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Biomedical subjects

W Gruber

Publications and source records attributed to W Gruber.

At least 19 recordsLinked to original sources

Effect of specific immunotherapy with house dust mite extract on the bronchial responsiveness of paediatric asthma patients.

BACKGROUND AND OBJECTIVE: Allergic asthma is common in children, and house dust mite (HDM) is an important source of perennial allergens. Bronchial hyperresponsiveness is a functional hallmark of asthma. Specific immunotherapy (SIT) with HDM extracts were shown to decrease symptoms, but its effect on bronchial responsiveness, as measured by non-pharmacological challenges, has not been evaluated. METHODS: Twenty-six paediatric asthma patients allergic to HDM participated in this study. Fourteen patients received SIT with a HDM extract (Alavac, Bencard) for 2 years, and 12 served as controls. Bronchial responsiveness was assessed non-pharmacologically by cold dry air challenge (CACh) before and 3, 6, 12 and 24 months after SIT, and 12 months after termination of SIT. RESULTS: After 24 months, the SIT group showed a statistically significant reduction of the mean CACh-induced changes of both forced expiratory volume in one second (-21.8+/-2.7% vs. -13.7+/-2.4%; P = 0.03) and maximal expiratory flow at 25% remaining vital capacity (-48.9+/-4.9% vs. -27.9+/-6.2%; P = 0.01). In contrast, no significant changes of bronchial responsiveness were observed in the control group. In the SIT group more patients lost their bronchial hyperresponsiveness than in the control group (6/14 vs. 1/12; P<0.05). One year after terminating SIT, the treatment group showed a tendency towards returning bronchial hyperresponsiveness. CONCLUSION: These results demonstrate that during 2 years of SIT there was a reduction of bronchial hyperresponsiveness in HDM-allergic paediatric asthma patients.

Adolescent

Association between female sex hormones and biochemical markers of bone turnover in peri- and postmenopausal women.

In an epidemiological study, markers of bone formation (serum osteocalcin and C-terminal propeptide of type I collagen) and bone resorption [urinary type I collagen peptides (Crosslaps), urinary total pyridinoline (TPYRI), urinary deoxypyridinoline (DPYRI) as well as female sex hormones (serum estradiol)], follicle-stimulating hormone (FSH) and luteinizing hormone were measured in 237 women. This cohort aged 44-66 years, came for their first medical examination since menopause to the outpatient menopause clinic at the Kaiser-Franz-Josef-Hospital, Vienna. The women were all 0.5-5.0 years since cessation of menses and were not taking medications other than hormone replacement therapy [52 cases, 21.9%)] and had no diseases known to affect bone and mineral metabolism. The best correlation was found between urinary DPYRI and urinary TPYRI (r = 0. 63, P = 0.0001), followed by urinary Crosslaps and urinary DPYRI (r = 0.47, p = 0.0001). Only weak but significant correlations between E2 and urinary Crosslaps (r = -0.21, P < 0.0001) as well as serum E2 and serum osteocalcin (r = -0.16, P = 0.0007), were observed. Of the 237 women 53% suffered from a severe E2 deficiency (E2 < 10.0 ng/liter). In these patients, urinary Crosslaps (+48%) and serum osteocalcin (+22%) were significantly higher (P < 0.0001) compared with those patients with E2 levels > 10 ng/liter. Women with E2 levels >10 ng/liter were further subdivided into those with and without sex hormone replacement therapy, whereby no statistical differences in any of the biochemical markers could be observed between these groups. We could clearly demonstrate that in postmenopausal women suffering from severe E2 deficiency (E2 < 10 ng/liter), urinary Crosslaps and serum osteocalcin are significantly increased, indicating in principle a clear correlation between E2 deficiency and these markers of bone turnover.

Adult

Complications after shunting isolated IV ventricles.

