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Biomedical subjects

B Lindborg

Publications and source records attributed to B Lindborg.

At least 19 recordsLinked to original sources
PubMed2003

The effect of straining maneuvers on G-protection during assisted pressure breathing.

INTRODUCTION: Pilots flying high-performance aircraft increase their acceleration tolerance by using straining maneuvers and anti-G suits. Recently, assisted positive pressure breathing has been added in some aircraft systems. This study assessed the effect of anti-G straining maneuvers on the G-protective properties of one such system, the AGE-39 anti-G ensemble used in the Swedish JAS 39 Gripen aircraft. METHODS: Ten subjects were studied in a centrifuge using each of the following: 1) the AGE-39 in combination with anti-G straining maneuvers (AGSM) throughout each high-G exposure (full maneuver; FM); 2) the AGE-39 in combination with AGSM only during the initial part of each high-G exposure (reduced maneuver; RM). G-tolerance was established during exposures to rapid onset rate (ROR) G profiles with plateau levels ranging from 6.5 to 9.0 G. RESULTS: Mean G-tolerance was > or = 8.8 G (range: 8.5 to > or = 9.0 G) in the RM condition and > or = 9.0 G in all subjects in the FM condition. Mean arterial pressure was 30-50 mm Hg higher (p < 0.001) in the FM than in the RM condition at any given ROR G-load. CONCLUSIONS: AGE-39 in combination with a brief period of straining provide efficient G-protection as illustrated by the finding that all subjects could tolerate 8.5 G while performing AGSM during the initial part of the high-G exposures. However, at 9.0 G, 40% of the subjects had to perform AGSM throughout the duration of the G-exposure. That arterial pressure was only 30-50 mm Hg higher in the FM than RM condition suggests that in the presence of straining maneuvers, pressure breathing makes only a minute contribution to the arterial-pressure response.

Adult↗
PubMed2002

A new hydrostatic anti-G suit vs. a pneumatic anti-G system: preliminary comparison.

HYPOTHESIS: A newly developed hydrostatic anti-G suit is now commercially available. The suit is said to offer a high level of protection against +Gz acceleration. However, past experience shows that it is difficult to produce a hydrostatic suit with effective high-G protection. Careful testing is, therefore, needed to verify its efficacy. METHODS: The G-protective properties of the hydrostatic anti-G suit (Libelle; L) were compared with those of a pneumatic anti-G ensemble (AGE-39) used in the Swedish JAS 39 Cripen aircraft. Three pilots were studied during vertical (+Gz) acceleration in a centrifuge using the following: 1) the L-suit with varied straining maneuvers; 2) the AGE-39 in combination with full anti-G straining maneuvers (AGSM) throughout each high-G exposure (full maneuver; FM); and 3) the AGE-39 in combination with AGSM during the initial part of each high-G exposure (reduced maneuver; RM). G-intensity tolerance was established during exposures to rapid onset rate (ROR) profiles with G-plateau levels ranging from +6.0 to +9.0 Gz. G-endurance was studied during simulated aerial combat maneuvers (SACM) consisting of 10 cycles of 5.5 to 7.5 G. RESULTS: All three pilots tolerated 9.0 G with the pneumatic system both in the RM and FM conditions; their tolerances averaged 6.3 G (range 6.0 to 7.0 G) for the L suit. Thus, during the ROR exposures only the 6.0 G profile was completed by all subjects in all three conditions. At this G-load both muscle straining (as indicated by electromyographic activity in thigh and abdomen) and heart rate were higher in the L than in the RM condition. Mean arterial pressure at eye level was higher in the FM than in the L and RM conditions. Only one subject was able to complete the SACM profile in the L condition. In the RM condition all subjects completed the SACM profile and in the FM condition two subjects completed the SACM. CONCLUSIONS: Whether the AGE-39 was used in combination with maximal AGSM throughout the duration of each high-G exposure or with AGSM only during the initial part of the high-G exposure, G-intensity tolerance was 9.0 G. While wearing the L-suit, G-tolerance was 6.3 G. Thus, under the conditions tested, the G-protection afforded by the L-suit is not adequate for use in a 9-G aircraft.

Acceleration↗
PubMed1998

Lower leg fluid displacement during a simulated space shuttle launch.

