Serum calcitonin gene-related peptide levels in untreated prostate cancer patients

BACKGROUND: The role of calcitonin gene-related peptide (CGRP) in prostate cancer has not been fully understood. Moreover, the serum CGRP level in prostate cancer patients has never been reported. We measured the serum CGRP levels in untreated prostate cancer patients to elucidate its clinical significance. MATERIALS AND METHODS: We used 36 serum samples from prostate cancer patients. All patients had never received any treatment. Serum CGRP was measured by immunoradiometric assay, and we analysed the association between serum CGRP level and clinicopathological factors. RESULTS: Serum CGRP levels in the patients with higher clinical stages and histological grade were significantly higher than in those with lower stages and grade, respectively. But the levels did not correlate with the patient's age, liver or renal functions, serum prostate-specific antigen levels. CONCLUSION: Serum CGRP levels were significantly elevated in the patients with high grade or high stage untreated prostate cancer patients. Measurement of the serum CGRP may be a useful predictor of staging or grading of prostate cancer in the untreated prostate cancer patients.     

Enzymatic Hydrolysis of Zenarestat 1-O-Acylglucuronide

Abstract— Zenarestat, (3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-1-y1) acetic acid, an aldose reductase inhibitor is metabolized mainly to the glucuronide in rat and man. The glucuronide was purified from urine of volunteers after ingestion of zenarestat. The structure of the glucuronide was confirmed by LC-MS and NMR as 1-O-acyl-β-glucuronide. This compound was unstable at physiological pH, being converted to its structural isomers and the aglycone with half-life of 25 min at pH 7·4 and 37°C in aqueous solution. Enzymatic hydrolysis of the glucuronide was studied in urine, blood and tissues. β-Glucuronidase in human urine contributed little to the hydrolysis of the glucuronide, while in rat urine at pH 6, it was degraded by β-glucuronidase and the formation of zenarestat was clearly faster than its formation in buffer at pH 6. In both rat and human blood, these reactions were accelerated by albumin, although rat red blood cells may also contribute. The rate of degradation was not affected by red blood cell membrane, haemoglobin, globulin, esterases or β-glucuronidase. Arylesterase in rat liver, arylesterase and acetylcholinesterase in the kidney, and β-glucuronidase in both tissues may contribute. Thus, enzymatic degradation of zenarestat 1-O-acyl-β-glucuronide is dependent not only on pH and temperature but also on species and the type of tissue or body fluid.     

Congenital Malformations in Newborns from Diabetic Mothers*

It has been well known that there is a high incidence of congenital malformations in newborns from diabetic mothers when the mothers' diabetes control before and during pregnancy is poor. We treated 438 pregnant diabetics who bore 443 children between February 1964 and June 1992. Among these children, there were 51 cases (11.5%) with congenital malformations, 21 cases with major anomalies (4.7%) and 30 cases with minor anomalies (6.8%). The type of malformations are not related to special organs; heart malformations and cleft lips are relatively frequent compared to other types of malformations. The mechanism of the congenital malformations in newborns from diabetic mothers remains unclear. However, clinically and experimentally it has been found to be due to fuel-mediated teratogenesis. Since October 1978, HbAi has been used as an index of diabetic control and the relationship between congenital malformations and the mother's diabetes control has been observed. 1) There is no difference in the incidence of malformations in children from IDDM and NIDDM mothers. However, there are more severe malformations in the children from IDDM mothers compared to those from NIDDM mothers. 2) Mothers who bore children with major malformations had all made their first visit to our hospital after pregnancy. HbAi in the IDDM mothers who had children with malformations at the first visit was 11%. 3) In the NIDDM mothers, even if HbAi levels are near normal, children with major malformations were born and there was little relationship between congenital malformations and the mothers' diabetes control. These data suggest that there are two kinds of congenital malformations in children from diabetic mothers, fuel-mediated teratogenesis, and malformations as seen in children from non-diabetic mothers.     

Primary serous adenocarcinoma of the retroperitoneum with a response to platinum-based chemotherapy: a case report

A CAT-scan-guided biopsy of the retroperitoneal tumor of a 54-year-old female revealed a serous adenocarcinoma resembling a serous adenocarcinoma of ovarian origin. Partial response to platinum-based chemotherapy was observed. Exploratory laparotomies and an autopsy found no possible primary lesion for the tumor. Therefore, we concluded that this tumor is a primary serous adenocarcinoma of the retroperitoneum. Although further accumulation of cases is required, it appears that primary treatment for serous adenocarcinoma of the retroperitoneum is platinum-based chemotherapy if surgical removal is incomplete.     

Malignant transformation of renal angiomyolipoma

In the present paper, two cases of malignant transformation of renal angiomyolipoma without tuberous sclerosis are reported. Pathological examination revealed that, in both cases, in addition to the areas affected by typical angiomyolipoma, there were areas that contained elevated numbers of perivascular epithelioid cells with prominent nuclear pleomorphism. Immunohistochemical examination revealed that both cases were negative for keratin and epithelial membrane antigen, but were positive for the melanogenesis-related marker HMB-45. Metastatic diseases appeared 40 months after radical nephrectomy in the first case and 18 months in the second case.     

Quantitative Analysis of Concealed Conduction into Accessory Atrioventricular Pathways in Wolff-Parkinson-White Syndrome

Concealed conduction is demonstrated to occur in an accessory AV pathway (AP). To test the hypothesis that anterograde and retrograde concealed conduction in the AP would have different characteristics, 35 consecutive patients with single APs were studied. The anterograde or retrograde ERP of the AP could be determined in 23 of those patients. Anterograde concealed conduction in the AP was assessed in the first 13 patients with retrograde AP conduction (8 APs with retrograde conduction only and 5 with both directions) (group A). Retrograde concealed conduction in the AP was evaluated in the remaining 10 patients with anterograde AP conduction (6 APs with anterograde conduction only and 4 with both directions) (group B). The concealed conduction in the AP was quantified by determining the ERP of the AP using a “probe” extrastimulus (S_p) introduced in the opposite chamber. The ERP was determined both during conventional extrastimulus (S₁S₂ method; ERP_c) and during that with an S_p (S₁S_pS₂ method; ERP_p). The S_p was delivered before or after the last S₁ with various S₁S_p intervals. The ERP_p was determined at each S₁S_p interval. Three distinct patterns in concealed conduction in the AP were noted. In the first pattern, the ERP_p was always shorter than the ERP_c, whereas the reverse relation was noted in the second pattern. The third pattern showed a combination of the two. In group A, only the first pattern was noted. In group B, the first, second, and third patterns were noted in 4, 2, and 4 patients, respectively. The first pattern was noted only in septal APs and the second and third were seen only in left free-wall APs. The second pattern was seen in patients with retrograde AP conduction, whereas the third one was mainly noted in patients without retrograde AP conduction. These observations indicate that anterograde and retrograde concealed conduction in the AP have different characteristics. Shortening of the ERP_p might be due to the “peeling back” phenomenon, and its lengthening might be caused by the presence of the inhomogeneous refractory periods of the AP. (PACE 1997; 20[Pt. I]:1342-1353)