Joanne A. P. Wilson

Phylogeny of the Whipple's-disease-associated bacterium.

Efforts to culture and identify the intracellular bacteria associated with Whipples disease have been unsuccessful. Nucleotide sequencing and amplification by the polymerase chain reaction was done on the bacterial 16 S ribosomal DNA present in a small-bowel biopsy specimen taken from a patient with Whipples disease. A search by computer for similar rRNA sequences filed in databases showed the Whipples-associated organism to be most similar to bacteria of the Rhodococcus, Streptomyces, and Arthrobacter genera, and more weakly related to mycobacteria. The biopsy specimen was estimated to contain around 10(7) cells of the organism. The probable aetiological agent for our patients illness has not been identified previously in a patient with Whipples disease.

Hepatic cytochrome P-4503A (CYP3A) activity in the elderly

Elderly patients exhibit decreased clearance of multiple drugs biotransformed by the hepatic cytochromes P-450. The cytochromes P-450 are a superfamily of enzymes, which comprise a central component of phase I drug metabolism. Distinct isoforms metabolize specific drugs. In human liver microsomes, the glucocorticoid-inducible cytochrome P-450IIIA, CYP3A, catalyzes the N-demethylation of erythromycin. To examine the activity of hepatic CYP3A in elderly males and females, erythromycin N-demethylation was examined, as reflected by the recently described [14C]erythromycin breath test in 24 healthy volunteers, age 70-88. The [14C]erythromycin breath test was measured in normal elderly males and females to: (a) determine persistence of the gender-related dimorphism (evident in younger subjects) of CYP3A activity in the elderly population, (b) examine the effect of % ideal body weight, age, diet, and medication use on the activity of human hepatic CYP3A, and (c) compare breath test results obtained in normal geriatric volunteers with published results obtained in younger subjects, to determine aging-related alterations in CYP3A enzyme activity. Erythromycin N-demethylation varied fivefold among these patients. Similar to earlier studies examining erythromycin N-demethylation in younger subjects, CYP3A activity was found to vary with gender in the geriatric cohort. [14C]Erythromycin N-demethylation at 60 min was 3.14% +/- 0.75 (n = 13) in females and 2.15% +/- 0.77 (n = 11) in males (P = 0.005). In evaluating the role of % ideal body weight and % dietary fat using multivariable linear regression analyses, [14C]erythromycin N-demethylation, was found to decline significantly as % ideal body weight increased (P = 0.001). This was not confounded by gender. [14C]Erythromycin N-demethylation was not related to dietary fat intake (P less than 0.13). [14C]Erythromycin N-demethylation in the elderly volunteers was similar to values reported for subjects aged 20-60. Performance of a new non-invasive test of the human hepatic glucocorticoid-inducible CYP3A in a geriatric cohort suggests that: (a) the gender-related heterogeneity in function of the glucocorticoid inducible human CYP3A persists during normal aging, (b) that the activity of CYP3A may decrease in obesity, and (c) that the activity of CYP3A is stable throughout normal ageing.

Medication-induced esophagitis

Clinical, radiographic, and endoscopic features of medication-induced esophagitis (MIE) in 4 patients are described. When the clinical history and symptoms raise a high index of suspicion for MIE, a double-contrast esophagram or endoscopic examination should be performed. The proximal esophagus, particularly the aortic segment, and occasionally the distal esophagus are the sites most commonly affected by MIE. Superficial mucosal erosions, shallow ulcers, and subtle mucosal alterations can be demonstrated by double-contrast esophagrams if careful attention is paid during performance and interpretation of these studies in an appropriate clinical setting.

Crohn's disease in the elderly. Prolonged delay in diagnosis.

Crohn’s disease typically afflicts younger patients, with a peak incidence in the third decade of life. As Crolin’s disease infrequently presents in the elderly, the nature and course of tlie disease among older patients has not been well defined. The presenting symptoms of abdominal pain, fever, and diarrhea so commonly seen with Crohn’s disease may suggest other more frequently encountered illnesses in the elderly such as diverticulitis, ischemic colitis, or malignancy.2 One easily can see that attributing these complaints to these more common disorders or a failure to consider tlie diagnosis of Crohn’s disease can lead to delay in diagnosis and appropriate therapy in tlie elderly. In reviewing the experience with Crohn’s disease presenting in elderly patients at the University of Michigan, the authors hope to determine clinical characteristics of the disease in these patients and to assess the degree to which specific diagnosis or appropriate therapy was delayed after presentation with symptoms.

