Occupational exposure to cholinesterase inhibiting pesticides: a Greek case.

The determination of plasma or serum cholinesterase is absolute and it is considered as a reliable index of exposure in workers of organophosphorus pesticides industries. In the present study the plasma cholinesterase of 28 persons working in the packaging of an ortho-thio-phosphate was determined, before and after their exposure to this agent. The results of this study showed a plasma cholinesterase depression of 37%, a decrease which was statistically significant (P<0.001).

Long-term (7 to 8-year) experience with finasteride in men with benign prostatic hyperplasia.

OBJECTIVES: To evaluate the effects of finasteride, a specific type II 5-alpha-reductase inhibitor, on symptoms of benign prostatic hyperplasia, prostate volume, and urinary flow during a 7 to 8-year period. METHODS: A total of 190 men with symptomatic benign prostatic hyperplasia and enlarged prostates entered one of two Phase II double-blind 3 to 6-month studies. Of these, 156 patients continued taking open-label finasteride, and more than 70 patients completed 7 to 8 years of treatment. The symptoms were scored using a patient self-administered modified Boyarsky symptom questionnaire. Prostate volume was measured by magnetic resonance imaging or ultrasonography, and the maximal urinary flow rate was assessed noninvasively. RESULTS: Treatment with finasteride for 7 to 8 years led to sustained improvement in symptoms, reduction in prostate volume (28% from baseline), and increased urinary flow (median 2.5 mL/s from baseline). Decreases in dihydrotestosterone (86%) and prostate-specific antigen (54%) levels were also maintained. Long-term finasteride treatment was safe and generally well tolerated. CONCLUSIONS: Long-term treatment with finasteride was well tolerated and resulted in durable symptom relief and improvement in prostate volume and urinary flow.

Lead content of fresh milk samples from different sites in Athens.

Milk and dairy products constitute a major food, especially for infants and children, and relatively low levels of toxic elements can contribute significantly to dietary intakes and be hazardous for public health. The purpose of this survey was to define the levels of lead in milk samples of different origin, to establish the presence or absence of contamination. The milks from different sites of the metropolitan area of Athens contained negligible traces of lead and thus are safe for the public health.

Prostate volume and serum prostate-specific antigen as predictors of acute urinary retention. Combined experience from three large multinational placebo-controlled trials.

OBJECTIVES: We evaluated prostate volume and prostate-specific antigen (PSA) as predictors of acute urinary retention (AUR) in men with benign prostatic enlargement (BPE). METHODS: Data were pooled from 3 identical 2-year, multinational, multicenter, non-US, placebo-controlled finasteride trials in 4,222 men with BPE and no evidence of prostate cancer. RESULTS: The 2-year incidence of spontaneous AUR was higher in placebo patients with enlarged prostates (4.2% in men with prostate volume > or =40 ml vs. 1.6% in the <40 ml group) and higher PSA levels (3.9% in men with PSA > or =1.4 ng/ml vs. 0.5% in the <1.4 ng/ml group) at baseline. Finasteride reduced AUR incidence by 61% in men with larger prostates, by 63% in men with higher PSA levels, and by 47% in men with smaller prostates, compared with placebo. CONCLUSIONS: BPE patients with larger prostate volumes, higher PSA levels and no evidence of prostate cancer have an increased risk of developing AUR and therefore derive the greatest benefit from the risk reduction seen with finasteride therapy.

Impact of baseline symptom severity on future risk of benign prostatic hyperplasia-related outcomes and long-term response to finasteride. The Pless Study Group.

OBJECTIVES: To evaluate the long-term effects of finasteride on symptoms, acute urinary retention (AUR), and the need for benign prostatic hyperplasia (BPH)-related surgery in relationship to baseline symptom severity. METHODS: A total of 3040 men with BPH were treated for 4 years with finasteride or placebo. The changes from baseline in symptoms and the incidence of BPH-related surgery and AUR were determined in men with mild (less than 8), low-moderate (8 to 12), high-moderate (13 to 19), and severe (greater than 19) baseline quasi-American Urological Association symptoms for all patients and for the subgroup with a baseline prostate-specific antigen (PSA) level of 1.4 ng/mL or greater. RESULTS: In patients who completed the 4-year study, the change in symptom score, stratified by baseline symptom severity, was +1.4 +/- 0.5 (mild), -0.8 +/- 0.3 (low-moderate), -3.6 +/- 0.3 (high-moderate), and -7.7 +/- 0.5 (severe) in finasteride-treated patients and, respectively, +3.4 +/- 0.5, +0.7 +/- 0.3, -1.4 +/- 0.3, and -5.3 +/- 0.6 in placebo-treated patients (between-group P <0.01). The between-group differences were greater in the subgroup of patients with a baseline PSA of 1.4 ng/mL or greater. The risk of BPH-related surgery increased among placebo patients with increasing baseline symptom severity to a greater extent than the risk of AUR. Finasteride reduced the risk of AUR or the need for BPH-related surgery in all subgroups (P <0.001), especially in men with a baseline PSA of 1.4 ng/mL or greater. CONCLUSIONS: Compared with placebo, finasteride had a beneficial effect on symptoms, AUR, and BPH-related surgery in all symptom categories. BPH-related surgery, but not AUR, occurred more commonly in placebo-treated men with more severe baseline symptoms. The greatest absolute benefit of finasteride on symptoms and the reduction in risk of AUR and surgery was in men with higher baseline symptom scores and a baseline PSA level of 1.4 ng/mL or greater.

