An opportunity for commitment.
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Cost Control↗
Biomedical subjects
A Evans
Publications and source records attributed to A Evans.
Shortage of professional nursing practice: a reframing of the shortage problem.
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Cost Control↗
The effects of gamma interferon on the natural killer and tumor cells of children with neuroblastoma. A preliminary report.
Human neuroblastoma cells lack HLA-A,-B,-C molecules which can be induced in vitro by gamma interferon (gamma IFN). To test the hypothesis that the same induction would occur in vivo leading to tumor regression, a Phase I study was initiated. Seven patients with neuroblastoma were entered on a Phase I study of recombinant gamma IFN in children. Three received 0.05 mg/m2 intravenously (IV) three times a week, three received 0.1 mg/m2 for 4 weeks, and one patient withdrew from study before receiving adequate treatment for evaluation. No significant clinical response was seen. The side effects were fever and chills, and no serious toxicity occurred. Natural killer (NK) and lymphocyte activated killer (LAK) precursor activity of peripheral blood mononuclear cells was determined before and during treatment, and expression of HLA-A,B,C molecules was looked for on the tumor cells in the bone marrow of five patients. The NK activity initially low, reached control levels in six patients, but the increase was transient. The LAK precursor activity remained normal. Expression of HLA-A,B,C, initially absent, was induced on the neuroblastoma cells in four of six patients.
Antigens, Neoplasm↗
Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study.
The Third National Wilms' Tumor Study sought to reduce treatment for low-risk patients and find better chemotherapy for those at high risk for relapse. Eligible patients (1439) were randomized according to stage (I-IV) and histology (favorable [FH] or unfavorable [UH]), and contributed data to survival and relapse-free survival (RFS) analyses. Four-year (postnephrectomy) survival percentages and randomized treatment regimens for low-risk patients were 96.5% for 607 Stage I/FH patients who received dactinomycin (Actinomycin D [AMD], Merck Sharp & Dohme, West Point, PA) and vincristine (VCR) for 10 weeks versus 6 months; 92.2% for 278 Stage II/FH patients; and 86.9% for 275 Stage III/FH patients who received AMD + VCR +/- Adriamycin (ADR, Adria Laboratories, Columbus, OH) for 15 months. Stage II/FH patients also had either zero or 2000 cGy irradiation (RT) postoperatively and Stage III/FH patients either 1000 or 2000 cGy. Four-year survival was 73.0% for 279 high-risk patients (any Stage IV, all UH) who received postoperative radiation therapy (RT) and AMD + VCR + ADR +/- cyclophosphamide (CPM). Statistical analysis of survival and RFS experience shows that the less intensive therapy does not worsen results for low-risk patients and CPM does not benefit those at high risk.
Adolescent↗
King's Fund nursing developments. Primary nursing in Camberwell.
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Female↗
Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis.
In patients with Hodgkin's disease, titers of IgG antibody against viral capsid antigen of Epstein-Barr virus and the prevalence of antibodies against early antigen are higher than expected. To evaluate whether this condition antedates diagnosis, we identified 43 persons with Hodgkin's disease, from whom blood had been drawn and stored for an average of 50.5 months before diagnosis, and 96 controls from the same populations, from whom blood had been drawn at the same time. The relative risks of Hodgkin's disease associated with elevated levels of IgG and IgA antibodies against capsid antigen were 2.6 (90 percent confidence interval, 1.1 to 6.1) and 3.7 (1.4 to 9.3), respectively. For Epstein-Barr nuclear antigen, the relative risk was 4.0 (1.4 to 11.4), and for early antigen D it was 2.6 (1.1 to 6.1). However, the prevalence of IgM antibody against capsid antigen was substantially lower in patients with Hodgkin's disease (0.22 [0.04 to 1.3]). These associations were stronger in serum samples obtained at least three years before diagnosis than in serum samples obtained closer to diagnosis. We conclude that the development of Hodgkin's disease may in some patients be preceded by enhanced activation of Epstein-Barr virus. Whether Epstein-Barr virus has a direct role in the pathogenesis of the disease or is simply a marker for a more fundamental factor affecting the immune control of latent infections is unknown.
Antibodies, Viral↗
Minitracheotomy in the early respiratory management of patients with spinal injuries.
