Low Hartmann's procedure for severe anorectal Crohn's disease. Perineal wounds often fail to heal following proctectomy for Crohn's disease. Twenty-five patients with severe anorectal Crohn's disease and perineal fistulas, necessitating excisional surgery, underwent a low Hartmann's procedure in lieu of a standard proctectomy. Fifteen of the 25 (60 percent) patients had a completely healed perineum and required no further surgical therapy. Although perineal disease persisted in the other 10 patients, their perinea were much improved compared with the initial presentation. Following a low Hartmann's procedure, the rectal stump becomes atrophic and anoperineal disease regresses, thereby permitting subsequent perineal proctectomy in less inflamed tissues. Since only a 3-cm to 5-cm cuff of rectum was retained from the initial surgery, a perineal intersphincteric approach could be employed and no abdominal dissection was necessary. Of the 10 patients who subsequently underwent perineal proctectomies, three patients still have an unhealed perineum. Twenty-two of the 25 (88 percent) patients have a completely healed perineum (mean follow-up period, 69.1 months). No attempt was made to establish intestinal continuity in any of the 25 patients. We conclude that the problem of the unhealed perineal wound can be averted with this approach, thereby reducing the long-term morbidity to the patient.


Accuracy of colonoscopy for the detection of colorectal polyps. The findings at colonoscopy were compared with the pathologic findings of the surgical specimen in 235 patients who underwent a colon resection for a primary colorectal neoplasm from January 1980 to December 1987 at Roswell Park Cancer Institute. Seven patients (3 percent) were found to have synchronous primary colon carcinomas, and 100 patients (43 percent) were found to have synchronous adenomatous polyps identified by colonoscopy and/or pathology. In patients with polyps 10 mm or greater in diameter, the findings on colonoscopy agreed with the pathology report 96 percent of the time. When polyps of all sizes were included, with many less than 5 mm in diameter, colonoscopy agreed with the pathology in 89 percent of patients. When only the area of the colon resected was used to determine the ability of colonoscopy to locate polyps, 58 percent of polyps of all sizes were located. The majority of the missed polyps were adjacent to a carcinoma. One cecal carcinoma was not seen by colonoscopy because of technical inabilities to reach the cecum. A second carcinoma (20 mm x 17 mm) was not seen at the splenic flexure.


Colon trauma--clinical staging for surgical decision making. Analysis of 119 cases. A retrospective study is presented of 119 patients admitted to the Central Hospital of the Venezuelan Institute of Social Security, in Caracas, between 1982 and 1990, with the diagnosis of colon trauma. Several parameters including age, etiology, time elapsed between the accident or assault and hospital admission, preoperative and postoperative hemoglobin and diastolic blood pressure, associated lesions, procedure practiced, complication rate, and hospital mortality are reviewed. The second and third decades of life appear most often involved. Most patients reached the hospital within the first four hours of the accident or assault. Anemia, sustained diastolic hypotension, and number of organs involved in addition to the colon were important prognostic factors for complications. Apparently the surgical procedure, with simple suture or resection, mostly without "protective" colostomy, was not very relevant. Hospital mortality was 2.4 percent. A staging system based on clinical conditions for decision making in the operating room was used in an attempt to inject some objectivity into the surgical approach.


Role of wrapping in concomitant intra-abdominal aneurysm and colorectal carcinoma. Report of three cases. The therapeutic measure against concomitant intraabdominal aneurysm and colorectal carcinoma is still a dilemma. Here we report the clinical courses of three cases of colorectal carcinoma coincidental with moderate-sized abdominal aortic or iliac artery aneurysm in those who underwent operations during a recent three-year period. Resection of malignant lesion and wrapping of aneurysm were carried out in all three patients simultaneously. Carcinoma was staged by Dukes classification as A in one patient and B in two patients. All tolerated surgery well without any signs of complications. Two-year or three-year follow-up shows that they have continued to do well, with no further symptoms of abdominal aortic aneurysm, peripheral vascular disease, or recurrence of colorectal carcinoma. We conclude that, if the aneurysm is not about to rupture and the carcinoma is in an advanced stage, then the carcinoma should be resected, associated with interim aneurysmal wrapping. However, both lesions need to be resected eventually for long-term survival.


Technical modification to laparoscopic appendectomy. An alternative technique for laparoscopic appendectomy is described. The isolated appendix is exteriorized through the trocar wound, ligated, and resected. The cecum is then returned to the abdomen.


Chronic administration of cyclosporin A induces a decrease in hepatic excretory function in man. Chronic administration of cyclosporin A may induce cholestasis in a few patients. The purpose of this study was to examine the effect of chronic administration of cyclosporin A on serum bile acid levels, serum bilirubin concentration, and bromosulfophthalein plasmatic fractional clearance. Twenty heart-transplanted patients with normal serum alanine aminotransferase activity receiving cyclosporine A during a mean duration of 33 months (range 7-54) were compared to 20 matched kidney-transplanted patients with normal serum alanine aminotransferase receiving azathioprine for a mean duration of 34 months (range 6-72). As compared to azathioprine-treated patients, patients treated with cyclosporin A had an increase in serum bile acid levels of 32% (P < 0.01), an increase in serum bilirubin concentration of 100% (P < 0.001), and a decrease in bromosulfophthalein plasmatic fractional clearance of 60% (P < 0.001). These results suggest that cyclosporin A induces a decrease in hepatic excretory function in man.


Effects of interferon-alpha therapy on serum and liver HBV DNA in patients with chronic hepatitis B. The aim of this study was to evaluate the effect of interferon-alpha therapy on serum and liver HBV DNA in 20 patients with chronic hepatitis B and to correlate the presence or absence of HBV DNA with the clinical response. There were 11 responders and all lost HBV DNA from the serum. Ten of the 11 were followed for 36 months following IFN treatment and remained well with absence of HBeAg and HBV DNA from the serum and with normal ALT. Five also lost HBsAg. HBV DNA became undetectable in the liver of nine of 10 of these patients in whom liver tissue was available for study. HBV DNA persisted in the liver of seven of nine nonresponders and was not detected in two in spite of the presence of HBV DNA and HBeAg in the serum of these two patients. We conclude that IFN may induce long remissions in patients with chronic hepatitis B with loss of HBV DNA from the serum and that occasionally HBV DNA may persist in the liver of such patients.


Profile of alkaline phosphatase isoenzymes in ten patients poisoned by mushrooms of the genus Lepiota. Mushrooms of the genus Lepiota (helveola and bruneo-incarnata), similar to those of the genus Amanita, contain amatoxins. Amatoxins, especially amanitin, cause cellular destruction by inhibiting RNA polymerase. Due to the hepatic toxicity of these mushrooms, we have assessed their incidence on alkaline phosphatase levels and on its isoenzymes. Total alkaline phosphatase activity levels were not found to be increased except in two patients, and then only moderately. As regards isoenzymes, the occurrence of a double hepatic fraction in five of the 10 patients, is the most remarkable finding. There seems to exist a relatively close correspondence between the occurrence of a hepatic2 fraction correlating with those of urine amanitin. We conclude that the hepatic2 fraction proves to be important in assessing liver damage by mushroom poisoning because of its correlation with the patient's degree of poisoning.


Analysis of clinical course and prognosis of culture-positive spontaneous bacterial peritonitis and neutrocytic ascites. Evidence of the same disease. The clinical significance and prognosis of culture-negative neutrocytic ascites in cirrhotic patients is a controversial topic. In the present study, the clinical and humoral presentation and the short- and long-term prognosis were analyzed in 36 patients with cirrhosis and culture-positive spontaneous bacterial peritonitis and in 28 patients with cirrhosis and ascitic fluid polymorphonuclear count greater than 250/mm3, a negative ascitic fluid culture, and without previous antibiotic therapy. On admission there were no significant differences between groups related to age, sex, alcoholism, fever, abdominal pain, serum albumin, serum urea, serum creatinine, Child-Pugh score, polymorphonuclear count, and total protein concentration in ascitic fluid. A greater frequency of positive blood culture was found in patients with spontaneous bacterial peritonitis (15/21 vs 2/18) (P < 0.001). Mortality during the first episode was 36% in patients with spontaneous bacterial peritonitis and 46% in patients with culture-negative neutrocytic ascites (NS). Mortality during follow-up was high and survival probability at 12 months was 32% in spontaneous bacterial peritonitis and 31% in culture-negative neutrocytic ascites. The probability of recurrence at 12 months was 33% in spontaneous bacterial peritonitis and 34% in culture-negative neutrocytic ascites. Our results show that spontaneous bacterial peritonitis and culture-negative neutrocytic ascites are variants of the same disease with a high mortality and poor prognosis.


Disturbance of plasma thyroid hormone levels after experimental liver transplantation. Is there an association with primary graft nonfunction? It has been suggested recently that preoperative plasma thyroid hormone levels may be used to predict the success of liver transplantation in prospective recipients and also perhaps that postoperative levels may be used to identify rejection. In the present study of unimmunosuppressed porcine recipients of liver allografts, two groups of animals were identified--those that died within five days postoperatively and the other group that were longer survivors. On the first postoperative day plasma levels of total and free T4 and total and free T3 declined and of total rT3 increased. In survivors these levels returned towards normal within three days, while they persisted in nonsurvivors. As there was no obvious cause of graft failure in nonsurvivors, the state might be considered to represent primary graft nonfunction in pigs, and the changes in plasma thyroid hormone levels may be predictive of this condition; a study in patients may confirm this.


Hepatic cavitation. A marker of transient hepatocellular injury during biliary lithotripsy. Sonographically visible microbubbles attributable to cavitation effects have been observed in bile (within the gallbladder), in hepatic vessels, and within the liver of patients undergoing biliary lithotripsy. Cavitation effects are believed to contribute to stone fragmentation and possibly tissue injury during lithotripsy. To study the latter, the relationship between intraparenchymal hepatic cavitation and serum transaminase activity and clinical follow-up was analyzed in 81 patients undergoing 164 lithotripsy treatments. Seventy-one treatments (43%) resulted in sonographically evident microbubbles in the liver parenchyma during lithotripsy. A temporary, yet statistically significant (P < 0.01) rise in SGOT and SGPT was observed within 2 hr of completion of lithotripsy compared to those patients without hepatic microbubbles. All but one patient had a return to pretreatment baseline levels of SGOT and SGPT by two weeks after lithotripsy. In this patient, persistent elevation of transaminases was attributed to the delayed passage of fragments and not to any sequelae from hepatic cavitation effects. Ultrasound immediately after, two weeks after, and 3-12 months after lithotripsy showed no hepatic structural abnormalities. Ursodiol administration at the time of treatment did not predispose to hepatic cavitation or elevation of transaminase. Detection of hepatic microbubbles during lithotripsy is a marker of hepatocellular injury. Their correlation with transaminase elevation refutes the contention that transaminasemia results solely from fragment passage after lithotripsy. Although not associated with recognizable structural damage or long-term sequelae, cavitation effects and transaminasemia reiterate that shockwaves are not entirely benign as they traverse parenchymal organs.


