Ultralow doses of vasopressin in the management of diabetes insipidus

Management of postoperative diabetes insipidus (DI) frequently requires intermittent treatment with multiple subcutaneous injections of pituitrin or vasopressin, in doses averaging 20 IU/24 h. Use of a syringe pump for a continuous infusion of ultralow doses of pituitrin produced uniform, constant, and sustained reduction of urinary output, thus facilitating regular fluid replacement. Twelve patients with postoperative DI received iv pituitrin at a dose of 1.6 +/- 0.26 mIU/kg X h (1 to 2 IU/24 h). The antidiuretic effect began at the third hour of treatment, peaked by the sixth hour (diuresis of 37 ml/h, specific gravity of 1.018 +/- 0.002), and was sustained throughout infusion. Polyuria recurred 3 h after the infusion was discontinued; this rapid reversibility is highly advantageous when excessive fluid intake causes overhydration. Pressor effects were not observed during the treatment period.     

Multidetector spiral CT renal angiography in the diagnosis of renal artery fibromuscular dysplasia

OBJECTIVE: The aim of this study was to evaluate the role and detection rate of multidetector spiral CT renal angiography (CTA) as compared with conventional angiography (CA), the commonly accepted gold standard, in the diagnosis of renal artery fibromuscular dysplasia (FMD). In addition, the role of CTA reconstructions (multiplanar reformatted images (MPR), maximum intensity projections (MIP) and shaded-surface display (SSD)) in the detection of FMD was also evaluated. MATERIALS AND METHODS: CTA results were retrospectively reviewed in 21 hypertensive patients with CA-proven FMD. Clinical indications for referral included resistant hypertension (requiring greater than three antihypertensive medications), labile hypertension, hypertension in combination with renal impairment and the presence of abdominal bruits in the context of systemic hypertension. In some cases, these clinical indications were supplemented by positive results in other tests, including plasma renin assay, captopril scintigraphy and/or Doppler ultrasound. The findings of CA in these 21 patients were compared to CTA. RESULTS: Mean patient age was 62.33+14.32 years (range 24-85 years). CTA identified all 42 main renal arteries (100%) and all 10 accessory renal arteries (100%) visualized on CA. In the diagnosis of FMD, CTA detected all 40 (100%) lesions detected by CA. No single CTA reconstruction technique was able to detect all lesions noted on corresponding CA, however, upon review of all CTA reconstructions (MPR, MIP and SSD) in each case, every lesion was correctly identified by CTA. CONCLUSION: Our experience suggests that CTA is a non-invasive, reliable and accurate method for the diagnosis of renal artery fibromuscular dysplasia. Moreover, in our experience CTA has many advantages as a diagnostic screening tool over CA, including accessibility, speed, lower complication profile, versatility and cost-effectiveness. CTA shows great potential as a guiding tool for directing subsequent procedures such as CA+balloon angioplasty.     

Identification of a Novel ANKK1 and Other Dopaminergic (DRD2 and DBH) Gene Variants in Migraine Susceptibility

The dopaminergic system plays an important role in migraine and its clinical subtypes. Hypersensitization of dopamine receptor type 2 (DRD2) in migraine led to successful administration of receptor antagonists in antimigraine therapy. Ankyrin repeats and kinase domain containing 1 (ANKK1) gene in DRD2 loci is linked to comorbid neurological disorders. Dopamine beta hydroxylase (DBH) is responsible for maintaining dopamine-to-norepinephrine ratio implicated in migraine pathophysiology. Therefore, we aimed to look for association of functional variants in ANKK1 (rs1800497), DRD2 (rs6275 and rs1799732) and DBH (rs7239728 and rs1611115) genes with migraine susceptibility. The present study was carried out in two dependent cohorts (n _primary = 208, n _secondary = 127, n _controls = 200). The results of the cohorts were pooled by meta-analysis using Fisher’s and Mantel–Haenszel test. Benjamini–Hochberg false discovery rate test was used to correct for multiple comparisons. Computer algorithm-based TANGO, WALTZ and LIMBO predictions were used to evaluate the effect of missense polymorphism (rs1800497). For ANKK1 polymorphism, variant genotype and allele showed significant associations with migraine risk. A significant protective effect of variant DRD2 rs6275 polymorphism was noticed. DBH rs7239728 imparted significant risk at genotypic, allelic and carrier analyses. We identified a risk haplotype in DRD2 loci. Two genotype interactions between ANKK1rs1800497 and DBHrs72393728 polymorphisms showed significant risks. The variant gene product of ANKK1 rs1800497 was predicted with decreased aggregation of ANKK1 protein. In conclusion, we identified novel genetic variants, haplotype and gene interactions in dopaminergic pathway as potential risk factors for migraine susceptibility.     

