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Biomedical subjects

J Ludwig

Publications and source records attributed to J Ludwig.

At least 73 records · Page 4Linked to original sources

Anatomy of the human biliary system studied by quantitative computer-aided three-dimensional imaging techniques.

The branching geometry of the normal, cholangiographically identifiable human biliary tree was studied with an innovative computer-aided three-dimensional (3D) imaging technique. In addition, a serially sectioned conventional paraffin block from a normal donor liver was used to create and quantitatively study a microscopic 3D image. Finally, a geometric model was developed to estimate the enlargement of biliary surfaces imparted by microvilli. The images created by these techniques could be viewed in stationary modes or rotating around any preselected axis. Approximately 7 (+/-3) intrahepatic duct orders were cholangiographically identified. Computerized measurements of the images from three normal livers suggested that the mean total volume of duct orders 1 to 7 shown in the cholangiograms was 16.6 cm3. The volume of the entire macroscopic duct system was estimated to be between 14 and 24 cm3 (mean, 20.4 cm3), with an internal surface of 336 to 575 cm2 (mean, 398 cm2). A geometric model based on electron micrographs suggested that this surface is magnified approximately 5.5-fold by the presence of microvilli. Volume and surface area (SA) measurements of all ducts in the same orders increased nearly exponentially from the first toward the seventh branching order (i.e., from the hilus toward the periphery of the liver), and probably beyond. The microscopic computerized reconstruction of a septal bile duct with its tributaries also allowed volume measurements; the imaged duct system represented 2.7% of the portal tract volume. The data presented herein may help to better evaluate branching patterns of the biliary tree and, eventually, the quantitative aspects of site-restricted cholangiocyte function and their role in the development of biliary diseases.

Biliary Tract↗

[Management of old neglected posttraumatic acromioclavicular joint instability and arthrosis].

UNLABELLED: Resection arthroplasty of the AC joint was performed in 42 cases of osteoarthrosis and residual instability of traumatic origin including 26 shoulders with horizontal instability of more than half of the width of the clavicula and lesions of the deltotrapezoid fascial complex (Rockwood type II: 7; type III: 9; type IV: 17; type V: 9). 23 cases were treated with a sole Weaver-Dunn procedure. 26 cases with horizontal instability and lesions of the deltotrapezoid fascia (Rockwood IV and V type) were treated in 7 cases with the standard Weaver-Dunn procedure and in 19 cases with a modified Weaver-Dunn procedure in combination with a coracoclavicular (3 x 1) and acromio-clavicular (1 x 1) 1 mm PDS string augmentation and double breasting fascioplasty of the deltotrapezoid complex. RESULTS: Successful results (in Patte-Score) after a minimum follow-up of 2 years (mean: 32 months) were reached in 88.4% of cases with only Weaver/Dunn procedure with a significant difference of good and excellent results in the horizontally stable group (93.8%) versus the horizontally unstable group (57.2%). In the group with horizontal instability and Weaver-Dunn procedure and complex additional stabilization with fascioplasty and PDS augmentation, 89.5% excellent and good results were found. CONCLUSION: Cases with horizontal instability (type Rockwood IV and V) seem to be over-represented among patients with failed conservative treatment. Resection arthroplasty with ligament transposition after Weaver/Dunn gives excellent results in posttraumatic osteoarthrosis with mainly vertical and moderate horizontal instability. In cases with advanced horizontal instability after Rockwood IV and V injuries, almost equal results can be reached by an additional coracoclavicular and acriomioclavicular PDS augmentation with deltotapezoid fascioplasty.

Acromioclavicular Joint↗

Port-Access coronary artery bypass grafting with the use of cardiopulmonary bypass and cardioplegic arrest.

