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Biomedical subjects

J D Klein

Publications and source records attributed to J D Klein.

At least 55 records · Page 3Linked to original sources

Characterization of Lyme meningitis and comparison with viral meningitis in children.

OBJECTIVES: The objectives of this study were to characterize Lyme meningitis (LM) in the pediatric population; to compare LM with viral meningitis (VM) with respect to epidemiology, history and physical examination, and laboratory data; and to provide means of early distinction of Lyme neuroborreliosis from other forms of aseptic meningitis. METHODS: This retrospective analysis involved children admitted to Alfred I. duPont Hospital for Children between 1990 and 1996 whose discharge diagnoses indicated viral or aseptic meningitis or Lyme disease. LM was defined as the presence of cerebrospinal fluid (CSF) pleocytosis with positive Lyme serology and/or erythema migrans. Patients were considered to have VM if they exhibited CSF pleocytosis and had a positive viral culture. Demographic, clinical, and laboratory data were collected for each patient, and patients with LM were compared with age-matched patients with VM. RESULTS: Of 179 patient records, 12 patients with LM and 10 patients with VM (all, >2 years old) were identified by using the above criteria. In comparing LM patients with VM patients, we noted no differences among demographic variables. Children with LM had significantly lower temperatures at the time of presentation. The presence of headache, neck pain, and malaise was similar for the two groups, but the duration of these symptoms was significantly longer among LM patients. Five children with LM had cranial neuropathies. All but 1 LM patient exhibited either papilledema, erythema migrans, or cranial neuropathy. These three findings were absent in the VM group. On CSF analysis, LM patients had fewer white blood cells (mean, 80/mm3 versus 301/mm3) and a significantly greater percentage of mononuclear cells than the VM patients. CONCLUSIONS: In this study, in a Lyme-endemic area, LM was about as common as VM in older children who were hospitalized with aseptic meningitis. Attention to pertinent epidemiologic and historical data, along with physical and CSF findings, allows early differentiation of LM from VM.

Child↗

UT-A urea transporter protein expressed in liver: upregulation by uremia.

In perfused rat liver, there is phloretin-inhibitable urea efflux, but whether it is mediated by the kidney UT-A urea transporter family is unknown. To determine whether cultured HepG2 cells transport urea, thiourea influx was measured. HepG2 cells had a thiourea influx rate of 1739 +/- 156 nmol/g protein per min; influx was inhibited 46% by phloretin and 32% by thionicotinamide. Western analysis of HepG2 cell lysate using an antibody to UT-A1, UT-A2, and UT-A4 revealed two protein bands: 49 and 36 kD. The same bands were detected in cultured rat hepatocytes, freshly isolated rat hepatocytes, and in liver from rat, mouse, and chimpanzee. Both bands were present when analyzed by native gel electrophoresis, and deglycosylation of rat liver lysate had no effect on either band. Differential centrifugation of rat liver lysate showed that the 49-kD protein is in the membrane fraction and the 36-kD protein is in the cytoplasm. To determine whether the abundance of these UT-A proteins varies in vivo, rats were made uremic by 5/6 nephrectomy. The 49-kD protein was significantly increased 5.5-fold in livers from uremic rats compared to pair-fed control rats. It is concluded that phloretin-inhibitable urea flux in liver may occur via a 49-kD protein that is specifically detected by a UT-A antibody. Uremia increases the abundance of this 49-kD UT-A protein in rat liver in vivo.

Animals↗

Cloning and characterization of two new isoforms of the rat kidney urea transporter: UT-A3 and UT-A4.

Urea transport in the kidney is important for the production of concentrated urine and is mediated by a family of transporter proteins, identified from erythropoietic tissue (UT-B) and from kidney (UT-A). Two isoforms of the renal urea transporter (UT-A) have been cloned so far: UT-A1 and UT-A2. We used rapid amplification of cDNA ends to clone two new isoforms of the rat UT-A transporter: UT-A3 and UT-A4. UT-A3 and UT-A4 are 87% homologous. The UT-A3 cDNA encodes a peptide of 460 amino acids, which corresponds to the amino-terminal half of the UT-A1 peptide and is 62% identical to UT-A2. The UT-A4 cDNA encodes a peptide of 466 amino acids, which is 84% identical to UT-A2. Transient transfection of HEK-293 cells with the UT-A3 or UT-A4 cDNA results in phloretin-inhibitable urea uptake, which is increased by forskolin. Thus, both new isoforms encode functional urea transporters that may be vasopressin-regulated. UT-A3 and UT-A4 mRNA are expressed in the renal outer and inner medulla but not in the cortex; unidentified UT-A isoforms similar to UT-A3 may also be expressed in the testis. It is concluded that there are at least four different rat UT-A urea transporters.

