Bone morphogenetic protein 2 gene transduction enhances the osteogenic potential of human urine-derived stem cells.

INTRODUCTION: Urine-derived stem cells (USCs) have the ability to differentiate into osteogenic lineage. Previous studies have raised the possibility that USCs could be used for bone repair. To harness the power of USCs in promoting bone regeneration, methods must be developed to induce USCs to osteogenic lineage efficiently. The present study investigates the effect of lentivirus-encoded bone morphogenetic protein 2 (BMP2) gene transduction on the osteogenic potential of USCs. METHODS: USCs were isolated from voided urine and transduced with Lentiviral vector encoding BMP2. An in vitro study was performed to detect Lentiviral-BMP2 transduced USCs differentiated towards osteogenic lineage. Furthermore, Lentiviral-BMP2 transduced USCs were transplanted in vivo to examine the ectopic bone formation ability. After six weeks, retrieval samples were obtained for immunostaining and histological analysis. RESULTS: The results showed that the transduction efficiencies were over 90%, and transduced USCs had high expression levels of the BMP2 gene and secreted BMP2 protein. Alkaline activity and mineral deposition staining demonstrated that transduced USCs differentiate into osteogenic lineages without the addition of osteogenic supplements. Transduced USCs also showed high expression of bone-related markers, including runt-related protein-2 (Runx2) and osteocalcin (OCN), confirming this lentiviral-BMP2 construct provides sufficient stimuli for osteogenic differentiation. Histological analysis indicated that the transduced USCs induced robust new bone formation in nude mice. Six weeks after transplantation, human derived cells were observed to participate in bone formation. CONCLUSIONS: These results demonstrate that BMP2 gene transduction provides an effective method to enhance the osteogenic potential of USCs.

Positive urine cytology and carcinoma in situ prior to second transurethral resection of the bladder correlate with positive second resection histology and the need for subsequent cystectomy.

OBJECTIVE: A second transurethral resection of the bladder (TURB) is recommended for high-grade bladder cancer (BC) yet yields negative results in over half of the cases. Aim of this study was to identify prognostic indicators of a positive second TURB or the need for a subsequent cystectomy. MATERIALS AND METHODS: The study cohort consisted of 101 patients with high-risk BC (T1G2-3, TaG3, Carcinoma in situ) who underwent second TURB after complete first resection. Age, gender, stage, grade, carcinoma in situ (Cis), tumour number, size, localization, surgeon experience and bladder wash cytology before the second TURB were considered as potential prognostic factors of positive histology at second TURB or the need for subsequent cystectomy. RESULTS: The mean follow-up period was 23.8 months. The study cohort was comprised of 82 males and 17 females. Cytology on bladder wash urine was performed in 85/101 patients and in 39 was negative; 55.5 % of second TURB specimens were negative. The rate of upstaging to ≥T2 was 4.9 %. Cis (OR 8.4; 95 % CI 1.3-54.2; p = 0.03) and positive cytology (OR 6.8; 95 % CI 2.3-19.9; p = <0.01) were independent prognostic factors of a residual tumour in the second TURB. Cytology also correlated with clinical need for cystectomy in the follow-up (HR 6.5; 95 % CI 1.3-30.5; p = 0.02). CONCLUSIONS: CIS and positive cytology prior to second TURB increased the risk of a positive second TURB specimen. A positive cytology also increases the risk of the subsequent need for cystectomy.

Improved diagnostics of chronic inflammatory prostatitis.

AIM: Prostatitis is a prevalent condition that encompasses a large array of clinical symptoms with significant impacts on men's life. The diagnosis and treatment of this disorder presents numerous challenges for urologists, most notably, a lack of specific and effective diagnostic methods. METHODS: To improve the diagnostics the comparison of classic 4-glass test Meares and Stamey, 2-glass tests and 3-glass test was conducted in 177 men suspicious for chronic prostatitis. RESULTS: Four-glass test is uncomfortable both for patients and doctors, and leads to contamination of urine with prostatic secretion. Two-glass test is insufficiently effective too. Three-glass test (three urine specimens obtained from one continuous micturition stream) gives more adequate results and may be used for screening. CONCLUSION: Three-glass test as screening test with the option of an additional EPS investigation in those patients the final diagnosis of chronic prostatitis has to be confirmed is more convenient for patients and doctors than the standard M&S 4-glass test and "false-positive" (contaminated with EPS) midstream urine results are avoided thus improving discrimination of urethritis, cystitis and prostatitis. Therefore, we recommend the KE 3-glass test as a new standard for screening patients with signs and symptoms of chronic inflammatory prostatitis.

