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Biomedical subjects

M Harrison

Publications and source records attributed to M Harrison.

At least 127 records · Page 7Linked to original sources
PubMed1996

Cyclo-oxygenase-2 messenger RNA induction in focal cerebral ischemia.

We have characterized the induction of the mitogen-inducible form of cyclo-oxygenase, COX-2, during focal cerebral ischemia following permanent middle cerebral artery occlusion (MCAO) in the rat. Marked unilateral induction of COX-2 mRNA was detected in ischemic regions ipsilateral to the occlusion. A significant increase in COX-2 mRNA was detected in "core" and "penumbra" regions of the cerebral cortex between 4 and 24 h after occlusion; this was most marked at 4 h in the penumbra region, in which a 19-fold increase above untreated control levels was detected. A smaller but significant induction was also detected at 4 h in the caudate. A correlation was demonstrated between the extent of COX-2 mRNA induction in cortical regions at 4 h and the severity of tissue damage subsequently detected at 24 h post MCAO. MK-801 significantly attenuated the induction of COX-2 mRNA in the penumbra region at 4 h. The demonstration of COX-2 induction following experimental ischemia highlights the importance of this reaction and its products and by-products, for example, free radicals, in the tissue response to this insult.

Animals↗
PubMed1996

Pulmonary edema in a woman following fetal surgery.

Most cases of acute lung injury in pregnancy are attributed to hydrostatic pulmonary edema. In this report, however, we describe a 20-year-old pregnant woman who developed a unique case of increased permeability pulmonary edema following surgery for the repair of a fetal congenital diaphragmatic hernia. Two days after surgery, the patient developed acute respiratory failure and diffuse alveolar edema, requiring intubation and positive pressure ventilation for 5 days. The diagnosis of increased permeability pulmonary edema was confirmed by the ratio of pulmonary edema fluid to plasma protein (ratio=0.99). The patient received IV nitroglycerine for tocolysis. As a nitric oxide donor, the nitroglycerine may have combined with exogenous oxygen to form peroxynitrite, a known impediment to alveolar epithelial cell function. Many cases of pulmonary edema in pregnancy are diagnosed as hydrostatic based on clinical parameters, such as positive maternal fluid balance. In this case, these parameters would have been misleading. Measurement of the protein concentration in the pulmonary edema fluid allowed us to accurately determine that the patient had increased permeability pulmonary edema as the cause of her acute respiratory failure. Sampling of pulmonary fluid can differentiate the type of edema formation and in some cases help to identify mechanisms of acute lung injury.

Adult↗
PubMed1996

Impact of laparoscopic cholecystectomy on surgical training.

All cholecystectomies in a single health district were studied during a 5-year period spanning the introduction of laparoscopic cholecystectomy (LC). The number of LCs increased from 2 (1.3%) in year 3 to 86 (56%) in year 5. The number of operative cholangiograms and explorations of the common bile duct performed both fell substantially. The age distribution did not change significantly during the study period, but the percentage of females undergoing cholecystectomy increased. The percentage of trainee operations remained constant in those Firms performing only open cholecystectomy (OC), but fell from 67% to 9% in those adopting LC. An increase in annual cholecystectomy rate was seen with the laparoscopic surgeons, with a corresponding fall for those surgeons performing only OC. There was a threefold increase in the percentage of operations performed privately from years 2 to 5, with 73% being laparoscopic in year 5. The consequences for training of the introduction of LC must be addressed.

Adolescent↗
PubMed1996

Long-term engraftment following in utero T cell-depleted parental marrow transplantation into fetal rhesus monkeys.

A major concern with allogeneic BMT for treating most inherited diseases is the need to overcome graft rejection with conditioning chemotherapy which is associated with a relatively high morbidity and mortality. This can be eliminated if the transplant is done in utero when the fetus is unable to reject donor hematopoietic stem cells (HSC). We studied the efficacy of T cell-depleted (TCD) parental bone marrow as a source of HSC for transplantation into early gestation non-defective fetal rhesus monkeys. Thirteen opposite sexed TCD transplants were done into 44 day fetal recipients and 12 into 61 day recipients (165 day total gestation). The procedure-related mortality was 8%, all in the earlier age group. The overall survival was 60% at birth with a projected survival of 44 +/- 10% at 1.5 years with no difference between the two age groups. We used a PCR assay for the rhesus Y chromosome to detect male donor cells in female recipients (six animals transplanted at 44 days and five at 63 days). The overall engraftment rate was 73% with no difference as a function of gestational age at transplant. In six long-term surviving engrafted females we detected donor cells in the peripheral blood and bone marrow up to 3 years of age. We found a delay in the appearance of donor cells in the peripheral blood in engrafted animals, in some cases for up to 6 months post-BMT. In vitro mixed lymphocyte reaction and cell-mediated lymphocytotoxicity studies between the recipient and donor cells indicate that tolerance was induced to donor cells. Individual and pooled erythroid and myeloid marrow colonies grown in methyl cellulose were collected and analyzed for donor origin by PCR. The amount of donor cells in marrows from long-term engrafted animals was < 0.1%. In a fetal recipient studied at 35 days post-BMT, donor cells were detected in bone marrow and liver in both erythroid and myeloid lineages. These results indicate that TCD parental marrow can durably engraft in utero. While the engraftment rate is similar to that seen with fetal liver as the source of HSC, the degree of peripheral blood engraftment (percent donor cells) in this non-defective primate model is low. It will require increasing the percent pre-or postnatally for this approach to be clinically relevant in those disorders in which there is no selective survival advantage for normal engrafted donor cells.

