Biomedical subjects
J Smith
Publications and source records attributed to J Smith.
Health care system, cancer registration and follow-up of cancer patients in the United Kingdom.
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Streptomycin-loaded bone cement in the treatment of tuberculous osteomyelitis: an adjunct to conventional therapy.
Streptomycin-loaded bone-cement (7 g of streptomycin in 40 g of bone cement) beads were used in the treatment of tuberculous bursitis and osteomyelitis of the greater trochanter in a 76-year-old woman. Wound drainage, serum and urine concentrations of streptomycin were measured. For the first 96 hours, the streptomycin levels in the wound drainage ranged from 2932 mg/L to 414.4 mg/L, and in the serum, streptomycin levels ranged from 1.7 mg/L to 13.7 mg/L. The patient recovered without complication and at follow-up 2 years later was free of infection and walking without pain. The authors conclude that the use of streptomycin-loaded bone cement can safely and effectively eradicate mycobacterial tuberculosis osteomyelitis.
Birth weight and early lung compliance as predictors of short-term outcome in premature infants with respiratory distress syndrome.
In addition to birth weight (BW), respiratory mechanics during the first week of life have been reported to predict outcome in ventilated newborn infants with respiratory distress syndrome (RDS). Most measuring techniques are invasive, requiring the placement of an oesophageal tube or balloon. In the present study the compliance (Crs) and resistance (Rrs) of the total respiratory system were measured without an oesophageal tube , using a commercially available system (PEDS; MAS Inc., Hatfield, Pa.) . The Crs and Rrs were determined once, within 24 hours of birth, in 28 preterm infants requiring mechanical ventilation for RDS. Variables such as gestational age (GA) and BW were also evaluated for their predictive role in outcome. Poor outcome was defined as death from respiratory failure or the development of bronchopulmonary dysplasia (BPD) at 28 days. All non-survivors died of refractory respiratory failure, at a median of age of 6 days. The median Crs of the 21 survivors was 0.5 ml/cm H2O and of the non-survivors 0.21 ml/cm H2O (P = 0.01). Crs below 0.45 ml/cm H2O predicted 15 of the 16 infants who either developed BPD or died (positive predictive value 100%; negative predictive value 92%; sensitivity 94%; specificity 100%). Nine survivors, who subsequently developed B PD, had a median Crs of 0.38 ml/cm H2O. Their Crs was significantly lowe r than that of the infants without evidence of BPD (Crs = 0.61 ml/cm H2O ) (P = 0.01). All of the 12 babies without BPD who survived had median C rs values above 0.45 ml/cm H2O. The median Rrs of the 9 infants with BPD (96 cm H2O/l/s) was also significantly higher than the Rrs value of the non-BPD group (59 cm H2O/l/s) (P = 0.05). When stepwise multiple logistic regression was applied to predict outcome, the only variable that could be entered at a 0.05 level of significance was BW. Uncorrected compliance entered the second step, but did not reach statistical significance. We conclude that in premature infants with RDS, BW is a strong predictor of outcome. Although determination of the Crs within the first 24 hours after birth did not add significance to this predictive model, it was nevertheless a useful parameter to determine respiratory morbidity and mortality.
The effectiveness and cost of exogenous pulmonary surfactant replacement therapy.
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Improved perinatal mortality rates in 1001 patients with severe pre-eclampsia.
OBJECTIVE: To ascertain the change in perinatal mortality (PNM) rate over a period of 10 years in 1001 patients with severe pre-eclampsia. METHODS: Patients with severe pre-eclampsia before a gestational age of 34 weeks were managed expectantly. Initial treatment consisted of the administration of magnesium sulphate to prevent convulsions and dihydralazine to reduce blood pressure. Methyldopa alone or in combination with other oral antihypertensive drugs was started soon after admission. In order to prevent fetal death from abruptio placentae, the fetal heart rate was monitored at least four times per day. Patients were delivered either at 34 weeks' gestation or when fetal or maternal indications for immediate delivery were present. The 10-year study was divided into four successive time periods and the PNM rate was calculated separately for each of these time periods. RESULTS: Perinatal survival was low if patients were delivered before or at 26 weeks' gestation but improved rapidly if delivered thereafter. There were only 33 intrauterine deaths of babies who weighed 1000 g or more. The majority of these deaths were due to abruptio placentae which had occurred prior to admission to hospital. The PNM rate for babies of 1000 g or more decreased from 61 in the first time phase and 83 in the second to 19 in the last. The overall PNM rate during the 10-year study was 62. CONCLUSION: Improved knowledge about the management of patients with severe pre-eclampsia in early pregnancy resulted in a decline in the PNM rate. Although the exact cause of this reduction towards the end of the study is not known, several factors probably played a role. They are expectant management with a little gain in the gestational age, better fetal monitoring before and during labour, earlier detection of fetal distress, earlier referral to the tertiary hospital and improved neonatal care.
The outcome of babies of mothers with severe rhesus incompatibility treated at Tygerberg Hospital, 1980-1993.