Bacteriuria after bipolar transurethral resection of the prostate: risk factors and correlation with leukocyturia.

OBJECTIVES: To analyze the risk factors of postoperative bacteriuria and the correlation with leukocyturia after bipolar transurethral resection of the prostate (TURP). METHODS: A total of 121 noncatheterized patients with sterile preoperative urine undergoing bipolar TURP for benign prostatic hyperplasia (BPH) were entered into the prospective study. All patients received antibiotic prophylaxis with ceftriaxone. Two urine specimens of each patient, one for urinalysis (urinary leukocyte count) and one for urine culture, were collected on removal of the catheter, 1 and 4 weeks after surgery. The risk factors of postoperative bacteriuria and correlation with leukocyturia were investigated. RESULTS: The incidence of bacteriuria after bipolar TURP was 18.2% (22/121). Multivariate analysis documented 3 independent risk factors of postoperative bacteriuria: operating time >60 minutes (P = .014), duration of catheterization >3 days(P = .001), and disconnection of the closed urine drainage system (P <10(-3)). The mean leukocyte counts in urine were 405.3, 389.5, and 113.8/µL on removal of the catheter, 1 and 4 weeks after surgery, respectively. Of 363 urine specimens, the mean concentration of leukocytes with and without bacteriuria were 323.9 and 297.6/µL, respectively (P >.05). There was no significant correlation between bacteriuria and leukocyturia (>10 leukocytes/high power field (P >.05). CONCLUSIONS: The results of our study have shown that the operating time, duration of catheterization, and disconnection of the closed urine drainage system may influence the occurrence of bacteriuria after bipolar TURP, and leukocyturia cannot reflect the possibility of postoperative bacteriuria.

Treatment of chronic prostatitis/chronic pelvic pain syndrome category IIIA with Serenoa repens plus selenium and lycopene (Profluss) versus S. repens alone: an Italian randomized multicenter-controlled study.

OBJECTIVES: To evaluate the efficacy and safety of Serenoa repens + selenium and lycopene (Profluss) versus S. repens alone for the treatment of category IIIa chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS: 102 patients with IIIa CP/CPPS were enrolled and randomized into two groups each to receive Profluss or S. repens alone for 8 weeks. Evaluation was based on results of the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), IPSS, maximum peak flow rate (MPFR), and PSA measurements at baseline and at weeks 4, 8 and 8 after the end of treatment. The primary endpoint was a >50% reduction in NIH-CPSI score. Secondary endpoints evaluated were MPFR, IPSS, PSA and white blood cell count. RESULTS: No patients withdrew from the study. The mean NIH-CPSI score decreased significantly (p < 0.001) in both groups; we observed a decrease in the total score from 27.45 to 13.27 in group 1 (-51.64%) and from 27.76 to 20.62 in group 2 (-26.06%). IPSS improved significantly (p < 0.001) in both arms, but more in group 1. PSA and white blood cell count decreased significantly (p < 0.007) only in group 1. The MPFR improved more in group 1 (p < 0.005). CONCLUSION: Profluss is a triple therapy that is safe and well tolerated. It ameliorates symptoms associated with IIIa CP/CPPS.

Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage.

