Commercial managed care.
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Biomedical subjects
Publications and source records attributed to S Reynolds.
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We investigated the relative effectiveness of four differentiation-inducing chemicals to induce a more normal or benign phenotype in the human colon cancer cell lines Moser and HT29. The differentiation-inducing capability of all-trans retinoic acid (ATRA), difluoromethylornithine (DFMO), sodium butyrate (NaB) and sodium suramin (NaS) was evaluated in terms of the efficacy of these chemicals in inhibiting cellular proliferation, growth in soft agarose, invasion of matrigel and induction of morphological alteration. The relative ability of these chemicals to induce production of the differentiation-related molecules fibronectin and carcinoembryonic antigen was also determined. Overall, ATRA was found to be the most effective chemical in inducing differentiation as measured by these parameters. The Moser cells were more susceptible to differentiation induction by comparison with the HT29 cells. Both similarities and differences in the cellular responses to DFMO, NaB and NaS were also observed for the Moser and HT29 cells. The differences in cellular responses to these chemicals may be due to different phenotypic properties of these two cell lines and different mechanisms of action of these chemicals.
BACKGROUND: In the development of an antimelanoma vaccine, a critical factor is the identification of antigens that induce a strong immune response in humans and that are expressed by melanoma cells in vivo. The aim of this study was to identify candidate antigens for such vaccine. METHODS: Sixty-nine patients with surgically resected melanomas (American Joint Commission on Cancer [AJCC] stage III) were immunized with a polyvalent vaccine containing multiple melanoma antigens. Antimelanoma antibodies generated in the patients' sera were used as probes to identify the melanoma antigens that are immunogenic in humans and that are expressed on the tumor tissue in vivo. Such responses were determined by an immunoblotting assay that employed an antigen source prepared from membrane fractions of freshly excised melanoma tissue. RESULTS AND CONCLUSIONS: Vaccine treatment stimulated antibody responses in 35 (51%; 95% confidence interval [CI] = 39%-63%) of 69 sequentially enrolled patients. The antibodies were directed to one or more antigens with molecular masses of 45, 59, 68, 79, 89, 95, and/or 110 kd. The most immunogenic antigens were p110 and p68, which induced responses in 33% (95% CI = 22%-44%) and 25% (95% CI = 15%-35%) of patients, respectively. Both antigens were commonly expressed on different melanomas, but they were absent on autologous normal tissue and on an unrelated allogeneic tumor. All the above antigens are attractive candidates for vaccine construction.
Analyses of a nationally representative sample who completed a list recall task (weighted n = 6,446) and 2 mental status tasks (weighted n = 6,646) were conducted to determine whether specific medical conditions such as high blood pressure and diabetes as well as general health ratings predict cognitive performance in adults aged 70 to 103. Presence of stroke and poorer health ratings predicted poorer performance on the 3 tasks. Presence of diabetes predicted poorer performance on recall and 1 mental status task. Age interacted with medical conditions including high blood pressure and diabetes in predicting mental status, with condition-related deficits confined to the younger end of the age continuum. Global health ratings interacted with age, with poorer ratings associated with worse mental status in the younger participants. Findings suggest that stroke and diabetes are associated with cognitive deficits. Some deficits are more pronounced in younger old adults with high blood pressure and poorer health ratings.
OBJECTIVE: To identify psychological factors associated with chronic recurrent vaginal candidiasis. DESIGN: A cross sectional exploratory study of women with chronic, recurrent vaginal candidiasis. PATIENTS: 28 women found culture positive and treated for vaginal candidiasis by a clinic physician at least twice within the past 6 months. All women reported that they had experienced vaginal thrush six or more times within 1 year. A comparison group comprised 16 women with no history of recurrent vaginal candidiasis, of similar age range, and recruited from a women's family planning service. METHODS: Both groups were compared on demographic criteria, sexual health histories, mental health, and psychological health characteristics. A purpose designed structured interview was administered alongside a battery of standardised psychometric instruments measuring mood, satisfaction with life, self esteem, and perceived stress. RESULTS: The two groups showed considerable similarities, with no significant differences in demographic characteristics and most sexual health issues. However, women with recurrent vaginal candidiasis were significantly more likely to suffer clinical depression, to be less satisfied with life, to have poorer self esteem, and to perceive their lives as more stressful. Additionally, women with recurrent vaginal candidiasis reported that their candidiasis seriously interfered with their sexual and emotional relationships. CONCLUSIONS: Overall, this study identified many areas of psychological morbidity associated with chronic vaginal candidiasis, and indicates that development of appropriate psychological treatment initiatives in this area is long overdue.