An isolated IV ventricle in chronically shunted patients is being reported with increasing frequency. Complications associated with posterior fossa shunting, however, have seldom been described. Between January 1986 and December 1995, we treated 292 children younger than 16 years for hydrocephalus: 7 (2.4%) developed an isolated IV ventricle, and 5 of these were symptomatic with posterior fossa signs. These 5 patients required posterior fossa shunting, after which their neurological status improved. However, 1 week and 6 weeks after surgery, respectively, 2 patients developed new cranial nerve deficits related to a slit-like IV ventricle with secondary irritation of the brain stem by the IV ventricular catheter. Shortening the catheter and replacing the valve eliminated the cranial nerve palsies, implying that these complications were not caused by direct injury of the brain stem during placement of the shunt. Alternative surgical techniques and the use of different (flow-regulating) valves may avoid such complications.

Adolescent

Ganciclovir treatment of symptomatic congenital cytomegalovirus infection: results of a phase II study. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group.

Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns in the United States. A phase II evaluation was done of ganciclovir for the treatment of symptomatic congenital CMV infection. Daily doses of 8 or 12 mg/kg were administered in divided doses at 12-h intervals for 6 weeks. Clinical and laboratory evaluations sought evidence of toxicity, quantitative virologic responses in urine, plasma drug concentrations, and clinical outcome. A total of 14 and 28 babies received 8 and 12 mg/kg/day, respectively. Five additional babies received ganciclovir on a compassionate plea basis. Significant laboratory abnormalities included thrombocytopenia (< or = 50,000/mm3) in 37 babies and absolute neutropenia (< or = 500 mm3) in 29 babies. Quantitative excretion of CMV in the urine decreased; however, after cessation of therapy, viruria returned to near pretreatment levels. Hearing improvement or stabilization occurred in 5 (16%) of 30 babies at 6 months or later, indicating efficacy.

Alanine Transaminase

The effect of multidimensional exercises on balance, mobility, and fall risk in community-dwelling older adults.

BACKGROUND AND PURPOSE: This prospective clinical investigation examined the effects of a multidimensional exercise program on balance, mobility, and risk for falls in community-dwelling older adults with a history of falling. Factors used to predict adherence and a successful response to exercise were identified. SUBJECTS: A total of 105 community-dwelling older adults (> or = 65 years of age) with a history of two or more falls in the previous 6 months (no neurologic diagnosis) participated. They were classified into (1) a control group of fallers (n = 21), (2) a fully adherent exercise group (n = 52), and (3) a partially adherent exercise group (n = 32). METHODS: Following evaluation, each patient received an individualized exercise program addressing the impairments and functional disabilities identified during the assessment. The control group received no intervention. Changes in performance on five clinical tests of balance and mobility and fall risk were compared among groups. RESULTS: Both exercise groups scored better than the control group on all measures of balance and mobility. Although both exercise groups showed a reduction in fall risk compared with the control group, the greatest reduction was found in the fully adherent exercise group. Factors associated with successful response to exercise included degree of adherence to exercise program and pretest score on the Tinetti Mobility Assessment. CONCLUSION AND DISCUSSION: Exercise can improve balance and mobility function and reduce the likelihood for falls among community-dwelling older adults with a history of falling. The amount of exercise needed to achieve these results, however, could not be determined from this study.

Accidental Falls

Predicting the probability for falls in community-dwelling older adults.

BACKGROUND AND PURPOSE: The objective of this retrospective case-control study was to develop a model for predicting the likelihood of falls among community-dwelling older adults. SUBJECTS: Forty-four community-dwelling adults (> or = 65 years of age) with and without a history of falls participated. METHODS: Subjects completed a health status questionnaire and underwent a clinical evaluation of balance and mobility function. Variables that differed between fallers and nonfallers were identified, using t tests and cross tabulation with chi-square tests. A forward stepwise regression analysis was carried out to identify a combination of variables that effectively predicted fall status. RESULTS: Five variables were found to be associated with fall history. These variables were analyzed using logistic regression. The final model combined the score on the Berg Balance Scale with a self-reported history of imbalance to predict fall risk. Sensitivity was 91%, and specificity was 82%. CONCLUSION AND DISCUSSION: A simple predictive model based on two risk factors can be used by physical therapists to quantify fall risk in community-dwelling older adults. Identification of patients with a high fall risk can lead to an appropriate referral into a fall prevention program. In addition, fall risk can be used to calculate change resulting from intervention.

