Diagnosis of renal lymphoma by Wright-Giemsa-stained cytocentrifuged urine evaluation in a cat.

Lymphoma represents up to 30% of neoplasms diagnosed in cats. Diagnosis of lymphoma in the urinary system by examination of urine sediment has been described in a dog, but apparently not previously in cats. Concurrent samples of serum, EDTA whole blood, and urine were submitted from a 15-year-old spayed female domestic shorthair cat exhibiting weight loss, polyuria, and polydipsia. Hematology and biochemical abnormalities included a mild normocytic, normochromic, non-regenerative anemia; an inflammatory leukogram; and azotemia. Urinalysis evaluation revealed inadequate urine concentration and marked proteinuria. Wet-mount urine sediment examination revealed moderate numbers of leukocytes and erythrocytes. A uniform population of intermediate-to-large lymphocytes was observed on a fresh, Wright-Giemsa-stained preparation from cytocentrifuged urine. The cat was euthanized and necropsy was completed. Bilateral renomegaly was identified and characterized by multifocal, pale-yellow, coalescing, poorly defined, homogenous nodules. Microscopically, these nodules were composed of dense sheets of CD3-positive round cells, consistent with T-cell renal lymphoma. Key clinical message: Lymphoma is a common neoplasm in cats that can affect many organ systems, including the upper urinary tract. This case represents an uncommon method of identifying neoplastic lymphocytes via evaluation of cytocentrifuged urine, and emphasizes the benefits of examining Romanowsky-stained urine sediment in animals.

Diagnostic du lymphome rénal chez un chat par évaluation d'urine cytocentrifugée avec coloration Wright-Giemsa. Le lymphome représente jusqu'à 30 % des néoplasmes diagnostiqués chez le chat. Le diagnostic d'un lymphome du système urinaire par examen des sédiments urinaires a été décrit chez un chien, mais apparemment pas à ce jour chez le chat. Des échantillons simultanés de sérum, de sang total dans un tube avec EDTA et d'urine ont été soumis provenant d'une chatte domestique à poils courts stérilisée de 15 ans présentant une perte de poids, une polyurie et une polydipsie. Les anomalies hématologiques et biochimiques comprenaient une légère anémie normocytaire, normochrome et non régénérative; une formule leucocytaire inflammatoire; et une azotémie. L'analyse d'urine a révélé une concentration urinaire insuffisante et une protéinurie marquée. L'examen microscopique des sédiments urinaires a révélé un nombre modéré de leucocytes et d'érythrocytes. Une population uniforme de lymphocytes de taille intermédiaire à grande a été observée sur une préparation fraîche colorée au Wright-Giemsa à partir d'urine cytocentrifugée. Le chat a été euthanasié et une autopsie a été réalisée. Une rénomégalie bilatérale a été identifiée et caractérisée par des nodules multifocaux, jaune pâle, coalescents, mal définis et homogènes. Au microscope, ces nodules étaient composés de feuilles denses de cellules rondes CD3-positives, compatibles avec un lymphome rénal à cellules T.Message clinique clé :Le lymphome est une tumeur courante chez le chat qui peut affecter de nombreux systèmes organiques, y compris les voies urinaires supérieures. Ce cas représente une méthode rare d'identification des lymphocytes néoplasiques via l'évaluation de l'urine cytocentrifugée et met l'emphase sur les avantages de l'examen des sédiments urinaires avec coloration de Romanowsky chez les animaux.(Traduit par Dr Serge Messier).

Yield of Urinalysis Screening in Pediatric Cancer Survivors.