BACKGROUND: To reduce surgical trauma, we performed minimally invasive Port-Access (Heartport Inc, Redwood City, CA) coronary artery bypass grafting with cardiopulmonary bypass and cardioplegic arrest. METHODS: Thirty-six men and 6 women with a median age of 59 years (range, 31 to 75 years) and isolated lesions of the left anterior descending branch of the coronary artery underwent Port-Access coronary artery bypass grafting. A small (6- to 9-cm) incision was made parasternally on top of the fourth rib. The left internal thoracic (mammary) artery was dissected and taken down through the minithoracotomy either alone or using an additional thoracoscopic approach. Cardiopulmonary bypass was instituted through femoral cannulation, and an additional endoarterial balloon catheter (Heartport Inc) was introduced into the ascending aorta for aortic occlusion, aortic root venting, and the delivery of cold antegrade crystalloid cardioplegia. After cardioplegic arrest, the left internal mammary artery was anastomosed to the left anterior descending artery under direct vision. RESULTS: The median left internal mammary artery takedown time was 49.5 +/- 21.9 minutes, the duration of cardiopulmonary bypass was 59.5 +/- 32.8 minutes, the aortic occlusion time was 28.5 +/- 7.9 minutes, the intensive care unit stay was 1.0 +/- 3.2 days, and the total hospital stay was 5.0 +/- 2.5 days. Intraoperative angiograms were done in the first 10 patients and showed patent left internal mammary artery grafts without anastomotic complications in all cases. Two arterial dissections, including one aortic dissection, were observed in patients with preexisting peripheral vascular disease. The other complications were minor. All but 1 patient recovered well, with no major limitations in their daily activities. CONCLUSIONS: Using this minimally invasive method, sternotomy-related complications can be avoided, the hospital stay can be reduced, and a safe coronary artery bypass grafting procedure can be performed with the advantage of cardiopulmonary bypass and cardioplegic arrest as are used routinely in conventional coronary artery operations.

Adult↗

The gender gap in reporting household gun ownership.

OBJECTIVES: This study examined errors in estimating household gun ownership that result from interviewing only 1 adult per household. METHODS: Data from 2 recent telephone surveys and a series of in-person surveys were used to compare reports of household gun ownership by husbands and wives. RESULTS: In the telephone surveys, the rate of household gun ownership reported by husbands exceeded wives' reports by an average of 12 percentage points; husbands' reports also implied 43.3 million more guns. The median "gender gap" in recent in-person surveys is 7 percentage points. CONCLUSIONS: Future research should focus on respondents' reports about personally owned guns.

Adult↗

Idiopathic adulthood ductopenia: an update.

Idiopathic adulthood ductopenia (IAD), named only 10 years ago, is the latest entity to join the group of small-duct biliary diseases. On the basis of published data and my consultation practice, I am aware of 57 cases. Most commonly, IAD affects young or middle-aged adults (overall range of affected patients, 15 to 77 years) and occurs with a distinct male preponderance. The median age of male and female patients among 48 published and unpublished cases was 30 and 36 years, respectively (in 9 cases, the precise age had not been stated). The age range probably encompasses several etiologic groups with different age distributions. Biopsy specimens, by definition, show ductopenia and its complications but no other lesions. Laboratory studies reveal a cholestatic profile, but again, by definition, these cases show no changes that would be diagnostic or suggestive of another biliary disease. In approximately half the published cases in which the outcome was reported, the condition seemed to have a benign course; in contradistinction, the other cases of IAD were fatal or necessitated liver transplantation. Indirect evidence suggests that IAD is a syndrome with several causes, including (1) late-onset nonsyndromic paucity of intrahepatic bile ducts, (2) small-duct primary sclerosing cholangitis ("pericholangitis") without large duct involvement and without evidence of inflammatory bowel disease, (3) nonsuppurative viral cholangitis--for instance, in hepatitis C, and (4) autoimmune cholangitis or cholangitis in autoimmune hepatitis, in the absence of the typical autoantibodies (cryptogenic chronic hepatitis). For progressive cases of IAD, liver transplantation is necessary, whether or not a specific cause is suspected.

Adult↗

RERG is a molecular correlate of the inward-rectifying K current in clonal rat pituitary cells.

The rat homologue of the human ether-ä-go-go-related gene (r-erg) was cloned from rat brain using homology screening. RERG has a 96% amino acid identify to HERG. Membrane currents recorded in CHO cells after previous injection of r-erg showed that the voltage- and time-dependent properties are indistinguishable from h-erg-induced currents expressed in the same system. RT-PCR revealed the presence of r-erg mRNA in clonal rat pituitary cells (GH3/B6 cells). These cells exhibit a voltage-dependent inward-rectifying K current (IK, IR) which is highly sensitive to the class III antiarrhythmic E-4031. IK, IR recorded in GH3/B6 cells and ERG currents in CHO cells were compared using similar experimental conditions (same pulse protocols and isotonic KCl as extracellular solution). The voltage- and time-dependent properties of both currents were found to be almost identical. These results strongly suggest that RERG channels mediate IK, IR in GH3/B6 cells.

