Renal effects of acute exposure to toluene. A controlled clinical trial

Urinary excretion rates of beta 2-microglobulin and albumin were measured in 43 male printing trade workers and 43 age-matched male controls before and during exposure to toluene, 382 mg/m3, for 6 1/2 hours in a climate chamber. There were no significant changes in renal excretion rates of albumin and beta 2-microglobulin during toluene exposure indicating that no causal relationship exists between moderate exposure to organic solvents and renal injury.     

Neurotoxicity of chronic low-dose exposure to organic solvents: A skeptical review

The health effects of long-term, low-level exposure to organic solvents have been studied for many years. While the volume of literature is great, definitive conclusions regarding chronic neurobehavioral effects of environmental exposure are premature. Methodological shortcomings in research preclude confidence in studies allegedly supporting a causal link between chronic low-dose solvent exposure and lasting neurobehavioral deficits. In this article, the shortcomings reviewed include selection bias in recruitment of research subjects, overreliance on subjective recall in determining levels and duration of exposure, between-study variability in kinds of solvents examined, variability in tests selected to assess neurobehavioral functioning, and diversity in reported findings. The implications of these for characterizing the state of organic solvent research are discussed. © 1997 John Wiley & Sons, Inc. J Clin Psychol 53 : 699–712, 1997.     

Treatment of chronic oral candidiasis with clotrimazole troches. A controlled clinical trial.

Twenty patients with chronic oral candidiasis were assigned by random allocation to a two-week course of either 10-mg clotrimazole buccal troches or placebo taken five times daily in a double-blind clinical trial. Each of the 10 recipients of clotrimazole had marked regression of symptoms and mucosal lesions, and in nine patients potassium hydroxide preparations and cultures of mucosal scrapings gave no evidence of candidiasis. In contrast, only one of the 10 patients receiving placebo showed any improvement. The clinical outcome in the clotrimazole-treated group was significantly more favorable (P less than 0.001) than in the group receiving placebo. No adverse reactions to the drug were observed. After the blind phase of their trial, 15 patients were treated with clotrimazole troches in an open trial. One to three troches per day were found adequate to sustain remissions. We conclude that clotrimazole is highly effective treatment for chronic oral candidiasis.     

Long-term neuropsychological impact of brief occupational exposure to organic solvents.

This case series describes the cognitive functioning of 10 individuals who were briefly exposed to a mixture of organic solvents as a result of an industrial accident. Data were obtained 10 years after the exposure on measures of intellect, memory, attention, and executive functioning, using standardised neuropsychological measures including WAIS III, WMS III, Hayling and Brixton Tests, The Trail Making Test, Controlled Oral Word Association, Rey-Osterrieth Complex Figure Test, and The Speed and Capacity of Language-Processing Test. The group performed in the average range across the majority of measures but deficits (z > 1.0 S.D.) were observed on tests that measure speed of information processing, memory, attention, and verbal fluency. Discrepancy scores between the NART and the WAIS suggest subtle but statistically significant decline in performance IQ following solvent exposure.     

A controlled trial of therapy in chronic urticaria

Nineteen patients with chronic idiopathic urticaria (duration 2 to 192 mo) referred to our clinic as therapeutic failures were treated sequentially with five regimens. These were administered orally in a double-blind random sequence and included hydroxyzine pamoate (25 mg q.i.d.) plus one of the following: (1) placebo, (2) terbutaline (2.5 mg q.i.d.), (3) cyproheptadine (4 mg q.i.d.), (4) chlorpheniramine (4 mig q.i.d.), (5) cimetidine (300 mg q.i.d.). Therapeutic response was assessed by patient's subjective choice, symptom diary scores, and suppression of wheal response to intradermal injections of histamine and compound 48/80. At least 35% improvement was noted in all patients with an average optimal response of 70%. The hydroxyzine-cimetidine combination was favored by 11 of 19 (58%) patients, in addition to producing the lowest symptom scores and the greatest histamine-48/80 wheal suppression. These results support the efficacy of combination H1 and H2 antihistamines in the management of some patients with difficult chronic urticaria.     

A placebo controlled clinical trial of transfer factor in lepromatous leprosy.

