x 10(9)/l and 48% less than 0.5 x 10(9)/l at some stage of therapy. Thrombocytopenia was also common, and platelet counts of less than 50 x 10(9)/l occurred in 43% patients on ganciclovir. The concurrent use of zidovudine made the development of severe neutropenia and thrombocytopenia more likely. Median survival following the diagnosis of CMV disease increased from 5-8 months between 1984 and 1987, to over 12 months in 1988. Patients with CMV colitis had a worse prognosis than patients with CMV retinitis, with median survival of 4.5 and 7 months respectively. In conclusion, CMV is an important opportunist infection in AIDS and both the disease and its treatment cause considerable morbidity. Hence, it is important to develop more effective and less toxic forms of therapy for CMV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Mycobacterium malmoense infection in HIV positive patients.

Mycobacterium malmoense is a non-tuberculous mycobacterium which has previously been associated with underlying pulmonary pathology and depressed immunity. We describe two patients infected with human immunodeficiency virus from whom M. malmoense was isolated, and discuss its treatment and possible pathogenic role.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Cosmetic results after surgery, chemotherapy, and radiation therapy for early breast cancer.

Adjuvant chemotherapy (CT) is increasingly being used in conjunction with radiation therapy (RT) in the treatment of early stage breast cancer. To assess the effect of CT on the cosmetic outcome of the irradiated breast, we retrospectively reviewed the cosmetic results of patients who received either cyclophosphamide-methotrexate-fluorouracil (CMF) or doxorubicin-based chemotherapy in conjunction with breast irradiation between 1968 and 1985. The overall cosmetic results were evaluated by the physician as "excellent," "good," "fair," or "poor" using a standardized scale. The CT group consisted of 170 patients treated with CT and RT administered either concurrently or sequentially (CT before RT, after RT, or both) with a minimum of 24 months of cosmetic follow-up. These were compared to an RT alone control group of 170 patients who did not receive CT and were matched by tumor size, radiation technique, and year of treatment. At 36 months, the cosmetic scores for the CT group compared to RT alone were 47% versus 71% excellent (p less than 0.01), 36% versus 19% good, and 17% versus 9% fair or poor. For the 50 patients treated with concurrent CMF and RT, the scores were 31% excellent, 45% good, and 24% fair/poor, whereas for the 118 patients treated with sequential RT and CT they were 54%, 31%, and 14%, respectively. There was no difference between those patients who received sequential CMF and those treated with doxorubicin. We conclude that adjuvant chemotherapy adversely affects the cosmetic outcome of breast irradiation, but that this effect is not clinically significant unless CMF is administered concurrently with RT. Patients treated with either sequential CMF or doxorubicin-based CT had only a slight decrement in their cosmetic result compared to patients treated without CT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy.

The likelihood of radiation pneumonitis and factors associated with its development in breast cancer patients treated with conservative surgery and radiation therapy have not been well established. To assess these, we retrospectively reviewed 1624 patients treated between 1968 and 1985. Median follow-up for patients without local or distant failure was 77 months. Patients were treated with either tangential fields alone (n = 508) or tangents with a third field to the supraclavicular (SC) or SC-axillary (AX) region (n = 1116). Lung volume treated in the tangential fields was generally limited by keeping the perpendicular distance (demagnified) at the isocenter from the deep field edges to the posterior chest wall (CLD) to 3 cm or less. Seventeen patients with radiation pneumonitis were identified (1.0%). Radiation pneumonitis was diagnosed when patients presented with cough (15/17, 88%), fever (9/17, 53%), and/or dyspnea (6/17, 35%) and radiographic changes (17/17) following completion of RT. Radiographic infiltrates corresponded to treatment portals in all patients, and in 12 of the 17 patients, returned to baseline within 1-12 months. Five patients had permanent scarring on chest X ray. No patient had late or persistent pulmonary symptoms. The incidence of radiation pneumonitis was correlated with the combined use of chemotherapy (CT) and a third field. Three percent (11/328) of patients treated with a 3-field technique who received chemotherapy developed radiation pneumonitis compared to 0.5% (6 of 1296) for all other patients (p = 0.0001). When patients treated with a 3-field technique received chemotherapy concurrently with radiation therapy, the incidence of radiation pneumonitis was 8.8% (8/92) compared with 1.3% (3/236) for those who received sequential chemotherapy and radiation therapy (p = 0.002). A case:control analysis was performed to determine if the volume of lung irradiated (as determined using central lung distance [CLD]) was related to the risk of developing radiation pneumonitis. Three control patients were matched to each case of radiation pneumonitis based on age, side of lesion, chemotherapy (including sequencing), use of a third field, and year treated. Lung volumes were similar in the radiation pneumonitis cases and controls. We conclude that radiation pneumonitis following conservative surgery and radiation therapy for breast cancer is a rare complication, and that it is more likely to occur in patients treated with both a 3-field technique and chemotherapy (particularly given concurrently with radiation therapy). Over the limited range of volumes treated, lung volume was not associated with an increased risk of radiation pneumonitis.

