Work-place alcohol and other drug testing: a review of the scientific evidence

In this paper, scientific evidence for alcohol and other drug testing programs is compared to determine whether each approach is justifiable for improving work-place safety. Three types of studies are reviewed: laboratory, epidemiological and evaluation studies. Laboratory studies show that alcohol use decreases psycho-motor performance; however, for other drugs, some drugs deteriorate performance while others have little effect. Epidemiological studies in the work-place have not provided conclusive evidence that a strong causal link exists between either alcohol or other drug use and work-place injuries/accidents. Evaluation studies have not shown that either drug or alcohol testing significantly reduces work injuries/accidents. Other types of scientific evidence provide some justification of alcohol testing, but not for other drug testing. Alcohol use is much more common than other drug use in industrialized countries, suggesting that alcohol may be more related to industrial accidents than other drugs. As well, epidemiological studies suggest that alcohol is a major factor for traffic collisions, but research is inconclusive for other drugs. Finally, alcohol testing is more justifiable than drug testing because the results of alcohol tests closely correlate with psycho-motor performance while drug tests do not.     

Characterization of the P2 receptors in rabbit pulmonary artery

1. We have identified the P₂ receptors mediating vasomotor responses in the rabbit pulmonary artery.
2. Neither ATP nor UTP contracted intact or endothelium-denuded rings. However, both relaxed intact rings of rabbit pulmonary artery that had been preconstricted with phenylephrine (pD₂ 5.2 and 5.6, respectively).
3. The vasodilator effect of UTP was endothelium-dependent and abolished by the nitric oxide synthase inhibitor N^G-nitro-L-arginine (L-NOARG).
4. The vasodilator effect of ATP was only partially inhibited by removal of endothelium or addition of L-NOARG, suggesting an additional direct effect on vascular smooth muscle.
5. The endothelium-dependent vasodilator responses to UTP and ATP were competitively antagonized by suramin.
6. Preconstricted, endothelium-denuded rings were also relaxed by 2-methylthio ATP (pD₂ 6.6), a P_2Y receptor agonist.
7. Ca²⁺-mobilizing P_2U receptors were identified on smooth muscle cells on the basis of single cell responses to ATP (pD₂ 7.8) and UTP (pD₂ 7.9; 6.7 in the presence of 100 μM suramin).
8. There was no evidence of a Ca²⁺-mobilizing P_2Y receptor in these cultured cells.
9. The data suggest the presence of (i) a suramin-sensitive P_2U receptor on endothelial cells that induces vasorelaxation through NO release, (ii) a suramin-sensitive P_2U receptor on cultured smooth muscle cells that mobilizes Ca²⁺ but is not coupled to vasomotor responses and (iii) a putative P_2Y receptor on vascular smooth muscle cells that induces relaxation via a Ca²⁺-independent signal transduction pathway.

     

A comparison of skinfold thickness, body mass index, bioelectrical impedance analysis and dual-energy X-ray absorptiometry in assessing body composition in obese subjects before and after weight loss

The assessment of body composition in obese subjects by anthropometric means (skinfolds), presents many difficulties. This study compares the estimates provided of fat free mass in 21 obese subjects (mean body mass index 36.6 +/- 1.2 kg/m(2)) using body mass index and skinfold thickness, with those obtained using the more recently developed techniques of bioelectrical impedance analysis and dual-energy X-ray absorptiometry. Despite highly significant correlations between some of the methods (r(2) = 0.94 for dual-energy X-ray absorptiometry versus bioelectrical impedance analysis), there was a considerable lack of agreement in the measurements, particularly when skinfold thickness was compared with dual-energy X-ray absorptiometry (limits of agreement -21.9 to -1.5 kg for fat free mass estimated from dual-energy X-ray absorptiometry and skinfold thickness) and even for dual-energy X-ray absorptiometry and bioelectrical impedance analysis (limits of agreement -10.7 to 0.4 kg). After weight loss the intermethod differences were reduced.     

Effect of probenecid on the formation and elimination kinetics of the sulphate and glucuronide conjugates of diflunisal

The effect of probenecid on the pharmacokinetics of diflunisal and its glucuronide and sulphate conjugates was studied in 8 healthy volunteers. Diflunisal 250 mg b. d. was administered p. o. for 15 days and its steady state pharmacokinetics was evaluated on Day 16 after the last dose (control phase). Probenecid 500 mg b. d. was co-administered throughout the entire study period in the treatment phase of the study.The steady state plasma concentration of diflunisal was significantly higher during the probenecid treatment phase as compared to the control phase (104.0 vs. 63.1 g·ml^–1). This was the result of a significant decrease in the plasma clearance of diflunisal from 5.8 (control) to 3.4 ml·min^–1 (probenecid co-administration). The metabolite formation clearances of both glucuronides were significantly decreased by probenecid, -45 % and -54 % for the phenolic and acyl glucuronide, respectively. The metabolite formation clearance of the sulphate conjugate was not affected by probenecid co-administration.Steady state plasma concentrations of the sulphate and glucuronide conjugates of diflunisal were 2.5- to 3.1-fold higher during probenecid co-administration, due to a significant reduction in the renal clearance of the three diflunisal conjugates. Probenecid also reduced the plasma protein binding of diflunisal, but only to a minor extent; the unbound plasma fraction of diflunisal at steady state averaged between 5 and 30 % higher during probenecid co-administration.     

