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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 163 records · Page 9Linked to original sources

Pulmonary dysfunction related to immobility in the trauma patient.

Immobility is associated with multisystem pathophysiologic sequelae, especially in the critically ill trauma patient. Pulmonary embolus from deep vein thrombosis and nosocomial pneumonia are causes of pulmonary dysfunction that are directly related to immobilization in this population. Because of the high incidence of these complications, early identification of those at risk and institution of aggressive interventions to prevent nosocomial pneumonia and pulmonary embolus are crucial responsibilities of nurses caring for severely injured patients.

Bed Rest↗

Estimating the sexual mixing patterns in the general population from those in people acquiring gonorrhoea infection: theoretical foundation and empirical findings.

STUDY OBJECTIVES: To describe mathematically the relationship between patterns of sexual mixing in the general population and those of people with gonorrhoea infection, and hence to estimate the sexual mixing matrix for the general population. DESIGN: Integration of data describing sexual behaviour in the general population, with data describing sexual behaviour and mixing among individuals infected with gonorrhoea. Use of these data in a simple mathematical model of the transmission dynamics of gonorrhoea infection. SETTING: The general population of London and a genitourinary medicine (GUM) clinic in west London. PARTICIPANT: These comprised 1520 men and women living in London who were randomly selected for the national survey of sexual attitudes and lifestyles and 2414 heterosexual men and women who presented to the GUM clinic with gonorrhoea. MAIN RESULTS: The relationship between sexual mixing among people with gonorrhoea and sexual mixing in the general population is derived mathematically. An empirical estimate of the sexual mixing matrix for the general population is presented. The results provide tentative evidence that individuals with high rates of acquisition of sexual partners preferentially select other individuals with high rates as partners (assortative mixing). CONCLUSIONS: Reliable estimates of sexual mixing have been shown to be important for understanding the evolution of the epidemics of HIV infection and other sexually transmitted diseases. The possibility of estimating patterns of sexual mixing in the general population from information routinely collected in gonorrhoea contact tracing programmes is demonstrated. Furthermore, the approach we describe could, in principle, be used to estimate the same patterns of mixing, using contact tracing data for other sexually transmitted diseases, thus providing a way of validating our results.

Adolescent↗

Electron microscopy and biochemical characterization of a 350-kDa annular hemolymph protein from the keyhole limpet Megathura crenulata.

The isolation and biochemical characterization of an annular non-hemocyanin hemolymph protein from a marine gastropod, the Californian giant keyhole limpet (Megathura crenulata) is presented. By analytical ultracentrifugation, the protein has a sedimentation coefficient of 12S and molecular mass of approximately 350 kDa. The subunit mass, obtained by SDS/PAGE in the presence of -SH reagent and 8 M urea, is approximately 35 kDa, thereby indicating the presence of 10 subunits in the native molecule. By negative staining, the protein is revealed in one predominant image projection as a pentagonal approximately 8 nm ring-like structure with an approximately 2-nm stain-filled centre and, in another image projection, as a dimeric rectangular structure, approximately 8 nm x 14 nm. In deep stain, each of the components of the side-on dimer also shows an indication of stain penetration within a central channel. Unlike the hemolymph protein limulin/C-reactive protein from the horseshoe crab Limulus polyphemus, this Megathura protein does not possess any potential for the aggregation of phosphatidylcholine liposomes although it has an affinity for this phospholipid and causes bilayer destruction. It now appears likely that the previously reported lipid-bilayer ionic-conductance species in keyhole limpet hemolymph, attributed to hemocyanin, could indeed by due to the presence of this annular protein.

Animals↗

The relationship between microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy.

