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Biomedical subjects

B Oberg

Publications and source records attributed to B Oberg.

At least 37 records · Page 2Linked to original sources

Prevention of simian immunodeficiency virus, SIVsm, or HIV-2 infection in cynomolgus monkeys by pre- and postexposure administration of BEA-005.

OBJECTIVE: To study the possibilities and limitations of postexposure treatment to prevent the establishment of infection after accidental exposure to HIV. DESIGN AND METHODS: The effect of 2,3'-dideoxy-3'-hydroxymethyl cytidine (B1 A-005) was investigated on acute simian immunodeficiency virus (SIV) and HIV-2 infections in macaques in pre- and postexposure treatment experiments. RESULTS: Postexposure treatment with BLA-005 (3 x 10 mg/kg) for as short as 3 days prevented infection with SIVsm after intravenous or rectal inoculation. Infection with HIV-2 could also be blocked by postexposure BFA-005 treatment. CONCLUSION: This study shows that therapeutic intervention can block early systemic and mucosal infections with SIV and HIV-2. Further evaluation is ongoing.

Animals↗

Gait analysis, isokinetic muscle strength measurement in patients with Parkinson's disease.

The aim of this study was to describe motor performance in Parkinson patients in relation to controls. Gait, concentric isometric and eccentric strength in the ankle dorsiflexors were investigated in 25 patients with Parkinson's disease and in 37 control subjects of the same age. In patients concentric torque was significantly lowered but, eccentric torque was significantly lowered in male patients only. Among controls a significant difference in strength was found between sexes. This was not found in the patient group. No correlation between strength tests and clinical ratings was found in the patient group. Patients walked with significantly lower maximum and ordinary velocity, compared with controls. At constant velocity, stride length was shorter, single support had a shorter duration. The duration for heel on to ball on in males was shorter, reflecting the flat foot strike of Parkinson patients. Single support and the duration of heel on to ball on correlated significantly to the clinical ratings in male but not in female patients. In the male group of patients there was a relation between concentric strength on the one hand and gait velocity, stride length and stride frequency on the other. Female patients generally had fewer symptoms and less deviation from their respective controls in the measurements. The comparatively simple neurophysiological tests presented here may be suitable for evaluation of patients with Parkinson's disease.

Aged↗

Stretch-shortening contraction in Parkinson patients: evidence of normal muscle contraction execution with low efficiency.

The aim of this study was to compare different muscle contraction types in Parkinson patients and controls. Ten patients with mild to moderate Parkinsonism (7 men, 3 women, mean age 62.3) and 11 controls (7 men, 4 women, mean age 66.0) were investigated. Measurements in eccentric, concentric contraction and stretch-shortening contraction were made using modified Cybex 11 equipment. The torque areas in ankle dorsiflexors at 30 degrees/second, 120 degrees/second and 180 degrees/second were measured. The power (Nm/second) was calculated in a defined range of motion. The power at different angular velocities and contraction types was significantly lower in the patient group than in the control group. In both groups the power in eccentric and stretch-shortening contraction was significantly larger than in concentric contraction. The relative improvement in power in stretch-shortening contraction in patients was equal to the improvement made by the controls. Patients generated significantly more EMG than controls in concentric and eccentric contractions. The EMG in the stretch-shortening cycle was the same in both groups at higher velocities. The patients performed voluntary isolated muscle contraction in the same way as controls, but with a lower efficiency in contraction. The eccentric torque and the supplement of torque generated from the combined eccentric and concentric (stretch-shortening) contraction might be important for achievement of adequate dynamic movements in patients with Parkinson's disease.

Aged↗

Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs.

