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Biomedical subjects

R L Jenkins

Publications and source records attributed to R L Jenkins.

At least 73 records · Page 4Linked to original sources

Indications and technique for the use of the porto-renal shunt in the treatment of variceal hemorrhage.

Although hepatic replacement has emerged as the most definitive treatment for patients with chronic liver disease with variceal hemorrhage, a significant number of patients remain better served by porto-systemic shunting. Historically, for those patients with coexisting ascites requiring side-to-side shunting, synthetic or autogenous graft material has been interposed between the portal vein and inferior vena cava when the two veins could not be brought into direct apposition. The porto-renal shunt, described in 1964 but rarely used, allows shunt construction without the use of synthetic materials. Six patients who recently underwent porto-renal shunting are described in order to clarify the indications for the use of this technique and to describe the technical aspects of its construction.

Adult↗

Use of magnetic resonance angiography in the pretransplant evaluation of portal vein pathology.

The assessment of portal vein patency in patients selected as candidates for orthotopic liver transplantation should be accomplished noninvasively and with great accuracy. Magnetic resonance angiography (MRA) is a new technique that is completely noninvasive and is capable of graphically assessing portal vein anatomy and blood flow. In an attempt to establish the accuracy of portal venous MRA, 74 patients with established cirrhosis underwent abdominal MRA prior to liver transplantation. MRA findings were correlated with surgical findings at the time of transplantation in all patients, and were shown to be extremely accurate. The three-dimensional images generated by MRA and computer postprocessing allowed for correct identification of portal venous anatomy in all of the patients examined. We conclude that MRA is an extremely useful method of determining portal venous anatomy in potential liver transplant patients, and potentially offers greater definition and clarify compared with other non-invasive methods.

Humans↗

Biliary duct granular cell tumor: a rare but surgically curable benign tumor.

Granular [correction of Granulosa] cell tumors are rare benign tumors which may be found throughout the body. Rare cases are isolated within the biliary tree. If completely resected, surgical excision is curative. A case of biliary duct granular [correction of granulosa] cell tumor is presented with review of the world's literature on this topic.

Adult↗

Imaging of the portal venous system in patients with cirrhosis: MR angiography vs duplex Doppler sonography.

OBJECTIVE: To determine the relative performances of MR angiography and duplex Doppler sonography in the evaluation of the portal venous system in patients with portal hypertension, we compared two-dimensional time-of-flight MR angiography and duplex Doppler sonography in 60 sequential patients with cirrhosis. All 60 subsequently underwent liver transplantation. SUBJECTS AND METHODS: MR imaging and duplex Doppler sonography were performed on the same day, and in all patients the imaging findings were validated at surgical exploration. Five transplantation candidates had surgical portosystemic shunts in situ at the time of imaging. MR images were acquired during breath-holding, and flow in the portal vein was evaluated with presaturation bolus-tracking MR imaging. Sonography included color Doppler and pulsed gated Doppler images of the portal vein. MR angiograms and sonograms were analyzed independently and prospectively for patency of the portal vein, patency of surgical shunts, and grade and distribution of portosystemic collateral vessels. Scores on both imaging techniques were compared by using regression analysis. RESULTS: MR angiograms showed all five cases of portal vein occlusion and all 55 cases of patent portal veins. Sonograms showed three of five cases of portal vein occlusion and 52 of 55 cases of patent portal veins. The techniques concurred in assessing flow direction in 54 (90%) of 60 patients, and both procedures enabled detection of occlusive portal vein thrombus in one patient. We found a significant correlation (p < .001) between the grades of gastric varices detected with MR angiography and surgery but no significant correlation between the grades seen on sonography and found at surgery. Shunt patency in four of five patients and shunt occlusion in one were correctly assessed on MR angiograms, whereas three of these shunts were not visible on sonograms. CONCLUSION: Our results show that MR angiography is more reliable than duplex Doppler sonography for evaluating the portal venous system in patients with portal hypertension caused by cirrhosis.

Esophageal and Gastric Varices↗

[Quality of life following liver transplantation].

