Cigarette smoking and the risk of male factor subfertility: minor association between cotinine in seminal plasma and semen morphology.

OBJECTIVE: To evaluate the impact of cigarette smoking on male factor subfertility and the semen parameters of sperm count, motility, and morphology by questionnaire and determination of the cotinine concentrations in blood and seminal plasma of fertile and subfertile males. DESIGN: Case-control study of 107 fertile and 103 subfertile males who provided a standardized blood and semen specimen and completed a self-administered questionnaire about their smoking habits. SETTING: Outpatient fertility clinic of the University Medical Centre St. Radboud, Nijmegen, The Netherlands. PATIENT(S): One hundred seven fertile and 103 subfertile males. INTERVENTION(S): Vena puncture and semen collection. MAIN OUTCOME MEASURE(S): Blood and seminal plasma cotinine levels in relation to semen parameters. RESULT(S): A higher frequency of cigarette smoking was observed in subfertile males than in fertile males, with an odds ratio of 1.7 (95% confidence interval, 0.9-3.2). The self-reported number of cigarettes smoked per day correlated with the cotinine concentrations in blood and seminal plasma for both groups. A small but statistically significant correlation was found between cotinine concentrations in seminal plasma and the percentage of abnormal sperm morphology, but not for other semen parameters (r(s) = 0.19). CONCLUSION(S): Although the mechanism of the toxicity of cotinine on sperm morphology is not clear, this study indicates only a minor effect of cigarette smoking on male factor subfertility, which is probably due to compounds in cigarette smoke other than nicotine (cotinine).

A prognostic index as diagnostic strategy in children suspected of mitochondriocytopathy.

The aim of this study was to assess an optimal screening for paediatric patients suspected of mitochondriocytopathy to justify a muscle biopsy. Forty-five patients were included. Medical history, physical examination, cardiac and ophthalmologic evaluation, clinical chemical investigations, in vivo function tests, neuroimaging and a skeletal muscle biopsy were performed in all patients. The results of the biochemical muscle studies were compared with the results of the other investigations. First, parameters with a statistical relationship with the result in muscle, normal or deficient, were selected. Secondly, a prognostic index was constructed using these parameters. Five parameters were selected: age <4 years, elevated fasting lactate to pyruvate ratio, elevated thrombocyte count, elevated lactate, and elevated alanine. Each parameter was scored 0 (not present) or 1 (present). The chance of a normal biopsy with a given value of this index (sum of the scores) was calculated: logit (Pr) = alpha + beta x index; alpha: -0.8167 and beta: 0.8331. (Pr: probability of normal biopsy.) The chance of a normal biopsy with an index value of 5 is 0.03, 4 is 0.07, 3 is 0.16, 2 is 0.30, 1 is 0.50 and 0 is 0.69. This prognostic index is a valuable instrument in deciding whether the suspicion of mitochondriocytopathy is strong enough to merit a muscle biopsy.

Sexual dysfunction after renal replacement therapy.

The existence of a sexual problem as the subjective evaluation of sexual function was assessed with a simple questionnaire. Those questioned were patients undergoing dialysis treatment (n = 400) or with a functioning renal transplant (RTx; n = 300) and both men and women in the general Dutch population (n = 591). In the Dutch control population, 8.7% of the men and 14.9% of the women reported a sexual problem, showing a significant gender difference but unrelated to age. In patients, the prevalence of a sexual problem was significantly greater (hemodialysis, men, 62.9%; women, 75.0%; peritoneal dialysis, men, 69.8%; women, 66.7%; renal transplantation, men, 48.3%; women, 44.4%). In RTx recipients, sexual problems were significantly less prevalent than in patients undergoing dialysis (P < 0.001). Only in male patients was an association between prevalence of a sexual problem and age found. The results of the simple questionnaire were sufficiently validated when 102 of 104 patients confirmed their responses in a subsequent structured interview. This study shows that the prevalence of sexual problems in patients undergoing renal replacement therapy is high and clinically relevant.

Cerebrospinal fluid C3 and C4 indexes in immunological disorders of the central nervous system.