Phenylethylthiazolylthiourea (PETT) derivatives have been identified as a new series of non-nucleoside inhibitors of HIV-1 RT. Structure-activity relationship studies of this class of compounds resulted in the identification of N-[2-(2-pyridyl)ethyl]-N'-[2-(5-bromopyridyl)]-thiourea hydrochloride (trovirdine; LY300046.HCl) as a highly potent anti-HIV-1 agent. Trovirdine is currently in phase one clinical trials for potential use in the treatment of AIDS. Extension of these structure-activity relationship studies to identify additional compounds in this series with improved properties is ongoing. A part of this work is described here. Replacement of the two aromatic moieties of the PETT compounds by various substituted or unsubstituted heteroaromatic rings was investigated. In addition, the effects of multiple substitution in the phenyl ring were also studied. The antiviral activities were determined on wild-type and constructed mutants of HIV-1 RT and on wild-type HIV-1 and mutant viruses derived thereof, Ile100 and Cys181, in cell culture assays. Some selected compounds were determined on double-mutant viruses, HIV-1 (Ile 100/Asn103) and HIV-1 (Ile100/Cys181). A number of highly potent analogs were synthesized. These compounds displayed IC50's against wild-type RT between 0.6 and 5 nM. In cell culture, these agents inhibited wild-type HIV-1 with ED50's between 1 and 5 nM in MT-4 cells. In addition, these derivatives inhibited mutant HIV-1 RT (Ile 100) with IC50's between 20 and 50 nM and mutant HIV-1 RT (Cys 181) with IC50's between 4 and 10 nM, and in cell culture they inhibited mutant HIV-1 (Ile100) with ED50's between 9 and 100 nM and mutant HIV-1 (Cys181) with ED50's between 3 and 20 nM.

Animals↗

Development of an instrument for clinical evaluation after surgery for neuromuscular scoliosis.

Surgical treatment for neuromuscular scoliosis is effective for most patients. Although those afflicted constitute a heterogeneous group, the aim of surgical treatment is approximately the same for all patients: a spine balanced in the coronal and sagittal planes over a level pelvis. Surgery results in a more stable and straighter spine, which should in turn improve performance in different activities. Previous evaluations of surgery for neuromuscular scoliosis reported in the literature have focused primarily on Cobb angles; there are very few studies dealing with the ability to perform various activities. A new tool for evaluation was developed in several steps, starting with a telephone interview with patients who had undergone surgery and a literature search. The evaluation instrument was then developed, followed by a pilot study and validation of new parts of the instrument. The instrument focuses on performance components and on activity performance. Eight items are evaluated before and after surgery. These data are complemented by a questionnaire administered to the patient or relatives at follow-up. The new parts of the instrument were developed specifically for patients with neuromuscular scoliosis, and the data obtained have been shown to have a high correlation with established measures of activities of daily living of daily living). They should therefore provide us with useful information concerning functional gains as a result of surgery as well as the effect of surgery on activity performance.

Adolescent↗

Effects of an exercise program on musculoskeletal symptoms and physical capacity among nursing staff.

Musculoskeletal disorders are a major health problem, and nursing staff are often seen as a risk group. The purpose of this study was to evaluate the effect of a weekly exercise program among nursing staff on musculoskeletal symptoms and to study the relation to changes in physical capacity. A total of 106 nurses and nursing aides from four geriatric wards were invited to participate; 86 accepted. A cross-over design was used. The staff from two wards were assigned to an exercise period and the staff from the other wards to a control period for the first intervention period. After a wash-out period, the intervention changed. For the exercise periods the staff were invited to participate in an exercise program twice a week for 8 weeks. In total 50 subjects participated more than 8 times regularly during the exercise periods (participants = > or = 8 times regular participation, nonparticipants = < 8). During the control periods 78 subjects attended without intervention. Assessments were made with a standardized questionnaire for analysis of musculoskeletal and psychosomatic symptoms, testing of muscle strength in m. quadriceps with a Cybex dynamometer, and testing of cardiovascular capacity with a Dynavite computerized exercise bicycle before and after the exercise periods. The muscle strength in m. quadriceps increased more during the exercise periods compared with the control periods, explained primarily by the subgroup of nonregular exercisers and those > or = 40 years of age. The number of musculoskeletal symptoms tended to decrease more in the subgroup of nonregular exercisers (those who exercised less than once a week in their spare time) during the exercise periods compared with the nonregular exercisers during the control periods. Comparisons within groups showed a decrease in the number of musculoskeletal symptoms within the exercise periods, explained primarily by a decrease among the participants rather than among the nonparticipants. The decrease within the participants was explained primarily by the subgroup of nonregular exercisers and those > or = 40 years of age. An increase in cardiovascular capacity and a tendency to increase in muscle strength in m. quadriceps were seen among the participants, explained primarily by the effect in the subgroup of nonregular exercisers. The study suggests that a moderate weekly exercise program, performed in a group, among nursing staff affects physical capacity and the number of musculoskeletal symptoms for subjects who are nonregular exercisers and probably subjects > or = 40 years of age.

