Pancreas size and exocrine function is decreased in young children with recent-onset Type 1 diabetes.

AIMS: To measure pancreatic area and exocrine function in young children with recent-onset Type 1 diabetes to determine whether the exocrine pancreas is also affected in the pathophysiology of early childhood diabetes. METHODS: Thirty-two children (14 boys) aged 5.5 (4.5, 7.3) median (IQR) years presenting with recent-onset Type 1 diabetes and 90 controls (44 boys) of similar age had ultrasound imaging of the pancreas. Children with Type 1 diabetes were receiving insulin and were without ketosis. Transverse and longitudinal areas of the pancreas were measured by digitalized outline. Pancreatic faecal elastase-1 was analysed using an enzyme-linked immunosorbent assay kit in recent-onset Type 1 diabetes and 38 first-degree relative control children. RESULTS: Pancreatic area and exocrine function were reduced in Type 1 diabetes. Mean transverse area (SD) in Type 1 diabetes was 6.82 cm2 (1.61) vs. 8.31 cm2 (1.74) in controls, adjusted estimate (95% CI) 1.45 (-2.12, -0.79), P < 0.001; longitudinal area was 1.28 cm2 (0.44) vs. 1.55 cm2 (0.43), adjusted estimate (95% CI) -0.27 (-0.45, -0.09), P = 0.003. Faecal elastase-1 levels in Type 1 diabetes were 455 (323, 833) ug/g, median (IQR) vs. 1408 µg/g (1031, 1989) in controls, P < 0.001. CONCLUSION: Pancreatic area and accompanying subclinical exocrine function were reduced in very young children with recent-onset Type 1 diabetes. This supports changes in the exocrine pancreas in the pathophysiology of Type 1 diabetes presenting in early life.

Individualised mindfulness-based stress reduction for head and neck cancer patients undergoing radiotherapy of curative intent: a descriptive pilot study.

People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes. This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment. Primary aims were to explore feasibility, compliance, acceptability and fidelity. Secondary aims were to determine whether (1) participation in the intervention was associated with changes in post-intervention mindfulness and (2) post-intervention mindfulness was associated with post-intervention distress and QoL. Nineteen HNC patients participated in a seven-session IMBSR programme with pre- and post-test outcome measures of psychological distress, depression, anxiety and QoL. Primary aims were assessed by therapists or participants. Mindfulness, distress and QoL were assessed using self-report questionnaires at pre- and post-intervention. Longer time spent meditating daily was associated with higher post-intervention mindfulness. After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings.

Bacteriological Survey of Fresh Minced Beef on Sale at Retail Outlets in Scotland in 2019: Three Foodborne Pathogens, Hygiene Process Indicators, and Phenotypic Antimicrobial Resistance.

ABSTRACT: The health and economic burden of foodborne illness is high, with approximately 2.4 million cases occurring annually in the United Kingdom. A survey to understand the baseline microbial quality and prevalence of food-related hazards of fresh beef mince on retail sale could inform risk assessment, management, and communication to ensure the safety of this commodity. In such a survey, a two-stage sampling design was used to reflect variations in population density and the market share of five categories of retail outlets in Scotland. From January to December 2019, 1,009 fresh minced beef samples were collected from 15 geographic areas. The microbial quality of each sample was assessed using aerobic colony count and Escherichia coli count. Samples were cultured for Campylobacter and Salmonella, and PCR was used to detect target genes (stx1 all variants, stx2 a to g, and rfbO157) for Shiga toxin-producing E. coli (STEC). The presence of viable E. coli O157 and STEC in samples with a positive PCR signal was confirmed via culture and isolation. Phenotypic antimicrobial sensitivity patterns of cultured pathogens and 100 E. coli isolates were determined, mostly via disk diffusion. The median aerobic colony count and E. coli counts were 6.4 × 105 (interquartile range, 6.9 × 104 to 9.6 × 106) and <10 CFU/g (interquartile range, <10 to 10) of minced beef, respectively. The prevalence was 0.1% (95% confidence interval [CI], 0 to 0.7%) for Campylobacter, 0.3% (95% CI, 0 to 1%) for Salmonella, 22% (95% CI, 20 to 25%) for PCR-positive STEC, and 4% (95% CI, 2 to 5%) for culture-positive STEC. The evidence for phenotypic antimicrobial resistance detected did not give cause for concern, mainly occurring in a few E. coli isolates as single nonsusceptibilities to first-line active substances. The low prevalence of pathogens and phenotypic antimicrobial resistance is encouraging, but ongoing consumer food safety education is necessary to mitigate the residual public health risk.

