Vera H. Koch

Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis

Mutations in the

Comparison between casual blood pressure and ambulatory blood pressure monitoring parameters in healthy and hypertensive adolescents.

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First NIH/Office of Rare Diseases Conference on Cystinosis: past, present, and future

cotransporter NBC1 cause severe proximal tubular acidosis (pRTA) associated with ocular abnormalities. Recent studies have suggested that at least some NBC1 mutants show abnormal trafficking in the polarized cells. This study identified a new homozygous NBC1 mutation (G486R) in a patient with severe pRTA. Functional analysis in Xenopus oocytes failed to detect the G486R activity due to poor surface expression. In ECV304 cells, however, G486R showed the efficient membrane expression, and its transport activity corresponded to approximately 50% of wild-type (WT) activity. In Madin–Darby canine kidney (MDCK) cells, G486R was predominantly expressed in the basolateral membrane domain as observed for WT. Among the previously identified NBC1 mutants that showed poor surface expression in oocytes, T485S showed the predominant basolateral expression in MDCK cells. On the other hand, L522P was exclusively retained in the cytoplasm in ECV304 and MDCK cells, and functional analysis in ECV304 cells failed to detect its transport activity. These results indicate that G486R, like T485S, is a partial loss of function mutation without major trafficking abnormalities, while L522P causes the clinical phenotypes mainly through its inability to reach the plasma membranes. Multiple experimental approaches would be required to elucidate potential disease mechanism by NBC1 mutations.

Infecção do trato urinário: em busca das evidências

Blood pressure can be measured through the direct method by introducing a catheter coupled with a transducer in an artery, or through the indirect method by using the auscultatory or oscillometric technique. In clinical practice, we use the casual blood pressure measurement with the auscultatory technique. Blood pressure is measured in the arm with the aneroid or mercury column sphygmomanometer. However, that method has disadvantages, such as the possibility of error inherent to the indirect method with the auscultatory technique, subjectivity in blood pressure auscultation, rounding off of the measurements, in addition to mercury toxicity to the environment 1 . Currently, an increasing number of semi-automated or automated electronic devices are available at affordable prices. This equipment should be evaluated according to the validation norms required by international entities, such as the British Hypertension Society (BHS)

Infecção urinária comunitária: etiologia segundo idade e sexo

Casual blood pressure measurements were compared with mean ambulatory blood pressure values during wakefulness and sleep in 45 normotensive and 30 hypertensive adolescents of both sexes aged 10-18 years. Two sets of auscultatory casual blood pressure were obtained, one in a pediatric office setting (office blood pressure), performed by the physician, and one in the ambulatory blood pressure monitoring (ABPM) unit, performed by a trained nurse, prior to the initiation of ABPM (pre-ABPM blood pressure). In normotensive and hypertensive subjects of both sexes, the mean office systolic blood pressure (SBP) was lower than the mean pre-ABPM SBP, and the mean office diastolic blood pressure (DBP) was lower than the mean pre-ABPM DBP. In normotensive participants, the mean pre-ABPM SBP/DBP was lower than the mean ABPM SBP/DBP while awake, the mean ABPM SBP/DBP during sleep being lower than the mean ABPM SBP/DBP values while awake and the mean pre-ABPM SBP/DBP. No statistical difference was demonstrated between the mean office SBP and the mean ABPM SBP during sleep, the mean ABPM DBP during sleep being lower than the mean office DBP. The hypertensive adolescents presented a blood pressure profile similar to that of the normotensive group, albeit shifted upwards, with no significant difference between the mean pre-ABPM SBP and the mean ABPM SBP while awake but a higher mean pre-ABPM DBP than mean ABPM DBP while awake. This study suggests that, by evaluating the casual blood pressure in different environment/observer situations, the power of casual blood pressure to predict inadequate blood pressure control, manifested as abnormal ABPM parameters, can be enhanced. Our data indicate ABPM to be the method of choice for the early diagnosis and adequate follow-up of adolescent hypertension.

Health-related quality of life of children and adolescents with CKD stages 4–5 and their caregivers

OBJECTIVE To evaluate the effect of the environment and the observer on the measurement of blood pressure (BP) as well as to compare home BP (HBP) and ambulatory BP (ABP) measurements in the diagnosis of white coat hypertension (WCH) and masked hypertension (MH) in children and adolescents with hypertension (HT). METHODS BP of 40 patients with HT (75% of which had secondary HT and were on antihypertensive medication), mean age 12.1 years was evaluated through casual measurements at the clinic and at the HT unit, HBP for 14 days with the OMRON HEM 705 CP monitor (Omron, Tokyo, Japan) and ABP performed with SPACELABS 90207 (Spacelabs, Redmond, WA), for 24 h. RESULTS HT was diagnosed at the doctors office by ABP and HBP in 30/40, 27/40, and 31/40 patients, respectively. Based on office BP and ABP, 60% of patients were normotensive, 17.5% HT, 7.5% had WCH, and 15% had MH, whereas based on office BP and HBP 65, 12.5, 10, and 12.5% of patients were classified according to these diagnoses, respectively. There was considerable diagnostic agreement of HT by ABP and HBP (McNemar test, P < 0.01) (κ = 0.56). CONCLUSION In hypertensive children and adolescents, HBP and ABP present comparable results. HBP appears to be a useful diagnostic test for the detection of MH and WCH in pediatric patients.

Report of a Brazilian Multicenter Study on Nephropathic Cystinosis

Consensus Statement First NIH/Office of Rare Diseases Conference on Cystinosis: past, present, and future Robert Kleta, Frederick Kaskel, Ranjan Dohil, Paul Goodyer, Lisa M. GuayWoodford, Erik Harms, Julie R. Ingelfinger, Vera H. Koch, Craig B. Langman, Mary B. Leonard, Roslyn B. Mannon, Minnie Sarwal, Jerry A. Schneider, Flemming Skovby, Barbara C. Sonies, Jess G. Thoene, Doris A. Trauner and William A. Gahl 19

Influence of nephrotic state on the infectious profile in childhood idiopathic nephrotic syndrome

OBJECTIVE: to review urinary tract infection in children taking into consideration evidence-based medicine. SOURCES OF DATA: search of Medline and Cochrane databases, comprising the period between 1996 and 2002, with the following key words: urinary infection, vesicoureteral reflux, children, adolescents, diagnosis and treatment. Cohort studies, quality assurance studies, consensus, meta-analysis studies, randomized controlled trials and audits were selected. SUMMARY OF THE FINDINGS: the studies were selected according to their methodology, relevance and clinical applicability. Some studies were selected based on the parameters proposed by the American Academy of Pediatrics in 1999 for the diagnosis and treatment of urinary tract infection in children between two months and two years of age. CONCLUSIONS: consensus statements on diagnosis and treatment of urinary infection in children and adolescents are still mostly opinion-based. Randomized multicentric controlled trials, with double-blind allocation are necessary to improve quality of diagnosis and management of pediatric urinary tract infection.