Lack of efficacy of finasteride in postmenopausal women with androgenetic alopecia.

BACKGROUND: Finasteride, an inhibitor of type 2 5alpha-reductase, decreases serum and scalp dihydrotestosterone (DHT) by inhibiting conversion of testosterone to DHT and has been shown to be effective in men with androgenetic alopecia (AGA). The effects of finasteride in women with AGA have not been evaluated. OBJECTIVE: The purpose of this study was to evaluate the efficacy of finasteride in postmenopausal women with AGA. METHODS: In this 1-year, double-blind, placebo-controlled, randomized, multicenter trial, 137 postmenopausal women (41-60 years of age) with AGA received finasteride 1 mg/day or placebo. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, assessment of global photographs by a blinded expert panel, and histologic analysis of scalp biopsy specimens. RESULTS: After 1 year of therapy, there was no significant difference in the change in hair count between the finasteride and placebo groups. Both treatment groups had significant decreases in hair count in the frontal/parietal (anterior/mid) scalp during the 1-year study period. Similarly, patient, investigator, and photographic assessments as well as scalp biopsy analysis did not demonstrate any improvement in slowing hair thinning, increasing hair growth, or improving the appearance of the hair in finasteride-treated subjects compared with the placebo group. Finasteride was generally well tolerated. CONCLUSION: In postmenopausal women with AGA, finasteride 1 mg/day taken for 12 months did not not increase hair growth or slow the progression of hair thinning.

Bee pseudocholinesterase as an indicator of exposure to anticholinesterase insecticides.

The inhibition of pseudocholinesterase (butyrylcholinesterase) activity is a valid and sensitive biochemical indicator of exposure to anticholinesterase insecticides and is often mandatory of the agricultural use of these pesticides. In the present work we developed a modification of an easy and sensitive technique to detect the pseudocholinesterase inhibition due to pesticide exposure. Small amounts of head tissue are needed and low concentrations of the enzyme can be detected. The determination of pseudocholinesterase inhibition is a useful biomonitor of anticholinesterase pesticide exposure for bees in the same way that it is useful for the determination of exposure in humans.

Bee head acetylcholinesterase as an indicator of exposure to organophosphate and carbamate insecticides.

Insect acetylcholinesterase has received special attention following the discovery that inhibition of the enzyme is the mechanism of activity of the organophosphate and carbamate insecticides. Apiculture is an important source of Greek income and as the detection of anticholinesterase insecticides in bees is very difficult, investigation of the cause of death of honeybees due to acetylcholinesterase inhibition is of great value and will contribute to the differential diagnosis of bee diseases. The enzymatic assay is not capable of distinguishing between individual pesticides', but is an indicator of the exposure of bees to anticholinesterase insecticides.

Proscar: five-year experience.

We assessed the long-term safety and efficacy of finasteride, an orally active 5 alpha-reductase inhibitor, in 2 previously reported groups of patients with symptomatic benign prostatic hyperplasia (BPH). Prostate volume was measured by magnetic resonance imaging, and the maximum urinary flow rate was assessed noninvasively. Symptoms were scored utilizing a patient self-administered symptom score questionnaire. Total symptom scores ranged from 0 (or asymptomatic) to 35 (severely symptomatic). After an initial double-blind period, the patients in study 1 were treated with 10 mg finasteride for 1 year and then switched to 5 mg finasteride for an additional 4 years, whereas patients in study 2 were treated with 5 mg finasteride for the entire 5 years. A total of 190 patients were randomized in the double-blind studies, 156 entered year 1 of the open extension and 70 patients completed 5 years of finasteride therapy. In both studies prostate volume was reduced from baseline by 30%, dihydrotestosterone was reduced by 72%, and the maximum urinary flow rate improved by approximately 1.5 ml/s. Prostate-specific antigen was decreased by approximately 50%. Finasteride was well tolerated; approximately 10% of patients reported sexual adverse experiences during the 5-year study period, which were considered drug related by the investigators. The incidence in reporting sexual adverse experiences did not increase with the increased duration of treatment: findings consistent with previous reports. In summary treatment of BPH with finasteride for 5 years inhibits the progression of the disease with an excellent safety profile and represents a low-risk medical option for the treatment of symptomatic BPH.