Peritoneoscopy in the management of catheter malfunction during continuous ambulatory peritoneal dialysis

Continuous ambulatory peritoneal dialysis is widely used in the maintenance of patients with chronic renal failure. Obstruction or displacement of the chronic dialysis catheter, which prevents dialysate drainage, can compromise ongoing dialysis. Conservative approaches (body position change, saline infusion, and enema) are often unsuccessful and more aggressive therapy may be required. We report the use of peritoneoscopy to reposition malfunctioning peritoneal dialysis catheters. The procedure proved to be safe and gave excellent long-term results.

Intrahepatic Cholestasis of Pregnancy with Marked Elevation of Transaminases in a Black American

A case of intrahepatic cholestasis of pregnancy (ICP) in a black American is presented. This is the first case reported in a black. Marked elevation of transaminases with mild biochemical evidence of cholestasis was initially suggestive of viral hepatitis. A clinical course characterized by pruritis with minimal constitutional symptoms, rapid resolution of biochemical abnormalities after delivery, and negative hepatitis A and B serologies was consistent with the diagnosis of ICP. Review of the classic features of ICP with emphasis on some unusual aspects of the disorder is included.SummaryA case of intrahepatic cholestasis of pregnancy (ICP) in a black American is presented. This is the first case reported in a black. Marked elevation of transaminases with mild biochemical evidence of cholestasis was initially suggestive of viral hepatitis. A clinical course characterized by pruritis with minimal constitutional symptoms, rapid resolution of biochemical abnormalities after delivery, and negative hepatitis A and B serologies was consistent with the diagnosis of ICP. Review of the classic features of ICP with emphasis on some unusual aspects of the disorder is included.

Tumor necrosis factor alpha and colitis-associated colon cancer.

Mice that undergo ablation of a gene encoding a receptor of tumor necrosis factor α (TNF-α) or treatment with an antibody that binds TNF-α are partially protected against induced colitis and colitis-associated colon cancer.

Esophagitis caused by nonsteroidal anti-inflammatory medication: case reports and review of the literature on pill-induced esophageal injury.

We report six cases of pill-induced esophageal injury, two of which were caused by the nonsteroidal anti-inflammatory medications ibuprofen and piroxicam, which have not been implicated previously in pill-induced injury.

Characteristics of Ascitic Fluid in the Alcoholic Cirrhotic

A prospective study was conducted to define the characteristics of ascitic fluid in alcoholic cirrhotics with and without spontaneous bacterial peritonitis (SBP); to correlate these with findings in the peripheral blood; and to determine whether the use of counterimmunoelectrophoresis (CIE) for bacterial antigens will aid in the early diagnosis of SBP. Fifty-one alcoholic cirrhotics had simultaneous determination of their blood or serum and ascitic fluid for the following: WBC and differential count, RBC, LDH, amylase, glucose, total protein, and protein electrophoresis, CIE for pneumococcal andKlebsiella antigens, culture for aerobic and anaerobic bacteria and mycobacteria, and cytology. Of the 51 patients, 2 had SBP (4%). In the other 49 patients (54 sera and ascitic fluids), CIE was positive for pneumococcal antigen in 4/54 sera and in 3/54 ascitic fluids. The mean WBC count in the ascitic fluid was 349. In 4% the count was above 1000, in 18% between 501–1000, and in 32% between 301–500; polymorphs were >30% in 19/54 (32%). Specific gravity was >1.020 in 10/54 (22%), and ascitic fluid total protein of 3.0g/100 ml or above was noted in 24% (12/54). Mean ascitic fluid/serum ratios of total protein, albumin, and globulin were 0.31, 0.33, and 0.30 respectively, and mean ascitic fluid/serum ratios of LDH, amylase, and glucose were 0.54, 0.79, and 1.04. All cultures (except those with SBP) and cytology were negative. Our study confirmed the observation of others, that a significant number of noninfected cirrhotics have increased ascitic fluid WBC, % polymorphs, specific gravity, and total protein concentration. CIE was not helpful in the early diagnosis of SBP.

Gastric xanthomatosis and cholestasis. A causal relationship

We report two cases of gastric xanthomatosis which developed in patients with marked cholestasis. In both cases, one with acute and one with chronic cholestasis, the gastric xanthomas disappeared with resolution of the cholestasis. A review of the literature is also provided.