BACKGROUND: The Children's Oncology Group (COG) publishes consensus guidelines with screening recommendations for early identification of treatment-related morbidities among childhood cancer survivors. We sought to estimate the yield of recommended yearly urinalysis screening for genitourinary complications as per Version 3.0 of the COG Long-Term Follow-Up Guidelines and identify possible risk factors for abnormal screening in a survivor population. PROCEDURE: A database of pediatric cancer survivors evaluated between January 2008 and March 2012 at Children's Healthcare of Atlanta was queried for survivors at risk for genitourinary late effects. The frequency of abnormal urinalyses (protein ≥1+ and/or presence of glucose and/or ≥5 red blood cells per high power field) was estimated. Risk factors associated with abnormal screening were identified. RESULTS: Chart review identified 773 survivors (57% male; 67% Caucasian; 60% leukemia/lymphoma survivors; mean age at diagnosis, 5.7 years [range: birth to 17.7 years]; time from diagnosis to initial screening, 7.6 years [range: 2.3 to 21.5 years]) who underwent urinalysis. Abnormal results were found in 78 (5.3%) of 1,484 total urinalyses. Multivariable analysis revealed higher dose ifosfamide (odds ratio [OR] = 6.8, 95% confidence interval [CI] 2.9-16.0) and total body irradiation (TBI, OR = 3.0, 95% CI 1.0-8.4) as significant risk factors for abnormal initial urinalysis screening. CONCLUSIONS: Pediatric cancer survivors exposed to higher dose ifosfamide or TBI may be at higher risk of abnormal findings on urinalysis screening. Targeted screening of these higher risk patients should be considered.

Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance.

AIMS: The urinary coproporphyrin I/(I + III) ratio may be a surrogate for MRP2 activity. We conducted a prospective study in patients receiving methotrexate (MTX) to examine the relationship between this ratio and the pharmacokinetics of a MRP2 substrate. METHODS: Three urine samples were collected from 81 patients for UCP I/(I + III) ratio determination: one before (P1), one at the end of MTX infusion (P2), and one on the day of hospital discharge (P3). Three polymorphisms of ABCC2 were analysed and their relationships with basal UCP I/(I + III) ratio values assessed. All associated drugs were recorded and a drug interaction score (DIS) was assigned. Population pharmacokinetic analysis was conducted to assess whether MTX clearance (MTXCL) was associated with the basal UCP I/(I + III) ratio, its variation during MTX infusion, the DIS or other common covariates. RESULTS: The basal UCP I/(I + III) ratio was not associated with ABCC2 polymorphisms and did not differ according to the DIS. Significant changes in the ratio were observed over time, with an increase between P1 and P2 and a decrease at P3 (P < 0.001). No association was found between basal UCP I/(I + III) ratio and MTXCL. The final model indicates that MTXCL was dependent on the change in the ratio between P1 and P3, DIS and creatinine clearance. CONCLUSION: The basal UCP I/(I + III) ratio is not predictive of MTXCL. However, it is sensitive to the presence of MTX, so it is plausible that it reflects a function modified in response to the drug.

Early Urinary Potassium Level Predicts High-dose Methotrexate Elimination Delay in Primary Central Nervous System Lymphoma.

BACKGROUND/AIM: Treatment of primary central nervous system lymphoma (PCNSL) includes high dose methotrexate-based polychemotherapy (HD-MTX). This study aimed to identify early predictive factors of methotrexate (MTX) delayed elimination. PATIENTS AND METHODS: We prospectively included all patients with newly-diagnosed PCNSL. Daily serum and urinary creatinine and ionogram were collected. We generated two independent cohorts: a training cohort (TC) and a confirmatory cohort (CC). RESULTS: We included for analysis 64 cures of HD-MTX (20 patients) in the TC and 59 cures (22 patients) in the CC. Median elimination time of MTX was 95 h and 96 h in the TC and CC, respectively. In multivariate analysis, older age (p=0.004), low Karnofsky Performance Status (p=0.036) and high urinary K+ (p=0.001) were associated with delayed MTX elimination. An optimal cutoff for urinary K+ was defined. In the CC, we confirmed that high urinary K+ (p=0.004) remained associated with delayed MTX elimination. CONCLUSION: High urinary K+ may be predictive of delayed MTX elimination in primary central nervous system lymphoma. Its relevance as a decision-making factor needs to be validated in additional prospective studies.

Renal metastases from esophageal cancer and retroperitoneal lymphoma detected via chromosome duplications identified by fluorescence in situ hybridization in urine exfoliated cells: First 2 case reports.

