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Biomedical subjects

B Oberg

Publications and source records attributed to B Oberg.

At least 73 records · Page 4Linked to original sources

Effects of withdrawal of antiparkinson medication on gait and clinical score in the Parkinson patient.

Objective testing of medication is needed in Parkinson's disease. Gait analysis and clinical evaluation were done before and after a 24-h withdrawal of Parkinson medication. Twelve patients with stable, mild to moderate idiopathic parkinsonism (Hoehn and Yahr 1-3; seven men and five women mean age 59.9 years, mean duration of disease 6 years) were tested with gait analysis walking in five different paces. Velocity of gait, stride length and stride frequency, as well as stride length at constant velocity were calculated. Regression coefficients for the relation between stride length and stride frequency were also calculated. Clinical scoring according to the Webster rating scale and Hoehn and Yahr were performed for each test. Clinical functional assessment with a specially designed rise and gait test, an arm cycle test and the wooden rods test were done. Evaluated clinical score increased significantly (p less than 0.05) using both clinical tests. Maximum gait velocity (p less than 0.01), stride length at max. velocity (p less than 0.01), and stride length at constant velocity (p less than 0.03) were significantly decreased without medication. Stride frequency did not change. In the functional assessment tests only performance on the arm cycle test (p less than 0.03) was less well performed without medication. There was correlation between clinical score, gait and clinical functional assessment. The methods used detected significant changes in variables of gait as well as clinical scoring and some of the clinical functional assessments when medication was withdrawn for a 24-h period. The methods were useful in evaluation of pharmacological treatment.

Aged↗

Characteristics of tetanic muscle contraction in Parkinson patients.

The aim of this study was to examine contraction characteristics in striated muscles from Parkinson patients and to measure any changes in characteristics based on changes in medication. Fifteen patients, 9 men and 6 women, mean age 61.6 (range 43-70) with mild to moderate parkinsonism, (Hoehn and Yahr I-III) were investigated, and the results were compared with a group of 8 normal controls (mean age 59.6, range 50-70). Twelve of the patients (7 men and 5 women) were also tested after a 24-h period without medication. Using supramaximal electrical stimulation of the ulnary nerve at the wrist contraction, characteristics in the m. adductor pollicis muscle can be recorded. Stimulation results were printed on a fast paper writer. The following characteristics were recorded: 1) electromechanical delay of contraction EMDc; 2) contraction time to half tetanus CTT1/2; 3) electromechanical delay of relaxation EMDr; 4) relaxation rate RR for 10 ms RR-10; 5) the force produced in the tetanic contraction at stimulus frequencies 5, 10, 20, 50 Hz. The results showed that the in initiation of contraction (EMDc) was normal compared with controls. CTT1/2 was shorter (p less than 0.001) in the group of Parkinson patients compared with normals. EMDr was not changed when compared with normals, but RR-10 was increased, p less than 0.05. Force levels at the different stimulation rates were not significantly changed. After withdrawal of medication all parameters were unchanged. Muscle contraction characteristics in tetanic contraction were found to be abnormal indicating either a possible preactivation in the muscle contraction or a secondary change in the muscles of patients with Parkinson's disease.

Adult↗

Antiviral effects of 3'-fluorothymidine and 3'-azidothymidine in cynomolgus monkeys infected with simian immunodeficiency virus.

An acute infection with simian immunodeficiency virus (SIVSM) in cynomolgus monkeys was used to evaluate the antiviral effects of 3'-fluorothymidine (FLT) and 3'-azidothymidine [zidovudine (ZDV)]. Neither compound prevented the infection despite dosing prior to virus inoculation. FLT was about ten times more potent than ZDV in delaying the appearance of SIVSM antigen in the monkeys. The serum half-life of FLT was longer than that of ZDV and ZDV was bound to plasma proteins to about 60% while FLT was virtually unbound. It is proposed that the in vivo difference in potency between ZDV and FLT could, at least partly, be explained as the combined effects of a longer plasma half-life and a higher free concentration of FLT and possibly a higher intracellular concentration of the triphosphate of FLT.

Animals↗

Phosphorus-containing inhibitors of aspartate transcarbamoylase from Escherichia coli.

