Abnormal neuromuscular junctions in the lateral rectus muscle of wobbler mice

We have studied the lateral rectus muscles and neuromuscular junctions (NMJs) of abducens motoneurons in wobbler (wr/wr) mutant mice from 26 to 58 days of age. The muscles of wr/wr weighed about 70% of the weight of littermate controls and were composed of fiber types comparable to those of controls, as assayed by succinate dehydrogenase activity. The most obvious difference between wr/wr and control NMJs was a reduction in the length of the postjunctional membrane of wr/wr mice. The mutant muscle endplate membrane was only about 70% (6.58 micron) the length of control muscle regions (9.44 micron). There were no obvious differences at the light microscopic level in the distribution of acetylcholine (ACh) receptors at junctional regions or staining of acetylcholinesterase, as assayed with alpha-bungarotoxin binding or enzyme histochemistry. Indirect immunocytochemical studies using antibodies directed against the subunits of the ACh receptor failed to indicate an abnormal presence of immature receptors clustered at the NMJs of wr/wr mice. Our findings suggest that the formation or maintenance of normal postjunctional folds and the differentiation of receptors at the junctions are under independent control during development. Furthermore, the wobbler mutation may affect muscle cell differentiation as well as neuronal differentiation. This mutant mouse should prove a useful model for study of postjunctional fold formation and function.     

Colonic Motility in Profoundly Disabled People: A comparison of massage and laxative therapy in the management of constipation

This pilot study compared abdominal massage with laxative treatment in the management of constipation in 32 profoundly disabled, institutionalised adults. A randomised cross-over design was used. After an initial 16-day baseline measurement phase without any treatment, there followed two seven-week treatment phases separated by a one-week washout period. Each subject received seven weeks of massage and seven weeks on his or her previous laxative regimen. Primary outcome measures were gastro-intestinal and segmental transit times, measured at the end of the baseline phase and of each treatment phase. Secondary measures included stool frequency, size and consistency, the requirement for enemas and an assessment of patient well-being.The median value of total colonic transit time was 183 hours for the baseline phase and 159 hours for all treatment phases. There was no evidence of any statistically significant treatment differences between laxative and massage therapy for right, left or rectosigmoid segments either separately or in total. Analysis of secondary outcome measures also failed to find any treatment preferences.These results reveal the grossly abnormal colonic transit times of the study population at all times. The effects of laxative and massage therapy within this environment were not demonstrably different.     

Methimazole as a protectant against cisplatin-induced nephrotoxicity using the dog as a model

Dexniguldipine-HCl (DNIG) — a prospective clinical modulator of p170-glycoprotein (pgp170)-mediated multidrug resistance (MRD) — was evaluated in a drug-accumulation assay in MDR murine leukemia cell strain F4-6RADR expressing pgp170. The compound elevated low accumulation of either doxorubicin (DOX), daunorubicin (DNR), or mitoxantrone (MITO) in resistant F4-6RADR cells to the very levels observed in drug-sensitive F4-6 precursor cells. In parallel with the increase in DNR content (F4-6RADR, solvent: 303±27 pmol/mg protein; DNIG (3.3 mol/l): 1,067±174 pmol/mg protein; F4-6P, solvent: 948±110 pmol/mg protein;n=8–9, SEM), the amount of DNR tightly bound to the acid precipitate pellet obtained from F4-6RADR (i.e., protein, DNA, RNA) increased 3.9-times to the levels observed in sensitive F4-6 cells. The main pyridine metabolite of DNIG displayed similar activity. Concentration-response analysis revealed that DNIG and R,S-verapamil (VER) induced 100% reversal of the DNR accumulation shortage associated with the MDR phenotype but DNIG was 8 times more potent than VER (50% inhibitory concentration (IC₅₀), 0.73 vs 5.4 mol/l). In keeping with the accumulation assay, DNIG was about 10 times more potent than VER in sensitizing F4-6RADR cells to the cytostatic and cytotoxic effects of DNR in proliferation assays. In conclusion, DNIG is a potent in vitro modulator, improving (a) the accumulation of anthracycline-like cytostatics, (B) drug access to cellular binding sites, and (c) the cytostatic action of DNR in F4-6RADR leukemia cells of the MDR phenotype.Abbreviations DOX doxorubicin - CSA cyclosporin A - DMSO dimethylsulfoxide - DNIG dexniguldipine-HCl - DNR daunorubicin - MDR multidrug resistance - MITO mitoxantrone - pgp170 permease glycoprotein 170 - VER R.S.-verapamil Dexniguldipine-HCl is the proposed INN for compound B859-35, the R-enantiomer of niguldipine. Segments of this work have been reported in the abstract form     

