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Biomedical subjects

S Greene

Publications and source records attributed to S Greene.

At least 19 recordsLinked to original sources

Life-threatening autoimmunity with diabetes: management with an insulin pump.

A 2-yr-old boy presented initially with type 1 diabetes (T1D). Over the next 9 yrs, he developed multiple autoimmune conditions including Evans' syndrome, alopecia, and autoimmune bowel disease. Autoimmune polyendocrinopathy, candidiasis, ectodermal dystrophy (APECED) syndrome was considered, but no mutations were found in the autoimmune regulator-1 (AIRE-1) gene, making this diagnosis unlikely, and he did not fulfill the clinical criteria for immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. We describe the challenges created by the combination of these diseases and how introduction of insulin pump therapy revolutionized his care.

Autoimmunity↗

Development, reliability and validity of the Diabetes Illness Representations Questionnaire: four studies with adolescents.

AIMS: This article reports on the development and validity of a Diabetes-specific Illness Representations Questionnaire (DIRQ) to assess all five dimensions of an individual's perception of diabetes, for adolescents with Type 1 diabetes mellitus. METHODS: There were two development studies. Study 1: participants (n = 115) completed a questionnaire assessing perceptions of the consequences of diabetes and the effectiveness of treatment, along with a questionnaire assessing self-care. Study 2: participants (n = 79) completed a questionnaire assessing their identity, timeline and causal beliefs, along with a diabetes self-efficacy and barriers to adherence questionnaire. Subsequently there were two validation studies. Study 3: participants (n = 44 adolescents and 28 parents) completed the DIRQ and questionnaires assessing their self-care and psychological well-being. Glycaemic control was assessed through retrieval of routine assay results. Study 4: participants (n = 70) completed the DIRQ and questionnaires to assess their psychological well-being, with glycaemic control assessed through retrieval of routine assay results. RESULTS: The development studies suggest that the perceived consequences of diabetes consist of two subscales, perceived threat and perceived impact, and provide further support for the distinction between treatment effectiveness to control diabetes and treatment effectiveness to prevent complications. Along with the validation studies, the results indicate that the questionnaire scales showed good internal consistency and construct validity through their associations with measures of self-care and psychological well-being. CONCLUSION: The data reported here suggest that the DIRQ has the potential to be a useful tool for clinical assessment and evaluating the impact of psycho-educational and medical interventions.

Adaptation, Psychological↗

Insulin pumps.

Explore the source record for details and available documents.

Adolescent↗

Cross-cultural differences in the management of children and adolescents with diabetes.

Glycaemic control deteriorates frequently in adolescents with diabetes. There is a considerable body of work on the effect of psychological aspects of management in this age group, but few randomized controlled trials of the effect of specific behavioural therapy and lifestyle modification on the improvement of glycaemic control. Of recent interest have been the observations from the Hvidøre Study Group on cross-cultural differences in glycaemic control. The average glycosylated haemoglobin in 22 centres, across 18 countries, varied in young people, with HbA1c levels ranging from 7.6 to 10.2%. No obvious differences in management were identified in this survey that could account for the disparities in glycaemic control. Data from the Scottish Study Group demonstrated similar variation in average glycaemic control in centres across a single culture. Using the qualitative methodology of anthropological research, some specific factors were identified that appear to influence young people's response to diabetes management and strategies employed by health professionals in their advice and care of the diabetes, particularly in relation to intensive insulin regimens. The main cultural factors influencing glycaemic control appear to be communication, reciprocal support between young people and professional heart carers and family structure within an individualistic, as against an egalitarian, society. Shared beliefs about teenage risk behaviour together with the medicalization of adolescence within medical culture also appears to be highly influential. The aim of this educational discussion group was to explore how a variety of health care professionals from distinctive cultures approach diabetes care delivery in this age group. The specific success and difficulties in different cultures in managing the young person with diabetes were investigated. Also discussed was how qualitative research methodology may generate further research in this area.

Adolescent↗

HIV testing in the setting of inpatient acute substance abuse treatment.

