Biomedical subjects

R A Clark

Publications and source records attributed to R A Clark.

At least 127 records · Page 7Linked to original sources

PubMed1996

Transient functional expression of alphaVbeta 3 on vascular cells during wound repair.

During early granulation tissue formation of wound repair, new capillaries invade the fibrin clot, a process that undoubtedly requires an interaction of vascular cells with the wound provisional matrix composed mainly of fibrin, fibronectin, and vitronectin. Integrin alphaVbeta3 is the vascular cell receptor for these wound-associated adhesive proteins. Therefore, we investigated the expression of this receptor on new capillaries of healing full-thickness cutaneous porcine wounds. During granulation tissue formation, alphaVbeta3 was expressed specifically on capillary sprouts invading the central fibrin clot whereas the closely related integrin alphaVbeta5 failed to localize to these cells. Cyclic peptides or antibody antagonists of alphaVbeta3 specifically inhibited granulation tissue formation in a transient manner during the period of invasive angiogenesis. Immunolocalization studies revealed that alphaVbeta3 became aggregated and lost from sprouting vessels after treatment with a peptide antagonist. In contrast, beta 1 integrins were not modulated by this treatment. Once granulation tissue filled the wound and invasive angiogenesis terminated, the alphaVbeta3 showed little or no expression in the granulation tissue microvasculature. These data demonstrate that integrin alphaVbeta3 plays a fundamental, but transient, role during invasive angiogenesis and granulation tissue formation in a healing wound.

Analysis of Variance↗

PubMed1996

Do self-management plans reduce morbidity in patients with asthma?

BACKGROUND: Self-management plans may help patients with asthma intervene when symptoms deteriorate, thus preventing asthma attacks. AIM: A study set out to test whether a self-management plan tailored to the circumstances of the individual reduces morbidity from asthma. METHOD: General practitioners who had participated in a national audit of asthma attacks were randomized into intervention and control groups. Six months after the intervention group had issued self-management plans to patients with asthma, both groups of practitioners completed morbidity questionnaires on patients. Morbidity outcomes were compared for the 6-month periods before and after the issue of the plans. RESULTS: In the 6 months before the study, the 376 patients enrolled by the intervention group experienced higher levels of morbidity than the 530 patients for whom details were recorded by the control group. In the 6 months after the issue of the plans, control group patients showed little change in levels of morbidity, but intervention group patients showed significant reductions in hospital admissions, consultations for asthma symptoms, asthma review consultations, courses of oral steroids and use of emergency nebulized bronchodilators. CONCLUSION: General practitioners appeared to operate enthusiast bias' and issued more self-management plans to patients with uncontrolled asthma. The reduction in morbidity in this group is probably a result of the use of the plans, but the verdict on whether plans reduce morbidity must be deemed 'not proven'.

Asthma↗

PubMed1996

Re-epithelialization of normal human excisional wounds is associated with a switch from alpha v beta 5 to alpha v beta 6 integrins.

During cutaneous wound repair, keratinocytes move laterally across the wound surface. For this lateral movement epidermal cells must disassemble their tenacious connections to the basement membrane and their neighbouring cells, and express surface receptors that permit translocation over the wound surface extracellular matrix. If the basement membrane is disrupted, the epidermis migrates over a provisional matrix that contains fibrinogen, fibronectin, vitronectin and tenascin. Although alpha 5 beta 1 integrin, a fibronectin receptor, is expressed by human epidermis during re-epithelialization of excisional and incisional wounds, the spatial and temporal patterns of vitronectin, tenascin, and other fibronectin receptors are less clear. Other potential receptors include alpha v beta 5 for vitronectin and alpha v beta 6 for fibronectin and tenascin. To study provisional matrix integrin expression during human wound healing, full-thickness 4-mm punch biopsies were performed on the inner surface of the upper arm in adult volunteers. At 3, 7 and 14 days after injury wound sites were excised, bisected, quick frozen in liquid nitrogen, and examined for the expression of alpha 5, beta 1, alpha v, beta 5 and beta 6. At 3 days, alpha 5 beta 1 and alpha v beta 5, but not alpha v beta 6, appeared around the basal and suprabasalar cells of the migrating epidermis. At 7 days, alpha 5 beta 1, alpha v beta 5, and alpha v beta 6 appeared around the perimeter of the basal cells of the migrating epidermis. By 14 days, when re-epithelialization was complete, all basal and suprabasalar cells overlying the wound expressed alpha 5 beta 1 and alpha v beta 6, but not alpha v beta 5. Thus, alpha v appeared to switch its heterodimeric association from beta 5 to beta 6 subunit during re-epithelialization.

