Postmenarchal development of chylous ascites in acrocephalosyndactyly with congenital lymphatic dysplasia.

BACKGROUND: Acrocephalosyndactyly is a syndrome characterized by congenital malformation of the skull with craniosynostosis, midface hypoplasia, and symmetrical webbed fusion of the fingers and toes. We describe a possible pathophysiologic mechanism for chylous ascites that developed several months after menarche in a woman with acrocephalosyndactyly and congenital lymphatic dysplasia. CASE: A 25-year-old nulligravid woman with acrocephalosyndactyly, at 18 months after menarche, developed persistent abdominal distension at age 18 years. Laparoscopy at age 25 years revealed chylous ascites with marked chronic peritoneal inflammation, and lymphatic dysplasia with lymphocysts. With hormone manipulation, the chylous ascites fluctuated. CONCLUSION: After menarche in a woman with acrocephalosyndactyly, ovarian steroid hormones might have increased lymph production and hydrostatic pressure, causing rupture of congenitally dysplastic lymph vessels resulting in chylous ascites.

Approach to the patient with abnormal liver tests.

Patients with abnormal liver blood tests are frequently encountered by primary care practitioners. An understanding of the cellular implications of these abnormalities is helpful in determining the etiology of liver injury. Elevated serum aminotransferases suggest injury of hepatocytes. Elevations in alkaline phosphatase suggest injury to any part of the biliary tree. Neither of these enzymes measures liver function. Serum bilirubin and albumin levels, as well as prothrombin time, do measure function and can be used in conjunction with the physical examination and the specific etiology of the patient's disorder to determine a patient's prognosis. Many diverse disorders result in similar biochemical patterns of liver injury. The history, physical examination, and use of specific disease markers (hepatitis serology, autoimmune markers, and so forth) help to narrow the differential diagnosis. The definitive diagnosis of all liver diseases usually rests on histology: the liver biopsy is the gold standard. With the advent of treatments for liver disease, identifying and accurately diagnosing patients with liver disorders will result in improved quality of life and survival.

Electrocautery and patients with implanted cardiac devices.

Implanted cardiac devices, pacemakers, and automatic cardioverter/defibrillators are becoming more common in the general population. There are more than one-half million persons with pacemakers living in North America, and approximately 20,000 patients have received automatic implantable cardioverter/defibrillators. As pacemaker and defibrillator patients experience common gastrointestinal afflictions, it is likely that more will require endoscopic procedures. Appropriate precautions must be undertaken during electrosurgical procedures in order to avoid damage and interruption of pacemaker/defibrillator devices. Through careful assessment, intervention, and discharge planning, the GI nurse and associate can reduce electrosurgical risks to the gastrointestinal patient with an implanted cardiac device. Specific recommendations for preprocedure patient assessment and intraprocedure interventions are discussed, and an actual case is presented to illustrate a successful plan of care.

Primary biliary cirrhosis: survival of a large cohort of symptomatic and asymptomatic patients followed for 24 years.

We extended by 10 years, a follow-up study of 279 patients with primary biliary cirrhosis initially evaluated at the Yale Liver Study Unit between 1955 and 1979. Thirty-six patients (13%) were asymptomatic at the time of diagnosis. Accurate follow-up survival data were available for 247 patients (89%), ranging up to 24 years after the original diagnosis. Median predicted survival of patients in this study from the time of diagnosis is twice as long for patients who present without symptoms compared to symptomatic patients (16 vs 7.5 years, p < 0.0001). However, overall survival of those asymptomatic patients is shorter than that predicted for an age- and gender-matched control population (p < 0.0001), a difference that became apparent only after 11 years of follow up. With a median follow up of 12.1 years, 33% of the asymptomatic patients remained free of symptoms of liver disease, However, once symptoms develop, their survival is similar to those presenting with symptoms. Independent predictors of diminished survival include: elevated bilirubin, increasing age, ascites, advanced fibrosis and the degree of portal bile stasis on liver biopsy. It was not possible to predict which asymptomatic patients would remain symptom free.