The effects of repeated injections of transfer factor over a period of 20 weeks were investigated in fourteen bacteriologically positive patients at the lepromatous side of the leprosy spectrum. All patients showed negative (0 mm induration) skin tests to M. leprae antigens (i.e. leprolin and lepromin). Of these patients, seven were treated with transfer factor with a total of 9 units (1 unit being equivalent to 5 x 10(8) lymphocytes) and seven with a placebo. Maintenance treatment with clofazimine was continued. Transfer factor was prepared from the lymphocytes of donors who showed positive skin tests to M. leprae antigens (i.e. leprolin greater than or equal to 12 mm induration, average 15.5 mm or lepromin greater than or equal to 8 mm induration, average 13.6 mm), as well as a positive lymphocyte transformation in vitro to M. leprae (the average transformation being higher than the average transformation of lymphocytes of tuberculoid leprosy patients). No differences were found between the two groups as regards the clinical course of the disease, the histopathological and bacteriological evaluation of skin biopsies, changes in skin test reactivity to various antigens (i.e. lepromin, leprolin, PPD, Mumps, C. albicans, Tr. rubrum and Varidase), as well as the lymphocyte transformation in vitro to various mitogens (i.e. PHA, PWM, Con A) and antigens (i.e. M. leprae, leprolin, PPD, BCG, Mumps, C. albicans, Trichophyton and Varidase). No evidence was found to suggest that transfer factor is a valuable adjuvant in the treatment of lepromatous leprosy patients or that it increases cell-mediated immune reactivity towards M. leprae.     

Heparin-induced increase in serum levels of aminotranferases. A controlled clinical trial

Sixty-four patients over the age of 40 years, undergoing elective surgery of at least one hour's duration, were randomized to treatment with either a thromboembolic deterrent ( TED ) stocking (Kendall Co.) or subcutaneous low-dose heparin 5 000 IU every 12 hours. Serum levels of alanine aminotransferase (S-ALAT), aspartate aminotransferase (S-ASAT), gamma-glutamyl transpeptidase (S-gamma-GT) and alkaline phosphatase (S-ALP) were measured. S-ALAT increased significantly on the 5th and 10th postoperative day, from 27 +/- 2 (x +/- SE) to 40 +/- 4 (p less than 0.01) and 55 +/- 7 U/l (p less than 0.001), respectively, in the heparin group and was significantly higher in the heparin than in the TED group both on the 5th (p less than 0.01) and 10th (p less than 0.05) postoperative day. S-ASAT and S-gamma-GT increased significantly during heparin treatment, but did not differ significantly from the values of the TED group. No change in S-ALP was registered in either group. It is concluded that prophylactic treatment with low-dose heparin induces a significant increase in S-aminotransferase levels, especially in S-ALAT. The phenomenon has profound differential diagnostic implications in conditions such as pulmonary embolism and acute myocardial infarction.     

Reduction of chronic non-specific low back pain: A randomised controlled clinical trial on acupuncture and baclofen

Background  

Chronic non-specific low back pain (LBP) is a prevalent (80%) and multi-dimensional illness. This study aims to test whether acupuncture, baclofen, or combined treatment with acupuncture and baclofen alleviates symptoms of non-specific chronic LBP in men.     

Clinical course of neuropsychological functioning after chronic exposure to organic and inorganic lead.

This case series describes the clinical course (12- to 28-month follow-up) of neuropsychological functioning in 23 workers who had chronic occupational exposure to a mixture of organic and inorganic lead. Significant improvement in performance was seen in 123 tests and deterioration in 323 tests. However, there was no significant change in the majority of tests (1923). Tests that showed deterioration were all tests of psychomotor/motor speed. In addition, 10 of 13 workers who completed a symptom checklist twice reported more frequent physical, cognitive, and affective symptoms at follow-up. This increase in symptoms was associated with psychomotor/motor slowing as compared to initial test performance. Many workers subjectively reported an increased frequency of memory and concentration problems at follow-up, although this change could not be documented objectively. Individual worker demographic and exposure characteristics were not predictive of changes in neuropsychological performance at retest. We propose a psychosocial mechanism to explain the increase in symptom severity and the psychomotor/motor slowing because environmental levels of lead declined during the inter-test interval.     

Tolerance of bacteria to organic solvents

Organic-solvent-tolerant bacteria are a relatively novel group of extremophilic microorganisms. They overcome the toxic and destructive effects of organic solvents due to the presence of various adaptive mechanisms. Extensive studies done on the toluene tolerance of certain Pseudomonas strains have led to an understanding of the mechanisms of organic solvent tolerance involving novel adaptations such as the toluene efflux pumps, cis-trans isomerisation of membrane fatty acids, rapid membrane repair mechanisms, etc. Organic-solvent-tolerant mutants of Escherichia coli have been constructed and genes enhancing such tolerance characterised. However, there is practically no information available on the tolerance mechanisms of the reported Gram-positive organic-solvent-tolerant bacterial strains like Bacillus, Rhodococcus and Arthrobacter. This review discusses the general aspects of organic-solvent-tolerant bacteria, their history, biodiversity, mechanisms of tolerance and proposes certain probable adaptations of Gram-positive bacteria in tolerance to organic solvents.     

