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M Lewis

Publications and source records attributed to M Lewis.

At least 181 records · Page 10Linked to original sources
PubMed1996

Crystal structure of the lactose operon repressor and its complexes with DNA and inducer.

The lac operon of Escherichia coli is the paradigm for gene regulation. Its key component is the lac repressor, a product of the lacI gene. The three-dimensional structures of the intact lac repressor, the lac repressor bound to the gratuitous inducer isopropyl-beta-D-1-thiogalactoside (IPTG) and the lac repressor complexed with a 21-base pair symmetric operator DNA have been determined. These three structures show the conformation of the molecule in both the induced and repressed states and provide a framework for understanding a wealth of biochemical and genetic information. The DNA sequence of the lac operon has three lac repressor recognition sites in a stretch of 500 base pairs. The crystallographic structure of the complex with DNA suggests that the tetrameric repressor functions synergistically with catabolite gene activator protein (CAP) and participates in the quaternary formation of repression loops in which one tetrameric repressor interacts simultaneously with two sites on the genomic DNA.

Allosteric Regulation↗
PubMed1996

Acute lymphoblastic leukaemia: the Wellington experience 1980-92.

AIMS: The study was designed to compare two populations of children with acute lymphoblastic leukaemia treated in the Wellington regional oncology unit over two six year periods, 1980-6 and 1986-92 when two different treatment protocols were used. METHODS: Fifty-eight cases were identified from the children's cancer registry and the relevant data collected from the hospital records. Overall survival and disease free survival in the two populations were compared. RESULTS: There was a significant difference for both outcomes between the two study populations, those treated prior to August 1986 having an actuarial survival of 53% and a disease free survival of 47% compared with 93% and 88% in those children treated after August 1986 (p=0.01 and 0.001 respectively). This was not explained by differences in sex, age, area of residence at diagnosis or disease risk. CONCLUSIONS: Increased intensity and duration of the induction and consolidation phase of treatment has significantly improved outcome for standard and high risk disease in children who have received the intensive phases of this treatment at a regional paediatric oncology centre. Outcome is not compromised if children receive the less intensive maintenance therapy close to their homes at the district or base hospital and close links are maintained with the regional unit.

Adolescent↗
PubMed1996

A process model for understanding adaptation to sexual abuse: the role of shame in defining stigmatization.

While sexual abuse in childhood places the individual at-risk for a variety of problems, research indicates wide variation in victims' adjustment. Limited work is available that attempts to systematically explain processes by which children adjust to the trauma. Few studies have been undertaken to examine any theory about what causes children to be symptomatic. This article presents a theoretical and testable model that specifies psychological processes related to the traumagenic dynamics of stigmatization in child and adolescent victims of sexual abuse. The model proposes that sexual abuse leads to shame through the mediation of cognitive attributions about the abuse and shame, in turn, leads to poor adjustment. Three factors, social support, gender, and developmental period are hypothesized to moderate the proposed stigmatization process. Developmental and clinical research supporting the model is reviewed, specific hypotheses are made, and the relevance of developmental psychopathology for future theory and research is discussed. Unless future research elucidates the process and circumstances whereby the experience of sexual abuse leads to poor adjustment, little progress will be made toward developing more effective treatments.

Adaptation, Psychological↗
PubMed1996

Prenatal diagnosis and the pediatric surgeon: the impact of prenatal consultation on perinatal management.

