Urinary Enzymes and Protein Patterns as Indicators of Injury to Different Regions of the Kidney

Urinary Enzymes and Protein Patterns as Indicators of Injuryto Different Regions of the Kidney. STONARD, M. D., GORE, C.W., OLIVER, G. J. A., AND SMITH, I. K. (1987). Fundam. Appl.Toxicol. 9, 339–351. Acute experimental models of renaldamage to the proximal tubular, glomerular, and papillary regionsof the rat were produced by administration of hexachloro 1:3-butadiene(HCBD), puromycin aminonucleoside (PAN), and 2-bromoethylamine(BEA), respectively. Several routine indicators of nephrotoxicity,the enzymes alkaline phosphatase and N-acetyl-ß-glucosaminidase,and the molecular weight pattern of protein excretion were determinedon urine samples. Tubular damage produced by HCBD or BEA wasdiscriminated both quantitatively and qualitatively from glomerulardamage produced by PAN. The latter was characterized by a pronouncedincrease in protein excretion, especially proteins with molecularweight >40,000 Da. In contrast, protein excretion in tubulardamage was raised only slightly and characterized by excretionof proteins of a wide range of molecular weights. Proximal tubulardamage caused by HCBD and papillary damage caused by BEA weredistinguished both by conventional urinalysis (volume and specificgravity) and by measurement of the two urinary enzymes. Alkalinephosphatase and glucose were markedly and transiently elevatedin proximal tubular damage and N-acetyl-ß-glucosaminidaseshowed a sustained elevation in papillary damage. It is concludedthat both selective urinary enzymes and the molecular weightpattern of urinary proteins can be used to provide diagnosticinformation about the possible site of renal damage.     

Myocarditis associated with acute and subacute glomerulonephritis

One hundred sixty cases of anatomically proved acute and subacute glomerulonephritis, exclusive of those subsequent to scarlet fever, typhus fever, or prolonged septicemia, were reviewed to ascertain the presence and the character of any concomitant myocarditis. Such a myocarditis was found to have occurred in sixteen patients; there were clear-cut clinical manifestations of myocardial failure in twelve, and in two others the clinical records suggested it. The symptoms were those common in other forms of heart disease; namely, cyanosis, arrhythmia, temperature-pulse disproportion, and hypotension. Electrocardiographic tracings were abnormal in three of the four cases in which they were available.The increased heart weights, which were observed frequently, could be correlated better with the presence of myocarditis than with arterial hypertension, which had been noted in only four patients. The myocarditis had a distinctive character that differentiated it easily from that occurring as a result of sulfonamide hypersensitivity or after acute nasopharyngeal and tonsillar infections. Characteristically there was a widespread serous effusion into the interstitial tissues, increasing the space between the muscle fibers. The cellular elements were relatively sparse, consisting of lymphocytes, endothelial leucocytes, and Aschoff cell. The suggestion that myocardial damage is related to increased capillary permeability appears to coincide with the pathologic evidence. With regard to treatment, caution is recommended in the administration of intravenous fluids.     

Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxytryptamine receptor (type 3) antagonist

Ondansetron (GR38032F) is a selective antagonist of 5-hydroxytryptamine (5-HT) type 3 receptors. This randomized, double-blind, cross-over study was undertaken to evaluate and compare the effect of ondansetron with placebo on gastrointestinal transit in 10 healthy male volunteers. There were no significant differences between the effects of placebo and ondansetron on gastric emptying or mouth-to-caecum transit time. However, significant differences in mean whole-gut transit time were observed, that is 54.8 h with ondansetron and 32.1 h with placebo. Therefore, 5-HT3 receptors may be involved in the regulation of colonic transit and ondansetron may prove useful as an anti-diarrhoeal agent.     

A comparison of vincristine and doxorubicin infusional chemotherapy with methylprednisolone (VAMP) with the addition of weekly cyclophosphamide (C-VAMP) as induction treatment followed by autografting in previously untreated myeloma

In a sequential nonrandomized study, 204 consecutive unselected patients aged < 70 years received induction chemotherapy with infusional vincristine and adriamycin with oral methyl prednisolone (VAMP; n =75) or with additional cyclophosphamide, C-VAMP ( n =129). 38/129 C-VAMP patients also received verapamil during induction as part of a controlled trial with the aim to overcome drug resistance. A median of five courses (range 1–11) of chemotherapy were required before maximal response was attained and this was similar in both groups. An over-all response rate of 71% was noted at the end of induction. The complete remission (CR) rate with C-VAMP was 24%, which was significantly higher ( P =0.04) than the CR rate with VAMP alone (8%). The addition of verapamil did not alter the response rate of C-VAMP. Compliance to VAMP was overall 83% and not affected by the addition of cyclophosphamide. The proportion of patients going on to receive high-dose chemotherapy and an autograft was the same for VAMP and C-VAMP treated patients (71%). The median overall survival (OS) and progression-free survival (PFS) for the whole group were 4.4 years and 2.0 years and no difference in outcome was observed between the different treatment groups. Therefore the addition of weekly cyclophosphamide to VAMP induction therapy has significantly improved the response rates of previously untreated myeloma patients. C-VAMP was not more toxic and did not compromise the chances of receiving an autograft. Verapamil was without influence on any parameters in this study.