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Biomedical subjects

M Harrison

Publications and source records attributed to M Harrison.

At least 55 records · Page 3Linked to original sources

Squamous cell carcinoma of the anus in patients with AIDS.

Squamous cell carcinoma of the anus accounts for 2%-3% of all malignancies of the lower gastrointestinal tract. There is an increased incidence in homosexual males who practise receptive and anal intercourse [1]. We report on three cases of squamous cell carcinoma of the anus in patients with the acquired immune deficiency syndrome (AIDS), all of whom were treated with conventional radiotherapy. Increased normal tissue damage with delayed healing was a severe problem in each patient. This led to prolonged delays in delivering an adequate dose of radiotherapy to the site of disease. Reasons for this are explored and suggestions made for the treatment of such patients in the future.

AIDS-Related Opportunistic Infections

Mitochondrial hyperoxidation signals residual intracellular dysfunction after global ischemia in rat neocortex.

Reperfusion after global ischemia (10-60 min in duration) in rat neocortex most commonly provoked transient hyperoxidation of mitochondrial electron carriers, tissue hyperoxygenation, and CBF hyperemia. These responses were normally accompanied by recovery of K+ homeostasis and EEG spike activity. Goals of this research were to understand putative relationships among these postreperfusion events with special emphasis on determining whether mitochondrial hyperoxidation results from intracellular changes that may modulate residual damage. The amplitude of postischemic mitochondrial hyperoxidation (PIMHo) did not increase when CBF increased above an apparent threshold during reperfusion, and tissue hyperoxygenation was not required for PIMHo to occur or to continue. These findings suggest that PIMHo is not merely a response to increased CBF and tissue hyperoxygenation; rather, PIMHo is modulated, at least in part, by residual intracellular derangements that limit mitochondrial electron transport. This suggestion was supported by observations that NAD became hyperoxidized after reoxygenation in anoxic hippocampal slices. Also, PIMHo occurred and subsequently resolved in many animals, but K+o never was cleared fully to baseline and/or EEG spike activity never was evident. One suggestion is that PIMHo signals or initiates residual intracellular derangements that in turn impair electrical and metabolic recovery of cerebral neurons after ischemia; an alternative suggestion is that PIMHo and tissue hyperoxygenation are not the sole factors modulating the immediate restoration of electrical activity after ischemia. Present data also support the following: Decreased oxygen consumption, despite adequate oxygen delivery, likely contributes to tissue hyperoxygenation after ischemia; and mitochondrial hyperoxidation is modulated by a limitation in the supply of electrons to the mitochondrial respiratory chain.

Animals

The National Prostatectomy Audit: the clinical management of patients during hospital admission.

OBJECTIVE: To determine everyday practice in the hospital management of men undergoing prostatectomy and the extent of its variation. PATIENTS AND METHODS: A total of 5361 patients, who represented 89% of all those undergoing prostatic procedures in four health regions (Mersey, Wessex, Northern and South West Thames) and one test site (within Trent) were recruited by 103 (97%) surgeons. Clinical information was collected on a pre-coded data collection form which was completed during the hospital stay by the principal operator. Patient identification occurred at the time of surgery. RESULTS: Important findings included: (i) both older men and those of higher social class were more likely to undergo prostatectomy with fewer symptoms; (ii) men who waited longer for surgery had worse symptoms by the time of their operation; (iii) there were unexplained differences in routine pre- and post-operative investigation and treatment. Half the men had their flow rate or residual urine measured as part of their pre-operative assessment. About half the men received prophylactic antibiotics; (iv) when large groups were analysed, a consistent proportion of men throughout the study (12%) were undergoing the operation for a second time. The clinical course of men having a repeat operation differed in many ways from those having a first time procedure; (v) the larger proportion of men (62%) had surgery for strong indications as opposed to symptoms alone; (vi) although most operations were performed by consultants, emergency admissions, though symptomatically more severe and sicker, were more likely to be operated on by trainee surgeons; (vii) significant variation in mean pre-operative symptom severity and bother scores were seen between surgeons. CONCLUSION: The clinical management of prostatectomy has been defined in a large and representative UK sample. In some circumstances consistent variations have been identified. It is not yet clear whether these variations influence outcome. These data can be used by surgeons wishing to compare their own patient management with that described here.

