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Biomedical subjects

J Ludwig

Publications and source records attributed to J Ludwig.

At least 181 records · Page 10Linked to original sources
PubMed1990

Effects of nisoldipine on stress-induced changes in haemodynamics and plasma catecholamines in normotensives and hypertensives.

In a double-blind, placebo-controlled crossover study 10 mg nisoldipine was given orally twice daily for 3.5 days to 12 normotensives and 12 essential hypertensives. In each study period, subjects were exposed to 6 min of physical exercise and 3 min of mental stress following the morning dose on day 3 and 4, respectively. Blood pressure, heart rate, systolic time intervals (day 3 only) and plasma levels of noradrenaline, adrenaline, dopamine as well as dihydroxyphenylglycol (DOPEG; the main presynaptic metabolite of noradrenaline) were determined at rest and at the end of both tests. Nisoldipine increased resting heart rate in normotensives and hypertensives, but reduced resting BP and BP during mental stress in hypertensives only. It also increased plasma concentrations of noradrenaline and DOPEG at rest and plasma noradrenaline concentrations during mental stress in both groups. However, nisoldipine affected neither exercise- nor stress-induced changes in any of the parameters monitored here. There was a correlation between the drug-induced percentage fall in resting BP and the height of BP during placebo treatment. While the resting values of plasma DOPEG were higher in hypertensives than in normotensives, those of plasma noradrenaline were not. Consequently, the linear relationship that existed between the resting plasma concentrations of DOPEG and noradrenaline in both groups was shifted to higher DOPEG levels in hypertensives when compared with normotensives. In conclusion, the effectiveness of nisoldipine in lowering BP was the more pronounced the higher the BP to begin with. Nisoldipine did not attenuate exercise- or stress-induced increases in plasma catecholamines. Essential hypertension may be associated with an enhanced presynaptic formation of DOPEG.

Adult↗
PubMed1990

The liver in autosomal dominant polycystic kidney disease. Implications for pathogenesis.

A histomorphometric and clinico-pathologic analysis of 26 autopsy cases of autosomal dominant polycystic kidney disease (ADPKD) showed that (1) the density of biliary microhamartomas (BMHs) and the stage of polycystic liver disease were strongly correlated, and (2) both were positively correlated with the stage of renal dysfunction and age at autopsy. Using multiple linear regression analysis, only the stage of renal dysfunction was significantly predictive of the density of BMHs, but both variables were simultaneously predictive for the stage of polycystic liver disease. On serial sections, 41.4% of cysts were connected to BMHs and 81.0% of BMHs to portal tracts. Bile-like material was found in 10.7% of BMHs. Flat or polypoid hyperplasia of the epithelium was observed in 2.7% of cysts. These results support the long-maintained view that hepatic cysts in ADPKD result from cystic dilatation of BMHs. They indicate, however, that the number of BMHs increases during life. These observations are consistent with the hypothesis that hepatic and renal cysts in ADPKD have similar pathogeneses, that BMHs and hepatic cysts result from hyperplasia of the bile duct epithelium, and that as they grow, the hepatic cysts become disconnected from the biliary ducts from which they are derived.

Adult↗
PubMed1990

UW solution improves duration and quality of clinical liver preservation.

Prolonged liver preservation (up to 17 hours) with UW solution had no adverse effect on perioperative blood loss or results of postoperative serum biochemistry studies. After use of this solution, biliary and vascular complications as well as evidence of histologic damage were less. The advantages of the extended preservation time permit liver transplantation to be done as a semi-elective procedure; more patients can be waiting at home instead of near the transplant center. The availability of UW solution also makes it possible to send grafts long distances throughout the nation. Furthermore, surgeons can arrange for backup patients in case the recipient proves to be inoperable. This capability should reduce organ wastage, even before the time limits of preservation with UW solution have been determined definitely. We feel that UW solution undoubtedly has improved both the duration and quality of liver graft preservation.

Adenosine↗
PubMed1990

Histologic diagnosis of rejection by using cystoscopically directed needle biopsy specimens from dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder.

