Showing papers by "St Bartholomew's Hospital published in 1994"

Elevation of Systemic Oxygen Delivery in the Treatment of Critically Ill Patients

Abstract: Background Elevation of systemic oxygen delivery and consumption has been associated with an improved outcome in critically ill patients. We conducted a randomized trial to determine whether boosting oxygen delivery by infusing the inotropic agent dobutamine would improve the outcome in a diverse group of such patients. Methods On the basis of previously published recommendations, we established the following goals: a cardiac index above 4.5 liters per minute per square meter of body-surface area, oxygen delivery above 600 ml per minute per square meter, and oxygen consumption above 170 ml per minute per square meter. If these goals were not achieved with volume expansion alone, patients were randomly assigned to a treatment or control group. The treatment group received intravenous dobutamine (5 to 200 μg per kilogram of body weight per minute) until all three goals had been achieved. Dobutamine was administered to the control group only if the cardiac index was below 2.8 liters per minute per square met...

Inducible isoforms of cyclooxygenase and nitric-oxide synthase in inflammation

Abstract: Cyclooxygenase (COX) converts arachidonic acid to prostaglandin H2, which is further metabolized to prostanoids. Two isoforms of COX exist: a constitutive (COX-1) and an inducible (COX-2) enzyme. Nitric oxide is derived from L-arginine by isoforms of nitric-oxide synthase (NOS; EC 1.14.13.39): constitutive (cNOS; calcium-dependent) and inducible (iNOS; calcium-independent). Here we have investigated inducible isoforms of COX and NOS in the acute, chronic, and resolving stages of a murine air pouch model of granulomatous inflammation. COX and NOS activities were measured in skin samples in the acute phase, up to 24 h. Activities in granulomatous tissue were measured at 3, 5, 7, 14, and 21 days for the chronic and resolving stages of inflammation. COX-1 and COX-2 proteins were assessed by Western blot. COX activity in the skin increased over the first 24 h and continued to rise up to day 14. COX-2 protein rose progressively, also peaking at day 14. COX-1 protein remained unaltered throughout. The iNOS activity increased over the first 24 h in the skin, with a further major increase in the granulomatous tissue between days 3 and 7, followed by a decrease at day 14 and a further increase at day 21. The rise in COX and NOS activities in the skin during the acute phase reinforces the proinflammatory role for prostanoids and suggests one also for nitric oxide. However, in the chronic and resolving stages, a dissociation of COX and NOS activity occurred. Thus, there may be differential regulation of these enzymes, perhaps due to the changing pattern of cytokines during the inflammatory response.

Third degree obstetric anal sphincter tears: risk factors and outcome of primary repair

Abstract: Objectives To determine (i) risk factors in the development of third degree obstetric tears and (ii) the success of primary sphincter repair. Design (i) Retrospective analysis of obstetric variables in 50 women who had sustained a third degree tear, compared with the remaining 8553 vaginal deliveries during the same period. (ii) Women who had sustained a third degree tear and had primary sphincter repair and control subjects were interviewed and investigated with anal endosonography, anal manometry, and pudendal nerve terminal motor latency measurements Setting: Antenatal clinic in teaching hospital in inner London. Subjects (i) All women (n=8603) who delivered vaginally over a 31 month period. (ii) 34 women who sustained a third degree tear and 88 matched controls. Main outcome measures : Obstetric risk factors, defaecatory symptoms, sonographic sphincter defects, and pudendal nerve damage. Results - (i) Factors significantly associated with development of a third degree tear were: forceps delivery (50% v 7% in controls; P=0.00001), primiparous delivery (85% v 43%; P=0.00001), birth weight >4 kg (P=0.00002), and occipitoposterior position at delivery (P=0.003). No third degree tear occurred during 351 vacuum extractions. Eleven of 25 (44%) women who were delivered without instruments and had a third degree tear did so despite a posterolateral episiotomy. (ii) Anal incontinence or faecal urgency was present in 16 women with tears and 11 controls (47% v 13%;20P=0.00001). Sonographic sphincter defects were identified in 29 with tears and 29 controls (85% v 33%; P=0.00001). Every symptomatic patient had persistent combined internal and external sphincter defects, and these were associated with significantly lower anal pressures. Pudendal nerve terminal motor latency measurements were not significantly different. Conclusions Vacuum, extraction is associated with fewer third degree tears than forceps delivery. An episiotomy does not always prevent a third degree tear. Primary repair is inadequate in most women who sustain third degree tears, most having residual sphincter defects and about half experiencing anal incontinence, which is caused by persistent mechanical sphincter disruption rather than pudendal nerve damage. Attention should be directed towards preventive obstetric practice and surgical techniques of repair.