Patients with uncomplicated cholelithiasis acidify bile normally. Reports have suggested that patients with gallstones have gallbladder bile that is less acidic and more saturated with calcium carbonate than patients without gallstones. This failure to acidify bile may play a role in the formation of gallstones. We, therefore, compared gallbladder bile pH, ionized calcium, and calcium carbonate saturation index from patients undergoing either incidental gallbladder removal (controls, n = 23) or elective cholecystectomy for gallstones (n = 55). Gallstones were classified as either cholesterol (n = 39) or black pigment (n = 16) stones. No difference in gallbladder bile pH was noted among the controls, cholesterol stone, and pigment stone patients. In addition, no difference in ionized calcium concentration or CCSI was noted among the three groups. The pH in additional patients (n = 49) with acute cholecystitis, common bile duct obstruction, biliary tract infection, and cystic duct obstruction was significantly more acidic. We conclude that neither a defect in bile acidification nor increased saturation of calcium carbonate explains why human cholesterol or pigment gallstones form.


Secretion of biliary calcium is increased in dogs with pigment gallstones. We have previously demonstrated that gallbladder bile is supersaturated with calcium bilirubinate in a canine dietary model of pigment gallstones. Supersaturation resulted from combined increases in the concentrations of both biliary calcium and unconjugated bilirubin. The elevations in biliary calcium and unconjugated bilirubin concentrations remain unexplained but could possibly be due to increases in hepatic or ductular secretion, alterations in bile composition with respect to calcium-or bilirubin-binding affinity, decreases in absorption from the gallbladder lumen, or, in the case of unconjugated bilirubin, production within the lumen by hydrolysis of conjugated bilirubin. Here, we study a single possible cause for the observed increase in biliary calcium concentration during pigment gallstone formation in dogs. Secretion of calcium into bile in dogs with pigment gallstones before and after infusion of the bile salt, taurocholate, was compared to normal dogs. A significant increase in bile acid-independent bile flow and calcium output (CaO) was observed at any given bile acid output. Thus, plots of bile flow and CaO versus bile acid output yielded two separate functions in normal dogs and dogs with pigment gallstones. The slopes of these functions were similar, but intercepts extrapolated to zero bile acid output were markedly different, indicating that bile acid-independent, but not bile acid-dependent, bile flow and CaO was increased. The increase in CaO was not due to secretion of bile with increased concentrations of calcium but rather to the increases in the rate of bile flow. These findings might, in part, explain elevated calcium concentrations since increased amounts of calcium would be presented to the gallbladder in these animals during gallstone formation.


Biliary pressure variation in coordination with migrating motor complex of duodenum in patients with cholecystectomy and effects of morphine and cerulein. Pressures in the common bile duct and duodenum were continuously measured with two pressure microtransducers placed by endoscopy in 10 postcholecystectomy patients. A complete cycle of the migrating motor complex of the duodenum was obtained in seven patients, its length ranging from 62 to 174 min with a mean of 114 min. The biliary pressure showed a transient elevation of 5.0 +/- 0.6 (mean +/- SEM) mm Hg (P < 0.001) in concert with phase III of the duodenal cycle in all 10 patients, whereas it remained stable during other phases. Intramuscular morphine (0.2 mg/kg) given to induce spasm of the sphincter of Oddi 20 min after the passage of phase III invariably produced an activity front in the duodenum and a sustained increase in the biliary pressure, the magnitude of which was 8.3 +/- 0.9 mm Hg. The biliary pressure raised by morphine dropped after an intravenous injection of cerulein (0.1 microgram/kg) as a sphincter relaxant. These findings indicate that the biliary pressure rises transiently at phase III of the duodenal cycle in patients after cholecystectomy, probably due to contractions of the sphincter of Oddi.


Measurement of segmental transit through the gut in man. A novel approach by the biomagnetic method. The techniques commonly used to evaluate the transit of contents through the gut feature some limitations for being either inaccurate, invasive, inconvenient, or potentially dangerous for the subjects. Aim of this study was to establish a safe, noninvasive and accurate technique for the measurement of segmental oroanal transit time. We localized an orally ingested magnetic marker by means of a biomagnetic instrumentation that allows us to identify in a three-dimensional pattern the position of a biomagnetic source inside the body. The biomagnetic localizations were compared with the anatomical data obtained by magnetic resonance imaging investigations. The study was performed in 12 healthy subjects, and scans were taken every hour up to the arrival of the marker into the cecum; thereafter, scans were taken every 4 hr up to the elimination of the marker. In 99% of the isofield maps obtained from each field scan, the marker was localized within the bowel walls. The mean oroanal transit time was 56 +/- 5 hr, the mouth-to-cecum transit time was 13 +/- 1.7 hr, and the total colonic transit time was 43.5 +/- 5 hr (mean +/- SEM). Segmental colon transit did not show major differences among the regions considered, although most of the time was spent in the right colon. In fact, a good correlation was found between transit time through the right colon and oroanal and total colonic transit (r = 0.77, P < 0.02, r = 0.79, P < 0.02 respectively). In conclusion, this method might be a safe alternative to the techniques presently used in the clinical setting for the measurement of intestinal transit.


Cigarette smoking and nicotine delay postprandial mouth-cecum transit time. The acute effects of both cigarette smoking and nicotine on postprandial mouth-cecum transit were studied in 20 habitual smokers, 10 males and 10 females. Mouth-cecum transit time was measured by the breath hydrogen technique, following ingestion of a standard mixed liquid meal. Each subject was studied on four separate occasions, either (1) sham or actively smoking two standard cigarettes, commencing 20 min after the meal, or (2) chewing two placebo or nicotine tablets over a 60-min period, commencing immediately after the meal. The time of administration of these stimuli was designed to minimize the effects on mouth-cecum transit time of alterations in gastric emptying. Mouth-cecum transit time was prolonged in response to both smoking [median and interquartile range: 120 (95, 150) min vs 100 (75, 140) min, P = 0.01] and nicotine [120 (80, 170) min vs 100 (70, 140) min, P = 0.002]. No difference was observed between sexes with respect to nicotine; the effect of smoking on mouth-cecum transit time, however, was less pronounced in females compared to males [difference active-placebo: 10 (10, 20) min vs 35 (20, 60) min, P = 0.01]. We conclude that acute cigarette smoking delays mouth-cecum transit time, an effect most likely due to nicotine.


Effects of gender, age, and body mass index on gastrointestinal transit times. This study aimed to assess separately the effects of gender, age, and body mass index on gastric emptying, small intestinal transit, and colonic transit times of a meal containing 99mTc-labeled cellulose fiber and 2- to 3-mm 111In-labeled plastic particles. Seventeen healthy young subjects (nine men; eight women; age 21-27 years; body mass index 18.4-25.1 kg/m2) and 16 healthy older subjects (eight men; eight women; age 55-74 years; body mass index 19.8-36.0 kg/m2) were studied. All transit variables were unaffected by gender. The older subjects had a slower mean colonic transit time of radiolabeled plastic particles than the young subjects (P < 0.05). Age did not affect mean gastric emptying or mean small intestinal transit times of the radiolabeled markers. An inverse association was found between body mass index and mean gastric emptying time of radiolabeled cellulose fiber (P < 0.02). Body mass index had no influence on other transit variables. The study revealed a considerable intersubject and a somewhat smaller intrasubject variability in mean gastric emptying, mean small intestinal, and mean colonic transit times.


Differences between jejunal myoelectric activity after a meal and during phase 2 of migrating motor complexes in healthy humans. Using an intraluminal probe with six pairs of annular electrodes, the myoelectric activity of the proximal jejunum was recorded during 48-hr sessions in 16 healthy volunteers receiving evening and noon meals (1000 kcal) and breakfast (400 kcal). In 10 subjects receiving no drug, the characteristics of the migrating motor complexes (period, duration of each phase, velocity of propagation of phase 3, duration of the postprandial disruption) varied markedly between subjects but were relatively constant from the first to the second day of recording. Single spike bursts propagated at a rate of 2-5 cm/sec, clusters of 3-10 spike bursts propagated at a rate of 0.5-1 cm/sec, and similar clusters recurring repetitively each 1.5-2 min were observed after the meals and very rarely in the fasted state during phase 2 of nocturnal migrating motor complexes. In six subjects, oral administration of codeine (50 mg) 1 hr before a meal induced migrating motor complexes in the postprandial state, with characteristics similar to that observed in the fasted state except a longer duration of phase 2. Single spike bursts and isolated and repetitive clusters of spike bursts were observed during phase 2 of the codeine-induced migrating motor complexes and after meals preceded by placebo, but very rarely during the phase 2 of nocturnal (fasted state) migrating motor complexes. It is concluded that the patterns of jejunal contractions consisting of propagated single spike bursts and isolated or repetitive spike bursts characterize the postprandial state in healthy humans and are dependent upon digesta flow.


Mechanisms for postprandial release of motilin in humans. Plasma concentrations of motilin rise in the first 30 min following the ingestion of a meal in man. To elucidate the mechanisms of this postprandial motilin release, we verified the effect of cerebral stimulation and of gastric distension, both events normally occurring in the early postprandial period, on plasma motilin concentrations. Cerebral stimulation was induced by modified sham feeding (MSF) and gastric distension was done by inflating (with 0, 60, 240, or 480 cc of air) a latex balloon positioned in the gastric fundus. The experiments were performed in healthy volunteers where antroduodenal contractile activity was continuously recorded and where plasma motilin was measured each 10 min. The stimuli were administered 30 min after a phase III of the migrating motor complex (MMC) was seen migrating from the antrum to the duodenum. The interval period between two successive spontaneous peak increases in plasma motilin was estimated at 113.7 +/- 8.5 min in 24 historical control subjects, and it lasted 97 +/- 13 min in the five control volunteers here distended with 0 cc of air (P = NS). This interval was significantly (P < 0.05) shortened with MSF (70 +/- 6.3 min) or following distension with 60 cc (60 +/- 11.4 min), 240 cc (54 +/- 1.9 min) or 480 cc of air (45 +/- 3.2 min). During the 60-min period following the administration of the stimuli, phase IIIs were not seen in the subjects distended with 0 cc of air or in those submitted to MSF.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessment by prolonged ambulatory manometry of the effect of oral cisapride on proximal small bowel inter-digestive motility. The effects of cisapride, given orally at standard therapeutic dosage (10 mg tds), on proximal small bowel interdigestive motility in ten healthy volunteers was assessed by prolonged ambulatory manometry. Cisapride did not alter the duration of the MMC cycle, duration of phase II or the propagation rate of phase III in either the daytime or nighttime periods. However, when compared to studies, in which subjects received no drug, both nighttime and daytime phase II mean contractile amplitude, but not contractile incidence, were significantly increased (P < or = 0.001) by cisapride. Cisapride significantly increased the incidence of distally propagated clustered activity. We conclude that the major effects of cisapride on healthy small bowel motor function is to increase the mean contractile amplitude and incidence of distally propagated clustered activity.