Minitracheotomy is a new technique of tracheal suction by the introduction under local anaesthetic of a small bore tube into the trachea through the cricothyroid membrane. The use of minitracheotomy in the early management of respiratory problems in patients with spinal injuries is described with a few illustrative cases. This technique is an adjunct to good physiotherapy in clearing secretions from the trachea. Its advantages and disadvantages are discussed.
Adult↗
Myoclonus epilepsy and ragged-red fibres (MERRF). 1. A clinical, pathological, biochemical, magnetic resonance spectrographic and positron emission tomographic study.
Thirteen patients, including 6 from one family, with the syndrome of myoclonus epilepsy and ragged-red fibres (MERRF) were studied. There was considerable heterogeneity in the age of onset, severity and associated clinical features. Postmortem studies in 3 patients from the one family showed a particular system degeneration. In addition, the youngest and most severely affected family member showed the pathological changes of Leigh's syndrome. Cortical dysfunction is a prominent clinical feature in MERRF, but postmortem examination failed to reveal cortical abnormalities. Positron emission tomographic studies, however, showed decreased cortical metabolic rates for glucose and oxygen utilization, with normal cortical blood flow and cerebral pH. Analyses of kinetic rate constants for uptake and phosphorylation of the glucose analogue, fluorodeoxyglucose showed decreased hexokinase-mediated phosphorylation: normal K1 and k2 values but reduced k3. Phosphorus magnetic resonance spectroscopy studies suggested a normal cerebral intracellular pH. Biochemical studies on muscle homogenates in 6 patients showed partial deficiencies of the activities of certain mitochondrial enzymes in 4 cases, whereas in 2 patients no abnormality was found. Our data, combined with previous reports, show that MERRF is biochemically and genetically heterogeneous. Our experience, and analysis of the literature, suggests that many cases previously described as the Ramsay Hunt syndrome, as well as other hitherto unclassified system degenerations associated with myoclonus epilepsy, are examples of MERRF. These data permit the formulation of a hypothesis to explain the clinical, biochemical and genetic heterogeneity of MERRF, and its overlap with Leigh's syndrome. We suggest that different biochemical defects of the mitochondrial respiratory chain may cause similar cerebral metabolic effects, as measured by positron emission tomography, resulting in similar phenotypes. Reduced activity of one enzyme, however, may result in different phenotypes, depending on the severity of the defect and its tissue distribution. Moreover, the phenotypic expression of certain biochemical defects may be influenced by randomly occurring factors such as fever, which may increase metabolic demand and result in more deleterious cellular metabolic effects.
Adolescent↗
Prognostic factors for children with recurrent Wilms' tumor: results from the Second and Third National Wilms' Tumor Study.
The characteristics of 367 stage I-IV National Wilms' Tumor Study (NWTS) children who relapsed after initial treatment for unilateral disease in the second and third NWTS trials (NWTS-2 and -3) were analyzed to identify features predictive of survival. Although modifications in initial therapy resulted in a lower rate of first relapse in these two studies compared with NWTS-1, all previously identified prognostic factors after relapse remained statistically significant predictors of survival. Tumor histology, length of initial remission, initial therapy with two v three drugs, and site of relapse each were independently predictive of postrelapse survival. The 3-year postrelapse survival for all 367 patients was 30% +/- 3%; however, subgroups classified by these prognostic factors were identified that had 3-year postrelapse survival rates of greater than 40%. These subgroups included patients who had tumors of favorable histology (FH) that recurred (1) only in the lungs, (2) in the abdomen when radiotherapy (RT) was not initially given, or (3) that were originally stage I, (4) that were originally treated with only two drugs, or (5) that recurred 12 months or more after diagnosis. These results were achieved with the use of standard treatments, ie, surgery, RT, and chemotherapy using dactinomycin (AMD), vincristine (VCR), and Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH). It is suggested that patients in these groups might be managed with aggressive use of conventional therapies until newer chemotherapeutic agents and drug combinations are shown to be more effective. Patients with adverse prognostic features at relapse have a poor survival expectancy with standard measures. Salvage attempts for these patients are better based on experimental approaches.
Adolescent↗
A comparison of the toxicity and efficacy of cisplatin and carboplatin in advanced ovarian cancer. The Swons Gynaecological Cancer Group.