BACKGROUND: The relationships among the involvement of tumor at the final margins of resection, the presence of an extensive intraductal component (EIC), and the risk of local recurrence are important considerations in patients treated with conservative surgery and radiation therapy for early stage breast cancer but have not been defined adequately. METHODS: Between 1982 and 1985, 885 patients were treated for clinical Stage I or II invasive breast cancer. The study population was limited to 181 patients with an infiltrating ductal carcinoma who received a radiation dose to the surgical site of 60 Gy or greater, whose final microscopic margins of resection were evaluable, and who had at least 5 years of follow-up. A positive margin was defined as tumor present at the inked margin of resection, a close margin as tumor within 1 mm of the inked margin, and a negative margin as no tumor within 1 mm of the inked margin. A focally positive margin was defined as tumor at the margin in three or fewer low-power fields. In 157 patients (87%), the tumor was evaluable for the presence or absence of an EIC. The median follow-up was 86 months. RESULTS: In 12 of 181 patients (7%), a recurrence developed at or near the primary site (true recurrence/marginal miss [TR/MM]) within 5 years. The 5-year rate of TR/MM (with 95% confidence intervals) among patients with negative, close, focally positive, and more than focally positive margins was 0% (0-4%), 4% (0-20%), 6% (1-17%) and 21% (10-37%), respectively. Patients with positive margins also were more likely to have a distant failure within 5 years (14%, 8%, 25%, and 32% in the four groups, respectively). However, patients with positive margins more often had positive axillary lymph nodes than patients with negative or close margins (59% vs. 38%, P < 0.02). The 5-year rate of TR/MM was 20% for patients with an EIC-positive tumor and 7% for patients with an EIC-negative tumor. However, among the 127 patients with an EIC-negative tumor, the 5-year rate of TR/MM was less than 10% in all margin groups. Among the 30 patients with an EIC-positive tumor, the 5-year rate of TR/MM was 0% when margins were negative or close but 50% when margins were more than focally positive. CONCLUSIONS: These results provide support for the use of breast-conserving surgery and breast irradiation in all patients with uninvolved margins, whether the tumor is EIC-positive or EIC-negative. This study suggests that breast-conserving therapy (including a radiation boost to the primary site) also may be a reasonable option for some patients with an EIC-negative tumor and margin involvement.

Breast↗

The relation between the surgery-radiotherapy interval and treatment outcome in patients treated with breast-conserving surgery and radiation therapy without systemic therapy.

PURPOSE: This analysis was performed to clarify the relationship between the surgery-radiotherapy interval and the risk of recurrence in patients treated with breast-conserving therapy for early stage invasive cancers. METHODS AND MATERIALS: We retrospectively analyzed data from 653 patients with American Joint Commission on Cancer Stage I or II, pathologically node-negative breast cancer treated by breast-conserving therapy without adjuvant systemic therapy between 1968 and 1985. All patients received a dose of at least 60 Gy to the tumor bed. Two hundred and eighty-three patients started radiotherapy within 4 weeks of surgery, 308 started 5-8 weeks after surgery, and 54 started 9-12 weeks after surgery. Median follow-up in the 531 survivors was 100 months. RESULTS: Pathologic features and treatment characteristics were well balanced between the groups with surgery-radiotherapy intervals of 0-4 weeks and 5-8 weeks. There was no statistically difference in the risk of overall recurrence among patients starting radiotherapy 5-8 weeks after surgery compared with those treated within 4 weeks. Analysis of the 5-year crude rates of failure further demonstrated no difference in the distribution of sites of failure in the 5-8 week group compared with the 0-4 week group. A multivariate model controlling for known risk factors, as well as potential treatment-related confounders, also failed to demonstrate an increased risk of recurrence with the longer surgery-radiotherapy interval (risk ratio = 0.89, p = 0.44). CONCLUSION: This retrospective analysis suggests that a delay of up to 8 weeks in the interval between the last breast surgery and the start of radiotherapy is not associated with an increased risk of recurrence in patients with early stage breast cancer treated with breast irradiation to at least 60 Gy without systemic therapy.

Analysis of Variance↗

Microvessel density and distribution in ductal carcinoma in situ of the breast.