RATIONALE: Renal-occupying lesions positive for urine fluorescence in situ hybridization (FISH) are usually considered urothelial carcinomas. Here, we describe 2 cases of renal metastases with chromosome duplications in urine exfoliated cells. PATIENT SYMPTOMS: Patient 1, a 56-year-old male with a history of esophageal cancer, was admitted to our hospital on May 2017 after presenting with right back pain with microscopic hematuria for 1 month. Magnetic resonance imaging (MRI) showed right renal space-occupying lesions (5.4 cm × 4.6 cm) and multiple enlarged lymph nodes in the right renal hilum and retroperitoneum. The cystoscopy results were negative, and FISH analysis of urine exfoliated cells was positive, indicative of chromosome 3, 7, and 17 amplifications. Patient 2 was a 50-year-old male who was admitted to our hospital on May 2019 with no obvious cause of abdominal pain and abdominal distension (lasting for 7 days), with a serum creatinine level of 844 µmol/L. Patient 2 had no hematuria or fever, and MRI showed left renal inferior and medial space-occupying lesions, and multiple mesenteric nodules at the junction of the left adrenal gland, retroperitoneum, abdomen, and pelvis, which were partially fused. The tumor lesions were approximately 3.1 cm × 2.3 cm in size. The urine FISH results were positive, indicating chromosome 3, 7, and 17 amplifications. DIAGNOSES: Both patients were diagnosed with renal tumors with unknown pathology. INTERVENTIONS: Patient 1 underwent laparoscopic resection of the kidney and ureter, and sleeve cystectomy. The postoperative pathological diagnosis was metastatic keratinized squamous cell carcinoma, with squamous cell carcinoma in the right hilar lymph node. Histological FISH of the primary esophageal cancer and renal metastases were consistent with the urine FISH test results. Patient 2 underwent a biopsy of the left renal inferior and retroperitoneal areas, and was diagnosed with diffuse large B-cell lymphoma. OUTCOMES: Patient 1 survived 6 months after urological surgery. After treating patient 2 with the R-CHOP regimen and kinase inhibitors, his renal function recovered significantly and the mass become undetectable. LESSONS: Our results imply that FISH-positive renal occupying lesions should be considered as potential renal metastases with chromosome aberrations when making a differential diagnosis.

Cola beverage and delayed elimination of methotrexate.

AIMS: To report a case of severe delayed methotrexate elimination attributable to consumption of a cola beverage. METHODS: To investigate unexplained low urinary pH in a lymphoma patient treated with high-dose methotrexate. RESULTS: Unexpected urinary acidity, despite administration of large amounts of sodium bicarbonate, could be attributed to repeated consumption of a cola beverage. It resulted in a delayed elimination of methotrexate and acute renal failure. Discontinuation of cola drinks, increase in calcium folinate rescue and in sodium bicarbonate allowed satisfactory elimination of methotrexate on day 12 after infusion and recovery from renal impairment without other severe toxicity. No other cause of delay in methotrexate elimination could be identified. CONCLUSIONS: Cola beverages have a low pH due to their phosphoric acid content that is excreted by renal route. We recommend patients receiving high dose methotrexate abstain from any cola drink within 24 h before and during methotrexate administration and until complete elimination of the drug.

Massive uric acid crystalluria and cylinduria in a dog after l-asparaginase treatment for lymphoma.

A 10-year-old golden retriever bitch was treated for diarrhea and vomiting that lasted about 1 month without a specific diagnosis until a hepatic biopsy provided a histopathologic diagnosis of lymphoma. The dog was referred to the Swedish University of Agricultural Science and treated with one dose of l-asparaginase. The day after chemotherapy, the urine was dark yellow, very turbid, and had large amounts of small amorphous crystals and many casts made of similar appearing material identified by infrared spectroscopy to be 100% uric acid dihydrate. Serum uric acid was elevated at 224 µmol/L (RI 0-59). The dog's illness became worse after chemotherapy. Lymphoma treatment was not continued, and the dog was euthanized 9 days after the l-asparaginase treatment. Among other problems were persistent proteinuria with a urine protein-to-creatinine ratio of 2.3 and severe hypoalbuminemia. Serum protein electrophoresis performed 3 weeks prior to chemotherapy indicated hyperproteinemia (total protein 78 g/L) having a biclonal gammopathy with 35 g/L ß-2 globulins and 11 g/L γ globulins. Despite prominent cylinduria and crystalluria, the patient did not develop azotemia or isosthenuria.

Urinary Tract Cytology.

