bluuebunny/crossref_metadata_2025 huggingface dataset:
The [14C‐N‐methyl]‐erythromycin breath test dosimetry complies with the French regulations for radiation safety
Authors: Salvat Cécile , Mouly Stéphane , Rizzo‐Padoin Nathalie , Knellwolf Anne‐Laure , Simoneau Guy , Duet Michèle , Nataf Valérie , Bailliart Olivier , Bergmann Jean‐François
Published: June 2003

The [14C‐N‐methyl]‐erythromycin breath test (14C‐ERMBT) is one of the most valuable probes for liver cytochrome P450‐3A4 activity in humans. In order to extend the use of this test in France, we herein provide safety data regarding either patient dosimetry or worker exposure to [14C‐N‐methyl]‐erythromycin. In order to determine the maximum radiation exposure for patient and nuclear medicine technician following one intravenous 14C‐ERMBT [111 kiloBequerel (kBq)], we have used the dosimetric data gathered in animal studies and extrapolated to humans using a weight‐based method, approximate data provided by the French Society of Radioprotection and erythromycin pharmacokinetics in humans, considering always the worst conditions for the patient and worker exposure determination. The radioactivity administered to a patient after one 14C‐ERMBT was equal to 108.8 kBq (i.e. 98% of the total radioactivity in the 14C‐erythromycin vial) leading to a patient effective dose of 20 microsievert (μSv) and a maximum effective dose after 14CO2 inhalation by the exposed worker of 16 μSv compared with a mean individual annual effective dose from natural and artificial radioactivity exposure of 3500 μSv in France. The 14C‐ERMBT is safe and complies with the European regulations regarding the administration of 14C‐labelled compounds in humans. It can therefore be used in clinical research in France without any particular safety requirement.
Drug metabolism and disposition in children
Authors: Strolin Benedetti M. , Baltes E.L.
Published: June 2003

Key factors undergoing maturational changes accounting for differences in drug metabolism and disposition in the pediatric population compared with adults are reviewed. Gastric and duodenal pH, gastric emptying time, intestinal transit time, bacterial colonization and probably P‐glycoprotein are important factors for drug absorption, whereas key factors explaining differences in drug distribution between the pediatric population and adults are membrane permeability, plasma protein concentration and plasma protein characteristics, endogenous substances in plasma, total body and extracellular water, fat content, regional blood flow and probably P‐glycoprotein, mainly that present in the gut, liver and brain. As far as drug metabolism is concerned, important differences have been found in the pediatric population compared with adults both for phase I enzymes [oxidative (e.g. cytochrome CYP3A7 vs. CYP3A4 and CYP1A2), reductive and hydrolytic enzymes] and phase II enzymes (e.g. N‐methyltransferases and glucuronosyltransferases). Finally, key factors undergoing maturational changes accounting for differences in renal excretion in the pediatric population compared with adults are glomerular filtration and tubular secretion. It would be important to generate information on the developmental aspects of renal P‐glycoprotein and of other renal transporters as done and still being done with the different isozymes involved in drug metabolism.
Self‐medication: from European regulatory directives to therapeutic strategy
Authors: Bergmann Jean‐François
Published: June 2003

Self medications are drugs which can be used without a physician's advice or supervision. There is a clear emerging patient demand for efficient drugs available without prescription. This review summarizes the regulatory rules regarding the status of self‐medication drugs in Europe and describes some situations where specific clinical trials are needed for a new drug to be registered as a self medication. These drugs not only have to offer a very positive safety profile but also a well‐established level of efficacy. A nonprescription drug can only be proposed in situations where the patient himself can make a self‐assessment of the medical condition and its follow‐up. These products must be safe even in the event of incorrect use and must offer clear and complete information contributing to a proper use, i.e. a definition of situations where a physician's advice is necessary. For registration as an ‘over‐the‐counter’ drug, specific efficacy trials may be conducted in real self‐medication situation especially when the target populations, the dosage or the indications in self medication are not the same as those evaluated previously when the drug in question had prescription status. Specific pharmacovigilance is needed and the patient, pharmacist and physician encouraged to report any adverse events. A safety survey may be necessary in some situations such as insomnia or emergency contraception. It is important for the patient, pharmacist and public health in general to distinguish the efficient and safe self medications from the nonvalidated, nonevaluated alternative medicines.
Ultrastructural clues for glutamate‐induced necrosis in parietal and cerebellar neurons
Authors: Eşrefoğlu Mukaddes , Gepdiremen Akçahan , Kuruş Meltem
Published: June 2003