A tetrahedral intermediate is the prominent feature of the generally accepted mechanism for aspartate transcarbamoylase. We have synthesized N-pyrophosphoryl-L-aspartate as a charged analogue of the postulated intermediate. Surprisingly, its affinity for the enzyme from Escherichia coli was substantially lower than that of the previously known inhibitor phosphonoacetyl-L-aspartate which contained a trigonal carbonyl group. Similar results were obtained with the corresponding mercaptosuccinate derivatives. We also tested a number of new pyrophosphate analogues as inhibitors. Our results cast doubt on some aspects of the current model for the mechanism of this enzyme.

Aspartate Carbamoyltransferase↗

Screening for new agents.

Screening for new antiviral drugs is concentrated on a search for inhibitors of the human immunodeficiency virus, herpesviruses, influenza virus, hepatitis B virus and rhinovirus. The first step in the process is usually the screening of virus-infected cell cultures followed by secondary screening in infected animals. The relevance of the different screening methods for predicting clinical efficacy is at present uncertain due to the low number of compounds evaluated in double-blind placebo-controlled clinical trials. As a consequence of the con-siderable activity in ongoing research on antiviral drugs the predictive value of the screening systems is expected to improve.

Animals↗

Analgesic efficacy of i.m. alfentanil.

We have studied the analgesic, respiratory, cardiovascular and sedative effects of alfentanil 30 micrograms kg-1 i.m. in two experiments in six healthy volunteers. In the first experiment, recordings were made up to 120 min after injection. Thresholds (sensory and pain) and pain-related evoked potentials (amplitude and latency) to cutaneous argon laser stimulation were used for quantitative assessment of onset, efficacy and duration of analgesia. Pain was significantly reduced from 5 to 60 min after injection. The onset phase of analgesia was faster than the recovery phase. In the second experiment, the alfentanil-induced analgesia was antagonized by naloxone 0.4 mg i.v. The reaction time to pain was prolonged significantly 15 min after injection, whereas the latency of the pain-related potential remained constant. No clinically significant changes were observed in respiratory and cardiovascular measurements.

Adult↗

Quantitative assessment of extradural bupivacaine analgesia.

Bupivacaine (0.5%) 20 ml was administered extradurally to six healthy volunteers. It was found that simultaneous application of 10 needles to the skin could evoke pain when analgesia was obtained to one needle stimulation. In addition, a laser beam was used as a quantitative technique to activate simultaneously many cutaneous nociceptors. For 7 h, thresholds (sensory and pain) and pain-evoked brain potentials (amplitude and latency) to laser stimulation were monitored and used for quantitative assessment of onset, efficacy and duration of analgesia at various dermatomes (C7, T8, T10, T12, L1, L3, S1). The onset time of analgesia was shortest and conduction delay longest at the dermatome related to the site of injection (L3). Full analgesia was obtained at L1, L3 and S1, although the peak efficacy at S1 was delayed for 120-180 min after injection. A minor effect was found at dermatome C7 approximately 60 min after injection.

Adolescent↗

Group training in parkinsonism: quantitative measurements of treatment.

Ten patients with mild to moderate parkinsonism were tested before and after a 12-week training program. Strength was tested with simultaneous EMG registration in the ankle flexors at different angular velocities using a modified Cybex II equipment. Peak Torque (pT), Torque area (Ta) and Emg area (iEMGa) for the eccentric and concentric contractions were calculated. Quotients-q (Ta)/(iEMG) for evaluation of work per iEMG in concentric and eccentric contractions were calculated. Gait analysis and a questionnaire for evaluation of the functional level were also included. Mean peak torque values did not change with training. Concentric quotients-q between test one and control was significantly lower in 30 degrees/s and 120 degrees/s; eccentric quotient-q was significantly lower in the same velocities but between test 2 and control. No improvement in gait was found. Patient questionnaire ratings did not improve significantly though patients had an overall impression of a beneficial effect of physical therapy. No long term effect was found. The results showed with the measuring methods presented no consistent measurable effect from group training in Parkinson's disease.

Aged↗

An analysis of the inhibition of replication of HIV and MuLV by some 3'-blocked pyrimidine analogs.

