The sand rat (psammomys obesus) as an experimental animal in studies of diabetes mellitus

Summary The sand rat has some unique attributes, which make it a valuable experimental animal. The occurrence of increased plasma insulin levels and of hyperglycemia is linked to an increased food intake. As in the human maturity-onset type diabetes, there seems to be an element of insulin resistance, and this can be demonstratedin vitro by the relative unresponsiveness of sand rat adipose tissue to increasing doses of pork insulin. Prophylactic treatment with acetohexamide seems to have some protective effect against the diabetogenic results of a high calory diet. — It is expected that the diabetic syndrome in sand rats, which can be so easily induced by dietary manipulation, will be a valuable tool in helping to clarify some of the possible mechanisms in the syndrome of diabetes mellitus.This work was carried out during the tenure of Research Career Awards from the U. S. Public Health Service to Drs.Hackel (HE-K6-14, 188) andSchmidt-Nielsen, (K6-GM-21, 522) a Career Development Award to Dr.Lebovitz (K3-AM-17, 954), and a Research Fellowship to Dr.Horton (F3-AM-32, 326); supported by grants from the U. S. Public Health Service (AM-08949, AM-1324, and HE-0228), Eli Lilly Co., the Duke University Research Council, and the Mary Duke Biddle Foundation.     

Effects of obesity on mortality in patients with unstable angina or non-ST-elevation myocardial infarction.

In a recent article, Buettner et al.¹ proposed that obesityis associated with improved outcome in coronary artery diseasepatients after early revascularization because of UA/NSTEMIover a mean follow-up time of 17 months. The data presentedin the first figure     

Psychiatric and behavioural symptoms and the use of psychotropic medication in Special Care Units and Regular Units in Norwegian nursing homes

Background: In a number of countries Special Care Units (SCUs) have been established to meet the particular needs of patients with dementia. The criteria for SCUs are poorly defined and often not met. Aim: To assess the frequency distributions of dementia, psychiatric and behavioural symptoms and the use of psychotropic medication in SCUs and Regular Units (RUs) across different regions. Methods and material: By means of a structured interview, comprising the Neuropsychiatric Inventory, the Clinical Dementia Rating Scale and Lawton’s Physical Self‐maintenance scale, a representative sample of 1163 nonselected nursing home patients was assessed. In addition, information was collected from the patients’ records. Results: Overall SCU patients were significantly more likely to be younger, to have higher level of functioning, to have dementia, to exhibit clinically significant psychiatric and behavioural symptoms and to receive psychotropic medication. There were significant differences across regions in terms of psychiatric and behavioural symptoms and the use of psychotropic medication. The ratio of accommodation in SCUs to that in RUs varied across the regions. Conclusion: Patients in SCUs and patients in RUs are distinct nursing home populations. Regional differences, which might be due to diverse ratios of SCUs, are evident.     

Hemofiltrate CC chemokine 1[9-74] causes effective internalization of CCR5 and is a potent inhibitor of R5-tropic human immunodeficiency virus type 1 strains in primary T cells and macrophages

Proteolytic processing of the abundant plasmatic human CC chemokine 1 (HCC-1) generates a truncated form, HCC-1[9-74], which is a potent agonist of CCR1, CCR3, and CCR5; promotes calcium influx and chemotaxis of T lymphoblasts, monocytes, and eosinophils; and inhibits infection by CCR5-tropic human immunodeficiency virus type 1 (HIV-1) isolates. In the present study we demonstrate that HCC-1[9-74] interacts with the second external loop of CCR5 and inhibits replication of CCR5-tropic HIV-1 strains in both primary T cells and monocyte-derived macrophages. Low concentrations of the chemokine, however, frequently enhanced the replication of CCR5-tropic HIV-1 isolates but not the replication of X4-tropic HIV-1 isolates. Only HCC-1[9-74] and HCC-1[10-74], but not other HCC-1 length variants, displayed potent anti-HIV-1 activities. Fluorescence-activated cell sorter analysis revealed that HCC-1[9-74] caused up to 75% down-regulation of CCR5 cell surface expression, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) achieved a reduction of only about 40%. Studies performed with green fluorescent protein-tagged CCR5 confirmed that both HCC-1[9-74] and RANTES, but not full-length HCC-1, mediated specific internalization of the CCR5 HIV-1 entry cofactor. Our results demonstrate that the interaction with HCC-1[9-74] causes effective intracellular sequestration of CCR5, but they also indicate that the effect of HCC-1[9-74] on viral replication is subject to marked cell donor- and HIV-1 isolate-dependent variations.     

