Risk factors of recurrent sickness absence due to depression: a two-year cohort study among Japanese employees.

PURPOSE: Depression has a high recurrence rate among employees. There have been few studies investigating risk factors for recurrent sickness absence due to depression after return to work (RTW). The objective of this study was to identify potential risk factors. METHODS: Subjects were 540 full-time employees at the biggest telecommunication company in Japan who returned to work from April 2002 to March 2008 after their first leave of absence due to depression. The Cox proportional hazard model was employed to find risk factors for recurrent sickness absence by analyzing variables including demographic, work-related and work environmental factors. RESULTS: Of 540 study subjects, 200 employees (37.0 %) experienced recurrent sickness absence due to depression after RTW within the follow-up period. Higher organizational job demand evaluated by the Brief Job Stress Questionnaire (BJSQ) was found to be a risk factor (OR 1.46, 95 % CI 1.01-2.10) for recurrent sickness absence due to depression adjusted for confounding factors. CONCLUSIONS: High organizational job demand (evaluated by BJSQ) is a risk factor for recurrent sickness absence due to depression after RTW.

Effects of guanfacine monotherapy on blood pressure, heart rate, plasma renin activity, aldosterone, and catecholamines in hypertensive patients with chronic glomerulonephritis.

Effects of guanfacine, a centrally acting antihypertensive, on blood pressure, heart rate, plasma renin activity, serum aldosterone, plasma norepinephrine, and renal function were evaluated in 16 patients with hypertension with biopsy-proved chronic glomerulonephritis. Guanfacine monotherapy with a daily dose of 1 to 2.5 mg at bedtime for 6 months brought about a significant reduction in blood pressure (171 +/- 2/110 +/- 2 to 144 +/- 2/89 +/- 1 mm Hg; P less than 0.01), with concurrent decreases in heart rate (78 +/- 2 to 70 +/- 2 bpm; P less than 0.01), plasma renin activity (1.96 +/- 0.12 to 1.21 +/- 0.19 ng/ml/hr; P less than 0.05), aldosterone (14.6 +/- 1.5 to 9.7 +/- 0.9 ng/dl; P less than 0.05), plasma norepinephrine (220.5 +/- 24.2 to 132.8 +/- 27.7 pg/ml; P less than 0.05). There was no change in serum creatinine, beta 2-microglobulin, or endogenous creatinine clearance during guanfacine monotherapy. Our data suggest that guanfacine exerts its antihypertensive effect via the inhibition of sympathetic outflow and in part the suppression of the reninangiotensin-aldosterone system and that guanfacine is suitable for the effective treatment of hypertension associated with chronic glomerulonephritis.

Plasma beta-thromboglobulin to platelet factor 4 ratios as indices of vascular complications in essential hypertension.

The ratio of the plasma level of beta-thromboglobulin (beta-TG) to platelet factor 4 (PF-4) which is regarded as a most reliable indicator of platelet activation in vivo, was followed in 52 subjects at various stages of essential hypertension according to the WHO classification. These comprised 30 cases at stage I, 19 cases at stage II and three cases at stage III, and 20 age-matched normotensive control subjects. The observed beta-TG:PF-4 ratio in the hypertensive patients was 4.59 +/- 0.20, which was significantly higher than the value of 3.13 +/- 0.19 recorded in the normotensive control subjects. According to the WHO classification, beta-TG:PF-4 ratios in hypertensive patients at stages I, II and III were 3.93 +/- 0.19, 5.31 +/- 0.35 and 6.56 +/- 0.12, respectively. The beta-TG:PF-4 ratio revealed a tendency of platelet activation to increase with advanced progress of hypertensive vascular lesions. These results suggest that the abnormal platelet function observed in patients with essential hypertension plays an important role in the development of hypertensive vascular complications.

Participation of the sympathetic nervous system in hypertension in rats with subtotal renal ablation.

To clarify the role of the sympathetic nervous system in the development of hypertension in chronic renal failure, plasma levels and urinary excretions of catecholamines were evaluated in male Sprague-Dawley rats. The renal mass of the rats was reduced by removing one kidney and two-thirds of the contralateral kidney (5/6 nephrectomy). Five-sixths nephrectomy was followed by significant increases in serum creatinine (to 0.55 +/- 0.03 mg/dl) and urea nitrogen (to 42.9 +/- 3.8 mg/dl). There was a concomitant increase in mean blood pressure, measured directly by an implanted aortic catheter, in comparison with control rats (155.3 +/- 8.3 versus 123.6 +/- 3.3 mmHg, P less than 0.01). Both plasma levels and urinary excretion of norepinephrine and epinephrine were elevated in the 5/6-nephrectomized rats compared with controls. Mean blood pressure correlated negatively with 24-h creatinine clearance (r = -0.66, P less than 0.05), and positively with plasma norepinephrine (r = 0.83, P less than 0.01) and urinary excretion of norepinephrine (r = 0.63, P less than 0.05). These results suggest that not only the decrease in renal function, but also hyperactivity of the sympathetic nervous system, may be involved in the pathogenesis of hypertension in rats with subtotal renal ablation.

Alteration of vascular thromboxane in rats with subtotal renal ablation.