To determine the histologic features of rejection and to identify nonrejection causes of human pancreatic allograft dysfunction, we analyzed 31 needle biopsy specimens (17 pancreatic, 14 duodenal) obtained under cystoscopic direction from 15 dysfunctional pancreatoduodenal allografts with exocrine drainage into the bladder. Eight allografts undergoing rejection showed the most common histologic features of rejection to be diffuse mixed inflammatory infiltrates of pancreatic acinar tissue and duodenum wall. Diffuse infiltration of pancreatic acinar tissue by neutrophils was the earliest histologic change in rejection. Seven dysfunctional allografts not undergoing rejection ("nonrejection") showed a normal pancreas or various changes including acinar dilation with inspissation of secretions, fibrosis, cytomegalovirus inclusions, and enzymatic necrosis. The histologic changes in the duodenum paralleled those in the pancreas in both rejection and nonrejection allografts. We conclude that the histologic features of rejection in pancreatoduodenal allografts are distinctive. The changes seen in biopsy specimens accurately reflect the state of the graft and can be used to diagnose rejection and to identify other causes of graft dysfunction. Biopsy samples from the duodenum as well as the pancreas are diagnostically useful. The biopsy findings can be used to guide the clinical management of rejection and in the development of other noninvasive tests for rejection.

Biopsy, Needle↗
PubMed1989

The nature of unexplained chronic aminotransferase elevations of a mild to moderate degree in asymptomatic patients.

To determine the nature of unexplained chronic serum aspartate aminotransferase elevations of a mild to moderate degree in asymptomatic patients, we performed systematic clinical, biochemical and histologic examinations in 47 individuals who had been screened for virus-, alcohol- or drug-related disease. Serum aspartate aminotransferase levels ranged from 3- to 8-fold normal (mean: 156 +/- 7 units per liter) for at least 6 months (mean: 30 +/- 6 months). Serum alanine aminotransferase levels were also increased but to a lesser degree in most patients. Thirty-four patients (72%) had histologic features of chronic active hepatitis, including 16 with cirrhosis. Ten patients (21%) had steatohepatitis and three (6%) had miscellaneous disorders. Patients with chronic active hepatitis and cirrhosis could not be distinguished from counterparts without cirrhosis by individual clinical or laboratory findings. Antinuclear or smooth muscle antibodies were detected in 18 of the patients with chronic active hepatitis (53%). All patients with steatohepatitis were women, and they had laboratory changes at presentation, including seropositivity for antinuclear antibodies, that overlapped with those of patients with chronic active hepatitis. We conclude that asymptomatic patients with unexplained chronic aspartate aminotransferase elevations of a mild to moderate degree frequently have chronic active hepatitis and that many have cirrhosis. Immunoserologic findings compatible with autoimmune hepatitis are commonly present. Steatohepatitis is the most frequent alternative diagnosis, especially in women, and it is not excluded by the presence of antinuclear antibodies. Differentiation of the disorders is possible only by histologic examination.

Adult↗
PubMed1989

Floxuridine-induced sclerosing cholangitis: an ischemic cholangiopathy?

A 43-year-old man underwent abdominoperineal resection of a rectal adenocarcinoma, and left hepatic lobectomy for a single metastasis. He then received hepatic artery infusions of floxuridine. The tumor did not recur, but sclerosing cholangitis and liver failure developed which necessitated orthotopic liver transplantation. In the hilus of the native liver, obstructive arteriopathy and portal venopathy were found. These lesions probably had been caused by drug-induced intravascular thrombosis. Thus, the sclerosing cholangitis that develops in many patients after floxuridine infusion may be ischemic rather than toxic. The patient described here is well, 14 months after orthotopic liver transplantation. Therefore, in some cases of floxuridine-induced cholangitis, liver transplantation appears to be indicated despite a history of metastasizing carcinoma.

Adult↗
PubMed1989

Primary sclerosing cholangitis: natural history, prognostic factors and survival analysis.