Reductions in leg fluid volume of about 1/per leg or 10% of total leg volume have been reported during space flight. We wanted to test the hypothesis that a significant portion of these changes occur during the prelaunch and launch periods. Fluid volume changes in the lower leg were estimated in six men during a simulated Space Shuttle launch. After 2 h in the launch position, i.e. supine with elevated legs, the subjects were exposed to 500 s of two to three times increased g force in the anterio-posterior direction in a human centrifuge. During the prelaunch period one lower leg lost a mean of (113 SD 53) ml of fluid and there was little or no additional fluid reduction during the period of increased g force. This compares with the 178-ml reduction of lower leg volume that has been reported during the 1st day of Shuttle missions. We concluded that a significant portion of the fluid reduction observed in the lower leg during the early stages of space flight had already occurred before the launch.

Adult↗
PubMed1991

Acyclonucleoside analogue inhibitors of mammalian purine nucleoside phosphorylase.

A series of about 60 purine acyclonucleosides, most with guanine as the aglycone and a 4-carbon chain as the acyclic moiety, was examined for ability to inhibit purine nucleoside phosphorylase from human erythrocytes and calf spleen. Compounds with shorter and longer acyclic chains were less effective inhibitors. Synthetic procedures are described. About 25 of the analogues were competitive inhibitors (relative to inosine or 7-methylguanosine as substrates) with Ki values in the range of 2 to 100 microM. The more potent ones (Ki 2-5 microM) included guanine as the aglycone, with various substituents at C(2') of the acyclic chain and hydroxyls at C(3') and C(4'). In one instance, 9-(2-fluoro-3,4-dihydroxybutyl)guanine, the (+)erythro enantiomer was 10-fold more effective than its (-) counterpart (2.5 microM vs 27 microM). Replacement of guanine by 8-bromo- or 8-aminoguanine enhanced affinity for the enzyme by an order of magnitude or more; 7-deazaacyclovir was also 10-fold more effective than acyclovir. With some of the inhibitors, Ki (human)/Ki (calf) varied over the range 0.4 to 4, reflecting differences between the two enzymes; nonetheless, the much more stable, and commercially available, calf spleen enzyme is recommended for preliminary screening of potential inhibitors of the human or other unstable enzymes. The overall results provide useful indications for the synthesis of potentially more potent inhibitors of the enzyme, by simultaneous modifications of the aglycone and the acyclic chains.

Acyclovir↗
PubMed1989

Improvement of the absorption of oral (R,S)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine, an anti-varicella-zoster virus drug, in rats and monkeys.

In an effort to improve the gastrointestinal absorption of (R,S)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine [(+/-)2HM-HBG], various salts and esters of the compound were synthesized and pharmacokinetic experiments were performed in rats and monkeys. The sodium or hydrochloride salts and short-chain esters of (+/-)2HM-HBG showed bioavailability characteristics that were equally as poor as those of (+/-)2HM-HBG. However, the esters given as salts tended to be better absorbed than the parent compound. The 6-deoxy and 6-deoxydiacetate analogs were extensively oxidized in vivo and represent prodrugs with considerable potential in improving the absorption of oral (+/-)2HM-HBG.

Absorption↗
PubMed1988

Pharmacokinetics and antiviral activity in simian varicella virus-infected monkeys of (R,S)-9-[4-hydroxy-2-(hydroxymethyl) butyl]guanine, an anti-varicella-zoster virus drug.