We examined patients' attitudes toward HIV testing in the setting of acute substance abuse treatment and determined the prevalence of offering routine on-site testing for human immunodeficiency virus (HIV) in inpatient state-funded detoxification centers in New England. Voluntary questionnaires were administered to patients (N = 66 respondents) at the only two state-funded inpatient drug detoxification treatment centers in Rhode Island, and a telephone survey of all state-funded inpatient detoxification facilities across the New England area was conducted. In New England, 17/38 (44.7%) of all state-funded inpatient detoxification facilities didnot routinely offer on-site HIV testing to clients. Of participants, 97% responded positively to the question, "Do you think HIV testing should be available to patients in drug detoxification facilities such as this one?" There were 89% who reported that they would cope "about the same" or "better" with receiving a positive HIV test result while in detoxification treatment versus elsewhere. The greatest number of participants ranked the Orasure HIV test, an assay for HIV-1 transmucosal antibody, as the test they would most prefer while in drug treatment. However, 59% of patients responded that the type of test offered would not make a difference in whether they chose testing. Most patients indicated that they would want to see a physician within a few days of a positive diagnosis of HIV infection. Despite the controversy surrounding the provision of HIV testing to patients in inpatient acute substance abuse treatment, HIV testing is desired among these patients provided that HIV clinical care is readily available.

Acute Disease↗

Primary myxoma of the temporal bone in a 17-year-old boy: case report.

OBJECTIVE AND IMPORTANCE: Only two cases of primary intracranial myxomas have been described previously in the literature: one patient had a primary intracranial myxoma in the pituitary fossa, and the other patient's myxoma was located in the posterior fossa. CLINICAL PRESENTATION: A rare case of primary myxoma of the temporal bone in a 17-year-old boy is described. The patient presented with a history of progressive left-sided hearing loss and increasing headaches of a few months' duration. INTERVENTION: An initial draining procedure in the left ear revealed extant mucous material, and further investigation showed a large calcified lesion involving the petrous and temporal bones and filling the middle fossa. At surgery, a large mucoid-appearing tumor was removed. The tumor pathology revealed a primary myxoma with bone and meningeal involvement. No clinical or histopathological evidence that it was a metastatic lesion was found. CONCLUSION: The features of myxomas on computed tomographic and magnetic resonance imaging, the histopathology, and surgical considerations are discussed.

Adolescent↗

Nucleocytoplasmic shuttling by human immunodeficiency virus type 1 Vpr.

Human immunodeficiency virus type 1 (HIV-1) is capable of infecting nondividing cells such as macrophages because the viral preintegration complex is able to actively traverse the limiting nuclear pore due to the redundant and possibly overlapping nuclear import signals present in Vpr, matrix, and integrase. We have previously recognized the presence of at least two distinct and novel nuclear import signals residing within Vpr that, unlike matrix and integrase, bypass the classical importin alpha/beta-dependent signals and do not require energy or a RanGTP gradient. We now report that the carboxy-terminal region of Vpr (amino acids 73 to 96) contains a bipartite nuclear localization signal (NLS) composed of multiple arginine residues. Surprisingly, when the leucine-rich Vpr(1-71) fragment, previously shown to harbor an NLS, or full-length Vpr is fused to the C terminus of a green fluorescent protein-pyruvate kinase (GFP-PK) chimera, the resultant protein is almost exclusively detected in the cytoplasm. However, the addition of leptomycin B (LMB), a potent inhibitor of CRM1-dependent nuclear export, produces a shift from a cytoplasmic localization to a nuclear pattern, suggesting that these Vpr fusion proteins shuttle into and out of the nucleus. Studies of nuclear import with GFP-PK-Vpr fusion proteins in the presence of LMB reveals that both of the leucine-rich alpha-helices are required for effective nuclear uptake and thus define a unique NLS. Using a modified heterokaryon analysis, we have localized the Vpr nuclear export signal to the second leucine-rich helix, overlapping a portion of the amino-terminal nuclear import signal. These studies thus define HIV-1 Vpr as a nucleocytoplasmic shuttling protein.

Amino Acid Sequence↗

An open-label acceptability study of Norditropin SimpleXx--a new liquid growth hormone formulation.

A new liquid formulation of hGH (Norditropin SimpleXx) has been developed to avoid the need for reconstitution before administration. In addition, the liquid GH formulation has been combined with an advanced pen delivery system, either with or without a needle auto-insertion mechanism. This study was designed to assess the acceptability of the new system compared with the patient's previous system. A total of 103 children with GH deficiency received a daily injection of Norditropin liquid GH for 12 weeks with a choice of a pen/auto-insertion system. Acceptability was determined by nurse-supervised questionnaires administered to the patients and parents. Following treatment, 94% of patients preferred the Norditropin liquid GH system. This preference was irrespective of the previous system in use, patient age or length of GH therapy. More patients found it the less painful system (50% vs 13%), 92% of patients found it more convenient, and the formulation was well tolerated. In conclusion, Norditropin liquid GH was very well accepted and preferred by the majority of patients. It avoided reconstitution which had been a major cause of dissatisfaction with the patients' previous systems, and resulted in greater convenience and reduced levels of pain associated with injection.