Screening, detection and management of depression in elderly primary care attenders. I: The acceptability and performance of the 15 item Geriatric Depression Scale (GDS15) and the development of short versions.

Abstract: One-hundred and ninety-eight elderly subjects attending their general practitioners (GPs) were asked to complete the 15 item Geriatric Depression Scale (GDS15). Analysable results were obtained from 194 (98%). Of these, 67 (34%) scored above the GDS15 cut-off (4/5) for significant depressive symptomatology. 87.6% found the questionnaire to be acceptable and only 3.6% found it very difficult or very stressful. The GDS15 had a high level of internal consistency (Cronbach's alpha = 0.80). All the individual items of the GDS15 associated significantly (P < 0.01) with total score and 'caseness'. A single question "do you feel that your life is empty?" identified 84% of 'cases'. In an attempt to devise short scales to screen elderly primary care patients for depression, the data were subjected to logistic regression analysis. Ten (GDS10), four (GDS4) and on (GDS1) item versions were generated. Agreement between these short scales and the GDS15 in the original sample was 95, 91 and 79% respectively. Cronbach's alpha was 0.72 for the GDS10 and 0.55 for the GDS4. The short scales were then validated in an independent sample of 120 patients in whom both GDS data and the results of a detailed psychiatric interview (the Geriatric Mental Status Schedule, GMS) were available. The sensitivity and specificity of the GDS10 against GMS caseness were 87 and 77% (cut-off 3/4); those of the GDS4 were 89 and 65% (cut-off 0/1) and 61 and 81% (cut-off 1/2). Sensitivity and specificity for the GDS1 were 59 and 75%. It is concluded that these short scales may be useful in helping GPs and practice staff to identify elderly patients with significant depressive symptoms.

Linkage of the angiotensinogen gene to essential hypertension

Abstract: Background The renin-angiotensin system is a powerful pressor system with a major influence on salt and water homeostasis. Angiotensinogen (also called renin substrate) is a key component of this system; it is cleaved by renin to yield angiotensin I, which is then cleaved by angiotensin-converting enzyme to yield angiotensin II. The observation that plasma angiotensinogen levels correlate with blood pressure and track through families suggests that angiotensinogen may have a role in essential hypertension. We therefore investigated whether there is linkage between the angiotensinogen gene on chromosome 1q42-43 and essential hypertension. Methods Samples of DNA from 63 white European families in which two or more members had essential hypertension were tested for linkage of the angiotensinogen gene to this disorder. Affected cousins, nephews, nieces, and half-siblings were included when possible. To test for linkage, we used as a marker a dinucleotide-repeat sequence flanking this gene, and we employed the...

Brief, high-temperature heat denaturation (pressure cooking): A simple and effective method of antigen retrieval for routinely processed tissues

Abstract: The merits of microwave-based antigen retrieval methods for diagnostic immunohistochemistry have recently been emphasized. As such technology has drawbacks for busy routine laboratories, we have investigated an alternative method of heat-mediated antigen retrieval (HMAR), using a domestic pressure cooker as a source of superheating. A simple protocol, with superheating in 0.01 M citrate buffer (pH 6.0) for 2 min, gave results comparable to those obtainable in a microwave oven. The range of antigens retrieved and the antigens for which heating was ineffective matched the published microwave experience. The advantages included the speed of treatment, the reproducibility of results with large batches of slides, the ability to use metal slide racks, and economy of time and equipment costs.

