Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for ...Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health
. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics
. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.
To describe a clinical syndrome of cerebellar ataxia associated with muscle coenzyme Q10 (CoQ10) deficiency.
Muscle CoQ10 deficiency has been reported only in a few patients with a mitochondrial ...encephalomyopathy characterized by 1) recurrent myoglobinuria; 2) brain involvement (seizures, ataxia, mental retardation), and 3) ragged-red fibers and lipid storage in the muscle biopsy.
Having found decreased CoQ10 levels in muscle from a patient with unclassified familial cerebellar ataxia, the authors measured CoQ10 in muscle biopsies from other patients in whom cerebellar ataxia could not be attributed to known genetic causes.
The authors found muscle CoQ10 deficiency (26 to 35% of normal) in six patients with cerebellar ataxia, pyramidal signs, and seizures. All six patients responded to CoQ10 supplementation; strength increased, ataxia improved, and seizures became less frequent.
Primary CoQ10 deficiency is a potentially important cause of familial ataxia and should be considered in the differential diagnosis of this condition because CoQ10 administration seems to improve the clinical picture.
The purpose of this study was to investigate the prevalence of β-lactamase and the genomic clonality of a large collection of
Kingella kingae
isolates from Israeli patients with a variety of invasive ...infections and asymptomatic pharyngeal carriers. β-lactamase production was studied by the nitrocefin method and the minimum inhibitory concentrations (MICs) of penicillin and amoxicillin–clavulanate were determined by the epsilon (Etest) method. The genotypic clonality of isolates was investigated by pulsed-field electrophoresis (PFGE). β-lactamase was found in 2 of 190 (1.1 %) invasive isolates and in 66 of 429 (15.4 %) randomly chosen carriage organisms (
p
< 0.001). Overall, 73 distinct PFGE clones were identified (33 among invasive organisms and 56 among carriage isolates). β-lactamase production was found to be limited to four distinct PFGE clones, which were common among carriage strains but rare among invasive strains, and all organisms in the collection belonging to these four clones expressed β-lactamase. The penicillin MIC of β-lactamase-producing isolates ranged between 0.094 and 2 mcg/mL (MIC
50
: 0.25 mcg/mL; MIC
90
: 1.5 mcg/mL) and that of amoxicillin–clavulanate between 0.064 and 0.47 mcg/mL (MIC
50
: 0.125 mcg/mL; MIC
90
: 0.125 mcg/mL). The penicillin MIC of β-lactamase non-producing isolates ranged between <0.002 and 0.064 mcg/mL (MIC
50
: 0.023 mcg/mL; MIC
90
: 0.047 mcg/mL). Although β-lactamase production is prevalent among
K. kingae
organisms carried by healthy carriers, the low invasive potential of most colonizing clones results in infrequent detection of the enzyme in isolates from patients with clinical infections. The exceptional presence of β-lactamase among invasive organisms correlates with the favorable response of
K. kingae
infections to the administration of β-lactamase-susceptible antibiotics.
Three commercial photovoltaic panels based on single crystal silicon solar cells are investigated. Two types of transients are observed: instantaneous short-circuiting and instantaneous ...open-circuiting. It is shown that the transient currents under short-circuiting have a character of damped oscillations and the transient voltages under open-circuiting rise exponentially for all types of solar cell panels. The currently used equivalent diagrams cannot explain the results obtained.
Crohn's disease is a chronic inflammatory disorder of the bowel. In a preliminary study, we evaluated whether the administration of growth hormone (somatropin) as well as a high-protein diet would ...ameliorate the symptoms of the disease.
We randomly assigned 37 adults with moderate-to-severe active Crohn's disease to four months of self-administered injections of growth hormone (loading dose, 5 mg per day subcutaneously for one week, followed by a maintenance dose of 1.5 mg per day) or placebo. We instructed all patients to increase their protein intake to at least 2 g per kilogram of body weight per day. Patients continued to be treated by their usual physicians and to receive other medications for Crohn's disease. The primary end point was the change in scores on the Crohn's Disease Activity Index from base line to month 4. Scores can range from 0 to 600, with higher scores indicating more disease activity.
At base line, the mean (+/-SD) score on the Crohn's Disease Activity Index was somewhat higher among the 19 patients in the growth hormone group than among the 18 patients in the placebo group (287+/-134 vs. 213+/-120, P=0.09). Three patients in the placebo group withdrew before their first follow-up visit and were not included in the data analysis. At four months, the Crohn's Disease Activity Index score had decreased by a mean of 143+/-144 points in the growth hormone group, as compared with a decrease of 19+/-63 points in the placebo group (P=0.004). Side effects in the growth hormone group included edema (in 10 patients) and headache (in 5) and usually resolved within the first month of treatment.
Our preliminary study suggests that growth hormone may be a beneficial treatment for patients with Crohn's disease.
The transient processes in six different photovoltaic panels based on single-crystal, polycrystal and amorphous solar cells are analyzed. Two types of transients, arisen because of instantaneous ...changes in load, are investigated. The transients analyzed are: (a) an instantaneous short-circuiting from an open circuit condition and (b) an instantaneous open-circuiting from a short circuit condition. Different characters of transients are observed. The character of the instantaneous short circuit processes for all panels is damped oscillations. These oscillations are characteristic of a second order circuit, whereas the instantaneous open circuit process takes for all panels the form of an exponential growth that is characteristic of a first order circuit. The similarities and differences of results obtained for the different panels are compared, analyzed and discussed.