Adult↗

PubMed1996

School absence--a valid morbidity marker for asthma?

OBJECTIVE: To determine how often children with asthma are absent from school compared to the 'average' child and to assess the validity of school absence as a marker of morbidity for asthma. DESIGN: Case control study. SETTING: Children registered with 12 general practices, attending 98 primary and secondary schools in the Tayside region. SUBJECTS: 773 children with asthma or related symptoms and 773 controls from school registers. MAIN OUTCOME MEASURES: Episodes of school absence and days absent per term, recorded from school registers. RESULTS: Comparing children taking asthma medication against their controls showed a significant difference for both days absent and episodes of absence. This increase in absence was approximately one school day each term. Severity of asthma was not related to increased school absence. Children receiving no asthma medication, but with asthma related symptoms, were absent no more than their age/sex matched controls. Applying a deprivation index to the cases on asthma medication, gave a significant difference in episodes of absence between Primary children classified as highly deprived and other Primary children. CONCLUSION: The increase in school absence of around one day per term for children with asthma is less than previously reported and could be caused by clinic attendance rather than ill health due to asthma. Recorded absence varied according to deprivation index but not asthma severity. The use of school absence as a marker of morbidity in childhood asthma needs to be reassessed.

Absenteeism↗

PubMed1996

Mesenchymal cell activation is the rate-limiting step of granulation tissue induction.

During wound repair a 3-day lag occurs between injury and granulation tissue development. When full-thickness, 8-mm-round, excisional wounds were made in the paravertebral skin of outbred Yorkshire pigs and harvested at various times, no granulation tissue was observed before day 4. Day 4 wounds were 3% filled with granulation tissue, day 5 wounds 48% filled, and day 7 wounds 88% filled. The prerequisites for granulation tissue induction are not known but hypothetically include fibrin matrix maturation or cell activation. To examine whether matrix maturation was necessary, wounds were allowed to heal for 5 or 7 days and then aggressively curetted, resulting in the formation of fresh fibrin clots in the newly formed wound spaces. In contrast to original wounds, no lag phase was observed; wounds curetted on day 5 were 23% filled with granulation tissue 1 day later and 99% filled 3 days later, whereas wounds curetted on day 7 were 47% filled 1 day later and completely filled within 2 days. Thus, granulation tissue formation resumed promptly and independently of fibrin clot matrix maturation. This observation suggested that mesenchymal cell activation might be the rate-limiting step in granulation tissue formation. To address this hypothesis more directly, cultured porcine or human fibroblasts, grown to 80% confluence in Dulbecco's minimal essential medium plus 10% fetal calf serum, were added to new wounds. These wounds were sealed with a freshly made exogenous fibrin clot. In some wounds, platelet releasate was added to the fibrin clot. Granulation tissue did not form in day 3 wounds, which had received either fibrin alone, fibrin and platelet releasate, or fibrin and fibroblasts. In contrast, granulation tissue was observed in wounds receiving fibrin, human fibroblasts, and platelet releasate. By day 4, wounds receiving cultured human fibroblasts, fibrin, and platelet releasate were 14% filled with granulation tissue compared with less than 4% granulation tissue in control wounds. Thus, fibroblast activation is a limiting step of granulation tissue formation, and continued cell stimulation is required for accelerated development.

Animals↗

PubMed1996

Observations on the structure, process and clinical outcomes of asthma care in general practice.