Glutamate excitotoxicity has been postulated to underlie the neuronal death that occurs after ischemia. The most sensitive tissues to ischemic injury are hippocampus and cerebellum, whereas cerebrum is more resistant. We studied the glutamate‐induced ultrastructural alterations in rat parietal and cerebellar neurons comparatively. We observed that glutamate (45 min, 10−7 m) causes considerable nuclear, mitochondrial and cytoplasmic changes in both the neuron types. Mitochondrial and nuclear changes were particularly more severe in cerebellar granular, than the ones in parietal neurons. It has been concluded that glutamate induces necrotic changes in both parietal and cerebellar neurons. But cerebellar cortex was found to be more sensitive to glutamate excitotoxicity than cerebral cortex. We suggest that mitochondrial damage is, probably, an important factor in neuron necrosis, which is mediated by glutamate excitotoxicity.
Antihypertensive effects of the essential oil of Alpinia zerumbet and its main constituent, terpinen‐4‐ol, in DOCA‐salt hypertensive conscious rats
Authors: Lahlou Saad , Interaminense Leylliane Fátima Leal , Leal‐Cardoso José Henrique , Duarte Gloria Pinto
Published: June 2003

The present study investigated the hypotensive responses to intravenous (i.v.) treatment with the essential oil of Alpinia zerumbet (EOAZ) and its main constituent, terpinen‐4‐ol (Trp‐4‐ol), in the experimental model of deoxycorticosterone‐acetate (DOCA)‐salt hypertensive rat.

In both DOCA‐salt hypertensive and uninephrectomized, normotensive rats, i.v. bolus injections of EOAZ (1–20 mg/kg) or Trp‐4‐ol (1–10 mg/kg) decreased mean aortic pressure (MAP) in a dose‐related manner. However, hypotensive responses to Trp‐4‐ol were significantly greater than those evoked by the same doses of EOAZ (1–10 mg/kg). Treatment with DOCA‐salt significantly enhanced the maximal percentage decreases in MAP evoked by EOAZ or Trp‐4‐ol. Likewise, both maximal percentage and absolute decreases in MAP elicited by i.v. injection of the ganglion blocker, hexamethonium (30 mg/kg), were significantly greater in DOCA‐salt hypertensive than in control rats. In DOCA‐salt hypertensive rats, neither hexamethonium (30 mg/kg, i.v.) nor methylatropine (1 mg/kg, i.v.) pretreatment affected the enhancement of EOAZ‐induced hypotension.

These results show that i.v. treatment with either EOAZ or Trp‐4‐ol dose‐dependently decreases blood pressure in conscious DOCA‐salt hypertensive rats, and this action is enhanced when compared with uninephrectomized controls. This enhancement could be related mainly to an increase in EOAZ‐induced vascular smooth muscle relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model. The data further support our previous hypothesis that hypotensive effects of EOAZ are partially attributed to the actions of Trp‐4‐ol.
Caffeine as a promoter of analgesic‐associated nephropathy – where is the evidence?
Authors: Fox Johannes M. , Siebers Ute
Published: June 2003

Individual groups of nephrologists – in their responsibility for their patients – initiated a most controversial discussion whether or not caffeine – coformulated to analgesics – might initiate or sustain analgesic overdosing. The original sources (data) of such suspicion have got lost during the debate of the last two decades. Therefore, it seemed to be appropriate to investigate the original data background and the reasons why nephrologists started to suspect caffeine as a stimulant of analgesic overdosing by employing a systematic and exhaustive review of primary nephrological publications. Their selection followed a precise selection plan, including all epidemiological studies on analgesic‐associated nephropathy, the original papers of all groups having been involved in those studies, further originals from the mainly involved countries (academically, politically), and any literature thereof cited as a proof. The following results emerged from the investigation:

The epidemiological studies warranted no conclusion about a role of caffeine in prompting excessive analgesic use.

The identified groups of nephrologists provided not substantial data to advocate the said suspicion, except for the observation of a preferential choice of phenacetin‐containing combinations, especially powder preparations.

Only two cited original data sources revealed drug‐seeking behaviour with phenacetin‐containing preparations which subsided, after phenacetin was banned from the respective markets.

Conclusively, it appears that there is no substantial data to support a pivotal role of caffeine in initiating or sustaining analgesic overdosing. However, there is strong data that phenacetin, by its psychotropic properties, may have caused drug‐seeking behaviour and thus led to analgesic overdosing. This conclusion is convincingly supported by thorough pharmacokinetic investigations.