247 liver transplantations in 210 patients were done between June 1983 and April 1991 in our hospital. In this paper we have analyzed our experience with adult liver transplantation from the view point of quality of life after liver transplant. Indications for liver transplantation were the following: 46 patients with cirrhosis due to non A, non B hepatitis, 29 with alcoholic cirrhosis, 13 with hepatitis B, 34 with primary biliary cirrhosis, 26 with primary sclerosing cholangitis, 29 with acute hepatic necrosis, 10 with liver tumor, 13 with miscellaneous other diseases. Of the 210 patients, 125 are alive to date. One, three and five year survival rates (excluding perioperative death) of all patients were 80.2%, 70.6% and 65.45% respectively. The best rehabilitation is in 73 patients who are full time workers or full time students and in 16 patients who are homemakers. The degree of rehabilitation in these patients is very high: 6 patients died after achieving complete rehabilitation; 11 patients retired from employment after liver transplantation; 8 patients are chronically disabled; 79 patients died before rehabilitation could be achieved. Rehabilitation rates of one and five year survivors are 78% and 84.2% respectively. Quality of life has been satisfactory following liver transplantation.

Adolescent↗

Isolation and long-term culture of human hepatocytes.

Pressure-controlled perfusion of specimens of surgical hepatic resection produced improved yields of human hepatocytes for studies of long-term cultures. The effect of an extracellular matrix configuration on albumin secretion was evaluated by culture on a single layer of collagen or between double layers of collagen gel with Dulbecco's modified Eagle and Williams E media. Hepatocytes from 12 patients were maintained for more than 30 days, and in five of 12 experiments cells were cultured beyond 2 months. In the double gels the cells demonstrated typical polygonal liver cell morphology and higher albumin secretion (p < 0.01) up to 65 days; in contrast, in the single gels cells spread horizontally, and albumin secretion declined rapidly within 3 weeks. A comparison of media formulations showed that maximum albumin secretion occurred 5 days later but was maintained significantly longer with Dulbecco's medium (p < 0.01). The simple addition of a second layer of gelled collagen forming a collagen sandwich significantly stabilizes and supports the long-term culture of human hepatocytes.

Albumins↗

Studies on the acute lethality of diethylcarbamazine in the rat.

In spite of its effectiveness against microfilariae, very little is known about diethylcarbamazine's (DEC) therapeutic mechanism of action or the toxic sequelae which can result from overdose. In preliminary studies, a precipitous decrease in heart rate was noted in rats receiving 1000 mg DEC/kg ip. This effect was less pronounced at 750 mg/kg and was non-existent at 500 mg/kg. In the present study, attempts to attenuate DEC's cardiopulmonary insult by pretreating animals with cyproheptadine failed. Atropine pretreatment failed to block the negative chronotropic effects of DEC, but did restore respiratory function and reduce the lethality associated with the drug. Biochemical studies showed that ATP:ADP ratios in the hearts from rats given high dosages of DEC were elevated over those in controls (11:1 versus 5:1). Inosine levels decreased in cardiac tissues taken from DEC-treated rats. Subsequent enzyme studies revealed that DEC has a potent inhibitory effect on calcium-dependent ATPases from a variety of tissues. Taken together, our data indicate that the mode of acute DEC-lethality involves cardiopulmonary suppression. Furthermore, the cardiac depressant effect of DEC appears related to inhibition of calcium ATPases in cardiac myocytes. To our knowledge, this is the first report of ATPase sensitivity to DEC, a finding that has interesting toxicologic and pharmacologic ramifications.

Adenosine Diphosphate↗

Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases.

Careful patient selection for hepatic resection of colorectal cancer metastases is essential to improve current poor results. Carcinoembryonic antigen level and number of metastases were significant preoperative prognostic indicators of 5-year disease-free survival in patients selected clinically for hepatic surgery. Surgical margin, weight of hepatic tissue resected, carcinoembryonic antigen level, and flow cytometry were significant postoperative prognostic indicators. Patients with a carcinoembryonic antigen level less than 200 ng/mL, 1-cm surgical margins, and less than 1,000 g of liver tissue removed had a greater than 50% estimated 5-year disease-free survival rate. If the metastases were diploid on flow cytometry, an additional survival advantage may have been gained. Inadequate surgical margins led to high rates of liver-only recurrence. Nonhepatic recurrence was unrelated to surgical margins. Intraoperative liver examination by ultrasound during primary colon cancer resection and adjuvant chemotherapy may offer earlier selection of biologically appropriate patients and improved outcome; both recommendations require clinical trials.