PURPOSE: The diagnosis of localized prostate cancer is difficult due to a lack of cancer-specific biomarkers. Many patients require repeat prostate biopsies to diagnose the disease. We investigated whether aberrant promoter hypermethylation in prostatic fluid could reliably detect prostate cancer. EXPERIMENTAL DESIGN: Urine samples were collected after prostate massage from 95 patients with localized prostate cancer undergoing radical prostatectomy (63 pT(1), 31 pT(2), and 1 pT(3)) and from 38 control patients. Ten genes (GSTP1, RASSF1a, ECDH1, APC, DAPK, MGMT, p14, p16, RARbeta2, and TIMP3) were investigated using quantitative real-time methylation-specific PCR. Receiver operator curves were generated. RESULTS: The frequency of gene methylation ranged from 6.3% (p14) to 83.2% (GSTP1) in prostate cancer patients. At least one gene was hypermethylated in 93% of cancer patients. The specificity of methylation was 0.74. Methylation was significantly more frequent (P < 0.05) in cancer than control patients for all genes except p14 and p16. According to receiver operator curve analysis, the four-gene combination of GSTP1 (0.86), RASSF1a (0.85), RARbeta2 (0.80), and APC (0.74) best discriminated malignant from nonmalignant cases. The sensitivity and accuracy of this four-gene set were 86% and 89%, respectively. CONCLUSIONS: The presence of aberrant methylation in urinary cells obtained after prostate massage is significantly associated with prostate cancer. A panel of four genes could stratify patients into low and high risk of having prostate cancer and optimize the need for repeat prostatic biopsies.

How does the pre-massage and post-massage 2-glass test compare to the Meares-Stamey 4-glass test in men with chronic prostatitis/chronic pelvic pain syndrome?

PURPOSE: The Meares-Stamey 4-glass test is the standard method of assessing inflammation and the presence of bacteria in the lower urinary tract in men presenting with the chronic prostatitis syndrome. However, most urologists do not use it in daily practice because of the time and difficulty in performing it, as well as the additional expense. We evaluated a simpler test, the 2-glass pre-massage and post-massage test, and compared it with the Meares-Stamey 4-glass test to detect inflammation and bacteria in men with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: The study population included 353 men enrolled in the National Institutes of Health Chronic Prostatitis Cohort study with baseline leukocyte counts and 2-day bacterial cultures on specimens obtained from a standard 4-glass test (VB1, VB2, expressed prostatic secretions, VB3). The chi-square test was performed to assess associations of white blood cell counts in expressed prostatic secretions and VB3. A receiver operating characteristic curve was constructed to determine the optimal cut point of white blood cells in VB3 in predicting white blood cells in expressed prostatic secretions. Sensitivity and specificity of VB3 cultures predicting expressed prostatic secretions and positive Meares-Stamey results were calculated from 2 x 2 contingency tables. RESULTS: Analysis of binary leukocyte outcomes (no white blood cells vs any white blood cells) suggests that white blood cells tend to be present in expressed prostatic secretions when there are any white blood cells in VB3, p <0.0001, the optimal cut point being white blood cell counts of 3 in VB3 (best predictive ability with area under ROC 0.771) to predict 5+ in expressed prostatic secretions with a sensitivity of 76% and specificity of 70%. The optimal cut point of white blood cells in VB3 to predict 10 white blood cells in expressed prostatic secretions was 4 (62% sensitivity and 75% specificity). Uropathogens localizing to expressed prostatic secretions or VB3 confirms a positive 4-glass Meares-Stamey localization test. The sensitivity and specificity of a VB3 localizing culture only in predicting a positive Meares-Stamey 4-glass test result for any uropathogen were 44% to 54% (depending on definition) and 100%, respectively. The pre-massage and post-massage test predicted a correct diagnosis in more than 96% of subjects. CONCLUSIONS: The value of localizing leukocytes and uropathogens to prostate specific specimens remains controversial in chronic heavily pretreated patients, but these data may help direct therapy (anti-inflammatory or antimicrobial) when obtained at first presentation. The pre-massage and post-massage test has strong concordance with the 4-glass test and is a reasonable alternative when expressed prostatic secretions are not obtained.

[Prostatic exfoliative cytology obtained from urine samples after massage. Initial results]. / Citología exfoliativa prostática obtenida en muestras de orina tras masaje. Primeros resultados.