Note: All caffeine‐related statements within the reviewed literature have been collected in tables (referred to asTable SX) which are provided in full text for check on the following website:http://www.blackwellpublishing.com/products/journals/suppmat/FCP/FCP174/FCP174sm.htm
Changes in portal vein flow after adult living-donor liver transplantation: Does it influence postoperative liver function?
Authors: García-Valdecasas Juan C. , Fuster José , Charco Ramon , Bombuy Ernest , Fondevila Constantino , Ferrer Joana , Ayuso Carmen , Taura Pilar
Published: June 2003

In adult living donor liver transplantation, using small grafts in cirrhotic patients with severe portal hypertension may have unpredictable consequences. The so-called small-for-size syndrome is present in most series worldwide. The goal of this study was to prospectively evaluate the influence of hemodynamic changes on postoperative liver function and on the percentage of liver volume increase, in the setting of living donor liver transplantation. Twenty-two consecutive adult living donor liver transplantations were performed at our institution in a 2-year period. We measured right portal flow and right hepatic arterial flow with an ultrasonic flow meter in the donor, and then in the recipient 1 hour after reperfusion. Postoperative liver function was measured by daily laboratory work. We also performed duplex ultrasounds on postoperative days 1, 2, and 7. Liver volume increase was estimated by magnetic resonance imaging graft volumetry at 2 months posttransplantation. We compared the blood flow results with the immediate liver function and its liver volume increase rate at 2 months. There was a significant increase in portal flow in the recipients compared with the donors (up to fourfold in some cases). Higher portal flow increase rates significantly correlated with faster prothrombin time normalization and faster liver volume increases. Median graft volume increase at 2 months was 44.9%. The increase in blood flow to the graft is well tolerated by the liver mass not affecting hepatocellular function as long as the graft-to body weight ratio is maintained (>0.8) and adequate outflow is provided
Diagnosis and treatment of arterial steal syndromes in liver transplant recipients
Authors: Nüssler Natascha C. , Settmacher Utz , Haase Roland , Stange Barbara , Heise Michael , Neuhaus Peter
Published: June 2003

Arterial steal syndromes (ASSs) after orthotopic liver transplantation (OLT) are characterized by arterial hypoperfusion of the graft caused by shifting of blood flow into the splenic or gastroduodenal artery. Despite their potentially devastating consequences, such as ischemic biliary tract destruction or graft failure, ASSs have received little attention to date. We report the incidence, diagnosis, and treatment of ASS among 1,250 consecutive OLTs. ASS was observed in 69 patients (5.9%). All these patients presented with elevated liver enzyme levels, impaired graft function, or cholestasis. Treatment consisted of splenectomy (n = 18), coil embolization of the splenic or gastroduodenal artery (n = 29), or reduction in splenic artery blood flow through administration of an artificial stenosis (banding; n = 9). Mild symptoms of ASS did not warrant treatment in 13 patients. However, 3 of these patients developed ischemic biliary destruction requiring re-OLT. Serious complications also were observed after splenectomy and coil embolization, requiring re-OLT in 18%. Conversely, no complications were observed after banding the splenic artery. Prophylactic banding of the splenic artery was performed in 97 patients and was associated with a complication rate of 4%. In summary, the incidence of ASS is similar to that of other vascular complications. Untreated ASSs may lead to serious complications in more than 30% of patients. Of a variety of treatment options, banding the splenic artery was associated with the lowest complication rate. Banding also may be performed prophylactically in selected patients to prevent the development of ASS after OLT
Portal hyperperfusion injury as the cause of primary nonfunction in a small-for-size liver graft-successful treatment with splenic artery ligation
Authors: Lo Chung-Mau , Liu Chi-Leung , Fan Sheung-Tat
Published: June 2003

Dysfunction of a small-for-size graft is an important clinical problem after living donor liver transplantation in adults. We report a case of primary nonfunction after a small-for-size right lobe living donor liver transplant that was successfully salvaged by reduction of portal pressure and blood flow after splenic artery ligation. The case established portal hyperperfusion injury as a cause of primary nonfunction in a small-for-size graft and we recommend that portal pressure be measured when clinical suspicion arises. Splenic artery ligation is a technically simple procedure that can be applied for the prevention or treatment of such injury
Repeated graft loss caused by recurrent hepatic artery thrombosis after liver transplantation
Authors: Vivarelli Marco , La Barba Giuliano , Legnani Cristina , Cucchetti Alessandro , Bellusci Roberto , Palareti Gualtiero , Cavallari Antonino
Published: June 2003