Investigating the efficacy of baricitinib in new onset type 1 diabetes mellitus (BANDIT)-study protocol for a phase 2, randomized, placebo controlled trial.

BACKGROUND: Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function. METHODS: This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10-30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses. DISCUSSION: This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D. TRIAL REGISTRATION: ANZCTR ACTRN12620000239965 . Registered on 26 February 2020. CLINICALTRIALS: gov NCT04774224. Registered on 01 March 2021.

Australian experience with total pancreatectomy with islet autotransplantation to treat chronic pancreatitis.

BACKGROUND: This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP-IAT) in Australia. METHODS: Individuals selected for TP-IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post-transplantation HbA1c, C-peptide, total daily insulin and analgesic requirement. RESULTS: Sixteen individuals underwent TP-IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290-7300). The median C-peptide 1 month post-TP-IAT was 384 (IQR 210-579) pmol/L and at median 29.5 (IQR 14.5-46.5) months from transplant was 395 (IQR 139-862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P < 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. CONCLUSION: The TP-IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates.

Psychosocial adaptation in female partners of men with prostate cancer.

The objective was to explore the psychosocial adaptation of female partners living with men with a diagnosis of either localized or metastatic prostate cancer. Semi-structured qualitative interviews were conducted with 50 women at two time points (baseline and 6 months later). The interviews examined emotions, experiences, attitudes to sexual and continence issues and treatment decision making. As part of a larger prospective observational study, demographic data and scores for depression and anxiety were collected. Initial analysis demonstrated that the group of 11 women assessed as distressed on the anxiety and depression measures described reduced coping skills and poorer adaptation after 6 months. In contrast, the 39 women in the non-distressed group reported emotional adaptation that fitted the Lazarus and Folkman pattern of coping through appraisal of the impact of the diagnosis on their partner and themselves, appraisal of coping strategies and reappraisal of the situation. A surprise finding was the high level of resilience displayed by majority of these women. Results suggest that a psychosocial intervention could strengthen healthy adaptation and provide better coping skills for distressed couples.

The effect of maternal DHA supplementation on body fat mass in children at 7 years: follow-up of the DOMInO randomized controlled trial.

BACKGROUND: Animal studies have suggested that an increased supply of omega-3 long chain polyunsaturated fatty acids (LCPUFA), in particular docosahexaenoic acid (DHA), during the perinatal period can prevent later excess body fat mass. However, previous human studies have produced inconsistent findings, and few have assessed potential effects beyond 6 years of age. OBJECTIVE: To evaluate the effect of supplementing women in the second half of pregnancy with omega-3 LCPUFA, chiefly as DHA, on the percentage body fat of children at 7 years of age, as assessed by two methods: air displacement plethysmography (BOD POD) and bioelectrical impedance spectroscopy (BIS). DESIGN: A time-restricted follow up at 7 years of age of children born to mothers enrolled in DOMInO (DHA to Optimise Maternal Infant Outcome) randomized controlled trial, in which women took either high-DHA tuna oil (800mg/day DHA) or placebo capsules from 20 weeks' gestation to delivery, at Adelaide-based centers. Primary outcomes were the percentage body fat at 7 years of age as assessed by both BOD POD and BIS. Weight, height, waist/hip circumferences and BMI were also recorded. RESULTS: A total of 252 DOMInO children (n=135 males, n=117 females) completed the follow up study. There were no differences between the DHA and placebo groups in percentage body fat as assessed by either BOD POD [adjusted mean difference: -0.35, 95% CI: -1.46, 2.16; P=0.71] or BIS [adjusted mean difference: 0.64, 95% CI: -0.99, 2.27; P=0.44]. BMI z-scores were also similar between groups [adjusted mean difference: 0.18, 95% CI: -0.10, 0.45; P=0.21]. There were also no differences in height, weight or waist and hip circumference between the DHA and placebo groups at 7 years of age. CONCLUSION: DHA supplementation in the second half of pregnancy has no effect on childhood growth or fat mass at 7 years of age, supporting findings from follow ups of the DOMInO children at 3 and 5 years.