Adolescent↗

Good metabolic control is associated with better quality of life in 2,101 adolescents with type 1 diabetes.

OBJECTIVE: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families. RESEARCH DESIGN AND METHODS: The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires. RESULTS: Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores. CONCLUSIONS: In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.

Adolescent↗

Beta1,6-N-acetylglucosamine-bearing N-glycans in human gliomas: implications for a role in regulating invasivity.

The metastatic potential of tumor cells has been shown to be correlated with the expression of tri- and tetra-antennary beta1,6-N-acetylglucosamine (beta1,6-GlcNAc)-bearing N-glycans, which are recognized by Phaseolus vulgaris leukoagglutinating lectin (L-PHA). The expression of beta1,6-GlcNAc-bearing N-glycans also has been used as a marker of tumor progression in human breast and colon cancers. In this report, the role of N-glycan branching in regulating glioma migration and invasion was examined. The expression of beta1,6-GlcNAc-bearing N-glycans was found in human glioma specimens, whereas astrocytes from normal adult brain were negative. The expression of N-acetylglucosaminyltransferase V (GnT-V) mRNA, which is responsible for the biosynthesis of beta1,6-GlcNAc-bearing N-glycans, was high in glioma cell lines with robust ets-1 expression. To study the molecular mechanism of GnT-V expression in human glioma cells, an inducible ets-1 gene was stably transfected into SNB-19 cells using a tetracycline repressor system. GnT-V mRNA expression was increased by the induction of c-ets-1, suggesting that the Ets-1 transcription factor directly regulates the transcription of GnT-V. Stable transfection of GnT-V into human glioma U-373 MG cells resulted in changes in cell morphology and focal adhesions and a marked increase in glioma invasivity in vitro. L-PHA has little effect on cell migration. On the contrary, Phaseolus vulgaris erythroagglutinating lectin (E-PHA), which recognizes bisecting beta1,4-GlcNAc-bearing N-glycans, strongly inhibits cell migration (haptotaxis) on a fibronectin substrate in U-373 MG transfectants and other glioma cell lines tested. These results suggest that the increased beta1,6-GlcNAc-bearing N-glycan expression found in malignant gliomas is modulated by GnT-V through the Ets-1 transcription factor, and that the branching of complex type N-glycans plays a major role in glioma invasivity.

Adult↗

Diabetes mellitus in the pre-school child.

Diabetes mellitus presents rarely in the pre-school child and presents specific problems because of the peculiarity of the young child physiology. Pathogenesis involves the classic immunological mechanisms, with a higher incidence of other autoimmunity and family history of diabetes. Because of the rarity of the condition in this age group, the delay of the recognition of the signs and symptoms, which are often subtle at onset, determines the increased incidence of ketoacidosis. The reasons for the lower glycaemic control in this age group include the persistence of endogenous insulin, but also a more detailed involvement by the parents in organising diabetes. For the same reason ketoacidosis is an unusual occurrence after diagnosis. As to insulin therapy, three or more injections a day should be recommended, as in the older child, while the modern devices for blood glucose monitoring have proved useful to improve glycaemic control and to decrease the frequency of nocturnal hypoglycaemia, which gives particular concern given the vulnerability of the nervous system in this age group. Management of diabetes in the pre-school child may result very difficult for both parents and health carers because of the erratic daily pattern of activity, sleep and feeding; however, with a cautious strategy which involves insulin therapy, diet and monitoring it is possible to achieve satisfactorily the following aims: physical well-being of the young child, normal growth, lack of hyperglycaemia or hypoglycaemia, acceptable value of glycosilated haemoglobin.

Child, Preschool↗

Effect of frusemide and hypertonic saline on electrolytes during post exercise anaesthesia.