Cytologic evaluation of the urinary tract can be diagnostically rewarding in cases of renomegaly or when discrete kidney or bladder masses are identified. Cytology can often help to distinguish between cystic, inflammatory, and neoplastic disorders. Various types of cystic and benign urinary tract lesions, diseases associated with urinary tract inflammation, and the cytologic differences between primary and metastatic neoplasms of the kidney and bladder are described. Basic sampling techniques for urinary tract cytology are also discussed.

Renal handling of Zn-alpha2-glycoprotein as compared with that of albumin and the retinol-binding protein.

An unusual electrophoretic pattern of the urine from a patient with malignant lymphoma was observed. One of the major proteins, identified Zn-alpha2-glycoprotein (Zn-alpha2), was isolated from the urine and partly characterized. The Stokes radius was found to be 3.24 nm and the molecular weight, determined by sodium dodecyl sulfate polyacrylamide electrophoresis, 42,000. The plasma level in healthy individuals was 39 +/- 7 (SD) mg/liter. In 12 of 25 healthy individuals, Zn-alpha2 was measurable in the urine and was found to be 1.0 +/- 1.1 mg/liter. In 23 patients with chronic glomerulonephritis (CGN), in 9 with proximal tubular dysfunction (PTD), in 23 with various renal diseases (VRD), and in 10 with malignant lymphoma, the plasma level and the urinary excretion were compared with those of albumin (mol wt 67,000) and of the retinol-binding protein (RBP, mol wt 21,000). A close correlation was found between the urine-to-plasma (U/P) ratios of Zn-alpha2 and albumin in the patients with CGN, whereas in the PTD patients the U/P ratios of Zn-alpha2 and RBP were correlated. No significant renal arteriovenous difference in Zn-alpha2 could be demonstrated. The Zn-alpha2 excretion was increased also in two patients with malignant lymphoma and proteinuria of a tubular pattern. The plasma Zn-alpha2 varied inversely with the glomerular filtration rate in the patients with renal disease, but was normal in those with malignant lymphoma. The results are consistent with the assumption of a sieving coefficient of Zn-alpha2, substantially exceeding that of albumin, but notably lower than that of smaller low-molecular-weight proteins. An increased excretion of Zn-alpha2 may be due to increased glomerular permeability as well as to defective proximal tubular reabsorption.

Effect of urban traffic, individual habits, and genetic polymorphisms on background urinary 1-hydroxypyrene excretion.

PURPOSE: Potential sources of exposure to polycyclic aromatic hydrocarbons (PAHs) and genetic polymorphisms were investigated in relation to their contribution to interindividual variation in baseline levels of urinary 1-hydroxypyrene (1-OHP) excretion in subjects without occupational exposure to PAHs. METHODS: Urinary excretion of 1-OHP was measured in 114 subjects, including 48 women and 66 men. Questionnaire information was collected on possible environmental and individual sources of PAH exposure. A subset of 70 individuals also was evaluated for a single-nucleotide polymorphism (Ex7+295C-->T) in the cytochrome P-450 1A2 (CYP1A2) gene, and 61 of these also were evaluated for the glutathione transferase T1 (GSTT1) gene polymorphism. RESULTS: 1-OHP values did not show a significant seasonal variability and were unaffected by age; education; body mass index; smoking status, including passive smoking; or the C-->T base substitution in position 295 of exon 7 of the CYP1A2 gene. After reciprocal adjustment with logistic regression, living in a heavily trafficked urban area (odds ratio, 4.9; 95% confidence interval, 1.0-24.9), and frequent intake of grilled meat (odds ratio, 6.9; 95% confidence interval, 1.1-43.5) were significant predictors of background urinary 1-OHP levels of 0.50 microg/g creatinine or greater. Elevated risks also were associated with daily alcohol intake greater than 65 g and the nonnull GSTT1 genotype. CONCLUSION: Our study shows that exposure to urban traffic, dietary habits, and the nonnull GSTT1 genotype may contribute to interindividual variation in background levels of 1-OHP urinary excretion in subjects without occupational exposure to PAHs.

Calculated versus measured creatinine clearance for dosing methotrexate in the treatment of primary central nervous system lymphoma.