Eighty-eight patients with stage IIB-III epithelial ovarian cancer were randomised to receive first line single agent cisplatin (100 mg/m2) monthly or carboplatin (400 mg/m2) monthly for up to 5 cycles. Crossover to the opposite analogue occurred with progression or lack of response. All patients were premedicated with i.v. methylprednisolone (500 mg at 0 hours and 250 mg at 3 hours) and the first 20 patients in both groups received lorazepam and prochloperazine for nausea and vomiting. The median number of vomiting episodes per cycle with cisplatin was 16 and with carboplatin 2 (p less than 0.001). In the cisplatin arm 27/40 (67.5%) developed mild renal toxicity, 9/40 (22.5%) WHO grade I neurotoxicity and 18/40 (45%) evidence of ototoxicity at audiometry. To date we have seen no neuro- or ototoxicity with carboplatin and 1/40 (2.5%) have developed WHO grade I renal toxicity. Myelosuppression and anaemia was more common with carboplatin but only 1 episode of grade IV thrombocytopenia has been seen with first line carboplatin. The clinical response rate (CR+PR) for cisplatin was 19/40 and for carboplatin 27/40. Actuarial survival for cisplatin group at 24 months was 50% and for carboplatin group 58% with no significant difference. Carboplatin appears less toxic than cisplatin producing to date similar survival and response as a single agent.
Antiemetics↗
An outbreak of influenza in Jamaica (1986).
An outbreak of febrile illness at the Police Training Academy in St. Catherine, Jamaica in October, 1986 is described. Influenza A similar to type A/Taiwan/86 (H1N1) was confirmed serologically in 33 cases, and Influenza B similar to type B/Ann Arbor/86 in 1 case. Clinical findings included upper respiratory symptoms (97%) headache (74%), fever (68%), joint pains (39%) and retro-orbital pain (26%). The role of vaccination and chemoprophylaxis in the prevention of influenza is discussed, and the importance of surveillance is stressed.
Adolescent↗
Second malignant neoplasms in survivors of Wilms' tumor: a report from the National Wilms' Tumor Study.
Between October 1969 and December 1982, 2,438 patients were enrolled in the National Wilms' Tumor Study and contributed 14,381 person-years of observation to a follow-up study for the occurrence of second malignant neoplasms (SMNs). Fifteen SMNs were observed, whereas 1.77 would have been expected from U.S. incidence rates for 1973-1977 [relative risk = 8.5; 95% confidence interval (CI) = 4.7, 14.0]. Ten years after the Wilms' tumor diagnosis, the cumulative risk of SMN was 1%. The relative risks compared to standard rates were 12/1.11 = 10.8 (95% CI = 5.6, 18.9) for those who received radiation as part of the initial course of treatment and 3/0.60 = 5.0 (95% CI = 1.0, 14.6) for those who did not, but this difference was not statistically significant. Preliminary data suggest that substantial numbers of SMNs occur as patients are followed greater than 10 years from diagnosis.
Child↗
Workshop on schizophrenia, PET, and dopamine D2 receptors in the human neostriatum.
Recently, two research groups published numbers for D2 receptor sites in the neostriatum of drug-naive schizophrenic patients, obtained in vivo by positron emission tomography (PET). One study appeared to confirm the increase of D2 receptor numbers, while the other study did not. A workshop was convened in Montreal to examine the reasons for the discrepancy between the results obtained by the two groups. The workshop considered patient populations, PET instrumentation and scanning methods, pharmacology, and modeling. The workshop identified differences between the approaches of the two groups that could contribute to the divergent results, including age and chronicity of the patient samples, brain region selected for study, metabolism of the different radioligands in blood and brain, reversibility of binding, PET instrumentation, and complexity of data analysis. The workshop concluded that these initial efforts had made considerable progress in establishing the role of PET in the understanding of the biochemical processes underlying mental illness. In particular, the unique ability to quantify regional neuroreceptor density at different stages in the evolution of the disease has been implemented. At the same time, the work so far and this conference served to identify the main sources contributing to the different findings from the two centers. This information will be important in designing the next phase of the research which will build upon and reconcile these apparent discrepancies.
Adult↗
Bioactive LH in women with polycystic ovaries and the effect of gonadotrophin suppression.