Unreamed intramedullary nailing for pathological femoral fractures. Good results in 30 cases

We have used the AO unreamed femoral nail for stabilization of impending and complete pathological fractures since March 1994. 27 patients with 30 pathological fractures (23) or impending fractures (7) of the femur were retrospectively analyzed. These included 18 subtrochanteric fractures, 11 shaft fractures and 1 distal fracture. The mean age of the patients was 68 (51-84) years. All patients were treated with a solid femoral nail inserted by an unreamed technique. The nail was inserted through a minimally invasive approach and with a median surgical time of 55 (35-70) minutes. A reconstructive proximal locking option (spiral blade) was used in 25 cases. There were no intraoperative complications, no operative mortality. Reliable skeletal stability was obtained in all cases and most were able to mobilize early with minimum discomfort. 1 case was revised for a secondary fracture through a distal metastasis at 6 months. The median survival was 5 (2-9) months. Unreamed nailing with the AO solid femoral nail appears to be a good option for the stabilization of pathological femoral fractures.     

Channel properties determine the transient activation kinetics of recombinant GABA(A) receptors

To understand the mechanisms underlying activation and deactivation of GABA(A) receptor (GABAR) channels, we studied the properties of an identified GABAR isoform under conditions similar to those present at central GABAergic synapses. Recombinant alpha5beta3gamma2L GABARs were expressed in L929 fibroblasts and studied using patch-clamp recording techniques. Brief application of a high GABA concentration to outside-out membrane patches elicited transient currents that resembled those reported for miniature inhibitory postsynaptic currents (mIPSCs), as well as native GABAR currents recorded under similar conditions. Characteristic of these currents was a rapid activation phase followed by a prolonged biphasic deactivation phase that far outlasted GABA application. Single-channel recordings revealed unique patterns of channel activity with two channel conductance states of 22 and 16 pS. The prolonged deactivation phase appeared to be sustained by entry into and reopening from long-lasting closures or desensitized states. Agonist affinity determined the time course of deactivation, indicating that occupied receptors drove the channel activity underlying the decay of current. The time course of deactivation was also longer at depolarized membrane potentials. The similarities between transient activation kinetics of recombinant alpha5beta3gamma2L GABARs to activation of synaptic GABARs (rapid activation and prolonged, voltage-dependent deactivation) suggest that intrinsic channel properties determine much of the response patterns of native GABARs.     

Disseminated soft tissue infection and sepsis with Stenotrophomonas maltophilia in a bone marrow transplant patient

A 32-year-old female presented with aplastic anemia and subsequently underwent a one-antigen mismatched bone marrow transplant from her brother. She failed to engraft and a second graft was attempted. Protracted neutropenia of three months' duration despite the use of broad spectrum antibiotics occurred. Stenotrophomonas (Xanthomonas) maltophilia metastatic cellulitis developed that did not respond to appropriate antibiotics.     

Evidence for success in health promotion: suggestions for improvement

This paper argues that health promotion needs to develop an approach to evaluation and effectiveness that values qualitative methodologies. It posits the idea that qualitative research could learn from the experience of quantitative researchers and promote more useful ways of measuring effectiveness by the use of intermediate and indirect indicators. It refers to a European-wide project designed to gather information on the effectiveness of health promotion interventions. This project discovered that there was a need for an instrument that allowed qualitative intervention methodologies to be assessed in the same way as quantitative methods.     

Cessation of progesterone secretion by LH-RH in hypophysectomized pregnant and hypophysectomized, prolactin injected pseudopregnant rats

LH-RH causes pregnancy failure in hypophysectomized rats. This study investigated whether this failure was due to an action of LH-RH upon the fetus, placenta, uterus, or ovary. Pseudopregnant, hypophysectomized, prolactin treated rats were subjected to uterine trauma to develop the decidual cell response or were hysterectomized. Deciduoma formation and serum progesterone valves were significantly decreased in all LH-RH treated animals. These observations suggest that LH-RH inhibits prolactin maintained progesterone secretion in hypophysectomized rats by a direct action of the hormone on the ovary.