PURPOSE: Pediatric surgeons are increasingly called on by obstetrical colleagues to counsel parents about the implications of a prenatal ultrasound finding. Our understanding of the natural history of many prenatally diagnosed surgical conditions has grown significantly in recent years. Whether prenatal surgical consultation can influence perinatal course had not been investigated. METHODS: During an 21-month period, 12,865 prenatal ultrasound studies were performed on a total of 4,551 patients, and 221 prenatal surgical consultations were obtained through a newly established fetal treatment program at a tertiary care prenatal diagnostic center. To evaluate the impact of prenatal pediatric surgical consultation on perinatal course, the authors reviewed changes in management including termination of pregnancy, in utero intervention, and altered site, mode, or timing of delivery. RESULTS: Two hundred twenty-one fetuses were referred for consultation; their 234 congenital anomalies included genitourinary (36%), thoracic (16%), intraabdominal (14.5%), abdominal wall (10.6%), neurological (9%), skeletal (6%), and head and neck (2.5%) defects; 2.5% had tumors and 2.5% were twin pregnancies. Pregnancy was terminated in 9.5% of cases, because of patient request, chromosomal abnormality, or dismal prognosis. In 3.6%, the decision to terminate was changed as a result of consultation. Site of delivery was changed as a result of consultation in 37% to facilitate postnatal evaluation and initiate immediate treatment. Mode of delivery was changed in 6.8% to prevent dystocia, hemorrhage into a tumor, as in sacrococcygeal teratoma, or to provide an emergency airway, as in cervical teratoma. The timing of delivery was changed in 4.5% to avoid further damage to fetal organs in cases of obstructive uropathy, gastroschisis, sacrococcygeal teratoma with high-output failure, and hydrocephalus. Five percent (11) underwent treatment in utero for fetal hydrothorax, obstructive uropathy, twin-twin transfusion syndrome, or lymphangioma. The overall perinatal mortality rate was 2.5%. CONCLUSION: Prenatal pediatric surgical consultation may have a significant impact on the perinatal management of the fetus with a surgically correctable congenital anomaly. Providing obstetric colleagues and families with valuable insight into the surgical management of anomalies allows fetal intervention when appropriate, and delivery in an appropriate setting, by the safest mode of delivery, and at the gestational age appropriate to minimize effects of the anomaly.

Abortion, Therapeutic↗
PubMed1996

Mammalian 3 alpha-hydroxysteroid dehydrogenases.

Mammalian 3 alpha-hydroxysteroid dehydrogenases (3 alpha-HSDs) regulate steroid hormone levels. For example, hepatic 3 alpha-HSDs inactivate circulating androgens, progestins, and glucocorticoids. In target tissues they regulate access of steroid hormones to steroid hormone receptors. For example, in the prostate 3 alpha-HSD acts as a molecular switch and controls the amount of 5 alpha-dihydrotestosterone that can bind to the androgen receptor, while in the brain 3 alpha-HSD can regulate the amount of tetrahydrosteroids that can alter GABAa receptor function. Molecular cloning indicates that these mammalian 3 alpha-HSDs belong to the aldo-keto reductase superfamily and that they are highly homologous proteins. Using the three-dimensional structure of rat liver 3 alpha-HSD as a template for site-directed mutagenesis, details regarding structure function relationships, including catalysis and cofactor and steroid hormone recognition have been elucidated. These details may be relevant to all mammalian 3 alpha-HSDs.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention.

Left ventricular hypertrophy (LVH) is present in over 70% of patients commencing dialysis. It is an independent risk factor for cardiac death, which is the cause of death in approximately 45% of patients in dialysis. The prevalence of LVH in patients earlier in the course of renal insufficiency is unknown. As part of a prospective longitudinal study evaluating the progression of comorbid diseases in patients with progressive renal disease, we evaluated LVH. In 175 consecutive patients attending a renal insufficiency clinic we obtained technically adequate echocardiograms and estimated left ventricular mass index (LVMI) using two-dimensional targeted M-mode echocardiography. We calculated LVMI using the American Society of Echocardiography cube formula method regressed to anatomic validation. The population consisted of 115 men and 60 women ranging in age from 20 to 82 years (mean age, 51.5 years). The mean creatinine was 403 +/- 207 micro mol/L (+/-SD), representing a creatinine clearance (Ccr) of 25.5 +/- 17 mL/min. Left ventricular hypertrophy was defined as LVMI greater than 131 g/m(2) in men and greater than 100 g/m(2) in women, and was present in 38.9% of the population studied. We demonstrate that the prevalence of LVH increased with progressive renal decline: 26.7% of patients with Ccr greater than 50 mL/min had LVH, 30.8% of those with Ccr between 25 and 49 mL/min had LVH, and 45.2% of patients with severe renal impairment (Ccr <25 L/min) had LVH (P = 0.05). The mean LVMI was significantly different among the three groups (97.5 g/m(2) v 114.4 g/m(2), respectively; P < 0.001). Univariate analyses revealed that age, hemoglobin, systolic blood pressure and Ccr were significantly different between the groups with and without LVH. The logistic regression model confirmed the findings of the univariate analysis: an increase in age of 5 years was associated with an increase of 3% in risk of LVH (P = 0.0094), as was an increase in systolic blood pressure of 5 mm Hg (P = 0.0018). For each 10 g/L decrease in hemoglobin, the risk of LVH increased by 6% (P = 0.0062), and for each 5 mL/min decline in Ccr the risk increased by 3% (P = 0.0168). We demonstrate the high prevalence of LVH in patients with renal insufficiency prior to the need for dialysis, which is associated with severity of renal impairment, and identify two modifiable factors (systolic blood pressure and anemia) as important predictors of LVH. We suggest that future studies should focus on interventions aimed at attenuating the impact of these factors.

