Short-chain fatty acids in pouch contents from patients with and without pouchitis after ileal pouch-anal anastomosis. Fecal concentrations of short-chain fatty acids were markedly reduced in 6 patients with pouchitis (mean +/- SE, 56.2 +/- 13.3 mmol/L) compared with 28 patients without pouchitis (139.0 +/- 8.5 mmol/L; P less than 10(-3)). The ratios of acetate to propionate to butyrate were not changed (pouchitis, 75:12:11%; normal pouches, 76:12:11%), i.e., all acids were equally reduced. The 24-hour production of total short-chain fatty acids in 16.6% fecal homogenates from patients with pouchitis was decreased (17.5 +/- 5.3 mmol/L) compared with patients without pouchitis (33.3 +/- 3.4 mmol/L; P less than 0.05), which could be overcome by the addition of saccharides to the homogenates. Pouch excretions of saccharides were similar in the two groups, but dilution occurred during pouchitis because of the increased outputs. Concentrations and productions of short-chain fatty acids correlated with pouch concentrations and excretions of sodium and saccharides. L-Lactate was elevated in pouchitis outputs, but differences in stool culture counts, mucosal histology, fecal concentration, assimilation or production of ammonia, nitrogen excretion, pH, and osmolality were not found. Pouchitis is characterized by decreased fecal concentrations and productions of short-chain fatty acids possibly caused by low pouch concentrations of fermentable saccharides.


Lactase gene expression during early development of rat small intestine. Expression of lactase messenger (m) RNA and protein in rat small intestine during fetal and postnatal development was analyzed using in situ hybridization and immunohistochemistry. Lactase mRNA was first identified at 18 days of development, and lactase protein was first detected at day 20. Lactase mRNA and protein were present along the entire villus. Lactase mRNA increased, reaching a maximum at day 20. Just before birth a decrease in lactase mRNA was observed. In newborn intestine, lactase mRNA was present only from the base of the villus up to the mid-villus region and was undetectable up to the villus tips. Lactase protein continued to be expressed along the entire villus. These data show that expression of lactase mRNA and protein do not parallel, indicating a posttranscriptional control in fetal development. Lactase gene transcription is initiated late in gestation concomitant with villus formation and is exclusively seen in villus epithelial cells. The restriction after birth of lactase mRNA expression to cells at the villus base suggests the occurrence of a previously unknown step in postnatal differentiation of the enterocyte.


Boosted mucosal immune responsiveness in the rat intestine by actively transported hexose. Anaphylaxis-mediated intestinal fluid secretion was measured in Trichinella spiralis- or ovalbumin-immunized rats challenged intraduodenally with T. spiralis somatic antigen (1 mg protein/0.5 mL saline) or ovalbumin (1 mg/0.5 mL saline), respectively. Intestinal fluid volume was measured 30 minutes after challenge as an index of net secretion. Challenge with the antigenic bolus containing 40 mmol/L D-glucose induced twice the fluid secretion as that induced by either antigen alone. L-Glucose was an ineffective substitute for D-glucose. The enhancement of secretion by D-glucose was dependent on prior immunologic sensitization, was diminished in the presence of phlorizin, and was mimicked by beta-methyl glucoside. Results indicate that the active transport of D-glucose augments the antigen-mediated fluid secretion, possibly by enhancing permeation of the intestinal epithelium to antigen, thereby providing greater access to the mucosal immune system.


Scintigraphic demonstration of lactulose-induced accelerated proximal colon transit. Although lactulose, a widely used cathartic, is known to increase stool frequency, details of its site of action in the colon are obscure. In the present study a noninvasive scintigraphic technique was used to closely follow the movements of proximal colonic contents. Lactulose, 10-20 mL three times daily, significantly accelerated mean transit through the ascending colon from 12.9 +/- 3.7 to 7.0 +/- 2.5 hours (n = 11; P less than 0.01). This was associated with the occurrence of mass movements, with six such events seen during lactulose treatment whereas only one was seen during the control study (P less than 0.05). Lactulose also accelerated movement through the rest of the colon so that at 24 hours after dosing the geometric center of the isotope bolus was distal to that seen during the control study (6.6 +/- 1.2 vs. 4.7 +/- 1.3; n = 11, P less than 0.001). This model of diarrhea in otherwise normal subjects was subsequently used to study the effects of viscous gels in diarrhea. The viscous and relatively poorly fermented gel ispaghula, 3.5 g three times daily, abolished mass movements and was associated with a small but significant increase in proximal colonic transit time, which increased from 6.1 +/- 2.1 to 7.7 +/- 1.5 hours (n = 8; P less than 0.05). By contrast, the viscous but readily fermentable gelling agent guar gum, 5 g three times daily, further accelerated the cathartic effect of lactulose, with the mean transit time decreasing from 6.4 +/- 2.3 to 4.7 +/- 1.7 hours (n = 8; P less than 0.05). The acceleration of proximal colonic transit by lactulose may be a useful model to study diarrhea and its modification by therapy.


In vivo bicarbonate secretion by human esophagus. The capacity of the human esophagus to secrete bicarbonate was studied in vivo in 10 healthy subjects. A 10-cm segment of the lower esophagus was isolated between two balloons, and the segment was perfused with an unbuffered isotonic saline solution (pH 7) for 30 minutes. The perfusate was collected, pooled, and analyzed for bicarbonate using a sensitive back-titration method. Measurements of aspirate amylase and salivary amylase and bicarbonate permitted correction of perfusate bicarbonate values for contamination by swallowed saliva. The esophagus of all 10 subjects were found to secrete bicarbonate in amounts ranging from 10 to 274 microEq/30 min (average, 78 microEq/30 min); based on in vitro studies, these amounts of bicarbonate were shown to be capable of neutralizing enough residual acid from an episode of reflux to increase pH from 2.5 almost to neutrality (pH 6-7). These findings document the presence within the human esophagus of an additional mechanism for defense against (acid) reflux damage, namely, through enhanced luminal acid clearance by the secretion of bicarbonate ions.


Effects of chronic superficial injury on the rat gastric mucosa. The effects of chronic superficial injury on the stomach were studied in rats dosed with a mild irritant (2 mol/L NaCl intragastrically) every 48 hours for 1 month followed by 1-month recovery. A single exposure to this mild irritant induced gross protection against 6 mol/L NaCl for 1 but not 2 days. Leukotriene C4 (LTC4) levels increased slightly. Prostaglandin E2 (PGE2) concentration was unchanged. After 2-week dosing, protection was concomitant with markedly elevated PGE2 concentration. LTC4 values remained unchanged. Superficial epithelial cells were more resistant to damage. After 4-week dosing, protection occurred at 1 but not 2 days after the dose with an inverse correlation of PGE2. LTC4 concentration increased significantly at both times. Chronic injury for 1 month did not alter rapid epithelial restitution or PGE2 and LTC4 released 15 minutes after challenge with 6 mol/L NaCl. The recovery period showed loss of protection. PGE2 values returned to control levels but LTC4 values remained slightly elevated. It is concluded that short- or long-term (4-week) "adaptive cytoprotection" is not mediated by endogenous PGE2. Only extremely high levels of LTC4 correlated with loss of protection. The role of the more resistant superficial epithelium remains unknown.


Monthly variation of hospital admission and mortality of peptic ulcer disease: a reappraisal of ulcer periodicity. The occurrence of peptic ulcer is characterized by a seasonal variation, the meaning of which is poorly understood. The present study examined the periodicity of hospital admissions and mortality resulting from gastric and duodenal ulcer to determine its etiologic relevance. Ulcer periodicity was studied in the nationwide data sets of the Department of Veterans Affairs, the Health Care Financing Administration, and the Vital Statistics. Both ulcer types were characterized by similar patterns of periodicity. Hospital admissions peaked during the first 3 months of the year, followed by a marked decline during summer and a second smaller peak around October. This pattern occurred independently of age, sex, race, and place of residence. It also pertained to ulcers complicated by hemorrhage or perforation. Although total admissions peaked earlier during the year and showed a less consistent peak in October, there was a close resemblance between the periodicity of all diseases and that of peptic ulcer. Mortality was highest in January and lowest in July for all disease and ulcer diseases alike. The similarity between the periodicity of peptic ulcer and other diseases suggests that the major factors responsible for the cyclic behavior of gastric and duodenal ulcer are not particular to these diseases but affect other unrelated diseases alike.


Effect of loxiglumide on basal and gastrin- and bombesin-stimulated gastric acid and serum gastrin levels. The effect of the specific cholecystokinin-receptor antagonist loxiglumide on basal and bombesin-, and gastrin 17-I-stimulated gastric acid secretion and serum gastrin levels was studied in 12 healthy subjects. Loxiglumide (10 mg.kg-1.h-1) significantly augmented basal gastric acid output from 1.8 +/- 0.3 to 3.9 +/- 0.6 mmol H+/h (P less than 0.005) but did not significantly influence integrated basal serum gastrin concentrations (2 +/- 21 vs. 32 +/- 21 pmol L-1.h-1). Both gastric acid secretion and integrated serum gastrin concentrations stimulated by bombesin infusion (92.6 pmol.kg-1.h-1) were significantly augmented by loxiglumide [from 4.0 +/- 0.3 to 10.0 +/- 1.3 mmol H+/h (P less than 0.005) and from 1251 +/- 93 to 2558 +/- 206 pmol.L-1.h-1 (P less than 0.005), respectively]. Gastric acid output and serum gastrin concentrations during infusion of 5 pmol.kg-1.h-1 of synthetic human gastrin 17-I (9.6 +/- 2.9 mmol H+/h and 1045 +/- 177 pmol.L-1.h-1) and during infusion of 15 pmol.kg-1.h-1 of gastrin 17-I (14.5 +/- 3.1 mmol H+/h and 2412 +/- 312 pmol.L-1.h-1) were not significantly influenced by loxiglumide (10.3 +/- 2.3 mmol H+/h and 1291 +/- 257 pmol.L-1.h-1 for the 5-pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide and 13.6 +/- 3.4 mmol H+/h and 2611 +/- 305 pmol.L-1.h-1 for the 15-pmol.kg-1.h-1 gastrin 17-I infusion dose with loxiglumide). These data indicate that endogenous cholecystokinin inhibits gastric acid secretion under basal conditions and gastrin release and gastric acid secretion during infusion of bombesin in humans and suggest that the augmented effect of loxiglumide on bombesin-stimulated gastric acid secretion may be explained largely by enhanced gastrin release.