BACKGROUND: There is a need to establish whether the structure of asthma care in general practice is associated with measures of process and with primary and secondary care clinical outcomes. Debate about how to resource general practice asthma care is hampered by a lack of observational data from throughout the United Kingdom (UK). AIM: To observe whether the present system of family health services authority (FHSA) accreditation of asthma clinics, based on measures of structure, is associated with measures of process or clinical outcome. METHOD: Two hundred and twenty-five UK practitioners enrolled in a project and recorded details of how they organized asthma care. Data from 6732 patients, concerning general practitioner and nurse consultations, asthma attacks, symptom control, emergency treatments and hospital attendances covering a 12-month period, were also provided. RESULTS: FHSA approval for a chronic disease management (CDM) asthma clinic was associated with favourable patterns of structure and process, but not of clinical outcome. Practice audit and the employment of a nurse with an asthma diploma were associated with favourable patterns of structure, process and clinical outcome. Practices (n = 143) that had recently audited asthma patient care (n = 4259) had fewer patients who had attended an accident and emergency department [121 (3%): 96 (4%), odds ratio 1.38, 95% confidence interval 1.04-1.83] or a hospital outpatients department [247 (6%): 180 (7%), 1.28, 1.04-1.56], or who had respiratory symptoms on assessment [2400 (56%): 1465 (59%), 1.34, 1.18-1.52] or days absent from work or school in the past 12 months [375 (9%): 296 (12%), 1.48, 1.25-1.74] than those that had not (82 practices, 2473 patients). CONCLUSION: Findings from a large UK sample of practices are subject to participant bias and show association rather than causal links. The present FHSA asthma CDM accreditation system, based on structure, is not associated with favourable clinical outcomes. This opens the debate as to whether accreditation should be linked to recent experience of audit, which does appear to be associated with favourable clinical outcomes.

Adolescent↗

PubMed1996

Nosocomial central venous catheter-related infections in intensive care units.

To examine the recent microbiology of catheter-related infections (CRIs) in the intensive care unit (ICU) setting and to determine the association between selected factors and mortality among ICU patients diagnosed with a CRI, a retrospective review of all ICU patients determined to have a CRI between January 1992 and December 1994 was undertaken. A total of 108 patients with 111 episodes of CRIs were identified. The most common isolate was coagulase negative staphylococcus (37.9%), followed by Staphylococcus aureus (20.9%). Methicillin resistance was common in both CNS (93%), and S aureus (42%) isolates. Factors predictive for death in a multivariate analysis were as follows: male sex (relative risk (RR) 2.43, 95% confidence interval (CI) 1.0, 6.07), hypotension (RR 6.90, 95% CI 1.56, 12.2), American Society of Anesthesiologist physical status score greater than 3 (RR 4.36, 95% CI 1.56, 12.2), and underlying medical condition (RR 3.50, 95% CI 1.17, 10.5). This study demonstrated the increasing proportion of CRIs due to methicillin-resistant organisms in the ICU. Functional status and degree of illness were the strongest predictors for survival in this population.

Adult↗

PubMed1995

A domain of p47phox that interacts with human neutrophil flavocytochrome b558.

The NADPH-dependent oxidase of human neutrophils is a multicomponent system including cytosolic and membrane proteins. Activation requires translocation of cytosolic proteins p47phox, p67phox, and Rac2 to the plasma membrane and association with the membrane flavocytochrome b to assemble a functioning oxidase. We report the location of a region in p47phox that mediates its interaction with flavocytochrome b. From a random peptide phage display library, we used biopanning with purified flavocytochrome b to select phage peptides that mimicked potential p47phox binding residues. Using this approach, we identified a region of p47phox from residue 323 to 342 as a site of interaction with flavocytochrome b. Synthetic peptides 315SRKRLSQDAYRRNS328, 323AYRRNSVRFL332, and 334QRRRQARPGPQSPG347 inhibited superoxide (O2-.) production in the broken cell system with IC50 of 18, 57, and 15 microM, respectively. 323AYRRNSVRFL332 and its derivative peptides inhibited phosphorylation of p47phox. However, the functional importance of this peptide was independent of its effects on phosphorylation, since 323AYRRNAVRFL332 inhibited O2-. production, but had no effect on phosphorylation. None of the peptides blocked O2-. production when added after enzyme activation, suggesting that they inhibited the assembly, rather than the activity, of the oxidase. Furthermore these peptides inhibited membrane association of p47phox in the broken cell translocation assay and O2-. production by electropermeabilized neutrophils, thereby supporting the interpretation that this region of p47phox interacts with flavocytochrome b.