Hepatic artery thrombosis (HAT) is a main cause of graft loss and patient mortality after orthotopic liver transplantation (OLT). Several surgical and nonsurgical risk factors have been associated with HAT. Retransplantation often is the only possible treatment for this complication; however, the incidence of recurrence of HAT after retransplantation and the underlying conditions of this occurrence have never been investigated. Of 629 consecutive recipients transplanted at a single institution, 24 underwent retransplantion for HAT: in 4 of them (16%), HAT recurred in the second graft; 3 of these patients lost their first graft because of late HAT, whereas another one lost 4 consecutive grafts for early HAT. Antiphospholipid syndrome and paroxysmal nocturnal hemoglobinuria were diagnosed in three and one of these patients, respectively. Recurrent HAT is an uncommon occurrence that, in our experience, was linked to specific thrombophilic conditions; careful screening of these disorders should be included in the pretransplant workup, and adequate prophylaxis is advisable.
Hepatic arterial reconstruction in 95 adult right lobe living donor liver transplants: Evolution of anastomotic technique
Authors: Marcos Amadeo , Killackey Mary , Orloff Mark S. , Mieles Luis , Bozorgzadeh Adel , Tan Henkie P.
Published: June 2003

The success of adult right-lobe living donor liver transplants (RLDLT) would not have been possible without the experience of the early pioneers of pediatric living donor liver transplants (LDLT). Our experience with 95 RLDLTs from July, 2000 to May, 2002 at a single institution is reported with specific emphasis on arterial reconstruction. The evolution of technique using the autogenous Y extension graft and the reverse extension bifurcated graft for arterial revascularization, which we believe has reduced the incidence of hepatic artery thrombosis, is described. Outcome and the incidence of hepatic artery thrombosis are reported
Recurrent primary biliary cirrhosis
Authors: Neuberger James
Published: June 2003

Liver transplantation remains the only effective treatment for end-stage primary biliary cirrhosis (PBC). It appears now well accepted that the disease recurs in the allograft. The diagnosis of recurrent PBC is made on the basis of a consistent history and demonstrating the histologic features of PBC on liver biopsy and exclusion of other causes of bile duct damage
Hepatic artery thrombosis after adult liver transplantation
Authors: Stange Barbara J. , Glanemann Matthias , Nuessler Natascha C. , Settmacher Utz , Steinmüller Thomas , Neuhaus Peter
Published: June 2003

The incidence, clinical presentation, therapeutic options, and outcome of hepatic artery thrombosis (HAT) were analyzed in a series of 1,192 consecutive adult orthotopic liver transplantations (OLTs). HAT after OLT was observed in 30 cases, resulting in an incidence of 2.5%. The incidence of HAT increased 5.76-fold when the donor hepatic artery was reconstructed with an interposition graft to the supraceliac aorta (P < .05). Early HAT (within the first 30 days after OLT) occurred in 14 of these patients (46.7%), whereas in 16 patients (53.3%), HAT occurred beyond 30 days post-OLT. Clinical presentation of HAT ranged from an increase in serum transaminase levels with or without cholestasis to liver abscess and biliary complications, including cholangitis, bile duct stenosis or necrosis, to liver dysfunction and failure. Impairment of graft function was observed in patients with early HAT, whereas biliary tract destruction was seen more often in patients with late HAT. In only 1 patient was HAT clinically asymptomatic. Therapy consisted of recombinant plasminogen lysis with hepaticojejunostomy, liver abscess drainage, endoscopy or surveillance, and surgical thrombectomy. In 14 of 30 patients (46.7%), the occurrence of HAT required re-OLT. Nine patients with HAT died during follow-up; however, only 4 of these deaths were related to HAT, resulting in a mortality rate of 13.3%. Our results indicate that HAT is a rare but serious complication after OLT, requiring re-OLT in almost 50% of patients. In particular, conservative treatment modalities may significantly prolong graft survival, thus postponing re-OLT
Early steroid withdrawal after liver transplantation: The canadian tacrolimus versus microemulsion cyclosporin a trial: 1-year follow-up
Authors: Greig Paul , Lilly Leslie , Scudamore Charles , Erb Siegfried , Yoshida Eric , Kneteman Norman , Bain Vince , Ghent Cameron , Marotta Paul , Grant David , Wall William , Tchervenkov Jean , Barkun Jeffrey , Roy Andre , Marleau Denis , McAlister Vivian , Peltekian Kevork
Published: June 2003