Adult↗

Animal model for the therapy of acquired immunodeficiency syndrome with reverse transcriptase inhibitors.

The reverse transcriptase (RT) of the human immunodeficiency virus type 1 (HIV-1) is the major target for antiretroviral therapy of the acquired immunodeficiency syndrome (AIDS). While some inhibitors exhibit activity against most retroviral RTs, others are specific for the HIV-1 enzyme. To develop an animal model for the therapy of the HIV-1 infection with RT inhibitors, the RT of the simian immunodeficiency virus (SIV) was replaced by the RT of HIV-1. Macaques infected with this SIV/HIV-1 hybrid virus developed AIDS-like symptoms and pathology. The HIV-1-specific RT inhibitor LY300046.HCl, but not zidovudine [3'-azido-3'-deoxythymidine (AZT)] delayed the appearance of plasma antigenemia in macaques infected with a high dose of the chimeric virus. Infection of macaques with the chimeric virus seems to be a valuable model to study the in vivo efficacy of new RT inhibitors, the emergence and reversal of drug resistance, the therapy of infections with drug-resistant viruses, and the efficacy of combination therapy.

Acquired Immunodeficiency Syndrome↗

Enhancement of HIV-1 proteinase activity by HIV-1 reverse transcriptase.

HIV-1 reverse transcriptase (RT) was found to increase the activity of HIV-1 proteinase in vitro and in eukaryotic cells. The effect of RT on proteinase activity was dose-dependent and independent of pH or salt concentration. The cleavage of sequences corresponding to all the naturally occurring cleavage sites that could be tested in vitro was enhanced. The effect of RT on cleavage was greatest at the cleavage site between RT and integrase. The enhancement of viral proteinase activity by the virus RT may contribute to regulation of the order and/or efficiency of cleavage at different sites during virus replication and maturation.

Base Sequence↗

Inhibition of human immunodeficiency virus type 1 wild-type and mutant reverse transcriptases by the phenyl ethyl thiazolyl thiourea derivatives trovirdine and MSC-127.

A new class of very potent and selective non-nucleoside inhibitors of HIV reverse transcriptase (RT) has recently been identified. The prototype compound trovirdine (LY 300046 HCl) and one analogue, MSC-127, have been studied with respect to inhibition of wild-type HIV-1 RT and RT with various mutations known to give rise to resistance to other non-nucleoside RT inhibitors, namely Leu100-->Ile (Ile100), Glu138-->Arg (Arg138), Tyr181-->Cys (Cys181) and Tyr188-->His (His188). The inhibition of HIV-1 RT by trovirdine and MSC-127 was reversible and template dependent. Trovirdine inhibited HIV-1 RT with an IC50 of 0.007 microM when employing heteropolymeric primer/template (oligo-DNA/ribosomal RNA) and dGTP as substrate. Enzyme kinetic studies showed that inhibition of RT by trovirdine was non-competitive with regard to deoxynucleoside triphosphates and uncompetitive with respect to varied primer/template under steady-state conditions. The amino acid changes Leu100, Tyr181 and Tyr188 gave rise to 25-, 147- and 12-fold decrease in inhibition by trovirdine. Enzyme-kinetic studies on trovirdine have been carried out using various RT mutants and compared to the properties of the earlier reported non-nucleoside RT inhibitors 9-Cl-TIBO, nevirapine and L-697,661.

Antiviral Agents↗

The effect of nasal oxygen flow and catheter position on the accuracy of end-tidal carbon dioxide measurements by a pharyngeal catheter in unintubated, spontaneously breathing subjects.

Reliable recordings of carbon dioxide concentrations during spontaneous respiration can be obtained from a catheter positioned in the hypopharynx. The present study investigated the possible influence on end-tidal carbon dioxide measurement of nasal oxygen administration, position of the sampling catheter and mouth breathing. The study demonstrated that not only can reliable capnographic tracings be obtained from a thin catheter placed in the unintubated airway, but the subject may also receive up to 6 l.min-1 of oxygen via the nasal route without interference with the accuracy of the measurements. Furthermore, the exact position of the sampling catheter tip in the airway is not critical, which means that it may be placed where it causes the patient least discomfort. Finally, mouth breathing caused a mean decrease in end-tidal carbon dioxide of 0.25 kPa compared to nose breathing.