Significance and regulation of gastric secretion of platelet-activating factor (PAF-acether) in man. Platelet-activating factor (PAF) has been implicated in the pathogenesis of acute inflammatory and ulcerative diseases of the upper gastrointestinal tract. In the present study, we compared the gastric output of PAF and its precursors with gastric acid output, in patients with various upper gastrointestinal tract diseases and healthy controls. PAF and precursors were also extracted from gastric biopsies from subjects with chronic gastritis and/or gastric colonization by Helicobacter pylori. Under basal conditions, hourly gastric PAF output increased in esophagitis and erosive gastritis, but not in duodenal ulcer or Zollinger-Ellison syndrome. In the gastric juice of duodenal ulcer patients, PAF output rose after secretin, but in patients with Zollinger-Ellison syndrome, PAF was only detected when gastric acid secretion had been reduced by antisecretory drugs and no concurrent changes were observed in serum gastrin levels. After pentagastrin, patients and controls exhibited a significant decrease in PAF output and a negative correlation was found between PAF and acid outputs (r = -0.57, p < 0.01). When PAF was incubated with gastric juice in vitro, it underwent degradation irrespective of the medium pH. We found no relation between the outputs of PAF and precursors and the severity of gastritis or gastric colonization by H. pylori. Overall, these results suggest that PAF might be released in the stomach by gastric epithelial cells and could be responsible for mucosal injury of the upper gastrointestinal tract.


Effects of antiulcer drugs on phosphatidylcholine synthesis in isolated guinea pig gastric glands. To better understand phosphatidylcholine synthesis in the stomach, we isolated guinea pig gastric glands and examined their [3H]choline incorporation into phosphatidylcholine in response to either antiulcer drugs such as geranylgeranylacetone (GGA) and H2-receptor antagonists or agents that cause phosphatidylcholine synthesis in other tissues. [3H]Choline incorporation was stimulated by GGA, palmitate, and 12-O-tetradecanoylphorbol-13-acetate (TPA). Dibutyryl cyclic-AMP had no effect. By contrast with GGA, famotidine, ranitidine, and cimetidine equipotently inhibited [3H]choline incorporation into phosphatidylcholine. GGA, palmitate, and TPA increased phosphatidyl-[3H]choline and decreased phosphoryl-[3H]choline as compared with control in tissues that had been pulsed with [3H]choline. On the other hand, no more decrease in [3H]choline incorporation at chase periods was observed in pulse-labeled glands in response to each H2-receptor antagonist. The particulate fraction of glands that had been incubated with GGA or palmitate had more CTP-phosphocholine cytidylyltransferase activity than that of glands incubated without agents. A decrease in choline kinase activity was not observed in the cytosolic fraction of glands that had been incubated with cimetidine. These results suggest that GGA and palmitate stimulate phosphatidylcholine synthesis by activating cytidylyltransferase, and H2-receptor antagonists may affect phosphatidylcholine synthesis by inhibiting choline uptake in the gastric glands.


Simultaneous occurrence of primary sclerosing cholangitis and autoimmune chronic active hepatitis in a patient with ulcerative colitis. The simultaneous occurrence of PSC and autoimmune CAH in a patient with ulcerative colitis is described. Although each disease is a well documented complication of UC, their combination has never been reported. The diagnosis of PSC was based on typical findings on ERCP and liver biopsy and that of CAH was based on typical findings on liver biopsy supported by HLA typings and a remarkable response to a combination of glucocorticoids and azathioprine. The difficulties in establishing the diagnosis and the management of such patients are discussed.


Multiple granular cell tumors of the gastrointestinal tract with subsequent development of esophageal squamous carcinoma. A 52-year-old woman initially presented to our medical center with synchronous, submucosal tumors of the esophagus, stomach, and transverse colon. The gastric and colonic tumors were resected, and both displayed infiltrating sheets of polygonal cells with coarsely granular cytoplasm and small vesicular nuclei. The neoplastic cells of both tumors were immunoreactive for S-100 protein. Ultrastructural studies revealed the lysosomal nature of the cytoplasmic granules. Although the esophageal mass was not resected, it was felt that this represented another focus of granular cell tumor of the gastrointestinal tract. Two years later, she presented with disseminated squamous carcinoma of the esophagus. At autopsy, a submucosal granular cell tumor was found adjacent to the squamous carcinoma of the esophagus. To our knowledge, this is the first reported case of synchronous granular cell tumors that involved multiple segments of the gastrointestinal tract, one of which was later associated with a squamous carcinoma of the esophagus.


Heterotopic bone formation in rectal carcinoma. Case report and literature review. A case of heterotopic bone formation in a primary rectal adenocarcinoma was recently observed in a 54-year-old woman. This unusual finding was present both in the diagnostic biopsy and in the subsequently resected bowel. Pertinent gross and microscopic features are presented. This report represents the twelfth case in the literature of heterotopic bone formation in a primary rectal adenocarcinoma and the first such finding in a colonic biopsy from one of these malignancies. The average age of these patients was 56 years (range 32-72) and the male-to-female ratio was 5:7. The rectum is the most common site of ossification in the gastrointestinal tract. The exact mechanism of heterotopic ossification is unknown, but it is probably the result of metaplasia of fibroblasts. Adenocarcinoma has been associated with 12 of the 16 reported cases of rectal glandular tumors with heterotopic bone.


Glycemic control and diabetic complications. The relationship between glycemic control and diabetic complications remains unclear. Epidemiological studies reveal that approximately 25% of diabetic individuals do not develop complications, irrespective of degree of glycemic control. Studies of genetic factors, including HLA type, capillary basement membrane thickness, genetic predisposition to hypertension, and familial clustering of diabetic complications, suggest that there is a genetic component to developing the complications of diabetes. On the other hand, clinical trials have demonstrated that the progression of early, mild background retinopathy, microalbuminuria, and parameters of nervous system function are stabilized with improved glycemic control. Other metabolic parameters, such as serum lipoprotein levels, are significantly improved with near normoglycemia. No studies to date have evaluated the effect of blood glucose control on the prevention of diabetic complications. The degree of glycemic control required to impact on diabetic complications is unknown. In addition, achieving near normoglycemia carries increased risk for severe hypoglycemia and weight gain. Further study is needed to determine the long-term benefits of blood glucose control and to weigh that against the risks of improving glycemic control. Further investigation also is needed to address the probable interrelationship of genetic factors and glycemic control on the development of diabetic complications.


Diabetes mellitus and macrovascular complications. An epidemiological perspective. It is clearly recognized that patients with NIDDM have an increased risk for CHD. Recent data indicate that persons with glucose concentrations in the nondiabetic range also may be at higher risk for CHD. These associations may not represent cause and effect, however. Emerging data suggest that hyperglycemia and CHD may both arise from hyperinsulinemia/insulin resistance. In support of this hypothesis are studies showing that NIDDM and CHD have many risk factors in common, including age, elevated blood pressure, dyslipidemia, adiposity, and a central pattern of fat distribution. Moreover, these risk factors are frequent concomitants of hyperinsulinemia, itself a risk factor for CHD and perhaps for NIDDM. Although the duration of NIDDM has been infrequently related to risk of CHD, the authors hypothesize that duration of hyperinsulinemia/insulin resistance would be a more sensitive marker for risk of CHD. The relation of IDDM to CHD is a different situation. The etiological process leading to IDDM, namely the destruction of beta-cells in genetically predisposed persons, is not related to cardiovascular risk. However, IDDM patients still have an excess of CVD, the risk factors for which may vary according to the location of the diseases (e.g., LEAD vs. CHD). There is a strong relationship between proteinuria and CVD, which has led to a general theory of vascular complications in IDDM based on defective heparan sulfate metabolism (Steno hypothesis). Recent evidence challenges parts of this hypothesis, and the possibility is raised that a higher case-fatality rate in a subgroup of patients with both renal and CVD explains part of the renal connection, as does the general worsening of CVD risk factors.


Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus. In this review, we have highlighted pivotal cellular and molecular events in the initiation and progression of atherosclerosis. Key components of lesion initiation are an enhanced focal intimal influx and accumulation of lipoproteins, including LDL in hemodynamically determined lesion-prone areas, focal monocyte-macrophage recruitment, intimal generation of ROS, and oxidative modification of lipoproteins (including LDL [Ox-LDL]). Modified lipoproteins are taken up by the non-downregulating macrophage scavenger receptor, with foam cell formation and the development of the so-called fatty streak. One transitional event in lesion progression is foam cell necrosis, likely attributable to the cytotoxicity of both intimal free radicals and Ox-LDL, with development of an extracellular metabolically inert lipid core. Another is the migration to and proliferation within the intima of medial SMCs, leading to the synthesis of plaque collagens, elastin, and proteoglycans. Mural thrombosis plays a significant role in the late-stage progression of lesions. Regression of lesions is considered a function of the dynamic balance among components of initiation, progression, plaque stabilization, and removal of plaque constituents--the so-called regression quartet. Here, we critically examine how components of diabetes mellitus might impact not only lesion development, but also lesion regression. It is concluded that some components of diabetes mellitus augment key mechanisms in lesion initiation and progression and will likely retard the processes of plaque regression. Specifically, we focus on the various influences of diabetes mellitus on lipoprotein influx and accumulation, free radical generation and Ox-LDL, monocyte-macrophage recruitment, thrombosis and impaired fibrinolysis, and the reverse cholesterol transport system. The importance of nonenzymatic protein glycosylation in modifying a number of these processes is emphasized.


Cell-cell interactions in diabetic angiopathy. Normally, both ECs and mural cells, pericytes in the microvasculature and SMCs in large vessels of the mature vasculature, are under stringent growth control and remain quiescent. Regulation of vascular growth is a complex process that is likely to take place at multiple levels. Evidence indicates that intercellular communication, which may take several forms, including diffusible factors, gap junctions, and CAMs underlies the maintenance of normal vessels. A disruption or imbalance in any of these factors may be responsible for the vascular remodeling associated with macro/microangiopathy.