BACKGROUND: Prior studies have suggested that microvessel density is an important prognostic factor in invasive breast cancer. However, the extent and distribution of microvessels in association with ductal carcinoma in situ (DCIS) have not been well defined. PURPOSE: Our goal was to determine the density and distribution of stromal microvessels in DCIS and to investigate the relationships among microvessel density, histopathologic features, HER2/neu oncogene expression, and tumor proliferation rate. METHODS: Of 61 consecutive cases of DCIS identified from hospital pathology reports, 55 cases were evaluated. Breast biopsy specimens had been preserved in paraffin blocks for each DCIS case. Histologic sections of formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin and immunostained for factor VIII-related antigen, the HER2/neu oncoprotein, and the proliferative-associated antigen detected by the Ki-S1 antibody. Factor VIII-stained sections from each case were independently examined by two pathologists and overall tumor-associated stromal microvessel density was scored semiquantitatively on a 1+ to 3+ scale by each observer. Quantitative microvessel counts of DCIS-associated stromal microvessel density were performed. The presence or absence of a cuff of microvessels in immediate apposition to the basement membrane of involved spaces was also evaluated. RESULTS: A variable number of microvessels were found to be present in a diffuse pattern surrounding spaces involved with DCIS. Semiquantitative microvessel scores were 2+ in the majority of cases (53%); 22% of cases were 1+, and 25% were 3+. Quantitative microvessel counts ranged from 17 to 80 vessels per 100x field (0.45 mm2), with a mean +/- SD of 42.9 +/- 16.6. Comedo-type lesions were significantly (P = .004) more often associated with 3+ microvessel density than non-comedo-type lesions by semiquantitative assessment. As determined by both semiquantitative and quantitative analysis, respectively, the presence of prominent microvessel density was significantly associated with marked stromal desmoplasia (P = .05 and P = .04), HER2/neu expression (P = .03 and P = .0002), and high Ki-S1 proliferation index (P = .05 and P = .01). Vascular cuffing around involved spaces was identified in 21 of the 55 cases (38%) and was not significantly associated with histologic features, HER2/neu expression, or Ki-S1 proliferation index. CONCLUSIONS: DCIS of the breast is characterized by two patterns of stromal microvessels. The first pattern is a diffuse increase in stromal microvessels surrounding involved spaces. This pattern is particularly prominent in comedo-type lesions with marked stromal desmoplasia. The second pattern is microvessel cuffing of involved spaces that is present in only a minority of cases and appears unrelated to histologic features evaluated, including DCIS subtype.

Breast Neoplasms↗

Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS.

The objective of this study was to assess the efficacy and toxicity of a novel Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II dose escalation study was carried out in a specialist HIV oncology unit in a teaching hospital (predominantly in an outpatient department). Fifteen patients with HIV related, biopsy confirmed, cutaneous Kaposi's sarcoma, with or without visceral involvement of sufficient severity to require systemic chemotherapy, were treated. Most patients had poor prognosis disease as assessed by the Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six patients had previously received combination chemotherapy. Primary treatment consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposi's sarcoma (KS) responded and the treatment was tolerated, the patient began maintenance therapy at the same dose every 2 weeks. If there was no clinical response, the dose was increased to 20 mg/m2 for the further two cycles, before proceeding to maintenance therapy. Treatment continued until other intercurrent disease, lack of further response, patient preference, or toxicity precluded further treatment. Tumour response was assessed 2 weeks after completion of at least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was well tolerated, and toxicity was manageable, the principal toxicity being haematological. A partial response rate of 11/15 (73%) was achieved, with disease stabilization in the remaining patients. We conclude that Doxil is an effective palliative treatment for epidemic KS in a patient group with a poor predicted outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

Changing use of hospital services and costs at a London AIDS referral centre, 1983-1989.