OBJECTIVES: Validation of cerebrospinal fluid (CSF) indexes as a measure for intrathecal C3 and C4 production. Examination of their role in differential diagnosis of immunological disorders of the central nervous system (CNS). MATERIAL AND METHODS: Correlative study in controls (low back pain without disk herniation) between the CSF/serum ratio (Q) for albumin, and Q C3 and Q C4. Comparative study of C3 and C4 indexes in patients with CNS dysfunction due to relapsing-remitting (RR) multiple sclerosis (MS), secondary progressive (SP) MS, systemic lupus erythematosus (SLE), and human immunodeficiency virus (HIV) infection. RESULTS: Strong and statistically highly significant correlations between Q albumin and Q C3 (r=0.89, P=0.0001), and Q C4 (r=0.68, P= 0.0001). In MS patients decreased mean values for serum (RR, SP) and CSF (RR) C3, and increased C3 index mean value (RR, SP). In CNS SLE increase of mean C3 and C4 index values. In CNS HIV increase of mean C3 and C4 index values, and CSF C3 and C4 concentrations. Most individual index values were within the reference range. CONCLUSION: CSF index is a valid tool to detect intrathecal C3 or C4 production. C3 or C4 index contributes little to the differential diagnosis of immunological CNS disorders. C3 might play a pathogenic role in various immunological CNS disorders.

Treatment for extended-mid and distal ureteral stones: SWL or ureteroscopy? Results of a multicenter study.

PURPOSE: In a randomized study, we analyzed the treatment results of ureterorenoscopy (URS) and shockwave lithotripsy (SWL) for extended-mid and distal ureteral stones. We investigated also, for reasons of cost effectiveness, the factors influencing the outcome, the complications, and the need for auxiliary procedures. PATIENTS AND METHODS: In three regional hospitals, we selected 156 patients with extended-mid and distal ureteral stones. After randomization, 87 were treated with URS, and 69 with SWL. The treatment results were studied in relation to complications, the need for auxiliary procedures and stone factors, urinary tract infection (UTI), dilatation, and kidney function. RESULTS: After retreatment of 45% of the patients, the stone-free rate after 12 weeks in the SWL group was 51%. After a retreatment rate of 9% of the patients in the URS group, the stone-free rate was 91%. Including the number of auxiliary procedures, we calculated the Efficiency Quotient (EQ) as 0.50 for SWL and 0.38 for URS. After correction and redefinition of auxiliary procedures, the EQ was 0.66. The mean treatment time for SWL was 52 minutes and for URS 39 minutes. General anesthesia was more frequently needed in URS patients. Complications occurred more often in the URS group (22 v 3 and 24 v 13, respectively). These were mostly mild, and all could be treated with a double-J stent, antibiotics, or analgetics. A lower stone-free rate was achieved in patients with larger (> or =11 mm) stones (75% v 85% for smaller stones in the URS group and 17% v 73% in the SWL group. In the URS group, the stone-free rate of patients with extended-mid ureteral stones was lower than that of patients with distal ureteral stones. Calculating the costs for URS and SWL appeared impossible because of the differences in available equipment. CONCLUSION: The stone-free rate after URS is much higher than after SWL, and the EQ in our series was strongly dependent on definitions. The decision about how to treat a patient with an extended-mid or distal ureteral stone therefore should not be made primarily on the basis of cost effectiveness but rather on the basis of the availability of proper equipment, the experience of the urologist, and the preference of the patient.

Composite cerebrospinal fluid score in relapsing-remitting and secondary progressive multiple sclerosis.

We investigated whether cerebrospinal fluid (CSF) analysis may differentiate between relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS). In 17 RR and 16 SP patients we determined: albumine CSF/PB ratio; mononuclear cell (MNC) number, CD4+, CD8+, and B1+ subsets, CD4+/CD8+ ratio; IgG, IgG index, IgM, IgM index, complement components C3 and C4, and C3 and C4 indexes; myelin basic protein; neuron-specific enolase (NSE); S100; and lactate. For each parameter the statistical distance was calculated. Then, using linear discriminant analysis, we computed a discriminant score, including only variables with a P value less than or equal to 0.15: albumin CSF/PB ratio, MNC number, IgM, IgM index, C3, C4, NSE, S100, and lactate. The discriminant score allocated all 17 RR patients to the RR group and 15 of 16 SP patients to the SP group. We conclude that RR and SP MS patients differ with respect to CSF profile and that in individual patients a composite CSF score may differentiate between RR and SP MS.