Adult↗
PubMed1996

Coronary heart disease mortality, morbidity, and case fatality in five east and west German cities 1985-1989. Acute Myocardial Infarction Register Teams of Augsburg, Bremen, Chemnitz, Erfurt, and Zwickau.

Cardiovascular mortality (CVD; International Classification of Diseases [ICD] 390-458) is higher in East than in West Germany, but the differences in official coronary heart disease mortality (CHD; ICD 410-414) are not so pronounced. The aim of this study was to validate the official mortality statistics based on the five German AMI registers and to analyze whether these mortality differences are due to differences in the attack rates of acute myocardial infarction (AMI) or to differences in the 28-day case fatality rates. This comparison includes the MONICA study cities of Augsburg and Bremen, both in West Germany, as well as the cities of Chemnitz, Erfurt, and Zwickau in East Germany (former the German Democratic Republic). The rates were calculated on the basis of all MONICA cases of definite AMI or coronary death aged 35 to 64 years occurring in the respective study populations between 1985 and 1989. All study populations except women in Augsburg showed higher coronary death rates compared to the rates based on the official cause of death statistics (ICD 410-414), but this difference was significant only for men in Chemnitz. In men there were no significant differences in the register-based coronary death rates between these urban areas (160/100,000 in Zwickau to 170/100,000 in Chemnitz) nor in the AMI attack rates (327/100,000 in Augsburg to 363/100,000 in Chemnitz), and consequently no significant center differences in the overall 28-day case fatality. However, the prehospital case fatality was significantly higher in Erfurt (34%) than in Bremen (27%). There were no significant differences in the AMI attack rates in women as well (60/100,000 in Chemnitz to 70/100,000 in Bremen and Erfurt), but the overall 28-day case fatality showed a clear gradient from the East (61-71%) to the West German cities (48-56%) and therefore also the register-based coronary death rates (38-50/100,000 and 34-38/100,000, respectively). However, the higher 28-day case fatality in women found in the MONICA registers in East compared to West Germany is not reflected in the CHD mortality statistics because of a stronger underestimation of the official mortality rates and in East than in West Germany, in particular in women. Nevertheless, the total mortality rates and in most cases also the CVD mortality rates were in women significantly higher in the East German compared to the West German cities. The East German official preunification CHD mortality data cannot be used for national and international comparisons. The results of the MONICA AMI registers in East and West Germany indicate, furthermore, the need to improve coronary care in women in the eastern part of the country. Nevertheless, because of the relatively high AMI attack rate in both parts of Germany primary prevention must generally be intensified.

Adult↗
PubMed1996

Anaesthetic characteristics and long-term backache after obstetric epidural anaesthesia.

Anaesthetic casenotes of 4700 women who had epidural anaesthesia for deliveries between 1978-1985 were examined to look for associations between various epidural characteristics and subsequently reported long-term backache. The data on long-term backache came from a postal questionnaire sent to the women. The only clear predictor of the occurrence of long-term backache was having experienced backache immediately after the birth whilst still in hospital. There were no relationships between long-term backache and the duration of the epidural or various indicators of the extent of motor or sensory block. Within the range of local anaesthetic concentration levels used in this series, the extent of block did not seem to affect backache, but the effect of minimal motor block with corresponding increased mobility, such as is available with low concentration anaesthetics mixed with opiates, merits further study.

