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S Robinson

Publications and source records attributed to S Robinson.

At least 217 records · Page 12Linked to original sources

Novel cAMP PDE III inhibitors: imidazo[4,5-b]pyridin-2(3H)-ones and thiazolo[4,5-b]pyridin-2(3H)-ones and their analogs.

The transformation of milrinone to 1,3-dihydro-5-methyl-6-(4-pyridinyl)-2H-imidazo[4,5-b]pyridin-2-one (13a), 5-methyl-6-(4-pyridinyl)thiazolo[4,5-b]pyridin-2(3H)-one (51), and 7-methyl-6-(4-pyridinyl)-1,8-naphthyridin-2(1H)-one (22) resulted in very potent cAMP PDE III inhibitors with in vitro activity in the nanomolar range. 1,3-Dihydro-2H-imidazo[4,5-b]pyridin-2-ones 13 were prepared from 2-aminopyridine-3-carboxylic acids (7, 10) via Curtius rearrangement. 1,8-Naphthyridin-2(1H)-one 22 and the corresponding 3,4-dihydro derivative 28 were prepared from 5-bromo-2-methyl[3,4'-bipyridin]-6-amine (21) and 5-bromo-2-methyl[3,4-bipyridin]-6(1H)-one (24), respectively, via Heck reaction. Thiazolo[4,5-b]pyridin-2(3H)-ones 35 were prepared from 6-bromo[3,4'-bipyridin]-6-amines 30 and 32 via a four-step sequence. Treatment of 6-amino-2-methyl[3,4'-bipyridine]-5-thiol (59) with ethyl bromoacetate and ethyl bromodifluoroacetate gave pyridothiazinones 60 and 61, respectively.

3',5'-Cyclic-AMP Phosphodiesterases↗

Removal/neutralization of hepatitis A virus during manufacture of high purity, solvent/detergent factor VIII concentrate.

Recent reports have suggested an increased risk of type A viral hepatitis in hemophilic patients treated with high purity factor VIII concentrates prepared using ion exchange chromatography coupled with solvent/detergent treatment for inactivation of viruses. To determine the capacity for removal or inactivation of hepatitis A virus during the factor VIII manufacturing process, human plasma and various factor VIII production intermediates were spiked with cell culture-propagated virus and subjected to scaled down conditions mimicking the manufacture of solvent/detergent factor VIII. The combination of antibody-mediated neutralization, cryoprecipitation, anion exchange chromatography, and lyophilization in the absence of sucrose resulted in a minimal reduction of 5.5 to 8.55 log10 in the infectivity of hepatitis A virus.

Animals↗

Professional development in midwifery: findings from a longitudinal study of midwives' careers.

Although much importance is attached to continuing professional education for nurses, midwives and health visitors, there is a paucity of empirical studies on the subject. This article reviews research in continuing education for midwives and adds to the body of literature by reporting on findings on continuing education obtained in the course of a longitudinal study of midwives' careers. The original impetus for the study was concern about attrition from the profession; the method chosen to examine the problem was a longitudinal study in which two large cohorts of midwives were followed-up by means of questionnaires sent to them at regular intervals from qualification onwards. Information has been obtained on the relationship to retention of career intentions, careers followed and many aspects of life as a midwife. Those aspects relating to continuing professional education and development include obtaining post-basic qualifications, opportunities for in-service education, professional development during breaks for child care, support and feedback from senior colleagues and views on the importance of continuing education and support in relation to retention.

Career Mobility↗

Approaches to the problem of respondent attrition in a longitudinal panel study of nurses' careers.

Longitudinal panel studies have several distinct methodological and analytical advantages over cross-sectional studies for gaining an understanding of nurses' careers and developing strategies to facilitate retention. Panel studies do, however, present the researcher with a number of substantial challenges if maximum potential is to be achieved from the investment of time and resources that such studies entail. Respondent attrition at successive phases of data collection, for example, is a major problem, often with the consequence that respondents are not representative of the study group as a whole. This paper discusses reasons for choosing a longitudinal panel design for a programme of research into careers of midwives and nurses. The way in which the problem of respondent attrition has been approached in one of the projects in the programme, that focusing on the careers of registered general nurses, is then described.

Bias↗

Insulin sensitivity in non-diabetic relatives of patients with non-insulin-dependent diabetes from two ethnic groups.