Pharyngeal (Zenker's) diverticulum is a disorder of upper esophageal sphincter opening. Pharyngeal coordination, sphincter opening, and flow pressures during swallowing were investigated in patients with pharyngeal (Zenker's) diverticula. Fourteen patients with diverticula and 9 healthy age-matched controls were studied using simultaneous videoradiography and manometry. Pharyngeal and upper esophageal sphincter pressures were recorded by a perfused side hole/sleeve assembly. Temporal relationships among swallowing events, extent of sphincter opening during swallowing, and intrabolus pressure during bolus passage across the sphincter were measured. The timing among pharyngeal contraction and sphincter relaxation, opening, and closure did not differ between patients and controls. Sphincter opening was significantly reduced in patients compared with controls in sagittal (P = 0.0003) and transverse (P = 0.005) planes. Manometric sphincter relaxation was normal in patients. Intrabolus pressure was significantly greater in patients than in controls (P = 0.001). It is concluded that Zenker's diverticulum is a disorder of diminished upper esophageal sphincter opening that is not caused by pharyngosphincteric incoordination or failed sphincter relaxation. Incomplete sphincter opening is likely to cause dysphagia. Increased hypopharyngeal pressures during swallowing are probably important in the pathogenesis of the diverticulum.


Effect of a catheter in the pharynx on the frequency of transient lower esophageal sphincter relaxations. Transient relaxation of the lower esophageal sphincter (LES) is observed fairly frequently during prolonged continuous monitoring of the LES. The aim of this study was to test whether the presence of a catheter in the pharynx through the stimulation of mechanoreceptors may induce transient LES relaxation. LES and esophageal pressure recordings were obtained for 1 hour in six subjects with a manometric catheter placed via a gastrostomy tube. Swallowing was monitored by submental electromyographic recording. Additional recordings were obtained in these subjects with a catheter placed in the pharynx for 1 additional hour. Transient LES relaxations were recorded in both study periods, i.e., with and without a catheter in the pharynx. The frequency of transient LES relaxations was significantly higher in the presence of manometric catheters in the pharynx (6.4 +/- 2.2 vs. 2.0 +/- 1.1 total LES relaxations). The frequency of transient LES relaxation during the first and second hour after placement of the manometric catheter in a group of seven healthy subjects was not significant different. It is concluded that the pharynx is one of the sites that may mediate the induction of transient LES relaxation.


Barrett's esophagus: age, prevalence, and extent of columnar epithelium. The development of Barrett's esophagus was studied using data from 51,311 patients undergoing upper gastrointestinal endoscopy between 1976 and 1989. Three hundred seventy-seven patients had greater than or equal to 3-cm columnar epithelium in the esophagus and no carcinoma. The prevalence of Barrett's esophagus increased with age to reach a plateau by the seventh decade. Half of the maximum prevalence was reached by age 40 years, the estimated median age of development of the disorder. Unlike prevalence, the mean length of columnar epithelium did not increase with age. No significant change in length was found in 21 patients followed up for a mean of 7.3 years (mean initial length, 8.29 +/- 0.85 cm; mean final length, 8.33 +/- 0.77 cm). The length of columnar epithelium did not increase in the presence of esophagitis or decrease when esophagitis was absent. Mean age at diagnosis of Barrett's esophagus was 63 years without carcinoma and 64 years in a separate group of patients with adenocarcinoma. The data are consistent with a fairly rapid evolution of Barrett's esophagus to its full length with little subsequent change. Barrett's esophagus may develop more than 20 years before the mean age of clinical recognition or the development of esophageal adenocarcinoma.


Effect of neurotensin on gut mucosal growth in rats with jejunal and ileal Thiry-Vella fistulas. Neurotensin (NT) stimulates growth of normal and atrophic small bowel mucosa; the mechanisms for this trophic effect of NT are not completely known. The purpose of this study was to (a) determine whether the trophic effect of NT is mediated by mechanisms involving luminal or nonluminal factors and (b) determine whether NT exerts a differential trophic effect on either jejunal or ileal mucosa. Twenty-eight male Sprague-Dawley rats underwent construction of either a jejunal or ileal Thiry-Vella fistula (TVF). After a 1-week recovery period, rats were further subdivided into groups to receive either saline (control) or NT (300 micrograms/kg). Rats were killed on day 6, and TVF as well as corresponding segments of intact jejunum or ileum were removed. Mucosa was scraped, weighed, and analyzed for DNA and protein content. In addition, representative sections of full-thickness bowel from each group were examined histologically. In the jejunal TVF group, NT increased mucosal growth measurements in both the TVF and the intact jejunum. However, in the ileal TVF group, NT stimulated proliferation of intact ileal mucosa only; it had no effect on ileal mucosa in the TVF. These results suggest that NT exerts a systemic effect independent of luminal factors on the proliferation of proximal gut mucosa in addition to an indirect effect produced by stimulation of endogenous luminal secretions. In contrast, an indirect mechanism appears to be the predominant action of NT on growth of distal gut mucosa.


Neutrophil-mediated nitrosamine formation: role of nitric oxide in rats. It is well known that chronic inflammation of the colon and rectum is associated with an increased risk of colorectal cancer, but the mechanisms by which inflammation promotes neoplasia remain undefined. The authors propose that inflammatory neutrophils may produce carcinogenic nitrosamines via the L-arginine-dependent formation of nitrogen oxides such as nitric oxide. Therefore, the objectives of the study were to characterize the L-arginine-dependent formation of nitrogen oxides by inflammatory (elicited) neutrophils using conditions that more closely mimic the extravascular (i.e., interstitial) compartment of the gut and to characterize the neutrophil-dependent N-nitrosation of a model amine to yield its nitrosamine derivative. In the absence of any metabolic activation, adherent, inflammatory neutrophils (2 x 10(6) cells) produced 12.8 +/- 1.4 mumol/L of nitrite during a 4-hour incubation period. Omission of L-arginine and/or inhibition of nitric oxide synthase by the addition of 1 mmol/L NG-nitro-L-arginine methyl ester (L-NAME) resulted in 35%-78% inhibition of nitrite production, suggesting that nitrite was derived from nitric oxide. By comparison, neither circulating rat neutrophils nor elicited rat macrophages produced significant amounts of nitrite under the same conditions. Furthermore, elicited neutrophils (2 x 10(6) cells) were capable of N-nitrosating 2,3-diaminonaphthalene to yield its nitrosamine derivative 1-naphtho-2,3-triazole (282 +/- 12 nmol/L) in a time- and cell-dependent pattern similar to that of nitrite production. Addition of a variety of antioxidants (e.g., ascorbic acid, reduced glutathione, alpha-tocopherol analog), 5-aminosalicylic acid, or L-NAME resulted in 80%-85% inhibition of neutrophil-mediated nitrosamine formation. Taken together, these data suggest that inflammatory neutrophils may represent an important metabolic source of endogenous carcinogens during times of active intestinal inflammation.


Norfloxacin prevents bacterial infection in cirrhotics with gastrointestinal hemorrhage. To assess the efficacy of selective intestinal decontamination with norfloxacin in the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage, 119 patients were included in a prospective randomized study. Group 1 (n = 60) received norfloxacin orally or through a nasogastric tube, 400 mg twice daily for 7 days beginning immediately after emergency gastroscopy; group 2 (n = 59) was the control group. We found a significantly lower incidence of infections (10% vs. 37.2%; P = 0.001), bacteremia and/or spontaneous bacterial peritonitis (3.3% vs. 16.9%; P less than 0.05), and urinary infections (0% vs. 18.6%; P = 0.001) in patients receiving norfloxacin, as a consequence of decrease in the incidence of infections caused by aerobic gram-negative bacilli. The decrease in mortality observed in the treated group (6.6% vs. 11.8%) did not reach statistical significance. The cost for antibiotic treatment showed a 62% reduction in the treated group compared with the control group. The results show that selective intestinal decontamination with norfloxacin is useful in preventing bacterial infections in cirrhotics with gastrointestinal hemorrhage.


Bromobenzene accelerates hepatocyte streaming in rats. Sixty male adult rats weighing between 250 and 300 g were divided in two equal experimental groups. The first experiment was designed to evaluate hepatocyte streaming. Animals were injected with 0.5 microCi [3H]thymidine and 1 hour later received one intraperitoneal injection of bromobenzene (3.8 mmol/kg, dissolved in corn oil). The animals were then killed in groups of five at 1 hour and 2, 4, 7, 14, and 30 days. The aim of the second experiment was to evaluate labeling index changes with time. Animals received one intraperitoneal injection of bromobenzene and were killed in groups of five at 1, 2, 3, 4, 7, and 14 days. They received [3H]thymidine 1 hour before killing. Bromobenzene induced a necrosis in the third acinus zone that disappeared within a week. On day 0 the labeling index of hepatocytes and littoral cells was 0.3% +/- 0.04% and 0.4% +/- 0.05%, respectively. On the second day, it reached 14.6% +/- 2.6% and 10.1% +/- 3.1% and returned to its initial value after 1 week. Dead cells in the third zone were replaced by inflowing cells from the intact zones. Hepatocytes and littoral cells streamed at the same velocity of 6 +/- 0.5 micron/day, faster than in untreated animals with velocity of 3.2 microns/day. Parenchyma and stroma responded to injury in a coordinated fashion. From the functional point of view, hepatocytes and littoral cells operate as a unit that is called proliferon. The maximal proliferon life span was 57 days after bromobenzene treatment and 108 days in controls.


Inhibition of nucleation and crystal growth of calcium carbonate by human lithostathine. Pancreatic juice is naturally supersaturated in calcium and bicarbonate ions. A mechanism controlling CaCO3 crystal formation and growth is therefore necessary to prevent duct clogging. The present study shows that lithostathine, a glycoprotein present in human pancreatic juice at a concentration in the range of 10 mumol/L, could be involved in such a control. Lithostathine in concentrations greater than 1.5 mumol/L significantly delayed crystal nucleation and inhibited growth of preformed CaCO3 crystals from supersaturated solutions. Adsorption of lithostathine on crystals was shown by immunodetection. Albumin also adsorbed on CaCO3 crystals, but neither albumin nor other pancreatic secretory proteins inhibited crystal nucleation or growth. Lithostathine adsorbed to sites specifically inhibiting crystal growth with a dissociation constant (Kd) = 0.9 x 10(-6) mol/L. The glycosylated amino-terminal undecapeptide generated by limited trypsin hydrolysis inhibited CaCO3 crystal growth with a Kd = 3.0 x 10(-6) mol/L, similar to that of lithostathine. On the contrary, the carboxy-terminal polypeptide was inactive. A synthetic undecapeptide identical to the N-terminal end but not glycosylated was equally active. The activity disappeared upon digestion of the undecapeptide with V8 protease. The N-terminal undecapeptide of lithostathine is therefore essential to the inhibitory activity of the protein on CaCO3 crystal growth.


Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis. To assess the frequency of antibodies to liver/kidney microsome type 1 (anti-LKM1) in patients with chronic active hepatitis, 131 such patients were tested by an indirect immunofluorescence assay. Of 62 patients with type 1 autoimmune hepatitis, none were seropositive. In contrast, 3 of 11 patients with autoimmune hepatitis and antimitochondrial antibodies (27%) were seropositive for anti-LKM1. Each had responded to corticosteroid therapy, and retesting of sera confirmed that each had been misclassified as antimitochondrial antibody positive. None of the patients with chronic active hepatitis B (14 patients) or C (24 patients) had anti-LKM1. Similarly, none of the 20 patients with cryptogenic disease had these antibodies. It is concluded that anti-LKM1 is specific for type 2 autoimmune hepatitis and is infrequent in adult patients seen at a referral center in the United States for chronic active hepatitis. Anti-LKM1 reactivity may be misinterpreted as antimitochondrial antibody reactivity by indirect immunofluorescence. Chronic hepatitis B and C virus infections are not important stimuli for the production of anti-LKM1, and testing for anti-LKM 1 is unlikely to clarify the nature of cryptogenic disease.


Immunoglobulin A and interleukin 6 form a positive secretory feedback loop: a study of normal subjects and alcoholic cirrhotics. Patients with alcoholic liver cirrhosis (ALC) have high serum levels and spontaneous in vitro production of immunoglobulin (Ig) A. Deposits of IgA are also found in liver sinusoids. Increased interleukin 6 (IL-6) production is another feature of this disease. This study shows a linear correlation between increased lipopolysaccharide (LPS)-induced IL-6 production and increased spontaneous IgA and IgG secretion by peripheral blood mononuclear cells (PBMCs). PBMCs and purified monocytes isolated from healthy control subjects and patients with ALC contain elevated IL-6 messenger RNA levels and produce IL-6 in response to stimulation with soluble polymeric IgA (p-IgA) or attached monomeric IgA (m-IgA) but not with soluble m-IgA. The addition of monospecific antibody to human IL-6 inhibits spontaneous IgA production by PBMC. This inhibition is more pronounced in patients with ALC. These data provide evidence that IgA, possibly by attachment to cells possessing Fc alpha receptors and secreting IL-6, is involved in the production of this major mediator and the amplification of Ig secretion. Circulating IgA and IgA deposits could therefore initiate a process of autoamplification implicated in the development of hypergammaglobulinemia in ALC.


Mobilization of malignant ascites with diuretics is dependent on ascitic fluid characteristics. Serial ascites and plasma volumes were measured during diuresis in nine patients with ascites caused by peritoneal carcinomatosis, four patients with chylous malignant ascites, and three patients with portal hypertension-related ascites caused by massive hepatic metastases. Oral diuretics were given to achieve an adequate natriuresis on a sodium-restricted diet. During the study period (7.8 +/- 3.2 days), patients with peritoneal carcinomatosis and chylous ascites lost 0.49 +/- 0.31 and 0.51 +/- 0.42 kg/day in weight, respectively, with negligible change in ascites volumes (-0.03 +/- 0.11 and 0.02 +/- 0.09 L/day). Patients with ascites caused by massive hepatic metastasis lost 1.06 +/- 0.15 kg/day in weight (P = 0.01 for massive hepatic metastasis vs. peritoneal carcinomatosis) and 0.23 +/- 0.13 L/day of ascites (P less than 0.05 vs. other groups). Plasma volume changes were not significantly different among the three groups. Patients with edema (9/16) had a greater natriuresis and daily weight loss. Three patients with peritoneal carcinomatosis and one with chylous ascites developed renal dysfunction or symptomatic hypotension. No patient with massive hepatic metastasis developed these complications. In patients with ascites caused by peritoneal carcinomatosis or chylous malignant ascites there is no mobilization of ascites, whereas in patients with massive hepatic metastasis, ascites may be mobilized with diuretics.


Fibrosing cytolytic liver failure secondary to recurrent hepatitis B after liver transplantation. Four patients who underwent transplantation for hepatitis B virus-related liver disease developed rapidly progressive liver failure attributable to recurrent hepatitis B disease typified by hyperbilirubinemia and distinctive hepatocyte ballooning and progressive fibrosis consistent with recently reported fibrosing cholestatic hepatitis. Among these four patients, the mean interval from transplantation to redocumentation of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) was 5 months, to development of malaise and jaundice 6 months, to histological diagnosis 7 months, and to graft failure 8 months. The only patient who underwent retransplantation had accelerated recurrence of the same syndrome with biopsy documentation 1 month later and graft failure 2 months later. Distinctive histological features included confluent hepatocellular ballooning and progressive periportal fibrosis followed by lobular collapse over 4-6 weeks without significant inflammation. Immunohistochemical staining showed marked HBsAg and hepatitis B core antigen (HBcAg) immunoreactivity. The rapid development of cytolytic hepatocellular necrosis and lobular collapse with prominent HBcAg immunoreactivity without significant inflammation suggests a cytolytic rather than immune pathogenesis for this unique and devastating form of recurrent hepatitis B that might better be termed "fibrosing cytolytic hepatitis."


Synthesis of cellular fibronectin by rat liver fat-storing (Ito) cells: regulation by cytokines. Fibronectins are multifunctional extracellular matrix glycoproteins that seem to play a pacemaker role in liver fibrogenesis. The expression of cellular fibronectin by rat liver fat-storing cells in primary culture and their modulation by cytokines was studied. Cellular fibronectin was localized in the cytoplasm and on the surface of cultured fat-storing cells as well as in extracellular matrix fibrils by indirect immunofluorescence. Immunoprecipitation of endogenously labeled fibronectin using type specific antibodies showed the synthesis and secretion of cellular fibronectin by fat-storing cells in vitro. ED1 positive sequences specific for cellular fibronectin and absent in plasma fibronectin were detected within the total RNA of fat-storing cells. Cellular fibronectin synthesis was severalfold enhanced in "activated" vs. "resting" fat-storing cells. Treatment of fat-storing cells with transforming growth factor beta 1 resulted in a dose dependent increase of fibronectin synthesis. In contrast, interferon gamma inhibited the synthesis of fibronectin. The stimulation of fibronectin synthesis by transforming growth factor beta 1 and the inhibition by interferon gamma might be of importance for pathophysiology and therapy of liver fibrogenesis.


Manometric characteristics of cervical dysphagia in a patient with the Kearns-Sayre syndrome. The manometric findings of deglutitive pharyngoesophageal function in a patient with the Kearns-Sayre syndrome and cervical dysphagia are described. These findings indicate that striated muscles of the pharynx, upper esophageal sphincter (UES), and proximal esophagus are involved. Near absence of pharyngeal peristalsis, abnormally low UES resting pressure, and absence of proximal esophageal peristalsis characterize the manometric findings in this patient. It is conceivable that in mild cases, a combination of various degrees of severity of the above findings may exist.


Fatal neonatal liver failure and mitochondrial cytopathy: an observation with antenatal ascites. Mitochondrial cytopathies are multisystemic diseases of extremely variable expression caused by a deficiency in oxidative phosphorylation. Only five cases of neonatal liver failure in the context of mitochondrial cytopathy have been reported, with incomplete morphological data of the liver in three. In the case presented here, ascites had been diagnosed prenatally and liver failure was particularly severe (factor V less than 15% with fatal coma the fourth day). Histologically there were incomplete cirrhosis, microvesicular steatosis, major canalicular cholestasis with proliferative neocholangioles, and bile duct thrombi. There were also some iron pigments in the periportal area and partial glycogen depletion. By electron microscopy, mitochondria in numerous hepatocytes appeared abnormal with occasional cristae in a fluffy matrix, some containing dense inclusions. Study of respiratory chain activity showed a defect in cytochrome c oxidase (complex IV), revealed by oxygraphic measurement on fresh muscle biopsy and confirmed by spectrophotometric enzymatic assays performed on muscle and liver homogenates. The association of neonatal liver failure with hyperlactacidemia warrants investigation into a deficiency in oxidative phosphorylation.


Clinical features and endoscopic management of Dieulafoy's disease. The experience of a specialized management team using urgent endoscopy in the management of acute gastrointestinal bleeding from Dieulafoy's disease is presented. Dieulafoy's disease was found in 19 of 1124 consecutive patients with upper gastrointestinal bleeding. Most patients with Dieulafoy's disease were elderly men with severe acute upper gastrointestinal hemorrhage. Endoscopic diagnosis was possible in all patients, but required multiple endoscopies in 37%. The lesions were in the proximal stomach (79%) and duodenal bulb (21%). Endoscopic therapy included epinephrine injection, then heater probe coagulation in 17 patients, bipolar electrocoagulation in 1, and Nd:YAG laser photocoagulation in 1. Endoscopic therapy was successful in 18 patients (95%); one patient had successful surgery after endoscopic therapy failed. There were no deaths due to bleeding and no endoscopic complications. Dieulafoy's disease is an unusual cause of acute gastrointestinal bleeding. Endoscopic diagnosis is sometimes difficult, but primary endoscopic therapy is safe, successful, and should be attempted.


Mechanical lithotripsy of large gallstones: correlation with CT characteristics. The CT characteristics of gallstones were correlated with mechanical forces required to fragment calculi in vitro. Forty-two gallstones > or = 11 mm in largest diameter were subjected to in vitro CT scanning and categorized as isodense, faint, laminated, rimmed, or dense as compared with saline. A mechanical lithotripter, attached to a dynamometer, was utilized simulating in vivo technique to accomplish lithotripsy. Significantly more force was required to fracture CT-dense (p < 0.02) and CT-rimmed (p < 0.05) gallstones than was required to fracture CT-isodense gallstones.


Barrett's esophagus: lack of association with adjuvant chemotherapy for localized breast carcinoma. This study was designed to prospectively, endoscopically, and histologically determine the prevalence of Barrett's esophagus in patients who had received adjuvant chemotherapy for localized breast carcinoma. Fifteen white women who received cyclophosphamide, methotrexate, and 5-fluorouracil (N = 8) or cyclophosphamide, adriamycin, and 5-fluorouracil (N = 7) chemotherapy underwent esophagogastroduodenoscopy and esophageal biopsy a mean 31.1 months (median, 11 months) after completion of full-course chemotherapy. Twelve of 15 patients had experienced oral ulcerations, diarrhea, or odynophagia during chemotherapy. In no patient was Barrett's esophagus identified endoscopically or histologically. This study fails to demonstrate an increased prevalence of Barrett's esophagus in breast carcinoma patients who had received adjuvant chemotherapy.


The effect of guidewires during electrosurgical sphincterotomy. We describe six electrosurgical incidents and one complication which occurred during guidewire-assisted sphincterotomy. Studies were conducted on three types of guidewires: Teflon painted, Teflon sheathed, and polymer coated. Scanning electron micrographs demonstrated surface imperfections in the painted Teflon guidewire coating, which allowed for potential electrical short circuits between cutting wire and guidewire through a septal defect in a double channel catheter. Septal defects were found in 25% (1 of the 4 tested) of the factory fresh sphincterotomes that were used in this study, and in 10% (6 of 57) of those used clinically. Induced current (capacitively coupled) present on the guidewires was measured at 13 to 30 mA for typical sphincterotomy settings. The induced current on sheathed guidewires, without any insulation defects, was measured at less than 1 mA at typical operating powers. As both short circuits and induced currents place the patient at risk for burns or perforation at the distal end of the guidewire, we suggest the use of a Teflon-sheathed rather than Teflon-painted guidewire, if the wire is to be left in place during sphincterotomy. The Teflon sheath offers the thickest insulation, a very low probability of surface defects, and therefore a high index of safety.