Influence of decay of laser fibers during laser prostatectomy on clinical results.

Three types of sidefiring laser fibers (34 Urolase, 20 Ultraline, and 114 Prolase II) were visually inspected after a laser prostatectomy, and transmission measurements were performed using a power meter (Aquarius). The results were correlated with the clinical outcome. Despite differences in the amount of loss in transmission for the fibers used, we could not establish any significant effect on clinical outcome measures, such as improvement in maximal flow rate or symptom score. The visual aspect of the Urolase fibers was significantly related to the amount of transmission loss, whereas no such relation was found for the other two types of fibers. Prostate size and the total amount of energy delivered by the laser source also did not correlate with the clinical outcome. To determine the relation between the energy absorbed by the prostate and clinical outcome, a large number of patients must be evaluated, and any factor that can be controlled needs to be monitored. For the latter, the power meter as presented here is a useful complementary tool.

Cerebrospinal fluid analysis differentiates between relapsing-remitting and secondary progressive multiple sclerosis.

OBJECTIVES: To find whether CSF analysis may differentiate between relapsing-remitting and secondary progressive multiple sclerosis. METHODS: In 17 patients with relapsing-remitting and 16 patients with secondary progressive multiple sclerosis, all without current or recent relapses, albumin CSF: peripheral blood ratio, mononuclear cell number, CD4+, CD8+, and B1+ subsets, CD4+:CD8+ ratio, IgG, IgG index, IgM, IgM index, complement components C3 and C4, and C3 and C4 indices, myelin basic protein, neuron specific enolase, S100, and lactate were determined. For each measure the statistical distance measure D2 was calculated. For computation of a discriminant score variables with a P value< or =0.15 were included (two sided univariate t test). These were albumin CSF: peripheral blood ratio, mononuclear cell number, IgM, IgM index, C3, C4, neuron specific enolase, S100, and lactate. Simultaneous distributions of the variables were compared between both groups (multivariate t test) and a discriminant score was computed (linear discriminant analysis). RESULTS: The discriminant score allocated all 14 relapsing-remitting patients to the relapsing-remitting group (positive score) and 12 of 13 secondary progressive patients to the secondary progressive group (negative score). One secondary progressive patient was allocated to the relapsing-remitting group. CONCLUSIONS: Patients with relapsing-remitting or secondary progressive multiple sclerosis differ in CSF profile and CSF analysis may help to differentiate between relapsing-remitting and secondary progressive multiple sclerosis.

A randomized study on the effects of intramuscular injections with urinary gonadotrophins (Humegon or Pergonal) on pain, local redness and fever in infertile women opting for in-vitro fertilization.

The objective of this open, multicentre, randomized controlled study in women opting for in-vitro fertilization was to compare the occurrence of pain and redness at the injection site and of post-injection fever after i.m. injection with Humegon (n = 89) or Pergonal (n = 92). Assessments were scoring of pain and redness at the injection site and of post-injection fever during the next 24 h using self-administered questionnaires. Injection site pain was reported in 48.9% of injections with Humegon and in 44.9% with Pergonal (P = 0.45). A trend was seen towards more redness after Pergonal injection (24.0 versus 15.5%; P = 0.08). Post-injection fever was reported in 1.4% with Humegon and in 1.1% with Pergonal (P = 0.80). It was concluded that there are no statistically significant differences between Humegon and Pergonal after i.m. injection with respect to the prevalence of pain and redness at the injection site and of post-injection fever.

The effect of ethyldeshydroxy-sparsomycin and cisplatin on the intracellular glutathione level and glutathione S-transferase activity.