OBJECTIVE: Non-insulin-dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non-insulin-dependent diabetes from two different ethnic groups. DESIGN: Subjects were studied on two separate occasions by an oral glucose tolerance test and a short insulin tolerance test. PATIENTS: Twenty-four glucose-tolerant first-degree relatives of patients with non-insulin-dependent diabetes (12 of European and 12 of Asian origin) were compared with 24 ethnically matched control subjects with no family history of diabetes. MEASUREMENTS: Insulin, proinsulin, glucose and intermediary metabolites were measured during a 75-g oral glucose tolerance test. Insulin sensitivity was assessed using a 15-minute insulin tolerance test (0.05 units/kg). RESULTS: Asian relatives compared to Asian controls had significantly higher fasting levels of immunoreactive insulin (83 +/- 17 vs 40 +/- 6 pmol/l, P < 0.05), which were not due to increased proinsulin. Blood glycerol concentrations were elevated (83 +/- 9 vs 51 +/- 4 mumol/l, P < 0.005), but fasting glucose and non-esterified fatty acid (NEFA) concentrations were similar. Relatives of European origin did not differ from their European controls in any of these measurements. The glucose response to oral glucose was similar in relatives and controls, irrespective of ethnic group. The insulin responses were non-significantly greater in relatives from both ethnic groups. Proinsulin levels were not significantly different. Asian relatives had higher circulating glycerol and NEFA levels after oral glucose than Asian controls, but these differences were not observed in the European group. Insulin sensitivity was reduced in the Asian relatives compared to their controls (183 +/- 7 vs 139 +/- 12 mumol/l/min, P < 0.01) but there was no difference in insulin sensitivity between the European relatives and European controls (167 +/- 11 vs 160 +/- 11 mumol/l/min). CONCLUSIONS: First-degree relatives of non-insulin-dependent diabetic patients of Asian, but not of European, origin are insulin insensitive in terms of both glucose metabolism and lipolysis, and have true hyperinsulinaemia. This suggests that insulin insensitivity may be an early abnormality in the development of non-insulin-dependent diabetes in the Asian population.

Adult↗

Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity.

OBJECTIVE: The assessment of insulin sensitivity requires an accurate and reproducible technique. The short insulin tolerance test is a simple and rapid method for screening large numbers of subjects when the fasting glucose level is normal. Conventionally, an insulin dose of 0.1 units/kg is used, but this may result in symptomatic hypoglycaemia in healthy thin subjects who are insulin sensitive. In order to overcome this problem we have employed a lower dose of insulin and have studied the reproducibility of this modified technique comparing it with the euglycaemic hyperinsulinaemic clamp. DESIGN: Subjects were studied on two separate occasions, once by a short insulin tolerance test and on a second occasion by either a euglycaemic hyperinsulinaemic clamp (insulin infusion of 40 mU/m2/min) or a repeat short insulin tolerance test. PATIENTS: Eleven healthy subjects were studied twice with a short insulin tolerance test. A further 10 healthy subjects received a short insulin tolerance test on one day and a euglycaemic hyperinsulinaemic clamp study on another occasion. MEASUREMENTS: Insulin sensitivity was measured in the short insulin tolerance test using the slope of arterialized blood glucose concentration from 3 to 15 minutes after an intravenous bolus of short-acting insulin, 0.05 units/kg body weight. In the clamp study, insulin sensitivity was derived from the average amount of glucose infused at steady state (M) and the mean plasma insulin level (I). RESULTS: In the short insulin tolerance test no subject developed symptomatic or biochemical hypoglycaemia, defined as a blood glucose < 2.2 mmol/l. The (mean +/- SEM) insulin sensitivities for the 11 subjects studied twice were 174 +/- 10 and 179 +/- 11 mumol/l/min with a coefficient of variation of 6.9 +/- 2.6%. There was a close correlation between insulin sensitivity derived from the short insulin tolerance test and that obtained from the euglycaemic clamp studies (so-called M/I ratio) in the same subjects (r = 0.81; P < 0.005). CONCLUSION: The short insulin tolerance test employing 0.05 units/kg insulin is a safe, valid and reproducible method for the assessment of insulin sensitivity.

Adult↗

Reduced postprandial energy expenditure in women predisposed to type 2 diabetes.