Amino Acid Sequence↗

Carboxy-terminal domain mediates assembly of the voltage-gated rat ether-à-go-go potassium channel.

The specific assembly of subunits to oligomers is an important prerequisite for producing functional potassium channels. We have studied the assembly of voltage-gated rat ether-à-go-go (r-eag) potassium channels with two complementary assays. In protein overlay binding experiments it was shown that a 41-amino-acid domain, close to the r-eag subunit carboxy-terminus, is important for r-eag subunit interaction. In an in vitro expression system it was demonstrated that r-eag subunits lacking this assembly domain cannot form functional potassium channels. Also, a approximately 10-fold molar excess of the r-eag carboxy-terminus inhibited in co-expression experiments the formation of functional r-eag channels. When the r-eag carboxy-terminal assembly domain had been mutated, the dominant-negative effect of the r-eag carboxy-terminus on r-eag channel expression was abolished. The results demonstrate that a carboxy-terminal assembly domain is essential for functional r-eag potassium channel expression, in contrast to the one of Shaker-related potassium channels, which is directed by an amino-terminal assembly domain.

Amino Acid Sequence↗

Amino terminal-dependent gating of the potassium channel rat eag is compensated by a mutation in the S4 segment.

1. Rat eag potassium channels (r-eag) were expressed in Xenopus oocytes. They gave rise to delayed rectifying K+ currents with a strong Cole-Moore effect. 2. Deletions in the N-terminal structure of r-eag either shifted the activation threshold to more negative potentials and slowed the activation kinetics (delta 2-190, delta 2-12 and delta 7-12) or resulted in a shift to more positive potentials and faster activation kinetics (delta 150-162). 3. The impact of the deletion delta 7-12 was investigated in more detail: it almost abolished the Cole-Moore effect and markedly slowed down channel deactivation. 4. Unlike wild-type channels, the deletion mutants delta 7-12 exhibited a rapid inactivation which, in combination with the slow deactivation, resulted in current characteristics which were similar to those of the related potassium channel HERG. 5. Both the slowing of deactivation and the inactivation induced by the deletion delta 7-12 were compensated by a single histidine-to-arginine change in the S4 segment, while this mutation (H343R) only had minor effects on the gating kinetics of the full-length r-eag channel. 6. These results demonstrate a functional role of the N-terminus in the voltage-dependent gating of potassium channels which is presumably mediated by an interaction of the N-terminal protein structure with the S4 motif during the gating process.

Amino Acid Sequence↗

Lumbar epidural perineural injection: a new technique.

Two controlled studies for a new epidural, perineural, single-shot, selective nerve root injection with a double-needle approach to the anterior epidural space of the lumbar spinal canal are presented. The results were analysed to determine the effectiveness of the new epidural perineural injection technique. The trial comprised two controlled studies on 182 patients. One study compared prospectively randomized results of patients with lumbar radicular syndromes who received epidural perineural injections (n = 47), conventional posterior epidural injections (n = 40) and, as a control group, paravertebral local anaesthetic (n = 46). A second, prospective, double-blind study compared the effect of epidural perineural injections with triamcinolone (n = 24) and pure saline (n = 25). Epidural perineural injections were more effective than conventional posterior epidural injections. Both epidural groups had better results than the paravertebral local injection group. Epidural perineural injections with steroids (10 mg triamcinolone) were more effective than saline alone. A systemic steroid effect was excluded by additional intramuscular steroid injections in the saline group. There were no severe complications or side effects in any of the three groups. The studies concluded that single-shot epidural perineural injection is effective in the treatment of lumbar radicular pain. It is a "one drop only" therapy to the source of pain.

Double-Blind Method↗

[Injection treatment of non-radicular lumbalgia].

