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Biomedical subjects

M Lewis

Publications and source records attributed to M Lewis.

At least 37 records · Page 2Linked to original sources
PubMed1997

Multidisciplinary predialysis programs: quantification and limitations of their impact on patient outcomes in two Canadian settings.

A 1993 National Institutes of Health Consensus statement stressed the importance of early medical intervention in predialysis populations. Given the need for evidence-based practice, we report the outcomes of predialysis programs in two major Canadian cities. The purpose of this report was to determine whether the institution of a multidisciplinary predialysis program is of benefit to patients, and to analyze those factors that are important in actualizing those benefits. Data from two different studies is presented: (1) a prospective, nonrandomized cohort study comparing patients who were or were not exposed to an ongoing multidisciplinary predialysis team (St Paul's Hospital) and (2) a retrospective review of outcomes before and after the institution of a predialysis program (The Toronto Hospital). Although created independently in major academic centers in Canada, the programs both aimed to reduce urgent dialysis starts, improve preparedness for dialysis, and improve resource utilization. The Vancouver study was able to demonstrate significantly fewer urgent dialysis starts (13% v 35%; P < 0.05), more outpatient training (76% v 43%; P < 0.05), and less hospital days in the first month of dialysis (6.5 days v 13.5 days; P < 0.05). Cost savings of the program patients in 1993 are conservatively estimated to be $173,000 (Canadian dollars) or over $4,000 per patient. The Toronto study demonstrated success in predialysis access creation (86.3% of patients), but could not realize any benefit in terms of elective dialysis initiation due to well-documented hemodialysis resource constraints. We conclude that an approach to predialysis patients involving a multidisciplinary team can have a positive impact on quantitative outcomes, but essential elements for success include (1) early referral to a nephrology center, (2) adequate resources for dedicated predialysis program staff and infrastructure, and (3) available resources for patients with end-stage renal disease (ESRD) (dialysis stations). In times of economic constraints, objective data are necessary to justify resource-intensive proactive programs for patients with ESRD. Future studies should confirm and extend our observations so that optimum and cost-effective care for patients approaching ESRD is uniformly available.

Canada↗
PubMed1997

Lac repressor-operator complex.

For many years the lac operon of Escherichia coli has been the paradigm for gene regulation. Recently, the structures of the lac repressor core bound to isopropyl-beta-D-1-thiogalactoside (IPTG), the intact apo lac repressor, the intact lac repressor complexes with IPTG and a 21-base-pair symmetric operator, and the refined headpiece of the repressor have been determined. These structures have provided a framework for understanding a wealth of biochemical and genetic information. An analysis of these structures, as well as a description of their function and a comparison to homologous proteins, is now possible.

Allosteric Regulation↗
PubMed1997

Lac repressor genetic map in real space.

Here, we present a graphic display of the phenotypes of more than 4000 single amino acid substitution mutations on the three-dimensional structure of the lac repressor tetramer bound to DNA. The genetic data and the X-ray diffraction studies contribute to define an allosteric mechanism and yield a visual demonstration of the importance of core or buried residues in protein structure.

Allosteric Site↗
PubMed1997

A phase I-II study of high-dose melphalan, mitoxantrone and carboplatin with peripheral blood stem cell support in patients with advanced ovarian or breast carcinoma.

The purpose of this study was to develop a high-dose chemotherapy (HDC) and peripheral blood stem cell (PBSC) regimen for treatment of patients with ovarian carcinoma that could be administered in an outpatient setting. Fourteen patients with advanced ovarian (n = 9) or breast (n = 5) carcinoma, who had failed conventional chemotherapy, were entered into a dose-escalation trial to determine the maximum tolerated dose (MTD) of carboplatin that could be administered with fixed doses of melphalan (160 mg/m2) and mitoxantrone (50 mg/m2). Twenty-five additional patients were included in a phase II trial at the MTD. Two of two patients had grade 4 severe regimen-related toxicities (RRT), one fatal, at a dose level of 1600 mg/m2. Two of 29 patients (6.9%) treated at the MTD (carboplatin, 1400 mg/m2) died of RRT. All three patients who died of toxicity had a calculated AUC for carboplatin >30 mg/ml/min. Thirty-one patients with ovarian cancer who had failed chemotherapy were treated, 24 at the MTD. Fourteen of 20 patients (70%) with ovarian carcinoma with evaluable disease achieved a CR and seven (35%) are alive disease-free a median of 20 months (range, 7-26). Five of seven patients with ovarian cancer who had failed chemotherapy but were rendered clinically disease-free following surgery survive without progression a median of 13 months (range, 9-19). Eight of 16 (50%) platinum-resistant and 4/12 (33%) platinum-sensitive patients with ovarian cancer survive disease-free.