Accuracy of assessment of the extent of examination by experienced colonoscopists. One hundred colonoscopies were done. The colonoscopist noted whether the cecum had been intubated as well as the markers used to make this determination. With the colonoscope in position at maximum penetration, a radiologist independently determined its position using fluoroscopy, with a contrast agent delivered through the colonoscope. The cecum was entered in 86 of 100 cases. The tip of the colonoscope was at the level of the ileocecal valve in nine additional cases; the colonoscopist judged that the cecum was well seen in five of these nine. In one case, the colonoscopist overestimated the extent of the examination when transillumination in the right lower quadrant was the only confirming marker. When the more reliable markers (ileocecal valve, appendiceal orifice, converging indentations of the taenia coli in the cecal pole) were seen, no errors were made. Experienced colonoscopists are accurate in assessing the extent of colonoscopy and fluoroscopic confirmation is not routinely needed. When reliable markers are not seen during the examination, a barium enema, preferably with air contrast, should be done.


Endoscopic diagnosis of colonic endometriosis. Involvement of the colon or rectum with endometriosis is uncommon but may be a cause of gastrointestinal symptoms such as diarrhea, pain, and bleeding. To determine whether endoscopy has a role in evaluating endometriosis of the colon, we reviewed all cases of endometriosis undergoing colonic resection from 1984 to 1989. There were nine patients, six of whom had intermittent hematochezia. All had lesions detected at endoscopy described as a polyp, mass, or stricture. Five of the six patients with symptoms of hematochezia had mucosal involvement in the resected specimen. Four of these five had a visible lesion at endoscopy with endometriosis on biopsy. The three patients without hematochezia had no mucosal endometriosis in the resected colonic specimen or endometrial tissue on biopsy. In patients with colonic endometriosis and hematochezia, endoscopy and biopsy can confirm the diagnosis of colonic endometriosis.


Pain following colonoscopy: elimination with carbon dioxide. Fifty-six patients have been examined in a prospective randomized study on the effects of air and carbon dioxide on post-procedural discomfort following colonoscopy. A significant reduction in post-procedural pain was observed at 6 hours (p = < 0.0005) and was still present the next day (p = 0.01). This was associated with a difference in the grading of flatus at 6 and 24 hours (p = < 0.0001 and < 0.05, respectively). An abdominal radiograph 1 hour after the procedure showed minimal gas in the CO2 patients, while the patients who had air showed distention of large and small bowel (p = < 0.0001 and < 0.01, respectively). Seventeen of 29 patients who had air suffered post-procedural pain, compared with 2 of 27 of the CO2 patients. Fifty-seven percent of the patients who were given air had colonic diameters over 6 cm on a 1-hour post-colonoscopy radiograph and 18% over 10-cm diameter. Provision by equipment manufacturers of simple and safe devices for routine delivery of CO2 for lower gastrointestinal endoscopy is long overdue.


Serum electrolyte, mineral, and blood pH changes after phosphate enema, water enema, and electrolyte lavage solution enema for flexible sigmoidoscopy. Hypertonic sodium phosphate (Fleet) enema is a commonly used preparation for fiberoptic flexible sigmoidoscopy. Unfortunately, Fleet has been associated with complications in children and adults. The purpose of this study was to compare the serum electrolytes, mineral, and blood pH changes before and after the administration of Fleet with water and polyethylene glycol electrolyte lavage solution (Golytely) as enemas in an adult population undergoing flexible sigmoidoscopy. Sixty-six patients were randomized in a double-blind fashion to receive two enemas of either Fleet (N = 22), water (N = 20), or Golytely (N = 24). The cleansing ability was graded from 1 to 4 (1 = poor, 4 = excellent). The Fleet had significantly better optimal cleansing efficacy compared with water (p < 0.05) but not to Golytely (p > 0.05). There was a significant increase in the serum phosphorus in the Fleet group compared with water (p < 0.001) or Golytely (p < 0.001). However, absolute serum phosphorus values after Fleet enema always remained within normal range in all but one patient. The changes in other electrolytes, minerals, and venous pH were insignificant.


Low sodium solution for colonic cleansing: a double-blind, controlled, randomized prospective study. The standard polyethylene glycol electrolyte solution for colonic cleansing has a salty unpleasant taste resulting in limited patient acceptance. Introduced as a major advance allegedly providing a distinctly better taste, a new low sodium cleansing solution was recently described. In a double-blind controlled fashion, 66 colonoscopy outpatients were interviewed about general palatability and tolerance of the solution they had ingested for the preparation of endoscopy. Preparation quality was assessed endoscopically. Similar results were obtained for both solutions concerning palatability, tolerance, and cleansing quality. Furthermore, a small quantity of both solutions was tasted and directly compared for taste qualities before endoscopy. Fifty-one and one-half percent of patients preferred the new solution and 48.5% preferred the standard solution or had no preference (not significant). Of the patients, 39.2% were unable to differentiate between the more and the less salty solution. Moreover, 39.6% of patients preferred the solution they judged more salty. We conclude that the new low sodium lavage solution is not superior to the standard solution regarding patient acceptance, compliance, and cleansing quality. Thus, the reduction of salt concentration does not appear to be the appropriate approach to improve patients compliance with colonic cleansing solutions.


Effects of endoscopic injection sclerotherapy on portal hypertensive gastropathy: a prospective study. The effect of endoscopic injection sclerotherapy (EIS) for esophageal varices on portal hypertensive gastropathy (PHG) was investigated in 137 patients who underwent EIS from July 1987 to March 1990. Two groups, PHG(+) (N = 35) and PHG(-) (N = 102) were distinguished by endoscopic findings obtained before EIS. PHG was classified into four grades by endoscopy scored as 0, 1, 2, or 3. The PHG score significantly worsened after EIS (p < 0.01), and PHG became worse 6 to 9 months after the eradication of varices followed by gradual improvement. Recurrent small veins, which required additional EIS, appeared more frequently in the PHG(+) group (p < 0.05). New gastric varices appeared or gastric varices enlarged after EIS more frequently in the PHG(+) group (7 patients, 20.0%) than in the PHG(-) group (12 patients, 11.8%), but this was not statistically significant. Thus, frequent endoscopy after EIS is needed with special attention directed to development of PHG and gastric varices, especially for patients with PHG prior to treatment.


Endoscopic diagnosis of segmental colonic tuberculosis. We report colonoscopic findings in 29 proven cases of segmental colonic tuberculosis. The colonoscopic appearances of tuberculosis included: mucosal nodules and ulcers, stricture with nodules and ulcerations, and mucosal nodules with or without pseudopolypoid folds. In 12 (41%) of 29 patients colonoscopy biopsies enabled a histologic diagnosis to be made on the basis of typical granulomas. Culture of biopsy tissue on Lowenstein Jensen media isolated Mycobacterium tuberculosis in six (40%) of 15 patients. Combined histologic and bacteriologic evaluation established the diagnosis in 60% of patients. We conclude that even though target biopsy is an effective method of diagnosis, anti-tuberculous chemotherapy may be started on the basis of the endoscopic appearance if there is a high clinical suspicion of tuberculosis.


[Myelomeningocele--what can be done? Aids for evaluating rehabilitation from the orthopedic viewpoint]. Shortly before or shortly after the delivery of a child suffering from congenital paraplegia (myelomeningocele or spina bifida) the obstetrician is obliged to give advice as to what will follow after neurosurgical closure of the cele and shunting of the hydrocephalus. The parents' understanding of therapy and integration of the patient is developed to assess and utilise the future chances of the disabled child. Integration of children with congenital paraplegia is performed by an interdisciplinary team of therapists. However, the obstetrician's advice is of great value in preparing the parents for their decision for or against total care post partum. They must in fact be fully aware of the chances, that the disabled child actually has with regard to integration in life, and of what can be done in this respect. Besides the neurological, paediatric and urological care, it is the task of the orthopaedist to preserve or even to improve verticalization and mobility in paraplegic patients. In this manner he exercises an influence on the quality of life of the disabled children and on their social integration. Improvement and further development of physiological orthoses for walking enable even children suffering from a thoracic level of paralysis to walk independently and to achieve integration into society. Orthopaedic aspects of integration must be part of the information given to the parents by the obstetrician, so that they may be able to assess in what way their disabled children can participate in the future at various levels of everyday life.


[Follow-up of 551 patients with node-negative breast cancer]. To evaluate the prognostic significance of established clinical, histological, and biochemical factors, we examined the survival data of 551 node-negative breast cancer patients. At a median follow-up of 5 years, we found 114 recurrences, 79 of them at distant sites. 41 patients died. 84 patients with less than 8 examined lymph nodes, adjuvant systemic treatment, or treatment differing from standard procedures, had a statistically significant shorter overall survival and were excluded from further analysis. With regard to relapse-free and overall survival univariate and multivariate analyses of the remaining 467 patients revealed only few factors with prognostic significance. In multivariate analysis of overall survival by the Cox regression model, statistically significant prognostic value was limited to three factors: lymphangiosis carcinomatosa (relative risk 4.8, 95%-confidence interval 2.0-11.7), postmenopausal status (0.38, 0.17-0.84), and positive progesterone receptor status (0.37, 0.14-1.0). In addition, there was a trend (p = 0.075) of prolonged survival in patients with Bloom and Richardson grade I cancers. The few prognostic factors found were able to identify patients with very good, as well as very bad prognosis. However, for the majority of node-negative breast cancer patients, estimation of prognosis remains unsatisfactory. Therefore, further independent prognostic factors are necessary.


[Recurrence of vulvar cancer--treatment, experiences and results]. At the University Hospitals of Heidelberg (1970-1988) and Homburg/Saar (1988-1990), 182 patients with vulvar carcinoma were treated. 51 patients had a recurrence of vulvar carcinoma and 21 patients showed a persistence of this tumour. 19 women had a second recurrence of vulvar disease. In these cases, therapy ranged from local surgery to exenteration, depending on the site and tumour extension. 18 patients underwent successful reconstructive surgery. Prognosis was better in cases with local recurrence in comparison to distant sites of metastatic progression (i.e. inguinal nodes or disseminated disease) (p less than 0.001). The five-year survival (after diagnosis of recurrent disease) for patients with early onset of recurrence (less than 20 months after initial therapy) was 28% compared to 68% for patients with late onset of recurrent disease (p less than 0.01).