Low back pain is the most expensive condition in industrialized countries. Approximately 65-80% of the population will be afflicted with low back pain at some point during their life. Low back pain has many causes and can originate from any of several pain-sensitive foci, among which are facet joints, sacroiliac joint, muscle and ligaments. Primary care in the acute phase consists of nonsteroidal anti-inflammatory drugs to address the biochemical and inflammatory mediators of pain or skeletal muscle spasmolytics to reduce low back pain symptoms. Injection procedures should be reserved for the patients with low back pain who fail to respond to a directed, conservative treatment trial and have had pain for at least 2 weeks duration. Eliminating sensation from a certain pain source has been proposed as a way to allow an examiner to determine if that joint is responsible for the patient's pain. Injections of local anesthetic into the facet joint or around its nerve supply are clinical methods of eliminating pain from focal areas such as facet joints or myofascial trigger points. When a particular joint is determined to be the source of pain, long-term relief can be sought by directing therapeutic interventions at that joint. The anatomic accessibility of the most common pain sources of low back pain make diagnostic blocks and therapeutic instillation of corticosteroids particularly appealing. If used, their potential benefit for the individual case needs to be carefully weighed. They should be used to facilitate more aggressive conservative care and not as an isolated treatment. Certainly, if response to corticosteroids does not occur after the first injection, no further administration of corticosteroids is indicated.

Adrenal Cortex Hormones↗

The pathobiology of biliary epithelia.

Our understanding of the pathobiology of biliary epithelia is rapidly growing because of a surge of investigative activity. This became possible after suitable experimental models and techniques were developed with which to study cholangiocyte biology. Although the molecular mechanisms of bile formation by cholangiocytes and the role of these cells as a major cellular target in a variety of severe hepatobiliary diseases are currently being investigated, many questions remain unanswered, particularly regarding cholangiocellular functions, both in normal and abnormal conditions. As current experimental models become more refined, scientists with interests as diverse as cell biology and physiology, morphology, pharmacology, immunology, genetics, and oncology can be expected to further clarify the pathobiology of biliary epithelia.

Autoimmune Diseases↗

Are patients with cirrhotic stage primary sclerosing cholangitis at risk for the development of hepatocellular cancer?

BACKGROUND/AIMS: The risk of cholangiocarcinoma in primary sclerosing cholangitis is widely recognized to be 8-30%, whereas the risk of acquiring hepatocellular carcinoma in primary sclerosing cholangitis is unknown. As in other chronic liver diseases, the presence of hepatocellular carcinoma in a patient with primary sclerosing cholangitis undergoing evaluation for orthotopic liver transplantation would clearly impact on the candidacy, diagnostic evaluation, and alternative treatment options. Thus, the aim of our study was to determine the prevalence of hepatocellular carcinoma in patients undergoing liver transplantation for primary sclerosing cholangitis. METHODS: The records of the 520 patients undergoing orthotopic liver transplantation at our institution between 1985 and May 1995 were reviewed. Of the 134 patients with primary sclerosing cholangitis, three (2%) had hepatocellular carcinoma. In the 386 patients without primary sclerosing cholangitis undergoing orthotopic liver transplantation, 22 (6%) had hepatocellular carcinoma. RESULTS: Neither the duration of primary sclerosing cholangitis (range 7-23 years) nor the presence of ulcerative colitis (two of three patients) distinguished those patients with primary sclerosing cholangitis plus hepatocellular carcinoma from those with primary sclerosing cholangitis alone. None of the three patients with primary sclerosing cholangitis plus hepatocellular carcinoma had evidence for hepatitis B or C, alpha-1-antitrypsin deficiency, or hemochromatosis. None of the tumors was of the fibrolamellar variety of hepatocellular carcinoma. CONCLUSIONS: The prevalence of hepatocellular carcinoma in patients with primary sclerosing cholangitis undergoing orthotopic liver transplantation is 2%. These data suggest that patients with advanced cirrhotic-stage primary sclerosing cholangitis are at increased risk for developing hepatocellular carcinoma and should be screened for hepatocellular carcinoma as well as for cholangiocarcinoma prior to orthotopic liver transplantation.

Adolescent↗

Hemosiderosis in cirrhosis: a study of 447 native livers.