Corticosteroid therapy contributes significant toxicity to liver transplantation. The safety and efficacy of early steroid withdrawal were determined in patients treated with either tacrolimus or microemulsion cyclosporin A (micro-CsA). The primary outcome was the proportion of patients who were steroid-free 1 year posttransplantation. From the seven Canadian adult liver transplant centers, 143 patients were randomly allocated oral treatment with either tacrolimus (n = 71) or micro-CsA (n = 72), together with corticosteroids and azathioprine. Eligibility criteria for steroid withdrawal included freedom from acute rejection for a minimum of 3 months, and prednisone ≤0.15 mg/kg/d. In eligible patients, the daily steroid dose was reduced by 2.5 mg each month until complete discontinuation was achieved. At 1 year after transplantation, 75% of the tacrolimus patients and 63% of the micro-CsA patients were steroid-free (P = .20). Of all of the patients who became eligible for steroid withdrawal, steroid discontinuation was achieved in over 80%. One-year patient survival was 97% with tacrolimus and 89% with micro-CsA (P = .052). Graft survival was 97% and 86%, respectively (P = .017). The overall incidence of acute rejection during the first year was 35% with tacrolimus and 43% with micro-CsA (P = .26). There was no difference in survival, acute rejection, or rate of steroid withdrawal when adjusting for hepatitis C. All acute rejection episodes experienced during steroid withdrawal were steroid-responsive. Steroid-resistant rejection occurred in 5.6% of the tacrolimus and 9.7% of the micro-CsA patients. One patient, in the micro-CsA group, experienced refractory rejection. Chronic rejection was not observed in either group. The toxicity profiles were similar. Postoperative serum creatinine levels were similar, and dialysis was required in less than 10% of patients in each group. Infectious complications were similar in both groups. Neurotoxicity was a serious adverse event in 13% and 10% of patients receiving tacrolimus and micro-CsA, respectively. Early steroid withdrawal is safe and effective after liver transplantation using either tacrolimus plus azathioprine or micro-CsA plus azathioprine immunoprophylaxis.
Chemoembolization followed by liver transplantation for hepatocellular carcinoma impedes tumor progression while on the waiting list and leads to excellent outcome
Authors: Graziadei Ivo W. , Sandmueller Heiko , Waldenberger Peter , Koenigsrainer Alfred , Nachbaur Karin , Jaschke Werner , Margreiter Raimund , Vogel Wolfgang
Published: June 2003

Orthotopic liver transplantation (OLT) has been considered the best treatment option for patients with hepatocellular carcinoma (HCC). Because of a steadily increasing waiting time, a noteworthy proportion of patients are excluded from OLT because of tumor progression. A 20% and more dropout rate from the waiting list has recently been reported. In this prospective study, we evaluated the effect of preoperative transarterial chemoembolization (TACE) on preventing tumor progression while on the waiting list in patients meeting current selection criteria (solitary lesion ≤ 5 cm, three lesions ≤ 3 cm). In addition, we analyzed the outcome of a separate group of patients with advanced-stage HCC outside the selection criteria but with at least 50% tumor reduction after TACE (downstaging) to expand current criteria. Forty-eight patients met the selection criteria and were eligible for this study. Seven patients are still on the waiting list; 41 underwent OLT. None of these patients had to be removed from the list because of tumor progression after a mean waiting time of 178 days (23 patients ≥180 days). The 1-, 2-, and 5-year intention-to-treat survival was 98%, 98%, and 94%. The outcome after OLT was also excellent with 1-, 2-, and 5-year survival rates of 98%, 98%, and 93%. Tumor recurrence occurred only in 1 patient (2.4%). Fifteen patients with advanced-stage HCC were included in this study. Three developed a tumor progression and had to be removed from the list (20% dropout rate). Despite tumor reduction before OLT, these patients had a significantly less favorable outcome in the intention-to-treat analysis as well as in the posttransplantation survival. Tumor recurrence was seen in 30% of patients after OLT. In conclusion, TACE followed by OLT is associated with an excellent outcome in selected patients. Furthermore, TACE is highly efficacious in preventing tumor progression while waiting for OLT. Although TACE reduced tumor preoperatively, it failed to show a beneficial effect on patient survival in advanced-stage HCCs.
Outcome analysis in adult-to-adult living donor liver transplantation using the left lobe
Authors: Soejima Yuji , Shimada Mitsuo , Suehiro Taketoshi , Hiroshige Shoji , Ninomiya Mizuki , Shiotani Satoko , Harada Noboru , Hideki Ijichi , Yonemura Yusuke , Maehara Yoshihiko
Published: June 2003