The effect of recombinant human growth hormone on responses to alloantigens in the pediatric transplant patient

Recombinant human growth hormone (rhGH) improves growth in children after renal transplantation, but may be associated with augmented immune responses. We previously demonstrated that rhGH augments proliferative and cytotoxic responses and interferon-gamma (IFN-) mRNA expression during a mixed leukocyte culture (MLC). In this study, we evaluated 12 pediatric patients after receiving a renal allograft from one of their parents. Peripheral blood mononuclear cells (PBMC) were isolated from patients and cultured with either donor or unrelated third-party PBMC in an MLC. Patients developed significant donor-specific hyporesponsiveness (DSH), however, no correlation was seen between the amount of DSH and graft function. Of the 12 patients, 2 developed augmented responses in the presence of rhGH. rhGH augments proliferation, cytotoxicity, and IFN- expression during an MLC. Some patients develop increased responses to donorspecific alloantigens after renal transplantation. Further study is needed to better determine the significance of this finding.     

Thromboelastography as a perioperative measure of anticoagulation resulting from low molecular weight heparin: a comparison with anti-Xa concentrations

Low molecular weight heparin (LMWH) is commonly used to prevent postoperative thromboembolism. Currently, there is no convenient test to measure the degree of anticoagulation from LMWH. This prospective study examines the relationship of thromboelastography and serum anti-Xa concentration in patients treated with enoxaparin. Twenty-four adult patients scheduled for orthopedic surgery using epidural anesthesia were enrolled. Epidural catheters were removed the morning after surgery before the commencement of subcutaneous enoxaparin 30 mg twice daily. Venous blood samples were obtained at 1) the induction of anesthesia (baseline), 2) immediately before the third dose of enoxaparin postoperatively (Day 2-trough), 3) 4 h after the third dose postoperatively (Day 2-peak), and 4) immediately before the fifth dose postoperatively (Day 3-trough). Whole blood samples were obtained for thromboelastography, activated clotting time, and anti-Xa level analyses at each of the four time intervals. At the four sample intervals, the r time (mean +/- SEM). (20 +/- 1, 25 +/- 2, 51 +/- 6, 31 +/- 3 mm) and the k time (9 +/- 0. 7, 12 +/- 1, 27 +/- 5, 14 +/- 2 mm) of the thromboelastograph were significantly correlated with the expected peak and trough levels of LMWH and serum anti-Xa levels (P: < 0.05). At the Day 3-trough, thromboelastograph r times exceeded the normal range in 6 of 25 patients (25%). Prolongation of r time and k time on postoperative Day 3 may indicate an exaggerated response to LMWH. Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. Implications: Thromboelastography is a test that could potentially correlate with the degree of anticoagulation produced by low molecular weight heparin. The r time from the thromboelastogram correlates with serum anti-Xa concentration.     

An Integrative Review of Adolescent Smoking Cessation Using the Transtheoretical Model of Change

IntroductionThe purpose of this literature review is to report the effectiveness of trials using the Transtheoretical Model of Change for achieving smoking cessation among adolescents.MethodAn integrative literature review was performed. Two reviewers searched the Internet for randomized, controlled trials or observational studies of adolescent smoking cessation trials reported between 1999 and June 2009 that used the Transtheoretical Model of Change.ResultsSix randomized controlled trials remained after all inclusion and exclusion criteria were met. Each study was reviewed qualitatively and odds ratio and quit rates were calculated. Four studies demonstrated an odds ratio of greater than 1.0, and in four studies significantly better quit rates were found in the intervention arm versus the control arm at the endpoint evaluation.DiscussionEvidence exists for the effectiveness of stage-based interventions in promoting smoking cessation in adolescents.     

The role of social workers in addressing nonmedical needs in primary health care

Nonmedical needs are intricately linked to health. Unaddressed nonmedical needs often result in poorer health and increased healthcare costs. Although social workers are well positioned to address nonmedical needs, their role in healthcare environments to address nonmedical needs is limited. The limited role relates to a lack of reimbursement streams, which stems from poor articulation about their unique contributions. An analysis of a case study in which a social worker using AIMS, a protocolized care coordination model, was undertaken to highlight specific activities performed by social workers. Implications for patient health outcomes and healthcare costs are discussed.