Ethyldeshydroxy-sparsomycin (EdSm) is a ribosomal protein synthesis inhibitor which synergistically enhances the antitumor activity of cisplatin against L1210 leukemia in vivo. Because cellular glutathione (GSH) and glutathione S-transferases (GST) are reported to interfere with the antitumor activity of cisplatin, we analyzed the effect of EdSm and cisplatin on GSH and GST activity in selected tumor cells. For this purpose we used three murine leukemia tumors with different sensitivities towards EdSm and cisplatin: L1210-WT, sensitive to both drugs, L1210-Sm, resistant to EdSm, and L1210-CDDP, resistant to cisplatin. No significant differences were detectable between these three cell lines regarding the population doubling time, the cell size, and the cellular level of protein and glutathione. Neither of the resistant L1210 subclones showed P-glycoprotein expression. Drug exposure, however, changed the intracellular dynamics. Exposure to EdSm strongly decreased the amount of cellular protein, decreased the overall GST activity and led to GSH depletion, whereas exposure to cisplatin induced a rise in the amount of protein, in GSH, and in the total GST activity. These effects are dose-dependent and correlate well with the sensitivity of the tumor cells for EdSm or cisplatin. In addition, exposure to EdSm lowered the V(max) of GST in L1210-WT and L1210-Sm; however, in L1210-CDDP both the V(max) and the K(m) were increased. That this was not a direct effect of EdSm on GST was shown in a cell-free system, where EdSm did not influence the GST activity nor could it act as a substrate for GST. Our results suggest that the synergistic combination of EdSm and cisplatin might be explained by EdSm switching off the cellular detoxification mechanism for cisplatin, i.e. by inhibition of de novo synthesis and subsequent depletion of GSH and GST.

Incidence and effect on survival of abdominal wall metastases at trocar or puncture sites following laparoscopy or paracentesis in women with ovarian cancer.

The aim of this retrospective study was to examine the incidence and prognostic significance of abdominal wall metastases in patients with ovarian cancer present at the primary debulking at the entry sites of previous laparoscopy or paracentesis. The clinical records of 219 patients were studied. In 7 of 43 patients (16%) who had undergone laparoscopy and 3 of 30 patients (10%) who had undergone paracentesis previous to the primary debulking, an abdominal wall metastasis had developed at the entry sites. All metastases occurred in patients with FIGO stage IIIC-IV including ascites. Survival analysis using the Cox proportional hazards model showed that after adjustment for age, FIGO stage, histology, grade, ascites, and residual disease after primary debulking, the presence of abdominal wall metastases in the entry sites of previous laparoscopy or paracentesis was negatively, although not statistical significantly, correlated with survival (P = 0.14).

Improving survival for patients with high-risk congenital diaphragmatic hernia by using extracorporeal membrane oxygenation.

The benefit of extracorporeal membrane oxygenation (ECMO) in cases of high-risk congenital diaphragmatic hernia (CDH) was studied by comparing pre-ECMO (1987-1990) and post-ECMO (1991-1994) 3-month survival statistics. Fifty-five CDH patients who presented in respiratory distress within 6 hours after birth were referred--18 in the pre-ECMO era and 37 in the ECMO era. During the entire study period (December 1987 through July 1994) the patients were treated by the same protocol of preoperative stabilization and delayed surgery; the only difference was the addition of ECMO beginning in January 1991. The patients were stratified based on the response to conventional treatment: 1, no response (irretrievable); 2, stable; 3, unstable. The 3-month survival rate for the unstable neonates (who could not be stabilized by conventional therapy) improved from 0% (0 of 9) in the pre-ECMO era to 61% (11 of 18) in the ECMO era (P = .004). This highly significant difference shows that ECMO is a very valuable addition to the management of high-risk CDH patients whose conditions remain unstable despite maximal conventional therapy.

Fasting studies in cerebrospinal fluid and blood in children with epilepsy of unknown origin.

Alterations in the cerebral energy supply are likely to cause cerebral function disturbances. Fasting is a suitable method for studying the energy metabolism. As the cerebrospinal fluid (CSF) compartment reflects the brain metabolism, data in CSF might give information about the metabolism of fuel substrates in brain. We compared the biochemical data on several fuel-related components in blood and CSF at the end of a 40-hours fast of epileptic children with unknown origin of epilepsy (aged 6-15 years) with the values of a reference group of children. In children with primary generalized epilepsy no abnormalities were found. In children with complex partial epilepsy many significant abnormalities were found, such as low blood lactate and alanine and low CSF ketones and CSF blood ratio for ketones. The possible significance of the observed abnormalities are discussed.

Schedule-dependent enhancement of antitumor activity of ethyldeshydroxy-sparsomycin in combination with classical antineoplastic agents.

