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K L Lindsay

Publications and source records attributed to K L Lindsay.

12 recordsLinked to original sources

Application of six hepatitis C virus genotyping systems to sera from chronic hepatitis C patients in the United States.

Serum samples from 139 US patients with chronic hepatitis C virus (HCV) infection were studied using six different genotyping systems, including both molecular and serologic methods, to determine the applicability of these approaches and the prevalence of various HCV subtypes. The concordance of genotyping results based on the various systems (except for core polymerase chain reaction genotyping) was good (93.5%). Subtypes 1a and 1b were prevalent (37.4%). Subtypes 2a (2.2%), 2b (8.6%), and 3a (5.8%) were less common. HCV genotypes could not be determined in 3.4%-16.5% of samples depending on the method used. HCV type 2 was associated with greater histologic activity but lower serum HCV RNA levels (P < .05), whereas type 3 was associated with lower serum alanine aminotransferase levels (P < .05). These data demonstrate a high concordance between HCV genotyping systems and provide a foundation for comparison of genotyping data between studies using different systems. HCV types 1a and 1b are both prevalent in the United States.

Adult

Management of chronic hepatitis in special populations.

Over the last several years, much progress has been made in the treatment of adult patients with chronic viral hepatitis and compensated liver disease in the absence of significant other illnesses. However, the treatment of chronic viral hepatitis in other patient populations is still experimental. These groups include children, patients immunocompromised by human immunodeficiency virus infection or immunosuppression following organ transplantation, those with end-stage renal disease, and patients with extrahepatic manifestations of hepatitis viral infection. Data on the treatment of chronic hepatitis in these special populations are reviewed.

Child

Neutrophil cytoplasmic antibodies: a link between primary sclerosing cholangitis and ulcerative colitis.

Whether serum autoantibodies to neutrophil cytoplasmic components, previously found in ulcerative colitis, are also associated with primary sclerosing cholangitis was determined. In an enzyme-linked immunosorbent assay for immunoglobulin G neutrophil antibodies, neutrophil binding by primary sclerosing cholangitis sera was significantly greater than that for primary biliary cirrhosis, chronic hepatitis B, and chronic non-A, non-B hepatitis. Similar differences were seen when sera from patients with primary sclerosing cholangitis without evidence for ulcerative colitis were compared with sera from liver disease controls. Perinuclear immunofluorescence staining of neutrophils was exhibited by the majority of ulcerative colitis, primary sclerosing cholangitis, and primary sclerosing cholangitis without ulcerative colitis sera. The combination of elevated immunoglobulin G neutrophil antibodies and a perinuclear pattern was 65% sensitive and 100% specific for primary sclerosing cholangitis compared with the liver disease control sera. It is concluded that neutrophil cytoplasmic antibodies in ulcerative colitis and primary sclerosing cholangitis may be markers of shared underlying immunopathogenic mechanisms. Identification of the target antigen(s) may facilitate understanding of the underlying immune response and development of an improved disease marker assay.

Autoantibodies

Ultrastructure of hypertensive rat aorta. Increased basement membrane-like material.

To determine the effect of elevated blood pressure on the ultrastructure of rat aorta, hypertension (average mean pressure 163 +/- 17 mm Hg) was produced by suprarenal aortic coarctation. After 3 weeks, the subendothelium of the hypertensive thoracic aorta showed significantly increased volume measurements for mononuclear leukocytes and basement membrane-like material compared with the sham-operated control group. Focal areas of rarefaction of the subendothelial extracellular material were associated with the nearby presence of mononuclear leukocytes. None of these alterations were found in the normotensive abdominal aorta. The tunica media of hypertensive thoracic aorta also contained significantly increased basement membrane-like material. This new finding in an animal hypertension model is the direct result of the quantitative morphological approach employed in this study. In some rats, the partially constricting aortic ligature compromised the right renal artery leading to ischemic atrophy of the right kidney and hyperreninemia in addition to hypertension. In this group, excluded from the previous analysis and evaluated separately, subendothelial thickening and accumulation of basement membrane-like material in the thoracic aorta were greatly increased compared with the control group and other hypertensive rats. This result could not be attributed to an effect of blood pressure alone and might have been caused in part by humoral factors. Basement membrane accumulation appears to be an important early response of the arterial wall to hypertension or other factors in this rat model.

Animals

Endothelial denudation and myointimal thickening in the rat carotid artery induced by the passage of bubbles.

A new technique for the selective removal of endothelium in the rat carotid artery has been developed, and subsequent events in the vascular wall have been examined. To achieve de-endothelialization, more than 2,000 bubbles of nitrogen in phosphate-buffered saline are passed through a temporarily isolated segment of rat carotid over a period of 3 min. Bubbles are generated by a simple apparatus, consisting of a pressurized tilting chamber and catheter. Endothelium is removed while subendothelial basement membrane and other subjacent structures remain intact. Platelets attach to the denuded surface within minutes after re-establishment of blood flow. Myointimal thickening is found at 5 weeks and 4 months after de-endothelialization. The method is quite reliable and will facilitate further studies of reactions to carotid endothelial injury in young adult rats.

