Quantitative analysis of muscle fibre type and myosin heavy chain Distribution in the frog hindlimb: implications for locomotory design

To investigate the design of the frog muscular system for jumping, fibre type distribution and myosin heavy chain (MHC) isoform composition were quantified in the hindlimb muscles of Rana pipiens. Muscles were divided into two groups: five large extensor muscles which were predicted to shorten and produce mechanical power during jumping (JP), and four much smaller muscles commonly used in muscle physiology studies, but that do not shorten or produce power during jumping (NJP). Fibres were classified as one of four different types (type 1, 2, 3 or tonic) or an intermediate type (type 1–2) based ontheir relative myosin-ATPase reactivity and MHC immunoreactivity in muscle cross-sections according to previous nomenclature established for amphibian skeletal muscle. Type 1 fibres correspond to the fastest and most powerful of the twitch fibres, and type 3 fibres are the slowest and least powerful. Myosin-ATPase histochemistry revealed that the JP muscles were co mposed primarily of type 1 fibres (89%) with a small percentage of type 2 (7%) and intermediate type 1–2 fibres (4%). The fibre type composition of NJP muscles was more evenly distributed between type 1 (29%), type 2 (46%) and type 1–2 (24%) fibres. Tonic fibres comprised less than 2% of the muscle cross-section in both JP and NJP groups. Similarly, MHC composition determined by quantitative SDS–PAGE revealed that JP muscles were composed predominantly of type 1 MHC (86%), with a balance of type 2 MHC (14%). The opposite pattern was found for MHC composition in the NJP muscles: type 1 (28%), type 2 (66%) and type 3 (6%). These results demonstrate that the large extensor muscles that produce the power required for jumping have a fibre type distribution that enables them to generate high levels of mechanical power, with the type 1 isoform accounting for 85–90% of the total M HC content.     

Comparison of total body irradiation versus non-total body irradiation containing regimens for de novo acute myeloid leukemia in children

With limited data comparing hematopoietic cell transplant outcomes between myeloablative total body irradiation (TBI) containing and non-TBI regimens in children with de novo acute myeloid leukemia, the aim of this study was to compare transplant-outcomes between these regimens. Cox regression models were used to compare transplant-outcomes after TBI and non-TBI regimens in 624 children transplanted between 2008 and 2016. Thirty two percent (n=199) received TBI regimens whereas 68% (n=425) received non-TBI regimens. Five-year non-relapse mortality was higher with TBI regimens (22% vs. 11%, P<0.0001) but relapse was lower (23% vs. 37%, P<0.0001) compared to non-TBI regimens. Consequently, overall (62% vs. 60%, P=1.00) and leukemia-free survival (55% vs. 52%, P=0.42) did not differ between treatment groups. Grade 2-3 acute graft versus host disease was higher with TBI regimens (56% vs. 27%, P<0.0001) but not chronic graft versus host disease. The 3-year incidence of gonadal or growth hormone deficiency was higher with TBI regimens (24% vs. 8%, P<0.001) but there were no differences in late pulmonary, cardiac or renal impairment. In the absence of a survival advantage, the choice of TBI or non-TBI regimen merits careful consideration with the data favoring non-TBI regimens to limit the burden of morbidity associated with endocrine dysfunction.     

Inherited disorders of the IL-12-IFN-γ axis in patients with disseminated BCG infection

Disseminated BCG infection is a rare complication of vaccination that occurs in patients with impaired immunity. In recent years, a series of inherited disorders of the IL-12-IFN- axis have been described that predispose affected individuals to disseminated disease caused by BCG, environmental Mycobacteria, and non-typhoidal Salmonella. The routine immunological work-up of these patients is normal and the diagnosis requires specific investigation of the IL-12-IFN- circuit. We report here the first two such patients originating from and living in Iran. The first child is two years old and suffers from complete IFN- receptor 2 deficiency and disseminated BCG infection. He is currently in clinical remission thanks to prolonged multiple antibiotic therapy. The other, a 28-year-old adult, suffers from IL-12p40 deficiency and presented with disseminated BCG infection followed by recurrent episodes of systemic salmonellosis. He is now doing well. A third patient of Iranian descent, living in North America, was reported elsewhere to suffer from IL-12R1 deficiency. These three patients thus indicate that various inherited defects of the IL-12-IFN- circuit can be found in Iranian people. In conclusion we recommend to consider the disorders of the IL-12-IFN- circuit in all patients with severe BCG infection, disseminated environmental mycobacterial disease, or systemic non-typhoidal salmonellosis, regardless of their ethnic origin and country of residence.     