Type 2 (non-insulin dependent) diabetes is so common that it has been hypothesized that in the course of evolution the predisposition to it may have conferred some advantage, before or during the reproductive years. It is frequently preceded by gestational diabetes. In order to test the basis for the hypothetical advantage, energy expenditure was investigated in 10 women with documented transient diabetes in a previous pregnancy. They were studied early in a subsequent pregnancy while glucose tolerance wa still normal and 9 were re-studied after pregnancy. Their results were compared with normal matched controls. During pregnancy, resting energy expenditure was similar in the study group and controls (6.58 (5.77-7.55) median (range) vs 6.91 (6.56-7.36) MJ day-1, respectively). However, the energy response to a mixed meal (42 kJ, kg-1 lean body mass) was decreased in the study group (45 (33-68) vs 76 (50-89) kJ, p < 0.05). After pregnancy resting energy expenditure was again similar in the two groups, but the decrease in postprandial thermogenesis persisted (78 (59-84) vs 92 (79-105) kJ, p < 0.05). The patients were resistant to exogenous insulin, 0.05 U kg-1 intravenously (slope of the plasma glucose decline in the 15 min after insulin; during pregnancy patients 52 (37-92) vs controls 111 (104-121) mumol l-1 min-1, p < 0.01; after pregnancy 130 (88-156) vs controls 186 (152-221) mumol l-1 min-1, p < 0.01). The postprandial energy saving in these women could constitute an evolutionary advantage. Insulin resistance may be the mechanism for limiting postprandial thermogenesis.

Adult↗

The present state of people who survived the holocaust as children.

A total of 103 Holocaust survivors who suffered from Nazi persecution during their childhood years were interviewed in 1992. The interviews were conducted using a questionnaire specially prepared for statistical studies of Holocaust survivors. The study demonstrated that most survivors in this sample still suffer today, more than 50 years after the outbreak of the Second World War, from symptoms of the survivor syndrome. Their mental suffering is in positive correlation to the intensity of the trauma they suffered in their childhood. Those who were in death camps suffer more than those who suffered during their childhood from other forms of persecution by the Nazis. The coping and adjustment of child survivors of death camps were also less successful than the coping and adjustment of child survivors who went through other forms of persecution.

Adaptation, Psychological↗

Retraumatization of Holocaust survivors during the Gulf War and SCUD missile attacks on Israel.

The purpose of this work was to study the reaction to a new threat and a new trauma of people severely traumatized in the past, when the new trauma had associations with the original one caused by the Holocaust. The situation created during the Gulf War gave a rare occasion to study it. We also wanted to check if the reaction of Holocaust survivors to the war differed from that of the general population. In addition we wanted to find out if there was a difference in reaction to the war between two clinical populations: Holocaust survivors and patients who are not Holocaust survivors. Sixty-six Holocaust survivors living in Israel, 31 of them undergoing psychiatric or psychological treatment either as in-patients or as out-patients, were interviewed during the Persian Gulf War. In addition to the clinical group, there was a non-clinical group of 35 Holocaust survivors--21 whose homes were not damaged by SCUD missiles, and 14 whose homes were damaged by missiles. Those whose homes were damaged by SCUD missiles were retraumatized, and showed reactivation or exacerbation of the survivor syndrome. Six of them displayed the full syndrome of PTSD.

Aged↗

Quantitative bone scanning after asymptomatic Charnley arthroplasty.

To establish the normal pattern of postoperative tracer uptake we performed 73 99mtechnetium methylene diphosphonate scans following primary Charnley hip replacements for arthrosis in 68 patients without clinical, hematological and radiographic complications. The patients were divided into 7 subgroups according to the period, 6-24 months, between surgery and scan. There were 10-12 patients in each subgroup. A high-resolution gamma camera with a large field of view was used. Ratios of uptake in each of 10 peri-prosthetic zones to normal bone were calculated. Femoral uptake was found to decrease in linear fashion from 6 to 12 months after surgery. Thereafter the uptake remained unaltered at levels nearly twice the normal ones in the greater trochanter and nearly 1.5 times in the lesser trochanter, returning to almost normal levels in other zones. Acetabular uptake remained elevated throughout.

Acetabulum↗

Psychological, social and sexual effects of gestational trophoblastic disease on patients and their partners.

The psychological, social and sexual effects of gestational trophoblastic disease in both patients and their partners are reviewed. The results suggest that despite the favorable prognosis of this disease, mood disturbances, sexual disturbances and fertility concerns can persist in both patients and their partners. Recommendations are made concerning providing supportive care to meet the needs of patients and their partners.

Affect↗

Isolation of HTLV-II from a patient with chronic, progressive neurological disease clinically indistinguishable from HTLV-I-associated myelopathy/tropical spastic paraparesis.

An increasing spectrum of diseases has been shown to be associated with the human T-cell lymphotropic virus type I (HTLV-I), most notably a chronic, progressive myelopathy termed HTLV-I--associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia. HTLV-II is a close relative of HTLV-I and is structurally similar but molecularly distinct. This virus is endemic in Amerindian populations and a high seroprevalence rate has been observed in intravenous drug abusers. Here, for the first time, we have identified a patient with a chronic, progressive neurological disease clinically indistinguishable from HTLV-I--associated myelopathy/tropical spastic paraparesis from whom we have isolated and characterized HTLV-II in the absence of any other detectable human retrovirus. Antibodies to HTLV were detected in both serum and cerebrospinal fluid, with typical HTLV-II banding patterns on Western blots. HTLV-II viral sequences were detected in high copy number from peripheral lymphocytes by polymerase chain reaction techniques, and cloning and sequencing of this virus revealed a 99.5% homology with prototype HTLV-II. These results serve to alert the medical community to the possibility that in addition to HTLV-I, HTLV-II may be associated with a neurological disorder.

