Neurological dysfunction of the bladder in workers exposed to dimethylaminopropionitrile

Neurogenic bladder dysfunction, characterized by hesitancy, need to strain, decreased stream, and increased duration of urination, developed in 104 (63%) of 166 employees working in the manufacture of polyurethane foam. Highest rates of illness (69%) occurred in production workers, and no illness occurred in office or warehouse workers. Onset of the epidemic coincided with introduction of a catalyst, dimethylaminopropionitrile (DMAPN), and monthly case incidence rates increased as DMAPN use increased. Outbreak ceased abruptly when DMAPN use was stopped. Of eight patients who underwent neurourologic testing during recovery, seven lacked either detrusor reflex or normal sensation of bladder filling; seven had a subclinical sensory abnormality; three had prolonged sacral-evoked responses; and two of these three had limb motor neuropathies. Dimethylaminopropionitrile is unique among known neurotoxins in producing urinary symptoms more frequently than limb nerve symptoms.     

A 23-pS Ca2+-activated K+ channel in MCF-7 human breast carcinoma cells: an apparent correlation of channel incidence with the rate of cell proliferation

In studies on the apical membranes of cultured MCF-7 human breast carcinoma cells, we found two conspicuous K⁺ channel types with conductances of 23 and 70 pS, respectively. Of these, the 23-pS K⁺ channel was most conspicuous. In cell-attached patches with KCl in the pipette, it had a linear current/voltage (I/V) relation and was activated by depolarisation and in excised insideout patches it was highly selective for K⁺ over Na⁺ (permeability ratio of Na⁺ to K⁺, P _Na/P _K=0.02). Rubidium (Rb⁺) had a similar permeability to K⁺, although it was only conducted at 20% of the rate of K⁺, and cesium (Cs⁺) had a permeability less than 30% that of K⁺ and was not conducted at all. Both Cs⁺ and Rb⁺ acted as partial blockers when applied internally but the channel was not blocked by external tetraethylammonium (TEA, 10 mmol/l), quinidine (200 mol/l) or apamin (50 nmol/l). It was activated by Ca^{2 +} in the range 10^–7–10^–6 mol/l. In cell-attached patches at a pipette potential of 0 mV, the open-time histogram was described by a single exponential (time constant 1.6 ms) and the closed-time histogram by two exponentials (time constants 0.5 and 1.5 ms). The incidence of the 23-pS but not the 70-pS channel depended on the rate of cell proliferation. Thus, in studies on cell-attached patches from cells in the exponential growth phase, the 23-pS channel was observed in 78% of patches. However, when the proliferation rate was decreased, whether as a result of allowing the monolayer to reach confluence, or of cell treatment with an anti-oestrogen (tamoxifen, 10 mol/l), or a phorbol ester [phorbol 12-myristate 13-acetate (TPA), 2.6 nmol/l], the channel incidence was reduced to 42%, 60% and 42%, respectively. The activity of the 23-pS channel is not obligatory for cell division, however, since the rate of cell proliferation remained the same in MCF-7 cultures in which the channel was not expressed.     

Solid dispersions based on inulin for the stabilisation and formulation of delta 9-tetrahydrocannabinol.

The aim of this study was to develop a dry powder formulation that stabilises the chemically labile lipophilic Delta(9)-tetrahydrocannabinol (THC), that rapidly dissolves in water in order to increase the bioavailability and that opens new routes of administration. It was investigated whether these aims can be achieved with solid dispersions consisting of a matrix of inulin, an oligo-fructose, in which THC is incorporated. These solid dispersions were prepared by lyophilisation of a solution of THC and inulin in a mixture of water and tertiary butyl alcohol (TBA). Both 4 and 8 wt.% of THC could be incorporated in a glassy matrix of inulin. In the solid dispersions only 0.4-0.5 wt.% of residual TBA was present after storage at 20 degrees C/45% relative humidity (RH) for 7 days. Unprotected THC was completely degraded after 40 days of exposure to 20 degrees C and 45% RH. However, solid dispersions exposed to the same conditions still contained about 80% non-degraded THC after 300 days. Dissolution experiments with tablets compressed from inulin glass dispersion material showed that THC and inulin dissolved at the same rate. Tablets weighing 125 mg and containing 2mg THC were prepared from a mixture of THC containing solid dispersion, polyvinylpolypyrrolidone (PVPP) and mannitol. Dissolution tests revealed that from these tablets 80% of the THC was dissolved within 3 min, which makes them promising for sublingual administration. It was concluded that THC can be strongly stabilized by incorporating it in a matrix of inulin. The aqueous dissolution rate was high which may improve bioavailability.     

