Comparison of high and low dose of cyclophosphamide in lupus nephritis patients: a long-term randomized controlled trial.

To evaluate the outcome of low doses of cyclophosphamide (Cyclo) therapy in lupus nephritis (LN) patients, we studied 117 biopsy-proven, de novo LN WHO class IV patients double-blinded and randomized in December 1997 to receive Cyclo in different doses; Group I (n=73) received Cyclo 10 mg/kg monthly for six months then every two months for 12 months. Group II (n=44) received Cyclo 5 mg/kg monthly for six months then every two months for 36 months. The patients were followed-up till January 2007. Six months post-induction values for creatinine clearance were significantly higher in Group I (67.7 ± 28.6 mL/min) compared with Group II (55.1 ± 30.1 mL/min), P = 0.026. Serum C4 and ANA were not significantly different between the groups (P > 0.05). At the mean follow-up of 6.77 ± 3.3 years, the mean creatinine clearance was 44.74 ± 31.7 mL/min in Group I vs. 49.3 ± 38.8 in Group II. Urinary protein was 1.65 ± 1.8 g/dL in Group I vs. 1.02 ± 1.01 in Group II (P = 0.03). The survival curve showed that kidney survival overtime was comparable in both groups (P = 0.2). Complete remission was observed in 25 (34.2%) patients in Group I vs. 11 (25%) in Group II (P = 0.288), while partial remission was similar in both groups; 43 (58.9%) patients in Group I vs. 26 (59%) patients in Group II. End-stage renal disease was observed in 10 (13.7%) patients in Group I vs. 9 (20.4%) patients in Group II (P = 0.359). Side-effects were more frequent in Group I patients than in Group II patients; gonadal toxicity and malignancy were lower in Group II patients (P = 0.0000). Moreover, different infections occurred in 23 (31.3%) patients vs. six (13.6%), digital infarcts occurred in 1.35% vs. 0%, diabetes in 4.1% vs. 2.27%, and vasculitis in 4.1% vs. 2.27% in Group I vs. Group II, respectively. Sustained amenorrhea without pregnancy was observed in both groups; however, significantly more in Group I patients, P ≤ 0.05. We conclude that low-dose Cyclo therapy is sufficiently effective for WHO class IV LN patients with lower side-effects compared with standard dose.

Effect of cement dust exposure on phagocytic function of polymorphonuclear neutrophils in cement mill workers.

OBJECTIVES: Exposure to cement dust can cause various occupational health problems due to its increasing incidence and long-term complications. However, the influence of cement dust on phagocytic function of polymorphonuclear neutrophils (PMNs), has not as yet been investigated. Therefore, the aim of the study was to measure the phagocytic activity of PMNs by assessing chemilumiscence (CL) response in cement mill workers and controls. MATERIAL AND METHODS: In this study, 50 volunteer males, aged 25-60 years, apparently healthy and nonsmoking, were randomly selected from among cement mill workers. These workers were further classified into subgroups based on exposure duration of less than 10, 10-20, and more than 20 years. The controls were 50 healthy, nonsmoking, males who matched the study group with respect to age, height, weight, and socioeconomic status. The phagocytic function of PMNs, stimulated with opsonized zymosan, was determined by measuring CL response. RESULTS: The findings show a significant decrease in phagocytic activity of PMNs [PMNs OPZ p < 0.005] in cement mill workers compared to controls. CONCLUSION: It is concluded that exposure to cement dust can impair the phagocytic function of PMNs which is reflected in decreased chemiluminescence response.

Chronic granulomatous disease with recurrent hepatic abscesses in an adult.

Chronic granulomatous disease CGD is a condition of inability to deal with bacterial and fungal infections, due to defective respiratory burst in neutrophils leading to recurrent cutaneous and visceral infections. Usually a disease of childhood, but patients nowadays survive to adulthood, and diagnosis might be difficult if not considered. We describe a 20-year-old female with previously undiagnosed CGD, presenting with recurrent cutaneous and hepatic abscesses.

