Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa

To investigate the role of increased seminal leukocytes in enhancing reactive oxygen species (ROS) production by human spermatozoa.A prospective study.Male infertility clinic.Forty-eight infertile men.Standard semen analysis. Assessment of sperm nuclear DNA damage by sperm chromatin structure assay. Incubation of spermatozoa from nonleukocytospermic samples with blood neutrophils.Spontaneous and phorbol 12-myristate 13-acetate (PMA)-induced ROS production in pure-sperm suspensions (after removal of leukocytes) as measured by a chemiluminescence assay.Levels of spontaneous and PMA-induced ROS production in pure-sperm suspensions from the infertile men with a diagnosis of leukocytospermia (n = 16) were significantly higher compared with the case of infertile men without leukocytospermia (n = 32) and with the case of a control group of healthy volunteers (n = 13). A similar pattern of increased ROS was observed when spermatozoa were incubated with blood neutrophils. Leukocytospermia was associated with a significant decrease in sperm motility and increase in DNA damage.Increased seminal leukocytes may play a role in stimulating ROS production by human spermatozoa. Such stimulation may be mediated via direct cell-cell contact or by soluble products released by leukocytes. Poor sperm quality in leukocytospermic samples may be due to leukocyte-mediated oxidative stress.     

Effects of whole blood, crystalloid, and colloid resuscitation of hemorrhagic shock on renal damage in rats: an ultrastructural study

Purpose:

The aim of this study was to determine the effects of whole blood, crystalloid, and colloid treatment on histopathologic damage of kidney induced by hemorrhagic shock in rats.

Methods:

Fifty-six male Sprague Dawley rats were divided into 8 groups. The carotid artery was cannulated, and systolic arterial pressure (SAP), diastolic arterial pressure (DAP), heart rate (HR), and rectal temperature (RT) were observed during the procedure. The jugular vein also was cannulated, and the SAP was decreased by aspiration of 75% of blood through the jugular vein in the control (nonresuscitated) and study (resuscitated) groups, whereas blood was not diminished in the sham group. The hemorrhagic shock was permitted to last 45 minutes; then, the study group rats were resuscitated with heparinized shed autologous whole blood (WB), normal saline (NS), Lactated Ringer’s solution (LR), hydroxyethyl starch 6% (HES6), hydroxyethyl starch 10% (HES10), or dextran 40 (D40). Histopathologic evaluation was performed under light and electron microscope.

Results:

The RT, SAP, and DAP decreased, and HR increased significantly in the control and study groups during the shock period compared with those of sham group. After volume resuscitation, these parameters changed to preshock levels. Electron and light microscopic examinations of kidneys showed severe proximal tubular degeneration with moderate glomerular damage in the control group; moderate proximal tubular degeneration with mild glomerular damage in the NS, LR, HES6, and HES10 groups; and mild proximal tubular degeneration with no evidence of glomerular damage in the WB and D-40 groups.

Conclusions:

The characteristic ultrastructural features of hemorrhagic shock appear to be severe tubular degeneration and mild to moderate changes in glomeruli. Resuscitation of hemorrhagic shock with whole blood or dextran 40 solution appears to be most favorable therapy in preventing ultrastructural renal damage in rats.     

Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer

OBJECTIVE: In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. METHODS: A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. RESULTS: An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. CONCLUSIONS: We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.     