Adult↗

The high-risk liver allograft recipient. Should allocation policy consider outcome?

The Boston Center for Liver Transplantation has accumulated one of the larger series of liver allograft recipients. This review has provided an opportunity to examine recent pronouncements by Medicare regarding patient selection and survival and to question whether the current allocation scheme best utilizes a scarce supply of donor liver allografts. Patients with primary biliary cirrhosis, sclerosing cholangitis, and metabolic derangements have enjoyed excellent survival: in aggregate, 78.9% at 1 year. In contrast, patients suffering from acute hepatic failure, patients requiring life support, or patients with primary graft failure who need a second liver transplant did poorly compared with other recipient groups: 45% 1-year survival. This center's experience reflects a more realistic expectation of patient survival because it considers the high-risk recipient by diagnosis and urgency status. This study also suggests that assessment of outcome should be a component of allocation planning in the future.

Adult↗

Liver transplantation for primary hepatic cancer.

Although early survival following transplantation for primary hepatic cancer is excellent, previously reported high recurrence rates have generally discouraged liver replacement for this indication. Since the inception of the Boston Center for Liver Transplantation (BCLT) in 1983, 33 of 383 (8.6%) liver allograft recipients have undergone orthotopic transplantation as definitive treatment for otherwise unresectable cancer. Diagnoses included hepatocellular carcinoma (HCCA) in 24 patients (73%), and cholangiocarcinoma (CHCA) in 9 patients (27%). Actuarial survival rates for patients with hepatocellular carcinoma were 71%, 56%, and 42% at 1, 2, and 3 years, respectively. The actuarial survival rates for patients with cholangiocarcinoma were 89% at 6 months, and 56% at 1, 2, and 3 years. Of the nine patients with cholangiocarcinoma, 56% (5/9) developed recurrent disease. Although this recurrence rate is disheartening, because of the lack of other morbidity, long-term survival in these patients is comparable to patients with HCCA. In contrast, recurrent hepatocellular carcinoma developed in 25% of recipients (5/20) who survived longer than 3 months posttransplantation. Other causes of death in patients with hepatocellular carcinoma included perioperative complications, 16.6% (4/24); sepsis, 8.3% (2/24); coronary artery disease, 4.2% (1/24); and lymphoma, 4.2% (1/24). Favorable prognostic factors included: primary tumor less than 3 cm in size and absence of associated cirrhosis. These results emphasize that orthotopic liver transplantation can provide a long-term cure for approximately 50% of patients whose primary hepatic malignancy is unresectable by conventional procedures.

Adenoma, Bile Duct↗

Combined liver and whole pancreas procurement in donors with a replaced right hepatic artery.

Aberrant donor arterial anatomy, such as a replaced right hepatic artery, is often considered a contraindication to combined liver and whole pancreas procurement for transplantation. With the increasing interest in transplantation of the pancreas and the demand for cadaver organs, methods for simultaneous procurement despite aberrant donor anatomy are essential. We describe the surgical techniques used successfully in six instances of combined liver and whole pancreas procurement in donors with a replaced right hepatic artery and suggest that a replaced right hepatic artery should not preclude simultaneous procurement in otherwise suitable donors.

Anastomosis, Surgical↗

Acute hepatic failure associated with oral minocycline: a case report.

A 39-year-old woman was evaluated for possible liver transplantation due to rapidly developing hepatic failure 4 weeks after initiation of oral minocycline 100 mg twice a day for the treatment of acne. The patient developed a maculopapular rash, malaise, fever, nausea, and vomiting 2 weeks prior to admission to the hospital. On admission, her symptoms rapidly progressed to liver failure characterized by rapidly rising liver enzyme levels, worsening encephalopathy, and coagulopathy. Viral hepatitis serologies and blood cultures were all negative. After intensive supportive care for 2 weeks, the patient's condition gradually improved and she was discharged with mildly elevated liver enzyme levels and pruritus, without need of liver transplantation. Minocycline-induced hepatic injury is an idiosyncratic reaction with a sensitization period that appears to be 3-4 weeks in duration. The characteristic features include rash, fever, lymphadenopathy, and eosinophilia, as well as severe alterations in liver function. The high liver enzyme levels and the significant prolongation of the prothrombin time suggest massive hepatocellular damage. In light of the profound liver damage that occurs with this adverse reaction, care should be taken in administering minocycline to patients who have concomitant liver disease. It is recommended that patients should be instructed as to the possible signs and symptoms of toxicity and be monitored for evidence of idiosyncratic reaction or liver failure.

