Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

In Vitro Validation of Tissue Doppler Left Ventricular Regional Wall Velocities by Using a Novel Balloon Phantom

Velocity data from tissue Doppler imaging (TDI)can provide valuable information on regional leftventricular wallmotion. Validation of TDImyocardialvelocity measurements has been carried out indirectlyfrom gray- scale M- mode images,and discrepancieshave been reported.Mc Dicken[1] and Miyatake etal[2 ]have reported the accuracy and validity of the TDIsystem using a rotating sponge model.However theoverall motion of the heart should be considered.Inthe present study,we described a new TDI…     

Cement dermatitis in underground workers during construction of the Channel Tunnel

The construction of the Channel Tunnel is one of the largestcivil engineering projects ever undertaken. The British driveemployed 5900 underground workers, and a number developed dermatitisduring 1990/1991. As a result, the Translink Joint Venture (TLJV)Medical Centre set up a surveillance programme aiming to monitorand investigate the men working closely with cement as wellas other groups of workers with skin problems. Men attendedthe Medical Centre voluntarily and were assessed, includinghistory, examination and patch tests to a series of 15 testsubstances (from the European standard series) where indicated.A programme of education about the hazards of working with cementwas instituted, including leaflets, videos, local newspaperarticles and personal explanation by the Medical Centre staff.Between January 1990 and January 1992, 1138 men were seen atthe Medical Centre regarding their skin and 332 were diagnosedas having occupational dermatitis, past or present. Patch testswere performed on 180 men from all trades. Of the 800 grouters,466 (58 per cent) were assessed and 111 had a history of occupationaldermatitis at some time. Many gave a history of a single episodeof dermatitis during a particularly hot and wet phase of tunnelling.Patch tests performed on 86 grouters showed allergy to chromatein 56 (65 per cent). Of the 466 grouters assessed, 17 per centhad positive patch tests to chromate but men with no skin problemspast or present were not patch tested. Cobalt allergy was oftenfound with chromate allergy (50 out of 56). Allergy to epoxyresin was also found in 30 per cent of grouters who were patchtested. Only three men had to change their occupation becauseof their skin disease. Most cases of occupational dermatitisimproved with regular medical supervision, education and personalprotective measures, with relocation to less exposed work wherenecessary. Many cases cleared as the tunnel entered better terrain.The addition of ferrous sulfate has been shown to decrease thelevel of the allergenic hexavalent chromate in cement and itscompulsory use in Scandinavia has reduced the incidence of cementdermatitis in construction workers. The rest of Europe shouldnow follow the Scandinavian lead and consider legislation tomake cement less hazardous to workers' health.     

Randomized trial of radiation for age-related macular degeneration.

PURPOSE: To assess external beam radiation efficacy for subfoveal neovascularization associated with age-related macular degeneration. METHODS: All patients were evaluated in the same institution. In this prospective trial, 27 eyes (27 patients) with subfoveal neovascularization associated with age-related macular degeneration were randomized to either single fraction radiation (750 centigray) or observation. Endpoints were assessed by fluorescein angiography and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity. Examiners were masked to patient treatment status. Parametric and nonparametric statistical analyses were performed. RESULTS: Twenty-seven patients were entered into the trial with a mean age of 76 years (range, 64 to 89) and a mean follow-up of 17 months (range, 7 to 32). The visual acuity loss was slightly less in the irradiated group, a finding of borderline significance (P < .046). There was no significant difference in fluorescein angiographic evidence of subretinal neovascular membrane change in the control group vs the irradiated group. CONCLUSIONS: External beam radiation, at this dose and fractionation, did not appear harmful. There was slightly less visual loss in irradiated eyes. No difference in fluorescein angiographic characteristics of subfoveal neovascularization size or progression in eyes with age-related macular degeneration was noted.     

Cardiovascular changes during morphine administration and spontaneous withdrawal in the rat

Morphine maintenance doses of 10 mg kg(-1) day(-1), 20 mg kg(-1) day(-1) and 30 mg kg(-1) day(-1) were administered to three groups of rats via miniosmotic pumps for 7 days to induce physical dependence. They were then allowed to undergo spontaneous withdrawal. Radiotelemetric blood pressure measurements showed that morphine increased systolic and diastolic blood pressure on the first day of morphine treatment and produced a dose dependent decrease in heart rate, systolic and diastolic blood pressure thereafter. After the peak depressive effect, development of tolerance to morphine was observed in systolic and diastolic blood pressure, but not in the heart rate. During spontaneous withdrawal, both systolic and diastolic blood pressure increased beyond pre-morphine levels for all doses and there was a rebound increase in heart rate at the 30 mg kg(-1) day(-1) dose. These results suggest that the improved sensitivity of telemetric measures combined with the use of minipumps for morphine treatment provide an animal model of spontaneous opioid withdrawal.     

Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols

In order to study the biological activities of tea preparations and purified tea polyphenols, their growth inhibitory effects were investigated using four human cancer cell lines. Growth inhibition was measured by [3H]thymidine incorporation after 48 h of treatment. The green tea catechins (-)-epigallocatechin-3-gallate (EGCG) and (-)- epigallocatechin (EGC) displayed strong growth inhibitory effects against lung tumor cell lines H661 and H1299, with estimated IC50 values of 22 microM, but were less effective against lung cancer cell line H441 and colon cancer cell line HT-29 with IC50 values 2- to 3- fold higher. (-)-Epicatechin-3-gallate, had lower activities, and (-)- epicatechin was even less effective. Preparations of green tea polyphenols and theaflavins had higher activities than extracts of green tea and decaffeinated green tea. The results suggest that the growth inhibitory activity of tea extracts is caused by the activities of different tea polyphenols. Exposure of H661 cells to 30 microM EGCG, EGC or theaflavins for 24 h led to the induction of apoptosis as determined by an annexin V apoptosis assay, showing apoptosis indices of 23, 26 and 8%, respectively; with 100 microM of these compounds, the apoptosis indices were 82, 76 and 78%, respectively. Incubation of H661 cells with EGCG also induced a dose-dependent formation of H2O2. Addition of H2O2 to H661 cells caused apoptosis in a manner similar to that caused by EGCG. The EGCG-induced apoptosis in H661 cells was completely inhibited by exogenously added catalase (50 units/ml). These results suggest that tea polyphenol-induced production of H2O2 may mediate apoptosis and that this may contribute to the growth inhibitory activities of tea polyphenols in vitro.      

Preventing symptomatic vitamin D deficiency and rickets among Indigenous infants and children in Canada

Vitamin D deficiency (VitDD) rickets and other manifestations of severe VitDD, such as cardiomyopathy and hypocalcemic seizures, continue to be diagnosed in Canada. Breastfed Indigenous infants, particularly those living in northern communities, are disproportionately impacted, although formula-fed infants are not exempt in cases where the mother’s vitamin D status is critically low. This statement deals with the prevention of rickets and hypocalcemia due to VitDD for Indigenous children, and revises an earlier document from the Canadian Paediatric Society. An assessment of the risk for VitDD is recommended for each maternal-infant dyad because of the link between maternal and infant VitDD. Along with supports for enhanced adherence, additional VitD supplementation is recommended for prenatal women and infants deemed at high risk and, in certain situations, intermittent higher dose supplementation may be required. Food insecurity can also contribute to rickets, so advocacy is required to prevent VitDD rickets in Indigenous children.