A piece of my mind: familial hepatitis.
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Family↗
Biomedical subjects
T V Nowak
Publications and source records attributed to T V Nowak.
Evolution of acute cytomegalovirus gastritis to chronic gastrointestinal dysmotility in a nonimmunocompromised adult.
A 30-year-old nonimmunocompromised woman developed chronic gastrointestinal dysmotility as a consequence of acute cytomegalovirus infection. The acute nature of the infection was documented by high immunoglobulin M antibody titer to cytomegalovirus (CMV); the chronicity of the infection was shown by persistence of CMV in biopsy specimens of her gastrointestinal tract over a 21/2-year period. Gastrointestinal dysmotility was confirmed by delayed emptying on gastric nuclear scintigraphy, by retrograde propagation of migrating myoelectric complexes on small intestinal manometry, and by presence of tachygastria on cutaneous electrogastrography. The patient's nausea, vomiting, abdominal pain, and early satiety resolved after a short course of treatment with leuprolide acetate but returned after medication was discontinued. Her symptoms persisted despite clearance of CMV from the gastrointestinal tract after a course of treatment with ganciclovir. These observations show that acute CMV infection can cause gastrointestinal dysmotility in nonimmunocompromised individuals and that the disturbance in gastrointestinal motor function may persist for years after viral infection of the gastrointestinal tract has been eradicated.
Acute Disease↗
5-year incidence of adenomas after negative colonoscopy in asymptomatic average-risk persons [see comment].
BACKGROUND & AIMS: Cost-effectiveness of colorectal cancer screening will be maximized by selecting the widest screening intervals that effectively prevent cancer mortality. However, data on the incidence of neoplasia in persons with no abnormal findings on initial examination are limited. The aim of this study was to describe the incidence of colonic neoplasia 5 years after negative screening colonoscopy in asymptomatic average-risk persons. METHODS: We previously reported the results of screening colonoscopy in 496 asymptomatic average-risk persons, 368 of whom had no neoplasia identified. Colonoscopy to the cecum was performed in 154 of these persons at a mean of 66 months after the initial negative colonoscopy. RESULTS: Forty-one (27%) had at least one adenoma, but only 1 person had an adenoma > or = 1 cm and none had cancer, severe dysplasia, or villous or tubulovillous histology. Hyperplastic polyps at the initial examination did not predict incident adenomas. Regular nonsteroidal anti-inflammatory drug use was associated with a decreased rate of incident adenomas. CONCLUSIONS: In average-risk persons, the interval between screening examinations can be safely expanded beyond 5 years, provided the initial examination is a carefully performed complete colonoscopy that is negative for colonic adenomas or cancer.
Adenoma↗
Management of upper gastrointestinal tract dysfunction.
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Deglutition↗
Effect of streptozotocin-induced diabetes mellitus on release of vasoactive intestinal polypeptide from rodent small intestine.
Representative longitudinal muscle strips (6 x 10 mm) from proximal and distal small intestine were excised from control and streptozotocin-treated rats after one month of untreated and insulin-treated diabetes. Untreated diabetes significantly reduced tissue concentrations of vasoactive intestinal polypeptide (VIP) at both intestinal loci. Insulin treatment of the diabetic animals restored tissue VIP concentrations to control group levels, although the beneficial effect of insulin treatment was only significant in the duodenum. Spontaneous release of VIP was significantly attenuated by untreated diabetes at both intestinal sites. In the duodenum, insulin treatment of the diabetic animals restored VIP release to levels indistinguishable from control group values. In the ileum, insulin treatment produced levels of VIP release that were not significantly different from those of the control and untreated diabetic groups. Tetrodotoxin (5 x 10(-6) M) significantly--but incompletely--inhibited VIP release from control group animals at both intestinal sites. These observations indicate that diabetes mellitus significantly diminishes VIP tissue concentrations and release from intestinal myenteric nerves. These abnormalities improve with insulin treatment. However, the mechanisms of VIP release from proximal and distal intestine appear to differ not only in their response to the diabetic state, but also in their response to insulin treatment.
Animals↗
Highly variable gastric emptying in patients with insulin dependent diabetes mellitus.