Adult↗
PubMed1997

Decision making by elderly patients with cancer and their caregivers.

This study explored the scope of decisions encountered by elderly cancer patients and/or their family caregivers, and the types of decision-making assistance requested and required within one practice setting. Semistructured interviews were conducted with five cancer center nurse coordinators (CCNCs). The CCNCs were interviewed weekly for 16 weeks to identify decision-making topics addressed, assistance requested, and perceptions of assistance required during telephone conversations. The CCNCs' reports of 41 telephone conversations revealed 44 specific decision-making topics. Content analysis uncovered 11 categories: symptom management, use of chemotherapy, ancillary choices selection of a medical provider, planning for end-of-life care, alternative therapy, vacation planning, weekend-pass planning, discharge planning, family survivor issues, and involvement of adult children in the elder's care. Elderly patients and/or their family caregivers requested information and assistance with making decisions. CCNCs perceived that callers also needed information clarification, reassurance about their decisions, a listener, permission to change the treatment regimen, and help with communication among health professionals, the elderly patient, and the family.

Adult↗
PubMed1997

Role of growth hormone status in the outcome of total knee replacement.

The objective was to assess whether the aging related, variable decline in growth hormone influences total knee replacement outcome. In this prospective cohort study, consecutive patients who underwent unilateral total knee replacement and who met criteria were enrolled from the practice of 1 orthopaedic surgeon at a university hospital. Participants were evaluated 1 month before and 3 months after total knee replacement. Evaluators were not involved in patient care. The primary outcome measure was the Medical Outcome Study 36-item Short Form Health Survey Physical Functioning Scale score 3 months after total knee replacement. In a multiple regression analysis performed to assess the influence of growth hormone status, controlling for social support, body mass index, gender, previous reconstruction, mental health, motivation, and baseline physical functioning, only mental health contributed significantly to outcome. Mental health accounted for 18% of outcome variance. Growth hormone levels did not predict functional status after total knee replacement. Psychological status contributes significantly to total knee replacement physical functional outcome.

Age Factors↗
PubMed1997

The impact of childhood non-malignant life-threatening illness on parents: gender differences and predictors of parental adjustment.

Mental health, family functioning, effects on employment and relationships, coping style, and perceptions of prognosis were assessed in 93 mothers and 78 fathers of children with a life-threatening non-malignant condition. Results indicated high levels of psychological distress, significant effects upon employment and relationships, and a family environment characterised by low expressiveness, cohesion, and high conflict. Differences between mothers and fathers were found on a number of variables. Length of time since diagnosis, level of family cohesion, and sex of parent significantly predicted parental mental health.

Adaptation, Psychological↗
PubMed1997

Role of epinephrine and norepinephrine in the metabolic response to stress hormone infusion in the conscious dog.

The role of epinephrine and norepinephrine in contributing to the alterations in hepatic glucose metabolism during a 70-h stress hormone infusion (SHI) was investigated in four groups of chronically catheterized (20-h-fasted) conscious dogs. SHI increased glucagon (approximately 5-fold), epinephrine (approximately 10-fold), norepinephrine (approximately 10-fold), and cortisol (approximately 6-fold) levels. Dogs received either all the hormones (SHI; n = 5), all the hormones except epinephrine (SHI-Epi; n = 6), or all the hormones except norepinephrine (SHI-NE; n = 6). In addition, six dogs received saline only (Sal). Glucose production (Ra) and gluconeogenesis were assessed after a 70-h hormone or saline infusion with the use of tracer ([3-(3)H]glucose and [U-(14)C]alanine) and arteriovenous difference techniques. SHI increased glucose levels (108 +/- 2 vs. 189 +/- 10 mg/dl) and Ra (2.6 +/- 0.2 vs. 4.1 +/- 0.3 mg x kg(-1) x min(-1)) compared with Sal. The absence of an increase in epinephrine markedly attenuated these changes (glucose and Ra were 140 +/- 6 mg/dl and 2.7 +/- 0.4 mg x kg(-1) x min(-1), respectively). Only 25% of the blunted rise in Ra could be accounted for by an attenuation of the rise in net hepatic gluconeogenic precursor uptake (0.9 +/- 0.1, 1.5 +/- 0.1, and 1.1 +/- 0.2 mg x kg(-1) x min(-1) for Sal, SHI, and SHI-Epi, respectively). The absence of an increase in norepinephrine did not blunt the rise in arterial glucose levels, Ra, or net hepatic gluconeogenic precursor uptake (they rose to 195 +/- 21 mg/dl, 3.7 +/- 0.5 mg x kg(-1) x min(-1), and 1.7 +/- 0.2 mg x kg(-1) min(-1), respectively). In summary, during chronic SHI, the rise in epinephrine exerts potent stimulatory effects on glucose production principally by enhancing hepatic glycogenolysis, although the rise in circulating norepinephrine has minimal effects.