Some 3'-blocked pyrimidine analogs were synthesized and tested as inhibitors of replication of human immunodeficiency virus (HIV) and Moloney-murine leukemia virus (MuLV). The analogs were of 3 kinds: (1) analogs of 3'-azido-3'-deoxythymidine (AZT) in which the C-5 CH3 of the base was exchanged for H (AZU) or C2H5 (AZEU); (2) 3'-fluoro-3'-deoxythymidine (FLT) and analogs thereof, in which the C-5 CH3 of the base was exchanged for H (FLU), C2H5 (FLEU) or nC3H7 (FLPU); (3) the threo analogs of AZT (AZT increases) and AZU (AZU increases). All analogs were less active inhibitors of HIV replication than AZT, except FLT, which was as active as AZT. The 3'-fluoro analogs and AZEU did not inhibit MuLV replication at non-cytotoxic concentrations. Oral administration of FLT to MuLV-infected mice result in antiviral effects only at toxic drug levels. AZU and FLU were less potent inhibitors of HIV replication than AZT or FLT, but the 2'-deoxy uridine analogs were less cytotoxic to human embryonic fibroblasts than the thymidine analogs. The 5'-triphosphates of AZU, AZT, AZEU, FLT and FLEU were tested as inhibitors of the HIV- and MuLV-reverse transcriptases. Ranking of the Ki/Km values for HIV-RT resulted in the following order of potency of the 5'-triphosphates AZT = FLT greater than AZU greater than AZEU greater than FLEU. The 5'-triphosphates of AZEU, FLT and FLEU did not inhibit the MuLV-RT, which explains, in part, the lack of effect of these analogs against MuLV replication. The threo forms (azido "up") of AZU and AZT were less active inhibitors of HIV replication than the erythro forms (azido "down"). A 15N-NMR and 1H-NMR study showed that the furanose moieties of analogs with the azido function "up" assume a conformation distinct from that of the analogs with azido "down". This is due to intramolecular stabilisation of the "N" conformer in the threo ("up") diastereomer, due to interaction of the azido functions with the nucleobase and possibly the OH group of C-5' of the furanose. As discussed, this conformation might explain the decreased biological activity of threo forms compared with the erythro forms.

Animals↗

Antiviral effects of phosphonoformate (PFA, foscarnet sodium).

This article describes the antiviral properties of foscarnet (trisodium phosphonoformate) at the enzyme level as well as in cell cultures and in vivo. The mechanism of action against herpesvirus DNA polymerases and reverse transcriptases is outlined. Clinical studies using topical foscarnet against mucocutaneous herpes simplex virus infections are presented. The clinical use of intravenous foscarnet against severe viral infections caused by cytomegalovirus, hepatitis B virus and human immunodeficiency virus is discussed.

Adolescent↗

Inhibition of HIV-1 reverse transcriptase by 5'-triphosphates of 5-substituted uridine analogs.

The 5'-triphosphates of some 5-substituted 2'-deoxyuridine analogs were investigated for their effects on purified recombinant reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) as well as cellular DNA polymerase alpha. The triphosphates were competitive inhibitors of the viral enzyme with dTTP as the variable substrate and poly(rA)oligo(dT) as template, and preferentially inhibited the viral polymerase. Ordering the compounds according to their decreasing binding affinities, as reflected by their increasing inhibition constants for the reverse transcriptase, gave nPrearaUTP greater than nPrdUTP greater than EtdUTP greater than nPredUTP greater than HMdUTP greater than CEdUTP. Although nPredUTP was less inhibitory than nPrearaUTP under conditions of competitive inhibition, nPredUTP caused a time- and concentration-dependent inactivation of reverse transcriptase activity when preincubated with template. This inactivation was not reversed by excess dTTP. The decrease in template-primer activity did not occur with nPrearaUTP, but was shown with the chain-terminating 5'-triphosphates of 3'-fluoro- and 3'-azidothymidine. As nPredUTP, but not nPrearaUTP, was an alternative substrate, shown by the ability to support DNA synthesis in absence of competing substrate, the incorporation of nPredUTP into the primer-template apparently leads to increased inhibition of the enzyme.