Accidental Falls

Atopy, lung function and bronchial responsiveness in symptom-free paediatric asthma patients.

In adolescence, some paediatric asthma patients will become symptom-free and require no further treatment. There is little information on the atopic status, lung function and bronchial responsiveness of these patients. Symptom-free asthma patients (n=118) aged 7.7-19.2 yrs, were evaluated 1 year after termination of therapy. Bronchial asthma had previously been diagnosed on the basis of recurrent wheezing episodes. Atopic status was assessed by skin-prick testing. Baseline lung function was measured by spirometry, flow-volume curve and plethysmography. Bronchial responsiveness was assessed nonpharmacologically by cold dry air challenge. Eighty one patients had at least one positive skin test result, and the remaining 37 were defined as nonatopic. In atopic subjects, the prevalence of bronchial hyperresponsiveness was significantly higher than in nonatopic patients (41 out of 81 versus 7 out of 37; p=0.001). Atopic subjects showed a significantly lower maximal expiratory flow at 25% remaining vital capacity (p<0.05) and a higher residual volume (p<0.05) than nonatopic subjects. Nonatopic subjects were significantly younger than atopic patients (p<0.01). These symptom- and medication-free paediatric and adolescent asthma patients could, thus, be divided into two groups: 1) atopic subjects with a tendency towards bronchial hyperresponsiveness; and 2) nonatopic subjects with better lung function and normal bronchial responsiveness In view of the increased understanding of the epidemiology of early childhood wheezing, these findings support the concept of different pathogenic mechanisms underlying wheezing episodes in early childhood.

Adolescent

Biochemical markers in menopausal women.

Markers of bone formation (osteocalcin and C-Terminal Propeptide of Type I Collagen [CICP]) and of resorption (Crosslaps, total pyridinoline [Pyd] and deoxypyridinoline [Dpd]) as well as female sex hormones (estradiol [E2], follicle stimulating hormone [FSH] and luteinizing hormone [LH]) were measured in 237 women aged 44-66 years coming for the first medical examination to the outpatient clinic of menopause at the Kaiser-Franz-Josef-Hospital, Vienna. All women (0.5-5.0 years since cessation of menses) selected were not taking medications other than hormone replacement therapy in 52 cases (21.9%) and did not have diseases known to affect bone and mineral metabolism. The best correlation was found between Dpd and Pyd (r = 0.63, p = 0.0001), followed by Crosslaps and Dpd (r = 0.47, p = 0.0001). Only weak but significant correlations between E2 and Crosslaps (r = 0.21, p < 0.0001) as well as E2 and osteocalcin (r = 0.16, p = 0.0007) were observed, 53% of the 237 women suffered from a severe E2 deficiency (E2 < 10.0 ng/L). In these patients Crosslaps (approx. +48%) and osteocalcin (+22%) were significantly higher (p < 0.0001) compared to those with E2 concentrations > 10 ng/L. Women with E2 concentrations > 10 ng/L were further subdivided into women with and without sex hormone replacement therapy, whereby no statistical differences in any of the biochemical markers could be observed between these both groups. In conclusion, we could clearly demonstrate that in postmenopausal women suffering from severe E2 deficiency (E2 < 10 ng/L) Crosslaps and osteocalcin are significantly increased, indicating in principle a clear correlation between E2 deficiency and these markers of bone turnover.

Adult

Initial evaluation of cystatin C measurement by particle-enhanced immunonephelometry on the Behring nephelometer systems (BNA, BN II).