INTRODUCTION: The same as the exfoliative cytology is a routine method to diagnose bladder tumour, the prostatic cytology obtained after massage may become a useful procedure to diagnose prostate cancer. OBJECTIVE: To obtain suitable prostatic cytologic material. To establish the role of the exfoliative cytology to diagnose cancer. MATERIAL AND METHODS: We made a prospective longitudinal descriptive study with 60 patients out of 150 (all of them with possible prostate cancer) for two years. We compared cytologic discoveries (urine after massage) with histological parameters (biopsies). RESULTS: When the cytology fulfills a series of requirements (a high number of prostatic cells, anisokariosis and antibodies Ki-67+) and these are compared with the histological data, we obtained a specificity of 100% and a sensibility of 67% for prostatic cancer. With this information the cytology reaches a predictive value of 100% and negative of 92%. CONCLUSIONS: It is possible to obtain prostatic cytologic material in a simple and easy way. The prostatic cytology may become a valid and useful method to diagnose the carcinoma of the prostate. Also this material can be used for multiple diagnostic, follow-up and research procedures.

DNA-based detection of prostate cancer in urine after prostatic massage.

OBJECTIVES: Promoter hypermethylation of the glutathione-S-transferase P1 (GSTP1) gene is a specific feature of prostate cancer. This epigenetic DNA alteration served as the target for molecular detection of prostate cancer cells in urine sediments after prostatic massage. METHODS: Bisulfite treatment followed by methylation-specific polymerase chain reaction was used to detect GSTP1 promoter hypermethylation in DNA isolated from urine sediments obtained after prostatic massage of men with and without prostate cancer. RESULTS: GSTP1 promoter hypermethylation was demonstrated in the sediments of 1 (2%) of 45 patients diagnosed with benign prostatic hyperplasia, 2 (29%) of 7 patients with prostatic intraepithelial neoplasia, 15 (68%) of 22 patients with early, intracapsular cancer, and 14 (78%) of 18 patients with locally advanced or systemic prostate cancer, resulting in a specificity of 98% and an overall sensitivity of 73% for the detection of prostate cancer. CONCLUSIONS: Urinalysis for GSTP1 promoter hypermethylation constitutes a sensitive and highly specific DNA-based marker for molecular detection of prostate cancer, including early stages.

The use of telomerase activity for the detection of prostatic cancer cells after prostatic massage.

PURPOSE: Prostate cancer is the most commonly diagnosed cancer in the United States. The diagnosis or followup of prostate cancer in men older than 50 years is based on digital rectal examination, measurement of the free-to-total prostatic specific antigen ratio and transrectal ultrasound assisted needle biopsy of the prostate. We developed and evaluated a noninvasive method for diagnosing prostate cancer based on the measurement of telomerase activity after prostatic massage in fresh voided urine or after urethral washing. MATERIALS AND METHODS: We obtained 36 specimens of cells after prostatic massage in the fresh voided urine of 16 patients who subsequently underwent radical prostatectomy and after urethral washing in 20 who underwent prostate needle biopsies. Ethylenediaminetetraacetic acid was immediately added to the collected urine or washing to a final concentration of 20 mM. After protein extraction by CHAPS buffer each specimen was tested for telomerase activity in a 2-step modified telomeric repeat amplification protocol assay. The 2 prostate cancer cell lines PC-3 and LNCaP with high telomerase activity were used as a positive control. RESULTS: Telomerase activity was detected in 14 of 24 samples with known prostate cancer (sensitivity 58%). In contrast, no telomerase activity was found in the 12 cases without histological evidence of prostate tumor (specificity 100%). Eight of 9 poorly differentiated cancers expressed telomerase activity (89%), while only 6 of 15 well and moderately differentiated cancers showed telomerase activity (40%). CONCLUSIONS: Our data illustrate that telomerase activity may be detected in voided urine or washing after prostatic massage in patients with prostate cancer. Sensitivity was higher for poorly differentiated tumors. This approach is not currently available for detecting prostate cancer in clinical practice. However, these results are promising and further studies are ongoing.

Immunocytological analysis of leukocyte subpopulations in urine specimens before and after prostatic massage.