Lack of association between duration of breast-feeding or introduction of cow's milk and development of islet autoimmunity.

The hypothesis that early exposure to cow's milk or lack of breast-feeding predisposes to type 1 diabetes remains controversial. We aimed to determine prospectively the relationship of, first, duration of exclusive breast-feeding and total duration of breast-feeding, and second, introduction of cow's milk protein as infant formula, cow's milk, or dairy products, to the development of islet antibodies in early life. Some 317 children with a first-degree relative with type 1 diabetes were followed prospectively from birth for 29 months (4-73). Mothers kept a home diary and answered infant feeding questionnaires at 6-month intervals. No systematic feeding advice was given. Insulin autoantibodies (normal range <5.5%), anti-GAD antibodies (<5.0 U), and anti-IA2 antibodies (<3.0 U) were measured at 6-month intervals. Cox proportional hazards model of survival analysis detected no significant difference between children who did not develop islet antibodies (225 of 317 [71%]), children with one islet antibody raised once (52 of 317 [16.4%]), children with one antibody raised repeatedly (18 of 317 [5.7%]), or children with two or more antibodies raised (22 of 317 [6.9%]), in terms of duration of exclusive breast-feeding, total duration of breast-feeding, or introduction of cow's milk-based infant formulas, cow's milk, or dairy products (relative risk: 0.91-1.09). Four of the children with two or more islet antibodies developed type 1 diabetes. We conclude that there is no prospective association between duration of breast-feeding or introduction of cow's milk and the development of islet autoimmunity in high-risk children.

Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes.

Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by viruses in genetically susceptible individuals. Rotavirus (RV), the most common cause of childhood gastroenteritis, contains peptide sequences highly similar to T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA-2), suggesting T-cells to RV could trigger islet autoimmunity by molecular mimicry. We therefore sought an association between RV infection and islet autoantibody markers in children at risk for diabetes who were followed from birth. There was a specific and highly significant association between RV seroconversion and increases in any of these antibodies: 86% of antibodies to IA-2, 62% to insulin, and 50% to GAD first appeared or increased with increases in RV IgG or IgA. RV infection may therefore trigger or exacerbate islet autoimmunity in genetically susceptible children.

Low-birth-weight infants show earlier onset of IDDM.

OBJECTIVE: Pancreatic beta-cell mass increases rapidly during gestation and early infancy. Infants who are small for gestational age, which is a marker for poor intrauterine nutrition, have reduced beta-cell mass. We examined whether weight and length in early infancy, and in inference beta-cell mass, is related to age at onset of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Data from infant records of 232 patients with IDDM, including birth weight, birth length, gestational age, weight at 6 months of age, and feeding history during the first 6 months of life, were analyzed. Maternal recall was not used for data collection. RESULTS: Low-birth-weight infants (<2.5 kg) showed a significantly earlier onset of diabetes (4.3 [3.2-6.0] years vs. 9.0 [5.3-11.8] years, median [25-75th percentile]; P < 0.0001). Infants small for gestational age also had earlier onset than those with birth weight above the 10th percentile after correction for gestational age (6.2 [3.6-10.5] vs. 9.2 [5.4-11.8] years; P < 0.0001). Infants with corrected birth weight: length ratio below the 10th percentile had earlier onset, as did infants with corrected 6-months weight below the 10th percentile (4.9 [2.8-6.0] years vs. 8.8 [5.2-11.8] years; P < 0.0001). Infants who were exclusively breast-fed for 6 months showed a slightly later onset of diabetes than those who were bottle- or mixed-fed, independent of weight (9.4 [5.0-11.3] years vs. 8.3 [4.2-11.7] years; P < 0.0001). CONCLUSIONS: Weight and growth parameters in utero and early infancy may influence the age at onset of IDDM. beta-cell mass is likely to be a significant factor.

