Does wearing a necktie influence patient perceptions of emergency department care?

This study compared the early clinical course of 9 pediatric heart transplantation recipients treated with cyclosporine A-based immunosuppression with 10 similarly aged recipients treated with tacrolimus-based therapy. One-year follow-up after transplantation revealed that tacrolimus-treated children had similar left ventricular function, experienced fewer episodes of severe rejection, were more rapidly weaned from corticosteroids, and had relatively few side effects from immunosuppression compared with cyclosporine A-treated children.     

Robertsonian chromosomal rearrangements in the short-tailed shrew, Blarina carolinensis, in western Tennessee

We report significant heterozygosity for numerous Robertsonian translocations in the southern short-tailed shrew (Blarina carolinensis) in western Tennessee. Eight Robertsonian rearrangements were documented using G-banding techniques that explain the variability in diploid numbers from 46 throughout most of the range of the species to 34-40 in western Tennessee. These fusions resulted in the loss of telomere sequences and were not associated with nucleolar organizer regions. When heterozygocity is considered, the lowest diploid number possibly present would be 30. Four localities with distances of over 180 km apart were sampled, and 80-90% of the collected animals were heterozygous for at least one rearrangement. No putative parental type was found in western Tennessee. Heterozygosity for the same rearrangements was found in these different localities, and no monobrachial fusions were noted. Thus, this is a very wide hybrid zone with rare or absent parental types in the areas sampled or is an evolutionary stage preceding establishment of Robertsonian races. Selective forces, if any, were minimal, as evidenced by the wide area of polymorphism, significant heterozygosity, and the fact that the Robertsonian translocations were in Hardy-Weinberg equilibrium. The origin of such extensive polymorphism in western Tennessee is discussed, especially in light of putative effects of the New Madrid seismic activity. Similarities and differences are noted between the Blarina model and the well-documented variation in the European common shrew (Sorex araneus) and Mus musculus groups.     

Apolipoprotein(a) induces monocyte chemotactic activity in human vascular endothelial cells

BACKGROUND: Elevated levels of lipoprotein(a) [Lp(a)] are associated with premature atherosclerosis; however, the mechanisms are not known. Recruitment of monocytes to the blood vessel wall is an early event in atherogenesis. METHODS AND RESULTS: This study has found that unoxidized Lp(a) induced human umbilical vein endothelial cells (HUVECs) to secrete monocyte chemotactic activity (MCA), whereas LDL under the same conditions did not. In the absence of HUVECs, Lp(a) had no direct MCA. Endotoxin was shown not to be responsible for the induction of MCA. Actinomycin D and cycloheximide inhibited the HUVEC response to Lp(a), indicating that protein and RNA synthesis were required. The apolipoprotein(a) [apo(a)] portion of Lp(a) was identified as the structural component of Lp(a) responsible for inducing MCA. Lp(a) and apo(a) also stimulated human coronary artery endothelial cells to produce MCA. Granulocyte-monocyte colony-stimulating factor (GM-CSF) antigen was not detected in the Lp(a)-conditioned medium, nor was monocyte chemoattractant protein-1 mRNA induced in HUVECs by Lp(a). CONCLUSIONS: These findings suggest that Lp(a) may be involved in the recruitment of monocytes to the vessel wall and provide a novel mechanism for the participation of Lp(a) in the atherogenic process.     

Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen

We show that 9-cis-retinoic acid (9cRA) is a potent inhibitor of mammary carcinogenesis induced by N-nitroso-N-methylurea in Sprague-Dawley rats. Rats were first treated with a single dose of N-nitroso-N-methylurea (50 mg/kg body weight) and then fed non-toxic levels of 9cRA (120 or 60 mg/kg of diet). 9cRA was highly effective in reducing tumor incidence, average number of tumors per rat, and average tumor burden, as well as extending tumor latency. The combination of 9cRA with low levels of tamoxifen (TAM; fed at either 1.0 or 0.5 mg/kg of diet) was particularly effective; addition of 9cRA to a TAM regimen doubled the number of animals that were tumor-free at autopsy and significantly diminished tumor number and tumor burden. For suppression of carcinogenesis in vivo, 9cRA was much more potent than all-trans-retinoic acid, both as a single agent or in combination with TAM, although both retinoids had equivalent inhibitory effects on DNA synthesis in cultured human breast cancer cell lines. Both 9cRA and all-trans-retinoic acid induce the expression of the adhesion molecule, E-cadherin, in the SK-BR-3 cell line. We suggest that clinical evaluation of the combination of 9cRA and TAM, either for chemoprevention or for adjuvant therapy, should be considered.     