Cigarette smoking by socioeconomic group, sex, and age: effects of price, income, and health publicity

Abstract: Objective: To assess effects of price, income, and health publicity on cigarette smoking by age, sex, and socioeconomic group. Design: Econometric multiple regression analysis of data on cigarette smoking from the British general household survey. Subjects: Random sample of adult population in Britain interviewed for biennial general household surveys 1972-90. Main outcome measures - Changes in cigarette consumption and prevalence of smoking. Results: Price elasticities of demand for cigarettes (percentage change in cigarette consumption for a 1% change in price) were significant at -0.5 (95% confidence interval -0.8 to -0.1) for men and -0.6 (-0.9 to -0.3) for women, were highest in socioeconomic group V (-1.0 for men and -0.9 for women), and lowest (not significantly different from zero) in socioeconomic groups I and II. The gradient in price elasticities by socioeconomic group was significant for men (F=5.6, P=0.02) and for women (F=6.1, P=0.02). Price was a significant factor in cigarette consumption by age for women in every age group and for men aged 25-34. Cigarette consumption by young men aged 16-34 increased with income. There was a significant decrease in smoking over time by women in socioeconomic groups I and II and by men in all age and social groups except socioeconomic group V attributable to health publicity. Price significantly affected smoking prevalence in socioeconomic group V (-0.6 for men and -0.5 for women) and for all women (-0.2). Conclusions: Men and women in lower socioeconomic groups are more responsive than are those in higher socioeconomic groups to changes in the price of cigarettes and less to health publicity. Women of all ages, including teenagers, appear to have been less responsive to health publicity than have men but more responsive to price. Response to health publicity decreased linearly with age. Real price increases in cigarettes could narrow differences between socioeconomic groups in smoking and the related inequalities in health, but specific measures would be necessary to ameliorate effects on the most deprived families that may include members who continue to smoke. The use of a policy to steadily increase cigarette tax is likely to help achieve the government9s targets for smoking and smoking related diseases.

Beneficial effects and improved survival in rodent models of septic shock with S-methylisothiourea sulfate, a potent and selective inhibitor of inducible nitric oxide synthase

Abstract: Enhanced formation of nitric oxide (NO) by both the constitutive and the inducible isoforms of NO synthase (NOS) has been implicated in the pathophysiology of a variety of diseases, including circulatory shock. Non-isoform-selective inhibition of NO formation, however, may lead to side effects by inhibiting the constitutive isoform of NOS and, thus, the various physiological actions of NO. S-Methylisothiourea sulfate (SMT) is at least 10- to 30-fold more potent as an inhibitor of inducible NOS (iNOS) in immunostimulated cultured macrophages (EC50, 6 microM) and vascular smooth muscle cells (EC50, 2 microM) than NG-methyl-L-arginine (MeArg) or any other NOS inhibitor yet known. The effect of SMT on iNOS activity can be reversed by excess L-arginine in a concentration-dependent manner. SMT (up to 1 mM) does not inhibit the activity of xanthine oxidase, diaphorase, lactate dehydrogenase, monoamine oxidase, catalase, cytochrome P450, or superoxide dismutase. SMT is equipotent with MeArg in inhibiting the endothelial, constitutive isoform of NOS in vitro and causes increases in blood pressure similar to those produced by MeArg in normal rats. SMT, however, dose-dependently reverses (0.01-3 mg/kg) the hypotension and the vascular hyporeactivity to vasoconstrictor agents caused by endotoxin [bacterial lipopolysaccharide (LPS), 10 mg/kg, i.v.] in anesthetized rats. Moreover, therapeutic administration of SMT (5 mg/kg, i.p., given 2 hr after LPS, 10 mg/kg, i.p.) attenuates the rises in plasma alanine and aspartate aminotransferases, bilirubin, and creatinine and also prevents hypocalcaemia when measured 6 hr after administration of LPS. SMT (1 mg/kg, i.p.) improves 24-hr survival of mice treated with a high dose of LPS (60 mg/kg, i.p.). Thus, SMT is a potent and selective inhibitor of iNOS and exerts beneficial effects in rodent models of septic shock. SMT, therefore, may have considerable value in the therapy of circulatory shock of various etiologies and other pathophysiological conditions associated with induction of iNOS.

