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Biomedical subjects

S C Gordon

Publications and source records attributed to S C Gordon.

At least 55 records · Page 3Linked to original sources

Antibodies to carbonic anhydrase in patients with immune cholangiopathies.

BACKGROUND/AIMS: Bile duct epithelia contain an abundance of carbonic anhydrase. Antibodies to this enzyme have been described in autoimmune disorders. Serum from patients with immune-mediated liver diseases was studied to determine whether antibodies to carbonic anhydrase II and/or pyruvate dehydrogenase could distinguish autoimmune cholangitis as immunologically distinct from primary biliary cirrhosis. METHODS: Antibody assays to carbonic anhydrase II (Western blot) and pyruvate dehydrogenase (flow cytometry) were performed on the sera of patients with autoimmune cholangitis (6), primary biliary cirrhosis (12), primary sclerosing cholangitis (12), autoimmune hepatitis (12), and control (Gilbert syndrome; 8). RESULTS: Reactivity to carbonic anhydrase II was detected in 5 of 6 patients with autoimmune cholangitis, 1 of 12 patients with primary biliary cirrhosis, 1 of 12 patients with autoimmune hepatitis, and no other patients. Individuals with autoimmune cholangitis were more likely than the other patients to be reactive to carbonic anhydrase II (P < 0.001). Patients with primary biliary cirrhosis were more reactive to pyruvate dehydrogenase compared with all other groups (P < 0.001). CONCLUSIONS: An antibody to human carbonic anhydrase II is frequently detected in the sera of patients with autoimmune cholangitis and is uncommon or not present in other cholangiopathies. These data provide evidence that autoimmune cholangitis and primary biliary cirrhosis represent distinct entities with unique patterns of immunoreactivity.

Aged↗

Histologic spectrum of cryptogenic chronic liver disease and comparison with chronic autoimmune and chronic type C hepatitis.

Most histologic studies of cryptogenic chronic liver disease were done before the discovery of hepatitis C, and therefore encompass the histologic spectrum of this disease. The authors report the histopathologic findings of 18 liver biopsies of presumed cryptogenic chronic liver disease patients and compared them to chronic autoimmune hepatitis and hepatitis C virus biopsies. Severe bridging fibrosis or cirrhosis was present in 55%. Eighty percent of biopsies had minimal necroinflammatory activity including those with cirrhosis; 20% had moderate activity. Histologic distinction from chronic hepatitis C was difficult in the minimally active cryptogenic chronic liver disease biopsies because 20% of biopsies had portal lymphoid follicles and 33% had macrovesicular steatosis. Chronic autoimmune hepatitis had more parenchymal necroinflammatory activity and plasma cells than did either cryptogenic chronic liver disease or chronic hepatitis C biopsies. These findings suggest that one form of cryptogenic chronic liver disease is a persistent, low grade hepatitis that can progress to cirrhosis despite an innocuous histopathologic appearance. Pathologists should be aware that cryptogenic chronic liver disease biopsies may have minimal histologic abnormalities. These biopsies should not be reported as normal. Such cases require long-term clinical follow-up.

Autoimmune Diseases↗

Species identification of Cecidophyopsis mites (Acari: Eriophyidae) from different Ribes species and countries using molecular genetics.

Cecidophyopsis mites were studied by PCR amplification of parts of their ribosomal DNA, followed by restriction enzyme analysis. Mite specimens on Ribes nigrum (black currant) from six countries gave the same digestion pattern, which was distinct from the pattern for mites found on R. rubrum from Poland and Finland and for R. grossularia from the USA. This suggests that each Ribes species is host to a different mite species: C. ribis, C. selachodon and C. grossulariae, respectively. Two other mite samples from R. alpinum and R. aureum were identical but were distinct from each of the other species.

Animals↗

Self-administered versus nurse-administered epidural analgesia after cesarean section.

OBJECTIVE: To compare two methods of administering analgesia by the epidural route after cesarean sections. DESIGN: Quasi-experimental. SETTING: The postpartum area of a large community hospital. PARTICIPANTS: Fifty women undergoing planned cesarean sections with epidural anesthesia. INTERVENTIONS: The control group received continuous epidural analgesia with nurse-administered boluses and the experimental group with self-administered boluses. MAIN OUTCOME MEASURES: Pain control, side effects from medication, amount of medication required, postoperative activity levels, and patient satisfaction. RESULTS: Subjects receiving continuous epidural analgesia with self-administered boluses of analgesic used significantly less fentanyl and fewer supplemental intravenous pain medications than subjects receiving continuous epidural analgesia with nurse-administered boluses of analgesic. CONCLUSIONS: Subjects in self-administered group required less pain medication than subjects in nurse-administered group.

