Efficacy of Zoladex LA (goserelin) in the treatment of girls with central precocious or early puberty

OBJECTIVE: To assess the efficacy of a longer acting preparation of the gonadotrophin releasing hormone (GnRH) analogue goserelin (Zoladex LA, 10.8 mg) in 12 girls with central precocious or early puberty. METHODS: Two girls started treatment de novo; the remainder had been on suppressive treatment for a median duration of 1.5 (range, 0.2-5.6) years. Assessment comprising auxology, pubertal staging, and pelvic ultrasound examination was carried out at weeks 0, 4, 8, 10, and 12 (first cycle) and weeks 8, 10, and 12 (second cycle) to evaluate the required injection frequency. Thereafter, assessment was performed on the day of injection. Zoladex LA was given every 12 weeks unless pubertal progression occurred. RESULTS: Satisfactory control was achieved in eight patients using this regimen, and three patients required more frequent injections. One girl was removed from the study because of clinical progression and extreme mood swings. No serious adverse effects occurred. Mean height velocity during the study period was 4.5 cm/year (range, 3.1-6.6) compared with 6.5 cm/year (range, 3.8-9.6) before treatment in nine patients for whom data were available. CONCLUSIONS: Zoladex LA was effective in controlling precocious puberty in girls when given at intervals of 9-12 weeks and it is recommended that an initial assessment is made eight weeks after beginning treatment.     

Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog

Inactivation of the p53 tumor suppressor gene has been implicated in the pathogenesis of numerous human cancers, including osteosarcomas. Appendicular osteosarcomas of the dog appear to be a good model for their human equivalent with regard to biologic behavior, epidemiology and histopathology. We individually screened exons 5-8 of the p53 gene for mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to compare the role of this gene in human and canine osteosarcoma tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with one tumor possessing two mutations within different exons. Of these, seven were missense mutations and the eighth was a 'silent' mutation potentially affecting the exon 6-7 splicing region. Five of the missense mutations were located in highly conserved regions IV and V, while another corresponded with the highly conserved codon 220 mutational hotspot located outside the conserved domains. The locations and types of mutations were nearly identical to those reported in human cancer. These findings provide strong evidence of the involvement of p53 mutations in the development of canine appendicular osteosarcomas. Canine osteosarcomas appear to be a promising model for their human equivalent on a clinical, pathologic, and molecular level.      

SOMATIC NEUROPATHY IN DIABETES MELLITUS

One hundred patients of Diabetes Mellitus (70 with and 30 without clinical somatic neuropathy) were studied to correlate clinical severity with the magnitude of nerve conduction abnormalities. Age range was 10-79 years (mean 49) with equal number of males and females. Incidence of neuropathy was more in patients over 40 years of age (60 out of 70 patients) with duration of disease over two years (78.33%). The grades of severity were mild in 22 (31.33%), moderate in 25 (35.71%) and severe in 23 (32.86%) patients. Nerve conduction studies were carried out in 48 (27 with and 21 without clinical neuropathy) patients, using the apparatus Dantec (Cantata TM). The nerves (median, peroneal and sural) were stimulated at two points and the recording of latency; amplitude (micro V) and motor and sensory nerve conduction velocities (m/s) were done under identical environmental conditions. Sensory nerve conduction velocity was more affected than motor velocity. In the 21 patients without clinical neuropathy, 14 showed abnormalities indicating early involvement of peripheral nerves. Reduction of motor nerve conduction velocity was more in patients with moderate and severe grades. The reduction was more in lower than in upper limbs. Nerve conduction abnormality helps in diagnosis in diabetic neuropathy even in preclinical state and correlates with severity, in clinical neuropathy.KEY WORDS: Diabetic neuropathy, Nerve conduction abnormality, Peripheral neuropathy     

Global myocardial revascularization without cardiopulmonary bypass using innovative techniques for myocardial stabilization and perfusion