Microalbuminuria. Implications for micro- and macrovascular disease. Microalbuminuria is diagnosed when the UAER is greater than 20 but less than 200 micrograms/min. The prevalence of microalbuminuria among diabetic patients is 15-20%. Persistent microalbuminuria in diabetic patients is a risk marker not only of renal disease, but also of proliferative retinopathy and cardiovascular morbidity and mortality. Even among nondiabetic individuals, those with microalbuminuria tend to have an increased cardiovascular morbidity. The established cardiovascular risk factors, such as smoking, elevated plasma cholesterol, fibrinogen, and hypertension, are seen more frequently in diabetic patients with persistent microalbuminuria than in normoalbuminuric diabetic patients of similar age, sex, and diabetes duration. However, these risk factors cannot by themselves explain the cardiovascular overmortality in these patients. In addition, insulin resistance or genetic disposition to hypertension or cardiovascular disease fails to be the missing link. Accumulating evidence suggests a common pathogenetic mechanism for microalbuminuria and premature atherosclerosis (i.e., qualitative alterations of the extracellular matrix, including decreased density and sulfation of HS-PG). Decreased density of HS in the glomeruli may lead to albuminuria and mesangial proliferation. In the intima of large vessel walls, decreased density and/or sulfation of HS may enhance several of the processes involved in premature atherosclerosis. Diabetes affects the composition and structure of the extracellular matrix in many ways and leads to decreased density and sulfation of HS-PG by several mechanisms. Genetic differences in the sulfation of HS and/or genetic defects in the coordinated biosynthesis of HS-PG might contribute to decreased concentration and sulfation of HS-PG in susceptible individuals. It is hoped that susceptibility genes can be identified soon, thereby making prevention of severe late diabetic complications more successful.


Blood pressure elevation versus abnormal albuminuria in the genesis and prediction of renal disease in diabetes. A number of risk factors associated with the development of diabetic nephropathy has been described, such as elevated blood pressure, poor metabolic control, hyperlipidemia, and smoking. Abnormal albuminuria also is associated with progression of renal disease, but has until recently been considered principally a marker of disease activity rather than a risk factor. This article discusses the role of elevated blood pressure versus abnormal albuminuria in a genesis and prediction of renal disease in diabetes. Controversy exists regarding parental disposition to hypertension and early blood pressure elevation in the course of diabetes, but all studies agree that elevated blood pressure--in the presence of abnormal albuminuria--constitutes a risk factor. Because abnormal albuminuria is associated with progression disease, it may itself be a risk factor because increased macromolecular traffic over the glomerular membrane may produce glomerulopathy. Problems related to blood pressure measurement are important, and 24-h recordings of blood pressure may be recommended in some situations. Regarding renal structure, preliminary results suggest that structural lesions precede blood pressure elevation. The solid end point for evaluation of renal disease progression is the fall rate of GFR, with abnormal albuminuria as an intermediate end point, also in drug trials. Abnormal albuminuria may constitute a new indication for antihypertensive treatment, being, as it is, a clear indicator of organ damage, whereas elevated blood pressure with normal AER may not increase risk substantially.


Diabetic nephropathy. Metabolic versus hemodynamic considerations. Not all patients with diabetes develop clinically significant nephropathy and, for this reason, attention has begun to focus on the risk factors for development of this serious complication. These risk factors have not been quantified to the same degree as those factors associated with more common progressive vascular diseases, such as atherosclerosis. However, studies of pathogenesis and clinical and epidemiological surveys of diabetic nephropathy point to numerous risk categories. Glycemic control, genetic and familial predispositions, renal and glomerular enlargement, glomerular hyperfiltration, and capillary and systemic hypertension can be invoked as contributors to this disease process. This review focuses on hemodynamic alterations and their role in the development and progression of diabetic nephropathy. Increases in GFR, largely driven by increases in plasma flow and capillary pressure, appear in early IDDM and NIDDM. This abnormality of renal vascular control probably is derived from alterations in several vasoactive control systems. In addition, the elevations in capillary pressure may be damaging to the glomerular capillaries. Arterial hypertension is not necessarily present before clinical nephropathy appears; however, it is a usual concomitant of progressive diabetic renal disease. The strongest evidences for the roles of altered systemic and renal hemodynamics in the progression of diabetic renal disease are clinical and experimental studies demonstrating attenuation of the disease process by lowering systemic and capillary pressures with antihypertensive agents, and dietary and glycemic modifications. Thus, although multiple factors probably interact to determine risk for the development of diabetic nephropathy, hemodynamic forces are a particularly important contributor and are especially amenable to therapeutic intervention.


Diabetic nephropathy. Future avenue.

Diabetic nephropathy. Future avenue. Diabetes mellitus has become the leading cause of ESRF in the United States. Patients with diabetic nephropathy suffer high cardiovascular morbidity and mortality. Because only 40% of diabetic patients eventually develop diabetic kidney disease, it may be possible to devise primary prevention measures targeted at the subset of patients at risk. Recently, a predisposition to hypertension, a family history of diabetic nephropathy, and a family history of CVD disease each have been associated independently with the development of diabetic renal complication in IDDM. Risk factors for macrovascular damage, including raised arterial BP, dyslipidemia, and insulin resistance, can be detected early in the course of progression to diabetic nephropathy. These risk indicators recently have been shown to be already present at the stage of normoalbuminuria in those patients who eventually will progress to microalbuminuria. Treatment of established renal disease can only delay the onset of ESRF, and lowering of microalbuminuria has been shown to retard the onset of persistent proteinuria. However, no study to date has demonstrated prevention of renal disease in these patients. The ultimate aim should, therefore, be the prevention of the transition from normoalbuminuria to microalbuminuria in individuals who are at higher risk of diabetic renal disease and CVD.


Diabetic nephropathy. Management of the end-stage patient. Diabetic nephropathy is currently the leading cause of new patients requiring dialysis in the United States. Management of the diabetic patient with ESRD is complicated by the frequent coexistence of complications affecting other organ systems, including retinopathy, cardiovascular disease, peripheral neuropathy, or autonomic neuropathy, manifested as gastroparesis, diarrhea or obstipation, cystopathy, or orthostatic hypotension. Associated clinical syndromes must be followed and treated, if possible, while preparing the patient to receive renal replacement therapy. Both the clinical condition and the psychosocial environment are key factors in choice of ESRD therapy for an individual patient. Rehabilitation data are best for patients who undergo kidney transplantation, but these data are confounded by the fact that the healthiest patients are referred for this treatment modality. Living, related kidney transplant is the preferred initial choice for the diabetic patient with kidney disease. At most centers, both in the United States and abroad, the cadaveric transplant is the second choice for uremia therapy. At the appropriate institution, the patient with type I diabetes may also be considered for a simultaneous cadaveric pancreas transplant. While awaiting cadaveric transplantation, or if contraindication to transplantation is present (chronic infection, recent malignancy, or severe cardiac disease), diabetic patients with severe impairment of the glomerular filtration rate (less than 10-15 ml/min) are referred for vascular access placement and/or insertion of a peritoneal catheter. The decision regarding the choice of CAPD vs. hemodialysis must be made on an individual basis. Rehabilitation and survival data for these therapies are similar, although technique survival rates for CAPD decline dramatically as time progresses because of infectious complications. In-center hemodialysis has the worst survival and rehabilitation profile, but the sickest, most debilitated patients with the highest number of comorbid conditions tend to be referred for that therapeutic modality. Most studies of rehabilitation were performed before use of recombinant human erythropoietin, and comparison between ESRD treatment modalities will have to be reevaluated now that the drug is routinely used.


Cytodiagnosis of lesions presenting as salivary gland swellings: a report of seven cases. The cytologic and histologic findings of seven cases presenting clinically as salivary gland swellings are described. These included two cases of pilomatrixoma of skin in the parotid region, two cases of neurilemmoma in the submandibular area, a case of Kimura's disease in the peri-mandibular gland lymphoid tissue, a case of Castleman's disease in intraparotid lymph node, and a case of branchial cleft cyst in the parotid region. It is important to recognize lesions that masquerade as salivary gland tumors so that misdiagnosis and overdiagnosis on smears can be avoided and the patients can be treated appropriately.


Fine-needle aspiration cytology of localized fibrous tumor of pleura. Fine-needle aspiration (FNA) biopsy findings are presented in three cases of localized fibrous tumor of pleura (LFTP). Clinically, two of the tumors behaved benignly, although one showed frequent mitoses and foci of necrosis. The third tumor exhibited local aggressiveness as evidenced by rib destruction. Cytologically, these tumors exhibited a wide range of cellularity, composed mainly of small, bland oval to spindle cells with moderate numbers of stripped nuclei. Small bits of collagen were seen in the smears. In all cases, cell blocks were instrumental in making the diagnosis. Previous cytologic descriptions of the tumor are briefly reviewed and the cytologic differential diagnosis is discussed. The peripheral location of this uncommon tumor makes it an ideal target for FNA biopsy.


Diagnosis of tuberculosis of bone and soft tissue by fine-needle aspiration biopsy. Fine-needle aspiration biopsy is a well-established procedure in the detection of various neoplastic processes. However, there are only limited reports on the efficacy of this technique in nonneoplastic conditions. In this study, fine-needle aspiration cytology findings of bone and soft tissue lesions in 11 patients with tuberculosis are reported. Spine, scapula, chest wall, flank areas, tibia, ring, and index fingers were the sites of fine-needle aspiration biopsies. The age of the patients ranged from 21 to 65 years. Granulomatous reaction with or without caseation necrosis was seen in 73%. The aspirated material was acellular or predominantly composed of necrotic material and inflammatory infiltrates in 27%. Acid-fast bacilli (AFB) could be demonstrated in 64%. Culture for Mycobacterium tuberculosis was positive in 83%. This study supports previous suggestions that fine-needle aspiration biopsy is a simple alternative to open biopsy for the diagnosis of TB of bone and soft tissue lesions.