Some diabetic patients--particularly those with nausea and vomiting--frequently have evidence of delayed gastric emptying while other diabetic patients may in fact exhibit accelerated gastric emptying. Whether the presence or absence of symptoms of upper gastrointestinal dysfunction correlated with objective measures of gastric emptying in insulin dependent diabetic subjects was investigated. Twenty one insulin dependent diabetic patients underwent a solid phase gastric emptying scintiscan using in vivo labelled chicken liver. Thirteen patients had symptoms suggestive of gastrointestinal dysfunction (nausea, vomiting, early satiety, or constipation), while eight patients had no gastrointestinal symptoms. Eleven patients had orthostatic hypotension. All patients had been diabetic since childhood or adolescence. As a group, the diabetic patients showed a half time (T50) of gastric emptying (mean (SD) 150.0 min (163.7) that was not significantly different from that of 12 healthy control subjects (148.1 min (62.4)). Those diabetic patients without gastrointestinal symptoms and without orthostatic hypotension, however, showed a gastric emptying half time (70.1 min (41.6)) that was significantly faster than that of the control subjects. Conversely, those diabetic patients with nausea, vomiting, and early satiety (or early satiety alone) showed T50 values that were significantly greater than those of the diabetic patients without these symptoms. No correlation was found between the T50 value and the duration of diabetes, the fasting blood glucose at the time of study, or the respiratory variation in heart rate (E:I ratio). These observations indicate that highly variable rates of gastric emptying occur in insulin dependent diabetic patients, and that accelerated gastric emptying may occur in diabetic patients who have no symptoms of gastrointestinal dysfunction.
Adult↗
Impaired rodent vagal nerve sodium-potassium-ATPase activity in streptozotocin diabetes.
Experimental diabetes in rodents is associated with diminished activity of sodium-potassium-adenosine triphosphatase (Na+ -K+ -ATPase) in the sciatic nerve, an abnormality that has been invoked as being factorial in the genesis of diabetic peripheral neuropathy. Whether a parallel metabolic abnormality occurs in the autonomic vagus nerve is unknown. To answer this question, adult male rats made diabetic with streptozotocin (45 mg/kg) and age-matched nondiabetic controls were killed at 1 and 3 months after induction of diabetes. The cervical vagi and sciatic nerves were excised, weighed, and homogenized, and Na+ -K+ -ATPase activities were determined. After 1 month, the diabetic animals showed a significantly reduced sciatic nerve Na+ -K+ -ATPase activity as compared with respective controls, whether expressed in micromoles per gram wet weight per hour (20.5 +/- 4.9 [mean +/- SEM] vs 61.6 +/- 13.0) or micromoles per milligram of protein per hour (0.77 +/- 0.21 vs 2.48 +/- 0.57, p < 0.05, diabetic vs control, respectively). Diabetic vagus nerve Na+ -K+ -ATPase activity was also diminished (40.6 +/- 6.9 mumol/gm wet weight per hour vs 63.2 +/- 9.7 mumol/gm wet weight per hour and 3.83 +/- 0.81 mumol/mg protein per hour vs 5.86 +/- 0.73 mumol/mg protein per hour), but the results did not reach statistical significance. After 3 months, diabetic sciatic nerve Na+ -K+ -ATPase activity was still significantly less than the control group value (16.89 +/- 3.91 mumol/mg wet weight per hour vs 38.9 +/- 4.24 mumol/gm wet weight per hour and 0.48 +/- 0.11 mumol/mg protein per hour vs 1.04 +/- 0.14 mumol/mg protein per hour; p < 0.05, diabetic vs control, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Diabetic gastroparesis. What to do when gastric emptying is delayed.
Diagnostic evidence or symptoms of gastroparesis develop in about 20% to 30% of patients with long-standing diabetes. Diabetic gastroparesis is likely caused by autonomic neuropathy involving the nerves that regulate gastric motor function. The following are necessary for diagnosis: thorough history taking and physical examination to eliminate factors that might further delay gastric emptying; esophagogastroduodenoscopy or barium contrast studies to exclude structural abnormalities; and a radionuclide gastric emptying study. The three main agents available for therapy in the United States are metoclopramide (Maxolon, Octamide, Reglan), erythromycin, and cisapride (Propulsid). All have been shown to offer benefit in improving gastric emptying and symptoms, although use of metoclopramide is limited by a significant incidence of side effects. Surgical intervention should be avoided if possible.