γ-Aminobutyric acid (GABA) concentration inversely correlates with basal perfusion in human occipital lobe

Commonly used neuroimaging approaches in humans exploit hemodynamic or metabolic indicators of brain function. However, fundamental gaps remain in our ability to relate such hemo-metabolic reactivity to neurotransmission, with recent reports providing paradoxical information regarding the relationship among basal perfusion, functional imaging contrast, and neurotransmission in awake humans. Here, sequential magnetic resonance spectroscopy (MRS) measurements of the primary inhibitory neurotransmitter, γ-aminobutyric acid (GABA+macromolecules normalized by the complex N-acetyl aspartate-N-acetyl aspartyl glutamic acid: [GABA⁺]/[NAA–NAAG]), and magnetic resonance imaging (MRI) measurements of perfusion, fractional gray-matter volume, and arterial arrival time (AAT) are recorded in human visual cortex from a controlled cohort of young adult male volunteers with neurocognitive battery-confirmed comparable cognitive capacity (3 T; n=16; age=23±3 years). Regression analyses reveal an inverse correlation between [GABA⁺]/[NAA–NAAG] and perfusion (R=−0.46; P=0.037), yet no relationship between AAT and [GABA⁺]/[NAA–NAAG] (R=−0.12; P=0.33). Perfusion measurements that do not control for AAT variations reveal reduced correlations between [GABA⁺]/[NAA–NAAG] and perfusion (R=−0.13; P=0.32). These findings largely reconcile contradictory reports between perfusion and inhibitory tone, and underscore the physiologic origins of the growing literature relating functional imaging signals, hemodynamics, and neurotransmission.     

Infectious meningitis: prospective evaluation with magnetization transfer MRI

The study was performed with the aim of prospectively characterizing infectious meningitis of different aetiology using magnetization transfer (MT) MRI. Spin-echo (SE) T(1), T(2) and pre- and post-contrast T(1) weighted MT images in 100 patients with aetiologically proven meningitis were evaluated for the visibility and enhancement of the meninges on pre- and post-contrast T(1) weighted MT images, respectively. The MT ratio (MTR) was calculated from the thickened meninges in tuberculous meningitis. In addition, the percentage difference in the mean signal intensity (SI) of the meninges and adjacent brain parenchyma was calculated and compared between different groups using 2-tailed student's t-test. T(1) weighted MT images were highly sensitive (96%) in the detection of abnormal meningeal enhancement. Meninges were visible on pre-contrast T(1) weighted MT images only in patients with tuberculous meningitis. The MTR from meninges in tuberculous infection was 19.10+/-1.02, and the percentage difference in the mean SI of the meninges and the adjacent T(2) normal brain parenchyma was significantly higher (p<0.05) in the tuberculous group compared with that in the non-tuberculous group. MT MRI is an important technique for the detection and characterization of infectious meningitis of different aetiology. Visibility of the meninges on pre-contrast T(1) weighted MT images may be considered highly suggestive of tuberculous meningitis.     

An in vitro and in vivo analysis of fibrin glue use to control bone morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth.

BACKGROUND CONTEXT: Recombinant human bone morphogenetic protein-2 (rh-BMP2) has become popular for augmenting spine fusion in the lumbar and cervical spine. Concerns exist, however, over bone morphogenetic protein (BMP)-stimulated soft-tissue swelling and bone growth stimulation in areas where bone is not desired, especially as the material "leaks" into such spaces. The most detrimental effects of such leakage might be airway compromise, while heterotopic bone formation into the spinal canal has been reported in animal and human studies. Fibrin glue has been used as a carrier of many osteoinductive materials; however, its efficacy at modulating the clinical effects of BMP are not known. The amorphous nature of fibrin glue makes it a candidate to control diffusion of BMP and possibly limit bone formation by limiting BMP diffusion to areas where such bone is not desired. PURPOSE: To evaluate the use of fibrin glue to limit BMP diffusion and BMP-stimulated bone growth. STUDY DESIGN/SETTING: This is an in vitro basic science study and an in vivo prospective randomized animal study. STUDY SAMPLE: Eighteen Lewis rats. OUTCOME MEASURES: In vitro study: Enzyme-linked immunosorbent assay measurement of rh-BMP2 concentration in saline. In vivo study: At day 60, rats were evaluated for neurologic deficits before sacrifice. Spines were harvested, and the following studies were performed: 1) manual testing for fusion and bone growth; 2) X-ray evaluation; 3) Micro-computed tomography (micro-CT) scans. METHODS: In vitro study: Collagen sponges soaked with BMP at two different concentrations were incubated in saline solution with and without encapsulation by fibrin glue. Saline BMP concentrations were measured at consecutive time points. In vivo study: A rat fusion model using rh-BMP2 for fusion has been developed and tested with resultant100% fusion in over 100 rats. Lewis rats were divided into two groups and treated as follows: I: Exposure of L4-L5 transverse processes, decortication, and placement of BMP sponge in the lateral intertransverse space. II: Exposure and decortication as above and placement of fibrin glue before BMP sponge placement. RESULTS: In vitro study: Peak rh-BMP2 concentrations in saline were 20% and 45% of the maximum possible for fibrin glue encapsulated sponges and controls, respectively, with a more gradual increase to peak concentration in samples encapsulated in fibrin glue. In vivo study: No rats exhibited any neurologic deficits. X-rays revealed at least partial bone formation in all rats. Manual testing of intertransverse fusion spines revealed 100% fusion in rats treated with BMP only, whereas rats treated with fibrin glue before placement of BMP sponges revealed only one possible fusion. Posterior-lateral bone formation was present on X-ray in both groups, and micro-CT imaging revealed bridging bone from transverse processes to the BMP-stimulated bone in the control groups. In spines treated with fibrin glue before rh-BMP2 placement, bone formation could still be seen within the soft tissues; however, bridging bone connecting to the transverse processes was either significantly decreased or not present. CONCLUSIONS: Fibrin glue can limit rh-BMP2 diffusion. Also, because it limited bone formation at the transverse processes, it can be inferred that fibrin glue can limit bone formation when used to separate areas of desired bone formation from areas where bone formation is not desired.     