Infantile patients with acid maltase deficiency have severe hypertrophic cardiomyopathy, left ventricular outflow obstruction, and generalized muscle weakness and die before 1 year of age. We ...identified 12 infants with acid maltase deficiency who had a similar clinical presentation but less severe cardiomyopathy and absence of left ventricular outflow obstruction, and 9 of 12 had longer survival with assisted ventilation and supplemental intubation. (J Pediatr 2000;137:283-5)
To determine the effectiveness of cardiopulmonary resuscitation (CPR) in the pediatric intensive care unit (ICU).
A nonconcurrent cohort study of consecutive admissions.
Thirty-two pediatric ICUs.
...Consecutive admissions to 32 pediatric ICUs.
None.
Pediatric ICU patients were followed for the occurrence of a cardiopulmonary arrest (external cardiac massage for at least 2 mins). Patients who were in a state of continuous cardiopulmonary arrest on admission, or who never achieved stable vital signs, were excluded from the study. A total of 205 patients, from a sample of 11,165 (1.8%) pediatric admissions, experienced a cardiopulmonary arrest. Overall, 28 (13.7%) patients survived to hospital discharge. Neither mean ages nor age distribution affected survival. Only two diagnostic categories, traumatic illness, and other etiologies, were associated with survival. None of the patients fitting this category survived (p = .0028). The durations of CPR for survivors and nonsurvivors were 22.5 +/- 10.1 and 24.8 +/- 1.9 mins, respectively (p = .015). For CPR durations of <15 mins, 15 to 30 mins, and >30 mins, the survival rates were 18.6%, 12.2%, and 5.6%, respectively (linear trend p = .022). Thirty-five (17.1%) patients had a cardiopulmonary arrest before pediatric ICU admission and another arrest in the pediatric ICU. Only two (5.7%) of these 35 patients survived to discharge. Pediatric ICU survival decreased as the number of pediatric ICU arrests increased. Patients with one arrest (n = 155), two arrests (n = 29), and more than three arrests (n = 21) experienced survival rates of 14%, 14%, and 9.5%, respectively. Severity of illness, as measured by the Pediatric Risk of Mortality III score, was a significant predictor of survival (p < .001).
Pediatric ICU cardiac arrest is an uncommon event. When it does occur, prehospital CPR, duration of resuscitation, traumatic etiology, and severity of illness are important factors associated with survival.
Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding ...event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults body mass index (BMI) > 30 kg/m2. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean +/- SE for age and BMI, 31 +/- 1 and 40 +/- 2, respectively) received DZ (2 mg/kg BW.day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean +/- SE for age an BMI, 28 +/- 1 and 43 +/- 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 +/- 0.69% vs. 4.6 +/- 0.61%, P < 0.001), greater decrease in body fat (P < 0.01), greater increase in fat-free mass to body fat ratio (P < 0.01), and greater attenuation of acute insulin response to glucose (P < 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified i.v. glucose tolerance test (Bergman's minimal model) and no significant difference in glycohemoglobin values.
8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.
Length of stay in the pediatric intensive care unit (PICU) is a reflection of patient severity of illness and health status, as well as PICU quality and performance. We determined the clinical ...profiles and relative resource use of long-stay patients (LSPs) and developed a prediction model to identify LSPs for early quality and cost saving interventions.
Nonconcurrent cohort study.
A total of 16 randomly selected PICUs and 16 volunteer PICUs.
A total of 11,165 consecutive admissions to the 32 PICUs.
None.
LSPs were defined as patients having a length of stay greater than the 95th percentile (>12 days). Logistic regression analysis was used to determine which clinical characteristics, available within the first 24 hrs after admission, were associated with LSPs and to create a predictive algorithm. Overall, LSPs were 4.7% of the population but represented 36.1% of the days of care. Multivariate analysis indicated that the following factors are predictive of long stays: age <12 months, previous ICU admission, emergency admission, no CPR before admission, admission from another ICU or intermediate care unit, chronic care requirements (total parenteral nutrition and tracheostomy), specific diagnoses including acquired cardiac disease, pneumonia, and other respiratory disorders, having never been discharged from the hospital, need for ventilatory support or an intracranial catheter, and a Pediatric Risk of Mortality III score between 10 and 33. The performance of the prediction algorithm in both the training and validation samples for identifying LSPs was good for both discrimination (area under the receiver operating characteristics curve of 0.83 and 0.85, respectively), and calibration (goodness of fit, p = .33 and p = .16, respectively). LSPs comprised from 2.1% to 8.1% of individual ICU patients and occupied from 15.2% to 57.8% of individual ICU bed days.
LSPs have less favorable outcomes and use more resources than non-LSPs. The clinical profile of LSPs includes those who are younger and those that require chronic care devices. A predictive algorithm could help identify patients at high risk of prolonged stays appropriate for specific interventions.
