Interaction of the leucine-rich repeats of polycystin-1 with extracellular matrix proteins: possible role in cell proliferation.

Polycystin-1, the product of the PKD1 gene, is a membrane-bound multidomain protein with a unique structure and a molecular weight of approximately 460 kD. The purpose of this study is to investigate the binding of the cystein-flanked leucine-rich repeats (LRR) of polycystin-1 to extracellular matrix (ECM) components. These interactions may play a role in normal renal development as well as the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). In vitro assays were used to assess the binding of a fusion protein containing the LRR of polycystin-1 and that of affinity purified polycystin-1 to a number of ECM components. The results showed that the LRR modulate the binding of polycystin-1 to collagen I, fibronectin, laminin, and cyst fluid-derived laminin fragments. The addition of the LRR fusion protein to cells in culture resulted in a significant dose-dependent reduction in the rate of proliferation. Cyst fluid-derived laminin fragments had a stimulatory effect on cell proliferation, which was reversed by the LRR fusion protein. These results suggest that the LRR of polycystin-1 act as mediators of the polycystin-1 interaction with the ECM. The observed suppression effect of the LRR on cell proliferation suggests a functional role of the LRR-mediated polycystin-1 involvement in cell-matrix and cell-cell interactions. These interactions may result in the enhanced cell proliferation that is a characteristic feature of ADPKD.     

Erythroleukemia with high fetal hemoglobin after therapy for ovarian carcinoma

The authors report the association of erythroleukemia (FAB M6) and fetal hemoglobin (HbF) level of at least 65% after therapy for ovarian carcinoma. The patient's erythrocytes had many signs of reversion to fetal-like erythropoiesis including: elevated HbF with a fetal G gamma/A gamma (gly/ala) of 3/1, low hemoglobin A2 (HbA2), macrocytosis, and increased i antigen. These data and data from other case reports suggest that elevation of HbF to greater than 25% with reversion to fetal-like erythropoiesis is useful in differentiating erythroleukemia from other preleukemic disorders.     

Statistical analysis of gait patterns of persons with cerebral palsy

Patients at Boston's Children's Hospital diagnosed as having cerebral palsy were filmed walking. These films were digitized and translated into measurements associated with leg motion. In this paper we use the gait measurements of 128 such patients to illustrate that the kth nearest neighbour clustering procedure results in a gait typology for patients with cerebral palsy. The procedure identifies four subpopulations from the sample data; the membership of a patient within this typology is mostly determined by the patient's motor control. The developed typology differs from the present diagnostic system which classifies a cerebral palsy patient as either quadriplegic, diaplegic or hemiplegic.     

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.     

Allergy to laboratory animals: a retrospective and a prospective study.

Twenty four volunteers who had been allergic to laboratory animals for some years were examined by means of a questionnaire paying particular attention to symptoms associated with rats and by serological and skin tests with extracts of rat urine (retrospective study). Nasal and eye symptoms were reported by 21 and 16 individuals respectively: 13 had asthma. Positive skin tests and high levels of specific IgE antibody to rat urine extract were found in 17 of the more severely affected individuals and this group included 12 of those with asthma. Latent periods of work with animals before symptoms appeared varied from 0.5 to 12 years. Also 148 individuals were studied during their first year of work with animals (prospective study). Symptoms developing during the year were reported by 15%, asthma by 2%. IgE antibody levels to rat urine were raised in 40% of affected and 6% of the unaffected individuals but there was no significant correlation between symptoms and either antibody levels or positive skin tests. Allergic symptoms developing during the first year of postemployment were, on the whole, much milder than those seen in the retrospective study. A tentative conclusion is that most individuals who become allergic to laboratory animals develop the condition in a mild form during their first year of employment but it appears probable that atopic individuals, although having an equal chance of developing allergy as compared with non-atopic individuals, may eventually progress to a more severe form of the disease.     

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.     

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.     

Indirect costs of teaching in Canadian hospitals.

We sought to determine whether there are indirect costs of teaching in Canadian hospitals. To examine cost differences between teaching and nonteaching hospitals we estimated two cost functions: cost per case and cost per patient-day (dependent variables). The independent variables were number of beds, occupancy rate, teaching ratio (number of residents and interns per 100 beds), province, urbanicity (the population density of the county in which the hospital was situated) and wage index. Within each hospital we categorized a random sample of patient discharges according to case mix and severity of illness using age and standard diagnosis and procedure codes. Teaching ratio and case severity were each highly correlated positively with the dependent variables. The other variables that led to higher costs in teaching hospitals were wage rates and number of beds. Our regression model could serve as the basis of a reimbursement system, adjusted for severity and teaching status, particularly in provinces moving toward introducing case-weighting mechanisms into their payment model. Even if teaching hospitals were paid more than nonteaching hospitals because of the difference in the severity of illness there should be an additional allowance to cover the indirect costs of teaching.     

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.