Age Factors

Liposomal-entrapped doxorubicin: an active agent in AIDS-related Kaposi's sarcoma.

PURPOSE: A phase II study was performed of single-agent liposomally entrapped doxorubicin ([LED] Doxil; Liposome Technology Inc, Menlo Park, CA) against locally advanced cutaneous/systemic AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: Thirty-four patients with AIDS-related advanced cutaneous/systemic KS were treated with 20 mg/m2 of LED every 3 weeks on an outpatient basis. The median age was 39 years and the median Karnofsky score was 70. All patients had poor prognostic disease as judged by AIDS Clinical Trials Group (ACTG) criteria. Nineteen of 34 patients had received prior chemotherapy for KS, although no patient had received prior anthracyclines. RESULTS: An overall response rate of 73.5% (25 of 34) was observed. Partial responses (PRs) occurred in 67.7% (23 of 34) and complete responses (CRs) in 5.8% (two of 34). In patients who had received previous chemotherapy, the response rate was 68.4% (13 of 19), and all responses were PRs. The median time to response was 6 weeks. The median duration of response was 9 weeks. Toxicity according to World Health Organization (WHO) criteria was as follows: neutropenia (grade > or = 3), 34%; alopecia (grade 1 only), 9%; and nausea and vomiting (grade 1), 18%. One patient died of heart failure, which was not considered to be anthracycline-induced. CONCLUSION: LED appears to be highly active against AIDS-related KS. The major toxicity is neutropenia, which seems to be progressive in patients who receive several cycles of therapy. Comparative studies of LED versus conventional chemotherapy are needed.

Acquired Immunodeficiency Syndrome

The relationship between cholecystectomy, unoperated gallstone disease, and colorectal cancer. A necropsy study.

BACKGROUND: There may be an increased risk of colorectal cancer after cholecystectomy, but the literature is not consistent. It is also possible that any risk might be associated with gallstones rather than cholecystectomy. METHODS: In a prospective necropsy study of 8563 cases, all 219 cases of a previous cholecystectomy were pair-matched to subjects with gallstones and to subjects with a normal gallbladder. In a second study all 192 cases of colorectal cancer were pair-matched to cancer-free subjects. RESULTS: The odds ratio (OR) for developing colorectal cancer after cholecystectomy compared with a normal gallbladder was 1.0 (95% confidence interval, 0.30-3.34) and with unoperated gallstones was 0.88 (0.27-2.76). CONCLUSIONS: This study fails to support an association between cholecystectomy or gallstones and colorectal cancer. For those cases of colorectal cancer versus controls, the OR for previous cholecystectomy was 0.70 (0.23-2.04) and for gallstone disease was 0.93 (0.58-1.48).

Cholecystectomy

Is it possible to reduce observer variability in skin score assessment of scleroderma? The ad hoc International Group on the Assessment of Disease Outcome in Scleroderma.

OBJECTIVE: A total skin thickness score based on summating the numerical severity grade at a specific number of skin sites is a widely accepted method of disease assessment in scleroderma. Our aim was to simplify the modified Rodnan skin thickness score (grade 0-3 at 17 sites) by either (1) reducing the number of grades or (2) reducing the number of sites, and to increase agreement without losing precision. METHODS: Eight patients were examined in random order by 16 experienced clinicians using the modified Rodnan method. The data were analyzed to determine (1) whether there was an improvement in agreement by reducing severity grades to a 0-2 scale, (2) whether the precision of the score could be maintained by using a reduced number of sites. RESULTS: Collapsing adjacent grades from the 0-3 scale to generate 3 new 0-2 scales performed similarly (intraclass correlation coefficients 0.66-0.72). A regression analysis showed that 95% of the variance in skin score can be predicted by inclusion of scores from just 5 sites: forearms, lower legs, anterior chest, upper arms, and fingers. CONCLUSION: A simpler skin score may be useful in clinical studies depending on the precision required.