Accuracy of diagnosis of malignant lymphoma by combining fine-needle aspiration cytomorphology with immunocytochemistry and in selected cases, Southern blotting of aspirated cells: a tissue-controlled study of 86 patients. Fine-needle aspiration (FNA) cytology of lymph nodes in malignant lymphoma is fraught with difficulty. In certain clinical situations, cytology has been documented to be useful in patients with malignant lymphoma. The intent of our investigation was to determine the accuracy of a multiparameter approach in diagnosing lymphoma. We reviewed the results of FNA cytology combined with the immunocytochemistry and, in some cases, the Southern blots of aspirated cell suspensions obtained from 86 suspected lymphoma patients who subsequently underwent surgical biopsy of the aspirated site. In four cases, in which FNA was unable to retrieve sufficient material for diagnosis, the histology showed extensive fibrosis. When the FNA diagnoses were compared with the histologic diagnoses, the diagnosis concurred in 69 cases (56 malignant lymphomas, 12 reactive, 1 atypical lymphoid proliferation). There was one false-positive, six false-negatives, and eight cases diagnosed as atypical lymphoid proliferation. Overall accuracy was 91%. There were two types of false-negative cases: those in which a diagnosis of another malignancy or unspecified malignant neoplasm was made and those that were diagnosed as reactive when the histology showed lymphoma. In seven cases, the DNA rearrangement studies of the antigen receptor genes were successfully performed on the aspirated cells and were useful in establishing lineage and clonality of both B and T lymphoid cells. Our study indicated that the use of a multiparameter approach in the diagnosis of malignant lymphoma by FNA enhanced the accuracy of diagnosis of the non-Hodgkin's lymphomas. In Hodgkin's disease, no benefit was derived from the approach.


Fine-needle aspiration biopsy diagnosis of rhabdomyosarcoma: cytologic, histologic, and ultrastructural correlations. A series of 15 cases of rhabdomyosarcoma diagnosed by fine-needle aspiration biopsy (FNAB) and confirmed by histopathology is reviewed. Cytologically, the tumors were composed of a variable mixture of cells, which according to the degree of differentiation were categorized as early, intermediate, or late rhabdomyoblasts. Histologically, the tumors were divided into embryonal 9, monomorphic round cell 4, and alveolar rhabdomyosarcoma 2. Comparison of histological and cytological features revealed that embryonal types were composed mainly of early rhabdomyoblasts. Recognition of these patterns may be helpful in FNAB diagnosis of rhabdomyosarcoma.


Aspiration biopsy cytology of papillary carcinoma of the breast. The fine-needle aspirates of two cases of noninfiltrating papillary carcinoma (PC) and three examples of early invasive PC of the breast were examined. In three cases in which the tumors displayed cuboidal or polygonal cells the aspirates showed papilla-like clusters of tumor cells with relatively "strong" cellular cohesiveness. Single and small aggregates of tumor cells as well as hemosiderin-laden or foamy macrophages were also present. Aspirates from the two PCs predominantly consisting of tall columnar epithelial cells revealed only monolayered and multilayered epithelial fragments with folding in one case. In the other case large epithelial fragments and small tight clusters of polygonal tumor cells were present. No bipolar nuclei of myoepithelial cells were identified in all cases. No specific cellular features permitting the differentiation between noninfiltrating and early invasive breast PCs were identified in this small series. Staining for carcinoembryonic antigen using the peroxidase-antiperoxidase technique was performed on aspiration smears of three cases. It revealed a positive cytoplasmic reaction in two cases.


Epidermoid cyst of the spleen: diagnosis suggested by fine-needle aspiration biopsy. The authors report a case of epidermoid cyst of the spleen, in which cytologic findings were characteristic and suggested this diagnosis. Histologic and immunohistochemical findings are described in the attempt to clarify the histogenesis of this cystic lesion.


Needle aspiration cytology, immunocytochemistry, and electron microscopic study of unusual pancreatic carcinoma with pleomorphic giant cells. Needle aspiration cytology, immunocytochemistry, and electron-microscopic findings are presented in three cases of an unusual pancreatic carcinoma in which pleomorphic giant cells formed an integral part of the tumour. All three patients were elderly males (age range 66-83 years) and had pancreatic masses. Notable cytologic features in all cases were the presence of bizarre mononucleated and multinucleated, poorly cohesive tumour giant cells, rare spindle cells, with occasional cannibalism and cytophagocytosis. Immunocytochemical study of aspirated material showed diffuse staining of cytokeratin and EMA within the tumour cells, while B 72.3 was seen as focal trace stain. Electron microscopy of aspirated material demonstrated epithelial features and these were characterised by the presence of tonofilaments and surface microvilli. Based on our findings, it is felt that the bizarre giant cells in this unusual variant of pancreatic carcinoma are of epithelial origin. The differential diagnosis of other tumours that may be associated with predominant giant cells in pancreatic aspirates is appropriately discussed.


Lipomas of anterior neck simulating thyroid nodules: diagnosis by fine-needle aspiration. The anterior neck is an unusual location for lipomas. Cervical lipomas can be mistaken for non-functioning thyroid nodules. We report eight cases from our files diagnosed by fine needle aspiration (FNA). Our purpose is to call attention to this simple technique in establishing an accurate diagnosis and how it can contribute to better patient management by avoiding unnecessary thyroid suppressive therapy and/or surgery. We advocate using FNA as the initial diagnostic test on palpable masses in the neck. The differential diagnosis must include thyroid lipomatosis, thyrolipoma or adenolipoma, amyloid goiter with fatty infiltration, and fat-containing thyroidal neoplasms (papillary carcinoma and follicular neoplasms).


Ovarian follicular cysts: a potential source of false positive diagnoses in ovarian cytology. The cytology samples of 22 benign ovarian cysts aspirated during laparoscopy (16) or laparotomy (6) were evaluated for clinicopathologic correlations. Clinically, most patients were evaluated for chronic pelvic pain. The cysts ranged in size from 1 to 5 cm (average 2.4 cm), and were described as having benign appearance. Cytologically, small granulosa cells arranged in clusters or isolated had granular cytoplasm with occasional microvacuoles. The nuclei were round to oval, uniform, and eccentrically placed. They had granular chromatin with chromocenters and one to two micronucleoli. Relative nuclear area averaged 50%. Mitoses were present in all but two cases, ranging from 0 to 38 mitoses per 10 high power fields (average 7.2 mitoses per 10 high power fields). Present in some cases were mesothelial cells and histiocytes. Three cases with follow-up histopathology specimens revealed two follicular cysts and a collapsed cyst without discernible lining. The immature appearance of the granulosa cells, the granular chromatin, and the presence of mitoses often suggested cytologically the possibility of a neoplastic process. Recognition of the cytopathology features, knowledge of the clinical history, and the laparoscopic findings may reassure the pathologist about the benign nature of the cysts.


Processing of needle rinse material from fine-needle aspirations rarely detects malignancy not identified in smears. When preparing FNA smears, we recover material left in the needle hub by forcefully striking the open hub against a slide. Material in the syringe tip is expressed by repeated forceful blasts of air (needle unattached). We investigated the utility of recovering additional material by rinsing the needle and syringe. Saline was used to flush the needle and syringe tip repeatedly. All material was processed by cytocentrifugation. We studied 159 needle rinse (NR) specimens from 152 patients (breast = 70, lymph node = 30, lung = 15, soft tissue = 14, salivary gland = 12, thyroid = 12, liver = 5, branchial cleft cyst = 1). Malignancy was identified in 21 FNAs (13%) from 21 patients (14%). All were diagnosed in smears (9 lung, 5 liver, 4 lymph node, 2 breast, 1 soft tissue). NR material identified 16 of these (76%). No case with benign smears (n = 138) showed malignancy in NR material. We conclude that if good technique is applied to preparation of smears and recovery of material from the needle hub and syringe tip, NR material will rarely identify additional malignancies. It thus represents an inefficient allocation of technical and human resources within the laboratory. However, NR may provide additional slides for special stains and may be useful for clinicians who do not always prepare high quality smears. Furthermore, the ease with which FNA of palpable masses can be repeated suggests that in the small number of cases requiring special stains, additional material can be readily obtained.(ABSTRACT TRUNCATED AT 250 WORDS)


AIDS: Part II.

AIDS: Part II. Great strides have been made in the therapy of human immunodeficiency virus (HIV) infection. Currently approved drugs include zidovudine and didanosine. A third drug, dideoxycytidine (zalcitibine), has recently been filed for approval with the Food and Drug Administration. All these drugs work through inhibition of the reverse transcriptase enzyme. Zidovudine is the only drug that has shown clinical efficacy against HIV. Treatment of patients with advanced HIV disease (i.e., acquired immune deficiency syndrome [AIDS] or symptomatic infection with < 200 CD4+ lymphocytes per mm3), results in a prolongation and improved quality of life. Zidovudine is the only antiretroviral agent approved for the treatment of asymptomatic patients. Early intervention with zidovudine has been shown to delay progression to AIDS when patients' CD4+ lymphocyte counts decline to less than 500/mm3, irrespective of clinical signs or symptoms of HIV infection. Didanosine is currently indicated for the treatment of patients with advanced HIV disease who are intolerant to or failing zidovudine therapy. The major toxicity of zidovudine is bone marrow suppression with anemia and granulocytopenia (which occurs in from 1% to 45% of patients, depending on the clinical stage of disease and the dose of the drug). Didanosine and zalcitibine have both been associated with a severe peripheral neuropathy, which is generally reversible on cessation of the drug. In addition, didanosine has been implicated as a cause of pancreatitis that has been fatal in a small percentage of cases. The toxicities of didanosine and zalcitibine range from 1% to 10%, depending on dose, duration of therapy, and the presence of underlying HIV-related peripheral neuropathy or a previous history of pancreatitis. The clinical hallmark of HIV infection is the development of opportunistic infections and malignancies, which are a consequence of the profound immunodeficiency. The risk of an opportunistic infection increases significantly as the T-helper lymphocyte count declines to less than 20%, or 200 to 250/mm3. The spectrum of opportunistic infections ranges from viruses to protozoa. Patients with advanced HIV disease are also at increased risk of infection with nonopportunistic, community-acquired pathogens. Primary and secondary prophylaxis against the most common AIDS-defining opportunistic infection, Pneumocystis carinii pneumonia, is now recommended. Studies are currently underway to determine the efficacy of prophylaxis against other opportunistic pathogens. Treatment of opportunistic infections associated with AIDS has improved significantly over the past 5 years as new drugs and combination regimens of antimicrobials have been developed.(ABSTRACT TRUNCATED AT 400 WORDS)


AIDS: Part I.