The natural history of primary sclerosing cholangitis was assessed in 174 patients; 37 were asymptomatic and 137 had symptoms related to underlying liver disease. At the time of diagnosis, the mean age was 39.9 years, 66% of the primary sclerosing cholangitis patients were male and 71% had associated inflammatory bowel disease, most commonly chronic ulcerative colitis. Long-term follow-up (mean: 6.0 years; range: 2.7 to 15.5 years) was available in all patients. During follow-up, 59 (34%) of the patients died: 55 in the symptomatic group and four in the asymptomatic group. Median survival from the time of diagnosis of primary sclerosing cholangitis at the Mayo Clinic was 11.9 years. Survival in the asymptomatic group was significantly decreased compared with that in a control population matched for age, race and sex. Multivariate analysis (Cox proportional hazards regression modeling) revealed that age, serum bilirubin concentration, blood hemoglobin concentration, presence or absence of inflammatory bowel disease and histologic stage on liver biopsy were independent predictors of high risk of dying. The development of a multivariate statistical survival model is a major step in identifying individual primary sclerosing cholangitis patients at low, moderate and high risk of dying. Such models will be useful for stratifying patients in therapeutic trials, in patient counseling and in patient selection and timing of liver transplantation.

Adult↗
PubMed1989

Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline.

The total body clearance and fractional extraction of isoprenaline (ISO) have been determined, and the relation between these parameters and cardiac output established. Whether desipramine, an inhibitor of neuronal uptake, altered the plasma catecholamine response to ISO was also investigated. Seven healthy subjects were given i.v., infusions of ISO in two, consecutive 25-min periods, at constant dose rates of 31-43 and 80-124 pmol.kg-1.min-1, respectively. The total-body (ER), pulmonary (ERp) and forearm (ERf) fractional extractions and the total body clearance (CL) of ISO were obtained from measurements of cardiac output and the steady-state ISO concentration in mixed central venous, arterial and forearm venous plasma. ISO-induced increases in cardiac output resulted in increases in CL, decreases in ER and no consistent change in ERf. ERp did not differ from zero. ISO also produced a dose-dependent increase in the mixed venous plasma concentrations of noradrenaline and 3,4-dihydroxyphenylglycol (DOPEG), and a decrease in that of adrenaline. Pretreatment with desipramine did not alter any of the pharmacokinetic parameters of ISO. Desipramine, however, reduced the mixed venous baseline plasma levels of noradrenaline (47%) and DOPEG (40%), and tended to reduce that of adrenaline (34%). It enhanced the plasma noradrenaline response 2.4-fold, abolished the plasma DOPEG response and did not alter the plasma adrenaline response to ISO. Hence, owing to its haemodynamic effects, ISO modifies its own pharmacokinetics which involve non-neuronal removal processes only. The increased DOPEG in plasma resulting from the ISO-induced increase in noradrenaline release was presynaptic in origin. Desipramine appears to reduce sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Hepatoportal arteriovenous fistula: morphologic features studied after orthotopic liver transplantation.

A 51-year-old woman underwent orthotopic liver transplantation because of a small-duct primary sclerosing cholangitis associated with chronic ulcerative colitis and a hepatoportal arteriovenous fistula. Arteriograms before liver transplantation and specimen arteriograms revealed a convolution of arteries in the right hepatic lobe which communicated with a massively dilated and partly thrombosed portal vein branch. The lesion was probably the result of a previous liver biopsy. Microscopic examination of the fistula and of specimens taken at a distance from the fistula showed prominent intimal fibroplasia of portal vein branches. The vascular changes were so severe that hepatic artery and portal vein branches closely resembled each other on routine sections. We are unaware of such a finding in other conditions and therefore believe that recognition of the described vascular abnormalities in liver biopsy specimens should lead pathologists to comment that an arterioportal fistula might be present.

Angiography↗
PubMed1989

An anatomy of the autopsy, Olmsted County, 1935 through 1985.

In this study, we examined in detail the patterns of autopsy rates for a half century (1935 through 1985) among residents of Olmsted County, Minnesota. The time trend of the autopsy in this community represents, in many respects, a microcosm of national trends. In the process of this analysis, we identified several medical and socioeconomic variables that may influence the rate of autopsy, including the age at death, physical location of death, gender, surgical procedures preceding death, immediate cause of death, and direct and indirect costs of the autopsy. In particular, the advancing mean age at death and the increase of the nursing home as a social phenomenon seem to have had a profound effect on autopsy rates both in Olmsted County and throughout the United States.

Adult↗
PubMed1989

Resurrecting the autopsy: benefits and recommendations.

Maintenance of high autopsy rates is associated with specific benefits, especially for clinical practice and for clinical and epidemiologic research. We have compiled and evaluated (on the basis of related costs and benefits) a comprehensive list of recommendations to resurrect the autopsy and reestablish it as a central contributor to medical practice, teaching, and research.

