Risk factors for infection in Malaysian patients with systemic lupus erythematosus

To determine the incidence, types and risk factors for infection in systemic lupus erythematosus (SLE) patients in Kuala Lumpur, Malaysia, we retrospectively reviewed the medical records of 102 patients with definite SLE attending a specialist clinic. Details of major infections (pneumonia or severe infection requiring intravenous therapy) and minor infections, and their time of onset in relation to immunosuppressive therapy and disease flares were recorded. There were 77 major and 163 minor infections during 564 patient-years of follow-up. In the month following a course of pulse methylprednisolone, the incidence of major infection was 20 times higher and the incidence of minor infection was 10 times higher than at other periods (p<0.0001). In the month after disease flare, the incidence of major infection was 10 times higher and the incidence of minor infection six times higher than at other times (p<0.0001). After allowing for methylprednisolone therapy and disease flares, there was no increase in the rate of infections during treatment with azathioprine, oral or intravenous cyclophosphamide. There was no effect of renal involvement on infection rate.      

Detection of fetal red cells in fetomaternal hemorrhage using a fetal hemoglobin monoclonal antibody by flow cytometry

BACKGROUND: The laboratory determination of the level of fetal cells in maternal circulation remains an important support in the obstetrical management of women with suspected uterine trauma and in the proper dose administration of anti-D for prevention of Rh hemolytic disease of the newborn. Limitations in the sensitivity and precision of the widely used manual Kleihauer-Betke test have prompted an increased utilization of flow cytometric methods for fetal cell detection in maternal blood samples. STUDY DESIGN AND METHODS: Murine monoclonal antibodies directed against fetal hemoglobin (HbF) were developed, conjugated to fluorescein isothiocyanate, and used in a multiparametric flow cytometric assay developed for the quantitation of fetal red cells. A rapid intracellular staining method using brief glutaraldehyde fixation and Triton X-100 permeabilization prior to monoclonal antibody incubation was developed, along with optimization of the flow cytometric analysis protocol for the analysis of 50,000 cells. The performance of the assay was assessed for linearity and precision and correlated with the Kleihauer-Betke acid elution method. RESULTS: The anti-HbF flow cytometric method showed good correlation with the Kleihauer-Betke method (r2 = 0.86) and superior precision with a CV < 15 percent for blood samples with > 0.1 percent fetal cells. Analysis of 150 blood samples from nonpregnant adults, including individuals with elevated HbF due to hemoglobinopathies and hereditary persistence of HbF, gave a mean value of 0.02 percent fetal cells, and all results were less than 0.1 percent. CONCLUSIONS: The anti-HbF flow cytometric method for detection of fetal cells offers a simple, reliable, and more precise alternative to the Kleihauer-Betke manual technique for the assessment of fetomaternal hemorrhage. The method has additional potential applications for the study of HbF levels or frequency of adult red cells with low levels of HbF (F cells) in individuals with hemoglobinopathies.     

The lowest effective dose of botulinum A toxin in adult patients with upper limb spasticity

Objective: To define the lowest effective dose of botulinum toxin type A (Dysport®) and safety in the treatment of adult patients with upper limb spasticity.

Design: This was a prospective, randomized, double-blind, dose-ranging study. Patients received either a placebo or one of three doses of Dysport® (350, 500, 1000?U) into five muscles of affected arm by anatomical and electromyography guidance. Efficacy was assessed periodically throughout the 6-month study period by the Modified Ashworth Scale (MAS), the Action Research Arm Test (ARA), the Barthel Index (BI) and the Visual Analogue Pain Scale (VAS).

Results: Fifty patients were recruited. The four study groups were comparable at baseline with respect to their demographical characteristics and severity of spasticity. All doses of Dysport® studied showed a significant reduction from baseline of muscle tone and pain compared to placebo. However, the effect of functional disability was best at a dose of 500?U and the peak improvement was at week 8 after injection. A dose of 1000?U Dysport produced such an excess degree of muscle weakening that the number of randomized patients was reduced to five. BI and ARA of all patients were decrease after injection. No other adverse event was considered related to the study medication.

Conclusion: This study suggests that treatment with Dysport® reduces muscle tone in adult patients with upper limb spasticity. The optimal dose for treatment of patients with residual voluntary movement in the upper limb appears to be 500?U.     