Diabetic Neuropathies↗
Accelerated gastric emptying in diabetic rodents: effect of insulin treatment and pancreas transplantation.
Gastric emptying of a suspended solid, digestible meal was examined after 30 to 90 days of diabetes in two strains of streptozotocin-treated rodents and in genetically diabetic BB/Wor rats. After a 14-hour overnight fast the animals were gavage-fed 1.0 gm of rat food suspended in water and were killed 30 minutes later. Ligatures were placed around the lower esophageal sphincter and the pylorus and the stomachs were removed intact. The stomachs were evacuated and the gastric contents and gastric remnant were separately dried and weighted. Both the streptozotocin-treated and BB/Wor rats showed significantly accelerated (1.5- to 2.2-fold) rates of gastric emptying of the meal compared with respective nondiabetic control animals. Streptozotocin-treated diabetic animals that received daily insulin supplementation or those that had undergone pancreas transplantation shortly after induction of diabetes showed a similar reduction in blood glucose levels and normal rates of gastric emptying. Diabetes had a significant but variable effect on gastric mass and body weight. This response was dependent on the strain of animal examined, whether or not insulin supplementation was administered, or whether the animal underwent pancreas transplantation. These observations indicate that early diabetes in rodents has a prokinetic effect on gastric emptying of a suspended solid digestible meal. Restoration of euglycemia by insulin treatment or pancreas transplantation is associated with return of the gastric emptying rate to normal. These changes in gastric emptying appear to be independent of the effects of diabetes on gastric mass.
Animals↗
Untreated diabetes mellitus promotes intestinal microbial overgrowth.
Gastrointestinal dysfunction is a common secondary complication of insulin-dependent diabetes mellitus, yet its etiology is unclear. Enteric microbial overgrowth may play a role. To quantitate the changes in mucosal-adherent enteric microbial populations in untreated diabetes mellitus and to assess the impact of two forms of insulin replacement therapy upon enteric microbial populations, age-matched male Lewis rats were rendered diabetic by the administration of intravenous streptozotocin (55 mg/kg). After diabetes was confirmed (blood glucose level greater than 250 mg/dL), rats were divided into three groups: no treatment (no insulin), treatment with daily insulin to maintain normoglycemia (3 to 7 units of protamine zinc insulin subcutaneously), or transplantation with a vascularized heterotopic duct-ligated pancreatic isograft. After 1 month, rats were killed, and segments of the proximal, middle, and distal small bowel were obtained. Mucosal samples were rinsed in phosphate-buffered saline to remove nonadherent bacteria prior to aerobic and anaerobic culturing. Microbial recovery was expressed as the log10 colony-forming unit/mg tissue wet weight. Untreated diabetes resulted in an overgrowth of mucosal-associated small bowel aerobic and anaerobic microbial populations compared with populations in normal nondiabetic age-matched control rats. Insulin treatment and pancreatic transplantation prevented microbial overgrowth in the diabetic small intestine. Pancreatic transplantation resulted in strict normoglycemia equivalent to that in nondiabetic control rats, whereas insulin treatment resulted in slightly higher blood glucose levels at sacrifice and wide fluctuations in blood glucose levels compared with nondiabetic control rats. These data suggest that sustained normalization of glucose levels is not required to prevent microbial overgrowth in diabetic rats.
Animals↗
Structural and functional characteristics of muscle from diabetic rodent small intestine.