BACKGROUND & AIMS: Hemosiderosis may have a detrimental effect on some chronic liver diseases. The aim of this study was to determine the prevalence and diagnostic implications of hemosiderosis in cirrhosis. METHODS: Tissue iron in 447 cirrhotic livers was studied histologically and chemically. RESULTS: Positive iron staining was found in 145 cases (32.4%), and increased chemical hepatic iron concentration was found in 91 cases (20.3%), including 38 cases (8.5%) with hepatic iron overload in the hemochromatosis range, defined by an iron index of > or = 1.9 (iron index equals hepatic iron concentration in micromoles per gram divided by age). However, homozygous hemochromatosis seemed to have caused the cirrhosis in only 5 instances. Stainable iron was found in 22%-67% of the cases with nonbiliary cirrhosis but in only 7%-20% of cases with biliary cirrhosis. Most available pretransplant biopsy specimens failed to show evidence of homozygous hemochromatosis. CONCLUSIONS: Iron overload is very common in many types of nonbiliary cirrhosis but rare in biliary cirrhosis. The hemosiderosis of affected livers seems to be acquired and to occur rapidly once cirrhosis has developed; cirrhosis alone may cause iron accumulation. In the presence of cirrhosis, hepatic iron indices of >1.9 should not be interpreted as proof of homozygous hemochromatosis.

Adult↗

Review: nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a reasonably well-defined clinicopathological entity; it has been reported more commonly in women than in men or children of both sexes and it appears to be most closely associated with obesity, diabetes mellitus and related abnormalities, such as hyperlipidaemia and hyperglycaemia. However, the association with female gender, obesity and diabetes may not be as close as suggested by the literature and an underlying condition cannot be discerned in all cases. The natural history of the disease is poorly understood; the associated biopsy features span a wide spectrum, reaching from uncomplicated, clinically non-progressive fatty liver (not NASH in a strict sense) to a slowly progressive fatty liver with inflammation and fibrosis, to steatohepatitis with submassive hepatic necrosis, which has a subfulminant course and is often fatal. Non-progressive fatty liver appears to be very common but is of little clinical importance. The slowly progressive form of the disease represents NASH as encountered by most clinicians and pathologists. It is a common liver disease in current practice; patients may present with cirrhosis and even HCC arising from steatohepatitic cirrhosis. Subfulminant NASH has become exceedingly rare because many clinicians are now aware of the hazards of sudden weight loss, particularly in morbidly obese patients. Treatment options for NASH are still limited. The promotion of gradual weight loss in obese patients is the most widely recommended therapy but, unfortunately, this is very difficult to achieve. Avoidance of precipitous weight loss and careful control of diabetes mellitus are important and undisputed parts of patient management. Administration of UDCA as a treatment of NASH is still under study; it may be effective in some patients. The treatment of established steatohepatitic cirrhosis does not differ substantially from that of other types of cirrhosis and includes orthotopic liver transplantation.

Diabetes Complications↗

Flawed gun policy research could endanger public safety.

A highly publicized recent study by Lott and Mustard concludes that laws easing restrictions on licenses for carrying concealed firearms in public substantially reduce violent crime. Several serious flaws in the study render the authors' conclusions insupportable. These flaws include misclassification of gun-carrying laws, endogeneity of predictor variables, omission of confounding variables, and failure to control for the cyclical nature of crime trends. Most of these problems should bias results toward overestimating the crime-reducing effects of laws making it easier to carry concealed firearms in public. Lott and Mustard's statistical models produce findings inconsistent with criminological theories and well-established facts about crime, and subsequent reanalysis of their data challenges their conclusions. Public health professionals should understand the methodological issues raised in this commentary, particularly when flawed research could influence the introduction of policies with potentially deleterious consequences.

Confounding Factors, Epidemiologic↗

Chromaffin granule membrane glycoprotein IV is identical with Ac45, a membrane-integral subunit of the granule's H(+)-ATPase.

Glycoprotein IV of bovine adrenal chromaffin granule membranes was purified by membrane fractionation with Triton X-114 and lectin affinity chromatography. An antiserum raised against this protein recognized the same component as one directed against subunit Ac45 of the proton-translocating adenosine triphosphatase in the granule membrane. Amino acid sequencing confirmed that glycoprotein IV and Ac45 are identical proteins, and also showed that they are derived from a larger precursor by removal of a 246-amino acid N-terminal sequence. Enzymatic deglycosylation indicated an apparent polypeptide molecular mass of 29 kDa for the mature Ac45/glycoprotein IV. Blue Native electrophoresis confirmed that this protein is a component of the membrane sector of the V-ATPase.

Adrenal Medulla↗