Cytologic distinctions between clinical groups using curette-probe compared to cytology brush.

BACKGROUND: We had previously used curette-probe (Rhinoprobe; Arlington Scientific, Springville, UT) to study nasal cytology in various types of patients. Because of the potential sampling ease of using a brush, we sought to compare cytological results obtained with a curette-probe with those obtained using a cytology brush (Cytobrush Plus; Medscand, Malm?, Sweden). OBJECTIVE: To compare the ability of samples of nasal leukocytes obtained with a curette-probe versus a cytology brush to distinguish clinical categories of patients attending an allergy clinic. METHODS: Adult allergy clinic patients were studied by both curette-probe and cytology brush sampling. Quantitation of eosinophils and total leukocytes was performed on samples. Comparisons of cell quantities for each sampling method were made in patients classified into clinical groups. Patients with rhinitis complaints and abnormalities of nasal mucosal appearance with or without aeroallergy were compared with other patients. The adjustment of leukocyte quantities for the numbers of epithelial cells observed was also analyzed. Sampling methods were also compared for receiver operating characteristics. RESULTS: Curette-probe sample leukocyte quantities distinguished patients with symptoms of rhinitis (SR) with abnormal nasal appearance from other patients. This between-group distinction was more significant for leukocyte numbers normalized for the number of epithelial cells. SR patients with both abnormal nasal appearance and aeroallergy had significantly more eosinophils and less goblet cells than other patients. Greater than five curette-probe eosinophils were only observed in patients with SR. Brush samples did not show differences between patients stratified in these ways, and eosinophils were observed in patients without SR. Receiver operating characteristics favored curette-probe samples in terms of leukocyte or eosinophil increases characterizing their respective symptomatic patient subgroups. CONCLUSIONS: Curette-probe-obtained nasal samples allow for leukocyte and eosinophil quantitations which characterize rhinitis patients better than brush-obtained samples. Total leukocyte quantitations obtained by curette-probe may represent a marker of inflammatory nasal disease in adults undergoing allergy evaluation and treatment for rhinitis.     

Inhibition of P-glycoprotein by newer antidepressants

Pharmacokinetic drug-drug interactions often occur at the level of P-glycoprotein (Pgp). To study possible interactions caused by the newer antidepressants we investigated citalopram, fluoxetine, fluvoxamine, paroxetine, reboxetine, sertraline, and venlafaxine and their major metabolites desmethylcitalopram, norfluoxetine, paroxetine-metabolite (paroxetine-M), desmethylsertraline, N-desmethylvenlafaxine, and O-desmethylvenlafaxine for their ability to inhibit Pgp. Pgp inhibition was studied by a fluorometric assay using calcein-acetoxymethylester as Pgp substrate and two different cell systems: L-MDR1 cells (model for human Pgp) and primary porcine brain capillary endothelial cells (pBCECs, model for the blood-brain barrier). Both cell systems proved to be suitable for the evaluation of Pgp inhibitory potency of drugs. All antidepressants tested except O-desmethylvenlafaxine showed Pgp inhibitory activity with sertraline, desmethylsertraline, and paroxetine being the most potent, comparable with the well known Pgp inhibitor quinidine. In L-MDR1 cells fluoxetine, norfluoxetine, fluvoxamine, reboxetine, and paroxetine-M revealed intermediate Pgp inhibition and citalopram, desmethylcitalopram, venlafaxine, and N-desmethylvenlafaxine were only weak inhibitors. The ranking order was similar in pBCECs. The fact that some of the compounds tested exert Pgp inhibitor effects at similar concentrations as quinidine suggests that pharmacokinetic drug-drug interactions between the newer antidepressants and Pgp substrates should now be thoroughly studied in vivo.     