Amino Acid Sequence↗

Developing quality measures for adolescent care: validity of adolescents' self-reported receipt of preventive services.

OBJECTIVE: To demonstrate the feasibility of directly surveying adolescents about the content of preventive health services they have received and to assess the validity of adolescent self-reported recall. DATA SOURCES/SETTING: Audiotaped encounters, telephone interviews, and chart reviews with 14-21 year olds being seen for preventive care visits at 15 pediatric and family medicine private practices, teaching hospital clinics, and health centers. DESIGN: 537 adolescents presenting for well visits were approached, 400 (75 percent) consented, 374 (94 percent) were audiotaped, and 354 (89 percent) completed telephone interviews either two to four weeks or five to seven months after their visits. Audiotapes were coded for screening and counseling across 34 preventive service content areas. Intraobserver reliability (Cohen's kappa) ranged from 0.45 for talking about peers to 0.94 for discussing tobacco. The sensitivity and specificity of the adolescent self-reports were assessed using the audiotape coding as the gold standard. RESULTS: Almost all adolescents surveyed (94 percent) remembered having had a preventive care visit, 93 percent identified the site of care, and most (84 percent) identified the clinician they had seen. There was wide variation in the prevalence of screening, based on the tape coding. Adolescent self-report was moderately or highly sensitive and specific at two weeks and six months for 24 of 34 screening and counseling items, including having discussed: weight, diet, body image, exercise, seatbelts, bike helmet use, cigarettes/smoking, smokeless tobacco, alcohol, drugs, steroids, sex, sexual orientation, birth control, condoms, HIV, STDs, school, family, future plans, emotions, suicidality, and abuse. Self-report was least accurate for blood pressure/cholesterol screening, immunizations, or for having discussed fighting, violence, weapon carrying, sleep, dental care, friends, or over-the-counter drug use. CONCLUSION: Adolescents' self-report of the care they have received is a valid method of determining the content of preventive health service delivery. Although recall of screening and counseling is more accurate within two to four weeks after preventive care visits, adolescents can report accurately on the care they had received five to seven months after the preventive health care visits occurred.

Adolescent↗

Cognitive effects of Lyme disease in children: a 4 year followup study.

OBJECTIVE: To measure cognitive effects of Lyme disease (LD) in a pediatric population 4 years after disease onset. METHODS: Prospective, blinded, multivariable controlled study of cognitive skills in children who have been treated for LD. The setting was a children's hospital in an area endemic for LD. Twenty-five children with strictly defined LD were compared with 17 control children (6 disease-control and 11 sibling-control). OUTCOME MEASURES: An extensive set of neuropsychological measures was administered. These included assessment of the cognitive areas of IQ, information processing speed, fine-motor dexterity, novel problem solving and executive functioning, short term and intermediate memory, and acquisition of new learning. Parents' ratings were also obtained concerning disease impact upon everyday activities. RESULTS: Seventeen of the 18 neuropsychological test measures showed the LD and control groups similar at time of 4 year followup. There were no differences between the groups regarding parents' impressions of disease impact. CONCLUSION: In contrast to studies of adults with LD, the results of longterm followup of the pediatric population continue to strongly support the finding that children treated appropriately for LD have an excellent prognosis for normal cognitive functioning.

Analysis of Variance↗

The effect of gammadelta T cell depletion on cytokine gene expression in experimental allergic encephalomyelitis.

In experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis, we showed previously that depletion of gammadelta T cells using the mAb GL3 immediately before disease onset, or during the chronic phase, significantly ameliorated clinical severity. We now report on the effect of gammadelta T cell depletion on expression of five cytokine genes, IL-1, IL-6, TNF, lymphotoxin, and IFN-gamma in spinal cords of mice during the pre-onset, onset, height, and recovery phases of EAE, and on expression of type II nitric oxide synthase. In control animals, the mRNAs for IL-1 and IL-6 rose dramatically at disease onset and peaked before disease height, whereas the mRNAs for TNF, lymphotoxin, and IFN-gamma rose more slowly and peaked with peak of disease. In GL3-treated animals, a dramatic reduction in all five cytokines was noted at disease onset, but only IFN-gamma remained significantly reduced at a time point equivalent to height of disease in control animals. ELISA data confirmed the reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and pathologic analysis demonstrated a marked reduction in meningeal infiltrates at the same time point. Studies of type II NOS also demonstrated a significant reduction in both mRNA and protein expression at the height of disease in GL3-treated animals. These results suggest that gammadelta T cells contribute to the pathogenesis of EAE by regulating the influx of inflammatory cells into the spinal cord and by augmenting the proinflammatory cytokine profile of the inflammatory infiltrates.

