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Biomedical subjects

J Hoefs

Publications and source records attributed to J Hoefs.

18 recordsLinked to original sources
PubMed2005

Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club.

Sepsis is a systemic inflammatory response to the presence of infection, mediated via the production of many cytokines, including tumour necrosis factor (TNF-), interleukin (IL)-6, and IL-1, which cause changes in the circulation and in the coagulation cascade. There is stagnation of blood flow and poor oxygenation, subclinical coagulopathy with elevated D-dimers, and increased production of superoxide from nitric oxide synthase. All of these changes favour endothelial apoptosis and necrosis as well as increased oxidant stress. Reduced levels of activated protein C, which is normally anti-inflammatory and antiapoptotic, can lead to further tissue injury. Cirrhotic patients are particularly susceptible to bacterial infections because of increased bacterial translocation, possibly related to liver dysfunction and reduced reticuloendothelial function. Sepsis ensues when there is overactivation of pathways involved in the development of the sepsis syndrome, associated with complications such as renal failure, encephalopathy, gastrointestinal bleed, and shock with decreased survival. Thus the treating physician needs to be vigilant in diagnosing and treating bacterial infections in cirrhosis early, in order to prevent the development and downward spiral of the sepsis syndrome. Recent advances in management strategies of infections in cirrhosis have helped to improve the prognosis of these patients. These include the use of prophylactic antibiotics in patients with gastrointestinal bleed to prevent infection and the use of albumin in patients with spontaneous bacterial peritonitis to reduce the incidence of renal impairment. The use of antibiotics has to be judicious, as their indiscriminate use can lead to antibiotic resistance with potentially disastrous consequences.

Antibiotic Prophylaxis↗
PubMed1998

Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group.

BACKGROUND: Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy, but most subsequently relapse. We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS: We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment. A total of 173 patients were randomly assigned to receive standard-dose recombinant interferon alfa-2b concurrently with ribavirin (1000 to 1200 mg orally per day, depending on body weight) for six months, and 172 patients were assigned to receive interferon and placebo. RESULTS: At the completion of treatment, serum levels of hepatitis C virus (HCV) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone (82 percent vs. 47 percent, P<0.001). Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients (49 percent) in the combination-therapy group, but in only 8 patients (5 percent) in the interferon group (P<0.001). Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response. Base-line serum HCV RNA levels of 2 x 10(6) copies per milliliter or less were associated with higher rates of response in both treatment groups. Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group. Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone. CONCLUSIONS: In patients with chronic hepatitis C who relapse after treatment with interferon, therapy with interferon and oral ribavirin results in higher rates of sustained virologic, biochemical, and histologic response than treatment with interferon alone.

Adult↗
PubMed1995

Perfused Kupffer cell mass. Correlation with histology and severity of chronic liver disease.

The perfused Kupffer cell mass determines sulfur colloid distribution by liver spleen scan (LSS) and is proportional to the perfused hepatocyte mass. This accounts for the correlation of sulfur colloid distribution with tests of hepatic function and raises the question of whether the LSS can be used as a quantitative test of hepatic function. The recent ability to precisely measure sulfur colloid distribution by single-photon-emission computerized tomography (SPECT) prompted us to evaluate the clinical value in 329 consecutive patients with adequate LSS and clinical information, of which 27 apparent normals and 220 patients with chronic liver disease (CLD) were included in this study. The liver-bone marrow index (LBI) indicated the distribution of counts between the liver and bone marrow. The liver-spleen index (LSI) indicated the distribution between liver and spleen adjusted for spleen size. The LBI and LSI correlated with each other (r = 0.753; P < 0.001). The arithmetic mean of LBI and LSI was defined as the severity score. Detailed clinical evaluation was available in these patients and included 109 who had liver biopsy. A severity score in 27 normals was 102 +/- 5 (mean +/- SD) with all values > 85. The severity score correlated with hepatic fibrosis (r = -0.694; P < 0.001) in 109 patients with benign liver disease who had recent biopsies and with the Child-Pugh classification (r = 0.78; P < 0.001) in 220 patients with CLD.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1993

5-Methyltetrahydrofolate transport in basolateral membrane vesicles from human liver.