Serum cystatin C has been suggested as a new marker of glomerular filtration rate (GFR). We describe a fully automated and rapid particle-enhanced nephelometric immunoassay (PENIA) for measuring serum cystatin C on the Behring nephelometer systems (BNA, BN II). Each sample is analyzed in 6 min with as many as 75 samples per batch. The assay covers the range 0.23-7.25 mg/L, up to seven times the upper limit of normal. The intra- and interassay imprecision are < 3.3% and < 4.5%, respectively. There is absolute linearity across the assay range (r2 = 0.997), with analytical recovery by cystatin C addition between 95% and 109% (mean 102%). Hemoglobin (< or = 8.0 g/L), bilirubin (< or = 488 microL), triglycerides (< or = 23 mmol/L), rheumatoid factor (< or = 2000 kIU/L), and myeloma paraprotein (< or = 41 g/L) do not interfere with the assay. This assay agreed well with an in-house particle-enhanced turbidimetric immunoassay (PETIA) (mean difference = 1.73 +/- 2.10) and a commercial PETIA (mean difference = 1.13 +/- 0.86). This is a new assay by which cystatin C may be effectively used as a marker of GFR estimation.

Animals

The WHO national diabetes programme initiative.

Epidemiological studies indicate that diabetes is a highly prevalent disease, with developing countries and minority populations now facing the highest risk. This places a strain on the health authorities, and consequently, has attracted increasing attention from the World Health Organization (WHO). The social and economic burden of diabetes is high, due to the seriousness of the complication of the disease. Many of these complications may be delayed or prevented, offering considerable opportunities for both reduction in costs to the authorities and improvements in quality of life for those affected. Following a resolution on the prevention and control of diabetes, adopted by the Forty-second World Health Assembly in 1989, the WHO diabetes programme prepared guidelines for the development of national diabetes programmes. Goals, targets and supporting materials have also been developed at the regional level by the WHO Regional Offices for Europe and for the Eastern Mediterranean. In 1994, WHO organized a meeting on the implementation of national diabetes programmes at its headquarters in Geneva. There were 70 participants and 32 counties were represented. The purposes of the meeting were to exchange information, motivate, consider evaluation, stimulate new programmes, define educational needs and prepare a written report. WHO plays a major role in the development of national diabetes programmes. In co-operation, WHO Headquarters and Regional Offices can act as clearing houses/information centres for data collection, programme monitoring and evaluation and the exchange of experience and technical information. The national diabetes programme initiative should result in improvements in diabetes control and care worldwide.

Diabetes Mellitus

Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a phase I/II trial.

BACKGROUND: Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. METHODS: Infants < or = 1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m2/dose given either twice daily or three times per day) was administered for 6 months. RESULTS: Twelve (46%) of the 26 infants developed neutropenia (< 1000 cells/mm3) while receiving acyclovir. Thirteen (81%) of the 16 infants who received drug 3 times per day experienced no recurrences of skin lesions while receiving therapy. In comparison, a previous Collaborative Antiviral Study Group study found that only 54% of infants have no cutaneous recurrences in the 6 months after resolution of neonatal HSV disease if oral acyclovir suppressive therapy is not initiated. In one infant, HSV DNA was detected in the cerebrospinal fluid during a cutaneous recurrence, and an acyclovir-resistant HSV mutant was isolated from another patient during the course of the study. CONCLUSIONS: Administration of oral acyclovir can prevent cutaneous recurrences of HSV after neonatal SEM disease. The effect of such therapy on neurologic outcome must be assessed in a larger, Phase III study. As such, additional investigation is necessary before routine use of suppressive therapy in this population can be recommended.

Acyclovir

Population pharmacokinetics of ganciclovir in newborns with congenital cytomegalovirus infections. NIAID Collaborative Antiviral Study Group.

The population pharmacokinetics of ganciclovir was investigated in a group of 27 newborns with symptomatic congenital cytomegalovirus infection by nonlinear mixed-effects modeling analysis. Individual characteristics including approximated creatinine clearance from serum (ASCC) and body weight (WGE) were identified to significantly influence total clearance from plasma (CL) and the apparent total volume of distribution (V) of ganciclovir, respectively. The regression equations used to model these relationships were expressed as CL (in liters per hour) = 0.262 + (0.00271 x ASCC) and V (in liters) = 0.627 + (0.437 x WGE). By using this model, typical values of the pharmacokinetic parameter CL and V were 0.428 +/- 0.079 liters/h and 1.773 +/- 0.320 liters, respectively. Upon validation with a larger number of newborns, this model should allow for the definition of possible relationships between the pharmacokinetic disposition of ganciclovir and pharmacodynamic events in neonates.