Adult↗
PubMed1991

Prostatodynia and herpes simplex virus infection.

The etiology of chronic abacterial prostatitis remains obscure, although viral agents have been postulated. Herpes simplex virus was isolated from the prostatic fluid of a patient with symptoms of prostatitis and the implications are reviewed.

Adult↗
PubMed1991

Cytomegalovirus ulceration of the oropharynx.

Cytomegalovirus (CMV) is a common opportunistic infection in both iatrogenic and HIV-induced immunosuppression. The usual sites of involvement are the gastro-intestinal tract, retina and lung. We present three cases of CMV ulceration of the oropharynx. All three patients presented with symptoms localized to the oropharynx and in each case the diagnosis was only made on histological examination of ulcer biopsy specimens. The patients all responded well to ganciclovir treatment and at writing none have required maintenance therapy (7-11 months post diagnosis).

Adult↗
PubMed1991

Field trial of oral cholera vaccines in Bangladesh: serum vibriocidal and antitoxic antibodies as markers of the risk of cholera.

The relationship of serum vibriocidal (VC) and IgG anti-cholera toxin (CT) antibodies to the risk of cholera was evaluated during the first year of follow-up of recipients of three oral doses of B subunit (BS)-whole-cell vaccine, whole-cell vaccine, or Escherichia coli K12 strain placebo in Bangladesh. Acute sera from 121 cholera patients were compared with sera from 2592 contemporaneous community controls. Each doubling of VC titer was associated, on average, with a 22%-47% reduction of cholera risk in the three groups. In contrast, in the two groups that did not receive BS, anti-CT titers were directly associated with cholera and thus served as markers of higher cholera risk. Each vaccine conferred approximately 65% protective efficacy against cholera, but antibody titers did not correlate with vaccine efficacy, indicating that serum VC and anti-CT antibodies are poor markers of the longitudinal pattern of vaccine efficacy.

Administration, Oral↗
PubMed1991

ABO blood groups and the risk of diarrhea due to enterotoxigenic Escherichia coli.

To determine whether blood group O persons are at higher risk for enterotoxigenic Escherichia coli (ETEC) diarrhea, a case-control study was done for 17 months among rural Bangladeshis who were under systematic surveillance for diarrhea. Cases were children less than 3 years old who presented between 1 January 1985 and 1 June 1986 for care of heat labile (LT) or heat stabile toxin-producing ETEC diarrhea. Controls were of similar ages and were randomly selected from three community-based serosurveys between July 1985 and May 1986. No association between blood group O and ETEC diarrhea was found for the 510 cases and 641 controls, nor was an association evident for cases of each toxin phenotype. Further refinement of the case definition to include only patients with LT-ETEC diarrhea, without enteric copathogens, also failed to reveal a substantial association with blood group O. These data suggest that a strong association with ABO groups, analogous to that for cholera, does not exist for ETEC diarrhea.

ABO Blood-Group System↗
PubMed1991

Antibody responses after immunization with killed oral cholera vaccines during the 1985 vaccine field trial in Bangladesh.