The occupational history in medical practice

An occupational history is critical not only to accurate diagnosis, treatment, and prevention of work-related diseases and injuries but also to appropriate placement of individuals in the workplace at the start of a new job or on return to work after a serious illness or injury. In this article, Drs Levy and Wegman discuss key parts of the occupational history, questions that will elicit helpful information, and correlation of the findings with diagnosis and treatment.     

Longitudinal changes in pulmonary function and respiratory symptoms in cotton textile workers. A 15-yr follow-up study

To evaluate the chronic effects of exposure to cotton dust, a 15-yr follow-up study in cotton textile workers was performed in Shanghai, China from 1981 to 1996. Testing occurred four times during the 15-yr period. The achieved follow-up rates were 76-88% of the original 447 cotton textile workers, and 70-85% of the original 472 silk textile workers (as a control group). Identical questionnaires, equipment, and methods were used throughout the study. The prevalence of byssinosis increased over time in cotton workers, with 15.3% at the last survey versus 7.6% at the baseline, whereas no byssinosis was found in silk workers. More workers in the cotton group consistently reported symptoms than in the silk group, although symptom reporting varied considerably from survey to survey. Cotton workers had small, but significantly greater, adjusted annual declines in FEV(1) and FVC than did the silk workers. Years worked in cotton mills, high level of exposure to endotoxin, and across-shift drops in FEV(1) were found to be significant determinants for longitudinal change in FEV(1), after controlling for appropriate confounders. Furthermore, there were statistically significant associations between excessive loss of FEV(1) and byssinosis, chest tightness at work, and chronic bronchitis in cotton workers. Workers who consistently (three or four of the surveys) reported byssinosis or chest tightness at work had a significantly greater 15-yr loss of FEV(1). We conclude that long-term exposure to cotton dust is associated with chronic or permanent obstructive impairments. Consistent reporting of respiratory symptoms, including byssinosis and chest tightness at work, is of value to predict the magnitude and severity of chronic impairments in textile workers.     

Machining operations and associated machining fluid exposures: Issues for health and safety intervention in manufacturing

The outline for a workshop discussion of intervention research in manufacturing industry is presented. The example used is the control of machining fluid exposures, a widespread exposure that is associated with risk of cancer, pulmonary disease, dermatitis, and several types of accident-related injuries. Relevant technical considerations for conducting intervention research include the selection of machining fluid for different machining purposes, the management of fluids in use, and the selection and maintenance of environmental controls. Equally important are nontechnical considerations including the need for creating labor-management health and safety committees, the use of administrative rules on job performance for both workers and management, and training on the role of individuals from either group in exposure control. Clarity concerning the objectives for an intervention study and plans for clear means to evaluate study outcomes is critical. Important study variables will include site selection, plant size, plant demographics, the involvement of workers in the study, a willing management, and concern for susceptible workers. © 1996 Wiley-Liss, Inc.     

Encoding and retrieval of landmark‐related spatial cues during navigation: An fMRI study

To successfully navigate, humans can use different cues from their surroundings. Learning locations in an environment can be supported by parallel subsystems in the hippocampus and the striatum. We used fMRI to look at differences in the use of object‐related spatial cues while 47 participants actively navigated in an open‐field virtual environment. In each trial, participants navigated toward a target object. During encoding, three positional cues (columns) with directional cues (shadows) were available. During retrieval, the removed target had to be replaced while either two objects without shadows (objects trial) or one object with a shadow (shadow trial) were available. Participants were informed in blocks about which type of retrieval trial was most likely to occur, thereby modulating expectations of having to rely on a single landmark or on a configuration of landmarks. How the spatial learning systems in the hippocampus and caudate nucleus were involved in these landmark‐based encoding and retrieval processes were investigated. Landmark configurations can create a geometry similar to boundaries in an environment. It was found that the hippocampus was involved in encoding when relying on configurations of landmarks, whereas the caudate nucleus was involved in encoding when relying on single landmarks. This might suggest that the observed hippocampal activation for configurations of objects is linked to a spatial representation observed with environmental boundaries. Retrieval based on configurations of landmarks activated regions associated with the spatial updation of object locations for reorientation. When only a single landmark was available during retrieval, regions associated with updating the location of oneself were activated. There was also evidence that good between‐participant performance was predicted by right hippocampal activation. This study therefore sheds light on how the brain deals with changing demands on spatial processing related purely to landmarks. © 2014 Wiley Periodicals, Inc.