The efficacy of the protein synthesis inhibitor ethyldeshydroxy-sparsomycin (EDSM) as a biochemical response modifier of several antitumor agents against L1210 leukemia and B16 melanoma is described. Seven drugs with different intracellular targets were selected for this combination study. Tumor implantation and drug treatment were both i.p., and the time interval between the administration of EDSM and the cytostatic agent was varied. Our results show that in the B16 tumor model EDSM is not able to potentiate any of these drugs, whereas antagonism is seen in combination with doxo-rubicin (DX). In the L1210 tumor model, however, no loss of activity is seen for this specific combination. The effect of the combination of cytosar (Ara-C), 5-fluorouracil (5-FU) or vincristine (VCR) with EDSM in the L1210 model is strongly time interval dependent. Loss of 5-FU antitumor activity is seen when EDSM is given 3 or 24 h after 5-FU; however, no effect is observed when EDSM is given 6 h after 5-FU. Enhancement of the 5-FU activity is not noticed. The VCR activity is potentiated when EDSM is given at least 6 h after VCR administration, which increases the antitumor response from 32 to > 60 days and the percentage survivors from 33 to 83% (p = 0.04). In combination with Ara-C, potentiation of antitumor activity is seen only when EDSM is given 24 h after Ara-C, which increases the antitumor response from 32 to > 55 days and the percentage survivors from 11 to 50% (p = 0.008). No modulatory effects are found when EDSM is combined with carmustine or DX.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized study of intravesical mitomycin C, bacillus Calmette-Guerin Tice and bacillus Calmette-Guerin RIVM treatment in pTa-pT1 papillary carcinoma and carcinoma in situ of the bladder.

Results of a randomized prospective study are reported in which mitomycin C, Tice bacillus Calmette-Guerin (BCG) and RIVM-BCG were compared in 437 patients with primary or recurrent pTa and pT1 bladder tumors, including carcinoma in situ. The followup (or time in study) varied from 2 to 81 months (mean 36 months). After complete transurethral resection of all visible tumors the patients were treated with 30 mg. mitomycin C once a week for 4 consecutive weeks and thereafter every month for a total of 6 months, and 5 x 10(8) colony-forming units Tice BCG or RIVM-BCG once a week for 6 consecutive weeks. For papillary tumors mitomycin C and RIVM-BCG treatments were equally effective (p = 0.53), and mitomycin C was more effective than Tice BCG therapy (p = 0.01).

Analytical and clinical performance of improved Abbott IMx CA 125 assay: comparison with Abbott CA 125 RIA.

We compared the improved Abbott IMx cancer antigen (CA) 125 assay (cat. no. 7A89) with the Abbott CA 125 RIA. Serum specimens were from healthy perimenopausal women (n = 124) and from patients with benign gynecologic and nongynecologic diseases (n = 124), ovarian carcinoma (n = 104), or other malignancies (n = 193). The IMx assay detected as little as 0.193 kAU/L CA 125 (AU = arbitrary Abbott unit), demonstrated up to 29% overestimation upon serum dilution, low within-assay (2.7-5.6%) and between-assay (4.8-8.2%) CVs, and no high-dose hook effect < or = 46,000 kAU/L nor influence from human anti-mouse antibodies in serum of women injected with OC 125 F(ab')2. Values by IMx were 20% lower than by RIA for healthy perimenopausal women (n = 100; IMx = 0.80 RIA - 2.5 kAU/L), and at least 50% higher for those with benign or malignant ovarian disorders at concentrations < 100 kAU/L. Receiver-operating characteristic (ROC) curve analysis of ovarian neoplasma vs perimenopausal controls indicated a gain of specificity and sensitivity with the improved IMx assay over the RIA, but ROC performance was the same with either assay if patients with benign ovarian disorders were used as controls.

Preclinical antitumor activity of ethyldeshydroxysparsomycin in combination with cisplatin.

The efficacy of cisplatin (CDDP) in combination with the protein synthesis inhibitor ethyldeshydroxysparsomycin (EDSM) has been tested in two tumor models at various schedules. Mice with L1210 leukemia or B16 melanoma were treated with CDDP alone or in combination with EDSM. Against L1210 leukemia, which is sensitive to CDDP, combinations elicited increases in life-span for all treatment schedules compared to those achieved with the corresponding dose of CDDP. Moreover, the combination of EDSM with this platinum compound yielded a cure rate > 80%, compared to < 35% for single CDDP treatment. Although the B16 melanoma is rather resistant to both CDDP and EDSM, combinations of these agents against B16 melanoma showed schedule dependent efficacy and in certain schedules significant therapeutic advantage over individual drug treatment, but cures were not observed. Our results suggest that EDSM has significant synergistic capabilities in both animal tumor models, but strong therapeutic enhancement of cisplatin efficacy is only seen when the tumor is sensitive to CDDP.