The acyclic guanosine analog (R,S)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine, (+/-)2HM-HBG, is an effective inhibitor of herpes simplex virus and varicella-zoster virus infections in vitro. This report is concerned with the pharmacokinetic evaluation of the drug in rats and monkeys and its antiviral activity in African green monkeys infected with simian varicella virus (SVV), a virus closely related to varicella-zoster virus that is also susceptible to inhibition by (+/-)2HM-HBG. Elimination half-lives in plasma following intravenous administration to monkeys (100 mumol/kg of body weight) ranged from 1.8 to 2.2 h, and total body clearance was 9.0 +/- 0.4 ml/min per kg (mean +/- standard error). After oral administration, levels in plasma were low, with a maximum concentration of the drug of only 3.1 +/- 0.8 microM, a time to reach maximum concentration of drug of 2.7 +/- 0.4 h, and an oral bioavailability of 10.6 +/- 1.4%. Because of the low oral bioavailability, SVV-infected monkeys were treated intramuscularly with (+/-)2HM-HBG. (+/-)2HM-HBG at a dosage of 10 mg/kg of body weight per day allowed moderate viremia, whereas a dosage of 30 mg/kg of body weight per day strongly suppressed viremia with minimal numbers of virus plaques from blood specimens collected at days 3, 5, and 7 postinfection and complete clearance at day 9 postinfection. Titers of antibody to SVV were also low. Treatment three times daily was somewhat more efficacious than treatment twice daily. Thus, (+/-)2HM-HBG is an effective inhibitor of SVV replication in vivo, despite the fact that leves of (+/-)2HM-HBG in plasma were low at extended periods of time and below the concentration of drug giving 50% inhibition of plaque formation obtained in vitro.

Administration, Oral↗
PubMed1987

Respiratory drive during sudden cold water immersion.

Sudden decreases in cutaneous temperature induce an immediate ventilatory response, which has been termed the inspiratory or 'gasp' reflex. This respiratory response has been implicated as a contributing factor to cold water immersion drowning. In the present study, five subjects wearing either shorts or a variety of thermal protective apparel were immersed on separate occasions in 10 degrees C water. The observed peak mean skin temperature cooling rates (dTs/dt) for the different conditions varied from 6.9 +/- 2.1 degrees C/min for the shorts condition to 1.8 +/- 0.3 degrees C/min for a helicopter pilot suit made of cotton ventile material. During the immersion, recordings were made of respiratory drive, as indicated by the mouth occlusion pressure at 100 msec following the onset of inspiration (P0.1). The respiratory drive, an indicator of central inspiratory activity, correlated well with peak dTs/dt. The slope P0.1/(dTs/dt) was subject dependent and did not appear to be related to body composition. The substantial intersubject variability in the respiratory response is suggested to result from differences in the central integration of thermoafferent information. It is concluded that the inspiratory reflex is the result of cutaneous thermoreceptor activity.

Adult↗
PubMed1987

Inhibiting effect of (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine on varicella-zoster virus replication in cell culture.

The activity and mode of action of the new nucleoside analog (RS)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine (2HM-HBG) against varicella-zoster virus (VZV) were determined. In cell culture, replication of different strains of VZV was inhibited to 50% by 0.4 to 0.7 microM 2HM-HBG, while 685 microM was required to inhibit 50% of the DNA synthesis in uninfected human lung fibroblasts. A thymidine kinase-negative VZV strain was not inhibited by 100 microM 2HM-HBG. Inhibition of VZV replication was not reversible after 7 to 14 days of incubation, depending on the multiplicity of VZV. 2HM-HBG was shown to be selectively phosphorylated by purified VZV thymidine kinase, with an inhibition constant of 32.5 microM. The antiviral activity of 2HM-HBG in cell culture was decreased by the addition of deoxythymidine and deoxycytidine but not by other ribo- or deoxyribonucleosides.

Antiviral Agents↗
PubMed1983

9-(3,4-dihydroxybutyl)guanine, a new inhibitor of herpesvirus multiplication.

A new compound, 9-(3,4-dihydroxybutyl)guanine, has been synthesized and its antiherpes activity determined. 9-(3,4-Dihydroxybutyl)guanine was selectively phosphorylated by herpes simplex virus thymidine kinase and had a high affinity for this enzyme, with an inhibition constant of 1.5 microM. In cell culture, replication of different strains of herpes simplex virus types 1 and 2 was inhibited to the extent of 50% by 4 to 18 microM (RS)-9-(3,4-dihydroxybutyl)guanine. The (R)-enantiomer of this compound was more inhibitory than the (S)-enantiomer. Herpesvirus DNA synthesis was selectively inhibited by (RS)-9-(3,4-dihydroxybutyl)guanine in infected cells, and a low cellular toxicity was observed. (RS)-9-(3,4-Dihydroxybutyl)guanine had a therapeutic effect when applied topically to guinea pigs with cutaneous herpes simplex type 1 infections and to rabbits with herpes keratitis. Oral treatment of a generalized herpes simplex type 2 infection in mice had a therapeutic effect.