Amino Acid Sequence↗

PubMed1995

Oral combination antiemetics in patients with small cell lung cancer receiving cisplatin or cyclophosphamide plus doxorubicin.

BACKGROUND: Intravenous antiemetic combinations containing a 5-HT3 receptor antagonist (like metoclopramide, ondansetron, or granisetron) with dexamethasone have become the standard therapy for the treatment of acute chemotherapy-induced vomiting. Intravenous antiemetics, however, can be more costly and take more time to prepare and deliver, and therefore are not preferred for home, outpatient, or office use. The objective of this study was to determine the antiemetic activity and safety of the oral combination antiemetic regimen of metoclopramide, dexamethasone, and diphenhydramine in patients with small cell lung cancer receiving standard outpatient chemotherapy programs. METHODS: Fifty-two patients receiving initial cisplatin (60 mg/m2) or cyclophosphamide (600-1500 mg/m2) plus doxorubicin (30-45 mg/m2) received an oral regimen of metoclopramide (3 mg/kg x 2 then 2 mg/kg x 2 or 4 doses), dexamethasone (20 mg) and diphenhydramine (50 mg x 2 or 3 doses) (oral MDD), beginning 30 minutes before chemotherapy. RESULTS: Vomiting was prevented in 15 of 21 (76%) patients (95% confidence interval [CI], 53%-92%) receiving cisplatin and 21 of 31 (71%) individuals (95% CI, 52%-86%) given cyclophosphamide plus doxorubicin. Adverse effects were mild and transient and included sedation, loose stools, akathisia, and hiccoughs. CONCLUSIONS: The oral MDD antiemetic regimen prevented acute emesis in 73% of the patients entered and was well tolerated in this population of patients with small cell lung cancer.

Administration, Oral↗

PubMed1995

Prognostic factors for all-cause mortality among hemophiliacs infected with human immunodeficiency virus.

To identify the prognostic significance of hemophilia- and virus-related factors, the authors undertook a survival analysis among 644 human immunodeficiency virus (HIV)-infected subjects enrolled in the Multicenter Hemophilia Cohort Study between 1985 and 1993. Acquired immunodeficiency syndrome (AIDS) was the leading cause of death, followed by hemorrhage and hepatic disease. Adverse prognostic factors included older age and CD4-positive lymphocyte values below 14 percent either at entry (age-adjusted mortality rate ratio (RR) = 6.4, 95% confidence interval (CI) 3.4-12.1) or after entry (time-dependent RR = 4.2, 95% CI 2.6-6.7); indeterminate antibody responses to hepatitis C virus (RR = 3.0, 95% CI 1.8-5.0); and inhibitory antibodies to factor VIII concentrates (RR = 1.8, 95% CI 1.1-3.1). Indeterminate hepatitis C virus status was associated with mortality from hepatic disease but not with AIDS mortality. Factors that were not prognostic included duration of HIV infection, hepatitis B virus infection, and other hemophilia variables. These findings suggest that fatal liver disease among coinfected subjects with an indeterminate hepatitis C virus status is probably related to an insufficient humoral response secondary to HIV immune dysfunction and that the risk of death among HIV-infected subjects is best evaluated with age and duration of low CD4 percentage.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Predictors of HIV disease progression in women.