Subclinical autonomic neuropathy in Saudi type 2 diabetic patients.

OBJECTIVE: To compare the results of autonomic function tests obtained from diabetic patients who had no symptoms or signs of somatic or autonomic neuropathy with those obtained from control subjects. METHODS: We studied 32 diabetic Saudi patients (17 males, 15 females) and 34 control subjects (17 of either gender) at King Khalid University Hospital, Riyadh, in the period 2004-2005. The mean age of patients was 50.3+/-5.04, and of controls was 49.9+/-5.86 years. In diabetics, the mean duration of the disease was 8.7+/-3.1 years (range 5-15 years), and the mean glycated hemoglobin was 7.76 +/-1.14. The same observer performed the autonomic function tests. RESULTS: In diabetics, the resting heart rate (beats/min) was 80.5+/-4.13, mean orthostasis ratio was 1.06+/-0.035, mean Valsalva ratio was 1.19+/-0.036, mean forced sinus arrhythmia was 12.66+/-0.8 beats/min, mean diastolic blood pressure increase in response to isometric exercise was 13.03+/-1.36 mm Hg, and sympathetic skin response was present in only 18 (56.3%) out of 32 patients. These results were significantly different from the control group (p<0.001). CONCLUSION: Diabetic patients, with no symptoms or signs of neuropathy, can have impaired autonomic function. We consider this subclinical autonomic neuropathy.

Hazards of X-ray radiation on the quantitative and phagocytic functions of polymorphonuclear neutrophils in X-ray technicians.

Over exposure to X-ray radiation is detrimental to the living cells and may lead to development of life-threatening diseases. It is intuitive to postulate that a low level exposure may lead to functional abnormalities in human immune cells. Therefore, the objective of the present study was to study the effects of X-ray radiation on the total leukocyte count (TLC) and phagocytic activity of Polymorphonuclear neutrophils (PMN). A group of 42 apparently healthy X-ray technicians were recruited with age ranging from 25-50 years. They were matched with another group of 42 control healthy volunteer subjects in terms of age, sex and ethnic variation. The mean exposure level of X-ray radiation in X-ray technicians was 72.4 mrem per calendar quarter and 289.6 mrem per year. TLC was performed by using a Beckman Coulter counter and phagocytic activity of whole blood and PMN was determined by measuring chemiluminescence (CL) response with a chemiluminescence luminometer. The mean value of CL response was significantly decreased (p<0.0005) in X-ray technicians, even though they had low levels of exposure, compared to their controls. However, no significant difference was observed in TLC between the two groups at this low level of exposure. Exposure to X-ray radiation decreases the physiological functions of PMN as measured by decreasing chemiluminescence response even at low levels of exposure.

The effect of vitamin E, L-arginine, N-nitro L-arginine methyl ester and forskolin on endocrine and metabolic changes of rats exposed to acute cold stress.

OBJECTIVE: It is a well documented fact that under stress conditions the hypothalamic-pituitary-adrenal axis (HPA) and the sympathetic nervous system (SNS) are stimulated. This results in a series of neural and endocrine adaptations known as the stress response. The current study assessed the effects of acute cold stress on adrenomedullin (ADM) levels in plasma and peripheral tissues (kidneys and heart) of rats, as well as on blood glucose, cholesterol, triglycerides (TG), total proteins both before and after intraperitoneal administration of each of the following: vitamin-E, L-arginine, forskolin and L-NAME. METHODS: The current study was conducted in the Department of Physiology, Faculty of Medicine, King Saud University, Saudi Arabia, between September 2003 and March 2004. We observed 6 groups of Wistar rats for their plasma ADM, tissue plasminogen activator (t-PA), total protein, glucose and cholesterol levels. Following exposure to cold stress (-10 degree C for 3 hours). RESULTS: Acute cold stress produced a significant increase in ADM levels in plasma, heart and kidney tissues of rats. Furthermore, acute cold stress produced a reduction in cholesterol and plasma protein levels. On the other hand, acute cold stress caused an increase in TG, glucose plasma levels and tissue plasminogen activator (t-PA). We found hormonal and metabolic changes caused by cold exposure to be decreased or even prevented after vitamin E treatment or after changing nitric oxide (NO) level by L-arginine or L-NAME treatment. CONCLUSION: The results suggest a regulatory or protective role for ADM in counteracting HPA activation following a variety of physiological and psychological stressors. Oxidative stress or changes in intracellular signals as NO, cyclic-AMP may play a role in explaining some of the metabolic and hormonal changes occurring during acute cold stress.