Autopsy↗
PubMed1989

The first 100 liver transplantations at the Mayo Clinic.

Between March 1985 and June 1987, the first 100 liver transplantations at the Mayo Clinic were performed in 83 patients (primarily adults). The most frequent diagnoses were chronic active hepatitis (in 24 patients), primary sclerosing cholangitis (in 22), and primary biliary cirrhosis (in 20). The median operating time was 406 minutes, and the median usage of erythrocytes was 13.2 units. A venovenous bypass was used in all patients older than 10 years of age. Hepatic artery thrombosis occurred in 10% of the 100 transplants. A choledochocholedochostomy was done in 58 patients and a choledochojejunostomy in 25 patients. Revision of the biliary anastomosis was necessary in 9 of the 83 patients (11%). Rejection, diagnosed by clinical and histologic criteria, occurred in 50 patients (60%) and was treated with a corticosteroid bolus, followed by OKT3 (monoclonal antibody) treatment if necessary. Selective bowel decontamination helped prevent infections; only 16 bacteremias occurred, 1 of which was caused by a gram-negative organism. Fungal infections were rare. Cytomegalovirus infection occurred in 47 patients (57%). Of the 83 patients, 16 required retransplantation, in 11 of whom graft rejection had occurred. One- and 2-year patient survival was 83% and 70%, respectively. Although problems still remain, liver transplantation is a reasonable option for patients with end-stage liver disease.

Academic Medical Centers↗
PubMed1989

Rapid shell vial culture and tissue histology compared with serology for the rapid diagnosis of cytomegalovirus infection in liver transplantation.

Sixty-six patients who had undergone 78 liver transplantations, with no detectable cytomegalovirus (CMV) infection before transplantation, were studied to assess the value of CMV serology compared with the rapid detection of the virus in shell vial cell cultures or histology for the diagnosis of (1) the first evidence of infection, (2) symptomatic disease, and (3) asymptomatic infection. Of 28 evaluable patients, shell vial cell culture assay and histologic findings provided the first evidence of CMV infection earlier in 22 (79%) or at the same time as the serologic response in 5 (18%). Serologic results yielded the first indication of CMV infection in only 1 of these 28 patients (3%). Of 17 evaluable transplantations in 15 patients in whom symptomatic invasive disease developed, shell vial culture or histology provided a laboratory diagnosis of CMV infection earlier or at the same time as serologic responses in 16 (94%). Similarly, shell vial culture or histology provided evidence of CMV infection in 10 of 11 patients (91%) who had asymptomatic CMV infection and remained asymptomatic. Urine surveillance cultures yielded the first evidence of CMV infection in 14 of 19 patients who initially had an asymptomatic infection, of which 6 became symptomatic. Culturing of the blood with use of the rapid shell vial technique showed that viremia preceded CMV organ involvement in 7 of 10 patients. We recommend culture by the shell vial assay as the most rapid and sensitive method of determining CMV infection in liver transplant patients.

Cytomegalovirus Infections↗
PubMed1989

Classification and terminology of hepatic allograft rejection: whither bound?

The current classification of hepatic allograft rejection recognizes "acute rejection" and "chronic rejection." Although these terms convey duration, implicitly they have been defined on the basis of their morphologic manifestations. This usage causes contradictions in reports and publications because features of "chronic rejection" may occur acutely and vice versa. In the future, biopsy reports, clinical communications, and, in particular, evaluation of treatment might benefit from use of a classification and terminology that more clearly distinguish clinical and morphologic findings and that reserve "acute" and "chronic" for describing the duration of episodes of rejection and terms such as "cellular rejection" or "arteriopathic rejection" for biopsy reporting. Severity should be graded independently for clinical, laboratory, and morphologic findings, inasmuch as an overall grading is not always meaningful--for example, severe cellular rejection may be mild in terms of prognosis, whereas histologically mild rejection may prove incurable. For an overall evaluation of graft rejection, adjectives such as "mild" or "severe" should be replaced or at least supplemented by terms that describe results of treatment and thus prognosis, and a designation should be added for duration and histology--for instance, "acute rejection, cellular, corticosteroid-responsive." Use of such a well-defined clinicopathologic classification of rejection and precise terminology might improve documentation and communication; it might even become a prerequisite for the evaluation of treatment trials.

Biopsy↗