Positron-emission tomographic localization of abnormalities of brain metabolism in patients with minimal hepatic encephalopathy.

Many patients with compensated cirrhosis without overt hepatic encephalopathy have deficits in visual-spatial perception, a condition we call minimal hepatic encephalopathy. Five patients with alcohol-induced cirrhosis and nine control subjects underwent positron-emission tomographic imaging of the brain with 18F-fluorodeoxyglucose. Patients also underwent neuropsychological and clinical chemistry tests. The patients had mild arterial hyperammonemia (62 +/- 13 mumol/L, range = 11 to 35 mumol/L) and other abnormalities typical of patients with cirrhosis. The patients' mean percentile scores on the digit symbol and block design subtests, from the Wechsler Adult Intelligence Scale (revised), and Purdue pegboard test were 11 +/- 7, 24 +/- 7 and 7 +/- 8 (right hand). Tests of vocabulary, memory, and new learning were normal. The technique of statistical parametric mapping was used to identify regions where cerebral 18F-fluorodeoxyglucose uptake and metabolism were abnormal. We noted significant reductions in the cingulate gyrus, a center mediating attention, target analysis and response formulation and significant increases in visual associative regions subserving motion and color perception and object orientation. We suggest that minimal hepatic encephalopathy is due to a deficit in the detection and formulation of responses to visual stimuli, a function of the cingulate, which is a part of the anterior attentional system of the brain. Increases in 18F-fluorodeoxyglucose metabolism may be compensatory. These studies show that brain regions differ in their sensitivity to the agents that cause hepatic encephalopathy and that positron-emission tomography is useful in studying the pathophysiology of this disorder.

Alpha interferon and hepatitis B and C. An integrated approach using practice guidelines.

Utilizing the techniques of total quality management, a team designed a clinical guideline for the use of alpha interferon as a treatment for patients with chronic hepatitis. The team included TEMINEX staff, a primary care physician, the plan's internal gastroenterologist, and its university-based consultant gastroenterologists. A synopsis of the available published research data and clinical opinion (a draft TEMINEX report) was used to focus discussions. The final TEMINEX report represented consensus on patient selection criteria and treatment regimens. All members of the team agreed to a review and approval process. Although quantitative data concerning the effects of guideline implementation are not yet available, it appears that the concerns of all members of the team have been satisfied. Patient selection criteria supported by the results of well-designed research are in place. Appropriate candidates for alpha-interferon therapy receive expedited treatment and the plan's internal monitoring processes are more efficient. Primary care physicians and consultant gastroenterologists feel that they made positive contributions both to the quality of care and to the consensus development process.

Interferon-alpha prevents endotoxin-induced mortality in mice.

Endotoxins, the lipopolysaccharide (LPS) moieties on the bacterial cell wall, cause many of the pathological features of Gram-negative septicemia. Tumor necrosis factor (TNF), primarily a product of monocyte/macrophages, has been shown to mediate many of the pathophysiological effects of endotoxin. Kupffer cells, the largest macrophage population in the body, release TNF when stimulated by LPS in vitro. A recombinant human hybrid interferon-alpha A/D (rIFN-alpha) markedly inhibited this LPS-elicited TNF production by Kupffer cells. The effects of rIFN-alpha were further tested in C57BL/6 mice receiving a lethal dose (400 micrograms/mouse) of LPS. All LPS-treated mice died within 2 days. Pretreatment with rIFN-alpha 1 h before LPS challenge improved the survival at 3 days to 22% (5/23, p < 0.04). In contrast, rIFN-alpha was more effective when administered 20 min after LPS injection, increasing the survival rate to 81% (13/16, p < 0.0001). TNF mRNA expression in the liver and spleen 50 min after LPS challenge, and plasma TNF 1.5 h after LPS were also reduced by either pretreatment or post-treatment with rIFN-alpha. Subsequently, experiments were carried out to test the efficacy of delayed rIFN-alpha treatment. A significant protective effect was still apparent when rIFN-alpha was administered 6, 10 and even 14 h (81%, 62% and 28% survival, respectively) after LPS challenge when serum TNF levels had already returned to near baseline. These experimental results suggest that rIFN-alpha might have a therapeutic potential for the prevention and treatment of the deleterious effects associated with endotoxemia besides mechanisms initially blocking TNF production.

