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.     

Controlled trial of clinical utility of serum salicylate monitoring in rheumatoid arthritis

A crossover double-blind controlled trial was performed on 36 patients with rheumatoid arthritis to assess the necessity for serum salicylate monitoring in determining optimal dosage. There was no clinically or statistically significant increase in the clinical improvement of patients associated with serum monitoring but potentially toxic serum levels occurred without tinnitus when serum monitoring was not used.     

Poisoning due to Pyrethroids

The first pyrethroid pesticide, allethrin, was identified in 1949. Allethrin and other pyrethroids with a basic cyclopropane carboxylic ester structure are type I pyrethroids. The insecticidal activity of these synthetic pyrethroids was enhanced further by the addition of a cyano group to give α-cyano (type II) pyrethroids, such as cypermethrin. The finding of insecticidal activity in a group of phenylacetic 3-phenoxybenzyl esters, which lacked the cyclopropane ring but contained the α-cyano group (and hence were type II pyrethroids) led to the development of fenvalerate and related compounds. All pyrethroids can exist as at least four stereoisomers, each with different biological activities. They are marketed as racemic mixtures or as single isomers. In commercial formulations, the activity of pyrethroids is usually enhanced by the addition of a synergist such as piperonyl butoxide, which inhibits metabolic degradation of the active ingredient. Pyrethroids are used widely as insecticides both in the home and commercially, and in medicine for the topical treatment of scabies and headlice. In tropical countries mosquito nets are commonly soaked in solutions of deltamethrin as part of antimalarial strategies. Pyrethroids are some 2250 times more toxic to insects than mammals because insects have increased sodium channel sensitivity, smaller body size and lower body temperature. In addition, mammals are protected by poor dermal absorption and rapid metabolism to non-toxic metabolites. The mechanisms by which pyrethroids alone are toxic are complex and become more complicated when they are co-formulated with either piperonyl butoxide or an organophosphorus insecticide, or both, as these compounds inhibit pyrethroid metabolism. The main effects of pyrethroids are on sodium and chloride channels. Pyrethroids modify the gating characteristics of voltage-sensitive sodium channels to delay their closure. A protracted sodium influx (referred to as a sodium ‘tail current’) ensues which, if it is sufficiently large and/or long, lowers the action potential threshold and causes repetitive firing; this may be the mechanism causing paraesthesiae. At high pyrethroid concentrations, the sodium tail current may be sufficiently great to prevent further action potential generation and ‘conduction block’ ensues. Only low pyrethroid concentrations are necessary to modify sensory neurone function. Type II pyrethroids also decrease chloride currents through voltage-dependent chloride channels and this action probably contributes the most to the features of poisoning with type II pyrethroids. At relatively high concentrations, pyrethroids can also act on GABA-gated chloride channels, which may be responsible for the seizures seen with severe type II poisoning. Despite their extensive world-wide use, there are relatively few reports of human pyrethroid poisoning. Less than ten deaths have been reported from ingestion or following occupational exposure. Occupationally, the main route of pyrethroid absorption is through the skin. Inhalation is much less important but increases when pyrethroids are used in confined spaces. The main adverse effect of dermal exposure is paraesthesiae, presumably due to hyperactivity of cutaneous sensory nerve fibres. The face is affected most commonly and the paraesthesiae are exacerbated by sensory stimulation such as heat, sunlight, scratching, sweating or the application of water. Pyrethroid ingestion gives rise within minutes to a sore throat, nausea, vomiting and abdominal pain. There may be mouth ulceration, increased secretions and/or dysphagia. Systemic effects occur 4–8 hours after exposure. Dizziness, headache and fatigue are common, and palpitations, chest tightness and blurred vision less frequent. Coma and convulsions are the principal life-threatening features. Most patients recover within 6 days, although there were seven fatalities among 573 cases in one series and one among 48 cases in another. Management is supportive. As paraesthesiae usually resolve in 12–24 hours, specific treatment is not generally required, although topical application of dl-α tocopherol acetate (vitamin E) may reduce their severity.     

