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Biomedical subjects

M Singer

Publications and source records attributed to M Singer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Commentary. Balancing sedation and analgesia in the critically ill.

The authors have presented a template for a systematic approach to comforting critically ill patients that can be modified to suit institutional preferences. In this algorithm, the cause of patient discomfort is sought with the priority given to pain and then to anxiety. Special attention is directed to the identification of correctable causes of pain and anxiety with application of nonpharmacologic techniques or medications to control patient discomfort. This step is followed by subsequent reassessment of the need for sedation or anxiolysis and titration or discontinuation of therapy as able. The benefits of protocol-driven care are becoming increasingly evident, and the authors believe the algorithm outlined here provides a rational and practical approach to patient management. It also prompts the caregiver to reevaluate patients' needs and to keep to patients at target sedation levels. Doing so can promote cost effectiveness, reduce side effects caused by drugs, and decrease morbidity and ICU stay. Any treatment protocol or algorithm is simply a guide to therapy and cannot address every clinical situation. The importance of individualized care and physician or care team judgment must be emphasized.

Algorithms↗
PubMed2001

Temporal variation in endotoxin-induced vascular hyporeactivity in a rat mesenteric artery organ culture model.

Endotoxin-induced vascular hyporeactivity to phenylephrine (PE) is well described in rodent aorta, but has not been investigated in smaller vessels in vitro. Segments of rat superior mesenteric artery were incubated in culture medium with or without foetal bovine serum (10%) for 6, 20 or 46 h in the presence or absence of bacterial lipopolysaccharide (LPS; 1 - 100 microg ml(-1)). Contractions to PE were measured with or without nitric oxide synthase (NOS) inhibitors: L-NAME (300 microM), aminoguanidine (AMG; 400 microM) 1400W (10 microM) and GW273629 (10 microM); the guanylyl cyclase inhibitor, ODQ (3 microM); the COX-2 inhibitor, NS-398 (10 microM). Contractile responses to the thromboxane A2 mimetic, U46619 were also assessed. In the presence of serum, LPS induced hyporeactivity at all time points. In its absence, hyporeactivity only occurred at 6 and 20 h. L-NAME and AMG fully reversed hyporeactivity at 6 h, whereas they were only partially effective at 20 h and not at all at 46 h. In contrast partial reversal of peak contraction was observed with 1400W (62% at 46 h), GW273629 (57% at 46 h) and ODQ (75% at 46 h). COX-2 inhibition produced no reversal. In contrast to PE, contractions to U46619 were substantially less affected by LPS. We describe a well-characterized reproducible model of LPS-induced hyporeactivity, which is largely mediated by the NO-cyclic GMP-dependent pathway. Importantly, long-term (2-day) production of NO via iNOS is demonstrated. Moreover, conventional doses of L-NAME and AMG became increasingly ineffective over time. Thus, the choice of inhibitor merits careful consideration in long-term models.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2001

Lowering HIV risk among ethnic minority drug users: comparing culturally targeted intervention to a standard intervention.

To test the efficacy of culturally targeted acquired immunodeficiency syndrome (AIDS) prevention programs on ethnic minority street drug users, 669 African-American and Puerto Rican drug users were assigned to receive either the National Institute on Drug Abuse (NIDA) standard intervention or a culturally competent enhanced intervention in a quasi-experimental study. The standard intervention was a two-session educational program, while both the African-American and Puerto Rican enhanced interventions provided additional AIDS information in a culturally appropriate fashion. Although human immunodeficiency virus (HIV) risk behaviors, as measured by Bell's risk indices, decreased, there were no meaningful significant differences between interventions. However, participants who went into drug treatment programs showed greater reduction in HIV risk behavior. Cultural interventions may provide better outcome if they concentrate on getting participants into drug treatment.

Acquired Immunodeficiency Syndrome↗
PubMed2001

SdeK, a histidine kinase required for Myxococcus xanthus development.