Transport of 5-methyltetrahydrofolate was studied in vesicles isolated from the basolateral membrane (BLM) of human liver. Uptake was mostly via transport into an osmotically active intravesicular space, with some membrane binding (approximately 20%). Transport was more rapid with an imposed pH gradient (pHout = 5.0, pHin = 7.5) as compared with either pHout = pHin = 5.0 or pHout = pHin = 7.5. Transport under the influence of a pH gradient showed a transient overshoot; uptake at 60 s was 4.2 times higher than at equilibrium (60 min). Transport in the presence of a pH gradient was saturable; apparent Km = 0.55 mumol/L and Vmax = 1.98 nmol.g protein-1.10 s-1. Transport was not saturable at pHout = pHin = 7.5. Transport was inhibited by the structural analogs 5-formyltetrahydrofolate, folic acid, and methotrexate, and was electroneutral in nature. These results suggest that 5-methyltetrahydrofolate transport in human BLM vesicles is via carrier-mediated cotransport with hydrogen ions.

Biological Transport↗
PubMed1993

Effect of chronic portal hypertension on glutamine transport across rat intestinal brush border and basolateral membranes.

The present study examined the effect of chronic portal hypertension on the intestinal transport of glutamine across the brush border membrane (BBM) and the basolateral membrane (BLM) of the rat enterocyte. Chronic portal hypertension was induced by partial portal vein ligation, and the results were compared with results in sham-operated rats. Transport studies were performed by using established techniques of isolated membrane vesicles. In chronic portal hypertensive rats, transport of glutamine in BBM vesicles (BBMVs) exhibited significant inhibition in the maximal velocity (Vmax) of both the Na(+)-dependent and the Na(+)-independent transport processes, with no significant changes in the apparent Michaelis-Menten constant (Km) of the carrier systems. Similarly, chronic portal hypertension caused a significant decrease in the Vmax of the Na(+)-dependent and the Na(+)-independent uptake processes in intestinal BLM vesicles (BLMVs), with no change in the apparent Km of the uptake systems. These changes in glutamine transport in BBMVs and BLMVs brought about by chronic portal hypertension are not due to differences in the relative purity of the vesicular preparations between the portal hypertensive and sham-operated rats, because similar degrees of enrichment and depurification of marker enzyme activities were seen in final vesicular preparations in the two rat groups. These results demonstrate that in chronic portal hypertension, glutamine transport across both poles of the enterocyte is impaired. At both the BBM and BLM domains, the impairment appears to be mediated via a decrease in the number (and/or activity) of the glutamine carrier systems, with no changes in their affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Biotin transport in human liver basolateral membrane vesicles: a carrier-mediated, Na+ gradient-dependent process.

The characteristics of biotin transport into human liver were examined using purified liver basolateral membrane vesicle (BLMV) preparations. Biotin uptake by BLMVs was mostly due to transport of the vitamin into the inside of vesicles. In the presence of an Na+ gradient (out greater than in), biotin transport with time was significantly higher than that in the presence of a K+ gradient and showed transient accumulation (overshoot). High concentrations of unlabeled biotin and related compounds caused significant cis inhibition in biotin transport in the presence of an Na+ (but not a K+) gradient. Transport of biotin as a function of concentration in the presence of an Na+ gradient included a saturable component, while it was lower and linear in the presence of a K+ gradient. Apparent Km and Vmax of the saturable Na+ gradient-dependent component were 1.22 mumol/L and 4.76 pmol.mg protein-1 x 10 s-1, respectively. Induction of a negative or positive intravascular potential using valinomycin-K diffusion methodology did not affect biotin transport into BLMVs. Also, neither the anion-exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid nor 4-acetamido-4-isothiocyanostilbene-2,2'-disulfonic acid caused significant inhibition in biotin transport. These results indicate that biotin transport into human liver occurs via a specialized, carrier-mediated transport system. This system is Na(+)-gradient dependent and transports the vitamin via an electroneutral process.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

Fatty infiltration of the liver: quantification with phase-contrast MR imaging at 1.5 T vs biopsy.