AIDS: Part I. Acquired immunodeficiency syndrome (AIDS) is caused by infection with a pathogenic human retrovirus known as human immunodeficiency virus (HIV). Approximately 1 million people are currently infected with HIV in the United States, with 8 to 10 million infected individuals worldwide. The virus is transmitted predominantly through genital sexual contact, although orogenital spread has been rarely reported. Heterosexual transmission has been most common in the Third World, whereas male homosexual transmission has predominated in the United States and western Europe. Transmission through homosexual contact has been steadily declining over the past 5 years as transmission through illicit intravenous drug use and promiscuous unprotected heterosexual activity has increased. Sexually transmitted diseases that cause inflammatory or ulcerative lesions of the genital tract act as important cofactors in increasing the risk of transmission through sexual contact. Perinatal transmission of HIV occurs in approximately 30% of infants born to infected mothers. Transmission to infants through breast-feeding has also been documented. Health care workers have been infected with HIV through accidental high-risk percutaneous or mucous membrane exposures, albeit at a low transmission rate of 0.3%. Infection of patients by infected health care professionals is a rare event, having been reported only once in 10 years of the epidemic. Infection with HIV results in a chronic lifelong infection. The major targets for HIV are CD4+ T-helper lymphocytes and cells of monocyte/macrophage lineage. Infection of the T-helper lymphocyte ultimately results in the death of the cell. Over time (measured in years), a progressive destruction of the T-helper lymphocyte population occurs, which results in profound immune suppression. Infection of monocytes/macrophages is not cidal, but these cells do have functional alterations as a result of the infection, which may contribute to the immune deficiency. In addition, chronically infected tissue macrophages may act as an important reservoir for HIV, particularly in the central nervous system. Infection of the T-helper lymphocytes and monocytes/macrophages is mediated through attachment of HIV through a specific binding interaction between CD4 expressed in the plasma membrane of these cells and a surface glycoprotein on the virus, gp120. Once the virus nucleocapsid (core particle) enters the cytoplasm of the target cell, the viral RNA genome is reverse transcribed by a reverse transcriptase enzyme into proviral DNA. This proviral DNA migrates into the nucleus where it integrates into the host cellular genome, which results in a chronically infected cell.(ABSTRACT TRUNCATED AT 400 WORDS)


[Study on significance of lymphocyte chemiluminescence measurements in cancer patients]. Chemiluminescent responses of peripheral blood lymphocytes were measured in patients with carcinomas and healthy donors. The intensity of lymphocyte chemiluminescence (Ly-CL) in 54 preoperative patients was significantly lower than that in 97 healthy donors (P less than 0.05). Compared to that before treatment, the Ly-CL intensity in 14 patients after radiotherapy was decreased (P less than 0.05). However, Ly-CL intensity in 12 patients after 6-8 days of thymosin therapy was significantly increased (P less than 0.05), and exceeded that of healthy donors (P less than 0.01). These data suggest that Ly-CL measurements may become a new method for monitoring lymphocyte activity or function, and evaluating therapeutic effectiveness in cancer patients.


[Characteristics and biologic significance of changes in DNA content of rat liver cells during hepatocarcinogenesis]. DNA content of hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DENA) in Wistar rats was quantitatively measured using flow cytometry. In normal adult rats, hepatocytes with tetraploid (4C) DNA content constitute the major cellular population (72.1%), whereas diploid (2C) hepatocytes were of a quite small number (16.9%). Under the persistent effect of DENA, the atavistic proliferation of 2C hepatocytes was obviously increased at the cirrhotic stage, which followed the pre-cirrhotic stage, and replaced 4C hepatocytes to become the major cellular population. HCC at its early cancerous stage was characterized by predominated of DNA 2C cells, and HCC at its progression stage showed a selective and advantageous growth of aneuploid(AN) stemline cells. The whole hepatocarcinogenesis course showed a change of DNA stemline from 4C to 2C to AN, which might be the essential biologic kinetic mechanism of the development and progression of HCC. It is also suggested that HCC at early and progression stages are characterized by predominance of DNA 2c and AN hepatocytes.


[Prognostic significance of DNA content in transitional cell carcinoma of the urinary bladder]. The cellular DNA content in paraffin-embedded specimens of recurrent transitional cell carcinoma of the urinary bladder were analyzed by quantitative image analysis in 48 and flow cytometry techniques in 44 cases. The results showed a positive correlation of cellular ploidy with malignant proliferation of the tumors. The aneuploidy was increased in cases of higher clinical stages and histological grades. The prognosis of patients with diploid cells was better than those with aneuploidy, while patients with aneuploidy and higher grading showed very poor prognosis. The recurrence rate of diploid tumors was considerably lower than that of aneuploid tumors. The results indicate that such a correlation might be of clinical significance in prognosis and predicting and controlling recurrence of tumors.


[Fusarin C induced esophageal and forestomach carcinoma in mice and rats]. Fusarium moniliforme, a fungus of established carcinogenic potential, is one of the most common fungal contaminants of maize, millet and other grains in Linxian, China, a high-risk county for human esophageal cancer. Fusarin C, a major product of F. moniliforme grown on corn in the laboratory, is mutagenic in Salmonella tester strains and in V79 cells. Fusarin C treated rat esophageal epithelial cell line showed several characteristics of malignant transformations including the growth in nude mice. The present work demonstrated that Fusarin C can induce esophageal and forestomach carcinoma in DBA mice and Wistar rats thus further substantiating the carcinogenicity of this mycotoxin.


[Expression of c-myc and c-ki-ras oncogene in human pancreatic carcinoma]. Using Northern blot technique, the oncogene expression in normal pancreatic tissue and human pancreatic carcinoma PC-2 and PC-3 cell lines was studied. Four oncogene probes (c-N-ras, c-ki-ras, c-myc and c-fos) consisting of recovered endonuclease digested fragments were nick translated. After hybridization and autoradiography, none of the four oncogenes was expressed in the normal human pancreatic tissue, but the human pancreatic carcinoma PC-2 and PC-3 cell lines expressed the c-myc and c-ki-ras genes. Their transcripts were 2.7 and 6.0 kb, respectively. Expression of the other two oncogenes (c-N-ras and c-fos) was not detected. The results of this study together with those reported in the literature verify the fact that the expression of c-myc and c-ki-ras oncogenes may play a very important role in the development of human pancreatic carcinoma.


[Effect of hematoporphyrin derivative (HPD) plus light on DNA repair synthesis and enhancement of HPD photosensitization by vitamin C in mouse hepatoma]. There are only a few reports in the literature on photodynamic effects of HPD on gene expression and the repair of DNA damage. Previously, we suggested that nuclear transcription activity was markedly suppressed by HPD plus light. In this study, we investigated the photodynamic effect or DNA repair synthesis as measured by unscheduled DNA synthesis (UDS) in hepatoma cells. The results indicated that DNA repair capacity was greatly inhibited by HPD plus light. When hepatoma cells were pretreated with HPD of different concentrations and then exposed to the same light dose, significant inhibitions of UDS over control were seen and appeared in a dose-dependent fashion. In addition, while hepatoma cells following the exposure to HPD of the same concentration were irradiated with different time, the UDS was markedly decreased as the duration of irradiation was prolonged. However, no changes were observed when either HPD or light was used alone. The present study also included an experiment to determine whether HPD combined with vitamin C gives an enhanced photosensitization. It was found that vitamin C significantly potentiated the suppressing effect on DNA repair synthesis.


[Estimating cancer latency using data from a case-control study with time-related factors. I. A general multivariate theory and algorithm]. In the present paper, a general multivariate approach, estimating cancer latency using data from a case-control study with time-related factors, is proposed based on the theory for risk analysis of states. Making use of a forward-analysis and backward-synthesis strategy and excess exposure fraction, this approach can simultaneously accomplish multivariate logistic regression analysis and estimation of susceptible exposure ages and latency distribution. The latency is resolved into a accumulative period and preneoplastic period. It gives a theoretical interpretation for primary and secondary prevention of cancer.


[Influence of dietary selenium level on immune function of rats with esophageal tumors induced by methylbenzylnitrosamine (NMBzA)]. The influence of dietary selenium of the incidence of esophageal tumor induced by NMBzA and the immune function during carcinogenesis were studied in rats fed with Torula yeast diet and survived for 18 weeks. The incidences of esophageal tumors were statistically not significant among rats on normal, high and low selenium intake (P greater than 0.05). The level of plaque forming cells (PFC), delayed type hypersensitivity (DTH), natural killer cell activity (NK) were significantly higher in the high selenium diet group than those of the low selenium diet group (P less than 0.05). The authors believe that the modulation of dietary selenium can alter the immune function of animals during carcinogenesis but the anticarcinogenic effect of selenium still needs further study.


[Pharmacokinetic study of pseudohainanensine with deuteriumlabeled analogue as internal standard]. Pseudohainanensine (HH08) is a synthetic compound which is active against L-1210. In order to study the pharmacokinetic characteristics of this compound in rats, 3', 4'-dideuteropseudohainanensine (DH08) was synthesized and used as internal standard in GC-MS determination for quantitative analysis of alkaloid HH08 in the blood of rats that had been given HH08 at a dosage of 10 mg/kg intravenously. Experiments demonstrated that the detection limit of HH08 was 3 micrograms/ml and the peak concentration in the blood was 13.1 +/- 0.2 micrograms/ml after a single intravenous injection (one min. after injection). The biological half life time can be divided into two phases; the fast phase (alpha) 2.61 min, and the slow phase (beta) 42.59 min. Two hours after the injection no drug could be detected in the blood.


[Spectrum distribution of ultra-weak luminescence of blood in lung cancer patients]. Using the single-photon counting detecting system manufactured by the Institute of Biophysics, Academia Sinica, the emission spectrum of ultra-weak luminescence of blood from 10 normal blood donors and 37 lung cancer patients were studied. The experimental results showed that ultra-weak photon emission of patients' was originated from the red region and three emission peaks were observed at 425-460, 535-595 and 620-660 nm. The intensity of photon emission at 425-460 nm of patient's blood was markedly higher than that of normal blood donors, with statistical significance. Furthermore, after operation, the spectrum distribution almost returned to that of what was seen in normal blood donors. Our observation shows that ultra-weak luminescence of blood may serve as an early detection of lung cancers.


[Immunohistochemical analysis of physicochemical properties of target antigens with anti-tumor monoclonal antibodies]. A new simplified assay for the identification of physicochemical nature of the antigen recognized by monoclonal antibodies (MAbs) against tumor using direct immunohistochemical methods of avidin-biotin peroxidase complex (ABC) is first described. The experimental results demonstrate that this method does not need to purify the target antigens or special equipment, but is as specific and sensitive as immunoblotting technique. For these reasons, this procedure is much simpler and less expensive than the methods previously published. This method may thus be useful to investigate the properties of antigens to which MAbs are directed.


[Clinical multivariate statistical analysis of nephrotoxicity induced by cisplatin]. Nephrotoxicity was studied in 47 patients who received combined chemotherapy with cisplatin (DDP, 50-100 mg/m2) as the chief agent. The treatment was given every 3-4 weeks with vigorous hydration and forced diuresis. The renal tubular toxicity was evaluated by urinary beta 2 microglobulin (beta 2-MG). It was found that the nephrotoxicity secondary to DDP was dose-dependent. Hypertonic saline was able to decrease the renal damage without any significant difference among the first, second and third course. The nephrotoxicity of DDP administered in one day was more severe than that given in two days. beta 2-MG was a good parameter of DDP nephrotoxicity. By multivariate statistical analysis, metoclopramid and chlorpromazine were found to alleviate DDP nephrotoxicity. Classification, examination and management of DDP nephrotoxicity is proposed.