A retrospective cohort study was conducted to analyze variables predictive of acquired immunodeficiency syndrome (AIDS), as defined by the Centers for Disease Control (CDC) in 1987, and death in 224 women infected with the human immunodeficiency virus (HIV) who were evaluated through two HIV outpatient programs in New Orleans between January 1987 and December 1991 and followed through February 1993. Variables predictive of AIDS in a multivariate proportional hazards model were an entry CD4 cell count < 200/mm3 (adjusted RR 8.2, 95% CI 3.2, 20.9) and rapid CD4 cell count decline (adjusted RR 6.0, 95% CI 2.4, 15.5). A baseline AIDS diagnosis (by the CDC 1987 definition) was highly predictive of death (RR 36.3, 95% CI 15.7, 70.1). In multivariate analyses none of the relative risks for predictive variables remained significant if adjusted for a diagnosis of AIDS at entry. Although immunological parameters were predictive of early HIV disease progression, an AIDS diagnosis was the strongest prognostic indicator of death in a cohort of North American women.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Controlled trial of an audit facilitator in diagnosis and treatment of childhood asthma in general practice.

OBJECTIVE: To test whether an audit facilitator could alter the pattern of diagnosis and treatment of childhood asthma. DESIGN: Randomised stratified controlled trial. SETTING: 12 general practices in Tayside. SUBJECTS: 3373 children aged 1-15 inclusive who had symptoms suggestive of asthma or possible asthma drawn from a systematic review of 10,725 general practice case records. INTERVENTION: Children were targeted for a clinical review by their general practitioner or practice nurses. MAIN OUTCOME MEASURES: Asthma related consultations, prescriptions, hospital attendances, and health service costs 12 months before and after study. RESULTS: Compared with controls (n = 1563) the intervention group (n = 1585) had more practice initiated consultations for asthma (relative risk 2.18 (95% confidence interval 1.74 to 2.73)), new diagnoses of asthma (2.83 (2.26 to 3.54)), and past diagnoses reaffirmed (1.30 (1.08 to 1.58)), and they were more frequently prescribed inhaled cromoglycate (1.52 (1.02 to 2.25)). Hospital inpatient day rates fell from 152 to 122 in the intervention group and rose from 69 to 117 in the control group between the year before and the year after study. Total primary care costs rose from 30,118 pounds to 37,243 pounds in the intervention group and fell from 29,131 pounds to 27,990 pounds in the control group. Hospital care cost fell in the intervention group from 25,406 pounds to 20,727 pounds and rose in the control group from 12,699 pounds to 19,650 pounds. CONCLUSION: An audit facilitator can favourably influence the pattern of diagnosis and treatment of childhood asthma in general practice. This may have an impact on health service costs.

Adolescent↗

PubMed1995

Calreticulin functions as a molecular chaperone in the biosynthesis of myeloperoxidase.

Myeloperoxidase (MPO), a lysosomal heme protein found exclusively in neutrophils and monocytes, is necessary for efficient oxygen-dependent microbicidal activity. Acquisition of heme by the heme-free MPO precursor apopro-MPO appears to be a prerequisite for its subsequent proteolytic processing and advancement along the biosynthetic pathway to mature MPO. We present data indicating that calreticulin (CRT), a high capacity calcium-binding protein residing in the lumen of the endoplasmic reticulum of a wide variety of cells, interacts specifically with fully glycosylated apopro-MPO. Biosynthetically radiolabeled CRT (60 kDa) and apopro-MPO (90 kDa) were coprecipitated from PLB 985 cells by monospecific antiserum against CRT when the immunoprecipitations were performed either under nondenaturing conditions or following reversible crosslinking. Nonglycosylated MPO precursors synthesized in the presence of tunicamycin did not interact with CRT. The CRT-apopro-MPO interaction was restricted to an early phase of MPO biosynthesis, and CRT did not interact with the later appearing, heme-containing species of MPO, i.e. pro-MPO or the heavy subunit of mature MPO. These data show that CRT participates in the post-translational processing of MPO, perhaps by maintaining apopro-MPO in a conformation competent to accommodate insertion of the heme group. In this general way, CRT shares certain functional properties with the structurally homologous transmembrane calcium-binding endoplasmic reticulum protein calnexin. Both interact with glycosylated biosynthetic precursors of proteins selectively expressed in specialized cells.