Humans

Rapidly cycled courses of high-dose alkylating agents supported by filgrastim and peripheral blood progenitor cells in patients with metastatic breast cancer.

Our purpose was to determine the feasibility of a regimen of multiple, rapidly cycled courses of high-dose alkylating agents, including paired courses of escalating doses of thiotepa, supported by peripheral blood progenitor cells and filgrastim, in patients with responding stage IV breast cancer. The regimen consisted of two courses of cyclophosphamide (3.0 g/m2/course) followed by two courses of thiotepa (500-700 mg/m2/course). All courses were supported by filgrastim. Leukaphereses were performed after each cyclophosphamide course to harvest peripheral blood progenitors (PBPs) for use as rescue following thiotepa administration. The planned interval for all courses was 14 days. Forty-two patients were enrolled. Thirty-eight received all four courses, and four did not receive the second thiotepa cycle due to poor PBP mobilization. The maximum dose of thiotepa that was administered was 700 mg/m2 x 2. At this dose, one patient developed encephalopathy, which resolved over several weeks. The median number of days to an absolute neutrophil count of 0.5 x 10(9)/liter after PBP reinfusion for cycles 1 and 2 of thiotepa were 9 (range, 7-16) and 9 (range, 8-13) days, respectively. The corresponding values for platelet recovery to >20 x 10(9)/liter were 11 (range, 8-39) and 12 (range, 10-28) days, respectively. There were no treatment-related deaths. Hospitalization was required following 28 of 84 cyclophosphamide courses and 76 of 80 thiotepa courses. Four patients developed grade III-IV mucositis. The median interval between courses of treatment was 15 (range, 13-29) days. Of 19 patients who entered the protocol with measurable disease in partial response from prior therapy, 8 (42%) achieved complete response following the high-dose therapy. Nine (21%) of 42 remain progression free at a median follow-up of 28 (range, 20-32) months. Therefore, we concluded that the administration of multiple, rapidly cycled courses of high-dose alkylating agents is feasible.

Adult

Design criteria for prompt radiation limits on the relativistic heavy ion collider site.

The Relativistic Heavy Ion Collider (RHIC) is a superconducting colliding beam accelerator facility that is currently under construction. Relatively small amounts of energy depositing in the coils of superconducting magnets can result in a "quench," the irreversible transition to the normal resistive state. The quench limit of superconducting magnets, therefore, constrains local beam loss throughout the injection, acceleration, and storage cycles to extremely low levels. From a practical standpoint, it follows that there is essentially no prompt radiation in most regions due to normal operations. The design of shielding is, therefore, principally driven by the consequences of a single pulse fault at full energy in one of the two storage rings. Since there are no regulatory requirements or guidance documents that prescribe radiological performance goals for this situation, the RHIC Project has proposed a scheme to classify the various areas of the RHIC complex based on Design Basis Accident faults. The criteria is then compared to existing regulatory requirements and guidance recommendations.

Equipment Design

The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning.