OBJECTIVE: To evaluate the presence of leukocyte subpopulations in urine after prostatic massage (VB 3) in symptomatic patients with > or =10 leukocytes/high power field (magnification x1,000) in expressed prostatic secretions, and who were classified as suffering from chronic bacterial prostatitis or inflammatory chronic pelvic pain syndrome. METHODS: 115 consecutive patients were investigated. Granulocytes in centrifuged midstream urine (VB 2) and VB 3 were counted after Papanicolaou stain. Macrophages, B and T lymphocytes were analyzed after immunocytological staining with monoclonal antibodies according to the alkaline phosphatase anti-alkaline phosphatase method. The counts were quantified as the number of cells per view field at a magnification of x400. In all patients, acute or chronic urethritis had been excluded before enrollment in the study. 16 men without signs or symptoms of urogenital inflammation served as controls. RESULTS: Of the 115 patients, 101 men demonstrated > or =10 leukocytes/view field in VB 3. In comparison to VB 2, the leukocyte subpopulations in VB 3 demonstrated an increase in granulocytes (9.2-fold), macrophages (7.6-fold), T lymphocytes (7.6-fold), and B lymphocytes (4-fold). The increase was statistically significant (p<0.001 each). The proportion of these cells in VB 3 was 81.6, 11.1, 5.5, and 1.8%, respectively. As compared to controls, all leukocyte subsets in VB 3 were significantly elevated (p>0.001 each). CONCLUSION: Elevated numbers of leukocytes in VB 3 are indicative of prostatitis provided that urethral inflammation and leukocyturia in VB 2 are excluded. Granulocytes are the predominant cell type of inflammation. The increase in macrophages, T and B lymphocytes in prostatic secretions indicate the participation of both the cellular and humoral immune system in the inflammatory process.

Membranes and their constituents as promoters of calcium oxalate crystal formation in human urine.

We have proposed that membranes of cellular degradation products are a suitable substrate for the nucleation of calcium oxalate (CaOx) crystals in human urine. Human urine is generally metastable with respect to CaOx. To demonstrate that cellular membranes present in the urine promote nucleation of CaOx we removed these substrates by filtration or centrifugation and induced crystallization by adding sodium oxalate, before and after filtration or centrifugation. In a separate experiment, membrane vesicles isolated from rat renal tubular brush border were added into the filtered or centrifuged urine before crystal induction. Crystals were counted using a particle counter. Urine, the pellet, and retentate were analyzed for the presence of membranes, lipids, and proteins. Lipids were further separated into different classes, identified, and quantified. Both filtration and centrifugation removed lipids, proteins, and membrane vesicles, causing a reduction in lipid and protein contents of the urine. More crystals formed in whole than in filtered or centrifuged urine. The number of crystals significantly increased when filtered urine was supplemented with various urinary components such as the retentate and phospholipids, which are removed during filtration. We also determined the urinary metastable limit with respect to CaOx. Filtration and centrifugation were associated with increased metastable limit which was reduced by the addition of membrane vesicles. These results support our hypothesis that urine normally contains promoters of CaOx crystal formation and that membranes and their constituents are the most likely substrate for crystal nucleation in the urine.

Methods of semen collection not based on masturbation or surgical sperm retrieval.

Although masturbation is the standard method for the collection of a sperm sample, both for diagnostic and therapeutic purposes, other approaches have been described and assessed. Production of semen using specially designed condoms has been shown to result in samples with better laboratory characteristics than samples obtained after masturbation or coitus interruptus. However, this has not resulted in a general acceptance and use of this approach, except in special circumstances where masturbation is impossible or unacceptable. Direct retrieval of spermatozoa from morning urine is another method which has been used to study spermache in boys, but not to treat infertility. Sperm production techniques such as vibro- and electrostimulation are dealt with elsewhere, as are surgical retrieval techniques used in azoospermia.

Molecular characterization of a newly identified heme-binding protein induced during differentiation of urine erythroleukemia cells.