Combined Analysis of Autoantibodies Improves Prediction of IDDM in Islet Cell Antibody-Positive Relatives

Abstract: Prediction of insulin-dependent diabetes mellitus (IDDM) is still largely based on islet cell antibodies (ICAs), but it may be improved by combined analysis with other humoral markers. We examined autoantibodies to insulin (IAAs), glutamic acid decarboxylase (GAD), and M r 37,000 and M r 40,000 fragments of islet antigens (37 and 40 kDa) together with ICA subtypes in 101 family members with ICAs ≥10 Juvenile Diabetes Foundation units (JDF U) followed for up to 14 years, of whom 18 have developed IDDM. Life-table analysis showed a 43% risk of IDDM within 10 years for those with ICAs ≥10 JDF U, rising to 53% for those with ICAs ≥20 JDF U. The risk for ICAs ≥10 JDF U was 62% in the family members in the youngest age quartile ( 40.7 years of age ( P = 0.03). ICAs ≥10 JDF U combined with IAAs gave a risk of 84% ( P = 0.03 compared with IAA − ), and ICAs ≥10 JDF U combined with GAD antibodies gave a risk of 61% ( P = 0.018). The risk for ICAs >10 JDF U with antibodies to 37-kDa antigen was 76% ( P 3 autoantibodies (14 cases detected) ( P + relatives came from the 27% with multiple autoantibodies and estimate that 88% of individuals within this category will need insulin treatment within 10 years. We propose a simple predictive strategy based on these observations.

Pursuit and practice of complementary therapies by cancer patients receiving conventional treatment

Abstract: Objectives: To determine what proportion of oncology patients receiving conventional medical treatment also use complementary treatments; to assess which complementary treatments are the most popular and to assess patients9 motivation for using them; to evaluate associated advantages and risks. Design: Postal screening questionnaire followed by semistructured interview. Setting: Two hospitals in inner London. Subjects—600 unselected oncology patients aged 18 or over who had known their diagnosis of cancer for at least three months. Main outcome measures: Prevalence and demography of use of complementary therapies; patients9 motivation and expectations of complementary therapies; areas of satisfaction and dissatisfaction associated with conventional and complementary therapies. Results: 415 (69%) patients returned the questionnaire. 16% had used complementary therapies. The most popular were healing, relaxation, visualisation, diets, homoeopathy, vitamins, herbalism, and the Bristol approach. Patients using complementary therapies tended to be younger, of higher social class, and female. Three quarters used two or more therapies. Therapies were mostly used for anticipated antitumour effect. Ill effects of diets and herb treatments were described. Satisfaction with both conventional and complementary therapies was high, although diets often caused difficulties. Patients using complementary therapies were less satisfied with conventional treatments, largely because of side effects and lack of hope of cure. Benefits of complementary therapies were mainly psychological. Conclusions: A sizeable percentage of patients receiving conventional treatments for cancer also use complementary therapies. Patient satisfaction with complementary therapies, other than dietary therapies, was high even without the hoped for anticancer effect. Patients reported psychological benefits such as hope and optimism.

Glucocorticoids and the genesis of depressive illness. A psychobiological model.