Quantification of hepatic fat content by application of MR phase-contrast imaging (Dixon method) at 1.5 T was compared with results of biopsy in 16 patients with a variety of liver abnormalities. Motion artifact was suppressed by employing six or eight averages of short TR in-phase (echo offset, 0 msec), out-of-phase (echo offset, 1.1 msec), and in-phase (echo offset, 2.2 msec) spin-echo pulse sequences. The 360 degree out-of-phase sequence was used to assess the impact of T2* decay on this method of estimating fat fraction. A standard two-echo long TR sequence also was obtained in all patients. Histologic preparations from the biopsy specimens were examined by a pathologist who had no knowledge of the MR results and were graded according to overall visual assessment as belonging to one of four categories of fat fraction. Results of the MR-calculated apparent fat fraction were compared directly with biopsy category and were also placed in MR fat fraction categories, allowing estimation of the statistical correlation between the biopsy and MR grading systems. Eight of eight patients with biopsy categories indicating a fat fraction of less than 0.25 were computed by MR to have a fat fraction of less than 0.1. Seven of eight patients with biopsy categories indicating a fat fraction of greater than 0.25 were computed by MR to have a fat fraction of at least 0.24. The MR-calculated apparent fat fraction category correlated significantly with the histologic biopsy category (r = .86, p less than .01). When compared with the in-phase image, decreased signal from liver was visually apparent on the 180 degree out-of-phase images in all cases in which the fat fraction was at least 0.24, but there was no indication of fatty liver on the standard T1- or T2-weighted images. Calculated T2 also showed no correlation with degree of fatty deposition. Correction for T2* decay by using the 360 degree out-of-phase acquisition in addition to the standard 0 degree and 180 degree out-of-phase images had little effect on fat fraction computation. Phase-contrast MR is a promising noninvasive method for quantitative assessment of fatty deposition in the liver.

Adult↗
PubMed1989

Geochemistry of Precambrian carbonates: II. Archean greenstone belts and Archean sea water.

Carbonate rocks with geological attributes of marine sediments are a minor component of the Archean greenstone belts. Despite their relative scarcity, these rocks are important because they record chemical and isotopic properties of coeval oceans. The greenstones containing such carbonates appear to cluster at approximately 2.8 +/- 0.2 and approximately 3.5 +/- 0.1 Ga ago. The samples for the younger group are from the Abitibi, Yellowknife, Wabigoon (Steep Rock Lake), Michipicoten and Uchi greenstone belts of Canada and the "Upper Greenstones" of Zimbabwe. The older group includes the Swaziland Supergroup of South Africa, Warrawoona Group of Australia and the Sargur marbles of India. Mineralogically, the carbonates of the younger greenstones are mostly limestones and of the older ones, ferroan dolomites (ankerites); the latter with some affinities to hydrothermal carbonates. In mineralized areas with iron ores, the carbonate minerals are siderite +/- ankerite, irrespective of the age of the greenstones. Iron-poor dolomites represent a later phase of carbonate generation, related to post-depositional tectonic faulting. The original mineralogy of limestone sequences appears to have been an Sr-rich aragonite. The Archean carbonates yield near-mantle Sr isotopic values, with (87Sr/86Sr)o of 0.7025 +/- 0.0015 and 0.7031 +/- 0.0008 for younger and older greenstones, respectively. The best preserved samples give delta 13C of +1.5 +/- 1.5% PDB, comparable to their Phanerozoic counterparts. In contrast, the best estimate for delta 18O is -7% PDB. Archean limestones, compared to Phanerozoic examples, are enriched in 16O as well as in Mn2+ and Fe2+, and these differences are not a consequence of post-depositional alteration phenomena. The mineralogical and chemical attributes of Archean carbonates (hence sea water) are consistent with the proposition that the composition of the coeval oceans may have been buffered by a pervasive interaction with the "mantle", that is, with the oceanic crust and the coeval ubiquitous volcanosedimentary piles derived from mantle sources.

Australia↗
PubMed1988

In vivo acoustic attenuation in liver: correlations with blood tests and histology.