A controlled trial of amino acid therapy in amyotrophic lateral sclerosis: I. Clinical, functional, and maximum isometric torque data

We conducted a two center, double-blind, placebo-controlled treatment trial with oral branched chain amino acids (BCAA) (L-leucine 12 g, L-isoleucine 8 g, and L-valine 6.4 g daily) or L-threonine (4 g daily) with pyridoxal phosphate (160 mg daily) for six months in patients with amyotrophic lateral sclerosis (ALS). The effect of treatment on disease progression was estimated every two months by recording clinical muscle strength, maximum isometric muscle torque in selected muscles, forced vital capacity (FVC), activities of daily living pertaining to the upper and lower limbs, and timed tasks. Ninety-five patients were randomized to receive BCAA (n = 31), L-threonine (n = 32), or placebo (n = 32), of whom 77 (81%) completed the trial. Mean weight loss in the placebo group was 1.1 kg and in the L-threonine group was 3.2 kg; the BCAA group gained 0.2 kg (p = 0.04). The estimated decline in FVC was about 2.5 times greater in the BCAA and L-threonine groups as compared to placebo (p = 0.03). Otherwise, no significant differences were found in the changes observed in clinical, functional, timed, or maximum torque measures among treatment groups. The amino acids were well tolerated. The results of our study failed to show a beneficial effect of BCAA or L-threonine treatment for six months on the disease course in ALS. The higher rate of loss of pulmonary function in patients treated with BCAA or L-threonine may have been due to chance, but an adverse effect of these amino acids cannot be ruled out.     

Familial renal disease or familial juvenile hyperuricaemic nephropathy?

PURPOSE: To investigate the difference of pharmacokinetics of thiol-containing drugs in various disease states, we studies the covalent binding of SA3786, a bucillamine derivative, with proteins in patient serum compared with that in healthy serum. METHODS: Sera from healthy volunteers and patients of various diseases were supplied by the Japanese Red Cross Kumamoto Hospital. For the formation of conjugate experiments, SA3786 was added to a final concentration of 7 x 10(-4)M. After 6 h incubation at 37 degrees C, HPLC analysis of 5 microliters aliquots of each sample was performed using a column of N-methylpyridinium polymer (4VP-Me). RESULTS: The extent of HSA-SA3786 conjugate formation was found to be lower in the sera from healthy volunteers (control) than those from patients of various diseases. Especially high reactivity with SA3786 was observed in sera from rheumatic patients and hepatic patients. With the exception of the fraction of mercaptoalbumin (fHMA), none of the parameters showed a good correlation with conjugate formation. CONCLUSIONS: The parameter fHMA must be considered to be one of the most important factors in formation of conjugates between plasma protein and thiol compounds. However, other factors may be involved in addition to fHMA although the nature of these factors is not clear.     

Megakaryoblastic termination of myeloproliferative disorders

Megakaryoblastic termination of myeloproliferative disorders is rare. The morphology of megakaryoblastic transformation can be subtle and is often mistaken for myeloid or lymphoid proliferations. Previously reported observations suggest a relatively poor prognosis for this category of patients, making precise diagnosis imperative. A multifaceted approach using morphology, ultrastructure, cytochemistry, and immunological membrane analysis may be helpful. We present two cases of myeloproliferative disorder with aggressive megakaryoblastic phases (myelofibrosis with agnogenic myeloid metaplasia and chronic myeloid leukemia with blast crisis). The clinical course is described and the results of the morphological, cytochemical, ultrastructural, and cytogenetic studies of both cases are presented. In addition, immunochemical studies (flow cytometry) and platelet function studies (aggregation, beta-thromboglobulin, and platelet factor IV release) were done for one of these patients.