The sdeK gene is essential to the Myxococcus xanthus developmental process. We reported previously, based on sequence analysis (A. G. Garza, J. S. Pollack, B. Z. Harris, A. Lee, I. M. Keseler, E. F. Licking, and M. Singer, J. Bacteriol. 180:4628--4637, 1998), that SdeK appears to be a histidine kinase. In the present study, we have conducted both biochemical and genetic analyses to test the hypothesis that SdeK is a histidine kinase. An SdeK fusion protein containing an N-terminal polyhistidine tag (His-SdeK) displays the biochemical characteristics of a histidine kinase. Furthermore, histidine 286 of SdeK, the putative site of phosphorylation, is required for both in vitro and in vivo protein activity. The results of these assays have led us to conclude that SdeK is indeed a histidine kinase. The developmental phenotype of a Delta sdeK1 strain could not be rescued by codevelopment with wild-type cells, indicating that the defect is not due to the mutant's inability to produce an extracellular signal. Furthermore, the Delta sdeK1 mutant was found to produce both A- and C-signal, based on A-factor and codevelopment assays with a csgA mutant, respectively. The expression patterns of several Tn5lacZ transcriptional fusions were examined in the Delta sdeK1-null background, and we found that all C-signal-dependent fusions assayed also required SdeK for full expression. Our results indicate that SdeK is a histidine kinase that is part of a signal transduction pathway which, in concert with the C-signal transduction pathway, controls the activation of developmental-gene expression required to progress past the aggregation stage.

Bacterial Proteins↗
PubMed2001

How treating psychoanalysts respond to psychotherapy research constraints.

The psychoanalytic community increasingly recognizes the importance of research on psychoanalytic treatments, yet a significant number of psychoanalysts continue to believe that research is either irrelevant to psychoanalysis or impossible to accomplish. Psychoanalysts who accept the value of research express concern that intrusions required by research protocols create significant distortions in the psychoanalytic process. The authors, all psychoanalysts, are studying the outcome of a brief (twenty-four-session) psychodynamic treatment of panic disorder. They report their experiences and struggles with the intrusions of videotaping, working with a treatment manual, and time-limited treatment. This research process required them to question old beliefs and to confront feelings of disloyalty toward their analytic training and identity, particularly with regard to keeping a "clean field" and routinely performing long-term analysis of character. The therapists' psychoanalytic knowledge, however, emerged as crucial for them in managing specific research constraints. Despite concerns about providing inadequate treatment, therapists were found to engage patients with psychoanalytic tools and focus in vibrant and productive therapies that led to significant improvements in panic symptoms and associated quality of life. The authors suggest that psychoanalysts have been overestimating the potential damage of research constraints on psychoanalytic process and outcome.

Adult↗
PubMed2001

The social functioning of persons with chronic mental illness: an empirical typology of consumers and correlates of social functioning.

This study examined the typology of consumers and correlates of their social functioning using the Social Functioning Scale (SFS). Data were obtained from 244 outpatients of two psychiatric hospitals and psychiatric ward inpatients in two general hospitals through a structured in-person interview. The typology was generated using Cluster Analysis, and the profile of each group was further examined. The results indicated that there were four distinct groups of consumers. Multiple regression analysis revealed that consumers' sex, age, education, diagnosis, behavioral problems, family caregivers' age, employment status, and overall social support were significantly associated with consumers' social functioning. The implications for previous research findings and psychiatric rehabilitation service are discussed.

Adolescent↗
PubMed2001

"War stories": AIDS prevention and the street narratives of drug users.

The day-to-day discourse of illicit drug users is replete with stylized narratives of street experience. These "war stories," as they are popularly known, are shared among drug users as they hustle for money, purchase drugs, get high, and hang out in diverse street locations. Drug-user narratives, which describe complex adventures and grave suffering, are primary ethnographic sources of information about patterns of drug consumption and risk behaviors. Importantly, in the time of AIDS, street narratives provide a much-needed window on the generally hidden lives of socially marginalized street drug users. As part of an effort to put the analysis of drug-user war stories to use in HIV prevention, in this article the authors analyze a corpus of street narratives told to members of an HIV-prevention research team in Hartford, Connecticut.

Adaptation, Psychological↗
PubMed2001

Gun violence exposure and trauma among rural youth.

This study compared rural youth exposed to gun violence and rural youth not exposed to gun violence on a number of variables: anger, anxiety, dissociation, depression, posttraumatic stress, total trauma, violent behavior, parental monitoring, and levels of violence in the home, school, and community. One-fourth (25%) of the rural youth in this study reported having been exposed to gun violence at least once. Youth exposed to gun violence reported significantly more anger, dissociation, posttraumatic stress, and total trauma. In addition, youth exposed to the violence of guns reported significantly higher levels of violent behaviors and exposure to violence in other settings and also reported lower levels of parental monitoring. The present study contributes to the growing body of literature addressing the stereotype that rural communities are not immune to the violence of firearms. This stereotype acts as a barrier to mental health practice, research, and policy issues in rural communities.