Calcium-Binding Proteins↗

PubMed1995

Clinical and epidemiologic features of infection with Mycobacterium genavense. Swiss HIV Cohort Study.

OBJECTIVES: To characterize clinical and epidemiologic features of infections with Mycobacterium genavense. DESIGN: Case series and case-control studies. Patients with M genavense were compared with two control groups: CD4 controls were matched on the basis of CD4 counts, and Mycobacterium avium-intracellulare complex controls had disseminated infection with M avium-intracellulare complex. RESULTS: Fifty-four patients with disseminated infections caused by M genavense were found, from Europe (37), North America (15), and Australia (two). All were infected with human immunodeficiency virus. The median CD4 count was 0.016 x 10(9)/L (16/mm3) (range, 0.001 to 0.082 x 10(9)/L). Eighty-seven percent had fever and weight loss, 44% had diarrhea, 43% had splenomegaly, 39% had hepatomegaly, and 72% had anemia. In Swiss university hospitals, M genavense was responsible for 12.8% of nontuberculous disseminated mycobacterial infections in patients with human immunodeficiency virus from 1990 to 1992. The median survival was 190 days after the first isolation of M genavense. Among the patients who had been treated with at least two antimycobacterial drugs for 1 month or more, median survival was 263 days (95% confidence interval, 144 to 382 days), compared with 81 days (95% confidence interval, 73 to 89 days) for those not treated (P = .0009). Survival in patients with M genavense was similar to the survival of M avium-intracellulare complex controls. However, patients with similar CD4 counts (CD4 controls) survived longer (median, 342 days; 95% confidence interval, 269 to 415 days; P < .0003). CONCLUSIONS: Infection with M genavense may be responsible for more than 10% of disseminated nontuberculous mycobacterial infections in patients with human immunodeficiency virus infection. Its clinical presentation and response to treatment are similar to those of infection with M avium-intracellulare complex.

AIDS-Related Opportunistic Infections↗

PubMed1995

Mast cells are potent regulators of endothelial cell adhesion molecule ICAM-1 and VCAM-1 expression.

To investigate the possible role of mast cells (MC) in regulating leukocyte adhesion to vascular endothelial cells (EC), microvascular and macrovascular EC were exposed to activated MC or MC conditioned medium (MCCM). Expression of intercellular and vascular adhesion molecules (ICAM-1 and VCAM-1) on EC was monitored. Incubation of human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) with activated MC or MCCM markedly increased ICAM-1 and VCAM-1 surface expression, noted as early as 4 hr. Maximal levels were observed at 16 hr followed by a general decline over 48 hr. A dose-dependent response was noted using incremental dilutions of MCCM or by varying the number of MC in coculture with EC. At a ratio as low as 1:1,000 of MC:EC, increased ICAM-1 was observed. The ICAM-1 upregulation by MCCM was > 90% neutralized by antibody to tumor necrosis factor alpha (TNF-alpha), suggesting that MC release of this cytokine contributes significantly to inducing EC adhesiveness. VCAM-1 expression enhanced by MCCM was partly neutralized (70%) by antibody to TNF-alpha; thus other substances released by MC may contribute to VCAM-1 expression. Northern blot analysis demonstrated MCCM upregulated ICAM-1 and VCAM-1 mRNA in both HDMEC and HUVEC. To evaluate the function of MCCM-enhanced EC adhesion molecules, T cells isolated from normal human donors were used in a cell adhesion assay. T-cell binding to EC was increased significantly after exposure of EC to MCCM, and inhibited by antibodies to ICAM-1 or VCAM-1. Intradermal injection of allergen in human atopic volunteers known to develop late-phase allergic reactions led to marked expression of both ICAM-1 and VCAM-1 at 6 hr, as demonstrated by immunohistochemistry. These studies indicate that MC play a critical role in regulating the expression of EC adhesion molecules, ICAM-1 and VCAM-1, and thus augment inflammatory responses by upregulating leukocyte binding.

Cell Adhesion↗

PubMed1995

A comparison of the effects of prednisolone and mianserin on ventilatory, exercise and psychometric parameters in patients with chronic obstructive pulmonary disease.