Activities of Daily Living↗

Cryptogenic liver disease in the United States: further evidence for non-A, non-B, and non-C hepatitis.

UNLABELLED: Since the advent of anti-hepatitis C virus (HCV)-testing, the current worldwide prevalence of cryptogenic cirrhosis is essentially unknown. OBJECTIVES: 1) determine if serum HCV RNA testing by the polymerase chain reaction (PCR) enhances the diagnostic yield for HCV in patients with anti-HCV-negative cryptogenic liver disease and 2) further define the epidemiology of patients with indeterminate causes of chronic hepatitis and cirrhosis. METHODS: We reviewed the records of 567 patients with chronic liver disease who were evaluated over a 3-yr period. A definite etiology for liver disease was established in all but 28 patients (4.9%). Histology was available in 20 patients. RESULTS: Twenty-one of the 28 patients were female (mean age, 52 yr). Thirteen patients (46%) had a history of previous blood transfusion, and one patient was a health care worker. Histology revealed CAH/cirrhosis in 17 patients, CPH in one patient, and no diagnosis in two patients. Five additional patients had clinically advanced cirrhosis. None of the 28 patients with cryptogenic chronic liver disease was HCV RNA positive by PCR. CONCLUSIONS: 1) Approximately 5% of patients with chronic hepatitis/cirrhosis remain cryptogenic despite the addition of HCV RNA testing. 2) PCR does not improve the diagnostic yield in this population. 3) Nearly half of the patients with presumed cryptogenic cirrhosis have been transfused, supporting the hypothesis of a non-A, non-B, and non-C hepatitis virus. 4) Screening donor blood for serum ALT may still be necessary to further reduce posttransfusion hepatitis.

Chronic Disease↗

HCV RNA is present in the menstrual blood of women with chronic hepatitis C infection.

OBJECTIVES: To further determine potential routes of sexual transmission of hepatitis C virus (HCV), we examined the menstrual blood of women chronically infected with this virus. METHODS: Ten premenopausal women with documented HCV infection were studied. All patients were anti-HCV positive by ELISA-II and positive for HCV RNA by polymerase chain reaction. Eight patients acquired their infection via intravenous drug abuse, one patient through blood transfusion, and one patient was a health care worker. Liver biopsies showed evidence of chronic hepatitis in all patients. Menstrual blood was collected on the first day of menses utilizing a sterile 15-ml conical centrifuge tube. Total RNA was isolated from serum by the one-step guanidinium method. Reverse transcriptase polymerase chain reaction was performed with "nested" primers from the 5' noncoding region of the HCV genome. All samples were run twice, and negative controls were run with each sample. Three anti-HCV negative volunteers served as controls. RESULTS: HCV RNA was present in the menstrual blood of all chronically infected patients tested. All controls were negative for menstrual blood HCV RNA. CONCLUSIONS: 1) HCV RNA is routinely present in the menstrual blood of women chronically infected with this virus. 2) Knowledge of the presence of HCV RNA in menstrual blood should help facilitate appropriate guidelines for the sexual counseling of patients with chronic HCV infection.

Adult↗

Levels of hepatitis C virus RNA and liver histology in chronic type C hepatitis.

BACKGROUND: The clinical and pathologic significance of quantitative serum hepatitis C virus (HCV) RNA levels in patients with chronic type C hepatitis is unknown. The aim of this study was to determine whether serum levels of HCV RNA were associated with mode of viral transmission or with histological severity of liver disease. METHODS: A branched DNA signal amplification assay for HCV RNA was done on the sera of 127 patients with well-defined risk factors for viral hepatitis. Seventy persons acquired HCV infection by blood transfusion and 57 via tattoo application or former intravenous drug use. Group I included 42 patients with chronic persistent hepatitis, group II consisted of 39 patients with chronic active hepatitis, and group III included 40 individuals whose liver biopsies showed both chronic active hepatitis and cirrhosis, as well as six patients with clinically decompensated cirrhosis. RESULTS: The median HCV RNA level [equivalents/ml (eq/ml) x 10(5)] for patients who acquired infection from transfusion [73.5 x 10(5) (eq/ml)] was not significantly different from that of patients who reported prior intravenous drug use [50 x 10(5) eq/ml] (p = 0.283). The median HCV RNA level for groups I, II, and III was 29.5, 76, and 71, respectively. Group I differed significantly from groups II and III combined (median = 73) (p = 0.02). No difference was noted between group II and group III (p = 0.947). Age did not correlate with level of viremia (r2 = 0.01). No relationship was found between serum alanine aminotransferase and the level of viremia (p = 0.52). Multivariate analysis showed that only the histological severity of the disease proved to be predictive of HCV RNA level (p = 0.04). CONCLUSION: The lowest levels of hepatitis C viremia are, in general, associated with minimal liver disease. Overall, histological severity of chronic hepatitis C infection best predicts HCV RNA levels.