Antiviral Agents↗

Inhibition of RNA- and DNA-dependent duck hepatitis B virus DNA polymerase activity by nucleoside and pyrophosphate analogs.

The DNA polymerase of hepadnaviruses has two different functions during virus replication. It acts both as an RNA-dependent DNA polymerase (reverse transcriptase) and as a DNA-dependent DNA polymerase. Duck hepatitis B virus (DHBV) preparations were used to investigate the inhibitory effects of selected compounds on these two enzyme activities. The reverse transcriptase activity was represented by an actinomycin D-resistant, phosphonoformate-sensitive DNA polymerase activity isolated from DHBV-infected duck livers. DHBV from serum was used as the source of the DNA-dependent DNA polymerase activity. Pyrophosphate and nucleoside triphosphate analogs were assayed for their inhibitory effects on the two enzyme preparations. A marked inhibition was obtained with 3'-fluoro-2',3'-dideoxythymidine 5'-triphosphate, acyclovir triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, 2',3'-dideoxyguanosine 5'-triphosphate and 2',3'-dideoxythymidine 5'-triphosphate. The two thymidine analog triphosphates showed a markedly lower inhibitory effect on the reverse transcriptase activity than on the DNA-dependent DNA polymerase activity. This was in analogy with earlier findings with 3'-azido-2',3'-dideoxythymidine 5'-triphosphate. Among the tested pyrophosphate analogs only phosphonoformate was inhibitory.

Animals↗

The cerebral arterio-venous oxygen content differences (AVDO2) during halothane and neurolept anaesthesia in patients subjected to craniotomy.

In 20 patients subjected to craniotomy for supratentorial cerebral tumours, the haemodynamic changes during halothane and neurolept anaesthesia were evaluated by measuring mean arterial blood pressure (MABP) and cerebral arterio-venous oxygen content differences (AVDO2) repeatedly during the operation. Ten patients were given 0.5% halothane anaesthesia and ten patients neurolept anaesthesia. MABP, AVDO2 and PaCO2 were measured after induction of anaesthesia, before and after incision, after opening and closure of the dura, at the time of extubation and 1 h later. Concerning MABP and PaCO2, no significant difference between the two groups was found. In both groups an increase in MABP was observed after incision (P less than 0.01 in the neurolept group and P less than 0.05 in the halothane group) and in the neurolept group after extubation (P less than 0.01). In both groups a decrease in AVDO2 was observed after incision (P less than 0.01) and after extubation (P less than 0.01 in the neurolept group and P less than 0.05 in the halothane group). During the operation AVDO2 values were significantly higher in the neurolept group (P less than 0.05). The results indicate that even a moderate increase in MABP after incision during neuroanaesthesia affects AVDO2 values, suggesting an increase in cerebral blood flow. The study suggests that autoregulation of cerebral blood flow might be better preserved during neurolept anaesthesia. A state of hyperperfusion of the brain after extubation was unveiled in both groups.

Adult↗

Inhibition of human immunodeficiency virus in vitro by combinations of 3'-azido-3'-deoxythymidine and foscarnet.

We describe a synergistic effect of combinations of foscarnet and 3'-azido-3'-deoxythymidine against human immunodeficiency virus type 1 multiplication in cell culture, an additive effect of foscarnet and 3'-azido-3'-deoxythymidine triphosphate against human immunodeficiency virus type 1 reverse transcriptase, and a low toxicity in cell culture of combinations of the two drugs.

Antiviral Agents↗

Experimental infection of cynomolgus monkeys (Macaca fascicularis) with simian immunodeficiency virus (SIVsm).