Abstract: Abnormalities in the hypothalamic-pituitary-adrenal axis (HPA) have been the most consistently demonstrated biological markers in depressive illness. Numerous other neuroendocrine disturbances have also been described, including blunted clonidine-induced growth hormone release and blunted fenfluramine-induced prolactin release. These disturbances are generally interpreted in terms of monoaminergic receptor dysfunction. The theory presented here suggests that chronic stress which activates the HPA will in certain susceptible people produce changes in central monoamines. The high level of glucocorticoid receptors on such central neurons is postulated as mediating the alterations. Thus monoamine abnormalities, rather than being a core aetiological feature of depression, are seen as secondary to HPA overdrive.

Systematic underestimation of association between serum cholesterol concentration and ischaemic heart disease in observational studies: data from the BUPA study.

Abstract: Objective : To estimate the size of the association between serum concentration of low density lipoprotein cholesterol and mortality from ischaemic heart disease. Design : Prospective study of total serum cholesterol concentration and mortality from ischaemic heart disease in 21 515 men (538 deaths) and study of total cholesterol concentration measured on two occasions an average of three years apart in 5696 men in whom low density lipoprotein cholesterol concentration was also measured on the second occasion. Subjects : Men who attended the medical centre of the British United Provident Association (BUPA) in London between 1975 and 1982. Main outcome measure : The difference in mortality from ischaemic heart disease for a 0.6 mmol/1 difference in concentration of low density lipoprotein cholesterol after adjustment for, firstly, regression dilution bias, which arises from the random fluctuation of serum cholesterol concentration in people over time, and, secondly, the surrogate dilution effect, which arises because differences in total cholesterol concentration between people reflect smaller differences in low density lipoprotein cholesterol concentration. Results : The observed difference in mortality from ischaemic heart disease associated with a difference of 0.6 mmol/1 in total serum cholesterol concentration was 17% but increased to 24% after correction for the regression dilution bias and to 27% (95% confidence interval 21% to 33%) after adjustment for both sources of underestimation, which provides an estimate of the difference in mortality for a true difference of 0.6 mmol/1 in low density lipoprotein cholesterol concentration. The association was greater at younger ages. The estimated decrease in mortality from all causes was 6% before and 10% (1% to 17%) after adjustment for the two sources of underestimation. There was no excess mortality from any cause associated with low cholesterol concentration. Conclusions : The association between serum cholesterol concentration and ischaemic heart disease is materially stronger than directly inferred from prospective studies. This has important implications for the health benefit of achieving low cholesterol concentrations.

Induction of cyclo-oxygenase-2 by cytokines in human pulmonary epithelial cells: regulation by dexamethasone