Biopsy↗

The pathology of hepatitis C as a function of mode of transmission: blood transfusion vs. intravenous drug use.

We reviewed the clinical records of 140 consecutively evaluated patients with chronic hepatitis C infection. One hundred twenty-four patients (89%) contracted infection through blood transfusion or intravenous drug use. The liver biopsy specimens of 83 patients (43 blood transfusion cases and 40 intravenous drug abuse cases) were examined without knowledge of the mode of disease transmission. The mean histological activity index score was significantly higher in the blood transfusion group (10.2 +/- 4.2) than in the intravenous drug use group (6.9 +/- 4.5) (p = 0.001). The transfusion group had more periportal bridging necrosis (p = 0.0015) and fibrosis (p = 0.0016) than did the intravenous drug use group, whereas significant differences between lobular degeneration and portal inflammation were not achieved across the two groups. The distribution of final biopsy interpretations also differed significantly between the two groups (p < 0.001), with chronic active hepatitis more frequent in the transfusion group. Moreover, lymphoid aggregates and bile duct damage were more common in patients with chronic hepatitis due to blood transfusion. Multivariate analysis showed that the mode of viral transmission was the most powerful predictor of histological activity index score when tested against patient gender, duration of disease or age at biopsy. One year after completion of this study, 9 of 70 transfused patients and 1 of 54 intravenous drug users had died of liver disease or are awaiting liver transplantation at this writing (p = 0.03). We conclude that transfusion-acquired hepatitis C is associated with more aggressive histological inflammatory activity than hepatitis resulting from intravenous drug use.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A flow cytometric method to detect anti-pyruvate dehydrogenase antibody in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is an autoimmune disease characterized by the presence of anti-mitochondrial antibodies specifically directed against the M2 group of mitochondrial antigens. Recently, the E-1, the E-2, and protein X components of pyruvate dehydrogenase enzyme complex have been identified as the major antigens within the M2 group of autoantigens. An immunoassay using pyruvate dehydrogenase enzyme complex as a specific antigen for the diagnosis of PBC was developed. Pyruvate dehydrogenase enzyme complex was attached to polystyrene microbeads, incubated with sera from PBC patients (n = 18), normal controls (n = 50), or patients with other autoimmune diseases (n = 26), followed by incubation with a second fluorescein isothiocyanate conjugated goat anti-human immunoglobulin and then analyzed by flow cytometry. High numbers of fluorescence channels (mean, 1,693 +/- 846) were obtained for all PBC sera except for two patients. Compared to the conventional anti-mitochondrial antibody assay, the assay had a sensitivity rate of 94% and a specificity rate of 100%. The reactive antibodies are predominantly of the immunoglobulin G3 subclass. Their levels could be correlated with the histopathologic stages of PBC. These results were corroborated by immunoblotting. Sera from patients with later stages of PBC strongly reacted with pyruvate dehydrogenase enzyme complex components, E1 alpha, and protein X.

Antibodies↗

Involving nursing staff in research. A non-traditional approach.

The staggering complexity of issues that affect nursing service requires the participation of nurses at all practice levels in the continuing development of the knowledge and practice of nursing. The authors describe a practical application of a nursing research and development method in which nursing values are integrated with elements of non-traditional research approaches.

Group Processes↗

Lack of evidence for the heterosexual transmission of hepatitis C.

To determine the potential for sexual transmission of the hepatitis C virus (HCV), we specifically studied a cohort of 42 young adults (median age, 39 yr) with chronic HCV infection and their stable sexual partners. All HCV assays were supplemented with the four-antigen recombinant immunoblot assay, and 39 of 42 partners were tested for HCV RNA by the nested polymerase chain reaction. Ninety percent of the partners reported frequent and unprotected sexual intercourse with the index patients. Two of 42 partners tested positive for the anti-HCV antibody and both were HCV RNA positive; one had independent risk factors for viral hepatitis. Therefore, one of 41 partners, (2.4%; 95% CI, 0.6-12.9%) without independent risk factors for HCV was anti-HCV positive. This woman was one of five partners (20%; 95% CI, 1-66%) who reported frequent razor-sharing with the index patient. The partner frequently sustained skin lacerations, with bleeding, secondary to this shared razor blade. We conclude that heterosexual transmission of hepatitis C is extremely uncommon, despite frequent and unprotected sexual intercourse.