Prolonged treatment with finasteride (a 5 alpha-reductase inhibitor) does not affect bone density and metabolism.

OBJECTIVE: Since it is not clear whether testosterone or dihydrotestosterone is the active hormone in bone metabolism, we wished to assess the effect of finasteride, a 5 alpha-reductase inhibitor, or vertebral bone mineral density and parameters of bone and mineral metabolism. DESIGN: Patients were treated in a randomized, double-blind controlled study with either placebo, 1 or 5 mg/day finasteride. PATIENTS: Twenty-three men with benign prostatic hyperplasia (BPH) were included in this study; eight received placebo, seven were allocated to treatment with 1 mg/day, and eight to 5 mg/day finasteride for 12 months. MEASUREMENTS: Vertebral bone mineral density was measured at the lumbar spine by dual energy X-ray bone densitometry. Serum calcium, phosphorus, parathyroid hormone, osteocalcin and vitamin D metabolites were measured regularly. Urinary calcium and creatinine excretion were monitored as well. RESULTS: Finasteride caused a significant decrease in serum dihydrotestosterone after 6 and 12 months, but no effect on serum testosterone. Vertebral bone mineral density remained unaltered. None of the other parameters monitored were affected except for a small unexplained increase in 1.25-dihydroxyvitamin D in the group receiving 5 mg finasteride/day. CONCLUSIONS: Testosterone is probably the active hormone in bone metabolism. However, oestradiol, the product of testosterone aromatization (which remains unaltered under finasteride) may yet be another possible responsible steroid in the maintenance of bone density. We can also not rule out that the small amount of dihydrotestosterone remaining under finasteride administration is sufficient for maintaining normal bone metabolism.

Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia.

The oral administration of finasteride, a 4-aza-steroid inhibitor of 5 alpha-reductase, decreases serum dihydrotestosterone levels, but has little effect on serum testosterone. The current study was designed to assess the effect of finasteride on dihydrotestosterone levels in the prostates of men with benign prostatic hyperplasia. In a double blind, placebo-controlled study, 69 men with symptomatic prostatic hyperplasia were treated with placebo or 1, 5, 10, 50, or 100 mg/day finasteride for 7 days before transurethral resection of the prostate. In the placebo group the mean concentration of prostatic dihydrotestosterone was 10.3 +/- 0.6 nmol/kg (+/- SE), and the mean concentration of testosterone was 0.7 +/- 0.1 nmol/kg. After 7 days of treatment with all doses of finasteride, prostatic dihydrotestosterone declined to 15% or less of control levels, and the testosterone concentration increased in a reciprocal fashion. Compared to the placebo group, there was no significant difference in the mean prostatic dihydrotestosterone level achieved in any of the finasteride-treated groups. However, prostatic dihydrotestosterone levels were lower in the groups receiving higher doses of the drug. In two additional patients, finasteride treatment for 2 days also caused a decrease in prostatic dihydrotestosterone levels. No significant adverse experiences occurred during the study. We conclude that finasteride causes profound decrease in prostatic dihydrotestosterone.

Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia.

The effects of finasteride, a potent 5 alpha-reductase inhibitor, were assessed in patients with benign prostatic hyperplasia. Patients were treated with finasteride or placebo for 24 weeks in a double-blind multicenter study followed by a 12-month open-extension period. After 24 weeks, finasteride-treated patients, when compared to placebo-treated patients, showed a significant reduction in prostate volume (22.5% median decrease) and prostate significant antigen (32.4% median decrease), a significant increase in maximum urinary flow (1.6 ml/s mean increase from baseline) and a significant improvement in their obstructive symptom scores (two-point decrease from baseline). Finasteride was well tolerated, and the improvements in prostate volume, maximum urinary flow rate and obstructive symptom scores observed in the controlled study were maintained throughout the extension study.

Somatosensory evoked potentials predict neuromotor outcome after periventricular hemorrhage.