Assessed parent attributions for child behavior using open-ended questions. Sixty-one parents of children with attention deficit hyperactivity disorder (ADHD) and 49 parents of nonproblem children participated. An open-ended, thought-listing question asked following child behavior indicated that parents spontaneously offer causal attributions for their children's behavior. Responses to a second open-ended question asking specifically for attributions for the child behavior indicated that both groups of parents attributed prosocial (PRO) child behaviors more than problem behaviors to internal, controllable, and stable causes or to the external situation and attributed problem behaviors most often to uncontrollable and unstable causes within the child or to factors within the parent. Compared with parents of nonproblem children, parents of children with ADHD were less likely to see themselves as the cause of child behavior and were more likely to mention medication. Analyses indicated that, although attributions elicited by rating scales were related to attributions provided in an open-ended format, each method provided unique information.
As part of a recent animal facility refurbishment, a cubicle containment system was designed to increase the amount of experimental space and also provide containment facilities to support the holding and use of specialized animal models. In order to achieve this, a series of computational fluid dynamic (CFD) studies was undertaken to evaluate the effects of different airflows and in order to optimize ventilation, a variety of exhaust/supply arrangements and animal loads was employed. These studies showed that air delivered via two, opposed, low level ducts, at a rate of 20 air changes per hour and exhausted high in the cubicle above the rack, was the optimal configuration resulting in minimal turbulence, stagnation and entrainment.
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Liver tumors were induced in infant male B6C3F1 mice by preweaning administration of furan, either as a single dose of 400 mg/kg body weight or six doses of 200 mg/kg body weight. Six doses of 200 mg/kg furan resulted in an increased incidence and multiplicity of liver tumors relative to the multiple-dose vehicle control group and the single-dose furan group. In the single-dose group, there was an increase in overall tumor multiplicity but not prevalence of liver tumors. After polymerase chain reaction amplification of isolated DNA, slot-blot oligonucleotide hybridization was used to screen for mutations at known mutational hot-spots in the first three exons of Ha-ras-1 (Hras1). The relative frequency of Hras1 activation was 82% in the 28 tumors analyzed from the single-dose group and 32% in the 28 tumors analyzed from the multiple-dose group. The lack of histomorphologic evidence of chronic cytotoxicity in the livers and the pattern of Hras1 activation suggest that a genotoxic mode of action is responsible for at least part of the hepatocarcinogenicity of furan in B6C3F1 mice. These findings confirm previously documented hepatocarcinogenicity of furan in B6C3F1 mice and provide evidence that carcinogen dose may influence the frequency of Hras1 activation in mouse liver tumors.
This article describes a comparative stress management intervention study. The impacts and outcomes of an individual level intervention (counseling) and an organizational level intervention (increasing employees' participation and control) are compared. The results suggest that counseling has clear benefits for employees' psychological well-being and that the organizational intervention does not. Neither intervention had any impact on perceptions of work characteristics, physical symptoms, or absenteeism. It is suggested that the causal relationship between the work environment and psychological distress have not been demonstrated and that techniques for bringing about change in complex organizations are poorly developed. For these reasons, the strategy of changing work conditions cannot, at present, be expected to improve the psychological states of employees. Thus, whereas organizational interventions that aim to prevent psychological distress may be "better" in ethical and moral terms, individual interventions that aim to treat existing psychological problems or help individual employees manage difficult working conditions appear to be "better" in terms of efficacy and efficiency.