[Status of fractionated abrasion and vaginal endocervical cytology in diagnosis of endometrial cancer]. The predictive value of cervical cytology and uterine curettage in 150 endometrial carcinoma was investigated. Cytology proved negative in 56% of all carcinomas and in 42.2% of those in stage 2 or 3. Uterine curettage was found to have a false-negative rate of 6%, endocervical curettage of 5.3%. By contrast, we found a high false-positive rate of 70.8% for endocervical curettage. 13.2% of the 129 endometrial carcinoma stage 1 had a false-positive endocervical fraction. No residual disease was found in 4.7% of all 150 hysterectomy specimens. Negative cervical cytology seems to be a reasonably good predictor of actual cervical involvement, if a positive endocervical curettage is to be interpreted.


[The significance of prostaglandin F2 alpha (PGFM)--and plasma oxytocin level in patients with premature labor]. In the present study, plasma oxytocin and prostaglandin F2 alpha metabolite (PGFM) concentrations were measured in 46 patients admitted for preterm labour. Gestational age ranged from 20-34 weeks. Samples were collected 12 hours before and after initiation of tocolysis. Patients with a premature rupture of the membranes and/or intra-amniotic infection were excluded in this study. There was a significant difference in the oxytocin (p = 0.05) and PGFM levels (p = 0.007, after 12 hours: p = 0.004) between a control group without preterm labour and women with preterm labour. No differences were seen between the successfully treated (delivery more than 5 days after start of tocolysis) and the failure group. There was no significantly different increase or decrease in PGFM and Oxytocin plasma levels between treatment failures and successfully treated patients.


[Cytogenetics of unfertilized or uncleaved oocytes within the scope of in vitro fertilization. Relations to hormone content of follicular fluid]. Constituents of the follicular fluid (FF) have been suspected to influence fertilizability and cytogenetic constitution of human oocytes. Therefore, we analysed the FF concentrations of 17 beta-estradiol (E2), progesterone (P), testosterone (T), and prolactin (PRL) of 114 oocytes recovered for in vitro fertilisation (IVF). 46 of these oocytes were fertilised and transferred to the maternal uterus. Among the unfertilized gametes, 27 were not analysable. 30 were normal haploid, and 11 were classified as abnormal. There was no significant difference between fertilised and unfertilized oocytes for FF concentrations of E2, P, T, and PRL and for the E2/P ratios. Similarly, we detected no significant difference between normal and abnormal oocytes for these parameters.


[Steroid and protein hormone concentrations in serum and follicular fluid after stimulation for in vitro fertilization]. Sixty patients with tubal infertility were stimulated for IVF with a fixed schedule consisting of clomiphene and pure follicle stimulating hormone. They responded with an optimal estradiol increase and 2 to 4 embryos were transferred. Conception cycles (n = 17) could be differentiated from non-conception cycles (n = 43) by serum estradiol, serum progesterone, the serum progesterone/estradiol-ratio and serum LH concentrations. Testosterone, androstenedione and FSH in serum and follicular fluid showed no significant relation to a possible therapy outcome. We conclude from our findings, that, during the peri-implantation period, certain LH patterns followed by an optimal progesterone/estradiol-ratio in the serum support an embryo survival after transfer to the uterus.


[Spontaneous conception after laparoscopic coagulation of the ovarian surfaces in a patient with primary normogonadotropic hyperandrogenemic amenorrhea]. A patient with primary amenorrhoea was kept under hormonal replacement therapy and oral contraceptives since the age of sixteen. At the age of 30 she first consulted the endocrinologist because of infertility after one year of "post-pill-amenorrhoea". This first hormone check detected a severe hypertestosteronaemia (1.3 ng/ml). During four stimulation cycles using gonadotropins she showed a polyfollicular reaction and finally developed a hyperstimulation WHO II. During the following cycle she underwent hystero- and laparoscopy; laparoscopic electrocoagulation of the ovarian surface (LEOS) was carried out during this treatment. She subsequently conceived spontaneously twice.


[Infiltrating tubo-ovarian abscess in IUD-associated actinomycosis]. We report on a case of a 55-year old patient with a great adnexal tumour (10 x 5 x 8 cm), on the left side with infiltration of the bladder and the pelvis with recurring urinary retention in the kidney. Histological examination revealed an intrauterine device-associated actinomycosis. Following a 6-month high dose penicillin therapy, the abdominal hysterectomy with adnexectomy and partial resection of the bladder with new implantation of the ureter (Boari) was performed. The postoperative period was uneventful, the urogram normal.


[Struma ovarii maligna].

[Struma ovarii maligna]. Benign and malignant struma ovarii are very rare ovarian teratomas. Specific therapy guidelines should be established. A case of a malignant struma ovarii is presented and results of therapy discussed.


[Mastopathy in partial testicular feminization]. We report on a patient with synchrony of mastopathic alterations and incomplete testicular feminization. In the 54-year old patient, typical climacteric complaints as well as mastopathy-associated symptoms occurred. After orchiectomy and subsequent oestrogen substitution, clinical symptoms disappeared.


[Harmful substances and infertility. Substances of abuse]. Contaminants exercise an influence on different levels of reproduction, resulting in disturbances of the cycle, abortion and diverse complications during pregnancy among women, whereas, in the case of men, alterations of the spermiogram have been observed. Numerous unfavourable influences on reproduction are known from toxins such as alcohol, cigarettes and caffeine. By means of a survey of references and own results, these secondary effects are demonstrated in order to warn couples of the serious consequences with regard to the abuse of toxins, e.g. coffee, tobacco etc., when seeking advice in questions of infertility and pregnancy.


[Clinical and immune hematologic problems in prenatal prevention of Rhesus sensitization]. Various studies have provided impressive evidence of the efficacy of antenatally administered anti-D in the prevention of rhesus (D) alloimmunisation in rhesus-negative women. However, possible clinical and immunohaematological problems associated with this prophylactic therapy have received little attention. We describe perinatal and immunohaematological problems, which occurred in four cases after antenatal rhesus prophylaxis. Classical immunohaematological techniques were employed, to detect and specify irregular red cell antibodies. It was found, that the antenatal administration of anti-D could mask sensitization to other red cell antigens or the production of maternal immune anti-D antibodies later in pregnancy. A further problem encountered was that of neonates with a positive direct Coombs' test (the uncertainty in the individual case being, whether this is a result of the antenatal administration of anti-D) and marked hyperbilirubinaemia. Antenatal immunoprophylaxis for rhesus disease can give rise to immunohaematological and clinical findings, of which the interpretation is extremely difficult and requires intensive cooperation between the obstetrician, neonatologist, and haematologist/clinical biochemist.


[Three-dimensional ultrasound imaging of benign and malignant breast tumors--initial clinical experiences]. Previous experimental and clinical studies showed, that three-dimensional (3-D), i.e. dynamic spatial reconstruction of 2-D ultrasound images is feasible. A rotating acoustic plane helps to visualise the cross-sections serially and in a coordinated manner. When reconstructing the 2-D ultrasound images, surface reconstruction from planar contours of each cross-section is performed (so that the organ limits are defined) and the cross-sectional pictures are reconstructed into 3-D organ images. This approach had been described by the authors on a previous occasion. Another step forward is "transparent" spatial imaging eliminates the source of error involved in contouring. It is important to emphasise, that the 3-D system now described by the authors, yields a spatial image of the organ in question, and does not just present 3 planes of the organ (some authors have been claiming, that such an imaging method is also three-dimensional). Our system enables the imaging of several cross-sectional planes cut through the spatially calculated organ. This results in cross-sections, which cannot be performed by conventional sonography, thus disclosing new perspectives and possibilities. In the present article, the authors describe a clinical pilot study in the diagnosis of carcinomas of the breast. In our opinion, 3-D imaging of the tumours enables the physician to diagnose the status of the tumours; this is demonstrated by the examples of 35 malignant and benign tumours of the breast. In 95% of the cases of malignant tumours and 80% of the benign tumours, the diagnosis proved correct. This paper describes the fundamental possibilities and limitations of the new method.


[Prognostic significance of the CA 125 half-life for the further outcome of ovarian cancer]. Since only approx. 30% of patients with ovarian carcinoma present themselves in the early stages, and as a result of the lack of effective screening methods, primary interest has been applied to the improvement of the treatment quality in the later stages. Improvement of therapeutic strategies implies an adaptation of specific characteristics of the patient and the tumour. For instance, in cases of primary progression during chemotherapy, it is not justified to continue an aggressive treatment, which causes additional serious side effects. Surprisingly, it has not been possible, to utilize established or suspected prognostic factors for treatment strategies in ovarian cancer. This might result, in part, from the uncertainty of criteria such as stage of disease, residual tumour and histological grading. The single most relevant prognostic factor today is the residual tumour mass. In 1988 van der Burg suggested for the first time a potential prognostic relevance of the CA 125 half-life. This study was designed, to investigate the use of CA 125 half-life in therapeutic strategies. From January 1984 to June 1990, 346 patients with primary ovarian cancer were treated at our institution. Preoperative CA 125 levels were determined in 292 patients; in 220 patients the levels were complete for a period of more than 6 months so that the CA 125 half-life could be calculated. Survival times of patients with a half-life of less than 20 days were significantly (p less than 0.0001) different from patients with a half-life of more than 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)


[Primary, papillary serous carcinoma of the peritoneum; a report of experiences]. A total of fourteen patients with primary papillary serous carcinoma of the peritoneum (PPSCP) were treated at the Department of Obstetrics and Gynaecology of the University of Graz between 1980 and 1991. The presence of tumours from other sites, particularly the pancreas and the ovary, had been excluded. Due to extensive spreading of the disease mainly in the upper abdomen, only seven of the 14 patients underwent exploratory laparotomy. The median overall survival time was 10 months (range, 1-28 months). These results are due to the extent of spreading of the disease at diagnosis, and also to the fact, that optimal cytoreductive surgery was possible only in four of the 14 patients. The four patients with optimal cytoreduction showed a better survival than those, who underwent less radical surgery. These results seem to indicate, that, as in primary ovarian cancer, the amount of residual disease may be an important prognostic determining factor in PPSCP.


[Retrospective comparative study of the treatment of tubal pregnancy by pelviscopic surgery or prostaglandin injection]. The incidence of tubal pregnancy has been increasing in recent years. The improvement in diagnostic procedures leads to an early detection of tubal pregnancies. As a result, conservative treatment modalities are more feasible today. In this study, we compared the treatment of tubal pregnancy by means of locally applied prostaglandin with pelviscopic surgery. 75 patients with an early tubal pregnancy were included in each group. The comparison between the two groups showed, that prostaglandin treatment has a higher failure rate, than treatment by pelviscopic surgery. However, postoperative fertility indicated better results in the prostaglandin treated patients.


[Adolescent primiparous women, 17-years-old and younger]. Between January 1, 1983 and June 30, 1991, 107,420 primiparae were recorded in the Swiss Statistics, which cover approx. 60 hospitals. 573 primiparae were 17 years of age or less (= Group I). The control group consisted of 106,855 primiparae between 18 and 35 years of age (Group II). Comparison of these 2 groups showed the following results: A significantly higher risk in prematurity in Group I. There was no significant difference in perinatal mortality or in birth weight under 2,500 g. A significantly lower rate of caesarean sections and of surgical assisted vaginal deliveries were recorded in Group I.