Prognostic significance of microvessel density and vascular endothelial growth factor (VEGF) expression in non-Hodgkin's lymphoma

Angiogenesis has a major role in the pathogenesis of malignancies. Studies involving the role of angiogenesis have been most commonly performed in solid tumors. However, studies related to hemapoietic neoplasia and angiogenesis are relatively limited. We investigated the role of angiogenesis in non-Hodgkin's lymphomas (NHLs) and its relation with clinical and histopathologic prognostic indicators. In this respect, angiogenesis markers were evaluated in 71 patients with NHL and these were compared with other prognostic indicators including age, gender, histological grade, stage, extranodal involvement and survival. Microvessel density (MVD) using Factor VIII monoclonal antibody and vascular endothelial growth factor (VEGF) using monoclonal antibody for VEGF expression were studied in paraffin-embedded tissue samples. We did not find a significant relationship between MVD and patient characteristics including age, gender, stage, histological grade, nodal status, international prognostic index (IPI), and response to treatment. MVD was found to be greater in cases with B symptoms compared to those without B symptoms (14.6±5.7 and 11.4±5.3, respectively, p=0.002). No significant relationship was found between VEGF and age, gender, stage, histological grade, IPI, and overall survival. The complete and partial response rate to therapy was significantly higher in VEGF-negative patients than in the VEGF-positive patients (p=0.003). In conclusion, there appears to be a role for angiogenesis and angiogenic factors in NHLs. The combination of anti-angiogenic drugs with conventional anti-neoplastic treatment will probably be used in the future. Larger series of patients are needed to determine the prognostic value of angiogenesis in NHL.     

Effect of Weight Loss on Bone Metabolism: Comparison of Vertical Banded Gastroplasty and Medical Intervention

Background: We studied the effects of weight loss on bone metabolism. Methods: 16 consecutive surgically-treated (14 female, 2 male) morbidly obese patients and 65 obese (53 male, 12 female) medically-treated patients were enrolled in an observational study. Surgical treatment for morbidly obese patients was vertical banded gastroplasty (VBG). Studies were performed prior to and 12 months after the start of treatment. Bone mineral density (BMD), bone turnover markers, sex steroids, calcium excretion and parathyroid hormone measurements were done at each visit. Results: Weight loss was more prominent with surgical than with medical treatments. Bone loss was also pronounced in the surgical treatment group, and occurred at the hip level only (P<0.05). Compared to previously reported studies, where the effects of malabsorptive treatments for obesity on bone metabolism were studied, calcium excretion and parathyroid hormone levels did not change after VBG or medical therapy. For both groups, bone markers indicated an increased bone turnover, evidenced by increased urinary excretion of deoxypyridinoline and serum levels of osteocalcin (P<0.05). Sex steroid measurements revealed a decrease in estradiol levels in the surgical treatment group, but not in medical treatment group. This finding was thought to be secondary to less weight loss in the medical group. Conclusion: Our data indicate that weight loss causes bone loss. The bone loss is independent of the method of weight reduction. However, the mechanism of the bone loss is not clear. It may be explained partly by reduced estradiol levels in female patients. Because the mechanisms of bone disease after weight loss remain unclear, it is difficult to determine the most effective treatment. It is important to detect osteopenia early, before fractures occur. Measuring BMD appears to be the only reliable method for screening.     

Phenyramidol-associated liver toxicity

OBJECTIVE: To describe a case of hepatotoxicity associated with phenyramidol use that resolved after discontinuation of the drug. BACKGROUND: Phenyramidol is a moderately potent and relatively nontoxic analgesic with concomitant muscle-relaxant activity. A MEDLINE search in June 2003 revealed no reports associating hepatotoxicity with this agent. CASE SUMMARY: A 70-year-old man was investigated because of elevated liver function test values on routine biochemical screening. He had no clinical symptoms. Other etiologies of hepatitis were appropriately ruled out, and elevated enzymes were ascribed to phenyramidol treatment. DISCUSSION: This is the first case published in the English language literature describing probable hepatotoxicity, according to the Naranjo probability scale, resulting from use of phenyramidol. The mechanism of phenyramidol-induced liver damage is unknown. Several features, such as the absence of predictable dose-dependent toxicity of phenyramidol in previous studies and the absence of hypersensitivity manifestations in our patient, are suggestive of a metabolic type of idiosyncratic toxicity. CONCLUSIONS: Phenyramidol should be considered as a drug that possibly causes hepatotoxicity.