BACKGROUND: High-dose methotrexate (HDMTX) (>or=3 g/m2), the cornerstone of therapy for primary CNS lymphoma (PCNSL), is commonly dosed using a measured 24 h creatinine clearance (CrCl) every 2-4 weeks. Because these collections are cumbersome and at times unreliable, the use of a calculated CrCl was evaluated as a potential alternative. METHODS: A retrospective analysis was performed on data from all 287 treatment cycles from the 25 patients with PCNSL who participated in a multi-center phase II clinical trial of HDMTX conducted by the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium. RESULTS: The 25 patients had a median age of 61 years (range 32-75). Seventeen (68%) were men. The patients received a median of 14 (range 2-21) HDMTX treatments. For 256 of 287 treatments (89%), data were available to compare the measured and calculated (using the Cockcroft-Gault equation) CrCl. The average measured CrCl was 93 ml/min (95% CI, 89-96 ml/min), and the average calculated CrCl was 107 ml/min (95% CI, 102-112 ml/min). The Pearson correlation coefficient (r) was 0.49 (P<0.0001) between the measured and calculated CrCl. The average MTX dose determined using measured CrCl was 14.1 g (95% CI, 13.6-14.5 g), and the average MTX dose determined using calculated CrCl was 14.7 g (95% CI, 14.2-15.1 g). MTX doses based on measured and calculated CrCl were significantly correlated (r=0.72, P<0.0001). Of the 256 HDMTX treatments evaluated, 158 (62%) had reliable 48 h serum MTX levels documented. Forty-seven levels (30%) were within target range (0.3-1 micromol/l), 99 levels (62%) were below target range (<0.3 micromol/l), 12 levels (8%) were in the range associated with mild toxicity range (>1-3 micromol/l), and no levels were in the range associated with severe toxicity (>3 micromol/l). Of these 158 treatments, the use of a calculated rather than measured CrCl would have yielded an identical MTX dose for 48 treatments (30%), a higher MTX dose for 62 treatments (40%), and a lower MTX dose for 48 treatments (30%). This distribution was not significantly different among the subsets of below target, within target range, and above target MTX levels (P=0.87). CONCLUSIONS: In this cohort of patients with PCNSL, there is significant correlation between the calculated and measured CrCl. MTX doses determined using calculated and measured CrCl are not significantly different. For these patients, there is no clear association between the method of determining CrCl and serum MTX levels. As a result, calculated CrCl is a reasonable alternative to measured CrCl in this patient population and would avoid the inconvenience and potential inaccuracies associated with measured CrCl.

Urine cytology of nonurothelial malignancies-a 10-year experience in a large multihospital healthcare system.

BACKGROUND: Urine cytology is the most frequently utilized test to detect urothelial cancer. Secondary bladder neoplasms need to be recognized as this impacts patient management. We report our experience on nonurothelial malignancies (NUM) detected in urine cytology over a 10-year period. METHODS: A 10-year retrospective search for patients with biopsy-proven NUM to the urothelial tract yielded 25 urine samples from 14 patients. Two cytopathologists blinded to the original cytology diagnosis reviewed the cytology and histology slides. The incidence, cytomorphologic features, diagnostic accuracy, factors influencing the diagnostic accuracy, and clinical impact of the cytology result were studied. RESULTS: The incidence of NUM was <1%. The male:female ratio was 1.3. An abnormality was detected in 60% of the cases; however, in only 4% of the cases, a primary site was identified accurately. Of the false negatives, 96% was deemed as sampling errors and 4% was interpretational. Patient management was not impacted in any of the false-negative cases due to concurrent or past tissue diagnosis. CONCLUSION: Colon cancer was the most frequent secondary tumor. Sampling error attributed to the false-negative results. Necrosis and dirty background was often associated with metastatic lesions from colon. Obtaining history of a primary tumor elsewhere was a key factor in diagnosis of a metastatic lesion. Hematopoietic malignancies remain to be a diagnostic challenge. Cytospin preparations were superior for evaluating nuclear detail and background material as opposed to monolayer (Thinprep) technology. Diagnostic accuracy was improved by obtaining immunohistochemistry. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc. Diagn. Cytopathol. 2017;45:22-28. © 2016 Wiley Periodicals, Inc.

Urinary pseudouridine in patients with lymphoma: comparison with other clinical parameters.