Power spectral analysis of heart rate variability in children and adolescents with IDDM.

OBJECTIVE: To investigate power spectral analysis (PSA) of heart rate variability (HRV) in children and adolescents with IDDM, its relationship with other measures of HRV and standard cardiovascular responses, and factors associated with reduced HVR. RESEARCH DESIGN AND METHODS: A total of 130 subjects with IDDM aged 12.8 +/- 3.2 years and 108 healthy control subjects were studied. Power spectra were analyzed from supine electrocardiograph (ECG) recordings by processing into consecutive R-R intervals and analysis using fast Fourier transformation. Standard cardiovascular responses to deep breathing and standing were performed. RESULTS: IDDM subjects had a reduction in total power including both low-frequency (0.05-0.14 Hz; P = 0.0001) and high-frequency (0.14-0.40 Hz; P = 0.0002) components. These changes were seen from diagnosis. Other measures of HRV, coefficient of variation (CV) and standard deviation (SD) of mean resting heart rate, were also significantly lower in IDDM. All 20 (15%) of the 130 IDDM subjects with total power less than the 5th percentile in control subjects also had reduced HRV when measured by CV of heart rate. There was an independent relationship between age and the high-frequency component in IDDM subjects and control subjects. Total power correlated with mean heart rate (r = -0.56; P < 0.0001), CV of heart rate (r = 0.90; P < 0.00001), SD of heart rate (r = 0.91; P < 0.00001), heart rate response to deep breathing (r = 0.45; P < 0.0001), and duration in IDDM subjects. There was no correlation with short-term or long-term metabolic control. Retesting of 27 subjects showed a variability in total power and its components comparable to other measures of HRV and standard heart rate responses. CONCLUSIONS: Changes in HRV are a sensitive and reproducible measure of early autonomic dysfunction in childhood. In this age-group, PSA appears no more sensitive a measure of reduced HRV than other closely correlated measures of HRV.

Failure to maintain the benefits of home-based intervention in adolescents with poorly controlled type 1 diabetes.

OBJECTIVE: To determine whether a 6-month home-based intervention program in adolescents with poorly controlled diabetes improves metabolic control and whether benefits are maintained after the intervention. RESEARCH DESIGN AND METHODS: Adolescents with a mean HbA1c of > 9.0% over the preceding 12 months received either routine care in a diabetes clinic and an ambulatory intervention for 6 months (n = 37) or routine care only (n = 32). A diabetes educator provided monthly home visits and weekly phone contact to educate and support the adolescents in setting goals for insulin adjustment, blood glucose monitoring, and target blood glucose range. There was no systematic change in the frequency of insulin injections. After the intervention, there was a 12-month follow-up when the intervention and control groups both received only routine care. Outcome measures were HbA1c and Diabetes Knowledge Assessment (DKN). RESULTS: During the intervention, mean HbA1c fell (baseline: 11.1 +/- 1.3%, 6 months: 9.7 +/- 1.6%; P = 0.0001) and mean knowledge scores increased (P = 0.0001) in the intervention group but not in control subjects. However, this improvement in HbA1c and increase in knowledge was not maintained in the intervention group at 12- and 18-month follow-up assessments. Parents' knowledge scores also improved significantly from baseline levels in the intervention group at 6 and 12 months (P = 0.001, P = 0.005, respectively). CONCLUSIONS: An ambulatory program improves metabolic control and knowledge in adolescents with poorly controlled type 1 diabetes; however, it is effective only while the intervention is maintained.

Association of lipoprotein(a) with puberty in IDDM.