A heme-binding protein with a molecular mass of 22 kDa, termed p22 HBP, was purified from mouse liver cytosol, using blue Sepharose CL-6B. We identified a cDNA encoding p22 HBP, and sequence analysis revealed that p22 HBP comprises 190 amino acid residues (Mr 21,063) and has no homology to any other known heme-binding protein. The p22 HBP mRNA (approximately 1.0 kilobases) is ubiquitously expressed in various tissues and is extremely abundant in the liver. cDNA allows for expression of active p22 HBP, with a high affinity for 55Fe-hemin, with a Kd of 26 +/-1.8 nM. The Bmax of hemin binding to p22 HBP was 0.55 +/- 0.021 mol/mol of protein, a value consistent with one heme molecule binding per molecule of protein. The order of potency of different ligands to compete against 55Fe-hemin binding to p22 HBP was hemin = protoporphyrin IX > coproporphyrin III > bilirubin > palmitic acid > all-trans-retinoic acid. Treatment of mouse erythroleukemia (MEL) cells with dimethyl sulfoxide or hemin resulted in an increase in p22 HBP mRNA. The immunoblot analysis showed that p22 HBP increased with time in dimethyl sulfoxide- and hemin-induced MEL cells. Conversely, transfer of antisense oligonucleotides to p22 HBP cDNA resulted in a decrease of p22 HBP in dimethyl sulfoxide-treated MEL cells, and the heme content in these cells decreased to 66-71% of sense oligonucleotides-transferred cells. Thus, this newly identified heme-binding protein, p22 HBP, may be involved in heme utilization for hemoprotein synthesis and even be coupled to hemoglobin synthesis during erythroid differentiation.

Effect of intravenous calcium administration on gentamicin-induced nephrotoxicosis in ponies.

OBJECTIVE: To determine whether supplemental i.v. calcium administration would attenuate or prevent gentamicin-induced acute renal failure, defined as an increase in serum creatinine concentration > or = 50% above baseline. ANIMALS: 10 healthy pony mares. PROCEDURE: Pony mares were randomly assigned to receive calcium at a dosage of 20 mg/kg of body weight or saline solution i.v., twice daily for 14 days. All pony mares received gentamicin at a dosage of 20 mg/kg i.v. every 8 hours for 14 days. Gentamicin pharmacokinetic, serum biochemical, and urinalysis data were measured every other day for the 14-day study period. Renal histologic examination was performed, and results were scored at the end of the 14-day period. RESULTS: 4 of 5 mares not receiving calcium supplementation developed acute renal failure. Only 1 of the 5 mares receiving calcium supplementation developed acute renal failure. Over the course of the study, pony mares receiving calcium supplementation had significantly fewer changes in urinalysis variables, and significantly less microscopic renal damage. CONCLUSION: Daily i.v. administration of calcium attenuated gentamicin-induced acute renal failure. CLINICAL RELEVANCE: Calcium supplementation may help diminish the risk of acute renal failure associated with aminoglycoside antibiotics.

Effects of polyethylene glycol 400 (PEG 400) following 13 weeks of gavage treatment in Fischer-344 rats.

Fischer-344 rats (10/group/sex) were administered polyethylene glycol 400 (PEG 400) by gavage at 1.0, 2.5 or 5.0 ml/kg (1.1, 2.8 and 5.6 g/kg, respectively) body weight/day 5 days/wk for 13 wk. Animals in the control group received water by gavage (5.0 ml/kg body weight/treatment day). An additional 10 rats/sex/group were assigned to the control and high-dose groups for a 6-wk recovery period. Evaluation of potential renal toxicity was identified as a primary objective. There was no mortality or changes in haematology or clinical chemistry measurements attributed to PEG 400 toxicity. Loose faeces in the mid- and/or high-dose group of both sexes were attributed to bulk cathartic effects of PEG 400. Slight decreases in food consumption and body weights in the mid- and/or high-dose group of male rats and female rats were attributed to the physical presence of PEG 400 in the intestinal tract. However, a direct effect of PEG 400 on the intestinal tract was not ruled out. Increased water consumption was attributed to a possible increase in serum osmolality due to the absorption of the PEG 400 or a reflection of the water dosing received by the control animals. Increased urinary concentration and decreased urinary pH were at least partially attributed to absorption, possible metabolism, and urinary excretion of PEG 400. Small increases in absolute and/or relative kidney weights observed in many dose groups, were attributed to the osmotic effect of the test substance and/or metabolites in the urine. The significance of a slight increase in relative kidney weights in female rats following the recovery period was unknown. Although no microscopic changes were observed in the kidneys or urinary bladder, a slight, reversible renal toxicity may have resulted in male rats treated by gavage with 2.5 ml/kg/day and rats of both sexes treated by gavage with 5.0 ml PEG 400 kg/day. This was based on the increased concentration of protein and bilirubin, urinary vascular cell findings and N-acetyl-beta-D-glucosaminidase activity.