[The effect of smoking on the resistance index of the umbilical artery and the middle cerebral artery]. 23 healthy smokers with uneventful singleton pregnancies underwent Doppler-flow measurements of the foetal umbilical artery and middle cerebral artery before and ten minutes after smoking one cigarette. In both arteries the resistance indices (RI) did not change significantly. Maternal mean arterial blood pressure and heart rate increased significantly after the smoking of the cigarette. Neither the group with an RI increase of greater than or equal to 5% in the foetal umbilical artery (n = 7) nor the group with an increase of the RI in the foetal umbilical artery and, at the same time, a decrease of the RI in the arteria cerebri media (n = 5), showed a significant difference concerning maternal haemodynamic parameters and the number of cigarettes smoked before and during pregnancy. The results suggest, that the smoking of one cigarette in uneventful pregnancy does not produce acute haemodynamic effects in the foetus.


[Fetal outcome of premature infants less than 1,500 g birth weight with special reference to surfactant requirements]. The objective of our study was to examine therapeutic success within a study group of 108 premature babies weighing less than 1500 g at birth. The foetal outcome was divided according to intrauterine betamethasone administration, method of birth and surfactant requirement. 59 of the babies did not require a surfactant factor, because within 12 hours it was possible, to reduce respiration to an O2 partial pressure of 20%. In 49 of the premature babies, this was not possible, and therefore, surfactant substitution was required, whereby this subject group was divided into surfactant responders and surfactant non-responders. In addition, we examined the influence of the method of birth on later survival and the occurrence of intraventricular haemorrhages in the children. A noticeably higher survival rate was determined in 81% of the children, born via Caesarean section, compared with 63% of premature babies, born via vaginal delivery. Likewise, detectable intraventricular haemorrhages (IVH) were significantly lower amongst premature babies delivered via Caesarean section (25%) than those delivered vaginally (37.5%). A considerable improvement in survival rates and a reduction in IVH was achieved by means of completed lung maturation with betamethasone (16 mg in 48 hours). 62% of premature infants with completed prepartal lung maturity did not require the administration of a surfactant due to the favourable respiratory situation. However, for those cases, where it was no longer possible to conduct lung maturation, only 46% did not require surfactant substitution. Therefore, it would appear advisable, to delay the delivery of premature babies weighing less than 1500 g in order to carry out lung maturity treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


[Spontaneous abortion after vaginal hemorrhage in intact early pregnancy--an etiologic analysis]. 283 patients with vaginal bleeding before a gestational age of 16 weeks and positive foetal heart action were followed up by mean of ultrasound examination until termination of pregnancy. 18 pregnancies (7.5%) ended in spontaneous abortion. 44.4% of these abortions showed histological parameters of an infection, and in 16.6%, a sub-chorionic haematoma was diagnosed. In one case only a chromosomal anomaly (triploidy), was found. In 25 percent of the abortions, there was no evidence of histological abnormality. Since it could be demonstrated, that a bacteriological infection a possible cause of live abortions before 16 weeks of pregnancy, it could be concluded, that it might be possible to reduce live abortions by bacteriological examinations of the cervix and vagina followed by specific antibiotic treatment. If vaginal bleeding stopped during follow-up, the pregnancy outcome was normal.


[Operation of acute dissecting aortic aneurysm in the 25th week of pregnancy using hypothermic extracorporeal circulation]. We report on a 24 + 2 weeks pregnant woman with Marfan's syndrome, who acutely developed a dissecting aortic aneurysm with aortic valve insufficiency. Emergency surgery was performed by using hypothermic extracorporeal circulation, whilst the aortic valve and ascending aorta were replaced by a synthetic graft. Foetal heart rates, continuously monitored by using Doppler ultrasound, were shown to be closely correlated with perfusion pressures. By applying perfusion pressures of 90-100 mmHg, we were able to maintain foetal heart rates of approximately 100/min. During the first postoperative day, the CTG was normal for gestational age and no contractions were noted. During the second postoperative night, the patient prematurely delivered a dead 820 g infant (Apgar score 0/0/0/0). In view of this case report, opportunities and problems associated with an application of extracorporeal circulation during pregnancy are discussed.


[Fatal course of peracute fatty liver of pregnancy]. A fatal case of acute fatty liver of pregnancy (AFLP) is reported. After admission, the patient was delivered within 3 hours. Routine laboratory investigation revealed acute liver insufficiency with advanced coagulopathy. Despite substitution therapy, the severe coagulation defect progressed to lethal intracerebral bleeding. Advanced AFLP can only be satisfactorily diagnosed in time, if non-specific symptoms or icterus lead to studies of blood chemistry, especially liver function tests, coagulation parameters (including platelet count, fibrinogen, AT III), blood glucose and renal function (including uric acid). This will enable an adequate management of the patient. The clinical problem of AFLP still remains that of early diagnosis.


[Deformed ear after chorionic villi biopsy. Is there a causal relationship?]. A case of a deformed ear following chorion villus sampling is described. The possibility of a relation between the described malformation and other malformations following chorion villus sampling is discussed.


Proteins with abortifacient, ribosome inactivating, immunomodulatory, antitumor and anti-AIDS activities from Cucurbitaceae plants. 1. The biochemical characteristics and biological activities of eight Cucurbitaceae plant proteins designated trichosanthin (isolated from tubers of Trichosanthes kirilowii), beta-trichosanthin (isolated from tubers of Trichosanthes cucumeroides), alpha- and beta-momorcharins (isolated from seeds of Momordica charantia), momorchochin (isolated from tubers of Momordica cochinchinensis), luffaculin (isolated from seeds of Luffa acutangula) and luffin-a and luffin-b (isolated from seeds of Luffa cylindrica), were reviewed. 2. The isolation procedures for all eight proteins are based on aqueous extraction, acetone fractionation and ion exchange chromatography. Ammonium sulfate precipitation and gel filtration are steps which may be included to improve purification. 3. The proteins are basic in nature and possess a molecular weight of approx. 30,000. All except trichosanthin are glycoproteins. The content of Asx and Glx residues is high. The N-terminal amino acid residue is Asp. Their amino acid compositions and N-terminal amino acid sequences are similar. 4. Circular dichroism spectroscopic studies revealed that trichosanthin, alpha- and beta-momorcharins possess similar secondary but different tertiary structures. 5. Most of the proteins are immunologically distinct. 6. The proteins exhibit abortifacient, antitumor, ribosome inactivating and immunomodulatory activities. Trichosanthin manifests anti-human immunodeficiency virus activity.


Contractile effect and tissue content of arginine vasopressin in the urinary bladder of Brattleboro rats with hereditary diabetes insipidus. 1. Urinary bladders from male rats of the Brattleboro strain with hereditary diabetes insipidus (DI) were analyzed for presence of immunoreactive arginine vasopressin (ir-AVP). Healthy rats were used as controls. 2. Bladders from the DI rats were heavier than controls. Concentration of ir-AVP was lower in DI bladders, but total amount of ir-AVP was similar to that in controls. 3. EC50 values for the AVP concentration-response relations were similar for control and DI bladder strips. Maximum response to AVP relative to response to K+ high solution was lower in the DI group. 4. An AVP receptor antagonist that significantly blocked response to exogenous AVP had no effect on response to field stimulation. 5. We suggest that AVP is synthetized locally and that AVP is not the non-adrenergic non-cholinergic transmitter responsible for the atropine resistant contraction in rat bladder.


Effects of aminophylline on contractions and 45Ca uptake in isolated rat vascular smooth muscle. 1. Aminophylline inhibited the contractions induced in rat isolated aorta by high K and noradrenaline (NA) as well as the transient contraction induced by NA in Ca-free media and suppressed the spontaneous myogenic activity in portal vein segments. 2. Aminophylline had no significant effects on 45Ca influx in resting aorta but inhibited 45Ca influx stimulated by high K or NA. 3. It is concluded that aminophylline inhibited Ca entry through voltage- and receptor-operated channels and NA-induced Ca release from intracellular stores. A part of the vascular inhibitory effects of aminophylline may be mediated by a cAMP-dependent mechanism.


Developmental changes in morphine and clonidine sensitivity of isolated chick oesophagus. 1. Electrically evoked contractions of isolated newly-hatched and over 6 week-old chicks cervical oesophagus (pre-crop) were inhibited by morphine and clonidine in a dose-dependent manner. 2. The inhibitory effects of morphine and clonidine were antagonized by naloxone (3 x 10(-6) M) and yohimbine (10(-7) M), respectively. 3. IC50 for morphine was 1.01 x 10(-7) M for newly-hatched and 5.19 x 10(-6) M for adult chicks. 4. IC50 for clonidine was 2.34 x 10(-9) M for newly-hatched and 1.19 x 10(-8) M for adult chicks. 5. These findings indicate a significant decrease in inhibitory effect of morphine and clonidine during developmental stages.


Pancreastatin and its 33-49 C-terminal fragment inhibit glucagon-stimulated insulin in vivo. 1. Pancreastatin, a 49 amino acid peptide derived from chromogranin A, has been shown to have an inhibitory effect on insulin secretion in the perfused pancreas and isolated islets. 2. We have studied the effect of pancreastatin on glucagon-stimulated insulin release and the hyperglycemic of glucagon effect in vivo. 3. When administered in the mesenteric vein, pancreastatin inhibited the increase in insulin levels induced by glucagon stimulation, thereby potentiating the hyperglycemic effect of glucagon. 4. This study describes a regulatory role of pancreastatin on glucagon-induced insulin release in vivo.


Cefaclor concentrations in human serum, gingiva, mandibular bone, and dental follicle following a single oral administration. 1. Cefaclor concentrations in human serum (n = 59), gingiva (n = 46), mandibular bone (n = 39), and dental follicle (n = 42) following a single oral administration of cefaclor (500 mg) were measured by the paper disk method. 2. The peak times of serum, gingiva, mandibular bone, and dental follicle were 1.5, 2, 2, and 1.5 hr, respectively. 3. The mean peak concentrations of serum, gingiva, mandibular bone, and dental follicle were 7.58 micrograms/ml, 3.71, 1.59 and 2.42 micrograms/g, respectively. 4. The concentration ratios of gingiva/serum, mandibular bone/serum, and dental follicle/serum at peak times of the tissues were 0.49, 0.18, and 0.32, respectively. 5. Mean cefaclor concentrations in gingiva, mandibular bone, and dental follicle at peak times exceeded MIC for 90% for clinically isolated strains of alpha-hemolytic Streptococci.