Use of robotized DNA isolation and real-time PCR to quantify and identify close correlation between levels of Neisseria meningitidis DNA and lipopolysaccharides in plasma and cerebrospinal fluid from patients with systemic meningococcal disease

The present study, using robotized DNA isolation and quantitative PCR based on the Neisseria meningitidis-specific capsular transport A gene, demonstrates the ease, rapidity, specificity, and sensitivity of quantifying neisserial DNA in plasma (n = 65) and cerebrospinal fluid (CSF) (n = 12) from patients with systemic meningococcal disease. We found a close correlation between the levels of neisserial DNA and lipopolysaccharides in plasma (r = 0.905) and in CSF (r = 0.964). The median concentration of neisserial DNA in plasma in 23 patients with persistent shock was 2 x 10(7) copies/ml, versus <10(3) copies/ml in 42 nonshock patients. Furthermore, quantitative PCR made possible estimates of the total number of meningococci in plasma, as opposed to conventional blood cultures, suggesting about 1,000 dead meningococci for every viable bacterium. Finally, with logistic regression analyses, neisserial DNA may predict a patient's disease severity and outcome at hospital admission. The number of meningococci in plasma and CSF appears to be the main determinant of the lipopolysaccharide levels, clinical presentation, and outcome.     

Tubular absorption of filtered cystatin-C in the rat kidney

As shown in previous studies, the two basic proteins aprotinin (Ap, 6.5 kDa) and cystatin (Cy, 13.3 kDa) can be used to estimate whole kidney glomerular filtration rate by measuring the renal cortical uptake relative to plasma concentration after i.v. injection. Local uptake of Ap can also be used to estimate local filtration rate, and the present experiments were undertaken to examine whether Cy would give a similar uptake pattern. Ap and Cy were labelled with 131I and 125I, respectively, and injected as an i.v. bolus. Frequent blood samples provided information on the filtered load. Five to 20 min after injection the kidney was clamped, frozen, and five tissue samples of 5-10 mg each were cut out from outer (OC), middle (MC) and inner cortex (IC) to be weighed and assessed for radioactivity. Five minute clearance ratios, Cy:Ap, were 1.36 +/- 0.04, 1.27 +/- 0.03 and 1.19 +/- 0.04 in OC, MC and IC, respectively. The higher Cy clearance was expected from a higher glomerular filtrate:plasma ratio of the less basic Cy (Donnan distribution). However, this does not explain the increase of Cy:Ap clearances going from IC to the OC. A surplus of extracellular uptake of Cy in superficial layers was excluded, leading to the following interpretation. In all cortical layers the proximal convoluted tubule, i.e. the protein uptake segment, is located more superficially than its parent glomerulus. A longer uptake segment for Cy than for Ap will therefore lead to a relative greater transfer of filtered Cy from IC to MC, and from MC to OC. Anatomical studies on single nephrons presented in another article lend strong support to this interpretation.     

Norwegian General Practitioners’ Perspectives on Implementation of a Guided Web-Based Cognitive Behavioral Therapy for Depression: A Qualitative Study

Background

Previous research suggests that Internet-based cognitive behavioral therapy (ICBT) has a positive effect on symptoms of depression. ICBT appears to be more effective with therapist support, but it is unclear what this support should comprise. General practitioners (GPs) have positive attitudes toward ICBT. However, ICBT is rarely used in regular care in general practice. More research is warranted to integrate the potential of ICBT as part of regular care.

Objective

The aim of this study was to explore aspects perceived by GPs to affect the implementation of guided ICBT in daily practice. Understanding their perspectives may contribute to improving the treatment of depression in the context of general practice.