Animals↗
PubMed1997

Decreased Cu,Zn-SOD activity in asthmatic airway epithelium: correction by inhaled corticosteroid in vivo.

To investigate the antioxidant response of respiratory epithelium to the chronic airway inflammation in asthma, the major intracellular antioxidants [copper and zinc-containing superoxide dismutase (Cu,Zn-SOD) and manganese-containing SOD (Mn-SOD), catalase, and glutathione peroxidase] were quantitated in bronchial epithelial cells of healthy control and asthmatic individuals. Although catalase and glutathione peroxidase in bronchial epithelium of asthmatics were similar to control SOD activity in asthmatics not on inhaled corticosteroid (-CS) was lower than asthmatics on inhaled corticosteroid (+CS) and controls. Investigation of Mn-SOD and Cu,Zn-SOD activities revealed that the lower SOD activity in asthmatics -CS was because of decreased Cu,Zn-SOD activity. However, Mn-SOD and Cu,Zn-SOD mRNA and protein levels were similar among asthmatics -CS, asthmatics +CS, and controls. Importantly, Cu,Zn-SOD specific activity in asthmatics -CS was decreased in comparison with control and asthmatics +CS. Furthermore, in paired comparisons of asthmatics -CS and +CS, inhaled corticosteroids resulted in normalization of bronchial epithelial Cu,Zn-SOD specific activity. These findings suggest loss of Cu,Zn-SOD activity in asthma is related to inflammation, perhaps through oxidant inactivation of Cu,Zn-SOD protein.

Administration, Inhalation↗
PubMed1997

Objective documentation of child abuse and dissociation in 12 murderers with dissociative identity disorder.

OBJECTIVE: The skepticism regarding the existence of dissociative identity disorder as well as the abuse that engenders it persists for lack of objective documentation. This is doubly so for the disorder in murderers because of issues of suspected malingering. This article presents objective verification of both dissociative symptoms and severe abuse during childhood in a series of adult murderers with dissociative identity disorder. METHOD: This study consisted of a review of the clinical records of 11 men and one woman with DSM-IV-defined dissociative identity disorder who had committed murder. Data were gathered from medical, psychiatric, social service, school, military, and prison records and from records of interviews with subjects' family members and others. Handwriting samples were also examined. Data were analyzed qualitatively. RESULTS: Signs and symptoms of dissociative identity disorder in childhood and adulthood were corroborated independently and from several sources in all 12 cases; objective evidence of severe abuse was obtained in 11 cases. The subjects had amnesia for most of the abuse and underreported it. Marked changes in writing style and/or signatures were documented in 10 cases. CONCLUSIONS: This study establishes, once and for all, the linkage between early severe abuse and dissociative identity disorder. Further, the data demonstrate that the disorder can be distinguished from malingering and from other disorders. The study shows that it is possible, with great effort, to obtain objective evidence of both the symptoms of dissociative identity disorder and the abuse that engenders it.

Adult↗
PubMed1997

Social indicators and the prediction of psychiatric admission in different diagnostic groups.

BACKGROUND: Recent findings indicate that the established association between social indicators of deprivation and psychiatric admission rates may not hold across all diagnoses. METHOD: Admission rates in individuals aged 16-64 years for 71 electoral wards in North Staffordshire were calculated for six diagnostic groups using data from the Korner Episode System for 1987-1993. These were correlated with selected individual census variables, Townsend and Jarman indices. The ability of regression models to predict admission rates was tested. RESULTS: The strongest correlations were found for total admissions (r 0.44-0.79). Strong correlations were found for neurotic disorders/depression (r 0.29-0.62), schizophrenia (r 0.24-0.59), all non-psychotic disorders combined (r 0.41-0.71) and all psychotic disorders combined (r 0.33-0.67). Predicted admission rates for total admissions, psychotic and non-psychotic admissions using regression models showed strong positive correlations with observed admission rates. CONCLUSIONS: The strong correlations between social indicators of deprivation and total psychotic admission rates are consistent with the results of previous studies. The strong associations between social indicators and admissions for non-psychotic disorders is contrary to previous findings and may be partly explained by the relatively high admission rates for neurotic disorders.

Adolescent↗
PubMed1997

Increasing car seat use for toddlers from inner-city families.

OBJECTIVES: The purpose of this project was to increase toddler car seat use in low-income minority families. METHODS: Families from Newark, NJ, were divided into two study groups. Both groups were given car seats; one group also received education regarding car restraint use. Observations were made of car seat use before car seat distribution, immediately after distribution, 4 to 5 months later, and 1 year later. RESULTS: Car seat use increased markedly immediately after distribution and remained high 1 year later, regardless of education. CONCLUSIONS: These results indicate that distributing car seats results in long-term use among a currently low-use population.