Sera collected during the 1985 oral cholera vaccine trial in Matlab, Bangladesh, which demonstrated efficacy of a whole cell combined with cholera B subunit vaccine (WC/BS) and a whole cell only vaccine (WC), were analyzed for antitoxin and vibriocidal antibodies. Before vaccines were given, antitoxin titers were highest in children, especially those with O blood group, whereas vibriocidal titers rose throughout life. Two weeks after three doses of vaccine, geometric mean antitoxin titers were 2.5-4.5 times higher in vaccinees who received the WC/BS vaccine; the vibriocidal titers were 1.3-2.1 times higher in vaccinees who received either vaccine. The titer elevations were relatively brief and were barely detectable 7 months after the third dose even though significant levels of protection persisted greater than or equal to 3 years. Thus, the oral vaccines induced a serum response in this large field trial that was similar to that seen in earlier pilot studies, but the duration of the serum responses was much shorter than the duration of the protection.

Administration, Oral↗
PubMed1991

Experience with liposomal amphotericin B (AmBisome) in cryptococcal meningitis in AIDS.

Three patients with AIDS who had cryptococcal meningitis were treated with liposomal amphotericin B after unsuccessful treatment with fluconazole and conventional amphotericin B. One patient responded but relapsed nine weeks later; he responded to a second course of treatment but again relapsed and subsequently died. Another patient deteriorated despite an improvement in cryptococcal antigen titres. The third patient was found to have culture negative CSF and treatment was therefore stopped. None of the patients suffered any adverse effects and renal function improved in all after conventional amphotericin was stopped and liposomal amphotericin B commenced.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The optimal extent of resection for patients with stages I or II breast cancer treated with conservative surgery and radiotherapy.

The optimal extent of breast resection before irradiation for treatment of early breast cancer has not been defined. Increasing the size of the resection may decrease the risk of local recurrence but will also have an adverse impact on the cosmetic outcome. The 5-year likelihood of a recurrence of the tumor was analyzed in relation to the volume of resected breast tissue in 507 patients with infiltrating ductal carcinoma treated with conservative surgery and radiation therapy between 1968 and 1982. Patients were stratified by clinical T-stage and for each T-stage patients were divided into three groups of equal numbers based on the volume of excised tissue. All patients had at least a gross excision of the tumor and the extent of breast resection was determined at the discretion of the surgeon without knowledge of the histologic features of the tumor. The median follow-up time was 100 months. The 5-year actuarial recurrence rates were analyzed in relation to clinical T-stage (T1 or T2) and the presence or absence of an extensive intraductal component (EIC+ or EIC-). For patients with EIC+ tumors, the largest resections were associated with a substantially lower risk of recurrence in the breast than the smallest resections. This effect was seen both for T1 tumors (10% versus 29%, p = 0.07) and for T2 tumors (9% versus 36%, p = 0.04). For patients with EIC-tumors, recurrence rates were significantly lower than for EIC+ tumors and were not influenced by the volume of resection to the same degree as EIC+ tumors. In the absence of an EIC, recurrence rates for the largest and smallest resections were 0% and 9% (p = 0.02) for T1 tumors and 3% and 6% (p = NS) for T2 tumors. It is concluded that a limited breast resection is acceptable for an EIC- tumor but that a more extensive resection is required for an EIC+ tumor. These results stress the importance of assessing the presence or absence of an EIC in determining the optimal extent of breast resection required before radiation therapy.

Breast Neoplasms↗
PubMed1991

Disseminated pneumocystis carinii infection in AIDS.

Eight patients with AIDS and Pneumocystis carinii infection were studied. Protean manifestations were a feature not untypical of disseminated pneumocystosis. Aerosolised pentamidine as prophylaxis against P carinii pneumonia was ineffective at suppressing dissemination. The knowledge that extrapulmonary infection can occur has implications for the detection and treatment of, and prophylaxis against, P carinii infection. The survival of patients with disseminated pneumocystosis is particularly poor, and may be due to a lack of clinical awareness and consequent delay in diagnosis.

Acquired Immunodeficiency Syndrome↗