After 30 days of streptozotocin-induced diabetes, the small intestine from untreated diabetic, insulin-treated diabetic, and nondiabetic rodents was excised in toto and measured. Despite a net loss in body weight, the diabetic animals showed a near twofold increase in small intestinal weight. This was characterized by a 148% increase in mucosal mass as well as a 39% increase in intestinal smooth muscle mass (P less than 0.05, respectively). The diabetic intestine was significantly longer and had a greater diameter and surface area. Diabetes significantly increased mucosal mass per unit surface area but produced an insignificant decrease in smooth muscle mass per unit surface area. Insulin treatment of the diabetic animals prevented the increase in total mucosal mass and mucosal mass per unit surface area. Insulin treatment also prevented the increase in smooth muscle mass, but reduced smooth muscle mass per unit surface area to a level significantly less than that found in nondiabetic intestine. In vitro dose-response studies of circular and longitudinal small intestinal muscle from the diabetic animals showed normal tension development and sensitivity to both bethanechol chloride and physostigmine. These observations show that the diabetic state produces alterations in not only mucosal but also smooth muscle mass in the small intestine. However, despite these morphological changes, diabetic intestinal smooth muscle retains its sensitivity to cholinergic stimulation and its capacity for tension generation.
Animals↗
Adaptation of cholinergic enteric neuromuscular transmission in diabetic rat small intestine.
Representative longitudinal muscle strips (6 x 10 mm) from distal small intestine were obtained from rats after 1, 2, and 3 mo of streptozocin-induced diabetes. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (1-ms pulse duration, 30-270 mA, 10 Hz) in the presence of Krebs solution and Krebs solution plus 10(-6) M atropine. Field stimulation produced atropine-sensitive and atropine-resistant contractions in all strips. After 1 mo, significant differences in the amplitudes of the atropine-sensitive contractions were found between the diabetic rats and nondiabetic controls. Insulin-treated diabetic rats showed contraction responses that were intermediate in amplitude. After 2 mo, the difference between the control and diabetic groups was less evident but still significant. After 3 mo, the previously noted difference in the atropine-sensitive contractions between the diabetic and control groups had resolved. No significant differences among the three groups were noted in the amplitudes of the atropine-resistant contractions. Field stimulation delivered at pulse durations of 50 ms in the presence of neural blockade with tetrodotoxin (5 x 10(-6) M) produced similar contraction amplitudes among the three groups at any respective time phase of the study. Dose-response studies of intestinal muscle after 3 mo of untreated diabetes showed normal tension development to both bethanechol chloride and physostigmine. These results indicate that streptozocin-induced diabetes is acutely associated with defective cholinergic neuromuscular transmission in the myenteric plexus of the distal small intestine. The abnormality is less evident after 2 mo of untreated diabetes and resolves spontaneously after 3 mo. Insulin treatment appears to accelerate this resolution.
Animals↗
Age-related changes in enteric neuromuscular transmission.
Proximal and distal rat small intestine from 4-, 5- and 6-month-old rats were cut into strips measuring 6.0 X 10.0 mm. Longitudinal strips were cut along the oral-caudal axis of the intestine while circular strips were cut 90 degrees to that axis. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (0.1-1.0 msec pulse duration, 30-270 mA, 1-26 Hz) in the presence of Krebs' solution and Krebs' solution plus 10(-6) M atropine. Field stimulation produced atropine-sensitive and atropine-resistant contractions in these tissues. Significant differences among the three groups were found in the amplitudes of atropine-sensitive contractions in strips from proximal longitudinal muscle. The 6-month-old animals showed the highest amplitude contractions and the 4-month-old the lowest, whereas the 5-month-old animals showed contractions that were intermediate in amplitude. No significant differences were noted among the atropine-resistant contractions. Field stimulation delivered at pulse durations of 5.0 and 50.0 msec in the presence of neural blockade with tetrodotoxin (5 X 10(-6) M) produced similar contraction amplitudes among the three groups. These results show that tension development produced by field stimulation of the proximal intestine increases significantly with age. The increases appear to be due to age-related differences in cholinergic neuromuscular transmission.
Aging↗
Evidence for muscarinic inhibitory neurotransmission in rodent small intestine.