Journal Article↗
PubMed1996

Behavioural changes in people with learning disability and dementia: a descriptive study.

The behaviour of 12 people with mild and more severe learning disability and dementia is described using Past Behavioural History Inventory (PBHI), an instrument devised for the description of behaviour in people of normal intelligence and dementia. The PBHI appears sensitive to behavioural changes. The behavioural changes are described and are similar to those seen in people without a learning disability. Carers were unaware of the behavioural changes associated with dementia. The behavioural changes could be used to assist in the earlier diagnosis and management of dementia in people with learning disability.

Activities of Daily Living↗
PubMed1996

Prognostic factors for functional outcome of total knee replacement: a prospective study.

BACKGROUND: The objective was to investigate whether baseline physical functioning, medical, psychosocial, or demographic variables predict functional outcome in patients undergoing total knee replacement. METHODS: A prospective cohort study was performed between December 1991 and August 1993. Consecutive, unilateral tricompartmental total knee replacement patients aged > or = 55 yr with osteoarthritis, who met criteria, were enrolled and evaluated one month before and 3 months after total knee replacement. The primary outcome measure was the Medical Outcome Study 36 Item Short Form Health Survey (known as the SF36) Physical Functioning Scale score. The outcome evaluator was not involved in patient care. RESULTS: A hierarchical multiple regression analysis was performed to calculate the contribution of baseline variables to TKR outcome. Of the 27% of outcome variance explained by the model, demographic variables accounted for 4%, psychosocial variables (motivation, role functioning-emotional, and social functioning) for 19% (p = .013), medical variables (previous reconstruction, comorbidity, body mass index, bodily pain) for 2%, and baseline physical function for 2%. CONCLUSIONS: Psychosocial variables are significantly related to total knee replacement functional outcome. Assessment of baseline psychological and social functioning may identify a subset of patients at risk for worse outcome. Specific interventions for these patients should be developed and evaluated as components of patient management prior to and after the procedure.

Activities of Daily Living↗
PubMed1996

Effect of prenatal alcohol and cigarette exposure on two- and six-month-old infants' adrenocortical reactivity to stress.

Examined the effect of prenatal alcohol and cigarette exposure on infant adrenocortical reactivity to stress at 2 and 6 months of age. Cortisol response (pre- to poststressor increase) at 2 months was lower for the exposed than nonexposed infants, whereas cortisol response at 6 months did not differ between the exposed and nonexposed infants. The 2-month group difference in cortisol response reflected a higher prestressor cortisol level in the exposed infants.

Adrenal Cortex↗
PubMed1996

Long-term survival after myocardial infarction: relationship with thrombolysis and discharge medication. Results of the Augsburg Myocardial Infarction Follow-up Study 1985 to 1993.

A large number of randomized clinical trials have shown that thrombolysis, long-term treatment with beta-blockers, antiplatelet drugs, and angiotensin converting enzyme inhibitors improve survival after acute myocardial infarction (AMI). However, for calcium channel blockers (nifedipine, diltiazem, and verapamil) there was either no benefit, or positive effects have been reported in subgroups only. Recent studies have raised concern about the safety of this drug class, especially in patients with coronary heart disease. We studied the long-term survival, for a median follow-up time of 4.4 years, of 1197 non-diabetic patients in the population-based AMI registry in Augsburg, Germany, aged 25-74 years, who had survived a first Q wave acute myocardial infarction for at least 28 days. The impact of thrombolysis and prescribed medication at discharge (beta-blockers, antiplatelet drugs, and calcium channel blockers) on long-term survival was analysed using the Cox-Proportional-Hazard model, controlling for age, sex, and concomitant cardiac drug use. Thrombolysis (risk ratio, RR, 0.72; 95% confidence interval, CI, 0.48-1.08), long-term beta-blockade (RR 0.52; 95% CI 0.36-0.74) and antiplatelet drug use (RR 0.69; 95% CI 0.50-0.94) were associated with considerable reductions in total mortality. The use of calcium channel blockers was not associated with a reduction in total mortality (RR 1.23; 95% CI 0.89-1.69). Separate analyses for nifedipine (RR 1.00; 95% CI 0.68-1.48), and diltiazem (RR 1.55; 95% CI 1.04-2.32) showed an increased risk of death associated with the latter. Using patients on beta-blockers only (RR 1.00) as a reference, the prescription of these calcium channel blockers was consistently associated with an increased total mortality (nifedipine, without beta-blockers RR 1.20; 95% CI 1.12-3.57, diltiazem, without beta-blockers RR 2.87; 95% CI 1.75-4.70). These results from an observational study demonstrate a benefit of thrombolysis, beta-adrenergic blockade and antiplatelet drug use on long-term survival in acute myocardial infarction patients. Calcium channel blocker use appears to be associated with an increased risk of death. These data support the need for controlled trials to address this issue specifically.