BACKGROUND: Although IgE has been shown to play a role in the expulsion of intestinal parasites in experimental animals, its overall contribution to host defense in humans remains a subject of controversy. In order to clarify the potential role of IgE in host defense, we have studied the clinical characteristics of patient with serum IgE levels of < 2.5 IU/mL, using patients with normal or elevated IgE levels as controls. OBJECTIVE: To determine the clinical characteristics of IgE deficiency. METHODS: Serum IgE levels were measured in 420 adult patients seen in our Allergy-Immunology Clinic over a period extending from January, 1990 to March, 1996. All subjects were examined by one of the authors (JKS or GHK) using a standardized history and physical examination form. Patients with IgE levels of < 2.5 IU/mL also had measurements of serum IgG, IgG subclasses, IgA and IgM. All IgE-deficient patients and 73% of those with normal to elevated IgE levels underwent RAST and/or skin testing for Type I hypersensitivity, and, where clinically indicated, had serum drawn for autoimmune serologic profiles. Infectious complications were documented by culture. The American Rheumatology Association criteria were used to establish a diagnosis of autoimmune disease. RESULTS: Forty-four patients were found to have IgE levels of < 2.5 IU/mL; 57% of these had depressed serum levels of other immunoglobulins, and 43% had isolated IgE deficiencies. Respiratory symptoms were equally common in IgE-deficient patients and in patients with normal to elevated IgE levels. IgE-deficient patients, however, were more likely to complain of arthralgias (P < .0001), chronic fatigue (P < .0001), and symptoms suggestive of airway infection (P = .0119). Compared with controls, patients with IgE deficiency had a higher prevalence of autoimmune disease (46% versus 15%) (P < .0001) and nonallergic reactive airway disease (73% versus 20%) (P < .0001). There was no difference in the prevalence of these disease in patients with selective IgE deficiency as compared with those with IgE deficiency complicated by deficits in other immunoglobulin classes. IgE-deficient patients with multiple immunoglobulin deficiencies, however, were more likely to have serious infection involving both the upper and lower respiratory tract than those with isolated IgE deficiency. CONCLUSIONS: IgE-deficient patients have an increased prevalence of multiple immunoglobulin deficits, autoimmune disease, and nonallergic reactive airway disease when compared with a clinic population of patients with normal to elevated IgE levels.
There is extensive reprogramming of the ATPase regulators of the 26S proteasome before the programmed elimination of the abdominal intersegmental muscles (ISM) after eclosion in Manduca sexta [1]. This extensive ATPase reprogramming only occurs in ISM which are destined to die and not in flight muscle (FM). The MS73 ATPase also increases in the proleg retractor muscles which die at a developmentally different stage to ISM. The non-ATPase regulator S5a shows a similar increase to the ATPase regulators. We have cloned the Manduca SUG2 ATPase and shown that this ATPase is a component of the 26S proteasome. This ATPase shows a similar increase in concentration to the other ATPases in 26S proteasomes before muscle death. The SUG2 ATPase is also associated with other smaller complexes besides the 26S proteasome which act as activators of the 26S proteasome. Finally, in a yeast two-hybrid genetic screen we have identified a protein in human brain which interacts with the MS73 ATPase (and human S6). The interacting protein contains 6 ankyrin repeats and is co-immunoprecipitated with anti-MS73 antiserum after in vitro transcription/translation. The ankyrin repeat protein may interact with the MS73 ATPase as part of the substrate recognition process by the 26S proteasome. Many proteins degraded by the 26S proteasome contain ankyrin repeats, e.g. IkB and some cyclins: binding through ankyrin repeats to an ATPase regulator may complement protein ubiquitination and S5a binding as recognition signals by the 26S proteasome.