Animals↗
PubMed1995

Ductin--a proton pump component, a gap junction channel and a neurotransmitter release channel.

Ductin is the highest conserved membrane protein yet found in eukaryotes. It is multifunctional, being the subunit c or proteolipid component of the vacuolar H(+)-ATPase and at the same time the protein component of a form of gap junction in metazoan animals. Analysis of its structure shows it to be a tandem repeat of two 8-kDa domains derived from the subunit c of the F0 proton pore from the F1F0 ATPase. Each domain contains two transmembrane alpha-helices, which together may form a four-helix bundle. In both the V-ATPase and gap junction channel, ductin is probably arranged as a hexamer of subunits forming a central channel of gap junction-like proportions. The two functions appear to be seggregated by ductin having two orientations in the bilayer. Ductin is also the major component of the mediatophore, a protein complex which may aid in the release of neurotransmitters across the pre-synaptic membrane. It is also a target for a class of poorly understood viral polypeptides. These polypeptides are small and highly hydrophobic and some have oncogenic activity. Ductin thus appears to be at the crossroads of a number of biological processes.

Amino Acid Sequence↗
PubMed1995

Chromosome 1 aneusomy, identified by interphase cytogenetics, in mammographically detected ductal carcinoma in situ of the breast.

Because of the relative rarity of ductal carcinoma in situ (DCIS) in the premammographic screening era, the unavailability of adequate fresh tissue for culture, and the lack of cytogenetic expertise in most pathology departments, there is little information on karyotypic abnormalities in DCIS. The purpose of this study was to investigate the frequency of chromosome 1 aneusomy in DCIS, using interphase cytogenetic techniques, and to correlate the findings with nuclear grade. Twenty-one cases of DCIS, identified in a mammographically screened population, were studied by in situ hybridization. Chromosome 1 numbers were identified in interphase nuclei in conventional histology sections, using a specific centromeric probe (pUC 1.77). In each case, 100 tumour nuclei were compared with 100 normal nuclei. Eighteen of 21 (86 per cent) cases were aneusomic for chromosome 2. This included 15 of 16 (94 per cent) pure comedo or predominantly comedo DCIS. Fifteen of 16 (94 per cent) DCIS with grade 3 nuclei and 3 of 5 (60 per cent) cases with grade 2 nuclei were aneusomic. One case with grade 3 nuclei (a comedo carcinoma) was negative. We conclude that chromosome 1 aneusomy precedes invasion and is a relatively consistent occurrence in those DCIS with high nuclear grade.

Aged↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

The feasibility and cost of a large multicentre audit of process and outcome of prostatectomy.

Objective--To determine the feasibility of performing multicentre process and outcome audits of common interventions taking prostatic procedures as an example. Design--Prospective, cohort study. Setting--All National Health Service and independent hospitals in Northern, Wessex, Mersey, and South West Thames health regions. Patients--5361 men undergoing prostatectomy identified by 103 of the 107 urologists and general surgeons performing prostatectomy in the study regions. Main measures-- Rates of participation by surgeons and patients; completeness of clinical data provided by surgeons; patient response rate and completeness of patient derived data; and cost. Results--Most surgeons (103,96%) agreed to participate. Overall, the proportion of eligible patients invited to take part was high (89%), although this was only measured in South West Thames, where dedicated data collectors were employed. Few men (80, 1.5%) declined to participate. Of those surviving for three months after surgery, 82.4% (4226) completed and returned the postal questionnaire. The response rate was higher in South West Thames (86.7%) than in the other regions (80.6%-80.8%). The audit was well received: 91% of patients found the questionnaire easy to complete and only 2.3% of them disapproved. Completeness of data was high with both the hospital and patient questionnaires. Missing data occurred in less than 5% of responses to most questions. The attributable cost was 34.50 pounds per patient identified or 44 pounds for patients in whom either the treatment outcome or vital status was known three months after their prostatectomy. Conclusions--This multicentre audit of process and outcome of prostatectomy proved feasible in terms of surgeon participation, patient identification, and the quantity and quality of data collection. Whether the cost was warranted will depend on how surgeons use the audit data to modify their practice.

Aged↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