OBJECTIVE: To determine the outcome of babies of mothers with severe rhesus (Rh) incompatibility treated by elective delivery when the amniotic optical density at 450 nm crossed Whitfield's action line (group 1), by plasmapheresis and immunotherapy (group 2) or by means of intra-uterine intravascular transfusions (group 3). STUDY DESIGN: A retrospective study of 55 mothers and their 57 fetuses with severe Rh incompatibility at < 34 weeks' pregnancy duration. MAIN OUTCOME PARAMETERS: Number of mothers in each treatment group, prevalence of intra-uterine death, hydrops, intra-uterine intravascular transfusions, cord haematocrit, cord bilirubin, number of liveborn babies, birth weight, neonatal death, hyaline membrane disease (HMD) and exchange transfusions. STUDY POPULATION AND SETTING: All mothers and babies with severe Rh incompatibility (defined as an amniotic optical density of 450 nm in the upper and upper-mid zone on the Liley chart at < 34 weeks' pregnancy duration, previous fetal hydrops or Rh-related intra-uterine death (IUD), fetal hydrops on ultrasound or a fetal haematocrit < 30% at cordocentesis) treated at Tygerberg Hospital between January 1980 and January 1993. There were 20 fetuses each in groups 1 and 3, and 17 in group 2. RESULTS: A total of 48 babies (84%) were liveborn and of these 74% survived the neonatal period. (ABSTRACT TRUNCATED AT 250 WORDS)
Congenital syphilis associated with persistent pulmonary hypertension of the neonate--a clinico-pathological case study.
UNLABELLED: Congenital syphilis remains a significant clinical problem, especially in developing countries. We report a fatal case of congenital syphilis complicated by persistent pulmonary hypertension and hypoxic ischaemic encephalopathy. OBJECTIVE: To describe the association of congenital syphilis with persistent pulmonary hypertension of the newborn (PPHN). METHOD: Case report of a single patient. RESULTS: Fatal outcome of one baby with congenital syphilis and associated PPHN despite maximal conventional treatment. Histological examination of the lungs revealed pulmonary oedema, intra-alveolar haemorrhages, localised bronchopneumonia and marked interstitial infiltrates of lymphocytes, plasma cells, macrophages and fibroblasts with interstitial fibrosis. Examination of peripheral pulmonary arteries revealed focal excessive muscularisation with increased adventitial connective tissue. DISCUSSION: Reviewing our own experience and available literature, this case study supports the infrequent association of congenital syphilis with PPHN. However, when it occurs, this combination appears to be fatal. CONCLUSION: More research is warranted to clarify the role of inflammatory mediators in congenital syphilis of the lung.
Australia: remote area nurses' experiences of violence.
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Idiotype specific peptides bind to the surface immunoglobulins of two murine B-cell lymphoma lines, inducing signal transduction.
Using a random combinatorial synthetic peptide library method based on a one-bead one-peptide concept for ligand identification (Lam et. al, Nature 1991, 354, 82-84.), idiotype specific peptides were retrieved and optimized for interaction with the cell surface immunoglobulins [IgM(kappa)] of two murine B lymphoma cell lines. Several of the identified peptides were characterized with respect to cell binding and signal transduction. These peptides were able to bind specifically to the surface immunoglobulins of these lymphoma cells. In addition to binding, when synthesized in tetrameric or multimeric forms, the peptides were able to trigger signal transduction resulting in an increase in protein tyrosine phosphorylation. Since D-amino acid peptide libraries were used in some of our efforts to identify binding ligands, several of the idiotype-specific peptides are composed of all D-amino acids (e.g. wGeyvmvnG). These findings may have important therapeutic implications for targeted-therapy of B-cell lymphoma as these D-amino acid ligands are more resistant to proteolysis resulting in a prolonged pharmacokinetic disposition in vivo.
Localization of inducible nitric oxide synthase in acute renal allograft rejection in the rat.
There is increasing evidence for a role for nitric oxide (NO) in the alloimmune response and induction of NO synthesis occurs during allograft rejection. The aim of this study was to investigate the source of NO synthesis in rejecting allografts. Localization of inducible nitric oxide synthase (iNOS) was studied by immunohistochemistry, in a rat model of acute renal allograft rejection, in unmodified Lewis recipients in which rejection is complete 7 days after transplantation of F1 hybrid Lewis-Brown Norway kidneys. High levels of iNOS expression were found in infiltrating mononuclear cells in glomeruli and interstitium of rejecting kidneys; there was no expression in parenchymal renal cells, or in control isografts of either rat strain. Expression of iNOS in the cortex was present from 4 to 6 days posttransplantation, and had declined by the 7th day, where expression was principally in the medulla. The pattern of iNOS staining was similar to ED1 staining, a marker for rat macrophages. These findings suggest that infiltrating macrophages in the graft reaction are a prominent source of NO; this iNOS expression supports a role for NO in the modulation of local allogeneic responses, and possibly as a mediator of cytotoxic graft damage.
Gift authorship: a poisoned chalice?
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National Cancer Institute (phase II) study of high-grade glioma treated with accelerated hyperfractionated radiation and iododeoxyuridine: results in anaplastic astrocytoma.