There is controversy as to whether effects on mood play a role in mediating the response to corticosteroids in chronic obstructive pulmonary disease (COPD). If alterations in mood are important, it is conceivable that psychotropic drugs such as mianserin might produce similar responses to prednisolone in patients with COPD. Twelve patients age 62.5 y, with FEV1 29% of predicted and < 15% reversibility to salbutamol completed a randomised, double-blind crossover study. After an initial three week placebo run-in period patients received three weeks of prednisolone 40 mg daily or mianserin 60-90 mg daily with an intervening three week placebo washout period. Full respiratory function tests, bicycle ergometry and 6 minute walks were performed before and after the run-in and at the end of each period. Psychological and functional assessments were also made at each visit. Prednisolone significantly increased FVC, maximum ventilation (VEmax) and maximum heart rate (HRmax) compared with placebo, with mean for the difference of 0.25 l, 2.56 l.min-1 and 12 beats.min-1 respectively. FVC, maximum oxygen uptake (VO2max) and HRmax were also significantly increased with prednisolone compared with mianserin. Anxiety scores were significantly lower with prednisolone compared with placebo. In contrast, mianserin had no significant effects on lung function, exercise or psychological parameters compared with placebo. The improvements in ventilation, exercise and anxiety scores following treatment with prednisolone were not reproduced by mianserin, suggesting that the effects of prednisolone in COPD are unlikely to be due to alterations in mood.

Aged↗

PubMed1995

Mechanisms of multifocal breast cancer: an immunocytochemical study.

The issue of whether multifocal breast cancer represents intramammary spread from a single primary tumor or multiple synchronous tumors remains unresolved. We have used a series of immunocytochemical markers, B72.3, DF3, c-erbB-2, SP-1, CEA, and p53, to attempt to answer this question. Of 24 cases with separate discrete synchronous tumors in the same breast, 10 were histologically and immunocytochemically identical, five were histologically similar but immunocytochemically different, two were histologically different but immunocytochemically identical, and in seven cases the tumors were different both histologically and immunocytochemically. In seven of the 24 cases lymph nodes containing metastatic tumor were also available; in each instance, the immunoreactivity of the metastasis was similar to one or other of the tumors in the breast. This study indicates that multifocal breast cancer may result from either intramammary spread from a single primary tumor or multiple synchronous primary tumors.

Breast Neoplasms↗

PubMed1995

Evaluation of an antibiotic prescribing protocol for treatment of acute exacerbations of chronic obstructive airways disease in a hospital respiratory unit.

A prescribing protocol for infective exacerbations of chronic obstructive airways disease (COAD), specifying the use of oral amoxycillin 500 mg tid (or erythromycin 500 mg qid if allergic) as first line therapy, and oral ciprofloxacin 500 mg bd as second line treatment, was introduced in 1991. Every third sequential admission was screened for the year preceding (1990) and the year after (1991) the protocol was implemented. Only those patients with a discharge diagnosis of infective exacerbation of COAD, but without pneumonia, were included in the analysis. The two groups (1990 and 1991) were matched in terms of age, sex and pre-treatment given by their General Practitioner (GP), but differed with respect to severity score, with 1991 being more severe. The outcome measures showed that duration of hospital stay was comparable as was duration of treatment. Response to first line therapy was 68% and 67% for 1990 and 1991, respectively. Of those who had received antibiotics from their GP, 67% responded to first line therapy, while of those who had not received antibiotics from their GP 75% responded. Duration of therapy was shorter in first line responders (mean and 95% CI: 7.3 (6.3-8.3) days vs 12.7 (10.1-15.3) days). The mean cost per day antibiotic treatment was reduced by 54.6% (95% CI 52.3-56.9%) from 3.77 pounds to 1.71 pounds. In conclusion, the introduction of antibiotic prescribing guidelines for treatment of infective exacerbations of COAD showed no detrimental effect on outcome measures, but was associated with a significant reduction in the cost of antibiotic therapy.

Anti-Bacterial Agents↗