Lethal Tuberculosis in a Previously Healthy Adult with IL-12 Receptor Deficiency

A 33-year-old man was admitted in hospital due to fever, generalized lymphadenopathy, and hepatosplenomegaly. He had a history of anti-tuberculosis treatment in the previous 3 years. Despite normal chest radiograph, a sputum sample was smear-positive for acid-fast bacilli, and polymerase chain reaction was positive for Mycobacterium tuberculosis complex. Drug susceptibility test revealed resistance to isoniazid and rifampin. Evaluation of the patient’s immune system revealed IL-12Rβ1 deficiency. The patient died of disseminated tuberculosis (TB), despite appropriate antibiotic treatment. This is the first IL-12 receptor-deficient patient presenting with disseminated TB in adulthood, without any previous relevant medical history. This diagnosis should be considered in selected adult patients with unexplained, overwhelming TB. IL-12Rβ1 deficiency is a genetic etiology of severe TB in adults and should be considered in adult patients with disseminated TB.     

Early Echocardiographic Findings in ��-Thalassemia Intermedia Patients Using Standard and Tissue Doppler Methods

Heart complications are among the serious problems of patients with β-thalassemia intermedia. This study aimed to evaluate myocardial function in these patients. Clinical parameters and both standard Doppler and pulsed Doppler tissue imaging parameters were compared in 51 β-thalassemia intermedia patients (mean age, 17.05 ± 5.8 years) and 20 normal subjects (mean age, 17.81 ± 7.35 years, p = 0.98). In 11 patients (21.5%), pulmonary artery hypertension was detected. M-mode echocardiographic findings such as ejection fraction and fractional shortening did not show statistically significant changes (p > 0.005). Pulsed Doppler showed a significant difference in the early (E) to late diastolic (A) velocity ratio of the tricuspid and mitral valve between the patients and the control subjects (p < 0.05). In the pulsed tissue Doppler study, the peak systolic velocity of the septum (Ss), the peak atrial velocity of the septum (Aas), the peak systolic velocity of the tricuspid annulus (St), the peak early diastolic velocity of the tricuspid annulus (Eat), and the peak late diastolic velocity of the tricuspid annulus (Aat) were increased significantly (p < 0.05). The pulse tissue Doppler of the lateral mitral annulus did not change significantly (p > 0.005). The peak systolic velocity of the posterior wall and the peak late diastolic velocity of the anterior wall changed significantly (p < 0.05). This study showed that β-thalassemia intermedia patients with normal M-mode and two-dimensional echocardiography had statistically significant changes in pulsed Doppler and pulsed tissue Doppler imaging.     

Acceptability of once-a-month injectable contraceptives cyclofem® and mesigyna®: focus group discussion

This article presents the results of focus group discussion sessions conducted with a sample of continuers and discontinuers of the once-a-month injectable contraceptives Cyclofem® and Mesigyna®, as well as with some of the physicians who participated in the clinical trial. The sessions helped explain certain aspects related to the clients as well as the service delivery setting that affected the acceptability of these contraceptive preparations. Providing counseling and presence of a dedicated clinic staff were very essential to the success of the clinical trial. Social support in the form of both husband knowledge, approval, and support as well as the presence of other close relative or friend users helped in increasing the woman’s tolerance of side effects and sometimes helped overcome adverse rumors. Reaction of the women to vaginal bleeding in an Islamic society is discussed and the need for health education in this aspect is strongly recommended. The two preparations are best suited for women who were satisfied with the use of combined hormonal contraceptive pills but had a problem with compliance, and users of other hormonal methods who are free from menstrual irregularities. On the whole, the two preparations had high acceptability among Egyptian women, provided that procedures for the selection of the appropriate candidate are adhered to, and that pre- and postservice counseling and social support are present.