This study evaluated the effects of pre-exercise frusemide administration and hypertonic saline (H) infusion during anaesthesia on arterial pH, blood gases and electrolytes in 6 Thoroughbred horses anaesthetised immediately post exercise. Horses received either frusemide (F) (0.5 mg/kg, i.v.) or a saline placebo (P) injection 4 h prior to treadmill exercise. Exercise consisted of a 3 min warm-up at 40% VO2max followed by exercise to fatigue. Detomidine (40 micrograms/kg, i.v.) was given within 5 min of stopping and followed 5 min later by zolazepam-tiletamine (1.25 mg/kg, i.v.) to induce anaesthesia. During maintenance of anaesthesia using isoflurane in O2, either isotonic saline solution (I) or 7.5% H (4 ml/kg, i.v.) was administered. Arterial blood was sampled at the following times: prior to (Pre-F/P) and 4 h after (Pre-ex) F or P administration, 1 min after fatigue (Fatigue), 5 min after induction of anaesthesia (Post-ind), and just prior to and 15, 30 and 60 min after beginning isoflurane (ISFL) anaesthesia. Arterial pH and blood gas tensions, pulmonary arterial blood temperature, plasma [lactate], total protein and plasma [Na+], [K+], and [Cl-] were measured. Data were analyzed using 2-way ANOVA for repeated measures (P < 0.05). There were significant differences over time for all variables except total protein. Plasma [Na+] increased at Fatigue compared to Pre-F/P or Pre-ex in all treatment groups. Plasma [Na+] and [Cl-] increased during ISFL anaesthesia compared to Pre-F/P and Pre-ex in horses given H. During ISFL anaesthesia, plasma [Cl-] decreased compared to Pre-F/P in Group F+I horses. We conclude that acid-base, blood gas, and electrolyte changes associated with F are unlikely to influence management of horses anaesthetised immediately following supramaximal exercise to fatigue. Hypertonic saline infusion may help restore plasma [Cl-] faster in hypochloraemic horses requiring anaesthesia immediately after strenuous exercise.

Acid-Base Equilibrium↗

Diabetes in the pre-school child.

I have presented a personal view of the specific aspects of diabetes in the pre-school child compared with the older child and teenager. There is little in the literature that describes this age group separately from the management of older children. This is partly due to the small numbers of pre-school children that are our responsibility, even when looking after large numbers of young people with diabetes. While presenting a picture of rapid change and fluctuation, the children and their families eventually move into calmer waters, with the pre-school child becoming the school-child. Attention to the wellbeing of the child at this age is difficult and time consuming. A satisfactory outcome of a healthy and normally developed child and a family confident in their abilities in the management of the diabetes is a result of close co-operation, support and effective communication between the families and their health carers and advisors.

Adolescent↗

Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries. Hvidøre Study Group on Childhood Diabetes.

Insulin regimens and metabolic control in children and adolescents with Type 1 diabetes mellitus were evaluated in a cross-sectional, non-population-based investigation, involving 22 paediatric departments, from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from 2873 children from March to August 1995. HbA1c was determined once and analysed centrally (normal range 4.4-6.3%, mean 5.4%). Year of birth, sex, duration of diabetes, height, body weight, number of daily insulin injections, types and doses of insulin were recorded. Average HbA1c in children under 11 years was 8.3 +/- 1.3% (mean +/- SD) compared with 8.9 +/- 1.8% in those aged 12-18 years. The average insulin dose per kg body weight was almost constant (0.65 U kg(-1) 24 h(-1)) in children aged 2-9 years for both sexes, but there was a sharp increase during the pubertal years, particularly in girls. The increase in BMI of children with diabetes was much faster during adolescence compared to healthy children, especially in females. Sixty per cent of the children (n = 1707) used two daily insulin injections while 37% (n = 1071) used three or more. Of those on two or three injections daily, 37% used pre-mixed insulins, either alone or in combination with short- and intermediate-acting insulin. Pre-adolescent children on pre-mixed insulin showed similar HbA1c levels to those on a combination of short- and long-acting insulins, whereas in adolescents significantly better HbA1c values were achieved with individual combinations. Very young children were treated with a higher proportion of long-acting insulin. Among adolescent boys, lower HbA1c was related to use of more short-acting insulin. This association was not found in girls. We conclude that numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards intensive diabetes management, particularly in older adolescents. Nevertheless, the goal of near normoglycaemia is achieved in only a few.

Adolescent↗

Predicting key malaria transmission factors, biting and entomological inoculation rates, using modelled soil moisture in Kenya.