Phase-constrained data extrapolation method for reduction of truncation artifacts

The authors present an improvement to a sigma-filter extrapolation method for the reconstruction of magnetic resonance (MR) images from symmetric discrete Fourier data. By making use of the phase information in the image data, the proposed method can overcome the data inconsistency problem of the original method for handling MR image data with large phase variations, such as those obtained in gradient-echo pulse sequences. Reconstruction results show that its performance is comparable with that of the modified complex sigma-filter method proposed previously to handle the inconsistency problem. However, the new approach has the advantage of reducing computation time by a factor of two with use of a sigma filter applied to real instead of complex images. It is expected that this method will be more practical for use in clinical MR imaging systems.     

Helicobacter pylori; histological and cultural correlation in chronic gastritis.

Seventy seven antral biopsies were collected from patients attending endoscopy clinic at King Khalid University Hospital, Riyadh, Saudi Arabia during a period of six months between December 1988 to May 1989. Of these 69 (89.6%) showed chronic gastritis as well as Helicobacter-like organisms (HLOs) in the biopsy specimens while 63 (81.8%) of biopsies grew Helicobacter pylori on culture. These findings indicate a good correlation between the histological diagnosis of chronic gastritis and isolation of H. pylori on culture.     

Endourological experience with cystine calculi and a treatment algorithm

Between May 1984 and January 1988, 18 patients (31 pyeloureteral units) with documented symptomatic cystine stones were treated. Stone size ranged from 5 to 56 mm. in largest diameter, with an average of 21 mm. All pyeloureteral units were treated initially by endourological methods, including ureteroscopy in 10, percutaneous ultrasonic lithotripsy in 9, extracorporeal shock wave lithotripsy (ESWL) in 10 and chemolysis in 2. Of the patients 10 required a combination of these technologies and 2 required an open operation. Of the 31 units 23 were free of stones when the patient was discharged from the hospital. Of 8 patients with retained stones only 3 had fragments greater than 3 mm. in diameter. Based on this experience an algorithm was developed for the urological management of cystine stones. Ureteral calculi may be removed by ureteroscopic techniques or manipulated into the renal pelvis and managed as renal stones. Cystine renal calculi of less than 1.5 cm. may be treated with ESWL monotherapy. Stones of 1.5 to 3 cm. may be treated with ESWL and dissolution, or percutaneous ultrasonic lithotripsy plus dissolution. Staghorn calculi may be treated by percutaneous ultrasonic lithotripsy plus ESWL and/or dissolution for retained fragments.     

Circulating immune complexes in pre-eclampsia.

Serum samples from 20 non-pregnant women, 30 women with normal pregnancy and 50 women with pregnancy associated with pre-eclampsia were tested for circulating immune complexes using the polyethyleneglycol precipitation method. A highly significant positive correlation was found between circulating immune complexes and severe pre-eclampsia (BP greater than 140/90 mm Hg, albuminuria greater than 0.25 g/l). In contrast to this the difference in immune complex levels between non-pregnant subject, normal pregnancy cases and patients with mild pre-eclampsia was not statistically significant. A significant positive correlation was found between the level of circulating immune complexes and the severity of albuminuria. These findings suggest that circulating immune complexes, though not seeming to play an aetiological role in pre-eclampsia may very well be involved in its pathogenesis.     

Dermal absorption of niclosamide in rats and minipigs

The dermal absorption of niclosamide, a drug shown to prevent Schistosomiasis by blocking the dermal penetration of cercariae, has been examined in Sinclair minipigs and rats. Radioactivity in the urine and feces collected daily for 7 days after application of 14C-niclosamide accounted for less than 2 per cent and 10 per cent of the labelled compound applied to pig and rat skin, respectively. Approximately 20 per cent of the radioactivity from the dose solution was recovered on the skin excised from the area of application in both minipigs and rats. No radioactivity was detected in organs removed from the pig 7 days after application of radiolabelled drug while less than 6 per cent of the dose could be accounted for in the rat organs/carcass. Radioactivity in swine blood, removed 0.5, 1, 2, 4 and at 24 h intervals after dosing, was at or below three times background in all of the samples. Total recovery of the applied radioactivity was 78 per cent in pigs and 57 per cent in rats. These studies indicate that niclosamide is very poorly absorbed after dermal application. The results are consistent with earlier comparative studies showing that dermal penetration of xenobiotics in rats is generally higher than in swine.