Antiviral Agents

Breech infants: vaginal or cesarean delivery?

BACKGROUND: This study was undertaken to determine whether planned vaginal or elective cesarean delivery is better for singleton term breech infants and their mothers. METHODS: We studied deliveries of 388 singleton term breech infants that were born in our teaching hospital in Vienna. We follow well defined criteria for vaginal delivery versus cesarean section of term breech fetuses. We thus compared 280 (72%) cases scheduled for vaginal delivery with 108 (28%) scheduled cesarean sections with regard to neonatal mortality and morbidity, including Apgar score, umbilical artery pH, and postpartum maternal morbidity. RESULTS: Vaginally delivered fetuses of primiparas had lower five-minute Apgar scores (5% < Apgar 7) and a lower umbilical artery pH (39% below 7.2). This is significantly different from the abdominally delivered primiparas (no Apgar below 7, only 11% with an artery pH below 7.2). Multiparas did not show significantly different results with regard to Apgar scores and umbilical artery pH between the different modes of delivery. Postpartum maternal morbidity was not different between the two groups. CONCLUSION: The results suggest that planned vaginal delivery of singleton breech infants of primiparas result in newborns with lower Apgar-scores, a lower umbilical artery pH and a poorer fetal outcome. On the other hand, it seems that singleton term infants of multiparas do not profit from cesarean delivery.

Adolescent

The HA1 of cold-adapted influenza B vaccine is not altered during replication in human vaccinees.

Influenza viruses recovered from 14 children 2-10 days after vaccination with an egg-grown, cold-adapted influenza B vaccine (B/AA/1/86) were analyzed. Hemagglutination-inhibition (HI) assays using monoclonal antibodies did not detect antigenic differences between the vaccine strain and the viruses recovered from the vaccinees. Furthermore, nucleotide sequence analysis of the HA1 region did not reveal any changes compared to the sequence of the vaccine strain. These findings indicate that influenza B vaccine hemagglutinin is genetically stable during replication in human vaccinees.

Animals

The role of the pharmaceutical industry in promoting patient education.

The role of the pharmaceutical industry in patient education consists of information related to products, information related to disease states and stimulation of all parts and partners in patient education. The 'package inserts' have advanced far beyond basic dosage prescribing information and precautions. Audiovisual instruction aids and telephone hot lines are increasingly used. Information on disease states are mainly distributed through the health care providers and patient organisations. They range from tools for special provisions, e.g. foot care in diabetes, up to complete systems for patient education. The stimulating activities range from the funding of education funds or conferences to the organisation of courses for health care professionals up to close cooperation with non-governmental and governmental organisations involved in patient education. The persons involved from industry became highly respected, fully integrated partners in the development of patient education. It is hoped that the commitment of industry in this issue might continue.

Drug Industry

Group A streptococcal necrotizing fasciitis following varicella in children: case reports and review.

We report four cases of necrotizing fasciitis that occurred following varicella in children ranging in age from 2 to 8 years. The only organism isolated from each of these patients was Streptococcus pyogenes or group A beta-hemolytic Streptococcus (GABHS). Each child recovered; however, three required repeated surgical debridements in addition to therapy with antibiotics. An interesting finding in these patients was the development of hyponatremia and/or hypocalcemia. M-typing and T-typing of the isolates demonstrated that the GABHS strain in two children who attended the same school was M5; M1 and M3 strains were identified in the other two children. In addition to the children described in this series, eleven other cases of children with necrotizing fasciitis following varicella have been reported in the English-language literature since 1970. We believe that these cases provide further evidence that varicella is an important risk factor for necrotizing fasciitis that is caused by more-virulent strains of GABHS.

Chickenpox