Brain↗

The molecular specificity of action of the tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (AcSDKP) in the control of hematopoietic stem cell proliferation.

The hemoregulatory tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP, M(r) = 487 amu) prevents the recruitment of hematopoietic stem cells into S phase. AcSDKP does not possess inherent inhibitory activity against hematopoietic stem cells, rather it appears to act by "blocking" the action of a hematopoietic stem cell proliferation stimulator present in extracts of regenerating hematopoietic tissue. The molecular specificity of this action was investigated using a number of peptide analogues of AcSDKP and evaluating their ability to "block" the recruitment of a primitive murine hematopoietic precursor (high proliferative potential colony forming cell HPP-CFC) into S phase following incubation with a hematopoietic stem cell proliferation stimulator. The capacity of AcSDKP to compromise the action of the hematopoietic stem cell proliferation stimulator was not evident for either AcSDDKP or AcSD beta KP, two structurally distinct forms of the molecule; similar no stimulator-"blocking" activity was observed for the tripeptide Ala-Asp-Lys (ADK, M(r) = 332 amu), while the tripeptide Ser-Asp-Lys (SDK, M(r) = 348 amu) was active. It would appear that the hemoregulatory action of AcSDKP is specific and that the tripeptide sequence SDK may be a significant component of the molecule.

Amino Acid Sequence↗

Combining work with caring for children, findings from a longitudinal study of midwives' careers.

Facilities that enable women to combine work with caring for children are of particular importance to professions comprised primarily of women, such as midwifery. This article presents findings on four aspects of this topic obtained in the course of a 13-year longitudinal study of midwives' careers: the numbers who had children and had taken breaks for pregnancy and child care, opportunities for professional development during periods of child care; the effect of such breaks on career progression, and the importance of family commitments in relation to retention. The majority of both cohorts were single women in their twenties at the time that they qualified as midwives. During the course of the study more than half the respondents had children; pregnancy was cited as the main reason for leaving midwifery followed in later years by being unable to find posts with hours of work that could be combined with family commitments. Findings showed little evidence of employers keeping in touch with midwives during child care breaks about job opportunities and professional developments; the majority of respondents however, said that they would have welcomed such contact. In common with other work on women's careers, this study demonstrated that breaks for child care are associated with slower rates of promotion. A wide range of issues were identified by respondents as relevant to retention, with those relating to combining work and family rated consistently as among the most important. The study demonstrates the importance that should be accorded to this issue when overall policies to improve retention in midwifery are being considered.

Adult↗

Career guidance during nurse training: findings from an exploratory study.

This research into the career guidance experiences of nurses during their training was undertaken as an exploratory study upon which a series of larger studies will subsequently be based. Additionally, it contributed to a national cohort study of the careers of newly qualified registered general nurses. One hundred and twelve nurses were involved in the development and testing of questions for a postal questionnaire to be used in the cohort study of careers. Some problems encountered when investigating career guidance by questionnaire are described, in the light of which a revised research design is proposed and the career guidance experiences of 31 nurses presented. Twenty-one aspects of guidance were investigated, covering information and advice about applying for first post, post-basic courses and longer-term plans.

Career Choice↗

Evaluation of the efficacy of an instructional programme in the self-management of patients with asthma.

The restrictions imposed on patients with asthma is problematic to them, in that their physical disability interferes with personal, interpersonal and/or professional goals. Twenty-three patients under the care of general practitioners were surveyed by interview in their homes, doctors' surgery or at work to determine their current control of selected variables related to their asthma: exercise, use of drugs and related factors. An instructional programme was offered to interested participants to assist in complying with their prescribed medication regimens and to tailor exercise to their tolerance levels. Findings showed that 18 patients experienced moderate to severe restrictions when troubled with asthma. Although over one-half of the patients exercised regularly for fitness, including seven with aerobic exercise, some chose sports they thought could provoke an asthmatic attack. Half took precautionary measures when exercising. All patients used bronchodilators to relieve their asthma, yet one-third did not keep their inhalers accessible. None of the most troubled 18 lived in a smoke-free environment, and one-third kept furry animals as pets. Recommendations are made for further study of the effects of instructional programme to improve compliance to a healthy lifestyle.

Absenteeism↗