Adrenergic beta-Antagonists↗
PubMed1996

Risk factors for presenting problems in child psychiatric emergencies.

OBJECTIVE: To determine demographic and school-related risk factors for psychiatric emergencies presented by children in a hospital emergency room serving the majority of an urban community. METHOD: 1,436 consecutive psychiatric emergency room visits for children younger than 16 years of age seen over a 10-year period were broadly classified by presenting problem as exhibiting either suicidal ideation, suicide attempt, oppositional-defiance, or aggression. The strength of association of these classes of presentation with demographic risk factors (age, sex, and minority status) and with the school day (weekday or weekend) and school season (school year or vacation) of presentation were modeled using logistic regression. The capacity of these presenting problems and risk factors to predict whether the child was hospitalized was also assessed. RESULTS: Risk factors additively associated with suicidality included increasing age, being female, and presenting on weekdays and during the school year. Similar risk factors discriminated suicide attempters from suicidal ideators, and racial minority membership contributed additional risk for presenting with a suicide attempt. Risk factors associated with aggressive and oppositional presentation included younger age and male sex. Aggressive children presented relatively more often on weekends, and oppositional children presented more during school vacations. Independent risk factors for hospitalization included a suicidal or aggressive presentation, increasing age, and presentation during the school year. Hospitalization of children at the time of their initial visit protected against suicidality in subsequent presentations of the subset of children who had repeated emergency room visits. CONCLUSIONS: These findings are consistent with previously reported risk factors for suicidal behaviors and externalizing disorders. The distinctive profiles of risk discerned for the different groups of emergency room psychiatric subjects also suggest some degree of specificity for the risk factors associated with each class of presenting problem. They also suggest the importance of home and school environments as being variably either risk or protective factors for these presenting problems. The findings also suggest a role for hospitalization in the prevention of future suicidality.

Adolescent↗
PubMed1996

Hospital care and survival of acute myocardial infarction patients in Minnesota and southern Germany: a comparative study.

BACKGROUND: The hospital care of patients with acute myocardial infarction (AMI) is likely to vary among advanced industrialized countries, but only few studies have systematically documented such differences. Moreover, despite likely differences in medical care, it is not known whether the prognosis of AMI patients differs among countries. METHODS: Using two registries of hospitalized AMI, we compared the characteristics, medical care, and survival through 1 year of patients in Augsburg, South Germany (n = 464) and Minneapolis-St. Paul (the Twin Cities), Minnesota, USA (n = 504). The samples included patients aged 25-74 years who had been treated in a coronary care unit and survived the first 24 h after admission. RESULTS: The two groups of patients did not differ in age distribution, sex ratio, or delay before admission to hospital (70% admitted within 6 h of symptom onset). The risk profile with respect to cardiovascular disease (smoking, hypertension, and diabetes) was more unfavourable among Augsburg patients than it was among Twin Cities patients but Twin Cities patients were more likely (P < 0.05) than Augsburg patients to report a previous myocardial infarction (29 versus 20%), coronary bypass surgery (9 versus 4%), and coronary angioplasty (6 versus 1%). Revascularization procedures were performed more frequently (P < 0.005) during the index hospitalization in the Twin Cities than they were in Augsburg: thrombolytic therapy 38 versus 28%, angioplasty 27 versus 13%, and bypass surgery 9 versus 3%. In contrast, cardiovascular medications, such as beta-blockers and aspirin, were administered more frequently in Augsburg than they were in the Twin Cities. There were substantial differences in duratin of hospital stay between the two sites with a median stay of 22 days for Augsburg patients versus 7 days for Twin Cities patients. However, there were no significant differences in 28-day case-fatality (6% in both) or 1-year survival (89% in Augsburg versus 88% in the Twin Cities, P = 0.70). Likewise, in multivariate analysis, allowing for the effects of age, sex and a history of myocardial infarction, the registry site was predictive neither of 28-day nor of 1-year mortality. CONCLUSION: These data document significant differences in the medical care of AMI patients in Minnesota and Augsburg, which, nonetheless, did not translate into survival differences.