OBJECTIVE: To determine serum lipoprotein(a) in a large sample of IDDM and control children and to examine a possible association with puberty. RESEARCH DESIGN AND METHODS: Serum lipoprotein(a), apoB-100, and apoA-I were measured under identical conditions in 170 Caucasian children with IDDM aged 12.3 +/- 3.59 yr and 233 Caucasian control children aged 13.6 +/- 1.12 yr. Patients with persistent microalbuminuria were excluded. Lipoprotein(a), apoB-100, and apoA-I were measured by nephelometry using a specific monoclonal antibody. Pubertal assessment was performed using Tanner staging and testicular volume measurement. RESULTS: Lipoprotein(a) was higher in the IDDM than control group (geometric mean 237 mg/L, 25-75th percentile 134-465 vs. 172 [99-316] mg/L, P = 0.0008). When analyzed according to pubertal stage, only pubertal and postpubertal patients had higher levels than control subjects (265 [148-560] vs. 174 [101-320] mg/L, P = 0.0001), with prepubertal patients showing no difference. Pubertal and postpubertal patients showed both higher lipoprotein(a) (P = 0.01) levels and higher albumin excretion rates (P = 0.02) than prepubertal patients, correcting for the other variable. Lipoprotein(a) was not related to HbA1c, albumin excretion rate, duration, age, sex, mean arterial pressure, or a family history of premature coronary artery disease in the IDDM group. Lipoprotein(a) was not higher in patients with overnight albumin excretion rate above the 95th percentile but below the microalbuminuric range. ApoB-100 did not differ between IDDM and control children. ApoA-I was significantly lower in the IDDM group (1.04 [0.94-1.17] vs. 1.21 [1.10-1.31] g/L; P < 0.0001). CONCLUSIONS: Pubertal and postpubertal IDDM patients have higher serum lipoprotein(a) than Caucasian control subjects. Our findings suggest a rise in lipoprotein(a) may occur during puberty in IDDM. Longitudinal studies are required to clarify the relationship between lipoprotein(a), albumin excretion rate, and puberty.

IgG subclass antibodies to glutamic acid decarboxylase and risk for progression to clinical insulin-dependent diabetes.

Pancreatic islet beta cell destruction leading to insulin-dependent diabetes mellitus (IDDM) is believed to be mediated by a T-helper 1 (T(H)1) lymphocyte response to islet antigens. In the mouse, T(H)1 (IL-2, IFN-gamma) and T(H)2 (IL-4, -5, -6, -10) responses are associated with the generation of IgG2a and IgG1 subclasses, respectively. The equivalent human subclasses have not been defined. Because the IgG subclass response to an antigen may be a potentially useful marker of T(H)1/T(H)2 immune balance we measured IgG subclass antibodies to glutamic acid decarboxylase (GAD), a major islet autoantigen in IDDM, in 34 newly-diagnosed IDDM patients and in 28 at-risk, first-degree relatives of people with IDDM. In the newly-diagnosed patients, total IgG antibodies to GAD were detected in 74% (25/34); IgG1 and/or IgG3 were significantly more frequent than IgG4 or IgG4/IgG2 (14/34 versus 5/34, p = 0.01). GAD antibody-negative patients were significantly younger (p = 0.01). In 15 at-risk relatives who had not progressed to clinical diabetes after a median of 4.5 years, 10 had IgG2 and/or IgG4 antibodies compared to only 3/13 progressors (p = 0.02). Total IgG and IgG2 antibodies were higher in non-progressors. Non-progressors were older than progressors (p = 0.01), and relatives with IgG2 and/or IgG4 responses were also older (p = 0.01). These results suggest that IgG subclass antibodies to GAD may contribute to diabetes risk assessment in islet antibody relatives.

Ambulatory blood pressure and heart rate in adolescents with insulin-dependent diabetes mellitus.

There is little information regarding ambulatory blood pressure in adolescents with insulin-dependent diabetes. Twenty-four-hour ambulatory blood pressure and heart rate was studied in 28 normotensive adolescents with insulin-dependent diabetes mellitus (IDDM) and normoalbuminuria, and adolescent controls. Ambulatory heart rate was higher during day and night (P = .001) in the IDDM patients, with normal mean diurnal variation of heart rate and blood pressure. Duration of diabetes related to diastolic ambulatory blood pressure (r = 0.69, P = .0001) and diastolic blood pressure burden (r = 0.61, P = .0001) independent of age, gender, height, body mass index, metabolic control, and albumin excretion rate. The ambulatory blood pressure monitor was well accepted in patients and controls. Ambulatory blood pressure monitoring in adolescents detects early changes in relation to duration of insulin-dependent diabetes.

