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.      

Saccadic inhibition in voluntary and reflexive saccades

The present study investigated saccadic inhibition in both voluntary and stimulus-elicited saccades. Two experiments examined saccadic inhibition caused by an irrelevant flash occurring subsequent to target onset. In each trial, participants were required to perform a single saccade following the presentation of a black target on a gray background, 4 degrees to the left or to the right of screen center. In some trials (flash trials), after a variable delay, a 33-msec flash was displayed at the top and bottom third of the monitor (these regions turned white). In all experimental conditions, histograms of flash-to-saccade latencies documented a decrease in saccadic frequency, forming a dip, time-locked to the flash and occurring as early as 60-70 msec following its onset. The fast latency of this effect strongly suggests a low-level, reflex-like, oculomotor effect, which was referred to as saccadic inhibition. A novel procedure was developed to allow comparisons of saccadic inhibition even across conditions, which in the absence of a flash (no-flash trials) produce dissimilar saccadic reaction times (SRTs) distributions. Experiment 1 examined the effects of the fixation stimulus on saccadic inhibition by contrasting three conditions: a gap condition (fixation stimulus disappeared 200 msec prior to target onset), a step condition (offset of the fixation stimulus was simultaneous with target onset), and an overlap condition (the fixation stimulus remained on for the duration of the trial). The overlap condition produced substantially stronger saccadic inhibition, relative to the gap and the step conditions. Experiment 2 contrasted the saccadic inhibition effect obtained for prosaccades (saccades aimed at the target) with the effect obtained for antisaccades (i.e., saccades aimed away from the same target). The onset of saccadic inhibition was earlier, and its magnitude was stronger, for antisaccades, relative to prosaccades. The plausibility that the superior colliculus is the neurophysiological locus of the saccadic inhibition effect was explored.     

Invasive group A streptococcal infections in the San Francisco Bay area, 1989-99

To describe the epidemiology of invasive group A streptococcal (iGAS) infections in the San Francisco Bay Area, population-based active surveillance for laboratory-confirmed iGAS was conducted by the California Emerging Infections Program in three California counties. From January 1989 to December 1999, 1415 cases of iGAS were identified. Mean iGAS incidence was 4.06/100,000 person-years and case fatality ratio was 13%, with no linear trends over time. Incidence was lowest in adolescents, was higher in men than women (4.4 vs. 3.2/100,000 person-years), and was higher in African-Americans (6.7) than in non-Hispanic (4.1) or Hispanic (3.4) Whites, Asians (2.2) or Native Americans (17/100,000 person-years). Injecting drug use was the riskiest underlying condition and was associated with the highest attributable risk. Cases were associated with several underlying conditions, but 23% occurred in previously healthy persons. From 1989-1999, iGAS infections in the San Francisco Bay Area became neither more common nor more deadly.     

Light and electron microscope study of the neurotropism of Powassan virus strain P-40.

Brains of adult white mice inoculated with the P-40 strain of Powassan virus isolated in Primorsky Krai (U.S.S.R) from ticks were studied by light and electron microscopy. Accumulations of virus particles were found in neurons and their dendrites and axons, in glial cells, and in intercellular spaces. In the nerve cells, most prevalent were changes of the type of chromatolysis and formation of small vacuoles, associated with the alteration of the endoplasmic reticulum induced by virus morphogenesis. In virus-affected cells, multilayer dense membranes were found.     

Changing epidemiology of invasive pneumococcal disease among older adults in the era of pediatric pneumococcal conjugate vaccine

Context  A conjugate vaccine targeting 7 pneumococcal serotypes was licensed for young children in 2000. In contrast to the 23-valent polysaccharide vaccine used in adults, the 7-valent conjugate vaccine affects pneumococcal carriage and transmission. Early after its introduction, incidence of invasive pneumococcal disease declined among older adults, a group at high risk for pneumococcal disease. Objective  To determine among adults aged 50 years or older whether incidence of invasive pneumococcal disease, disease characteristics, or the spectrum of patients acquiring these illnesses have changed over the 4 years since pneumococcal conjugate vaccine licensure. Design, Setting, and Population  Population-based surveillance of invasive pneumococcal disease in 8 US geographic areas (total population, 18 813 000), 1998-2003. Main Outcome Measures  Incidence of invasive pneumococcal disease by pneumococcal serotype and other characteristics; frequency among case patients of comorbid conditions and other factors influencing mortality. Results  Incidence of invasive pneumococcal disease among adults aged 50 years or older declined 28% (95% confidence interval [CI], –31% to –24%), from 40.8 cases/100 000 in 1998-1999 to 29.4 in 2002-2003. Among those aged 65 years or older, the 2002-2003 rate (41.7 cases/100 000) was lower than the Healthy People 2010 goal (42 cases/100 000). Among adults aged 50 years or older, incidence of disease caused by the 7 conjugate vaccine serotypes declined 55% (95% CI, –58% to –51%) from 22.4 to 10.2 cases/100 000. In contrast, disease caused by any of the 16 serotypes only in polysaccharide vaccine did not change, and disease caused by serotypes not in either vaccine increased somewhat, from 6.0 to 6.8 cases/100 000 (13%; 95% CI, 1% to 27%). Between 1998-1999 and 2002-2003, the proportion of case-patients with human immunodeficiency virus infection increased from 1.7% (47/2737) to 5.6% (124/2231) (P<.001), and those with any comorbid condition that is an indication for pneumococcal polysaccharide vaccination increased from 62.3% (1842/2955) to 72.0% (1721/2390) (P<.001). Conclusions  Our findings indicate that use of conjugate vaccine in children has substantially benefited older adults. However, persons with certain comorbid conditions may benefit less than healthier persons from the indirect effects of the new vaccine.      