Efficacy of preadmission testing in ambulatory surgical patients.

A retrospective study was done with 325 patients who had preadmission testing prior to ambulatory surgery. At least one laboratory abnormality was noted in 84% of the patients. The serial multiple analysis (SMA)-7 was abnormal 63% of the time. Abnormalities were seen in 54% of the SMA-12 panels and 38% of the urinalyses performed. Twenty-four percent of the patients treated had an abnormal electrocardiogram (ECG). An abnormal chest roentgenogram was found in 19% of the patients. Only three (1%) patients potentially benefited from preadmission testing. Ninety-six percent of the abnormal laboratory results were ignored by the attending physicians. Therefore, we conclude that preadmission testing should be done on a selective basis. Patients older than 50 years of age should have an ECG. A hematocrit should be obtained only if major blood loss is anticipated. All other tests should be ordered based on the history and physical examination.

The presence of urinary cellular sediment and albuminuria in newspaper pressworkers exposed to solvents.

To investigate the relationship between exposure to organic solvents and the presence of increased urinary cellular sediment, we conducted a cross-sectional study of 215 newspaper pressroom workers who were exposed to solvent and lubricant mixtures. Thirty-two compositors were surveyed as referents. Industrial hygiene measurements showed low-level airborne exposures to organic solvents (primarily naphthas) and minimal airborne exposure to glycol ethers. There was a high prevalence of solvent-related dermatitis indicating there was significant dermal exposure to these substances. Pressworkers were exposed to solvent mixtures that were associated with dose-related increases in leukocyturia alone or in urinary cellular sediment (erythrocyturia and/or leukocyturia). The presence of urinary cellular sediment was associated with increasing frequency of use of five particular organic solvent mixtures. These results suggest that the increase in urinary cellular sediment may be due, at least in part, to the effects of solvents on the kidney. Consistent with this hypothesis, 16% of pressmen and no compositors were found to have primarily low-grade albuminuria detectable by dipstick. Workers with urinary cellular sediment were significantly more likely to have detectable albuminuria. Albuminuria was more likely to occur with increased frequency of use of four particular solvent mixtures. The presence of urinary cellular sediment was less likely to occur with occasional use of analgesics suggesting a possible etiologic role for acute or chronic urinary tract inflammation.

Use of exfoliated cells to study tissue-specific levels of beta-carotene in humans.

This study was designed to explore the feasibility of using exfoliated cells to study beta-carotene incorporation into different epithelial tissues in humans. Exfoliated cells were collected from the oral cavities (by brushing the oral mucosa) and from the urogenital tracts (by centrifuging urine samples) of 36 females and basal levels of beta-carotene (without oral supplementation) were determined. Beta-carotene levels in cells from the two sites differed significantly, although a weak correlation was observed. As a second aspect of the study, 10 of these females were given oral supplementation with beta-carotene (90 mg twice weekly for 4 weeks). Beta-carotene levels increased significantly in both exfoliated urogenital tract (6.8-fold) and oral mucosa (5-fold) cells. However, the supplemented levels remained significantly different for the two types of cells. Beta-carotene levels did not change in individuals receiving a placebo treatment (n = 7). These studies suggest that exfoliated cells collected from different sites may be of value in quantifying tissue levels of beta-carotene during cancer intervention trials.

Nephrotoxicity screening in rats; general approach and establishment of test criteria.

The concept of a nephrotoxicity screening test that is based on quantitative assessment of urine collected under standardized conditions for 15.5 h is presented. One to eight urine collections were performed in large numbers of untreated female Sprague-Dawley rats. Normal values for water consumption, urine volume, pH, and excretion of protein, gamma-glutamyltranspeptidase, malate dehydrogenase, electrolytes, glucose, amino acids, leukocytes, erythrocytes, epithelia, unspecified cells and cylinders were determined. Test criteria were established based on the statistical distribution of these measurements. In rats repeatedly placed in metabolism cages, a statistically significant decrease in leukocyte excretion and an increase in excretion of epithelia and unspecified cells were observed. All other variables did not change with time.