OBJECTIVE: To describe the use of hospital-based services and associated costs over time for HIV-infected individuals by disease stage and year of treatment. METHODS: Data on service use were abstracted from inpatient and outpatient case-notes of 459 HIV-infected patients (121 asymptomatic and 338 AIDS patients) treated at St Mary's Hospital, London between 1983 and 1989. Cost estimates were derived from a survey of the 37 departments involved with HIV-related care. The number and type of admissions and outpatient visits, referral and discharge venues, number and type of tests and procedures performed, drugs prescribed and associated costs for the study period were the outcome measures used. RESULTS: Most patients were homosexual men. At the time of first HIV-related visit, 80.7% lived in London. Most day cases and planned admissions were organized through the outpatient clinic; 31% of emergency admissions were initiated by patients themselves. For people with AIDS the number of day case admissions increased while planned admissions decreased. There was a marked reduction in the duration of inpatient stays, especially for AIDS patients. Costs associated with inpatient care decreased concomitantly. The number of outpatient visits for patients with symptomatic disease increased, resulting in increased outpatient expenditure. Asymptomatic patients had fewer inpatient tests, while outpatient tests did not change over time; costs followed similar patterns. Mean inpatient and outpatient drug-days prescribed did not change nor did average inpatient drug-costs although outpatient drug-costs increased. Inpatient tests performed on symptomatic non-AIDS patients decreased, while mean outpatient tests increased; average costs followed similar patterns. Inpatient drug-days prescribed and costs remained the same, while outpatient drug-days and average drug-costs increased during the study period. For AIDS patients, the number of inpatient tests performed and their average costs decreased but outpatient tests performed increased, though their average costs remained the same. Mean inpatient drug-days prescribed and average drug-costs decreased, while number of outpatient drug-days prescribed and average drug-costs increased markedly over time. For each disease category, expenditure on admissions and related tests decreased over time, while expenditure on outpatient visits and drug-costs increased. CONCLUSIONS: The shift from an inpatient- to an outpatient-based service has resulted in fewer patients being investigated and treated in hospital and more as outpatients. This has resulted in a reduction of inpatient-related costs, while outpatient-related costs have increased. The overall contribution of drug-costs to the total cost has increased greatly over time. With the anticipated advent of new antiviral compounds, the importance of ascertaining their effectiveness as well as their efficacy will become crucial.

Acquired Immunodeficiency Syndrome↗

Changing presentation and survival, service utilization and costs for AIDS patients: insights from a London referral centre.

OBJECTIVE: To describe the use of services and associated costs for HIV-infected patients by stage of infection in the context of changing patterns of presentation and survival. METHODS: A retrospective analysis of inpatient and outpatient case-notes of 335 AIDS patients and a survey of HIV-related care provided by 37 departments at St Mary's Hospital, London. Survival from time of diagnosis of AIDS, time from diagnosis of HIV infection to AIDS, and use and costs of services per patient-year were outcome measures. RESULTS: During the study period 1 January 1982 to 30 September 1989, 152 AIDS patients were diagnosed before 1987 (group 1) and 183 since 1987 (group 2), most of whom were homosexual men. The median interval of first HIV-related visit to diagnosis of AIDS increased from 0 (group 1) to 264 days (group 2; P < 0.0001). Median survival from AIDS diagnosis increased from 14.6 (group 1) to 21.0 months (group 2; P < 0.02). Group 2 patients used fewer inpatient services than group 1 patients irrespective of disease stage. Symptomatic patients in group 2 used more outpatient services than group 1 patients. Total HIV-related expenditure was lower for patients without AIDS in group 2 than in group 1, while expenditure for AIDS patients remained similar. CONCLUSION: Earlier patient presentation, a shift from inpatient- to outpatient-based clinical care and increased survival from time of AIDS diagnosis has occurred. Increased drug expenditure was offset by reduced inpatient expenditure. Total expenditure per patient-year was stable; increased survival and introduction of new drugs will increase future lifetime use of resources.

Acquired Immunodeficiency Syndrome↗

Long-term results of irradiation for basal cell carcinoma of the skin of the nose.

