Compensating for occupational lung disease

Workers' compensation for occupational lung disease in South Africa and in other countries is reviewed. Compensation legislation in South Africa has a long history of evolution, with important changes expected in the near future. The South African system is similar to that in other countries, but has some unique features. Problems for workers disabled by occupational lung disease include a limited range of compensable conditions, difficulty in establishing a diagnosis, delays in obtaining payment, and small amounts paid. International experience suggests that certain changes would be especially useful. Racial inequalities should be removed, the schedule of compensable occupational diseases needs to be extended, and presumptive standards should be developed for diagnosis and disability assessment.     

Phenytoin as a probe of drug metabolism. Predicting clearance with a salivary sample

Phenytoin (PHT) was administered in single 300-mg doses to each of 12 healthy, male subjects. Serial blood samples and salivary samples were collected for the next 48 h, and concentrations of plasma total PHT, unbound plasma PHT (plasma ultrafiltrates), and salivary PHT (salivary ultrafiltrates) were measured by immunofluorescence polarization. The following parameters were estimated: CLint/F, CL'int/F, V/F, and total and unbound PHT plasma disappearance half-lives. Estimates of CL'int/F (CL'int/F) were calculated from single 48-hour salivary PHT measurements. Mean (+/- SD) values were 0.026 +/- 0.009 1 . h-1 . kg-1, 0.385 +/- 0.148 1 . h-1 . kg-1, 12.6 +/- 3.5 l/kg (referenced to unbound drug), 28.0 +/- 12.1 h, and 25.9 +/- 13.5 h, respectively. When V/F referenced to unbound PHT was set at 14 l/kg, CL'int/F estimates were good predictors of the actual CL'int/F values demonstrating a mean prediction error of -9.012 1.h-1.kg-1. These data demonstrate that under specified conditions, intrinsic unbound PHT clearance can be estimated from a single PHT measurement in saliva, thereby permitting PHT to be used safely and sampled simply and noninvasively as a probe of hepatic mixed function oxygenase activity in humans.     

Intrathecal infusion of bupivacaine with or without morphine for postoperative analgesia after hip and knee arthroplasty

Postoperative pain after major orthopaedic operations can be controlled by continuous intrathecal administration of opioids or local anaesthetics. Effective intrathecal analgesia can be achieved through synergism of low doses of the two analgesic drugs and, possibly, less drug-related adverse effects. Therefore, we have evaluated the usefulness of a combined low-dose bupivacaine and morphine infusion in patients undergoing hip and knee arthroplasty. Spinal anaesthesia was induced in 55 ASA I-III patients with 0.5% bupivacaine 2 ml via a 28- gauge spinal catheter (L3-4 interspace) and 0.5-ml increments were given if needed. Intrathecal 24-h infusions consisted of bupivacaine 2 mg h-1 alone (n = 18), bupivacaine 1 mg h-1 alone (n = 18) or bupivacaine 1 mg h-1 combined with morphine 8 micrograms h-1 (n = 19). The interview after 3, 6, 12 and 24 h included assessment of pain at rest and on movement (VAS scale), occurrence of sensory and motor block and nausea/vomiting. Bupivacaine 1 mg h-1 combined with an infusion of morphine provided as good postoperative analgesia as bupivacaine 2 mg h- 1, but motor block disappeared earlier (P = 0.01). Patients in the bupivacaine 1-mg h-1 group required more supplementary doses of oxycodone i.m. than the other groups (P = 0.04). Time to first oxycodone dose from the start of intrathecal infusion did not differ between groups. The frequency of nausea and vomiting was similar in all groups. In spite of this, antiemetic medication was required more often in the bupivacaine 1-mg h-1 group (possible because of opioid rescue medication). On the ward, one patient in the bupivacaine 2-mg h-1 group experienced a new increase in sensory block with concomitant hypotension. One patient in the same group had minor decubitus on the heel of the operated leg, probably because of prolonged motor block. We conclude that intrathecal infusion of a combination of bupivacaine 1 mg h-1 and morphine 8 micrograms h-1 produced adequate postoperative analgesia. Unfortunately, postoperative nausea and vomiting was a frequent disturbing adverse effect.      

Deoxyspergualin, a potent antitumor agent: further studies on the cytobiological mode of action

Under otherwise identical conditions, deoxyspergualin preferentially inhibits the growth of the T-cell leukemia line L5178y; an effective dose for a 50% inhibition (ED50) of 0.0007 microM was determined. A much weaker cytostatic activity was found for murine lymphocytes (ED50: approximately 25 microM) and for CV-1 monkey kidney cells (ED50: 16.3 microM). Deoxyspergualin causes biphasic and differential effects on DNA metabolism of murine T and B lymphocytes. At lower concentrations (0.3 approximately 5 microM) the [3H]TdR incorporation into nonactivated or lipopolysaccharide-activated lymphocytes is significantly stimulated by the compounds; this effect was not observed with lymphocyte cultures stimulated with concanavalin A. This change of TdR incorporation rates was found to parallel with the variations of DNA polymerase alpha activity. Deoxyspergualin causes an additive effect together with bleomycin and a significant synergistic cytostatic effect in combination with avarol and avarone. Moreover, it is reported that deoxyspergualin causes neither a selective inhibitory effect on DNA-, RNA- or protein synthesis nor an alteration of the intracellular distribution pattern of the Ro and La antigens. However, detailed enzymic studies revealed that deoxyspergualin reduces DNA polymerase alpha but not beta activity in lymphocytes at the ED50 concentration of this compound. These results support previous documentations that deoxyspergualin is of potential clinical usefulness (a) in treatment of certain tumors and (b) in organ transplantation.     

Plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2 in various disease states

The association of increased PA-inhibitor (PAI) activity and of PAI-1 and PAI-2 antigen levels with different pathological conditions was studied in a collective of over 300 patients. PAI-1 and PAI-2 levels were measured by specific radioimmunoassays. A good correlation was observed of PAI activity with PAI-1 antigen (r = 0.718; p less than 0.0001) but not with PAI-2 (r = 0.070; n.s.). Both in the controls and in the patients, PAI activity and PAI-1 antigen showed an extremely large range of values. PAI activity ranged from 0.5 to 68 U/ml and PAI-1 antigen from 6 to 600 ng/ml. Increased PAI activity and PAI-1 antigen was observed in patients with malignant tumors, cardiovascular or thromboembolic disease, in the postoperative phase, with hepatic insufficiency, after trauma and after extracorporeal circulation. The large spectrum of disease states with increased PAI activity and PAI-1 antigen reinforces previous suggestions that PAI-1 is an acute phase reactant. After extracorporeal circulation, PAI activity and PAI-1 concentrations strongly increased within one hour, remained elevated for at least one week and returned to preoperation values within 7 days. PAI-2 values ranged from below detection limit (15 ng/ml), observed in half of the plasmas, to 485 ng/ml in a pregnant woman. High values of PAI-2 were only observed in pregnancy.     

Abbau von Mischsubstraten durch Hefen III. Wachstumsparameter

The growth characteristics of two Candida strains W₁, W₂, have been examined on the single substrates d-glucose, d-galactose, d-xylose, d-arabinose in batch culture. The importance of growth parameters μ_max, K_S and Y with regard to possible functions of single strains in mixed populations during degradation of mixed substrates has been discussed.     

Pitfalls in aminoacid and organic acid analysis: 3-Hydroxypropionic aciduria

Pitfalls in organic acid analysis can originate from inadequate methodology, analytical interferences, in vivo interactions and from pre-analytical conditions which often are unknown to the specialized analytical laboratory. Among the latter, ingested food and additives, metabolites of food processing or medications have to be considered. Bacterial metabolites from the gastrointestinal or urogenital system or formed after sample collection can lead to pitfalls as well. An example of such a patient whose urinary metabolites mimick at first glance inherited propionic aciduria is described.     

Accuracy of cervical transvaginal sonography in predicting preterm birth: a systematic review.

This review investigates the accuracy with which transvaginal cervical sonography predicts spontaneous preterm birth. Published studies were identified without language restrictions through nine different databases and manual searching of bibliographies of known primary and review articles. Studies were selected if they undertook antenatal transvaginal sonographic cervical assessment among a population of pregnant women with known gestational age of delivery. There were 46 primary articles, which included a total of 31,577 women, consisting of 33 studies in asymptomatic and 13 studies in symptomatic women. Data were extracted for the studies' characteristics and quality. Accuracy data were used to form 2 x 2 contingency tables for various cervical length measurements with birth before 32, 34 and 37 weeks' gestation as the reference standards. Data were stratified according to singleton or twin pregnancy, gestational age at testing, cervical length threshold, and the various reference standards, and were pooled to produce summary estimates of likelihood ratios (LRs). Our review showed that transvaginal cervical sonography identifies women who are at higher risk of spontaneous preterm birth, although there was a wide variation amongst studies with respect to gestational age at testing, definition of threshold of abnormality and definition of reference standard. The most commonly reported sub-group was testing of asymptomatic women at < 20 weeks' gestation using a threshold cervical length of 25 mm with spontaneous preterm birth before 34 weeks' gestation as the reference standard. The summary LR+ for this group was 6.29 (95% CI, 3.29-12.02), with corresponding LR- of 0.79 (95% CI, 0.65-0.95). Both cervical length measurement and funneling, whether alone or in combination, appear to be useful (depending on the threshold chosen to define the abnormality) in predicting spontaneous preterm birth in asymptomatic women. For symptomatic women there was a paucity of data, although the degree of funneling appeared to be predictive of spontaneous preterm birth.     

Hypofibrinolysis in patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism.

An impaired fibrinolytic activity after a venous occlusion test is the most common abnormality associated with thomboembolic disease. To better characterize the causes of abnormal responses we have measured different fibrinolytic parameters, before and after 10 and 20 min of venous occlusion, in 77 patients with a history of idiopathic deep vein thrombosis and/or pulmonary embolism and in 38 healthy volunteers. The patients had a lower mean fibrinolytic response to venous occlusion than the controls and higher antigen levels of tissue-type plasminogen activator (t-PA:Ag) and plasminogen activator inhibitor type 1 (PAI-1:Ag). Before venous occlusion, PAI-1 levels were at a molar excess over those of t-PA in all patients and controls. After 20 min of venous occlusion, the release of t-PA from the vascular endothelium resulted in a molar excess of t-PA over PAI-1 in the majority of controls (72%) but only in a minority of patients (39%). To identify patients with fibrinolytic abnormalities, reference intervals (RI) for fibrinolytic activity, t-PA:Ag and PAI-1:Ag were established in healthy controls. None of the patients had low levels of t-PA:Ag, but 17 (22%) had elevated PAI-1:Ag levels before venous occlusion and 12 (16%) exhibited low fibrinolytic activity after 20 min of venous occlusion. Ten of these were among the 17 subjects with high PAI-1:Ag levels before venous occlusion. Thus, the measurement of PAI-1:Ag levels before venous occlusion (i.e. in samples taken without any stimulation) is a sensitive (83%) and specific (89%) assay for the detection of patients with an impaired fibrinolytic response to venous occlusion.