PURPOSE: We report the outcome of a Phase II study of a cohort of patients with high-grade glioma treated with accelerated hyperfractionated radiation and the radiation sensitizer, iododeoxyuridine (IdUrd). METHODS AND MATERIALS: Between January 1988 and December 1990, 39 consecutive patients with high-grade glioma were enrolled and treated on a Phase II protocol including hyperfractionated radiation and IdUrd. Thirty-two patients were male and seven were female. Age range was 19 to 71 years with a median age of 38 years. IdUrd (1000 mg/m2 per day) was administered in two separate 14-day courses, the first during the initial radiation field and the second during the final cone-down field. All patients were treated consistently with partial brain technique and received 1.5 Gy/fraction twice daily to a mean total dose of 71.25 Gy (range 66-72 Gy excluding one patient who did not complete treatment). The initial field was treated to 45 Gy followed by a cone-down field covering the tumor volume plus a 1-cm margin to the final dose. Patients were assessed for acute and long-term morbidity and followed for outcome. Two patients had biopsies during the course of treatment. Flow cytometry and high performance liquid chromatography was used to evaluate the labeling index and the percent replacement of IdUrd in the biopsy specimen. RESULTS: Thirty-eight of 39 patients completed therapy. One patient died on treatment at 48 Gy and is included in the survival analysis. No patient was lost to follow-up. Twenty-one patients had Grade 3 (anaplastic astrocytoma) tumors and 18 patients had Grade 4 (glioblastoma multiforme). Median survival for the entire cohort was 23 months. For the glioblastoma multiforme patients, median survival was 15 months. The median survival of the anaplastic astrocytoma patients has not yet been reached. In the patients assessed, the range of IdUrd tumor cell incorporation was only 0-2.4%. CONCLUSION: Accelerated hyperfractionated radiation therapy with IdUrd was administered with acceptable acute toxicity. The major acute side effects of mucositis and thrombocytopenia were related to IdUrd infusion and were dose-dependent. There were no unacceptable acute toxicities referable to the radiation as delivered. With a median potential follow-up of 51 months, the actuarial median survival of the glioblastoma multiforme patients is comparable with the best previously published reports. The outcome of patients with anaplastic astrocytoma compares very favorably with even the most aggressive multi-modality approaches in the recent literature with a minimum of acute morbidity.
Public health gets a boost in NHS streamlining.
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Effect of increasing intravesicular pH on nitrite production and leishmanicidal activity of activated macrophages.
We examined the effect of bafilomycin A1 (BAF), an inhibitor of vacuolar-type H(+)-ATPases, on macrophages activation (measured as increased nitrite production and leishmanicidal activity) induced by interferon gamma alone or together with lipopolysaccharide or tumour necrosis factor alpha. BAF increased intravesicular pH and enhanced nitrite release by activated macrophages; however, the NO concentration necessary to kill parasites was higher in BAF-exposed than control macrophages, suggesting that microbicidal nitrogen derivatives were less active at alkaline pH. Antibody to tumour necrosis factor alpha inhibited BAF-induced nitrite production in interferon-activated cultures. To determine if enhanced NO synthesis was related to vesicular alkalinization, macrophages were incubated with the lysosomotropic bases NH4Cl and methylamine. These agents also increased intravesicular pH and nitrite production. Nitrite production was correlated with enhanced NO synthase activity in cytosolic extracts of the activated cells.
Exclusive W++ gamma production in proton-antiproton collisions. I. General formalism.
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Exclusive W++ gamma production in proton-antiproton collisions. II. Results.
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Prevention of the humoral response induced by an anti-CD3 monoclonal antibody by deoxyspergualin in a murine model.
Multiple treatments with the potent immunosuppressant murine antihuman CD3 mAb OKT3 is sometimes precluded by the onset of a neutralizing humoral response mostly consisting of anti-idiotypic antibodies. A hamster antimurine CD3 monoclonal Ab, 145-2C11, shares many properties with OKT3, in particular the ability to induce a strong Ab response in mice. Deoxyspergulain (DSG), a metabolite of the antibiotic spergualin, has been shown to reduce Ab production triggered by pathogens in a variety of infectious models and against common antigens. In this study, we examined the ability of DSG to inhibit the humoral response induced by 145-2C11. DSG prevented the Ab production triggered by the anti-CD3 mAb in an Ag-specific manner and significantly reduced the Ab production in mice previously primed with 145-2C11. We showed that DSG had a long-term effect on B cells and a transient effect on T cells. In effect, DSG was found to induce a prolonged Ag-specific unresponsiveness of B lymphocytes, and to transiently reduce the capacity of T lymphocytes to deliver help to B cells, in part by reducing IL-4 production. DSG did not reduce the immunosuppressive properties of the anti-CD3 mAb. In fact, the combination of DSG with 145-2C11 prolonged the survival of allogeneic skin grafts when compared with the administration of 145-2C11 or DSG alone. Thus, the coadministration of DSG with OKT3 may be of clinical interest to reduce the humoral response triggered by the mAb.