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OBJECTIVE: To evaluate the risk of professional liability to house staff within a pediatric hospital setting. METHODS: A retrospective study describing the patients, allegations, areas within the hospital where complaints originated, and outcome of all malpractice suits involving residents from 1968 through 1992 at a large pediatric teaching hospital. RESULTS: There were 49 malpractice cases involving residents with or without physicians from 886,000 hospital admissions or emergency department visits over the past 20 years (5/5/100,000 patient encounters) compared with 185 malpractice cases involving attending physicians alone at the hospital (20.5/100,000 patient encounters). The incidence of cases originating from the emergency department was 1.8/100,000 compared with 13.9/100,000 from all other areas of the hospital combined. Fifty-two percent of patients had preexisting chronic medical problems. Forty-nine percent of cases were settled out of court, 2% went to trial with a decision in favor of the plaintiff, 22% were dismissed, and 27% of cases remained open as of June 1993. The mean award on behalf of patients from 1968 through 1979 was $580,000 per case with a median payment of $163,000. The mean award from 1980 through 1992 was $760,000 per case with a median payment of $275,000. CONCLUSIONS: Malpractice risk is serious concern for residents and a financial liability for hospitals. Resident physicians in a pediatric teaching hospital were named in 26% of malpractice cases. Most cases were settled or were dismissed and did not go to trial. Risk management training during residency may reduce resident involvement, and by extension, the teaching institution's involvement in malpractice litigation.
Following the suggestion that therapeutic change is accelerated in time-limited psychotherapy, this study investigated the across-session patterns of session impact in the treatments of 117 depressed clients who were randomly allocated to 8 or 16 sessions of cognitive-behavioral (CB) or psychodynamic-interpersonal (PI) therapy. After each session, all clients completed the Session Evaluation Questionnaire and 75 of the clients completed the Session Impacts Scale. Session ratings indicated that sessions were perceived increasingly positively on most impact dimensions (e.g., session depth and smoothness, relationship with the therapist, feelings of understanding and problem solving, postsession positive mood) as treatment progressed. Early in treatment, PI therapy sessions were less smooth (i.e., more tense and uncomfortable) and less focused on problem solving, but PI sessions changed more rapidly than CB sessions on these dimensions, so that later in treatment, sessions of both treatments were equivalently positive. In both treatments, the trend toward more positive sessions was more rapid (i.e., the across-session slope was steeper) in 8-session treatments than in 16-session treatments. Such accelerated changes in session impact may reflect the suggested acceleration of therapeutic change associated with shorter time limits.
Criteria for reliable and clinically significant improvement were applied to standard and individually tailored outcome measures data from 212 depressed clients who had been randomly assigned to receive either 8 or 16 sessions of time-limiting psychotherapy. The data were used to address 2 questions: (a) Is the dose-effect curve for psychological symptoms negatively accelerated? and (b) is there a differential rate of response for acute, chronic, and characterological/interpersonal components of depression? The results supported the differential rate of response of different components of depression and suggested qualifications to the acute, chronic, and characterological/interpersonal components and evidence that both supported and qualified previous suggestions that the dose-effect curve is negatively accelerated.
The objective of this study was to describe the use of a pediatric emergency department (PED) by children with chronic conditions. The study design was retrospective and descriptive in an urban tertiary care pediatric hospital setting. We reviewed 8561 visits to a PED over a three-month time period. Two thousand twenty-four (24%) of the visits were by children with one or more chronic conditions. There were no interventions. The mean age of the patients was 4.9 years, and 61% were male. Thirty-one percent of the patients sought care between 8 AM and 5 PM Monday through Friday. Five subspecialty areas accounted for 86% of the chronic conditions seen: asthma (43%), neurology (15%), hematology/oncology (14%), neurosurgery (10%), and cardiology (4%). Twenty-eight percent of the chronically ill patients were admitted as compared to 11% of the nonchronically ill patients (P < 0.001). One percent of the chronically ill patients were admitted to the intensive care unit as compared to 0.03% of the nonchronically ill patients (P < 0.0001). It was concluded that children with chronic conditions account for one-quarter of all PED visits. Sixty-nine percent of those visits were made during evening/ nighttime hours or on the weekend. A relatively large percentage of these children were admitted. The pediatric emergency physicians provide an important service to both the children with chronic conditions and the subspecialists who care for them. PEDs may need to refine emergency department systems to serve this group of patients as efficiently and effectively as possible.