[Clinical pharmacokinetics of cis-diamminedichloroplatinum (DDP)]. We studied the pharmacokinetics of DDP in 9 cancer patients who received iv infusion of DDP (100-120 mg/m2). Platinum concentration was measured by high performance liquid chromatography (HPLC). Plasma clearance of platinum was biphasic. There was a short initial phase with a half life of 19.8 min and a long second phase with a half life of 41.13 hours. A small peak was noted in 5 hours after the end of DDP infusion in about 50% of patients. This suggested tissue reabsorption, release and entero-hepatic circulation. Plasma ultrafiltrable platinum concentration fell with a half life of 21 min. Nearly 75-96% of the platinum in the plasma was protein bound 24 minutes after DDP infusion. The urinary excretion of platinum was found to be 9.52-21.35% in 24 hours with 6.69-19.57% eliminated within the first three hours.


[Mechanism of cloned human lymphokine-activated killer (LAK) cells killing human leukemia cells in vitro]. The killing of human leukemia cells by cloned human LAK cell was investigated with 51Cr release, semisolid agar colony-formation and MTT assay. Human LAK cells were generated and cloned from normal peripheral blood mononuclear cells stimulated with IL-2. Cloned LAK cells showed significant cytotoxicity against human erythroleukemia cell line K 562, promyelocytic leukemia cell line HL 60 and T-lymphoblastic leukemia cell line Jurkat in standard 4-hr 51Cr release assay and the lytic percentage were 67.1%, 58.4% and 53.1% with E/T ratio of 40:1. Moreover, cloned LAK cells could also inhibit the 6-day spontaneous colony-formation of K 562 and HL 6 C cells in semisolid cultures when the LAK cells were preincubated with target cells for 4 hours in liquid medium at 37 degrees C. The degree of colony inhibition was 91% for K 562 and 96% for HL 60, which was quantitatively greater than that determined by 51Cr release at the same E/T ratio of 40:1. In addition, with MTT assay, cytotoxicity of supernatant of cloned LAK cells 3 days in culture against K 562 and HL 60 cells was observed. Our data indicated that cloned human LAK cells could kill both human leukemia cells and their stem cells and the mechanism may involve direct lysis and/or inhibition mediated by LAK cells and indirect inhibition of some soluble factors released from LAK cells.


[Nuclear morphometry and DNA cytometry in the grading of malignant tumors of the salivary gland]. Nuclear morphometry and DNA cytometry were performed in 6 normal salivary glands and 37 malignant tumors of the salivary gland. Multivariate discrimination analysis was used to grade the malignant salivary gland tumors. The discrimination rate was 100% for normal salivary gland, benign tumor, high malignant carcinoma and low malignant carcinoma. It was 66.7% for borderline malignancies. These results indicate that quantitative cytological analysis is effective and reproducible in the grading of salivary gland tumors. Stepwise multivariate regression analysis showed that there was a very complicated correlation between DNA content and nuclear morphometric parameters of salivary gland tumors.


[Relationship among expression of HLA antigen, cell ploidy and metastasis in human colorectal cancer]. HLA antigen expression, cell ploidy determined by DNA content with flow cytometry, and tumor metastasis were analysed and studied in 51 cases of human colorectal cancer samples. It was observed that the pattern of HLA expression and lymph node metastasis varied significantly when the cancer cells were categorized into distinct ploidies. For tetraploid cancer cells, the percentage of positive expression of class I and II antigens were all 90.0% with no detectable metastasis. On the contrary, the expression of class I and II antigens were as low as 13.3% and 40.0% with metastasis in 26.7% of the samples from diploid group. or 20.0% and 40.0% with a metastasis percentage of 60.0% for heteroploid group. The relevant patterns for triploidy and aneuploidy were between the above three groups. The significance of the unexpected low metastasis of the tetraploid cancer cells both in clinical prognosis and mechanism studies is further discussed.


[Biologic effects of Tween 80 in combination with hyperthermia on human stomach cancer cell line BGC-823]. Cells of human stomach cancer cell line BGC-823 were treated with Tween 80 and hyperthermia 39 degrees C to 43 degrees C for 20 to 100 minutes. Normal human fibroblasts and mitomycin C were used as controls. The results showed Tween 80 greatly reduced the activation energy of BGC-823 cells. Synergistic effect was observed if applied with heat 39 degrees C. With the increase in temperature and time, the inhibitory effect on the cancer cells was gradually intensified. The lethal rate of heat 41 degrees C associated with Tween 80 was 5.2 times as that of heat alone. The inhibitory effect of heat 41 degrees C for 100 minutes combined with Tween 80 was equivalent to 43 degrees C for 100 minutes. In other words, the heat critical Temperature of BGC-823 cells was reduced about 2 degrees C. The measurement of membrane fluidity, SDH activity and the rest also showed heat 41 degrees C produced the highest synergy with Tween 80. The specific and sustained action exceeded that of mitomycin C. The response of the normal cells was mild and reversible. These studies suggest that the synergistic mechanism of Tween 80 and hyperthermia possibly lies on the cell plasma membrane system.


[Morphometric study on nasopharyngeal carcinoma (NPC)]. Morphometric parameters of carcinoma cells in 78 NPC and columnar epithelium basal cells in 21 of these 78 NPCs were measured by Quantimet 520 analyser. The results showed that: 1. Prominent enlargement of nuclei was a pathognomonic feature of carcinoma cells, except small spindle carcinoma cells, as compared with the normal basal cells, 2. vesicular nucleus cell carcinoma and small spindle poorly differentiated squamous carcinoma had their own characteristic morphometric parameters as compared with those of the ordinary poorly differentiated squamous carcinoma, and 3. there was no significant morphometric difference between vesicular nucleus cell carcinoma and poorly differentiated adenocarcinoma.


[Significance of typing in the survival of malignant lymphomas]. The significance of typing and subtyping in the survival rate of 116 patients suffering from pathologically proved malignant lymphoma is presented. Our data show that Hodgkin's disease was least malignant, having the highest survival curve (P less than 0.005). Lymphoblastic lymphoma had the highest degree of malignancy, having the lowest survival curve. Yet, the middle portion of its curve resembled that of the peripheral T cell lymphoma. Although the degree of malignancy and the curve of peripheral T cell lymphoma and B cell lymphoma were similar (0.05 greater than P greater than 0.05), their middle portion were separated, a fact worthy of further study. Typing of malignant lymphomas is of practical importance.


[In vitro effect of catechin on cell growth]. Experimental study on the effect of catechin, an extract of Chinese green tea, on cell growth of HeLa, KB and 3T3 cell lines and its possible mechanism are reported. The proliferative survival curves showed that HeLa and KB were sensitive to catechin, while 3T3 was less so. The survival curve of HeLa cells treated with catechin varied with the dose and duration of exposure. 3H-TdR incorporation rate into HeLa cells was inhibited by catechin and the inhibition rate was also dose and exposure dependent. It suggests that one of the mechanisms of cell growth inhibition by catechin may probably due to inhibition of DNA synthesis.


[Immunohistochemical diagnosis in fine-needle aspiration cytology]. This paper reports 25 kinds of polyclonal or monoclonal antibodies by ABC immunohistochemical technique used for 253 cell smears by fine-needle aspiration. The results were: 1. Immunohistochemical diagnosis were classified into 136 metastatic cancers (K12+ EMA+ CEA+ LCA-), 92 lymphomas (LCA+ K12- EMA- CEA-), 4 mesenchymal tumors (Vimentin+), 3 melanomas (S-100+ NSE+), 15 reactive proliferations (K+ lambda+ CD4+ CD8+) and 3 unspecified. 2. The origin of 70 metastatic cancers were classified into 36 lung (HLC3-AB+), 4 gastrointestinal tract (MG7+), 8 thyroid (TGB+), 1 prostate (PSA+), 3 liver (AFP+) and 14 unknown. 3. Immunologic phenotype of 87 lymphomas were classified into 66 cases of B-cell, 4 T-cell, 3 histiocyte, 7 Hodgkin's diseases and 7 unclear. The above results suggest that immunohistochemical method may be used as a new method of diagnosing and differentiating epithelial and non-epithelial tumors, detecting primary focus of metastatic cancer, differentiating between reactive proliferation and lymphoma and specifying immunologic phenotype of lymphoma in cell smears of fine-needle aspiration.


[Histogenesis of esophageal carcinoma].

[Histogenesis of esophageal carcinoma]. Histopathologic and tritiated thymidine labelled autoradiography was carried out on 206 human esophageal biopsy specimens obtained in Linxian county, a high risk area of esophageal cancer in China. According to the histopathologic criteria, 6 cases showed atrophy, 151 normal, 31 hyperplasia, 14 dysplasia and 4 carcinoma. The index of labeled cells were: atrophy 3.3, normal 4.73, hyperplasia 4.9, dysplasia 5.6, carcinoma in situ 11.76 and invasive carcinoma 24.63. Significant increase in labeling was found in the esophageal mucosa with hyperplasia, dysplasia and carcinoma. There was a gradient of increased expansion in the basal layer as the proliferating cells progress from normal to hyperplasia, to dysplasia, and to carcinoma. These results show that the hyperplastic and dysplastic cells were fundamental phases of carcinomatous change in the esophageal mucosa. It shows a wide spectrum of cellular alterations in the course of malignant change and the close relationship between the morphological alterations and cell biology.


[Clinico-pathologic analysis of 60 patients with primary malignant lymphoma of the small intestine and mesentery]. Clinico-pathologic analysis of 60 patients with primary malignant lymphoma of the small intestine and mesentery is presented. It occurs mainly in the adult. Both of these two tumors were first presented by abdominal pain and mass. Secondary anemia was common. They were complicated by intestinal obstruction, perforation or intussusception. The prognosis was aggravated by a large tumor mass, advanced stage and pathology of diffuse large cell subtype. Combined surgery, chemotherapy and radiotherapy were effective.


[20 rare primary hepatic malignant tumors]. We collected 20 primary liver malignant tumors other than hepatocellular carcinoma from 1968 to 1990; sarcomas from mesenchymal tissue (hepatic leiomyosarcoma, hepatic fibrosarcoma, Kupffer cell sarcoma, hepatic lymphatic sarcoma), two subtypes of hepatocellular carcinoma (fibrolamellar carcinoma and clear cell carcinoma), hepatic carcinoid, squamous carcinoma, etc. Analysis with review of literature is given.