The phenylalanine response curve in relation to growth and mental development in the first year of life.

Thirty-three children with classical phenylketonuria were treated from 9 to 21 days of age onward. The standard for phenylalanine concentration was 0.2-0.5 mmol/l. During the first years of life phenylalanine concentrations were measured once every two to six weeks. For each child these values were graphically plotted in a so-called phenylalanine response curve. Growth and mental development indices were assessed at about one and two years of age. Measurements for weight, height and head circumference were normal at one month of age, showed a significant decline at the age of one year but were restored for normal values at the age of two. No associations were found with phenylalanine parameters. Mental development indices at one and two years were not different from normal. Significant negative correlations were found between mental development indices at one year and phenylalanine values above 0.5 mmol/l. Changes in mental development indices between the first and second years of life are significantly related to the phenylalanine levels during the second year of life.

Prognostic factors in pTa-pT1 superficial bladder tumours treated with intravesical instillations. The Dutch South-Eastern Urological Collaborative Group.

OBJECTIVE: To identify prognostic factors that enable patients with superficial bladder cancer to be divided into groups who will probably respond to therapy and those who will not. PATIENTS AND METHODS: In a prospective randomized study 387 patients with pTa-pT1 superficial bladder carcinoma received, after transurethral resection, intravesical instillations with immuno- or chemotherapy. A simultaneous computerized analysis of factors predicting the recurrence-free interval was performed. All these patients had negative random biopsies. Pretreatment factors analysed for recurrence were gender, age, history (primary or recurrent disease), location of tumour, number of tumours, pT-stage and grade. RESULTS MEDIAN: Follow-up was 27 months (range 12-56). During the follow-up period 37.2% of the patients had recurrence and eight patients (2.2%) had progression into muscle invasive disease. After a univariate analysis the number of tumours and location of the tumour in the bladder appeared to be a significant influence on the recurrence-free interval. Location of at least one of the tumours in the prostatic urethra, bladder neck, posterior wall, and trigone area was significantly related to a shorter recurrence-free interval; these areas were defined as high risk. Tumour stage showed borderline significance. By using multivariate methods to assess the relative importance of these factors, location of tumour in the high risk region was related especially to a short recurrence-free interval. The factor found to be of significance for the prognosis for recurrence was tumour multiplicity. Gender, age, history of recurrent disease, size of the largest tumour, tumour stage or grade gave no additional information about the risk of recurrence. CONCLUSION: Prognostic factor analysis, as an auxiliary study of trials of patients treated for superficial bladder tumours, is mandatory. The prognostic factors related to recurrence-free interval found in this study, location of the tumour and multiplicity, may be of use in the stratification necessary for current protocol design.

Erectile dysfunction in diabetic men: the neurological factor revisited.

In the literature the importance of the neurological factor in the etiology of erectile dysfunction in patients with diabetes mellitus is subject to debate. We report on the findings of neurophysiological investigations in 27 impotent and 30 potent diabetic patients, as well as 102 impotent nondiabetic patients. Additionally, hormonal and vascular evaluations were done. The neurophysiological evaluations consisted of assessment of somatic as well as autonomic sensory nerves, by measuring the latencies of somatosensory evoked potentials of the posterior tibial and pudendal nerves, and of the bulbocavernosus and urethro-anal reflexes. The results show a higher incidence of more severe peripheral and autonomic sensory neuropathy in impotent diabetic men. Also, a preponderance of abnormal intracavernous pharmacological tests, suggesting vasculogenic impotence, was found in impotent diabetic patients. No important endocrinological differences were found among the 3 groups under investigation. Significant differences occurred for plasma glucose and glycosylated hemoglobin. We conclude that diabetic urogenital sensory neuropathy has a crucial role in the etiology of diabetic impotence. Angiopathy seems to be of secondary importance. The results show that poor diabetes regulation is associated with diabetic impotence.