Animals↗

Adolescents' access to care: teenagers' self-reported use of services and perceived access to confidential care.

BACKGROUND: Most surveys on adolescents' use of health services rely on parental report, and this may underestimate adolescents' use of confidential services. OBJECTIVE: To investigate adolescents' report of their own use of health services, access to care, and knowledge and use of confidential services. METHOD: A random digit-dialed survey of 14- to 19-year-old adolescents was conducted in Monroe County, New York. We screened 11 800 numbers and identified 4449 households (40%) of which 393 families (8.8%) had eligible adolescents. Of these, 259 (66%) consented and completed an interviewer-administered survey. RESULTS: Almost all adolescents (92%) rated their health as excellent or good and 90% had visited a health care provider within the year. Most (88%) identified a source of primary care. As many as 27% of adolescents had used more than one source of care. Many youth identify school personnel as important resources for health and counseling needs. Only 8.4% of respondents have used services confidentially, but nearly half of all youth did not know where they could obtain confidential care if they needed to. Adolescents were least likely to know where to obtain mental health or substance abuse and reproductive services. CONCLUSIONS: While most youth have used primary care, a substantial minority have not. Many teenagers depend on multiple sources of care, and they rely on school personnel as important sources of health information. Many do not know where they could go to review confidential services or for other services that they may need. Managed care insurance and public health policies should recognize adolescents' access needs to meet them appropriately.

Adolescent↗

Health counseling in adolescent preventive visits: effectiveness, current practices, and quality measurement.

Most morbidity and mortality among adolescents results from their participation in health-compromising behaviors. Recent guidelines for clinical adolescent preventive services recommend that primary care clinicians routinely screen for and counsel adolescents about these behaviors, identify and address related social, psychological, and biologic factors. Office-based counseling can influence adult health behaviors, but little is known about the effectiveness of office-based counseling for adolescents. In this review we: (a) evaluate available information about the effectiveness of office-based health counseling to improve outcomes; (b) report what is known about the health counseling adolescents receive from primary care clinicians; and (c) critically review different approaches that have been, or might be, used to measure the content and quality of health counseling provided during adolescent medical visits. With the emphasis on accountability in the current health care environment, evidence supporting the effectiveness of counseling is needed to justify investment in this aspect of clinical adolescent preventive services. Challenges to studying the effectiveness of health counseling include the lack of well-defined theory-based models for adolescent office-based counseling, the complexity of measuring counseling quality, and the many factors that influence adolescent outcomes. Reliable and valid measures of counseling quality are needed both to study and to ensure the quality of counseling received by adolescents. No single measure can be expected to fully capture counseling quality, although patient self-report deserves further development.

Adolescent↗

Infective endocarditis in the premature neonate.

We describe a series of 11 high-risk neonates with infective endocarditis (IE) in this retrospective review. Previously IE has rarely been diagnosed in newborns and is usually fatal. The frequency was 4.3 cases per 100 patients. Five patients survived. Microorganisms included gram positives such as S. aureus and coagulase-negative Staphylococcus, gram negatives such as Klebsiella pneumoniae, Enterobacter cloacae, Enterococcus faecalis, Serratia marcescens, and Acinetobacter calcoaceticus. Echocardiographic location of the lesions showed four left sided, five right sided, and two bilateral. We conclude that IE may be more common than previously described. Prompt diagnosis and treatment led to survival in 45% of our patients. Prospective studies are needed to identify patients at risk and to establish the true incidence of IE in high-risk neonates.

Autopsy↗

Health care access and utilization among pregnant adolescents.

PURPOSE: To assess access to and use of health care by adolescents prior to their becoming pregnant. METHODS: An interviewer-administered questionnaire was completed by all pregnant adolescents (n = 65) entering the Rochester Adolescent Maternity Program (RAMP) between January and June 1994. Questions addressed access and utilization issues including routine care and other services used, and existence of a regular source of care prior to pregnancy. RESULTS: Sixty-one adolescents (94%) completed questionnaires. Almost all (93%) had made a doctor or clinic visit, and 77% had had a checkup in the prior year. Most had Medicaid (85%) or private insurance (13%). The median number of visits to a regular source of care was 2.0 (range 0-10). Most frequently reported sources of regular care were hospital clinics (43%), community health centers (26%), and private physician offices (15%). Two-thirds (66%) reported having used multiple sources of care. Of those who used other sources in addition to a primary care source, 40% used reproductive health clinics. Adolescents whose primary care source was a traditional physician's office were more likely to also use reproductive health clinics than those who reported using more comprehensive primary care sources. CONCLUSIONS: Most pregnant adolescents in this sample had previously used routine primary care, usually in hospital clinics or health centers. Many of those adolescents also use multiple sources of care, most often for reproductive services. Access to reproductive health services does not seem to have been a problem for these adolescents prior to their pregnancies.