BACKGROUND: In off-pump coronary bypass grafting (CABG), invasiveness is reduced but technically perfect anastomosis is jeopardized by cardiac motion and the need to hurry to reduce the time of ischemia. Also, a major cause of postoperative morbidity and mortality is ungrafted circumflex coronary artery disease. We have devised a means of overcoming these shortcomings and performing multivessel CABG. The objective of this study was to assess the safety and efficacy of our technique. METHODS: One hundred patients with severe triple-vessel disease underwent multivessel off-pump CABG. For cardiac stabilization, a combination of local pericardial stabilization sutures and lifting and rotating the heart by means of posterior pericardial sutures were used. For myocardial perfusion, a technique of retrograde coronary sinus perfusion by arterial blood from the ascending aorta was used. RESULTS: Each patient received an average of 3.8 grafts (range 3 to 5). Complications included conversion to cardiopulmonary bypass (CPB) in 1 patient and a perioperative myocardial infarction in the same patient. In all other patients we were able to perform a satisfactory grafting in all territories with no operative mortality. Rapid recovery allowed 95% of our patients to resume normal activity within 1 month. A predischarge graft angiogram in 35 patients showed 97.8% patency. CONCLUSIONS: These results suggest that off-pump CABG with our techniques is effective and safe. Early clinical outcome and excellent patency rates suggest its more widespread use in selected cases.     

Normative data of retinal arteriolar and venular calibre measurements determined using confocal scanning laser ophthalmoscopy system – Importance and implications for study of cardiometabolic disorders

Purpose:To determine and validate retinal vascular caliber measurements by using the confocal scanning laser ophthalmoscopy system. Retinal vasculature changes are often regarded as clinical markers for systemic disease.Methods:It was a prospective observational study conducted on 600 eyes of 300 normal subjects with no systemic or ocular illness from January 1, 2016 to June 30, 2017 in a tertiary referral eye center. Non-mydriatic infrared reflectance, blue reflectance, and blue peak blue autofluorescence fundus imaging were done on the confocal scanning laser ophthalmoscopy system. The dimensions of the retinal vessels were measured using inbuilt calipers at 1800 mm from the center of the optic disc. Internal and external dimensions were measured. Observer variation and its comparison using Image J software were assessed.Results:The median age was 29 years (18–50 years). Mean internal and external diameters for arterioles were 85.1 ± 12.4 mm and 105.0 ± 12.0 mm, and for venules were 133.8 ± 16.6 mm and 145.4 ± 16.1 mm, respectively. The mean internal and external wall thicknesses were 19.7 ± 8.0 mm and 11.0 ± 5.6 mm, and wall thickness-to-lumen ratios were 0.3 ± 0.1 and 0.1 ± 0.1, respectively. Arteriolar-to-venular ratio for lumen and vessel was 0.66 ± 0.1 and 0.74 ± 0.1, respectively. There was no statistically significant difference between age groups. Both inter- and intra-observer reproducibility was >95%. The Bland–Altman plot showed that the difference between measurements using both confocal scanning laser ophthalmoscopy and Image J software lies within the limits of agreement approximately 95% of the time.Conclusion:This is the first effort to develop a normative database by using a simple non-invasive confocal scanning laser ophthalmoscopy system with high observer reproducibility.     

Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.     

Diabetes Mellitus and Heart Failure: A Consensus Statement

International Journal of Diabetes in Developing Countries -     

Escherichia coli tetracycline efflux determinants in relation to tetracycline residues in chicken

ObjectiveTo screen for Escherichia coli (E. coli) resistant to tetracycline, followed by identification of tet efflux genes by polymerase chain reaction (PCR). In addition, detection of tetracycline residues in chicken livers and kidneys were conducted using high performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS-MS).MethodsStrains of E. coli were isolated from samples of chicken colon and screened for tetracycline resistance. Tetracycline genes conferring resistance (Tc^r) were detected by polymerase chain reaction (PCR). Most of the isolates were resistant to tetracycline (97.9%).ResultsPCR analysis indicated that Tc^r E. coli R-plasmids contained tet(A), tet(B) and a combination of both efflux genes. None of the isolates contained other efflux tet genes tet (C, D, E and Y). High performance liquid chromatography-tandem quadrupole mass spectrometry (HPLC-MS-MS), a sensitive technique, was used to detect residues of chlortetracycline (CTC), oxytetracycline (OTC), doxycycline (DC) in chicken livers and kidneys. The samples containing tetracycline residues were at 0.13-0.65 pg/μL levels.ConclusionsTetracycline and other antibiotics are commonly used in the poultry and meat production industry for prevention of microbial infections. Multiple antibiotic resistant bacteria in Oman have increased to alarming levels, threatening public health, domestic and may have adverse effect on environment.