Abstract: 1. Cyclo-oxygenase metabolizes arachidonic acid to prostaglandin H2 (PGH2) and exists in at least two isoforms. Cyclo-oxygenase-1 (COX-1) is expressed constitutively whereas COX-2 is induced by lipopolysaccharide (LPS) and some cytokines in vitro and at the site of inflammation in vivo. Epithelial cells may be an important source of prostaglandins in the airways and we have, therefore, investigated the expression of COX-1 or COX-2 isoforms in primary cultures of human airway epithelial cells or in a human pulmonary epithelial cell line (A549). 2. COX-1 or COX-2 protein was measured by western blot analysis using specific antibodies to COX-2 and selective antibodies to COX-1. The activity of COX was assessed by the conversion of either endogenous or exogenous arachidonic acid to four metabolites, PGE2, PGF2 alpha, thromboxane B2 or 6-oxo PGF1 alpha measured by radioimmunoassay. Thus, COX-1 or COX-2 activity was measured under two conditions; initially the accumulation of the COX metabolites formed from endogenous arachidonic acid was measured after 24 h. In other experiments designed to measure COX activity directly, cells were treated with cytokines for 12h before fresh culture medium was added containing exogenous arachidonic acid (30 microM) for 15 min after which COX metabolites were measured. 3. Untreated primary cells or A549 cells contained low amounts of COX-1 or COX-2 protein. Bacterial LPS (1 micro g ml-1 for 24 h) induced COX-2 protein in the primary cells, a process which was enhanced by interferon-gamma, with no further increase in the presence of a mixture of cytokines (interleukin-1 beta, tumour necrosis factor-alpha and interferon-gamma, 10 ng ml-1 for all). In contrast, A549 cells contained only low levels of COX-2 protein after exposure to LPS or LPS plus interferon-y, but contained large amounts of COX-2 protein after exposure to the mixture of cytokines.4. Untreated human pulmonary primary cells or A549 cells released low levels of all COX metabolites measured over a 24 h incubation period. This release was enhanced by treatment of either cell type with the mixture of cytokines (interleukin-1 beta , tumour necrosis factors- and interferon-gamma, 10 ng ml-1 for all).PGE2 was the principal COX metabolite released by cytokine-activated epithelial cells. The release of PGE2 induced by cytokines occurred after a lag period of more than 6 h.5. The glucocorticosteroid, dexamethasone (1 micro M; 30 min prior to cytokines) completely suppressed the cytokine-induced expression of COX-2 protein and activity in both primary cells and A549 cells.6. In experiments where COX-2 activity was supported by endogenous stores of arachidonic acid,treatment of A549 cells with interleukin-l beta but not tumour necrosis factor a or interferon-gamma alone caused a similar release of PGE 2 to that seen when the cytokines were given in combination. However, both interleukin-l beta and necrosis factor- alone produced similar increases in COX-2 activity (measured in the presence of exogenous arachidonic acid) as seen when the mixture of interleukin-l beta, tumour necrosis factor- alpha and interferon-gamma were used to stimulate the cells.7. These findings show that COX-2 expression correlates with the exaggerated release of prostaglandins from cytokine-activated human pulmonary epithelial cells and that the induction of the enzyme is suppressed by a glucocorticosteroid. These findings may be relevant to inflammatory diseases of the lung, such as asthma.

Placebo-controlled immunopathologic study of four months of inhaled corticosteroids in asthma.

Abstract: The effect of prolonged inhaled corticosteroid treatment on bronchial immunopathology was assessed in 25 nonsmoking mildly asthmatic subjects previously receiving intermittent inhaled beta 2-agonist alone. Inhaled beclomethasone dipropionate (BDP), 500 micrograms twice per day or placebo was administered for 4 mo in a double-blind parallel group study. Histamine bronchial provocation, fiberoptic bronchoscopic biopsy, and bronchoalveolar lavage (BAL) were performed before and after treatment. There was no difference in bronchial responsiveness or lung function between groups. In patients treated with BDP compared with placebo, there was a significant reduction in toluidine blue-staining mast cells (p = 0.028) and total (p = 0.005) and activated eosinophils (p = 0.05) in biopsies but no difference in eosinophils or eosinophil cationic protein in BAL. Granulocyte-macrophage colony-stimulating factor expression was significantly reduced in the bronchial epithelium, and the thickness of Type III collagen deposition in the bronchial lamina reticularis reduced from 29.7 +/- 4.4 to 19.8 +/- 3.4 microns (mean +/- 95% confidence interval) (p = 0.04). No change in helper or activated helper T cells occurred. Prolonged BDP treatment reduces inflammatory infiltration, proinflammatory cytokine expression, and subepithelial collagen deposition, a recognized abnormality in asthma.