Discrepancies between levels of bioactive LH (B-LH) and immunoreactive LH (I-LH) in polycystic ovarian syndrome (PCO) have been reported previously. Serum levels of I-LH, B-LH (by dispersed Leydig cell assay), FSH, oestradiol (E2) and progesterone (Prog) were measured once to three times weekly over 4 weeks in 13 women with classical clinical, ultrasound and endocrine features of PCO. Eleven women attending for infertility but whose profiles when studied three times weekly by combined endocrine and ultrasound assessment were normal and ovulatory served as controls. Seven of the women with PCO were evaluated during and after 3 weeks suppression with ethinyloestradiol (30 micrograms) plus 150 micrograms either of desogestrel or levonorgestrel; two were given both treatments. Both I-LH and B-LH levels were higher in PCO patients (20 +/- SD 5 U/l and 46 +/- 9 U/l respectively, P less than 0.0001), compared with all phases of the normal cycles except the mid-cycle peak. The B-LH to I-LH (B:I LH) ratio in PCO patients (2.5 +/- 0.7) was higher than in all the control cycle phases (P less than 0.05). I-LH, B-LH, B:I LH ratio, FSH and E2 were all suppressed from the second week of oestrogen-progestogen treatment (P less than 0.01) and returned gradually to pretreatment levels by the third or fourth week after suppression. The LH and FSH levels and B:I LH ratio in PCO patients during suppression were comparable with levels in the early and mid-follicular phases of control cycles but the LH/FSH ratio remained significantly raised (P less than 0.01) at 2.3 +/- 0.7.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Optical and nuclear magnetic resonance studies of hypoxia in human tissue and tumors.
Correlations of energy state with response to therapy are more difficult to analyze because of the large effect of tumor clearing and oxygenation upon the tumor energy state as detected by PMRS alone. The combination of time-resolved hemoglobinometry using picosecond laser technology and localized PMRS seems appropriate to unravel the complexities of therapeutic intervention, tumor energetics, and oxygenation.
Energy Metabolism↗
Patterns of physiological and biochemical changes in acute human cerebral infarction with and without hyperglycemia studied by positron emission tomography.
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Acute Disease↗
Effectiveness of self-monitored, home-based, moderate-intensity exercise training in middle-aged men and women.
The effects of 6 months of self-monitored, home-based exercise training on maximal oxygen uptake (VO2 max), body composition and plasma lipid levels of healthy, sedentary, middle-aged persons were evaluated in 60 men, aged 49 +/- 6 years, and 60 women, aged 47 +/- 5 years. Moderate-intensity training was performed 5 times per week in sessions of 47 +/- 7 minutes and 54 +/- 8 minutes for men and women, respectively. The individually prescribed range of heart rate corresponded to 65 to 77% of the peak value during symptom-limited treadmill testing (mean of 72% for men and 69% for women). Caloric expenditure per training session was approximately 345 kcal for men and 235 kcal for women. VO2 max increased 15% in men and 9% in women (both p less than 0.01). The greater increase in VO2 max in men than in women primarily reflected greater adherence to training in men (greater than or equal to 90% vs greater than or equal to 75%). The increase in VO2 max in women who showed very high adherence was comparable to that of men. Body weight decreased, by 1.5 +/- 10 kg, in men (p less than 0.05) but not in women undergoing training. No significant training-induced changes in plasma lipid levels were noted in either men or women. Baseline orientation and follow-up telephone calls required less than 1 hour of staff time per participant. Self-monitored, moderate-intensity, home-based exercise training significantly increases functional capacity in healthy, middle-aged men and women. Such training provides an alternative to group-based exercise training.
Adult↗
Effect of generalized spike-and-wave discharge on glucose metabolism measured by positron emission tomography.
Positron emission tomography was used to study the cerebral metabolic rate for glucose (CMRGlc) in 7 adult patients with generalized spike-and-wave activity in the electroencephalogram. No consistent changes were seen in the CMRGlc. There was a slight trend toward an increased CMRGlc in 2 patients with primary generalized epilepsy, while in the 5 other patients with minor deviations from this condition or with secondary generalized epilepsy, the CMRGlc was unaffected by spike-and-wave activity or was below the normal range. Neither the amount of spike-and-wave activity in the EEG nor the presence of clinically evident absence seizures appeared to influence the CMRGlc. Therefore, we conclude that neuronal activity underlying spike-and-wave discharge does not seem to require increased glucose utilization.
Adolescent↗