Results of in vivo attenuation measurements in the liver have been obtained in 26 normal controls and in 51 patients with chronic diffuse liver disease. A modified real-time sector scanner was used for narrow-band amplitude attenuation examination. In the control group (people without apparent liver disease), a statistically significant correlation was found between acoustic attenuation in liver and two blood tests reflecting liver function: serum albumin (n = 24, r = 0.67, p = 0.002) and prothrombin time (n = 23, r = 0.63, p = 0.019). There was a statistically significant positive correlation between attenuation and fat for all biopsied patients (n = 51, r = 0.32, p = 0.023) and for patients with minimal fibrosis (n = 25, r = 0.45, p = 0.027). Although no correlation with fibrosis was found for all patients, in the group of patients with minimal fat there was a correlation with portal fibrosis (n = 33, r = 0.37, p = 0.035). This double blind prospective study shows that in the liver: (1) attenuation estimates appear correlated with clinical parameters (blood tests) in normal volunteers, and (2) large changes in fat affect narrow-band acoustic attenuation estimates to a greater degree than severe portal fibrosis in patients with chronic diffuse liver disease. Further research is needed before these estimates can become a clinical tool.

Fatty Liver↗
PubMed1986

Frequency-demodulated US: evaluation in the liver. Work in progress.

Frequency modulated (FM) imaging is a new ultrasound (US) modality that uses pulse-echo signal instantaneous frequency in addition to the conventional envelope information. Eight features of the FM image in nondiseased livers are described. The technique is evaluated in a study of 34 patients with biopsy-proved diffuse liver disease. Visual grading of FM US image features shows good correlation with levels of biopsy-graded hepatic fibrosis. Patients with diffuse parenchymal liver disease often exhibit evidence of the abnormality when FM liver imaging is used, while such evidence is not as well demonstrated with conventional envelope (AM) imaging.

Humans↗
PubMed1984

Effect of short-term bile duct ligation on peripheral blood steroids, urinary PGE2 and the rate of sodium excretion in male rabbits.

Short-term bile duct ligation in male rabbits resulted in a significant reduction in the rate of sodium excretion after saline challenge (10 ml/kg/hr for 4 hr, P less than 0.03). The reduction in the sodium excretory rate (14.3 +/- 7.8 to 6.3 +/- 5 mu-equiv/min, P less than 0.03) was associated with an increased urinary PGE2 excretion (200.9 +/- 174 to 731.8 +/- 1039.8 pg/min, P less than 0.01) without significant change in serum aldosterone and cortisol concentrations. Serum progesterone concentration increased (37.2 +/- 15.6 to 119.2 +/- 34.6 ng/dl, P less than 0.01) whereas serum 17-hydroxyprogesterone concentration declined after bile duct ligation suggesting the development of a 17-hydroxylase enzymatic block.

17-alpha-Hydroxyprogesterone↗
PubMed1981

Intraperitoneal coagulation in chronic liver disease ascites.

Twenty patients with the ascites of chronic liver disease were investigated for in vivo evidence of active coagulation within ascites by detection of fibrin monomer. Increased levels of fibrin monomer, increased fibrin/fibrinogen degradation products, and absent or low levels of fibrinogen in the ascites of all patients tested confirmed the presence of intraperitoneal coagulation when ascites is present.

Ascites↗
PubMed1978

[C13/C12 Ratios in human urinary calculi].

Oxalate, uric acid, and phosphate stones have been analyzed for their carbon isotope composition. The oxalate stones show delta13C values between -17.0 and -19.5%, the uric acid stones between -14.9 and -19.4%, and the phosphate stones between -13.0 and -23.9%. It is proposed that endogenic rather than exogenic sources are responsible for the 13C/12C ratios of the stones. The isotopic composition of the phosphate stones seems to be influenced primarily by bacterial activity.

Carbon Isotopes↗
PubMedDate not supplied

Hepatocellular carcinoma in young, mentally retarded HBsAg carriers without cirrhosis.

In a Californian institution for the mentally retarded, surveillance by autopsy of all deaths (n = 138) identified three cases of hepatocellular carcinoma. Hepatocellular carcinoma cases occurred in young (mean age = 26 years) male carriers of HBsAg and were not associated with cirrhosis. They were of the nonfibrolamellar oncocytic type and were rapidly fatal. Hepatocellular carcinoma incidence in HBsAg carriers was estimated to be 246 times greater than United States males.

Adult↗