Factor VIII, ABO blood group and the incidence of ischaemic heart disease

Abstract: Relations of factor VIII activity, FVIIIC, and von Willebrand factor antigen (vWFAg), with ischaemic heart disease (IHD) were examined in 1393 men aged between 40 and 64 years at entry to the Northwick Park Heart Study (NPHS) who experienced 178 first major episodes of IHD during an average follow-up period of 16.1 years. After allowing for the large factor VIII differences between the main ABO blood groups, FVIIIC was probably associated with IHD incidence, possibly more strongly with fatal than non-fatal episodes. Thus, an increase of 1 standard deviation in FVIIIC raised the risk of fatal IHD by about 28%. vWFAg was also significantly associated with fatal events. The observed relation of FVIIIC with IHD incidence probably underestimates the true strength of the association because of the considerable within-person and laboratory variability in factor VIII measurements. FVIIIC and vWFAg were strongly correlated (r = 0.57) and in statistical terms there may be little to choose between them in long-term studies of IHD. Taking account of evidence that haemophiliacs seem to experience less IHD than expected, high factor VIII levels may contribute to the incidence of IHD by increasing thrombogenic potential. The incidence of IHD was significantly higher in those of blood group AB than in those of groups O, A or B, particularly for fatal events. There was no evidence that the FVIIIC and vWFAg associations with IHD are determined by ABO group. The factor VIII and ABO blood group effects therefore appeared to be independent. Group AB may be a genetic marker of characteristics influencing other indices of IHD risk such as short stature, NPHS men (though not women) of group AB being about 2 cm shorter than those of other groups.

Symptom relief and quality of life after stenting for malignant bile duct obstruction.

Abstract: Palliative treatment is appropriate for most patients with cancer of the head of pancreas. Insertion of a biliary stent relieves jaundice and pruritus but it is not known if stenting affects other symptoms or changes the quality of life. Nineteen patients have completed a standard questionnaire to assess symptom relief and quality of life after stent insertion. After stenting there was complete relief of jaundice and pruritus. Furthermore, there was also considerable improvement in anorexia and indigestion. All patients had anorexia before stent insertion, this was moderate/severe in 13 (68.4%). Anorexia was significantly better (p < 0.01) a week after stenting and this benefit was maintained at 12 weeks (p < 0.01). Sixteen (84.2%) patients complained of indigestion before stenting, moderate/severe in 11 (57.9%). This was significantly better (p < 0.01) a week after stenting with complete relief in six at eight weeks (p < 0.01). Fifteen (78.9%) felt that their mood was good/very good before stent insertion and this was unchanged even at the 12 week assessment. A similar result was obtained for physical health and level of activity. In conclusion stent insertion not only relieves jaundice and pruritus in these patients but also improves other symptoms and quality of life. The considerable improvement in appetite after stenting was of particular benefit.

Myeloablative therapy with autologous bone marrow transplantation as consolidation therapy for recurrent follicular lymphoma.

Abstract: PURPOSETo assess myeloablative therapy with autologous bone marrow transplantation (ABMT) in younger patients with follicular lymphoma in the hope of prolonging remission duration and survival.PATIENTS AND METHODSSince June 1985, 64 patients with follicular lymphoma have received cyclophosphamide (CY) 60 mg/kg x 2 and total-body irradiation (TBI) 2 Gy x 6 supported by ABMT as consolidation of second or subsequent remission. The marrow mononuclear cell (MNC) fraction was treated in vitro with three cycles of the monoclonal antibody (MAb) anti-CD20 and baby rabbit complement before cryopreservation. At the time of treatment, 34 patients were in complete remission (CR), and 30 had residual disease present.RESULTSThe median time to engraftment was 28 days (range, 15 to 46) for both a neutrophil count greater than 0.5 x 10(9)/L and a platelet count greater than 20 x 10(9)/L. Engraftment did not occur in one patient who died at 12 weeks, and three patients (excluded from the range) have had delayed recovery (> ...

Infections and diabetes: mechanisms and prospects for prevention.