Acne Vulgaris↗

Changes in AMP deaminase activities in the hearts of diabetic rats.

AMP deaminase from normal and diabetic rat hearts was separated on cellulose phosphate and quantitated by HPLC. From soluble fractions three different AMP deaminase activities, according to KCl elution from cellulose phosphate and percent of total activity were: 170 mM (85%), 250 mM (8%) and 330 mM (7%) KCl. The AMP deaminase activity which eluted with 170 mM KCl was resolved to two distinct peaks by HPLC anionic exchange. After 4 weeks of diabetes the heart enzyme profile change to: 170 mM (10%), 250 mM (75%) and 330 mM (15%). Once purified the four activities were kinetically distinct: 170 mM KCl cytosolic, AMP Km = 1.78, stimulated by ATP, GTP, NADP and strongly inhibited by NAD; 170 mM KCl mitochondria AMP Km = 17.9, stimulated by ATP, ADP; 250 mM KCl isozyme, AMP Km = 0.66, stimulated by ADP; and 330 mM KCl isozyme, AMP Km = 0.97, inhibited by ATP, NAD(P).

AMP Deaminase↗

Sequential interleukin 2 and interleukin 2 receptor levels distinguish rejection from cyclosporine toxicity in liver allograft recipients.

Previous studies of renal transplant recipients have demonstrated that allograft rejection is accompanied by an increase in plasma and urinary levels of interleukin 2 and its soluble receptor before the development of clinical symptoms. After measuring interleukin 2 and interleukin 2 receptor levels in the plasma, bile, and urine of liver transplant recipients, we found that rejection is preceded by elevation of plasma and biliary levels of both substances, that cyclosporine toxicity did not affect either of these levels, and that urinary levels of the substances are unaffected in either condition. Levels of interleukin 2 and interleukin 2 receptors increased in bile earlier than in plasma, and interleukin 2 levels did not overlap among stable patients and those experiencing rejection, whereas levels of interleukin 2 receptors did. Serial measurements of interleukin 2 levels, particularly in the product of the transplanted organ, provide a reliable assessment of the immunologic status of the allograft.

Bile↗

Surgical management of nonparasitic cystic liver disease.

We report clinical features, surgical management, recurrences, and follow-up study of 12 patients with simple hepatic cyst, 11 patients with polycystic liver disease, and 19 patients with cystadenoma who were surgically treated over a 25-year period. The median age of patients was 48 years, and 37 women and 5 men were in the series. The most common presenting symptom and physical finding were chronic abdominal pain and tenderness in the right upper quadrant. The most commonly associated disease was polycystic kidney disease, which was an associated finding in 5 of the 11 patients with polycystic liver disease (45%). The most valuable diagnostic studies in all groups were computed tomography and ultrasonography. The location of the disease was bilobar in patients with polycystic liver disease, with a right lobe predominance in 18% of patients. The right lobe was also predominant in 83% of patients with simple hepatic cyst and 58% of patients with cystadenoma. Of all solitary cystic lesions in the left lobe, 75% of them were cystadenomas. Of the 66 surgical procedures performed, aspiration was associated with a failure rate of 100%; partial excision, a failure rate of 61%; and total excision and liver resection, a failure rate of 0%. Orthotopic liver transplantation was performed in three patients and was associated with two early deaths. Partial excision relieved symptoms in three patients (43%) with polycystic liver disease. Total excision, enucleation, or liver resection with cyst(s) is the treatment of choice for non-parasitic cystic lesions of the liver.

Adult↗

Histopathology of the donor gallbladder removed at orthotopic liver transplantation: correlation with graft function.