[Surgical treatment of rectal carcinoid--report of 60 cases]. From 1973 to 1989, 60 patients with rectal carcinoid, as discovered by mass screening, were treated. It accounted for 0.02% of subjects screened and was the first among all G-I carcinoids. 96.7% of patients were asymptomatic and 86.6% were located within 8 cm of the anus. All were treated by surgery and none has died of this disease. The frequency of positive stump was 27% as observed in 31 specimens by local resection. Extended local resection still gave a positive residual rate of 9.4%. The authors believe that extended local resection is indicated even for small lesions less than 0.5 cm across.


[Pain-relief effect of tramadol HCL capsule for moderate and severe cancer pain]. Fifty-one patients with moderate (11/51) and severe (40/51) cancer pain were given a new non-narcotic analgesic -Tromadol HCL capsule (THC). In 42 of these patients, partial relief was obtained with an average relief time (ART) of 4.1 hours. The average starting time was 58 minutes. Pain relief rate (PRR) in moderate and severe pain was 82% (P = 0.945), and the ARTs were 7.4 hr. and 3.2 hr., respectively (P = 0.005). In 43 patients who were entered into a randomized study with control drugs of AT-237 (36 cases) or Anfendein (7 cases), the PRR was 60.4% (26/43), ART was 1.3 hours. The PRR and ART of THC and control drugs were statistically significant (P less than 0.001 and P = 0.023). Within adequate dose range, increase of THC dose could improve its analgesic effect (P = 0.011). The main side-effects were: somnolence (37.3%), nausea (35.3%), dizziness (33.3%), palpitation and anorexia (25.5%) and constipation (9.8%) which did not necessitate the suspension of THC administration.


[Five years' experience on intracavitary afterloading technique for carcinoma of the uterine cervix]. A series of 152 patients with carcinoma of uterine cervix treated from 1983-1984 by 3-channel (Cs-137) Buchler afterloading is presented. There were 1 Stage I, 89 Stage II (58.55%), 60 Stage III (39.47%) and 2 Stage IV lesions. The dose rate at point A was 10-25 cGy/min. The isoeffect correction factor of the afterloading and conventional methods at point A was 0.625. The over-all 5-year survival rate of the whole series was 70.39%, with 77.53% for Stage II and 61.67% for Stage III lesions. The frequency of late rectal and bladder reactions were 9.21% and 7.89%, respectively. It should be pointed out that the dose rate at the point 2cm from the external os was 1.7-8 times as high as that at point A, which caused more severe reactions in the surrounding tissues. A suggestion of reducing the number of fractions of intracavitary afterloading irradiation, the dose at point A delivered from vaginal irradiation and adopting partial whole pelvic external irradiation is put forward by the authors.


[Diagnosis and treatment of lung cancer in Shanghai--an analysis of present status]. The status of diagnosis and treatment of lung cancers as discovered in one year's interval in the Shanghai population is presented. A total of 940 lung cancers was detected from inhabitants 35-64 years of age, with a male-female ratio of 1.8:1. Pathology showed 35.7% adenocarcinoma and 35.1% squamous cell carcinoma. There was a predominance of adenocarcinoma (47.6%) in the female and squamous cell carcinoma (44.6%) in the male. Most (68.6%) of the lesions detected were already advanced in contrast to 14.7% of Stage I disease. The necessity of the doctor's vigilance was demonstrated by the fact that 23.3% of patients was seen by the doctor within one month after the presenting symptom and 44.5% of them had their diagnosis made within one month after their first hospital visit. The treatment consisted of surgery for 33.3%, chemotherapy for 35%, traditional Chinese medicine for 20% and symptomatic management for 9.7% of patients. As only 55.8% Stage I patients was treated by surgery, the protocol of treatment seemed to be improperly biased. Adequate training of the health workers was shown by the fact that 79.7% of these patients was confirmed by pathology and/or cytology and most of the Stage I lesions were diagnosed outside the hospital.


[Interventional radiology guided regional infusion chemotherapy for pelvic malignancy]. Retention transcatheter in the deep branch of femoral artery introduced by the Seldinger technique combined with the original arterial infusion was used in patients with pelvic malignancy. Infusion of chemotherapy and/or arterial embolization under the guide of pelvic arteriography was given. No 4-7 preshaped radiopaque catheter was passed from the femoral artery deep branch to the lower abdominal aorta. By turning the catheter tip and moving it up and down under TV monitor, it can be slipped into the uterine artery and/or common hepatic artery which supply blood to the tumor mass. Ten patients, including 7 with persistent or recurrent tumors, 2 with liver metastasis and 1 with vaginal botryoidies were treated. The immediate results were satisfactory in most patients with relief of symptoms and partial reduction of tumor. No side effects or complications were noted.


[Clinico-pathologic study of resection of low rectal cancer with preservation of anus--report of 48 patients]. Fourty-eight patients suffering from low rectal cancer were treated from 1987-1989 by operation with preservation of anus. Thirty-six similar patients as treated by Mile's operation during the same period served as controls. Follow-up results showed that recurrence developed earlier and in higher frequencies in the former group. The frequencies of recurrence in those with anus preserved were: 1 year 42% (5/12) and 2 years 50% (6/12) whereas those of Mile's operation were: 1 year 3% (1/36) and 2 years 11% (4/36) (P less than 0.01). The 1-year mortality rates also differed conspicuously: former group 17% (2/12) and the latter group 3% (1/36). The authors believe that for lesions of Dukes' B or C stages, pathological moderate or poor differentiation, larger than 4 cm across, deep crater or presence of peri-rectal or lymph node involvement as discovered on exploration should not be treated by resection with preservation of anus.


[Overexpression of p53 protein in human spontaneous esophageal carcinoma and fetal esophageal carcinoma induced by N-methyl-N-benzylnitrosamine (NMBzA)]. In normal cells, p53 protein is virtually undetectable by immunohistochemical methods. Mutation of p53 gene results in overexpression of the protein and thus levels of p53 detectable by immunohistochemistry may indicate expression of the mutant form of p53. Esophageal cancer (EC) samples obtained from patients who had undergone surgery were assayed for expression in p53 protein. Among 18 primary EC and their adjacent tissues, 7 cases of EC and 5 adjacent tissues overexpression of p53 protein was detected immunohistochemically. In cases with overexpression of the p53 in the adjacent tissues was detected 4 were also positive in the carcinomas. These results suggest that overexpression of p53 protein is a common molecular event in EC and may occur in the early stage of esophageal tumorigenesis. In addition, we found over expression of the p53 protein in the human fetal esophageal carcinoma induced by NMBzA, indicating that p53 gene mutation (s) might have occurred. The results provide further evidence that N-nitrosamine is a causative agent of human esophageal cancer.


[Detection of interferon-gamma in malignant peritoneal effusion in ovarian cancer patients]. Concanavalin A-induced human and mouse T cell proliferation assay was used to detect the suppressive activity of ascitic fluid (AF) in ovarian cancer patients. About 80% of AF specimens were found to be suppressive. However, when later tested for AF's effect on NK cell activity, instead of suppression, marked enhancement was observed. As IL-2 was barely detectable in AF, attention was focused on interferon (IFN). Its presence was then examined and confirmed by the ability of AF to protect HEp-2 cells from the cytopathic effect of vesicular stomatitis virus (VSV). As the protective effect against VSV was abolished by low pH treatment and by anti-human interferon gamma monoclonal antibodies (MAb), the IFN identified in AF was of the gamma type (IFN-gamma). The MAb could markedly inhibit not only AF's NK-enhancing effect but T cell suppressing effect as well. After removal of the IFN-gamma from AF by affinity chromatography, both activities of AF were lost. The possible clinical implication of this new finding with regards to host's anti-tumor resistance and prognosis is discussed.


[Experimental study on IL-6 activity against tumor: I. Regulation of IL-2-induced LAK cells]. The ability of human recombinant interleukin-6 (IL-6) to regulate the induction and function of lymphokine activated killer (LAK) cells from human fetal spleens was studied. The results showed that IL-6 alone was unable to induce fetal splenic mononuclear cells (FSMC) to develop functional LAK cells, nor was it able to affect the number of IL-2-induced LAK cells and to alter the lytic activity of the induced LAK cells in effector phase. However, when IL-6 was used in combination with IL-2 during the induction phase, the resulting LAK cells displayed considerably greater lytic activity than that with IL-2 alone (P less than 0.01), and this effect was IL-6 dose-dependent. The possible mechanism of the synergetic effect of IL-2 and IL-6 in LAK cell induction from human fetal spleens is discussed.


[Experimental expansion and antitumor effects of LAK cells from cancer patient's peripheral blood]. To augment the in vitro expansion of LAK cells, we added highly purified human recombinant interleukin-2, phytohemagglutinin and accessory cells (Uc cells) to the LAK culture system, with which huge number of LAK cells (LAK-L) were generated from originally small number of peripheral blood lymphocytes of cancer patients. These LAK-L cells exhibited similar antitumor activities in vitro and in vivo, as compared with LAK-S cells (LAK cells activated in short term culture). The phenotyping results suggested that there was more expression of IL-2 receptors in the LAK-L group than in the LAK-S group. The rapid proliferation of LAK-L cells was characterized by the expansion of OKT8 positive cells in the LAK-L populations.


[Detection of point mutations of C-Ki-ras oncogene in colon cancer by PCR using specific oligonucleotide probes]. Activation of C-Ki-ras oncogene by point mutation within codon 12,13 was determined by Polymerase Chain Reaction (PCR) using specific oligonucleotide probes. In 9 of 42 colon cancer specimens point mutations in codon 12 of C-Ki-ras oncogene were found. The point mutations identified were GGT(Gly)----GAT(Asp) (4 cases), GGT (Gly)----TGT (Cys) (3 cases) and GGT(Gly)----GTT(Val) (2 cases), respectively. Two types of point mutations (GGT----GAT, GGT----TGT) were found simultaneously in one specimen. The results showed that there was no relationship between the point mutation of C-Ki-ras oncogene and patient's sex, age, state of metastasis or prognosis.


[Action of calmodulin antagonist on the proliferation and cytoskeleton of A549 lung cancer cells]. Trifluoperazine (TFP) could inhibit the proliferation of A549 lung cancer cells and human embryo lung (HEL) cells. The inhibitory effects were dose dependent. The inhibitory effects were stronger in A549 lung cancer cells than in HEL cells at the same TFP dose. Cytoskeleton in A549 lung cancer cells treated with TFP was increased as observed electron microscopically. The role of calmodulin in the proliferation and the changes in cytoskeleton of A549 lung cancer cells is discussed.