To assess the roles of vascular prostaglandins in the hypertension of chronic renal failure, the release of prostacyclin and thromboxane (TX) from aorta was evaluated in male Sprague-Dawley rats, the renal mass of which was reduced by removing one kidney and two-thirds of the contralateral kidney ("5/6 nephrectomy"). Five-sixths nephrectomy was followed by significant rises in serum creatinine to 0.55 +/- 0.03 mg/dl and urea nitrogen to 42.9 +/- 3.8 mg/dl, with a concomitant rise in mean blood pressure from 121.6 +/- 1.6 mmHg to 155.3 +/- 8.4 mmHg. In 5/6 nephrectomized rats, the release of TX A2 from aorta, as measured by its stable metabolite TX B2, increased by 60% (p less than 0.01) and prostacyclin, as measured by its stable metabolite 6-keto-prostaglandin, F1 alpha (6-keto-PG F1 alpha) increased by 51% (p less than 0.05). The amounts of both TX B2 and 6-keto-PG F1 alpha released from aorta were closely related to the height of mean blood pressure. These results suggest that the enhanced vasoconstrictor TX production in the vascular walls may be relevant to hypertension in rats with subtotal renal ablation. The adaptive increase in prostacyclin production in the vascular walls may compensate for the elevation of blood pressure due to chronic renal failure in this animal model.

Dosage regimen of ranitidine in patients with renal impairment.

The validity of the Giusti-Hayton method for dosage regimen adjustment in patients with renal impairment was investigated using ranitidine. Five normal healthy volunteers received a single ranitidine recommended dose of 150 mg, and 20 patients with renal disease received single administration in doses individually calculated by the Giusti-Hayton method from each patient's creatinine clearance level, and the various pharmacokinetic parameters were compared. As a result, the area under the time-concentration curve 0----infinity (AUC0----infinity) in the renal disease patients was almost comparable to that in the normal healthy volunteers. The Giusti-Hayton method was considered useful to keep both the AUC0----infinity constant and the mean blood level of the drug in a steady state, in any degree of renal impairment.

Hemolytic-uremic syndrome in an adult.

This report describes a 45-year-old man who suffered from hemolytic-uremic syndrome. In his autopsy findings, kidney arteriolar walls showed marked hyaline degeneration and interlobular arteries were occluded by severe intimal proliferation. No vascular changes were found in other organs. There were no arteriosclerotic changes in either main branches from the aorta or the aorta. These vascular changes are correspond well with the early features of malignant nephrosclerosis without any clinical findings of malignant hypertension. This type is called primary malignant nephrosclerosis by Bohle et al. We would like to point out the significance of this case in the re-consideration of the pathogenesis of malignant nephrosclerosis.

Renovascular hypertension due to Buerger's disease.

In a 42-year-old man with severe hypertension, stenosis of the left renal artery at its origin and occlusion of the abdominal aorta below the level of the renal arteries were observed. His past history and clinical and laboratory findings suggested that the renal artery stenosis was due to Buerger's disease which was reported to be a rare cause of renovascular hypertension.

Effect of sodium restriction on platelet function in patients with essential hypertension.

The effects of sodium intake on blood pressure and platelet function were evaluated in 19 subjects with essential hypertension (10 men and 9 women; mean age 49.7 years). The study was conducted under 3 conditions: (1) normal sodium diet (12 g/day of salt was used in cooking), (2) after 5 days of mild sodium restriction diet (6 g/day of salt was used in cooking) and (3) after moderate sodium restriction (no salt was used in cooking). Blood pressure was significantly reduced following sodium restriction without any change in heart rate. The ratio of the plasma level of beta-thromboglobulin to platelet factor IV, regarded as the most reliable index for platelet activation in vivo, increased significantly after mild sodium restriction; this change was maintained after moderate sodium restriction. Plasma thromboxane B2, a stable metabolite of thromboxane A2, increased significantly after sodium restriction; the level of 6-ketoprostaglandin F1 alpha, a stable metabolite of prostacyclin, was unaffected. These results indicate that dietary sodium restriction induces both a reduction of blood pressure and an activation of platelet function in vivo. Thus, one must consider both antihypertensive effects and effects on platelet function as factors in adjusting the dietary sodium intake in the course of antihypertensive therapy.

Identification of puberty-accelerating pheromones in male mouse urine.

Gas chromatography-mass spectrometry was employed to identify the two volatile amines in male mouse urine. These amines were much less concentrated in urine of castrated males. The identified amines, isobutylamine and isoamylamine, were assayed for the potential of puberty acceleration in postweaning female mice. A total of 105 young female mice were exposed to one of the following five odors: distilled water (control), 0.1 M isobutylamine, 0.1 M isoamylamine, a mixture of 0.05 M isobutylamine and 0.05 M isoamylamine, or fresh male mouse urine. The mixture of these amines accelerated the vaginal opening of young females. Except for the control, all experimental odors accelerated the first vaginal estrus in ICR strain mice.

Captopril, an angiotensin I-converting enzyme inhibitor, decreases proteinuria in hypertensive patients with renal diseases.

A crossover study was planned in order to compare the effects of captopril and slow channel calcium entry blocker (Ca antagonist) on urinary protein excretion in 7 hypertensive patients with renal diseases, including 4 with IgA nephropathy, 2 with lupus nephritis and 1 with benign nephrosclerosis. Captopril decreased urinary protein excretion by 52% without any change in creatinine clearance, while Ca antagonist was having a slight effect on proteinuria even though the drug showed an equivalent antihypertensive effect as captopril. These results suggest that the attenuation of proteinuria induced by captopril may be related to an inhibition of angiotensin II formation and/or a direct action of this drug on protein permeability of glomerular basement membrane.