Adolescent↗

Vibrio fluvialis: an underrecognized enteric pathogen in infants?

We report a case of Vibrio fluvialis gastroenteritis in an infants 3 1/2 weeks old. The case was unusual because no likely epidemiologic risk factors were involved. Since several other such cases in young infants have been reported, V fluvialis should be considered in the differential diagnosis of infantile gastroenteritis.

Diagnosis, Differential↗

Shrinkage-induced activation of Na+/H+ exchange: role of cell density and myosin light chain phosphorylation.

Previously, we suggested that myosin light chain kinase (MLCK) is involved in shrinkage-induced activation of the Na+/H+ exchanger in rat astrocytes. Here we have studied the effects of hyperosmotic exposure in C6 glioma cells, a common model for astrocytes. Shrinkage-induced activation of the Na+/H+ exchanger in C6 cells is directly proportional to the degree of shrinkage, results in an alkaline shift in the pK' of the exchanger, is dependent on ATP, and is inhibited by ML-7 (an MLCK inhibitor) and by various calmodulin inhibitors. Cell shrinkage also results in increased phosphorylation of myosin light chain (MLC). Interestingly, shrinkage-induced activation of the exchanger does not occur in subconfluent C6 cells. However, phosphorylation of MLC still occurs in subconfluent cultures of C6 cells on shrinkage, suggesting that the lack of activation in these cells occurs at a point between MLC phosphorylation and Na+/H+ exchange activation. The lack of activation of Na+/H+ exchange in subconfluent C6 cells can be utilized to further elucidate the shrinkage-induced activation pathway.

Amiloride↗

Glucocorticoids mediate a decrease in AVP-regulated urea transporter in diabetic rat inner medulla.

Providing glucocorticoids to adrenalectomized (Adx) rats results in downregulation of the vasopressin (AVP)-regulated urea transporter (VRUT) in the renal inner medullary (IM) tip. To examine the physiological relevance of this response, we studied rats with uncontrolled diabetes mellitus induced by streptozotocin (STZ), since these rats have increased corticosterone production and urea excretion. We measured VRUT protein in extracts from the IM tip or base of pair-fed control and diabetic rats by Western analysis using an antibody to rat VRUT. In the IM tip, VRUT was significantly reduced by 39% in diabetic compared with control rats. In the IM base, there was no significant difference between diabetic and control rats. To determine whether the decrease in VRUT in the IM tip was mediated by glucocorticoids, the experiment was repeated using the following three groups of rats: 1) Adx alone, 2) Adx + STZ, and 3) Adx + STZ + replacement with a physiological dose of glucocorticoid. There was no significant difference in VRUT between Adx and Adx + STZ rats. However, VRUT was significantly reduced by 32% in the IM tip of glucocorticoid-treated Adx + STZ rats compared with control Adx + STZ rats. We conclude that glucocorticoids regulate the abundance of VRUT protein independently of insulin in diabetic rats.

Adrenalectomy↗

Glucocorticoids downregulate the vasopressin-regulated urea transporter in rat terminal inner medullary collecting ducts.

This study tested whether glucocorticoids regulate tubular urea transport. Urea permeability was measured in perfused inner medullary collecting duct (IMCD) subsegments from rats that underwent adrenalectomy, adrenalectomy plus replacement with a physiologic dose of glucocorticoid (dexamethasone), or sham operation. Compared with sham rats, basal urea permeability in terminal IMCD was significantly increased in adrenalectomized rats and reduced in dexamethasone-treated rats. Vasopressin significantly increased urea permeability in all three groups. In contrast, there was no difference in basal or vasopressin-stimulated urea permeability in initial IMCD between the three groups. Next, membrane and vesicle fraction proteins were isolated from inner medullary tip or base and Western analysis was performed by use of an antibody to the rat vasopressin-regulated urea transporter. Vasopressin-regulated urea transporter protein was significantly increased in both membrane and vesicle fractions from the inner medullary tip of adrenalectomized rats. There was no change in vasopressin-regulated urea transporter protein in the inner medullary base, and Northern analysis showed no change in urea transporter mRNA abundance in either inner medullary region. It was concluded that glucocorticoids can downregulate function and expression of the vasopressin-regulated urea transporter in rat terminal IMCD.

Adrenalectomy↗

Value-based formulas for purchasing. Pursuing value in Medicaid managed care: access to care and enrollee information management.

Medicaid and other publicly funded health coverage programs face special challenges in managed care purchasing. This article discusses two of those challenges based on the state of Minnesota's experience: how to develop, evaluate, and communicate access to care; and how to manage the transfer of enrollee eligibility and health status information.

Catchment Area, Health↗