Adolescent↗
PubMed2001

A pilot open trial of brief psychodynamic psychotherapy for panic disorder.

This is a complete report of an open trial of manualized psychodynamic psychotherapy for treatment of panic disorder, Panic-Focused Psychodynamic Psychotherapy (PFPP). Twenty-one patients with PD were entered into a trial of twice-weekly, 24-session treatment. Sixteen of 21 experienced remission of panic and agoraphobia. Treatment completers with depression also experienced remission of depression. Improvements in symptoms and in quality of life were substantial and consistent across all measured areas. Symptomatic gains were maintained over 6 months. This report was prepared specifically to describe 6-month follow-up on these patients. Psychodynamic psychotherapy appears to be a promising nonpharmacological treatment for panic disorder.

Adult↗
PubMed2000

Nitric oxide synthase localized in a subpopulation of vestibular efferents with NADPH diaphorase histochemistry and nitric oxide synthase immunohistochemistry.

Efferent innervation of the vestibular labyrinth is known to be cholinergic. More recent studies have also demonstrated the presence of the neuropeptide calcitonin gene-related peptide in this system. Nitric oxide is one of a new class of neurotransmitters, the gaseous transmitters. It acts as a second messenger and neurotransmitter in diverse physiological systems. We decided to investigate the anatomical distribution of the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), to clarify the role of nitric oxide in the vestibular periphery. NADPH diaphorase histochemical and NOS I immunohistochemical studies were done in the adult chinchilla and rat vestibular brainstem; diaphorase histochemistry was done in the chinchilla periphery. Retrograde tracing studies to verify the presence of NOS in brainstem efferent neurons were performed in young chinchillas. Our light microscopic results show that NOS I, as defined mainly by the presence of NADPH diaphorase, is present in a subpopulation of both brainstem efferent neurons and peripheral vestibular efferent boutons. Our ultrastructural results confirm these findings in the periphery. NADPH diaphorase is also present in a subpopulation of type I hair cells, suggesting that nitric oxide might be produced in and act locally upon these cells and other elements in the sensory epithelium. A hypothesis about how nitric oxide is produced in the vestibular periphery and how it may interact with other elements in the vestibular sensory apparatus is presented in the discussion.

Animals↗
PubMed2000

Inhibition by extracellular cAMP of phorbol 12-myristate 13-acetate-induced prostaglandin H synthase-2 expression in human pulmonary microvascular endothelial cells. Involvement of an ecto-protein kinase A activity.

Exposure of human pulmonary microvascular endothelial cells (HPMECs) to phorbol 12-myristate 13-acetate (PMA) leads to the increase of prostaglandin H synthase (PGHS)-2 protein levels. Under same conditions and according to its constitutive nature, no significant variation of PGHS-1 protein was noted. The elevation of the intracellular cAMP rate is known to enhance PGHS-2 levels through a protein kinase A pathway in various cells. To determine whether the extracellular cAMP also regulates the inducible expression of PGHS, cultured HPMECs were exposed to cAMP alone or in combination with PMA. The PMA-induced PGHS-2 protein was attenuated by the extracellular cAMP. In addition, PGHS-2 activity evaluated through 6-keto-PGF1alpha generation, which was enhanced by PMA was inhibited by extracellular cAMP. Furthermore, in HPMEC medium, PMA-induced PGHS-2 expression was accompanied by the generation of a transferable activity (TA) able to abolish platelet aggregation. This resulting TA was dependent from PGHS-2 pathway, because NS-398, a selective inhibitor of PGHS-2, suppressed its production. The inhibitory TA released by treated HPMECs was also prevented by extracellular cAMP. The specific protein kinase A (PKA) inhibitor blocked the extracellular cAMP effect on both PMA-induced 6-keto-PGF1alpha synthesis and inhibitory TA generation, suggesting the involvement of PKA signaling at the outer surface of HPMECs. Accordingly, we established, in phosphorylation experiments, the presence of an endothelial ecto-protein kinase activity, able to phosphorylate the synthetic substrate kemptide in a cAMP-dependent mode. Reverse transcription-polymerase chain reaction analysis showed that PMA-induced PGHS-2 mRNA was markedly reduced by extracellular cAMP. Together, these findings provide the first experimental evidence that extracellular cAMP is able to reduce HPMEC PGHS-2 expression in terms of mRNA, protein, and enzyme activity through an ecto-PKA pathway. In addition, they outline the potential role of endothelial PGHS-2 in the limitation of platelet activation during inflammatory processes.