Adult↗

Prevalence of anti-HCV in cryptogenic cirrhosis in a suburban Detroit community.

To assess the role of the hepatitis C virus in patients with unexplained chronic liver disease, we tested for the presence of anti-hepatitis C antibody (anti-HCV) in the stored serum of patients with cryptogenic cirrhosis and a variety of other chronic liver diseases. The anti-HCV assay was performed by both the enzyme-linked and recombinant immunoblot methods in 16 patients with cryptogenic cirrhosis. Eight of these 16 patients (50%) were seropositive. Six of these eight patients were born outside of the United States, compared with only one of eight seronegative patients (p = 0.021). Of the anti-HCV-positive cryptogenic cirrhotic patients, 50% also had markers of previous hepatitis B infection, compared with only 12.5% of seronegative patients. Evidence of anti-HCV positivity was found in 10%, 19%, 0%, and 0% in patients with alcoholic cirrhosis, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis, respectively. We conclude that in a suburban American population, hepatitis C accounts for a significant percentage of patients with presumed cryptogenic cirrhosis. Unrecognized risk factors may account for a higher prevalence of HCV in foreign-born patients with cryptogenic cirrhosis. A low prevalence of anti-HCV positivity is found in other forms of chronic liver disease.

Adolescent↗

Jaundice and cholestasis. Some common and uncommon causes.

Jaundiced patients may not always be as sick as they look, and cholestatic patients may be quite ill but not yet jaundiced. There is variability in presentation of cholestasis, and jaundice may be intrahepatic or extrahepatic and acute or chronic. Even though the diagnosis of jaundice can be elusive, an unnecessarily exhaustive search for a cause should be avoided, because some tests are not without dangers. Dr Gordon describes many possible causes, some of which are rare but are still worth consideration.

Cholangiography↗

Acute toxicity, genotoxicity, and dermal carcinogenicity assessment of isooctyl acrylate.

Isooctyl acrylate (IOA) monomer is a complex mixture comprised predominantly of isomeric, eight-carbon alkyl esters of acrylic acid. Limited evidence from animal studies suggests that certain acrylate esters may be carcinogenic by the dermal route of exposure. The following studies were performed with IOA monomer: acute oral toxicity limit test in rats, primary dermal and ocular irritancy in rabbits, Ames Salmonella microsome assay, Saccharomyces cerevisiae D3 recombinogenicity assay, L5178Y TK +/- mouse lymphoma cell assay, and C3H/10T1/2 mouse embryo cell transformation assay. Finally, a limited dermal carcinogenicity bioassay was performed in which aliquots (25 microliters) of IOA monomer (5% v/v in acetone), IOA polymer (19% w/v in 70:30 acetone/heptane), or acetone (vehicle control) were applied to the shaved backs of male C3H/HeJ mice three times per week for the animals' lifetimes. IOA monomer had an acute oral LD50 in rats greater than 5000 mg/kg, was slightly irritating to the eyes and skin of rabbits on single exposures, and exhibited no genotoxic or cell-transforming potential. In the dermal carcinogenicity bioassay, no significant difference in mean survival times was observed between either treatment group and the control group. Animals treated with IOA monomer exhibited moderate dermatitis, surface crusting, hyperkeratosis, epidermal hyperplasia, diffuse melanosis, and one benign melanoma at the treatment size. Animals treated with IOA polymer exhibited varying degrees of dermatitis, surface crusting, and hyperkeratosis. Neither IOA monomer nor IOA polymer was carcinogenic under the conditions of the study.

Acrylates↗

Budd-Chiari syndrome complicating pre-eclampsia: diagnosis by magnetic resonance imaging.

A 25-year-old primigravida with third-trimester pre-eclampsia developed severe right upper quadrant pain, marked serum aminotransferase elevation, and disseminated intravascular coagulation after cesarean delivery. Computed tomography of the liver showed a right hepatic abnormality that on magnetic resonance imaging had the appearance of hemorrhage; partial thrombosis of the right hepatic vein extending to the inferior vena cava was also seen. Anticoagulation was begun and the patient completely recovered; follow-up imaging 8 months later was normal. This case suggests that nonfatal forms of Budd-Chiari syndrome may complicate pre-eclampsia; predisposition to partial venous outflow obstruction in the pre-eclamptic patient may be pathogenetically related to disseminated intravascular coagulation. This entity may be clinically confused with, or misdiagnosed as, spontaneous hepatic hemorrhage, with or without capsular rupture. In such circumstances, magnetic resonance may be diagnostically useful.

Adult↗