BACKGROUND: Some patients with malignant lymphoma do not manifest superficial lymphadenopathy. In such cases, clinical parameters that indicate the number of tumor cells are important for the assessment of tumor growth and choice of proper treatment. We evaluated urinary pseudouridine (U-PU) as an indicator of the growth of malignant lymphoma by comparing its levels with serum concentrations of other clinical parameters in patients with various lymphomas at various stages. METHODS: Urine was obtained from 67 patients with lymphoma. U-PU was assayed by recombinant Fab-based inhibition ELISA. Serum soluble IL2 receptor (sIL2R), serum deoxythymidine kinase (dTK), serum beta-2 microglobulin (beta2MG) and serum lactate dehydrogenase (LDH) were also assayed. RESULTS: U-PU concentrations showed good correlations with serum concentrations of beta2MG, LDH, sIL2R and dTK. The level of U-PU was higher in stage IV than in stages I (P=0.023), II (P=0.006) and III (P=0.036). CONCLUSION: U-PU concentration correlates with the clinical stage of lymphoma and is a useful tool to assess the growth of lymphoma.

Urinary excretion of monoacetyl polyamines in patients with non-Hodgkin's lymphoma.

The pretreatment concentrations of polyamines were determined in the 24-hr urine of 14 patients with widespread non-Hodgkin's lymphoma. In ten of 14 patients, the ratio of N1-acetylspermidine to N8-acetylspermidine was significantly higher than the mean for normal subjects. These results confirm our previous observations that the urinary excretion of N1-acetylspermidine is increased in some patients with lymphoma and suggest that the determination of urinary acetyl polyamines may be useful in conjunction with other procedures in the diagnosis of lymphoma. The ratio of N1-acetylspermidine to N8-acetylspermidine in the postchemotherapy 24-hr urine was 25 in one patient who had diffuse histiocytic lymphoma. This is the highest ratio ever reported. The patient responded well to chemotherapy, and rapid lysis of lymphoma lesion was observed. The potential utility of the rapid increase in the ratio of N1-acetylspermidine to N8-acetylspermidine as a criterion of tumor lysis is of interest and is currently under further investigation.

Postchemotherapy purine excretion in lymphoma patients receiving allopurinol.

The urinary excretion of hypoxanthine, xanthine, and uric acid was measured prior to and following chemotherapy in 11 patients with rapidly growing chemotherapy-sensitive lymphomas who were receiving concomitant allopurinol therapy. Mean maximal total dairy urinary excretions of these purines postchemotherapy were: uric acid, 807 mg/day; hypoxanthine, 343 mg/day; and xanthine, 638 mg/day. The mean maximal postchemotherapy urinary concentrations of uric acid, hypoxanthine, and xanthine were 288, 115, and 179 mg/liter, respectively. Mean total daily urinary excretion of uric acid, hypoxanthine, and xanthine rose 2.2-, 6.6-, and 6.9-fold, respectively, following initiation of antineoplastic therapy. Although standard doses of allopurinol did not prevent a postchemotherapy increase in the excretion of uric acid or hypoxanthine, the urinary concentrations of both compounds remained below their solubility in urine at pH 7 in all 11 patients studied. However, the urinary concentration of xanthine exceeded its solubility in urine at pH 7 in six of the 11 patients. In three of the six patients whose urinary concentration of xanthine concentration exceeded its solubility in urine, transient renal failure developed in association with the increased excretion of xanthine. These studies indicate that, despite the use of conventional doses of allopurinol, the urinary excretion of uric acid may still increase following massive tumor lysis, and urinary excretion of xanthine can increase to concentrations potentially causing xanthine nephropathy.

Urinary putrescine, spermidine, and spermine in human blood and solid cancers and in an experimental gastric tumor of rats.

An improved method of assay of urinary polyamines (putrescine, spermidine, and spermine) was applied to the study of cancer patients and an experimental gastric tumor of rats. Although total polyamines (putrescine, spermidine, and spermine) in urine of patients with blood and solid cancers were significantly high, putrescine concentrations also increased significantly and were shown to be of diagnostic aid even in solid cancers. A significant increase in putrescine was also noted in the urine of rats with experimental stomach tumors induced by N-methyl-N-nitro-N'-nitrosoguanidine.

Urinary 6-sulfatoxymelatonin excretion in humans during domestic exposure to 50 hertz electromagnetic fields.

