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Cervical cancer incidence and mortality can be reduced by removal of precursor lesions detected at cytological screening. Organised screening, i.e. regular invitation of defined target groups, is generally considered more effective than opportunistic scre, Addresses: GUSTAFSSON L, UNIV UPPSALA HOSP, DEPT CANC EPIDEMIOL, S-75185 UPPSALA, SWEDEN. UNIV UPPSALA HOSP, DEPT PATHOL, S-75185 UPPSALA, SWEDEN. UNIV UPPSALA, DEPT STAT, S-75120 UPPSALA, SWEDEN. HARVARD UNIV, SCH MED, DEPT EPIDEMIOL, BOSTON, MA 02115.

Proximal duodenum was perfused with HCl for 5 min and the effects on blood-to-lumen clearance of 51Cr-EDTA (ED-Cl), morphology, luminal alkalinization, and blood flow determined in anesthetized rats. The rate of alkalinization was determined by back titration and blood flow assessed by laser Doppler flowmetry or by ultrasonic transit time flowmetry. Perfusion of duodenum with 30, 50 or 100 mM HCl for 5 min increased ED-Cl in a concentration-dependent manner and induced a small increase in alkalinization but had no effect on blood flow. At 55 min after cessation of perfusion with 100 mM HCl ED-Cl was 2.2-fold higher than control whereas the ED-Cl values in animals perfused with 30 or 50 mM HCl were not different from pre-acid control values. 100 mM HCl also induced an increase in 14C-mannitol and 14C-polyethylene glycol 4000 clearance, suggesting that HCl does indeed increase mucosal permeability. The 100 mM HCl-induced rise in mucosal permeability most probably reflects disturbance of mucosal integrity because three of five animals exhibited villous tip damage. The increases in ED-Cl in response to 100 mM HCl were the same in control rats as in rats with the renal pedicles ligated, indicating that the acid susceptibility is not affected by acute functional nephrectomy.

The duodenum in anesthetized rats was perfused with HCl, and mucosal integrity was assessed by measuring the clearance of 51Cr-labeled EDTA from blood to lumen and/or by morphological examination (lesion score). Duodenal blood flow was determined by laser Doppler flowmetry and luminal alkalinization as well as H+ disappearance by backtitration. Intravenous infusion of vasoactive intestinal polypeptide (VIP; 13.5 micrograms.kg-1.h-1) increased luminal alkalinization threefold and decreased clearance of 51Cr-EDTA by 50%. VIP also decreased arterial blood pressure and induced a small and irregular decrease in duodenal blood flow. Perfusion with 10 mM HCl increased clearance of 51Cr-EDTA 2.1-fold, but the lesion score was not different from that in saline-perfused animals. Perfusion with 20 mM HCl increased clearance of 51Cr-EDTA four-fold and induced a greater lesion score than did 10 mM. Perfusion with either 10 or 20 mM HCl did not affect the duodenal blood flow. VIP reduced the rise in clearance of 51Cr-EDTA in response to 10 mM but not that to 20 mM HCl. Intravenous injection of prazosin (50 micrograms/kg) decreased luminal alkalinization, clearance of 51Cr-EDTA, blood pressure, and duodenal blood flow. In prazosin-pretreated rats, perfusion with 10 mM HCl increased clearance of 51Cr-EDTA 2.6-fold, and the lesion score was greater in this group than in animals infused with VIP. A positive linear correlation was obtained between HCO3- secretion and the mean rate of H+ disappearance.(ABSTRACT TRUNCATED AT 250 WORDS)

The distribution of the mRNAs for chromogranin A and B was analyzed by in situ hybridization with 35S-labeled oligonucleotide probes in formalin-fixed paraffin-embedded carcinoid tumor tissues. All the 15 mid-gut carcinoid tumors examined contained both mRNAs for chromogranin A and B at high level in tumor cells. Sixteen of 18 bronchial carcinoid tumors but only 2 of 5 rectal carcinoid tumors expressed one or both species of chromogranin mRNAs. The same tendency was seen with the argyrophil reaction according to Grimelius where most of the mid-gut tumor cells were uniformly stained, while considerable variation in reactivity was seen in some of the bronchial and rectal carcinoid tumor cells. The sequential sections were stained with a monoclonal antibody against chromogranin A and a polyclonal antiserum which reacts with both chromogranins. The expression of the mRNA for chromogranin A on the carcinoid tumors was almost concordant with that of chromogranin B as well as with the chromogranin A protein, whereas almost all tumors stained positively with the polyclonal antibodies. Analyses of mRNA expression of chromogranin A before and after interferon therapy on 4 patients with mid-gut carcinoids indicated an inhibition at pre-translational level. In conclusion, the mRNAs for chromogranin A and B are good markers for the carcinoid tumors, especially of mid-gut origin. Fore-gut, mid-gut and rectal carcinoid tumors are different in their endocrine properties regarding the expression of the chromogranins.