Adult↗
PubMed1996

Paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a phase II trial.

PURPOSE: Studies conducted by the Eastern Cooperative Oncology Group (ECOG) indicate both paclitaxel and carboplatin are associated with an improvement in 1-year survival in patients with stage IV non-small-cell lung cancer (NSCLC). Based on these findings, a phase II trial of these agents in combination was conducted in patients with advanced NSCLC. PATIENTS AND METHODS: Eligibility included previously untreated stage IIIB or IV NSCLC patients with a good performance status (PS). Paclitaxel (135 or 175 mg/m2) was administered by 24-hour infusion on day 1, followed by a 1-hour infusion of carboplatin on day 2 (300 mg/m2 or dosed to an area under the concentration-time curve [AUC] of 6 mg/mL.min). Treatment was repeated every 28 days for a total of six cycles. Hematopoietic growth factors were not routinely used. RESULTS: Among 51 eligible patients, there were no complete and 14 partial responses, for an overall response rate of 27% (95% confidence interval [CI], 17% to 41%). The median progression-free survival time was 23.8 weeks (range, 12.1 to 73.9) and median survival time, 38 weeks. The survival rate at 1 year was 32%. Grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 47% and 3%, respectively, of the 184 treatment cycles administered. The most common nonhematologic toxicities included nausea and emesis, neuropathy, and arthralgia/myalgia. CONCLUSION: Paclitaxel plus carboplatin is a moderately active regimen in patients with advanced NSCLC and warrants comparison with existing cisplatin-based regimens in a prospective randomized trial. The toxicities of this regimen are well tolerated in patients with a good PS.

Adult↗
PubMed1996

Characteristics of pregnant substance abusers in two cities in the northeast.

This study examined the drug use patterns of pregnant women in two inner city sites, selected to overrepresent cocaine users. Women who used cocaine were much more likely to have used some combination of cigarettes, alcohol, and marijuana in addition to cocaine during pregnancy. There was little difference in the patterns of drug use in the two study sites, Trenton, New Jersey, and northwestern Philadelphia. A number of demographic and lifestyle variables of cocaine users, soft drug users (cigarettes, alcohol, and/or marijuana), and abstainers were compared. The cocaine-using group was significantly older and had more children, had less stable and more isolated living situations, was less likely to be employed and more likely to be receiving public assistance during pregnancy, and was more likely to have a higher drug- and alcohol-using social environment and family history than soft drug users or abstainers. Of significance was that many of the high-risk lifestyle factors exhibited by cocaine users were also seen, albeit to a lesser extent, among the soft drug users. These findings have implications for the timing of intervention strategies that would be most effective.

Adult↗
PubMed1996

Differences in pride and shame in maltreated and nonmaltreated preschoolers.

This study examined the expression of shame and pride in maltreated and nonmaltreated preschool children. 84 4-5-year-old children and their mothers participated in the study: 42 had a history of child maltreatment and 42 served as matched controls. Children were presented with easy and difficult tasks and their emotional responses of shame and pride were observed. No shame was shown when subjects succeeded on the tasks and no pride was shown when they failed. Maltreating mothers offered more negative feedback, particularly to their daughters, than nonmaltreating mothers. Maltreated girls showed more shame when they failed and less pride when they succeeded than nonmaltreated girls. The relation between differential socialization practices and the self-conscious emotions is explored as it relates to observed gender differences in emotionality and self-concept.

Affect↗