Impact of childhood vaccination on racial disparities in invasive Streptococcus pneumoniae infections

Context  Historically, incidence of pneumococcal disease in the United States has been higher among blacks than among whites. Following recommendation of a new 7-valent pneumococcal conjugate vaccine for children in October 2000, the incidence of invasive pneumococcal disease has declined dramatically, but the impact of vaccination on racial disparities in incidence of pneumococcal disease is unknown. Objective  To assess the effect of conjugate vaccine introduction on rates of pneumococcal disease among whites and blacks in the United States. Design, Setting, and Patients  Analysis of data from the Active Bacterial Core Surveillance (ABCs)/Emerging Infections Program Network, an active, population-based surveillance system in 7 states. Patients were 15 923 persons with invasive pneumococcal disease occurring between January 1, 1998, and December 31, 2002. Main Outcome Measures  Age- and race-specific pneumococcal disease incidence rates (cases per 100 000 persons), rate ratios, and rate differences. Results  Between 1998 and 2002, annual incidence rates for invasive pneumococcal disease decreased from 19.0 to 12.1 cases per 100 000 among whites and from 54.9 to 26.5 among blacks. Due to these declines, 14 730 fewer cases occurred among whites and 8780 fewer cases occurred among blacks in the United States in 2002, compared with 2 prevaccine years, 1998 and 1999. Before vaccine introduction, incidence among blacks was 2.9 times higher than among whites (95% confidence interval [CI], 2.7-3.0); in 2002, the black-white rate ratio had been reduced to 2.2 (95% CI, 2.0-2.4). Incidence among black children younger than 2 years went from being 3.3 times higher (95% CI, 3.0-3.7) than among white children in the prevaccine period to 1.6 times higher (95% CI, 1.1-2.2) in 2002. By 2002, 74% of white children and 68% of black children aged 19 to 35 months in the 7 states had received at least 1 dose of pneumococcal conjugate vaccine; 43% of white and 39% of black children received 3 or more doses. Conclusion  Although blacks remain at higher risk of invasive pneumococcal disease, introduction of childhood pneumococcal vaccination has reduced the racial disparity in incidence of pneumococcal disease.      

Performance of a bedside C-reactive protein test in the diagnosis of community-acquired pneumonia in adults with acute cough

PURPOSE: To evaluate the performance of a rapid, bedside whole blood C-reactive protein test as a diagnostic test for pneumonia in adults. METHODS: We enrolled consecutive adults who presented with acute cough (duration < or =3 weeks). A fingerstick blood specimen for C-reactive protein level was obtained. Patients also provided information about demographic characteristics and symptoms. Physical examination findings, diagnoses, and treatments were abstracted from the medical record; illness duration and subsequent office visits were determined with follow-up telephone calls. A clinical prediction rule for pneumonia was calculated for each patient and compared with C-reactive protein levels. RESULTS: Twenty (12%) of the 168 patients in the study had radiographic evidence of pneumonia. Median C-reactive protein levels were significantly higher for patients with pneumonia than in the remaining patients (60 mg/L vs. 9 mg/L, P <0.0001). The area under the receiver operating characteristic (ROC) curve for C-reactive protein level as a predictor of pneumonia was 0.83. C-reactive protein level and the clinical prediction rule were independently associated with pneumonia, yielding a combined area under the ROC curve of 0.93. C-reactive protein level was not associated with hospitalization or resolution of symptoms. CONCLUSION: C-reactive protein levels could be a valuable addition to clinical prediction rules for pneumonia. A C-reactive protein level > or =100 mg/L might be a useful indication for chest radiography or empiric antibiotic therapy when the diagnosis of pneumonia is in doubt.     

Gamma-knife radiosurgery for trigeminal neuralgia

Gamma knife was installed at the PD Hinduja National Hospital and Medical Research Centre, Mumbai, India, in January 1997. In the first year of gamma-knife radiosurgery to January 1998, we treated 110 patients, of whom six had medically refractory trigeminal neuralgia. Seven treatments were administered to this group of six patients (one had bilateral neuralgia). This report evaluates the effectiveness of radiosurgery treatment in these patients. The median age of the patients was 56 years and there were five males and one female. Following Leksell stereotactic frame fixation, a magnetic resonance imaging scan was done in all. The Leksell gamma plan was used for planning. A radiosurgery dose of 70–80 Gy was delivered to the trigeminal root entry zone, 2–4 mm anterior to the junction of the pons and trigeminal nerve with a single 4 mm collimator helmet. Complete pain relief was achieved in four patients. Two had partial relief. No patient developed any radiosurgery related morbidity during the follow-up period of 5–16 months. Radiosurgery seems to be an effective approach for medically or surgically refractory trigeminal neuralgia.