The histopathology of 50 consecutive donor gallbladders removed during orthotopic liver transplantation was reviewed and correlated with graft function. Multiple sections of the gallbladders were examined for the presence of mucosal congestion, hemorrhage, and necrosis, without prior knowledge of the clinical outcome. Each pathologic feature was graded as absent (0), involving less than 10% (1+), 10% to 50% (2+), or more than 50% (3+) of the histologically examined mucosa. Graft function was determined by two transplant surgeons, a poor diagnosis being worsening of liver function tests associated with declining mental status and resulting in immediate retransplantation or early postoperative death; all others were categorized as good. Of 39 patients with good graft function, 18 had normal donor gallbladders, 11 had congestion only, and 10 had hemorrhage and/or necrosis. Of 11 patients with poor graft function, eight had hemorrhage and/or necrosis (2+ in seven), three had congestion only, and none had a normal gallbladder mucosa. Congestion alone was found to be a poor predictor of graft damage. Presence of any grade of hemorrhage and/or necrosis in donor gallbladders as related to poor liver graft function had a sensitivity of 73%, a specificity of 74%, a positive predictive value of 44%, and a negative predictive value of 91%. When hemorrhage and/or necrosis of 2+ severity was separately grouped and correlated with poor graft function, the specificity rose to 97% and the positive predictive value to 88%, and the negative predictive value was similar at 90%. We conclude that donor gallbladders often show mucosal abnormalities consisting of varying degrees of congestion, hemorrhage, and necrosis. The finding of hemorrhage and/or necrosis affecting more than 10% of the mucosa appears to be a specific lesion of ischemic damage that correlates highly with poor liver graft function.

Gallbladder↗

Experimental hyperthermia: protective effect of oxygen carrying fluorocarbon and crystalloids intraperitoneally.

The treatment of hyperthermia produced by passive warming was studied in anesthetized rats weighing 250-300 grams. In the first set of seven experiments, the authors found that venous blood oxygen fell as core temperature rose. Intraperitoneal injection of 20 ml of the oxygen carrying fluorocarbon (perfluorotributylamine, FC-43) emulsion in three of the animals shifted the curve to the right improving venous oxygen content (p less than 0.1). In the second series of experiments, a catheter was placed in the carotid artery. This catheter was attached to a pressure transducer for continuous recording of blood pressure and heart rate. Periodic blood samples were removed for measurement of blood gases, pH, and lactate. Four of the animals received 20 ml of isotonic saline, three received 20 ml of FC-43 emulsion both given intraperitoneally, and four served as controls. In the control group, there was an increase in systolic blood pressure and heart rate which peaked at a colon temperature of 42 degrees C, followed by cardiovascular collapse and death around 43 degrees C. Arterial PO2 (corrected for temperature) remained relatively constant up to 42 degrees C, and then fell. The arterial PCO2 rose sharply when the core temperature exceeded 43 degrees C. Arterial lactate content began to increase at 42 degrees C and above 43 degrees C was 2.5 fold elevated. Isotonic saline provided circulatory support but did not change the hypoxia or mixed acidosis from CO2 and lactate above 43 degrees C. FC-43 emulsion decreased hypoxia and improved circulatory performance but was associated with a mild respiratory alkalosis as arterial PCO2 fell.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Serologic and DNA follow-up data from HBsAg-positive patients treated with orthotopic liver transplantation.

Fifteen hepatitis B surface antigen (HBsAg) positive patients treated with orthotopic liver transplantation were studied to determine whether any clinical, serologic, or histologic data were predictive for recurrent hepatitis B infection leading to graft failure. Six patients died early, one due to primary graft nonfunction and the remaining five due to septic complications. There were nine patients surviving longer than two months, eight of whom are alive at a mean follow-up of 556 days. HBsAg and hepatitis B core antibody (anti-HBc) reappeared in the sera of all survivors after a variable transient period of clearance. One patient died 3 months posttransplant of fungal sepsis and was found to have histologic evidence for recurrent hepatitis and positive immunoperoxidase staining postmortem. The remaining eight survivors are home and clinically well, with no histologic evidence of hepatitis. Seven of these eight patients have hepatitis B viral DNA in their sera. We conclude that while there is a high early mortality, usually from sepsis, none of the serologic, histologic, or DNA data analyzed can be used to predict graft loss from recurrent hepatitis. No grafts have been lost due to recurrent hepatitis B in this series, and therefore we believe that HBsAg positive patients should not be excluded from transplantation.

Adult↗