While malaria transmission varies seasonally, large inter-annual heterogeneity of malaria incidence occurs. Variability in entomological parameters, biting rates and entomological inoculation rates (EIR) have been strongly associated with attack rates in children. The goal of this study was to assess the weather's impact on weekly biting and EIR in the endemic area of Kisian, Kenya. Entomological data collected by the U.S. Army from March 1986 through June 1988 at Kisian, Kenya was analysed with concurrent weather data from nearby Kisumu airport. A soil moisture model of surface-water availability was used to combine multiple weather parameters with landcover and soil features to improve disease prediction. Modelling soil moisture substantially improved prediction of biting rates compared to rainfall; soil moisture lagged two weeks explained up to 45% of An. gambiae biting variability, compared to 8% for raw precipitation. For An. funestus, soil moisture explained 32% variability, peaking after a 4-week lag. The interspecies difference in response to soil moisture was significant (P < 0.00001). A satellite normalized differential vegetation index (NDVI) of the study site yielded a similar correlation (r = 0.42 An. gambiae). Modelled soil moisture accounted for up to 56% variability of An. gambiae EIR, peaking at a lag of six weeks. The relationship between temperature and An. gambiae biting rates was less robust; maximum temperature r2 = -0.20, and minimum temperature r2 = 0.12 after lagging one week. Benefits of hydrological modelling are compared to raw weather parameters and to satellite NDVI. These findings can improve both current malaria risk assessments and those based on El Niño forecasts or global climate change model projections.

Animals↗

Serum alpha 2-macroglobulin and alpha 1-inhibitor 3 concentrations are increased in hypoalbuminemia by post-transcriptional mechanisms.

In both the nephrotic syndrome (NS) and hereditary analbuminemia in the Nagase analbuminemic rat (NAR), the plasma protein concentration is nearly normal since albumin is replaced by several high molecular weight proteins. In rats these include the protease inhibitors alpha 2-macroglobulin (alpha 2M), a 720 kDa positive acute phase protein (APP) and alpha 1-inhibitor 3 (alpha 1-I3), a 180 kDa negative APP. There is no known stimulus to increase alpha 1-I3 synthesis, but like albumin and other negative APPs its synthesis decreases during inflammation by transcriptional down-regulation. In hypoalbuminemic states gene transcription of other positive and negative APPs is increased. We report that alpha 2M was increased significantly (12-fold) in NAR and by approximately 50-fold in rats with NS compared to control. The alpha 1-I3 concentration was twice normal in NAR or NS compared to controls, providing approximately half of the total plasma protein. Infusion of human albumin into NAR to raise albumin levels > 20 mg/ml for 24 hours caused a significant decrease in alpha 1-I3 (24.8 +/- 0.6 to 18.7 +/- 0.6 mg/ml, P < 0.0001), equal in magnitude to that caused by 250 micrograms/100 g of endotoxin (23.0 +/- 1.1 to 18.6 +/- 0.6, P < 0.01). The effect of albumin was not an acute phase response since it also suppressed alpha 2M (239 +/- 10 to 205 +/- 11 micrograms/ml, P < 0.005). Turnover of 125I labeled alpha 2M and alpha 1-I3 was then measured in controls, NAR and in two models of the nephrotic syndrome in rats (Heymann nephritis, HN; adriamycin-induced, ADR), yielding fractional catabolic rates (FCR), which at steady state equals synthesis. The serum alpha 2M concentration was increased approximately equal to 50-fold and was proportional to synthesis (r = 0.91 P < 0.001). alpha 2-Macroglobulin synthesis increased by 12-fold in NAR and 50-fold in NS. In contrast, hepatic alpha 2M mRNA increased only 30% in NAR and twofold in NS, suggesting post-transcriptional regulation. Fractional catabolic rates were not decreased and played no role in increasing serum alpha 2M in NS or NAR. The alpha 1-I3 concentration and synthesis increased twofold from controls in both NAR and NS. However, hepatic alpha 1-I3 mRNA was not increased in NAR and increased only 50% in NS. Unlike alpha 2M, serum alpha 1-I3 correlated negatively with FCR (-r = 0.66, P < 0.01). In conclusion, both alpha 1-13 and alpha 2M concentration are increased in hypooncotic states by increased synthesis regulated post-transcriptionally, supporting plasma protein concentration when albumin is lost in urine or not synthesized.

Acute-Phase Proteins↗