A randomized controlled clinical trial of 2295 ultrasound-guided embryo transfers

BACKGROUND: We wanted to test the hypothesis that using abdominal ultrasoundat the time of embryo transfer to guide replacement, improvedpregnancy rates by at least 5%. METHODS: An RCT in a large assisted conception unit. A pilot study andpower calculation suggested that at least 2000 embryo transferswere required to demonstrate a difference of 5%, for a testwith 80% power and Type 1 error 0.05. Randomization, data entryand analysis were arranged independently. Randomization wasstratified for age and fresh/frozen embryo transfer. Analysiswas by intention to treat. RESULTS: There was no difference in clinical pregnancy or live birthrates between the two groups. The clinical pregnancy rate forultrasound-guided embryo transfer was 22% and for non-ultrasound-guidedembryo transfer was 23% (odds ratio: 0.96; 95% confidence interval:0.79–1.18). CONCLUSIONS: We set out to determine whether ultrasound-guided embryo transferimproved clinical pregnancy rates and live birth rates in assistedconception. We used an appropriately powered RCT design. Wedid not demonstrate a difference. This outcome is at odds withthe UKs National Institute of Clinical Excellence recommendationsfor fertility treatment (Fertility Assessment and Treatmentfor People with Fertility Problems. London, UK: RCOG Press,2004, 112.) which used a meta-analysis of four smaller trials(range 362–800 patients, totalling 2051 embryo transfers)to conclude that ultrasound should be offered. We suggest thatthe current Cochrane review should be updated with data fromour trial and recommend that consideration is given to accountingfor heterogeneity between the included trials.     

A controlled trial of multiphasic screening.

A clinical controlled trial was designed to determine the impact of Automated Multiphasic Health Testing on morbidity and attitudes. Three strata comprising 574 families (lower-income group enrolled in health maintenance organization, lower-income not enrolled in such a project, and a middle-income group employed by a utility company) were interviewed to obtain information on utilization, morbidity, health status, and attitudes. Sixty percent of adults in each stratum were then screened. All families were interviewed again one year later. The only significant difference found between screened and non-screened subjects was an increase in nights hospitalized for screened subjects. Physicians were interviewed to determine what abnormalities were found and what treatment was required for project and privately referred patients of these physicians. Previously unknown abnormalities prompted retesting for confirmation in only 28 per cent of the cases and even less often led to treatment.     

Limitations of student-driven formative assessment in a clinical clerkship. A randomised controlled trial

Background  

Teachers strive to motivate their students to be self-directed learners. One of the methods used is to provide online formative assessment material. The concept of formative assessment and use of these processes is heavily promoted, despite limited evidence as to their efficacy.     

A trial of minocycline given after exposure to prevent gonorrhea.

In a prospective evaluation of antibiotic prophylaxis against gonorrhea, 1080 men were given 200 mg of oral minocycline or placebo after sexual intercourse with prostitutes in a Far Eastern port. Later, at sea, gonococcal infection was detected in 57 of 565 men given placebo and 24 of 515 men given minocycline (P less than 0.001). Minocycline prophylaxis completely prevented infection by gonococci susceptible to 0.75 microgram or less of tetracycline per milliliter, reduced the risk of infection or prolonged the incubation period in men exposed to gonococci susceptible to 1.0 to 2.0 micrograms per milliliter, but did not prevent infection or prolong incubation in men exposed to gonococci resistant to 2.0 micrograms. Minocycline did not increase the proportion of asymptomatic infections. Minocycline prophylaxis would probably have limited effectiveness as a public-health measure because of the tendency to select resistant gonococci.     

Behavioral toxicology of volatile organic solvents. I. Methods: acute effects of toluene

Behavioral toxicity of toluene has been assessed in mice. Because of its small size the mouse can be confined in a 20 l hermetically sealed chamber for several hours. Toluene was introduced through a port and volatilized by a hot-plate. Samples of chamber air for analysis were taken through another port. A smaller mesh cage held the mouse within the larger chamber. Schedule-controlled responding was developed by arranging that a response, breaking a beam of light, was followed by milk under an Fl 60 sec schedule. Responding was much more rapid in the presence of stimuli correlated with the Fl schedule than when the schedule was not operating. Standard sessions consisted of alternating series of 8 consecutive Fl 60 sec and inter-series 30 min time-outs. Toluene disappeared from the atmosphere of the unopened empty chamber at the rate of 0.2%/hr. When the mouse cage was in the chamber the disappearance was 1.5%/hr and when a mouse was also present it was 3.7%/hr. Concentration-effect curves were determined by exposing a mouse to incremental additions of toluene at 30 min intervals. Toluene increased the rate of responding in most mice at levels of about 700 ppm. Higher concentrations progressively reduced responding. The ED50 (the concentration reducing responding by 50%) averaged 1657 ppm in 10 mice. In the appendix, principles for the assessment of hazard from results of this type are presented. It is estimated that there is a 1/1000 chance of the responding of a mouse being reduced by as much as 10% by a concentration of toluene of 69 ppm.