Effects of changes in acid base and calcium concentration on fasting serum insulin, proinsulin, and glucose concentrations.

AIMS: To test the hypothesis that alterations in acid base or calcium concentration may affect proinsulin processing or the insulin secretion mechanism. METHODS: Changes in proinsulin secretion or cleavage were assessed by measuring serum intact proinsulin and immunoreactive insulin concentrations in three models of acid base and calcium disturbance: (1) subacute changes in acid base status in six volunteers who received oral placebo, ammonium chloride, or sodium bicarbonate for three five day periods; (2) acute changes in calcium concentration in eight subjects who received 25 mmol oral calcium; (3) chronic changes in calcium concentration in seven patients with primary hyperparathyroidism and five with pseudohypoparathyroidism. RESULTS: Acid base changes were confirmed by rises in serum bicarbonate concentrations (p < 0.01). No changes in serum insulin, intact proinsulin, or the proinsulin:insulin molar ratio were found. Serum calcium concentrations increased (2.49 v 2.38 mmol/l; p < 0.05) and parathyroid hormone concentrations decreased (1.1 v 1.9 pmol/l; p < 0.01) two hours after acute calcium loading. There were no significant differences in serum glucose, insulin, or intact proinsulin concentrations. Fasting proinsulin concentrations were significantly lower in the hyperparathyroid group (1.1 v 2.1 pmol/l; p < 0.05) and increased significantly after parathyroidectomy (2.1 v 1.1 pmol/l; p < 0.05). CONCLUSIONS: The results indicate that subacute acid base changes do not affect proinsulin cleavage. Although acute calcium loading has no demonstrable effect, chronic hypercalcaemia may influence the mechanism of insulin secretion.

Evidence for a functional hepatocyte growth factor receptor in human mesangial cells.

In this study we have investigated both the expression of c-met in cultured human mesangial cells and the proliferative effect of HGF on these cells. RNAse protection analysis using a c-met riboprobe showed c-met to be expressed and further that this expression was unaffected by the glucose concentration or osmolality of the media. Immunofluorescence studies performed using anti-HGF or anti-c-met antibodies clearly showed that both proteins are localised to human mesangial cells. Proliferation of human mesangial cells after 24-h treatment with HGF was also examined. HGF 10 ng/ml and 100 ng/ml stimulated 3-H-Thymidine incorporation 1.35-fold (P = 0.001) and 1.6-fold (P<0.00001) respectively in cells made quiescent for 24 h. A similar dose-dependent stimulation of proliferation was observed in cells made quiescent for 48 h. Finally, using RNAse protection analysis we have shown that HGF (10 ng/ml, 100 ng/ml) induces the expression of c-met in these cells in a dose-dependent manner. Together these results indicate for the first time a potential autocrine role for HGF in the human mesangium.

Factors predicting residual beta-cell function in the first year after diagnosis of childhood type 1 diabetes.

Twenty-five children aged 2-14 years (mean age 8.39 +/- 0.78 years) were studied prospectively during the first year after the diagnosis of type 1 diabetes. Of their clinical and metabolic features at diagnosis, only age showed a significant independent relationship with endogenous C-peptide production during the first year. Age was correlated with higher values for basal and stimulated plasma C-peptide at 7-14 days after diagnosis, at 6 months and at 12 months. At diagnosis, age was also associated with a higher value for HbA1c and a lower prevalence of insulin antibodies. C-peptide production peaked at 3 months and thereafter declined. Mean HbA1c and insulin requirement were both minimal at 6 months. At diagnosis, there were significant inverse relationships between basal C-peptide production and both insulin dose and HbA1c and between stimulated C-peptide production and HbA1c. Basal and stimulated C-peptide production were inversely related to insulin dose at 6 and 12 months. Stimulated C-peptide was higher at 12 months in children retaining islet cell antibodies. These findings confirm the importance of age as a predictor of residual beta-cell function in type 1 diabetes and indicate that older children present clinically following a slower course of beta cell destruction.