Detection of New Delhi Metallo‐beta‐Lactamase and Extended‐Spectrum beta‐Lactamase Genes in Escherichia coli Isolated from Mastitic Milk Samples

In this study, eight Escherichia coli isolates were obtained from milk samples of dairy cattle suffering from clinical/subclinical mastitis. Isolates were characterized for antimicrobial resistance traits and virulence genes. Results revealed that one isolate was harbouring New Delhi metallo‐beta‐lactamase gene (bla_NDM). Cloning and sequencing of the PCR amplicon confirmed the identity of the gene (GenBank accession no. KC769583 ) having 100% homology with bla_NDM‐5 (GenBank accession no. JN104597.1 ), and this isolate was susceptible to colistin, chloramphenicol and tetracycline only. Moreover, another isolate carried extended‐spectrum beta‐lactamase (ESBL) gene – bla_CTX‐M, and all isolates possessed bla_TEM gene. Of the eight isolates, only one isolate was positive for shiga toxin gene (stx2), and none were harbouring stx1 gene. Occurrence of New Delhi metallo‐beta‐lactamase (bla_NDM) in one E. coli isolate and ESBL genes in other isolates poses a potential threat to human health following possible entry and spread through food chain.     

Clinicopathological patterns of bladder carcinoma over 1 year: experience from University Hospital of Nepal

Purpose

To define the clinical and pathological patterns of urinary bladder carcinoma from the University Hospital of Nepal.

Methods

This is a retrospective analytical study. Patients with bladder mass who underwent surgery over 1 year and who had data record were included in the study. Demographic profile, type of surgery, findings on clinical examination, cystoscopy findings, histopathological report, tumor stage, and post-surgery adjuvant therapy were analyzed.

Results

Out of 86 patients who underwent transurethral resection of bladder tumor, 77 patients had biopsy-proven malignant bladder tumor. Urothelial cancer was present in 96.1%. Male were 78.6%. The mean age of diagnosis was 65.5?±?11.8 years. Non-muscle-invasive bladder cancer (NMIBC) was 3.7 times more common than muscle-invasive bladder cancer (MIBC). High-grade tumors (58.6%) were more common than low grade (41.4%). The detrusor muscle was present inthe biopsy specimen of 48 patients (64%). Re-TURBT within 2–6 weeks was considered based on histopathology reports for about half of the patients (45.3%). Upstaging and upgrading of the tumor was present in 5.8 and 5.8% of the patients, respectively. Residual tumor without upstaging and upgrading was present in 23.5%. One patient (1.3%) had Clavien–Dindo grade 1, three (4%) patients had grade 2 and two patients (2.7%) had grade 3b.

Conclusion

In the present study, patients with bladder cancer are younger than reported in other studies. Smokers are strongly predisposed. The histological pattern is similar to the Western and Asian populations. NMIBC and MIBC occur in proportion to that described as in other studies. We had a lower rate of recurrence, upstaging and upgrading. We had a lesser rate of acceptance for radical cystectomy in our patients.

     

Comparison of four habitual physical activity questionnaires in girls aged 7-15 yr

PURPOSE: Questionnaires provide a practical approach to measuring physical activity in children and adolescents, particularly for large-scale epidemiological studies. The purpose of the present study was to compare four habitual physical activity questionnaires and to assess their long-term reliabilities. METHODS: Subjects were female, aged 7-15 yr (and their parents), who participated in a cohort study in which predictors of the onset of menarche were being investigated. Questionnaires consisted of three single-item and one multi-item habitual physical activity questions and were sent to the 640 participants. Test-retest reliability of the questionnaires was assessed on 100 randomly selected participants 11 months later. RESULTS: The Spearman's correlation coefficient was highest (r = 0.40) between the Godin-Shephard Score and the Perspiration Score and was lowest (r = 0.10) between the Stairs Score and the Specific Activity Score. The correlation coefficients were higher when the questionnaires were reported to have been completed by the parents alone, rather than by parents with the assistance of their daughters. The test-retest reliabilities were r = 0.44 for the Perspiration Score, r = 0.59 for the Stairs Score, r = 0.48 for the Godin-Shephard Score, and r = 0.53 for the Specific Activity Score. The reliabilities were higher when the retest was reported to have been completed by the parents alone. CONCLUSIONS: This study suggests that the Perspiration Score, the Godin-Shephard Score, and the Specific Activity Score may provide simple and practical measures of habitual physical activity for children and adolescents.