Effect of diclofenac alone or in combination with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes in healthy and osteoarthritic individuals.

OBJECTIVE: To investigate the effects of diclofenac alone or when combined with alpha-tocopherol on the oxidative activity of polymorphonuclear leukocytes (PMNs) in healthy and osteoarthritic (OA) patients. METHODS: The study was carried out at the College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia, over the period 1999 to 2000. Twelve healthy controls and 12 osteoarthritic patients were recruited to the study. Twelve healthy controls and osteoarthritic patients were given diclofenac 50 mg thrice daily orally, initially for 5 days then alpha-tocopherol at 200 mg thrice daily orally, was added for another 5 days. Blood samples were drawn before the start of the study (pre-treatment) and at 5 days following treatment with diclofenac alone and 10 days following treatment with diclofenac and alpha-tocopherol. Chemiluminescence (CL) response was measured for whole blood and isolated polymorphonuclear leukocytes (PMNs) on all samples. RESULTS: Diclofenac enhanced CL response of whole blood and of PMNs of healthy controls when stimulated with phorbol myristate acetate (PMA) and opsonized zymosan (OPZ). Co-treatment with alpha-tocopherol resulted in no appreciable change in the CL response of whole blood when stimulated with PMA or OPZ but a further significant enhancement of CL response of isolated PMNs when these cells were stimulated by either PMA or OPZ. In osteoarthritic patients, diclofenac alone and when combined with alpha-tocopherol showed no significant change in CL response of whole blood. The CL response of PMNs from OA patients was decreased by diclofenac alone. However, this inhibitory effect was not observed when alpha-tocopherol was used together with diclofenac. CONCLUSION: The effect of diclofenac alone or in combination with alpha-tocopherol did not produce a consistent effect on the CL response of whole blood or isolated PMNs of healthy or osteoarthritic patients.

Effect of alpha-tocopherol on glucose uptake and contractility in rat skeletal muscle.

BACKGROUND: Free radicals and associated oxidative stress play an important role in the causation and subsequent complications of diabetes mellitus. Type I diabetes can be induced in experimental animals by administration of streptozotocin which causes selective destruction of B islet cells, probably by a free radical mediated mechanism. The objective of this study was to determine the effect of administration of alpha-tocopherol two weeks before and two weeks after streptozotocin injection on contractility and glucose uptake of rat hemidiaphragm. MATERIAL/METHODS: Male Wistar rats were used for this experiment. In the first phase, all the rats received an ordinary diet, while some were given alpha-tocopherol; in the second phase, diabetes was induced with streptozotocin, while the animals in the experimental group were given alpha-tocopherol two weeks before and two weeks after diabetes induction. RESULTS: Streptozotocin decreased the height of the indirect contraction and the time for 50% decrease in height of contraction of indirect responses. At the same time, the glucose uptake of the diaphragm muscle was also decreased. Administration of alpha-tocopherol (600 mg/kg-1, i.m.) ameliorated the inhibitory effect of diabetes on the skeletal muscle and reversed the decrease in time (s) of the 50% decrease in the height of contraction of the indirect responses of the rat hemidiaphragm preparation. Additionally, alpha-tocopherol increased glucose uptake by diaphragm muscles towards control level. CONCLUSIONS: Alpha-tocopherol supplementation probably protected against the inhibitory effect of oxidative stress observed in diabetes mellitus and contributed to improved contractility.