Administration, Intranasal↗

Reliability of CO2 measurements from the airway by a pharyngeal catheter in unintubated, spontaneously breathing subjects.

Although several short communications have appeared describing attempts to record the concentrations of carbon dioxide (cCO2) from the unintubated airway by a catheter placed in the nose, so far only few reports have documented the reliability of the method. To evaluate the reliability of CO2 measurements by a catheter in the open, unintubated airway during spontaneous respiration, a 12 CH PVC catheter was forwarded through the nostril to the hypopharynx and connected to a capnograph in nine healthy volunteers. Another capnograph was connected to a tightly fitting face mask and simultaneous CO2 recordings were attained from the two parts of the airway during normoventilation, hyperventilation and rebreathing. A corresponding blood sample was drawn from the radial artery for blood gas analysis. The configurations of the capnograms recorded from the pharyngeal catheter were similar to those recorded from the face mask. The results were analysed by a multifactor analysis of variance. The carbon dioxide tension (pCO2) was significantly influenced by degree of ventilation (P < 0.0001), subject (P < 0.0001), measurement site (P = 0.030) and interaction subject-ventilation (P = 0.015). In spite of the significant influence of the measurement site, the difference between end tidal carbon dioxide tension (pCO2(ET)) and carbon dioxide tension in arterial blood (pCO2(a)) was small. The mean differences between paired measurements (pCO2(ET)-pCO2(a)) were -0.10 kPa +/- 0.41 kPa (mean +/- SD) for the catheter and -0.20 kPa +/- 0.43 kPa for the face mask. The study demonstrates that reliable recordings of CO2 concentrations during spontaneous respiration can be obtained by a thin catheter positioned in the hypopharynx.

Adult↗

Oxygraphy in spontaneously breathing subjects.

BACKGROUND: Continuous monitoring of O2 and CO2 in the airways of spontaneously breathing patients can be carried out by sampling air to a gas monitor through a catheter placed in the upper airway. The graphical display of O2 (oxygraphy) is a rather new facility. OBJECTIVE: To describe the photo-acoustic and magneto-acoustic technique for CO2 and O2 monitoring in the open unintubated airway, to evaluate the efficacy of oxygen therapy by oxygraphy and to determine alveolar gas tensions and alveolar-arterial partial pressure gradients. DATA SOURCES: O2 and CO2 fractions in the airways were monitored in 9 healthy subjects. Blood samples were drawn from the radial artery. METHODS: The Multigas Monitor 1,304 (Brüel and Kjaer, Naerum, Denmark) was used; end-expiratory measurements were considered as representative for the alveolar gas composition. Arterial blood was analysed by ABL520 (Radiometer Medical A/S, Copenhagen, Denmark). RESULTS: Reliable tracings of gas fractions (FCO2 and FO2) were obtained during the respiratory cycle in all subjects. When oxygen was supplied, FO2 of the airway varied considerably during the inspiratory phase whereas it remained almost constantly during the expiratory phase. The end-expiratory FO2 increased from 0.15 breathing atmospheric air to 0.41 breathing oxygen 15 L/min through a Hudson mask. Alveolar-arterial partial pressure differences were: pO2(A-a): 1.07 +/- 0.85 kPa and pCO2(A-a): -0.04 +/- 0.33 kPa during normoventilation in atmospheric air. CONCLUSION: Continuous monitoring of CO2 and O2 in the airway gives information about the pulmonary gas exchange and the efficacy of oxygen supply. Combined with arterial blood gas analysis the method allows determination of alveolar-arterial CO2 or O2 gradients.

Acoustics↗

Pelvic floor exercises for children: a method of treating dysfunctional voiding.