Effects of antiandrogens and progesterone on isolated rat uterus. 1. The effect of progesterone (P, 6 x 10(-6)-6 x 10(-5) M) and the antiandrogens cyproterone acetate (CPA, 10(-7)-10(-5) M), flutamide (F, 10(-6)-6 x 10(-5) M) and spironolactone (S, 10(-6)-6 x 10(-5) M) on the KCl-induced tonic contraction of the isolated rat uterus have been assayed. 2. The antiandrogens relaxed, in a dose-dependent way, the KCl-induced contraction (EC50, 2.804 +/- 0.506 x 10(-6); 1.671 +/- 0.308 x 10(-5); and 3.042 +/- 0.14 x 10(-5) M, respectively for CPA, S and F). P also relaxed the KCl-induced contraction (EC50, 2.436 +/- 0.524 x 10(-5) M). 3. CaCl2 (0.1-10 mM) counteracted the relaxing effect of CPA, S, F, and P, respectively, up to 100, 80.63, 60.66 and 90.57%. 4. The 17-OH-progesterone derivative CPA, but not S or F, reduces at small doses (6 x 10(-8) M), but not at higher concentrations (6 x 10(-7)-6 x 10(-6) M), the relaxing effect of progesterone.


Antimuscarinic activity of telenzepine on isolated human urinary bladder: no role for M1-muscarinic receptors. 1. The antimuscarinic activity of the selective M1-blocking drug, telenzepine, was investigated on the isolated human urinary bladder, contracted with exogenous muscarinic agonists and with field stimulation. 2. Telenzepine (3 x 10(-8)-10(-5) M) concentration-dependently shifted to the right the dose-response curves of bethanechol, acetylcholine and McN-A343, and partially depressed the electrically-evoked twitch responses. 3. pA2 values of telenzepine against bethanechol and McN-A343 were very close. 4. McN-A343 did not modify twitch responses elicited by field stimulation up to 10(-5) M. 5. The lack of muscarinic M1 receptors in human detrusor muscle is confirmed.


Porphyrinogenic properties of the anesthetic enflurane. 1. The effect of enflurane, a volatile anesthetic, on heme metabolism was studied. Different doses (0.5-6.0 ml/kg) of this anesthetic were administered i.p. to mice and animals sacrificed at different times after administration (5-240 min). 2. The dose of 2 ml/kg was chosen as the optimum anesthetic dose producing more alterations in the heme pathway. 3. ALA-S was significantly induced at earlier times of anesthesia. 4. Blood PBGase and deaminase was greatly reduced. 5. This diminution coupled with ALA-S induction are in accordance with the known biochemical changes occurring in acute intermittent porphyria and include enflurane in the list of porphyrinogenic drugs, the use of which is not recommended for the management of anesthesia in porphyric patients.


Differential effects of hypothermia upon blood acid-base state and blood gases in sodium pentobarbital and urethane anaesthetised rats. 1. The effects of two anaesthetics, sodium pentobarbital and urethane, and the effects of anaesthesia-associated hypothermia on acid-base status and blood gases were studied in rats without assisted ventilation. 2. Manipulation of conscious rats produces a progressive increase in arterial lactate associated with slight hyperventilation. 3. Sodium pentobarbital anaesthesia produces mild respiratory acidosis accompanied by increase in lactate arterial values. Urethane anaesthesia leads to partially compensated metabolic acidosis. 4. Hypothermia reduces metabolic acidosis and hypercapnia induced by sodium pentobarbital anaesthesia. No difference between hypothermic and normothermic values was observed in urethane anaesthesia.


Selected biological activities of novel selenonium choline analogs. 1. The novel choline analogs selenonium choline (SeCh) and acetylselenonium choline (ASeCh) have been examined for selected biological activities. 2. ASeCh was found to be an alternative substrate for acetylcholine esterase with Km and Vmax values similar to acetylcholine. 3. ASeCh and SeCh inhibited acetylthiocholine hydrolysis by acetylcholinesterase with IC50 values similar to acetylcholine and choline. 4. SeCh exerted a protective action against physostigmine and DFP induced toxicity. 5. SeCh (85 mg/kg) was found to be 3 times more toxic in mice than choline.


Estrogen binding sites in peripheral blood monocytes and effects of danazol on their sites in vitro. 1. This study was designed to investigate the presence of estrogen type I (high affinity, low capacity) and type II (low affinity, high capacity) binding sites in human peripheral blood monocytes and the effects of danazol on these sites. 2. These two types of estrogen binding sites existed in human peripheral blood monocytes. 3. Danazol bound to these sites in high concentration (10(-6) M, clinical serum concentration during danazol therapy) and decreased the number of both sites. 4. It is suggested that danazol has an anti-estrogenic action to the monocytes through the competition and suppression of estrogen binding sites as seen in the estrogen target organ.


Isolation of sesbanimide from the seed of Sesbania vesicaria. 1. The HPLC separation of a water-soluble toxic fraction isolated from the seed of Sesbania vesicaria provided a potent antileukemic compound which was identified as sesbanimide (or sesbanimide A). The identity was established by comparison of the proton magnetic resonance spectra of the isolated sesbanimide and the authentic sample. 2. The IC50 value determined by the activity against the growth of murine leukemia (L1210) cells in vitro was 0.8 ng/ml.


Biphasic effect of histamine on spontaneously beating rat atria. 1. Effect of histamine (HA) (10(-4)-10(-2) M) on spontaneously beating rat atrium was investigated. HA produced a biphasic effect which is composed of an initial negative chronotropy followed by a positive chronotropic phase, at each single dose. 2. At a submaximal dose of HA (3 x 10(-3) M) we have investigated the effects of some antagonists on the biphasic effect profile. 3. Propranolol (10(-7) M) depressed the secondary phase by abolishing the biphasic pattern of the effect of HA leading it to a monophasic one (negative chronotropy). 4. On the other hand, combination with atropine (10(-7) M) was shown to reduce the negative inotropic effect (in the secondary phase) which was produced by HA in the presence of propranolol. 5. The initial negative chronotropic phase was significantly enhanced by propranolol and reduced by pheniramine (10(-6) M). 6. Pheniramine also potentiated the positive chronotropy at the secondary phase of the response, but cimetidine (10(-4) M) has no significant effect on both phases. 7. Theophylline (10(-4) M) abolished the initial negative chronotropic phase, but did not influence the secondary phase. Dipyridamole (10(-5) M) did not affect the secondary phase of the response of HA, but increased the initial negative chronotropic effect.


Enhancement of gastric mucosal epidermal growth factor and platelet-derived growth factor receptor expression by sucralfate. 1. The effect of an anti-ulcer agent, sucralfate, on the expression of gastric mucosal epidermal growth factor (EGF) and platelet derived growth factor (PDGF) receptors was investigated. 2. Gastric mucosal cell membranes, isolated from the stomach of groups of rats, one receiving twice daily for 3 consecutive days a dose of 100 mg/kg sucralfate, and the other only the vehicle, were used as source for EGF and PDGF receptors. 3. Binding assays revealed the presence of both types of receptors, activation of which led to the elevation of tyrosine kinase activity as evidenced by a marked increase in membrane protein tyrosine phosphorylation patterns. 4. The specific receptor binding in the control group was 2.46 fmol/mg protein for EGF and 1.46 fmol/mg protein for PDGF, whereas the respective binding values in the sucralfate treated group increased by 61 and 65%. 5. The results suggest that sucralfate is capable of enhancement of epithelial proliferative activities through the stimulation of gastric mucosal EGF and PDGF receptors.


Effects of oxazolidines derived from (-) ephedrine in the rat. 1. Five oxazolidines were synthesized by reaction of (-) ephedrine with aliphatic aldehydes. The aldehydes used were formaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde and trimethylacetaldehye. 2. These five oxazolidines were tested in rats for ephedrine-like pharmacological activity using the hyperthermia and anorexia models. 3. All five oxazolidines caused significant elevation of body temperature in the hyperthermia model. The oxazolidine synthesized from (-) ephedrine and butyraldehyde caused greatest hyperthermia. 4. Four oxazolidines caused significant anorectic responses. The oxazolidine synthesized from (-) ephedrine and isobutyraldehyde caused greatest anorexia. 5. A possible tolerance to the anorectic effects of some of the compounds was observed.


Calcium ion itself inhibits Ca-free contraction of various smooth muscles in response to adrenergic and cholinergic stimulations and to TPA in the absence of Ca channel blocker and EGTA. 1. Smooth muscles such as thoracic aorta, stomach and vas deferens contract tonically in the absence of Ca ion (Ca) in response to various agonists such as norepinephrine, carbachol and TPA. 2. Addition of Ca alone to the Ca-free medium relaxes the muscle that has been contracting in response to the agonist in the Ca-free medium. 3. Ca itself has an inhibitory action on the contraction. 4. Acidification of the medium relaxes the muscle as Ca does, but weakly.


Dexamethasone modifies morphine-, atropine-, verapamil-induced constipation in mice. 1. The effect of dexamethasone in gastrointestinal constipation induced by morphine, verapamil and atropine in mice has been studied. 2. These drugs caused a dose-related inhibition of charcoal meal transit, which was reversed by dexamethasone. 3. Dexamethasone resulted more active in reversing morphine and atropine constipation, than in modifying verapamil effect. 4. The authors concluded that the interaction of dexamethasone on its receptor could release a larger amount of acetylcholine resulting in a reversion of atropine- or morphine-induced constipation. 5. The minor effect of dexamethasone on verapamil-induced constipation suggest a reduced involvement of calcium influx. 6. The above results suggest a role for steroid in gastrointestinal transit and propose a possible mechanism through which dexamethasone could reverse morphine- and atropine-induced constipation.


One- and two-electron reduction of menadione in guinea-pig and rat cardiac tissue. 1. In both guinea-pig and rat heart, mitochondrial NADH-ubiquinone-reductase and soluble DT-diaphorase accounted for 49-50% and 48-50% of menadione metabolism, respectively. Microsomal NADPH-cytochrome P450-reductase was responsible for less than 1% of menadione reduction. 2. Menadione was a high-affinity substrate for all reductases (Km values from 1 to 10 microM). 3. Marked amounts of O2-. (superoxide anion) were generated as a consequence of cardiac metabolism of menadione. 4. Menadione-induced O2-. generation was about 3-fold higher in guinea-pig than in rat heart. 5. All results were compared with data obtained on guinea-pig and rat liver.


Effect of lithium on gastro-intestinal complications in alloxan-diabetic rats. 1. Decreased beta-adrenergic and serotonergic responses have been reported in gastro-intestinal tract of experimentally diabetic rats. Effects of lithium on the decreased beta-adrenergic and serotonergic responsiveness of the gastro-intestinal tract due to diabetes were investigated using gastric fundus strips and proximal duodenum from alloxan diabetic rats. 2. A 6-day treatment with lithium chloride (2 mEq/kg i.p. in saline) normalized the decreased gastro-intestinal responses of the alloxan-diabetic rats, whereas the lithium treatment did not affect the elevated blood glucose levels due to experimental diabetes. 3. Furthermore, the lithium treatments of control and alloxan-diabetic rats did not alter the relaxing effect of manganese chloride on the isolated duodenum. 4. These results strongly suggest that the improving effect of lithium is not related to adenylate cyclase activation and may be as a consequence of its direct action on the diabetic gastro-intestinal smooth muscles.