The long-term outcome of basal cell carcinoma of the nose in patients treated with radiation therapy has not been well documented. To make this evaluation, we assessed the cosmetic and oncologic results in 26 patients after an average interval of 9.3 years following radiation therapy. The majority of the patients were treated with only three doses of radiation from a superficial 50-kVp unit. The cosmetic result was evaluated independently by the patient and two of the authors using a defined grading system. The local control rate was 96 percent, with none of the patients having recurrence noted at the follow-up examination. The patient evaluated the cosmetic result as excellent or good in 81 percent (21 of 26) of cases and physicians in 77 percent (20 of 26) of cases. The cosmetic result appears to remain stable over time; 86 percent of the patients treated more than 13 years ago were rated as having an excellent or good cosmetic result. These data suggest that superficial irradiation is associated with good to excellent cosmetic results in most patients and should be considered an important treatment option for patients with basal cell carcinoma of the skin of the nose.

Adult↗

Infectious osteitis pubis in an HIV seropositive female.

We report a case of infectious osteitis pubis following a first trimester abortion in a female seropositive for the human immunodeficiency virus (HIV). Joint aspiration yielded Pseudomonas aeruginosa and the patient was successfully treated with oral ciprofloxacin.

Abortion, Induced↗

Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer.

PURPOSE: This analysis was performed to clarify the relationship of young age at diagnosis to the pathologic features of the tumor and prognosis in patients with early-stage breast cancer. PATIENTS AND METHODS: We retrospectively analyzed data from 1,398 patients with American Joint Committee on Cancer Staging stage I or II breast cancer treated by breast-conserving therapy between 1968 and 1985. One hundred seven patients were younger than 35 years at the time of diagnosis. The median follow-up duration for the 1,032 survivors was 99 months. RESULTS: Patients younger than 35 years had a significantly higher overall recurrence rate (P = .002), as well as a greater risk for developing distant metastases (P = .03), when compared with older patients. The cancers in younger patients more commonly showed factors associated with a worse prognosis (including grade 3 histology, lymphatic vessel invasion [LVI], necrosis, and estrogen receptor [ER] negativity) as compared with older patients. In a proportional hazards model that included clinical and treatment-related variables, as well as these pathologic features, age younger than 35 years remained a significant predictor for time to recurrence (relative risk [RR], 1.70), time to distant failure (RR, 1.60), and overall mortality (RR, 1.50). CONCLUSION: Breast cancer patients younger than 35 years have a worse prognosis than older patients. This difference is only partially explained by a higher frequency of adverse pathologic factors seen in younger patients.

Actuarial Analysis↗

Minimizing projected liability under FAS No. 106.

Although the Statement of Financial Accounting Standards No. 106: Employers' Accounting for Postretirement Benefits Other Than Pensions requires that the anticipated cost of providing medical services to an employee following his or her retirement be accrued while the individual is employed, hospitals that provide their retirees with medical services are in a position to minimize their projected liability. The values of actual expenditures to be incurred for providing medical services should be valued in a manner consistent with the recording of other expenditures.

Accounting↗

Pregnancy after breast-conserving surgery and radiation therapy for breast cancer.

Since the incidence of breast cancer is increasing in young women and young women are more commonly delaying child-bearing, the issue of considering a pregnancy subsequent to the diagnosis and treatment of breast cancer is becoming more common. The impact of a subsequent pregnancy on disease progression and quality of life is, however, not well defined. We evaluated treatment outcome and quality of life among 23 breast cancer patients treated with conservative surgery and radiation among the 1624 patients treated at the Joint Center for Radiation Therapy between 1968 and 1985 who had subsequent pregnancies as compared with 23 patients without subsequent pregnancy matched by age and stage at diagnosis and time to pregnancy without recurrence. Quality of life was evaluated using two self-report measures, Ferrans and Powers Quality of Life Index and the Adaptation to Surviving Cancer Profile, and a measure of parenting stress (Parenting Stress Index). Results showed no differences in recurrence or distant metastasis between the matched groups. In addition, subjects with subsequent pregnancy perceived that family issues had the greatest impact on quality of life and were not at higher risk for parental stress due to breast cancer than the normal population. Both groups of young women perceived that they were able to adjust well after treatment. Study results are consistent with other clinical studies comparing patients with and without subsequent pregnancy who have failed to demonstrate a survival disadvantage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