Carcinogens↗
PubMed2000

1,3-Diarylcycloalkanopyrazoles and diphenyl hydrazides as selective inhibitors of cyclooxygenase-2.

Novel 1,3-diarylcycloalkanopyrazoles 1, and diphenyl hydrazides 2 were identified as selective inhibitors of cyclooxygenase-2. The 1,3-diaryl substitution pattern of the pyrazole ring in 1 differentiates these compounds from most of the known selective COX-2 inhibitors that contain two aryl rings at the adjacent positions on a heterocyclic or a phenyl ring. Similarly, the two phenyl rings in 2 are also separated by three atoms. SAR of both phenyl rings in 1 and 2, and the aliphatic ring in 1 will be discussed.

Azides↗
PubMed2000

Microcystic adnexal carcinoma: forty-eight cases, their treatment, and their outcome.

BACKGROUND: Microcystic adnexal carcinoma, or sclerosing sweat duct carcinoma, is an uncommon cutaneous neoplasm associated with extensive local invasion. The standard of care with regard to the best excisional method in treating microcystic adnexal carcinoma has not been established. OBJECTIVES: To perform a retrospective study comparing patients treated by Mohs micrographic surgery with those treated by wide excision and to elucidate the epidemiological features of microcystic adnexal carcinoma. PATIENTS AND METHODS: A retrospective analysis of a case series involving 48 primary and referral patients diagnosed as having microcystic adnexal carcinoma using standardized criteria. All cases were reviewed by the same dermatopathologists. RESULTS: Microcystic adnexal carcinoma predominantly affects the left side of the face of middle-aged women. Microcystic adnexal carcinoma is misdiagnosed 30% of the time. The recurrence rate is 1.98% per patient-year. Mohs micrographic surgery and simple excision show comparable complication rates. Clear margins were obtained in fewer procedures and, therefore, fewer office visits when the lesions were treated with micrographic surgery. The defect surface area after full extirpation following Mohs micrographic surgery was a mean of 4 times that of the clinically apparent size. The wide range of difference between the pre- and the post-Mohs micrographic surgery surface area noted in our data indicates that a margin cannot be safely predicted. CONCLUSIONS: Microcystic adnexal carcinoma is a predominantly left-sided, locally aggressive facial tumor, which results in significant morbidity. Our data do not support the use of standardized predictable margins. Mohs micrographic surgery is a reasonable initial treatment, as it accomplishes cure in fewer office visits and does not rely on predicted margins.

Adult↗
PubMed2000

Treatment results of carcinoma in situ of the glottis: an analysis of 82 cases.

OBJECTIVES: To evaluate the results of different treatment modalities for carcinoma in situ of the glottis, and to identify important prognostic factors for outcome. DESIGN: Review of 82 cases treated definitively for glottic carcinoma in situ between 1958 and 1998. The median follow-up for all patients was 112 months, and 90% had more than 2 years of follow-up. SETTING: Academic tertiary care referral centers. INTERVENTION: Fifteen patients were treated with vocal cord stripping (group 1), 13 with more extensive surgery (group 2) including endoscopic laser resection (11 patients) and hemilaryngectomy (2 patients), and 54 with radiotherapy (group 3). Thirty patients had anterior commissure involvement and 9 had bilateral vocal cord involvement. Radiotherapy was delivered via opposed lateral fields at 1.5 to 2.4 Gy per fraction per day (median fraction size, 2 Gy), 5 days per week. The median total dose was 64 Gy, and the median overall time was 47 days. MAIN OUTCOME MEASURES: Initial locoregional control (LRC), ultimate LRC, and larynx preservation. RESULTS: The 10-year initial LRC rates were 56% for group 1, 71% for group 2, and 79% for group 3. Of those who failed, the median time to relapse was 11 months for group 1, 17 months for group 2, and 41 months for group 3. Univariate analysis showed that the difference in initial LRC rates between groups 1 and 3 was statistically significant (P =.02), although it was not statistically significant on multivariate analysis (P =.07). Anterior commissure involvement was an important prognostic factor for LRC on both univariate (P =.03) and multivariate (P =.04; hazard ratio, 1.6) analysis, and its influence appeared to be mainly confined to the surgically treated patients (groups 1 and 2). The 10-year larynx preservation rates were 92% for group 1, 70% for group 2, and 85% for group 3. Anterior commissure involvement was the only important prognostic factor for larynx preservation (P =. 01) on univariate analysis. All but 2 patients in whom treatment failed underwent successful salvage surgery. Voice quality was deemed good to excellent in 73% of the patients in group 1, 40% in group 2, and 68% in group 3. CONCLUSIONS: Treatment of carcinoma in situ of the glottis with vocal cord stripping or more extensive surgery or radiotherapy provided excellent ultimate LRC and comparable larynx preservation rates. Anterior commissure involvement was associated with poorer initial LRC and larynx preservation, particularly in the surgically treated patients. The choice of initial treatment should be individualized, depending on patient age, reliability, and tumor extent. Pretreatment and posttreatment objective evaluation of voice quality should be helpful in determining the best therapy for these patients.