Child, Preschool↗
PubMed1997

Dengue haemorrhagic fever/dengue shock syndrome. An unwelcome arrival in Trinidad.

This is the first report of dengue haemorrhagic fever and dengue shock syndrome in Trinidad. Dengue infection was confirmed serologically or by viral isolation in five patients, aged 15 to 53 years, who presented with fever, thrombocytopenia and haemoconcentration. Three patients developed dengue shock syndrome, which was fatal; although there was no haemorrhagic tendency among these patients, bleeding occurred shortly before death in one of them. Two patients who had dengue haemorrhagic fever survived. The co-circulation of dengue virus serotypes 1, 2, and 4 in the Caribbean facilitates the development of dengue shock syndrome (DSS) or dengue haemorrhagic fever (DHF). Clinicians should therefore be aware of their clinical features, laboratory diagnosis and clinical management. Appropriate public health interventions and improved surveillance should be implemented to reduce the risk of DHF/DSS associated mortality in Trinidad and Tobago.

Adolescent↗
PubMed1997

Stress reactivity and self-recognition.

This study examined longitudinally whether early differences in reactivity to stress are related to self-recognition at 18 months of age. Adrenocortical and behavioral stress responses to routine inoculation at 2 and 4 months and at 6 and 18 months were obtained. Previous findings indicated a developmental shift in adrenocortical functioning by 6 months of age that included the emergence of stable individual differences in cortisol response from this point in development. Self-recognition was related to a greater cortisol response and less rapid quieting at 6 to 18 months, whereas 2- to 4-month cortisol and quieting responses did not differentiate self-recognizers and non-self-recognizers. These findings indicate a role for temperament differences in facilitating the emergence of self-recognition.

Adrenal Cortex↗
PubMed1997

Systematic reviews of bed rest and advice to stay active for acute low back pain.

BACKGROUND: In the United Kingdom (UK), 9% of adults consult their doctor annually with back pain. The treatment recommendations are based on orthopaedic teaching, but the current management is causing increasing dissatisfaction. Many general practitioners (GPs) are confused about what constitutes effective advice. AIM: To review all randomized controlled trials of bed rest and of medical advice to stay active for acute back pain. METHOD: A systematic review based on a search of MEDLINE and EMBASE from 1966 to April 1996 with complete citation tracking for randomized controlled trials of bed rest or medical advice to stay active and continue ordinary daily activities. The inclusion criteria were: primary care setting, patients with low back pain of up to 3 months duration, and patient-centred outcomes (rate of recovery from the acute attack, relief of pain, restoration of function, satisfaction with treatment, days off work and return to work, development of chronic pain and disability, recurrent attacks, and further health care use). RESULTS: Ten trials of bed rest and eight trials of advice to stay active were identified. Consistent findings showed that bed rest is not an effective treatment for acute low back pain but may delay recovery. Advice to stay active and to continue ordinary activities results in a faster return to work, less chronic disability, and fewer recurrent problems. CONCLUSION: A simple but fundamental change from the traditional prescription of bed rest to positive advice about staying active could improve clinical outcomes and reduce the personal and social impact of back pain.

Acute Disease↗
PubMed1996

Apoptosis correlates with immune activation in intestinal lymphoid tissue from macaques acutely infected by a highly enteropathic simian immunodeficiency virus, SIVsmmPBj14.

The PBj14 isolate of simian immunodeficiency virus, SIVsmmPBj14, induces an acutely lethal disease in experimentally inoculated pigtailed macaques, that is characterized by severe enteropathy and extensive immune activation, particularly within gut-associated lymphoid tissue (GALT). Experiments were conducted to determine whether virally induced immune activation might promote the induction of apoptosis in GALT during acute SIVsmmPBj14 infection. In situ labeling studies revealed a significant increase in the number of apoptotic cells within GALT from macaques with acute SIVsmmPBj14 infection, compared to (i) other tissues from the same animals, (ii) GALT from virus-negative animals, or (iii) GALT from macaques that were sacrificed soon after infection with SIVmac239, which does not cause acutely lethal enteropathy. These findings were confirmed by biochemical assays of DNA fragmentation, using DNA laddering and ELISA techniques. Immunostaining experiments revealed a strong positive correlation between the extent of apoptosis and the degree of immune activation, as assessed either by the number of cells which contained nuclear (activated) RelA or by the number of cells immunoreactive for CD25, a T-cell activation marker. Additional analyses of SIV antigen expression revealed that the majority of the apoptotic cells were not productively infected by SIV (i.e., that they were bystander cells). Taken together, these findings support the hypothesis that SIVsmmPBj14 efficiently induces immune activation and that this results in extensive apoptosis within gut-associated lymphoid tissue during acute viral infection.

Animals↗