Methods

A training package (3-day course) introducing a Norwegian translation of the ICBT program MoodGYM was developed and presented to GPs in Norway. Following training, GPs were asked to include guided ICBT in their regular care of patients with symptoms of depression by providing brief, face-to-face follow-up consultations between modules. We interviewed 11 GPs who had taken the course. Our interview guide comprised open questions that encouraged GPs to frame their responses using examples from their experiences when implementing ICBT. Thematic analysis was chosen to explore patterns across the data.

Results

An overall belief that ICBT would benefit both the patients’ health and the GPs’ own work satisfaction prompted the GPs to take the ICBT course. ICBT motivated them to invest time and effort in improving treatment. The most important motivating aspects in MoodGYM were that a program based on cognitive behavioral therapy could add a structured agenda to their consultations and empower depressed patients. Organizational aspects, such as a lack of time and varied practice, inhibited the use of ICBT. Inadequate knowledge, recalling the program, and changing own habits were also challenging. The GPs were ambivalent about whether ICBT had a negative impact on the doctor–patient interaction in the module follow-ups. Generally, GPs made an effort to recommend MoodGYM, but the expected module follow-ups were often not provided to patients and instead the GPs returned to standard treatment.

Conclusions

GPs’ feedback in the present study contribute to our understanding of the challenges of changing treatment for depression. Our findings indicated that recommending ICBT could add to the GP’s toolkit. Offering training and highlighting the following aspects may increase recommendation of ICBT by GPs: (1) ICBT is theory-based and credible, (2) ICBT increases the GPs’ work satisfaction by having a tool to offer, and (3) ICBT facilitates empowerment of patients in their own health. In addition, the present study also indicated that complex aspects must be accommodated before module follow-ups can be incorporated into GPs’ treatment of depression.     

Cognitive outcome in children and adolescents treated for acute lymphoblastic leukaemia with chemotherapy only

Objective: To examine cognitive outcome in children and adolescents with acute lymphoblastic leukaemia (ALL) in remission, treated with central nervous system prophylactic chemotherapy only.
Method: Thirty-five children and adolescents, age 8.4–15.3 years in long-term remission from ALL, 4.2–12.4 years post diagnosis, without relapse and no prediagnosis history of neurodevelopmental disorder were compared with 35 healthy controls matched for gender and age, on measures of intellectual functioning Wechsler Intelligence Scale for Children-Third Edition (WISC-III).
Results: All but two of the ALL survivors treated by chemotherapy only obtained WISC-III Total Intelligence Quotient (IQ) scores in the normal range (M = 95.3), but their scores were significantly below levels for their matched controls and below normative standards for WISC-III. The difference between patients and controls was significant at the p < 0.001 level for the following measures: Total IQ, Verbal IQ, Verbal Comprehension Index, Freedom from Distraction Index and three verbal subtest scores.
Conclusion: The results indicate long-term sequelae in global cognitive functions, and indicate that verbal function, processing speed, attention and complex visual-spatial problem solving may be affected in the chemotherapy only group.     

Feeling what you hear: auditory signals can modulate tactile tap perception

We tested whether auditory sequences of beeps can modulate the tactile perception of sequences of taps (two to four taps per sequence) delivered to the index fingertip. In the first experiment, the auditory and tactile sequences were presented simultaneously. The number of beeps delivered in the auditory sequence were either the same as, less than, or more than the number of taps of the simultaneously presented tactile sequence. Though task-irrelevant (subjects were instructed to focus on the tactile stimuli), the auditory stimuli systematically modulated subjects tactile perception; in other words subjects responses depended significantly on the number of delivered beeps. Such modulation only occurred when the auditory and tactile stimuli were similar enough. In the second experiment, we tested whether the automatic auditory-tactile integration depends on simultaneity or whether a bias can be evoked when the auditory and tactile sequence are presented in temporal asynchrony. Audition significantly modulated tactile perception when the stimuli were presented simultaneously but this effect gradually disappeared when a temporal asynchrony was introduced between auditory and tactile stimuli. These results show that when provided with auditory and tactile sensory signals that are likely to be generated by the same stimulus, the central nervous system (CNS) tends to automatically integrate these signals.