A randomized study of propranolol on postprandial portal hyperemia in cirrhotic patients.

Propranolol, a nonselective beta-adrenergic blocker, has been shown to reduce portal pressure and the risk fo variceal bleeding. The portal pressure-reducing effect of propranolol is mediated by splanchnic arterial constriction, which decreases portal flow. A double-blind randomized control study (crossover on 2 consecutive days) was designed to compare the effects of propranolol vs. placebo on portal flow in cirrhotic patients during fasting and after a standardized meal. Portal flow was measured with an ATL Ultramark 8 echo-Doppler system (Advanced Technological Laboratories, Bothel, WA) in 23 cirrhotic patients. Fasting portal flow and heart rate were obtained at baseline and 2 hours after the administration of propranolol or placebo. A standard test meal was then given, and measurements were repeated 30 minutes later. Thirteen patients (group 1) received placebo on day 1 and propranolol on day 2, whereas 10 patients (group 2) received propranolol on day 1 and placebo on day 2. In group 1 patients, heart rate declined by 20% (P less than 0.0001) and portal flow decreased by 12% (P less than 0.05) after propranolol administration. Similar reductions were found in heart rate (-21%, P less than 0.0001) and portal flow (-17%, P less than 0.001) for group 2 patients. For all 23 patients, 2 hours after propranolol administration, heart rate declined by 21% (P less than 0.0001) and portal blood flow was reduced by 14% (P less than 0.0001). The 10 patients who received propranolol on day 1 (group 2) showed a carryover effect of propranolol on day 2. On day 2, baseline portal flow and heart rate values were significantly lower than baseline values on day 1. This long-lasting effect of a single dose of propranolol may be caused by the longer half-life of propranolol in cirrhotic patients. The postprandial portal blood flow percentage increase after the meal was similar for both placebo and propranolol. Propranolol did not blunt postprandial hyperemia. However, whereas the absolute value of blood flow after the meal increased significantly in comparison with baseline in placebo-treated patients (P less than 0.001), this did not occur with propranolol. Furthermore, in propranolol-treated patients the absolute value of blood flow after the meal was lower than in placebo-treated patients. This may constitute a protective effect of propranolol in portal hypertension.

Pathophysiology of portal hypertension and variceal bleeding.

Portal hypertension results from an interaction of abnormal intrahepatic resistance and increases in portal blood flow. Intrahepatic resistance is probably multifactorial in nature and may include compression of hepatic veins by regenerating nodules, collagen deposition in sinusoids and venules, hepatocyte enlargement, and constriction of sinusoids by contractile myofibroblasts. The increase in splanchnic blood flow observed is incompletely understood, but it may involve circulating vasodilators and alteration in volume and sodium balance. The end result of these interactions is the development of increased portal pressure and portosystemic collaterals, the most important of which are esophageal varices. The rupture of esophageal varices is a devastating complication of portal hypertension. Increased portal pressure is necessary for the development and rupture of varices but apparently not sufficient, because many patients with elevated portal pressures never bleed. Presumably, local factors must be involved. Variceal wall tension is probably the best single descriptor of risk from variceal hemorrhage. The wall-tension formula unites the contributions of portal pressure, varix size, and wall thickness to variceal rupture. Lowering portal pressure, reducing varix size, and supporting varices in scar tissue may all lower the risk of hemorrhage.