OBJECTIVE: To evaluate the clinical effect of a pelvic floor exercise programme developed for children. PATIENTS AND METHODS: Sixteen girls with non-neurogenic dysfunctional voiding were treated by a physiotherapist, mostly in small groups. The exercises were designed to increase the child's awareness of their pelvic floor musculature and to teach them how to contract and relax these muscles at will. The emphasis on pelvic floor relaxation served to improve the child's voiding pattern. RESULTS: After 1 year, nine girls were cured and seven improved. Another three girls were cured at the 3-4 year follow-up, giving a total cure rate of 12/16. CONCLUSION: This non-invasive method seems to be a useful alternative or complement to other treatments of children with dysfunctional voiding.

Adolescent↗

Adjunctive corticosteroid therapy in bacterial meningitis.

Experimental studies of bacterial meningitis have shown that components of bacterial cell walls stimulate the local production of inflammatory cytokines in the cerebrospinal fluid, leading to inflammation and alterations in the cerebral microvasculature. Animal studies and clinical trials have demonstrated that adjunctive corticosteroid therapy reduces the production of cytokines in the CSF. This results in decreased severity of the inflammatory process and fewer neurologic sequelae. These data support the use of adjunctive dexamethasone in infants and children with S. pneumoniae and H. influenzae type B (HiB) meningitis. There is not sufficient evidence supporting the use of adjunctive corticosteroid therapy in children with meningitis caused by N. meningitidis. Also, the routine use of dexamethasone in adult meningitis cannot presently be recommended. When using dexamethasone timing is crucial. Administration before or with antibiotics is optimal for attenuating the subarachnoid space inflammatory response. Patients receiving the therapy need careful monitoring for the possibility of gastrointestinal bleeding. Future studies of the pathogenesis and pathophysiology of bacterial meningitis may lead to the development of other adjunctive treatment strategies, improving the outcome of this serious disease.

Adrenal Cortex Hormones↗

Enzymatic properties and sensitivity to inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase with Glu-138-->Arg and Tyr-188-->His mutations.

Two mutants of HIV-1 reverse transcriptase (RT), Tyr-188-->His and Glu-138-->Arg have been prepared and their catalytic properties and sensitivities to inhibitors studied. As compared to wild type RT, a reduction in catalytic efficiency and turn over number was observed, especially for the Tyr-188-->His mutant. The non-nucleoside inhibitors nevirapine, L-697,661 and 9-Cl-TIBO caused a mixed type of inhibition of RT (Arg-138) with respect to substrate, and with the exception of a non-competitive inhibition by nevirapine, also a mixed type of inhibition of RT (His-188). Foscarnet (PFA) caused a non-competitive type of inhibition of RT (Arg-138) and a mixed inhibition of RT (His-188). The inhibition by ddG-TP was competitive with both mutant RTs. Inhibition by nevirapine gave IC50 values of 0.15, 0.23 and 0.72 microM; by 9-Cl-TIBO of 0.20, 2.50 and 10.3 microM; by L-697,661 of 0.064, 0.28 and 0.60 microM; by ddGTP of 0.13, 0.14 and 0.02 microM; by PFA of 17.0, 48.0 and 15.0 microM for RT wt, RT (Arg-138) and RT (His-188), respectively.

Amino Acids↗

Validity and reliability of a new assessment of lower-extremity dysfunction.

BACKGROUND AND PURPOSE: A 20-variable assessment system for evaluation of lower-extremity dysfunction has been constructed with special consideration of the needs of the physical therapist. The variables are classified into five subgroups: hip impairment, knee impairment, physical disability, social disability, and pain. SUBJECTS: One hundred five patients with osteoarthrosis of the hip and knee, all accepted for total joint replacement arthroplasty, were tested. The mean age of the patients was 69 years (SD = 9.0, range = 46-91). METHODS: The original grouping of the variables was analyzed for content validity with a factor analysis. The results from a subgroup of 42 patients were tested for intertester reliability with the Goodman-Kruskal gamma coefficient. RESULTS: The factor analysis indicated a factor solution consistent with the primary grouping except for two variables. The correlation between two independent physical therapists was .99 to 1.00 for different variables, indicating excellent intertester reliability. CONCLUSION AND DISCUSSION: In the authors' opinion, the new assessment system provides a reasonably valid, reliable, inexpensive, and easy-to-use measurement and fulfills the needs of the physical therapist for functional evaluation of the lower extremity.

Activities of Daily Living↗