BACKGROUND AND PURPOSE: Microemboli have been implicated in the etiology of neuropsychological deficits after cardiopulmonary bypass. This study examined the incidence of high-intensity transcranial signals (microemboli) and their relation to changes in neuropsychological performance after surgery. METHODS: Transcranial Doppler ultrasonography was used to measure middle cerebral artery blood flow velocity and detect microemboli. The number of high-intensity transcranial signals was determined and related to a neurological examination and absolute changes in neuropsychological performance as well as the number of patients considered to exhibit a neuropsychological deficit. Data were available on 100 consenting patients undergoing routine cardiopulmonary bypass. Fifty of the patients were randomly assigned to a procedure that included a 40-microns arterial line filter, and 50 had the procedure without any arterial line filter. RESULTS: Significantly more patients were found to have neuropsychological deficits in the group without the arterial line filter at both 8 days (P < .05) and 8 weeks (P < .03) after surgery. In addition, more "soft" neurological signs were found in the nonfiltered group 24 hours after surgery (P < .05). More high-intensity transcranial signals were found in the nonfiltered group, and the number of high-intensity transcranial signals was found to be related to the likelihood of a patient having a neuropsychological deficit at 8 weeks. CONCLUSIONS: These data suggest that neuropsychological deficits after routine cardiopulmonary bypass are related to the number of microemboli delivered during surgery. Furthermore, the numbers of microemboli may be reduced by including a 40-microns filter on the arterial line.

Cardiopulmonary Bypass

Development of a measure of nurses' AIDS attitudes and conservative views.

The literature concerning measurement of nurses' attitudes toward AIDS was reviewed. A short scale to measure nurses' attitudes toward AIDS was developed and evaluated. The instrument has three subscales on (a) willingness to care for those who are HIV positive, homosexuals, and intravenous drug users as patients, (b) attitudes toward homosexuals and intravenous drug users, and (c) general conservative views on religious, political, and family issues. The three subscales were supported by results of a factor analysis. Coefficient alpha ranged from .69 to .92.

Acquired Immunodeficiency Syndrome

Magnetic resonance imaging in pigmented villonodular synovitis.

The magnetic resonance imaging (MRI) appearance of pigmented villonodular synovitis of the knee is described for three patients. In the images for one patient diffuse areas of low signal intensity reflecting hemosiderin deposits suggested the diagnosis. For another patient with the diffuse form of the condition but minimal hemosiderin deposition, identification of diffuse synovial proliferation in the MRI images guided diagnostic percutaneous biopsy. For the third patient, who had localized pigmented villonodular synovitis, MRI after administration of a gadolinium chelate facilitated identification of localized synovial proliferation and guided diagnostic arthroscopic biopsy. The authors discuss the value of MRI in the diagnosis of all forms of this uncommon condition and the various signal characteristics that it may produce.

Adolescent

Nitric oxide synthase activity in the pregnant uterus decreases at parturition.

The mechanisms that mediate changes in uterine activity from a quiescent state during pregnancy to active labor at parturition are unknown. Nitric oxide (NO), a potent mediator of smooth muscle relaxation, and its presence in the uterus is the subject of this report. Nitric oxide synthase (NOS) activity was demonstrated in nerves, blood vessels and decidua of gravid rat uterus by the NADPH-diaphorase staining method. Uterine tissue fixed during labor demonstrated markedly less NOS. Quantitation of NOS activity in subcellular fractions of pregnant and laboring uterus revealed its presence in both the cytosolic and the membranous compartments of uterine homogenates. In both cellular subfractions the enzyme activity decreased significantly from pregnancy to term. We conclude NOS is present in multiple structures within the uterus. Its presence in two cellular compartments suggests more than one form of NOS may be present in the uterus. Reduction in NOS activity at parturition suggests NO may contribute to the maintenance of uterine contractile quiescence during gestation.

Amino Acid Oxidoreductases

The incidence and role of actinomyces in recurrent acute tonsillitis.

Although actinomyces has been identified in between 1.77% and 37% of resected tonsils its possible role in recurrent acute tonsillitis has received little attention. A histological and bacteriological study of 129 pairs of tonsils from patients with recurrent acute tonsillitis showed actinomyces to be present in 29.5%. The organism, however, was also present in 40% of tonsils from 10 patients with no history of tonsillar disease. In neither of these groups was there any specific evidence of tissue reaction to actinomyces nor was there a male preponderance as in clinical actinomycosis. The presence of actinomyces in the tonsil was not favoured by the concurrence of beta-lactamase producing bacteria. These data indicate that actinomyces does not have a causal role in recurrent acute tonsillitis.

Actinomyces