Aged↗
PubMed2000

Lack of IL-10 synthesis by murine alveolar macrophages upon lipopolysaccharide exposure. Comparison with peritoneal macrophages.

The central role of alveolar macrophages in the establishment of lipopolysaccharide (LPS)-induced lung inflammation is well demonstrated. They produce and release numerous proinflammatory molecules, among which is tumor necrosis factor alpha (TNF-alpha), a cytokine responsible in part for the neutrophilic alveolitis. Interleukin-10 (IL-10) produced by LPS-activated mononuclear phagocytes is a major anti-inflammatory cytokine that down-regulates TNF-alpha synthesis. We studied the ability of murine alveolar macrophages to produce IL-10 in vivo and in vitro, in response to LPS. Unexpectedly, the IL-10 protein was not detected in the whole lung and airspaces after LPS intranasal instillation. In addition, no IL-10 protein was found in supernatants of isolated and LPS-stimulated alveolar macrophages. The lack of IL-10 synthesis was confirmed by the absence of specific RNA transcripts. By contrast and as expected, autologous peritoneal macrophages produced IL-10 upon LPS challenge. Drugs that usually modify the TNF-alpha/IL-10 balance in favor of IL-10 were used without success. Thus, maneuvers allowing an increase in intracellular cAMP concentrations did not reverse this unexpected phenotype. Moreover, direct activation of protein kinase C with PMA was unable to trigger IL-10 formation by alveolar, by contrast to peritoneal, macrophages. The current findings describe a specific phenotype for murine alveolar macrophages during LPS-induced inflammation.

Animals↗
PubMed2000

Parental eating attitudes and the development of obesity in children. The Framingham Children's Study.

OBJECTIVE: To investigate the extent to which parents' degree of dietary self-control, as measured by self-reported dietary restraint, disinhibition, and perceived hunger, affects the development of excess body fat in the child. DESIGN: Prospective observational study. SUBJECTS: Ninety-two 3-5y old children and their parents, enrolled in 1987 in the Framingham Children's Study. MEASUREMENTS: Self-reported levels of parental dietary restraint, disinhibition and perceived hunger were estimated using Stunkard and Messick's Three-Factor-Eating Questionnaire. Anthropometric measurements (height, weight and skinfold measurements at five sites) were obtained yearly for children and parents. The child's activity level was measured on multiple days each year using Caltrac accelerometers. Energy intake and percentage of calories from total fat were estimated from multiple sets of food diaries, collected each year. All analyses were adjusted for the following potential confounders: child's sex and baseline values for age, height, mean physical activity level, total calories and percentage of calories from fat as well as the educational levels of the parents at baseline. RESULTS: Over 6y, children's body fat increased linearly with increasing levels of self-reported parental disinhibition (eg 6y increase in the child's sum of five skinfolds was 34.4, 45.8 and 59.2 mm across increasing tertiles of parental disinhibition, P=0.012). Overall, children whose parents had higher dietary restraint scores had greater increases in body fatness than children whose parents had the lowest levels of restraint. When both parents had above average scores on dietary disinhibition or restraint, the children had greater increases in body fat (on all anthropometry measures) than when only one parent or when neither parent had high scores on those factors. Parental scores on the perceived hunger scale had no clear effect on body fat change of children. Since disinhibition and dietary restraint frequently co-exist, we then examined the joint effect of these two factors. The children with the greatest increases in body fat were those whose parents scored high on both factors. In the final analysis, we found that dietary restraint adversely affected the child's body fat only when associated with high parental disinhibition. CONCLUSION: This study suggests that parents who display high levels of disinhibited eating, especially when coupled with high dietary restraint, may foster the development of excess body fat in their children. This association may be mediated by direct parental role modeling of unhealthy eating behaviors, or through other indirect, and probably subconscious, behavioral consequences such as the suppression of the child's innate regulation of dietary intake.

Anthropometry↗