The influence of cholinergic and noncholinergic inhibitory nerves was examined in circular and longitudinal muscle from the duodenum. Rodent proximal small intestine was cut into strips measuring 6.0 x 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, whereas those cut 90 degrees to that axis were called circular strips. The strips were stretched to their optimal lengths and subjected to electrical field stimulation in the presence of various concentrations of atropine, pirenzepine or McN-A-343-11. All three drugs inhibited field-stimulated contraction responses and produced or augmented relaxation responses in both muscle layers. All relaxation responses were abolished by tetrodotoxin, indicating they were due to excitation of inhibitory nerves. For each response examined atropine was significantly more potent than pirenzepine (relative potency ratio, 13.36-95.74). The inhibitory effect of McN-A-343-11 on longitudinal muscle was antagonized by both atropine and pirenzepine, indicating the recruitment of cholinergic inhibitory nerves. Neither atropine nor pirenzepine had any effects on inhibitory responses produced by McN-A-343-11 in circular muscle, indicating the recruitment of noncholinergic inhibitory nerves. McN-A-343-11 also increased spontaneous contraction amplitudes in both muscle layers by a direct (tetrodotoxin-resistant) effect on smooth muscle. This effect was also antagonized by atropine and pirenzepine. Thus, both cholinergic and noncholinergic nerves participate in inhibitory neuromuscular transmission in the small intestine. Circular muscle is dominated by a noncholinergic inhibitory innervation. Longitudinal muscle appears to be controlled by both cholinergic and noncholinergic inhibitory nerves.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
Familial occurrence of intrathoracic gastric volvulus.
This report describes the first documented familial occurrence of gastric volvulus in two consecutive generations. Consideration is given to familial transmission of other foregut disorders. The report reviews the different types of gastric volvulus and considers their pathogenesis, clinical presentation, and treatment.
Aged↗
Evidence for diminished inhibitory neuromuscular transmission in distal small intestine.
The influence of myenteric nerves on duodenal muscle contraction and relaxation was examined in vitro and compared with muscle responses from the ileum. Proximal and distal rat small intestine was cut into strips measuring 6.0 X 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, whereas those cut 90 degrees to that axis were called circular strips. The strips were stretched to their optimal lengths and subjected to electrical field stimulation (0.1-1.0 msec pulse duration, 30-300 mA, 2-26 Hz) in the presence of Krebs' solution and Krebs' plus atropine, 10(-6) M. Field stimulation produced contraction responses that were inhibited by atropine and relaxation responses that were augmented by atropine. Muscarinic blockade abolished completely contraction in circular muscle, but atropine-resistant contractions persisted in the longitudinal strips. Proximal muscle showed significantly greater relaxation responses compared to distal muscle (P less than .05) at nearly all parameters of pulse duration, current and frequency. Contraction and relaxation amplitudes were significantly greater in longitudinal than respective circular muscle (P less than .05) at either site in the intestine. Thus, not only do the two muscle layers differ in their respective nerve supplies, but inhibitory neuromuscular transmission appears to have a greater influence in proximal than distal intestine.
Animals↗
Evidence for abnormal cholinergic neuromuscular transmission in diabetic rat small intestine.
Proximal and distal rat small intestine from control, diabetic, and insulin-treated diabetic rats was cut into strips measuring 6.0 X 10.0 mm. Strips cut along the oral-caudal axis were called longitudinal strips, while those cut 90 degrees to that axis were called circular strips. The strips were stretched to their optimum lengths and subjected to electrical field stimulation (0.1-1.0-ms pulse duration, 30-270 mA, 1-26 Hz) in the presence of Krebs' solution and Krebs' solution plus 10(-6) M atropine. Field stimulation produced atropine-sensitive and atropine-resistant contractions in all strips. Significant differences among the three groups were found in the amplitudes of atropine-sensitive contractions in strips from distal longitudinal muscle. Controls showed the highest amplitude contractions and diabetics the lowest, whereas the insulin-treated diabetics showed contractions intermediate in amplitude. No significant differences were noted among the atropine-resistant contractions. Field stimulation delivered at pulse durations of 5.0 and 50.0 ms in the presence of neural blockade with tetrodotoxin (5 X 10(-6) M) produced similar contraction amplitudes among the three groups. These results suggest that streptozotocin-induced diabetes mellitus is associated with defective cholinergic neuromuscular transmission in the myenteric plexus of the distal small intestine. Insulin therapy seems to improve the abnormality.
Animals↗