Vasomotor responses in the isolated perfused external and internal carotid vascular beds of the rat. 1. The external (ECB) or the internal (ICB) carotid vascular beds of the rat were isolated and perfused with Krebs-Henseleit solution at constant flow (1 ml/min). Changes in perfusion pressure (PP) were recorded after cervical sympathetic stimulation and after the administration of norepinephrine (NE) and serotonin (5-HT). 2. Sympathetic stimulation induced an increase in PP (vasoconstriction) in both vascular beds, however, this effect was significantly higher in the ECB than in the ICB. 3. Exogenous NE also induced a significantly higher contractile response in the ECB. 4. Prazosin (10(-8) M) significantly inhibited the response to sympathetic stimulation and to NE both in the ECB and in the ICB, but yohimbine (10(-7) M) had no effect, suggesting that the vasoconstriction was mainly due to the activation of alpha 1-adrenoceptors. 5. 5-HT induced a contractile response both in the ECB and the ICB. In contrast with the response to NE, the contraction induced by 5-HT in the ICB was significantly higher than in the ECB. 6. Ketanserine (10(-8) M) antagonised both responses, indicating the involvement of 5-HT2 receptors. 7. The contractile effect of 5-HT in the ECB was significantly enhanced by a subthreshold sympathetic stimulation that did not modify the PP by itself. This effect was not seen in the ICB. 8. The differential perfusions of the ECB or the ICB demonstrated a different reactivity of ECB and ICB, both to sympathetic stimulation and to the administration of exogenous NE or 5-HT. 9. Furthermore, the response to 5-HT in the ECB was modulated by a subthreshold sympathetic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of methyl methacrylate on isolated atria and interaction with isoproterenol, atropine and calcium chloride. 1. Spontaneous rate and contractile force of isolated rat and rabbit atria suspended in a tissue bath were recorded before and after drugs. Methyl methacrylate monomer (MMA) alone both decreased force and increased rate dose-dependently. 2. Concentrations of calcium chloride or isoproterenol that alone increased both rate and force of rat atrial contraction were fully and only partially able, respectively, to restore force to normal after MMA. 3. Atropine prevented changes in rat atrial function from low-effective doses of MMA, but not higher ones; it also failed to prevent the reduction of contractile force by a calcium channel blocker, verapamil. 4. There are similarities but also differences between actions of MMA and verapamil on rat atria.


Footshock stress-induced supersensitivity to isoprenaline in the isolated pacemaker of the rat: effects of the compounds RU-38486 and RU-28362. 1. Three daily sessions of inescapable footshock stress of 30 min duration each increased the sensitivity of the isolated pacemaker of the rat to the chronotropic effect of isoprenaline. 2. The effect of inescapable footshock stress on the sensitivity of the isolated rat pacemaker to the chronotropic effect of isoprenaline was prevented by the daily administration of the compound RU-38486, a potent antiglucocorticoid which blocks the cytosolic receptor for corticosterone. 3. The administration of the compound RU-28362, a potent agonist of the cytosolic receptor for corticosterone, during 3 days to rats which were not submitted to footshock stress induces supersensitivity to the chronotropic effect of isoprenaline. 4. It is concluded that corticosterone plays an important role in the qualitative control of the rat pacemaker beta-adrenoceptor population during adaptation to repeated footshock stress.


The effects of daily injections of L-dihydroxyphenylalanine and 5-hydroxytryptophan in different temporal relationships on thyroid-gonadal interaction in an Indian finch, spotted munia, Lonchura punctulata. Daily injection of L-dihydroxyphenylalanine (L-DOPA, a dopamine precursor) given 12 hr after 5-hydroxytryptophan (5-HTP, a serotonin precursor) stimulated testicular growth and body weight increase in the spotted munia Lonchura punctulata. Daily injections of the same drugs given 8 hr apart had the opposite effect, inhibiting both testicular growth and body weight gain. These responses were not observed when either of the drugs were given alone, indicating that the effect was due to temporal synergism between serotonergic and dopaminergic functions. The inhibitory effect of daily injections of thyroxine on testicular and body growth were negated by injections of 5-HTP and L-DOPA separated by 12 hr. Conversely, the stimulatory effects of thyroidectomy in maintaining full testicular size and body weight after the breeding seasons were negated by daily injections of 5-HTP and L-DOPA separated by 8 hr. It is concluded that the inverse relationship between seasonal changes in thyroidal and reproductive functions may involve seasonal changes in phase relationships between daily rhythm in serotonergic and dopaminergic activity in the central nervous system.


Effects of fasting, medium glucose, and amino acid concentrations on prolactin and growth hormone release, in vitro, from the pituitary of the tilapia Oreochromis mossambicus. Previous investigations have shown that the release of PRL and GH from the tilapia pituitary is directly sensitive to osmotic pressure and a variety of endocrine and neuroendocrine factors. The present studies were aimed at determining whether the spontaneous release of PRL and GH, in vitro, is: (1) sensitive to the nutritional status of the fish, and (2) responsive to variations in the D-glucose and total amino acid content of the incubation medium. In the first series of experiments, male fish (50 to 60 g) were divided into two groups. One group was fed twice daily for 2 weeks while the second received no food. A nearly homogeneous mass of PRL-secreting cells was dissected from the rostral pars distalis (RPD) and incubated for 18 to 20 hr in either hyposmotic (300 mOsmolal) or hyperosmotic (355 mOsmolal) medium. Similarly, a mass of GH-secreting cells was dissected from the proximal pars distalis (PPD) and incubated for 18 to 20 hr in isosmotic (320 mOsmolal) medium. Fasting was found to alter the total amount of PRL and GH in the culture well (tissue + medium) at the end of the incubations, decreasing PRL and increasing GH. Fasting was also found to both reduce spontaneous PRL release in vitro and suppress its stimulation by reduced osmotic pressure (P less than 0.01). By contrast, fasting resulted in a substantial increase in spontaneous GH release from the PPD in vitro (P less than 0.01). In the second series of experiments, GH release was found to increase as the D-glucose concentration of the medium decreased (P less than 0.01), while prolactin release was unresponsive.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro induction of vitellogenin synthesis in Rana esculenta: role of the pituitary. Vitellogenin (VTG), a complex protein, is a precursor of yolk protein (lipovitellin and phosvitin) in all oviparous vertebrates studied to date. In amphibians, as in other oviparous vertebrates, VTG synthesis is hormonally dependent; estradiol-17 beta (E2) is especially important, although in vivo in the frog Rana esculenta the pituitary may be involved in hepatic VTG synthesis and secretion. The present in vitro experiments carried out during the main phases of the annual reproductive cycle of this frog showed that homologous pituitary homogenate (HPH), as well as E2, stimulated VTG synthesis in male and female livers, although their patterns of VTG secretion showed some differences with respect to the induction time and the rate of VTG secretion. The hepatic response to HPH occurred after a longer time than that of E2 VTG induction, and no cooperation between HPH and E2 was found in the VTG synthesizing response. It should be emphasized that during the refractory period (July), hepatic VTG synthesis in males and females could only be induced by HPH. These data demonstrate, for the first time, a direct action of HPH on VTG synthesis in male and female frog livers in all the periods tested; hepatic responsiveness to HPH and E2 varies with season and sex.


Steroid metabolism by ovarian follicles and extrafollicular tissue of the guppy (Poecilia reticulata) during oocyte growth and gestation. In the viviparous guppy, fertilization and gestation are intrafollicular. Fully developed embryos are ovulated at the end of gestation just prior to parturition. The metabolism in vitro of various radiolabeled steroid precursors by isolated ovarian follicles at various stages of the reproductive cycle and extrafollicular (EF) tissue of the guppy was investigated. While estradiol-17 beta was one of the end products of metabolism in vitellogenic follicles, 17 alpha, 20 beta-P and several 5-reduced metabolites were synthesized by postvitellogenic follicles. The yield of 17 alpha, 20 beta-P, however, was much lower than some 5 beta-reduced metabolites synthesized by postvitellogenic follicles. Gestation stage follicles rapidly converted the precursors into 5-reduced and polar 7-hydroxylated steroids, and their glucuronides. Although postpartum follicles showed very poor potential for steroid metabolism, they synthesized estradiol-17 beta from testosterone. These results demonstrate distinct changes occurring in the steroidogenic potential of the follicles during the reproductive cycle. Unlike in other viviparous vertebrates, no particular steroid seems to be involved in maintaining gestation in the guppy; all the steroid precursors are converted into highly polar metabolites and their conjugates during gestation, thereby facilitating their excretion. The EF ovarian tissue also synthesized 7-hydroxylated steroids and their glucuronides, providing evidence for the first time that the teleost ovarian EF tissue plays a role in steroidogenesis. The possible physiological significance of the synthesis of the novel polar steroids by the follicles and the EF tissue is discussed.


Stimulation of coho salmon growth by insulin-like growth factor I. The effect of insulin-like growth factor I on growth rate of coho salmon (Oncorhynchus kisutch) was examined. Juvenile coho salmon received implants of osmotic minipumps containing recombinant bovine insulin-like growth factor I (rbIGF-I) or saline for a period of 3 to 4 weeks. High doses of rbIGF-I (greater than 0.13 microgram.g-1.d-1) resulted in hypoglycemia and death. In 2-year-old coho salmon, 0.09 microgram.g-1.d-1 rbIGF-I administered for 25 days doubled linear growth rate and increased growth rate in weight by 40%. In rapidly growing, 1-year-old coho salmon, growth rate was not altered by rbIGF-I at 0.01 or 0.05 micrograms.g-1.d-1 for 31 days. In ration-limited fish exhibiting slow growth in the control group, rbIGF-I (0.02 microgram.g-1.d-1) increased linear growth rate by up to threefold and growth rate in weight by up to fourfold. The results indicate that exogenous treatment with mammalian IGF-I can stimulate coho salmon growth under some conditions, and that endogenous IGF-I may be an important factor in regulating growth of teleosts.


Neuropeptide Y-like immunoreactivity in the dogfish gastroenteropancreatic tract: light and electron microscopical study. The 36 amino acid neuropeptide Y (NPY) has been examined in mammals and is mainly located in the nerves. Its distribution in nonmammalian vertebrate and in some invertebrate nervous systems has been confirmed. Using antisera raised to porcine NPY, NPY immunoreactivity has been localized in endocrine cells of the pancreas and gastrointestinal tract of two dogfish, Scyliorhinus stellaris and Scyliorhinus canicula. Immunostained serial sections and cross-absorption experiments with related peptides, including avian and bovine pancreatic polypeptide and peptide tyrosine tyrosine, excluded any cross-reactivity. The fine structure of the cells containing NPY-like substance is described.