OBJECTIVES: Exposure to extremely low frequency electromagnetic fields (ELF-EMF) has been suggested to suppress melatonin secretion, which might result in higher cancer risks because of its missing oncostatic action. We investigated the effects of residential exposure to ELF-EMF on the excretion of urinary 6-sulfatoxymelatonin (6-OHMS), the major melatonin metabolite, as an indicator of nocturnal melatonin secretion. METHODS: 6-OHMS was measured in two spot urine samples, collected at 22.00 h and 08.00 h, in 29 men and 22 women. Spot ELF-EMF measurements were conducted at the centre and the four angles of the living room, the bedroom, and the kitchen of study subjects at low current configuration (all lights and appliances turned off), and they were repeated immediately at high current configuration (all lights and appliances turned on). RESULTS: Risk of a reduced 6-OMHS nocturnal secretion was elevated for daily alcohol intake (OR = 6.4; 95%C.I. 1.4,33.1), and body mass index (BMI) above the median (OR = 2.2; 95%C.I. 0.5,9.6). Risk of disrupted rhythm of 6-OHMS excretion was moderately elevated for domestic ELF-EMF exposure above the upper tertile at low current configuration (OR = 2.6; 95%C.I. 0.4,15.7). CONCLUSION: Alcohol consumption, BMI, and gender seem to affect nocturnal melatonin secretion, while an effect of residential exposure to ELF-EMF is uncertain. Future studies should properly account for the effect of such variables, when addressing the hypothesis of disturbances in melatonin secretion as a plausible explanation for the reported excess risk of several tumoral diseases associated with low level ELF-EMF exposure.

Green urine in a critically ill patient.

The development of discolored urine in the critically ill patient, although uncommon, may have many possible causes, with the most likely source related to medication administration. Studies were undertaken in a 39-year-old man who developed dark green urine while in the intensive care unit for neutropenic sepsis. Although the patient had developed prior nonoliguric renal failure stemming from his sepsis, his renal function at the time of presentation of urine discoloration was considered normal. Review of his medications and intravenous infusions suggested the most likely cause was the food dye placed in his enteral tube feedings. Spectrophotometric evaluation of the urine confirmed the presence of Food Dye and Color Blue Number 1 (FD&C Blue No. 1). This case shows that significant gastrointestinal absorption of FD&C Blue No. 1 can occur. FD&C Blue No. 1 should be considered in the differential diagnosis of dark green discolored urine.

The clinical significance of Bence Jones proteinuria.

The detection of monoclonal light chains in the urine by the Bence Jones heat test is a useful adjuvant to the diagnosis of myeloma and other related diseases. The test is particularly helpful when no serum spike is noted. Overall, it is positive in approximately half of all patients with myeloma. In order to assess the accuracy of the test, we reviewed the records of all patients with a positive heat test for Bence Jones proteinuria during a single calendar year. Myeloma accounted for 68%, but patients with amyloidosis, the adult Fanconi syndrome, and others also had positive results. One-fifth of the results were false positive in that urine protein electrophoresis showed no spike and immunoelectrophoresis, no monoclonal protein. This group consisted largely of patients with connective tissue diseases, chronic renal failure, or nonplasmacytic malignancies. We also have seen patients who had monoclonal light chains in their urine but failed to show positive results to the heat test and were thus considered false negative. Although the heat test for Bence Jones proteins is a useful clinical test, one must be aware of both false-positive and false-negative results. Electrophoresis and immunoelectrophoresis of concentrated urine are the methods of choice for detection of a monoclonal light chain in the urine.

Excretion of modified nucleosides during development of malignant lymphomas in mice after whole body irradiation.

During x-ray-induced development of malignant lymphomas in mice their urinary excretion of eight modified nucleosides was monitored and the values were compared to the results of the histological examination of the animals at time of their sacrifice. It was found that the pathologically augmented excretion of modified nucleosides begins as much as several weeks before the malignant lymphomas can be diagnosed clinically. Thus some mice had increased levels of modified nucleosides even 10 weeks before sacrifice, though at the time of sacrifice the histological investigation revealed only some small foci of reticulum cell neoplasm in their spleen. It is therefore stressed that the usefulness of the determination of urinary modified nucleosides as an early noninvasive screening test for cancer in man and as an in vivo carcinogenicity test should be evaluated.