Abstract: Infections remain a serious hazard for the diabetic patient. Good metabolic control is a major factor in limiting the development and spread of infections and, most importantly, the development of diabetic complications which predispose to infections. In some patients recurrent infections can pose a problem, particularly if there is evidence of secondary immunodeficiency. In these patients adjuvant therapies, including Biological Response Modifiers (BRMS) should be considered. Several factors could predispose diabetic patients to infections. These factors include: genetic susceptibility to infection; altered cellular and humoral immune defence mechanisms; local factors including poor blood supply and nerve damage, and alterations in metabolism associated with diabetes. In the context of a diabetic patient all or some of these factors may operate. The purpose of this review is to assess the relative contribution of these potential mechanisms in leading to infection in patients with diabetes.

Effect of hormone replacement therapy on bone mass in rheumatoid arthritis patients treated with and without steroids.

Abstract: Objective. To assess the effect of hormone replacement therapy (HRT) on bone mass in rheumatoid arthritis (RA) patients treated with and those not treated with steroids. Methods. Two hundred postmenopausal women with RA (ages 45-65 years) were randomly allocated to receive transdermal estradiol (hormone replacement therapy; HRT) (50 μg daily) or calcium supplementation (400 mg daily) for 2 years. Forty-two of the patients (21%) were taking corticosteroids. Bone mineral density of the lumbar spine (BMDLS) and of the proximal femur (BMDF) was measured at study entry and at 12 months and 24 months. Results. In the HRT group overall, mean BMDLS had changed by +2.22% (95% confidence interval [95% CI] +0.72, +3.72) and mean BMDF by −0.41 % (95% CI −1.89, +1.07) after 24 months. In the calcium group, mean BMDLS changed by −1.19% (95% CI −2.29, −0.09) and mean BMDF by −0.56% (95% CI −2.60, +1.48). Differences between treatment groups were significant for the spine only (P < 0.001). In the 21 HRT-treated patients taking steroids, BMDLS increased by 3.75% (95% CI +0.72, +6.78) and BMDF by 1.62% (95% CI −1.27, +4.51). Conclusion. This study shows that HRT increases spinal BMD and maintains femoral BMD in postmenopausal RA. HRT is also an effective agent in preserving bone mass in patients taking low-dose corticosteroids.

How effective is nicotine replacement therapy in helping people to stop smoking

Abstract: Objective : To assess the efficacy of nicotine replacement therapy in helping people to stop smoking. Design : Analysis of the results of 28 randomised trials of nicotine 2 mg chewing gum, six trials of nicotine 4 mg chewing gum, and six trials of nicotine transdermal patch. Subjects and setting : Subjects were self referred (responding to advertisements or attending anti-smoking clinics) in 20 trials and invited (general practice or hospital patients) in 20. Therapists in self referred trials were generally experienced in helping people stop smoking but not in invited trials. Main outcome measure - Efficacy was defined as difference in percentages of treated and control subjects who had stopped smoking at one year. Results - Efficacy was highly significant (P<0.001) for both gum and patch. Nicotine 2 mg chewing gum had an overall efficacy of 6% (95% confidence interval 4% to 8%), greater in self referred subjects than in invited subjects (11% v 3%). Efficacy depended on the extent of dependence on nicotine as assessed by a simple questionnaire; it was 16% (7% to 25%) in “high dependence” smokers, but in “low dependence” smokers there was no significant effect. The 4 mg gum was effective in about one third of “high dependence” smokers. The efficacy of the nicotine patch (9% (6% to 13%) overall) was less strongly related to nicotine dependence, perhaps because the patch cannot deliver a bolus of nicotine to satisfy craving. Conclusions : Both gum and patch are effective aids to help nicotine dependent smokers who seek help in stopping. Among the most highly nicotine dependent smokers (those craving a cigarette on waking) the 4 mg gum is the most effective form of replacement therapy; it could enable one third to stop. In less highly dependent smokers the different preparations are comparable in their efficacy but the patch offers greater convenience and minimal need for instruction in its use. Overall, nicotine replacement therapy could enable about 15% of smokers who seek help in stopping smoking to give up the habit.