Thirty-nine very low-birthweight (VLBW) preterm infants with periventricular hemorrhage (PVH) were studied with short-latency median nerve somatosensory evoked potentials (SEP) at two, four and/or six months corrected age, and subsequently were followed to a mean age of 22 months. All 12 infants with a single SEP showing unilateral absence or prolonged latency of the early cerebral (N1) response had motor abnormalities at follow-up. A single normal SEP predicted normal motor development in 19 of 36 infants; two normal SEPs did so in 15 of 26 infants, and three normal SEPs in 12 of 14 infants. These results demonstrate that SEPs play a useful rôle in predicting neuromotor outcome for VLBW preterm infants with PVH.

Intramuscular imipenem/cilastatin in the treatment of mild and moderate infections.

Imipenem/cilastatin is the combination of a broad spectrum beta-lactam antibiotic with dehydropeptidase I--an inhibitor of the metabolism of imipenem. Clinical trials have shown that imipenem/cilastatin given intravenously is effective in the treatment of mild, moderate or severe infections. A new milled form of imipenem has been developed for intramuscular use as a suspension with cilastatin, which provides a longer effective half-life of three to four hours with lower peak concentrations of imipenem. A multicenter clinical trial was instituted in the treatment of mild and moderate infections with 500 mg b.i.d. and 500 mg t.i.d. or 750 mg b.i.d., respectively. All 500 mg doses were suspended in saline while the 750 mg doses were in 1% lidocaine. A total of 346 (126 on 500 mg b.i.d., 70 on 500 mg t.i.d. and 128 on 750 mg b.i.d.) were entered. Another 22 patients received a combination of the two regimens. Of the total 346 patients entered, 286 were considered evaluable for efficacy. Skin and soft tissue infections were the most common followed by intra-abdominal, respiratory and urinary tract infections. Overall favorable outcomes were demonstrated in 98.7% with a range of 92 to 100%. All patients were included in the safety analysis. Clinical adverse experiences (AEs) were reported in 3.2% of patients with two AEs considered drug related. Both were pain at the injection site with 500 mg doses. No injection site pain was reported as AEs with the 750 mg doses. Laboratory AEs were reported in 17% and considered drug related in 7% (primarily liver enzymes changes).(ABSTRACT TRUNCATED AT 250 WORDS)

Imipenem/cilastatin: a multicentre international study of its clinical efficacy, safety and potential as empirical therapy.

Five hundred and sixty-nine patients were treated with imipenem/cilastatin in this multicentre, international noncomparative study of hospitalized patients with moderate to severe infections; 97.5% of 815 pathogens isolated were susceptible to imipenem, which reconfirms imipenem's broad in-vitro spectrum. Clinical efficacy could be assessed in 389 patients, the majority (72%) of whom received a daily dose of 1.5 g or less. Infections in the various body sites with the exception of the central nervous system were treated. A favourable clinical outcome was seen in 93% of the infections. Fifty-five of the 389 patients had been unsuccessfully treated with one or more antibiotics before being switched to imipenem/cilastatin. In these patients the daily dose was evenly distributed between 1.5 g/day (47%) or 2.0 g/day (40%); the rest of the patients received greater than 2 g/day. Intra-abdominal and respiratory tract infections were the most common, the majority (56%) of which were rated severe. Overall clinical efficacy (cured or improved) in these 55 patients was 82%. With the demonstrated clinical efficacy, particularly in the treatment of proven infections which have failed on other regimens, imipenem/cilastatin could have a distinct advantage as an initial choice for empirical therapy.

T cell responses to select Ia determinants using the I-A mutant mouse strain B6.C-H-2bm12.

The T cell repertoire of B6.C-H-2bm12 mice (an I-A mutant mouse strain) to wild-type Iab antigens was investigated using both secondary proliferative cultures and cloned T cell lines. Because bm12 mice have a gain-loss mutation of their gene encoding the Ia beta-chain polypeptide, bm12 anti-B6 T cell responses are specific for the select component of Iab specificities that was lost as a result of the mutation. Although stimulator cells bearing Iab antigens elicited the strongest responses, Iaq, d, and s antigens also resulted in reproducible stimulations of these bm12 anti-B6-primed T cells. Cloned T cell lines isolated from bm12 anti-b6 cultures revealed similar findings, with most clones recognizing determinants unique for Iab antigens; however, clones showing cross-reactions with Iad and/or q were also selected. Using F1 hybrid responder T cells (mutant x cross-reactive strain), we further dissected this cross-reactivity into several distinct cross-reactive determinants. Because bm12 mice lack the serologically defined Ia differentiation antigen W39, T cell recognition of this determinant was investigated by using bm12 anti-B6-primed cells. Stimulation by Ia.W39+ cells was appreciably better than by Ia.W39- (Xid-defective) cells, suggesting that bm12 T cells recognize an Xid-regulated, W39-like Ia differentiation antigen.