Five healthy cynomolgus monkeys were inoculated intravenously with simian immunodeficiency virus (SIVsm) propagated in human lymphocytes. All five animals became infected. Virus was recovered from blood mononuclear cells and viral antigen was detected in serum 12 days postinoculation (PI) in all inoculated animals. Virus was also isolated in all five animals tested 74 to 226 days PI. Antibodies to different structural proteins of SIV and HIV-2 were demonstrated by ELISA, Western blot, and radioimmunoprecipitation assay from day 31 PI concomitantly with a reduction of viral proteins in the serum. Reappearance of antigen accompanied by a fall in antibody to gag products (p26) was observed in two monkeys 69 days PI. All SIV-infected monkeys showed a pronounced decrease in CD4+ lymphocytes demonstrable already 12 days PI. They also developed persistent lymphadenopathy. Thus, infection of cynomolgus monkeys with SIVsm mimics events in human immunodeficiency virus infection in humans but the course of evolution of pathogenic events in the monkey is markedly compressed. This experimental model will be useful for evaluation of HIV vaccines and antiviral testing.

Acquired Immunodeficiency Syndrome↗

Isokinetic muscle torque in the dorsiflexors of the ankle in children 6-15 years of age. Normal values and evaluation of the method.

Isokinetic muscle torque of the dorsiflexors of the ankle was tested in 137 children 6-15 years old. Reference values in different age groups are given for girls and boys separately. Generally, peak torque values increased with age. However, the developed torque/kg bodyweight showed no significant difference in 15-year-old girls compared to 12-year-old girls. For prediction of normal torque the best parameters are age, weight and height. The maximal torque and work values generally increased with increasing weight and height. The prediction was not improved by adding factors like length of the lower leg, calf circumference and length of the foot. In the youngest age groups, the stronger leg, in the highest velocities, was on the dominant side, while in the older groups the strongest leg, at least in slow velocities, was on the non-dominant side. The boys seem to have their most intensive force development between 12 and 15 years while this occurs earlier in girls.

Adolescent↗

Enhancement of hepatitis A propagation in tissue culture with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

The adenosine analog 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) was found to increase the production of hepatitis A (HAV) antigen in two monkey kidney cell lines (Frhk-4 and Vero cells). DRB, a known inhibitor of the synthesis of messenger RNA, caused moderate changes in cell morphology. However, Frhk-4 cells could be maintained for several weeks at 80 microM of DRB, the concentration that caused maximal enhancement on HAV. DRB should be present from about the time of virus inoculation and its strongest effect was seen at low multiplicities of infection. Using radioimmunofocus assay it could be shown that DRB increased the amount of infectious virus. DRB treatment was applied in primary isolation of HAV from feces. In nine of ten strains HAV antigen expression was strongly increased and in six of the ten strains infectivity of harvested material increased by one 10log or more. DRB thus seems to be a useful enhancer of HAV growth in tissue culture.

Animals↗

Inhibition of human hepatitis B virus DNA polymerase and duck hepatitis B virus DNA polymerase by triphosphates of thymidine analogs and pharmacokinetic properties of the corresponding nucleosides.

Replication of hepadnaviruses involves a viral DNA polymerase containing both a DNA-dependent and an RNA dependent activity. This polymerase is a potential target for chemotherapy against hepatitis B. We have used human hepatitis B virus DNA-dependent DNA polymerase from human serum and duck hepatitis B virus DNA-dependent DNA polymerase from duck serum as well as RNA-dependent DNA polymerase activity from duck hepatitis B-infected duck liver. Triphosphates of thymidine analogs have been synthesized and tested for their inhibitory activities against these enzymes with the intention both to explore differences between these enzymes and structural requirements for inhibitors. The results showed that with the inhibitors tested, hepatitis B virus DNA-dependent DNA polymerase was the most sensitive enzyme and the triphosphate of 5-propenyl-2'-deoxyuridine was the most active inhibitor. In addition, the 5'-triphosphate of 5-propenyl-arabinofuranosyluracil also inhibited the hepadnavirus DNA-dependent DNA polymerases, and was a competitive inhibitor with respect to 2'-deoxythymidine triphosphate as showed by kinetic studies with duck hepatitis B virus DNA-dependent DNA polymerase from serum. Pharmacokinetic analysis showed 5-propenyl-2'-deoxyuridine to be well absorbed orally, but rapidly cleared from plasma. The arabinofuranosyl analog was also well absorbed but cleared less rapidly. Hence, these results indicate the potential of 5-propenyl-2'-deoxyuridine and 5-propenyl-arabinofuransyluracil for chemotherapy of hepatitis B.

Animals↗