Cognitive behaviour therapy for adults with chronic fatigue syndrome.

OBJECTIVES: 1. To systematically review all randomised controlled trials of cognitive-behaviour therapy (CBT) for adults with chronic fatigue syndrome (CFS); 2. To test the hypothesis that CBT is more effective than orthodox medical management or other interventions in adults with CFS. SEARCH STRATEGY: 1. Electronic searching of bibliographic databases, including Medline, PsycLIT, Biological Abstracts, Embase, SIGLE, Index to Theses, Index to Scientific and Technical Proceedings, and Science Citation Index, using multiple search terms in order to perform a highly sensitive search. 2. Electronic searching of the Trials Register of the Depression, Anxiety and Neurosis group. 3. Citation lists of relevant studies and reviews were perused for other relevant trials. 4. Contact with the principal authors of relevant studies, and with researchers in the field. SELECTION CRITERIA: All randomised controlled trials were included in which - adult patients with CFS; - received CBT or a control intervention, being either orthodox medical management or another intervention; - and whose outcomes were assessed in an appropriate way. CBT could be either type 'A' (encouraging return to 'normal' levels of rest and activity) or type 'B' (encouraging rest and activity which were within levels imposed by the disorder). DATA COLLECTION AND ANALYSIS: The two reviewers worked independently throughout the selection of trials and data extraction, comparing findings only when there was disagreement. Relevant trials were allocated to one of three quality categories. Full data extraction, using a standardised data extraction sheet, was performed on studies which were of high or moderate quality. Trials of low quality were excluded from the review. The comparisons made to test the review hypothesis were of type 'A' CBT versus other intervention(s), and of type 'B' CBT versus other intervention(s). Functional outcome was used as the main outcome for comparison, but other appropriate outcomes were compared where possible. Results were synthesised using the Review Manager software. For dichotomous data, the odds ratio was calculated for each study. For continuous data, effect sizes were obtained and the standardised mean difference, with 95% confidence intervals, was calculated. MAIN RESULTS: Only three relevant trials of adequate quality were found. These trials demonstrated that CBT significantly benefits physical functioning in adult out-patients with CFS when compared to orthodox medical management or relaxation. It is necessary to treat about two patients to prevent one additional unsatisfactory physical outcome about six months after treatment end. CBT appeared highly acceptable to the patients in these trials. There is no satisfactory evidence for the effectiveness of CBT in patients with the milder forms of CFS found in primary care or in patients who are so disabled that they are unable to attend out-patients. Additionally, there is no satisfactory evidence for the effectiveness of group CBT. REVIEWER'S CONCLUSIONS: Cognitive behaviour therapy appears to be an effective and acceptable treatment for adult out-patients with chronic fatigue syndrome. CFS is a common and disabling disorder. Its sufferers deserve the medical profession to be more aware of the potential of this therapy to bring lasting functional benefit, and health service managers to increase its availability. Further research is needed in this important area. Trials should conform to accepted standards of reporting and methodology. The effectiveness of CBT in more and less severely disabled patients than those usually seen in out-patient clinics needs to be assessed. Trials of group CBT and in-patient CBT compared to orthodox medical management, and of CBT compared to graded activity alone, also need to be conducted.

Dance therapy: effects of motor performance of children with learning disabilities.

This investigation studied effects of dance therapy on motor performance of children who have learning disabilities. An experimental group of five subjects who received dance therapy was compared with a control group of five subjects who received their usual sensory integrative therapy. Pretests and posttests of motor performance were given before and after a four-week treatment period to assess changes. Results indicate improved motor performance for both the experimental and control groups, with slightly greater gains made by the experimental group. Results of the study indicate that dance therapy could serve as a form of vestibular stimulation comparable to the usual play activities in a sensory integrative therapy program.