Acyclovir↗
PubMed1982

Therapeutic effects of foscarnet sodium and acyclovir on cutaneous infections due to herpes simplex virus type 1 in guinea pigs.

The therapeutic effects of topically applied foscarnet sodium and acyclovir on cutaneous infections due to herpes simplex virus type 1 (HSV-1) were studied in guinea pigs. Foscarnet cream (3%) reduced both the cumulative vesicle score and the time for healing when HSV-1 strains C42 and 79 were tested. The application of foscarnet in cream form resulted in a dose-dependent reduction in skin virus titers and vesicle scores at concentrations ranging from 0.05% to 3%. Infections due to HSV-1 strain 79, but not those due to strain C42, were sensitive to treatment with 5% acyclovir in polyethylene glycol ointment. Topical application of 3% acyclovir in dimethyl sulfoxide on infections due to HSV-1 strain C42 resulted in a reduction in the skin virus titers, lesion scores, and the time for healing. Acyclovir, in both polyethylene glycol and dimethyl sulfoxide, was consistently less active than foscarnet cream in these animal experiments.

Acyclovir↗
PubMed1980

Responses to continuous negative-pressure breathing in man at rest and during exercise.

We studied the respiratory and circulatory effects in six healthy supine volunteers of continuous negative-pressure breathing (CNPB) at -15 and -30 cmH2O at rest and during dynamic leg exercies at 50% of individual working capacity. CNPB had no significant effects on respiratory minute volume, tidal volume, or arterial carbon dioxide tension. Mean arterial pressure remained essentially unchanged both at rest and during exercise, signifying that the reductions in intrathoracic pressure caused corresponding increases in left ventricular afterload. Nevertheless, cardiac output increased significantly in both conditions, causing reductions of mean central venous pressure that were considerably greater during exercise than at rest. These responses were reflected by increments in left ventricular work, amounting to 24 and 20% at rest and during exercise, respectively, at -30 cmH2O. We conclude that in CNPB at rest the increased activity of the left ventricle with associated juxtathoracic venous collapse protects the right heart and pulmonary circulation from congestion and that it does so even more effectively during exercise.

Adult↗
PubMed1979

Respiratory and circulatory responses to sustained positive-pressure breathing and exercise in man.

To investigate the effects of sustained positive-pressure breathing (PPB) on the adaptation of respiratory and circulatory functions to exercise, 8 healthy volunteers were exposed to PPB of air at 15 and 30 cm H2O in the supine position at rest and while performing leg exercise at 50% of individual maximal working capacity. PPB was both subjectively and objectively better tolerated when combined with exercise than it was at rest. PPB at 30 cm H2O resulted in marked hyperventilation with alkalosis in the resting condition, but did not significantly affect respiratory minute volume, blood gases or acid-base balance during exercise. Cardiac output and left ventricular work were reduced by about one fifth and one third, respectively, both at rest and during exercise. In contrast to the case at normal airway pressure, exercise-induced increase in cardiac output was accompanied by an increment in stroke volume during PPB. Although mean arterial pressure (relative to atmospheric) was elevated by PPB at rest and during exercise, the driving pressure in systemic circuits (arterial minus central venous pressure) was reduced in both conditions. It is concluded that dynamic exercise counteracts deleterious effects of PPB by normalizing respiratory function and by improving cardiac filling by activation of the leg muscle and the abdominal pumps.

Acid-Base Equilibrium↗
PubMed1975

Assay of the major (4-hydroxylated) metabolites of diphenylhydantoin in human urine.

A modified gas chromatographic procedure for the determination of unconjugated and conjugated 4-hydroxydiphenylhydantoin (4-OH-DPH) in urine has been developed. Unconjugated 4-OH-DPH is determined after selective extraction with toluene-ether (1:1). For the assay of conjugated 4-OH-DPH, the urine is pre-extracted with isoamylalcohol before acid hydrolysis to avoid interference by the dihydrodiol metabolite of DPH. The sensitivity of the method is 0.1 mug per ml. The method has been used to determine the urinary metabolites in two adult volunteers, during steady state plasma concentrations of DPH and in the elimination phase.

Adult↗