Early life and later determinants of adult disease: a 50 year follow-up study of the Newcastle Thousand Families cohort

The relative contribution of socioeconomic, behavioural and biological factors operating in fetal and infant life, childhood and adulthood to risk for cardiovascular disease, respiratory diseases and non-insulin-dependent diabetes in middle age has become an important research issue. All 1142 babies born in Newcastle upon Tyne in May and June 1947 were recruited into a prospective cohort study of child health (the ‘Thousand Families’ study) and followed in great detail to the age of 15 y, with a brief further follow up at age 22 y. Children from poorer families were at greatest risk of severe respiratory tract infection in infancy. Children from professional and managerial families were on average taller and heavier throughout childhood than those from semi- and unskilled manual social classes. Repeated infections in early childhood greatly increased the risk of developing chronic respiratory disease by age 15 y. This paper outlines a new investigation designed to trace surviving members of this cohort and to chart the relationships between their socioeconomic circumstances, lifestyles, experiences and health from birth through to the present day. Existing data on socioeconomic circumstances and infections in infancy and childhood, infant nutrition, birthweight and physical development to age 22 y will be linked to information gained from a new study. This comprises a postal questionnaire survey of study members' adult health, socioeconomic circumstances and lifestyle, and a hospital based clinical examination including heart and lung function, glucose tolerance, blood lipids and anthropometric measurements at age 49–51 y. Out of a target sample of 979 people for whom sufficient data are available on the first year of life, 866 (88%) have been traced and 649 are still resident in the North of England. Those study members who have been traced are highly representative of the original cohort. The Thousand Families cohort provides a unique opportunity for detailed epidemiological study because of the wealth of data available on infant and childhood socioeconomic and family circumstances, all of which was collected prospectively. In addition, there has been comparatively little loss to follow-up since 1948.     

Development of a novel screening device permitting immunocytochemical screening of numerous culture supernatants during hybridoma production

A novel screening device is described which permits the simultaneous immunocytochemical processing of several hundreds or even thousands of hybridoma culture supernatants. The core of the screening apparatus is a foam-coated polymer plate that carries a 96-well pattern representing a modification of the actual 96-well template. This modification permits the use of conventional 26 X 76 mm microscopy glass slides. Each of these slides carries 24 carefully arranged histological sections. One 96-well plate is thus screened by mounting four of these slides in the apparatus during the primary antibody (i.e., culture supernatant) incubation stage. At all other stages of the immunocytochemical protocol, the slides are processed in the classical way. The screening apparatus has been used during the production of monoclonal antibodies against chicken pituitary glycoprotein hormones and against bovine neurohypophyseal peptides. In both instances, it proved to be the major contributory factor in the successful production of antibodies.     

Cerebral excitatory amino acids and Na+, K+-ATPase activity during resuscitation of severely hypoxic newborn piglets

We tested the hypothesis that early brain recovery in hypoxic newborn piglets is improved by resuscitating with an O₂ supply close to the minimum level required by the newborn piglet brain. Severely hypoxic 2-5-d-old anaesthetized piglets were randomly divided into three resuscitation groups: hypoxaemic (n = 8), 21% O₂ (n = 8), and 100% O₂ groups (n = 8). The hypoxaemic group was mechanically ventilated with 12-18% O₂ adjusted to achieve a cerebral venous O₂ saturation of 17-23% (baseline; 45±1%, mean±SEM). During the 2h resuscitation period, extracellular aspartate and glutamate concentrations in the cerebral striatum were higher during hypoxaemic resuscitation (p = 0.044 and p = 0.055, respectively) than during resuscitation with 21% O₂ or 100% O₂, suggesting an unfavourable accumulation of potent excitotoxins during hypoxaemic resuscitation. The cell membrane Na⁺,K⁺-ATPase activity of cerebral cortical tissue after 2 h resuscitation was similar in the three groups (p = 0.30). In conclusion, hypoxaemic resuscitation did not normalize early cerebral metabolic recovery as efficiently as resuscitation with 21% O2 or 100% O₂. Resuscitation with 21% O₂ was as efficient as resuscitation with 100% O₂ in this newborn piglet hypoxia model.     

The Effect of Myopenia on the Inflammatory Response Early after Colorectal Surgery

Background: Myopenia (low skeletal muscle mass) is associated with an increased risk of complications following colorectal surgery, however, the underlying mechanism is poorly understood. This study investigates the effect of myopenia on the early postoperative systemic inflammatory response. Materials and methods: In 78 patients undergoing colorectal surgery, the presence of myopenia was preoperatively assessed using computed tomography images of the third lumbar vertebra. Interleukin-8 (IL-8) and soluble tumor necrosis factor receptor-1 (TNFRSF1A) were measured in plasma before and 4 h after start of surgery as part of a randomized controlled trial investigating the effect of perioperative gum chewing on the inflammatory response. Multivariable linear regression analysis was performed to assess the effect of myopenia on inflammatory markers while correcting for possible confounders. Results: Four hours after start of surgery, IL-8 was higher in patients with myopenia than in patients without myopenia (352 ± 268 vs. 239 ± 211 pg/ml, P = 0.048), while TNFRSF1A was similar between groups. After adjusting for sex and the intervention with perioperative gum chewing, myopenia remained associated with higher postoperative IL-8 concentrations (P = 0.047). Conclusion: Myopenia may affect IL-8 early after colorectal surgery. However, more studies are needed to validate these findings.