Animals

Comparison of aortic intima and inner media in young adult versus aging rats. Stereology in a polarized system.

Age-related ultrastructural changes in the intima and inner media of rat thoracic aorta were examined by new morphometric techniques. Young adult male rats, 10 weeks old, were compared with 1-year-old male rats. The most marked changes were found in the sub-endothelium, which increased in thickness more than five-fold. Basement-membrane-like and granular material accounted for the bulk of this thickening. Certain other structures were increased sevenfold or more in subendothelium. These structures and the volume fractions they occupied in 1-year-old rats were as follows: banded collagen, 4.3%; mononuclear leukocytes, 4.5%; cystic structures, 3.3%; and fibrillar elastin, 1.0%. Changes were also demonstrated in the fenestrae of and at selected depth levels below the innermost, or alternatively the internal, elastic lamina. Collagen increased strikingly within fenestrae and just below the elastic lamina. This was associated with a 28% increase in the thickness of the elastic lamina and a recession of smooth muscle cytoplasm to a deeper position within the first musculoelastic medial layer. The alterations in subendothelial tissues imply an altered basis for mechanical support for aortic endothelium in aging rats. These results mark the successful application of micro-computer-based stereology to a situation of polarized geometry.

Aging

Spontaneous Arizona hinshawii peritonitis in cirrhosis with ascites.

Arizona hinshawii, a gram-negative enteric pathogen, causes serious infections in fowl, reptiles, and other animals. In humans, gastroenteritis, enteric fever, septicemia, and localized infections due to Arizona have occurred. There are no previous reports of spontaneous bacterial peritonitis secondary to Arizona, however. We report here a case of spontaneous bacterial peritonitis due to Arizona occurring in a patient with cirrhosis of the alcoholic type. The patient was treated with a 10-day course of gentamicin, and although she improved clinically, Arizona was cultured from the blood and bile postmortem.

Aged

Ascites.

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Ascites

Delayed HBsAg clearance in chronic hepatitis B viral infection.

Seven patients are described in whom HBsAg persisted for 13 to 98 months after acute viral hepatitis B and then became nondetectable. All patients subsequently developed anti-HBs. During the period of HBs-antigenemia, liver biopsies in five patients showed persistent viral hepatitis. Retrospectively, impending negativity of HBsAg was predictable in five patients by a decrease in HBsAg titer, and in four patients by persistent normalization of serum alanine aminotransferase. Although delayed clearance of HBsAg in patients with chronic hepatitis B virus infection is uncommon, it appears to be predictable.

Acute Disease

Hepatitis B vaccine: low postvaccination immunity in hospital personnel given gluteal injections.

Although other investigators have found excellent response rates to the hepatitis B vaccine, we report here an unusually low rate of seroconversion following hepatitis B vaccination in a group of apparently healthy medical center personnel. Only 67% of these individuals developed adequate postvaccination antibodies to HBsAg, in contrast to 85 to 96% in other studies. A significant decrease in seroconversion with increasing age was noted with a 54% seroconversion rate in vaccines over the age of 40; all of whom had received gluteal injections. Employees at another facility had been given deltoid injections from the same vaccine lot and had an overall seroconversion rate of 90%. Subsequently, nonresponders from the first group were revaccinated. Seven of the ten individuals tested developed anti-HBs. We believe the relatively low rate of seroconversion in individuals above the age of 40 may have been related to gluteal injection of the hepatitis B vaccine, and further investigation is warranted.

Adult

Diagnostic usefulness of testing for anti-HBc IgM in acute hepatitis B.

Numerous tests to detect anti-HBc IgM have been developed and shown to have different degrees of sensitivity and specificity. One of these assays, Corzyme-M (Abbott Laboratories, North Chicago, Ill.), recently became commercially available. The present study was undertaken to evaluate the clinical utility of this anti-HBc IgM test in establishing the diagnosis of acute hepatitis B using sera from a group of 42 prospectively followed individuals who had been exposed to hepatitis B virus. The Corzyme-M test was highly sensitive in detecting recent hepatitis B virus infection. All 30 patients with symptomatic and 12 with asymptomatic acute hepatitis B virus infection developed anti-HBc IgM. However, the timing of sample testing relative to onset of symptoms in symptomatic patients was important, inasmuch as 2 of 23 patients were negative for anti-HBc IgM early in the symptomatic period, although all were HBsAg positive. The duration of anti-HBc IgM positivity after acute infection was variable, ranging from 2 to 134 weeks. In 14% of patients, anti-HBc IgM remained detectable for more than 1 year. From the data, recommendations are given regarding the usefulness of anti-HBc IgM testing in the diagnosis of acute hepatitis B virus infection.

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