Graft size problems remain the greatest limiting factor for expansion of living donor liver transplantation (LDLT) to the adult population. The result of adult-to-adult LDLT using the left lobe with special reference to graft size has not been fully evaluated to date. In this study, we evaluated the outcome of adult-to-adult LDLT using the left lobe and also analyze the impact of using small-for-size grafts on outcome. Thirty-six recipients who underwent adult-to-adult LDLT using the left lobe (n = 14) or left lobe plus caudate lobe (n = 22) were included in the study. Variables including preoperative and operative data, patient and graft survival, complications, and causes of graft loss were studied. Furthermore, the incidence of small-for-size syndrome and its impact on graft survival were studied. Mean graft volume (GV) was 420 ± 85 g (range, 260 to 620 g), which resulted in 38.2% ± 8.1% (range, 22.8% to 53.8%) of the recipient standard liver volume (SLV). Overall 1-year patient and graft survival rates were 85.7% and 82.9%, respectively. Seven grafts were lost. Small-for-size syndrome occurred in 7 of 16 patients (43.8%) with cirrhosis and only 1 of 20 patients (5.0%) without cirrhosis (P = .005). Recipients who developed small-for-size syndrome had inferior graft survival to those who did not (P = .07). In conclusion, adult-to-adult LDLTs were found to be feasible without affecting patient or graft survival. Small-for-size syndrome developed more frequently in patients with cirrhosis. Minimum GV in adult-to-adult LDLT should be 30% less than the recipient’s SLV in patients without cirrhosis, whereas 45% less was required in patients with cirrhosis.
Extensive chimerism in liver transplants: Vascular endothelium, bile duct epithelium, and hepatocytes
Authors: ten Hove Rogier W. , van Hoek Bart , Bajema Ingeborg M. , Ringers Jan , van Krieken Johan H.J.M. , Lagaaij Emma L.
Published: June 2003

The transplanted liver has been shown to be particularly capable of inducing tolerance. An explanation may be the presence of chimerism. Cells of donor origin have been found in recipient tissues after transplantation of any solid organ. Evidence for the presence of cells of recipient origin within the transplanted liver is very limited. We investigated whether nonlymphoid cells of recipient origin can be found within human liver allografts. Five male patients who received a liver transplant from a female donor and 11 patients who received an HLA-I mismatched liver transplant were studied. We confirmed our observations with two different techniques in combination with double-staining techniques. To identify male cells in female liver transplants, we used in situ hybridization for sex chromosomes. To identify specific HLA class I antigens of recipient origin, we used immunohistochemistry with HLA class I-specific antibodies. Double staining was performed to discriminate different cell lineages and inflammatory cells. Endothelial cells of recipient origin were found in 14 of 16 donor livers. Bile duct epithelial cells of recipient origin were found in 5 of 16 cases. Hepatocytes of recipient origin were seen in only 1 of the 5 studied sex-mismatched donor livers. Our study provides evidence that cells of recipient origin can replace biliary epithelial cells, endothelial cells, and hepatocytes within the human liver allograft. This is consistent with the concept that circulating pluripotent progenitor cells exist, capable of differentiating into endothelial cells, epithelial cells, and hepatocytes.
Practice patterns for long-term follow-up of adult-to-adult right lobectomy donors at US transplantation centers
Authors: Beavers Kimberly L. , Cassara Joseph E. , Shrestha Roshan
Published: June 2003

Protocols used by transplant centers to care for donors after right hepatectomy for living donor liver transplantation are not well described in the medical literature. Our goal is to describe practice patterns for the long-term follow-up of adult-to-adult right lobectomy donors at US transplantation centers. All adult liver transplantation centers listed with the United Network for Organ Sharing were surveyed between October and November 2002. A transplant coordinator, hepatologist, or surgeon from each center completed a 10-item telephone questionnaire. Of 97 adult liver transplantation centers, 90 centers (92.8%) completed the survey. Ninety-six percent of participants were transplant coordinators; 2%, hepatologists; and 2%, surgeons. One thousand forty-four right lobectomies have been performed by 51 (56.7%) transplant programs (range, 1 to 101 per center). Thirty-eight percent of active programs have performed fewer than 10 donation right lobectomies. Fifty-one percent of programs have a transplant coordinator who works specifically with donors. Thirty-five programs (68.3%) have a formal follow-up protocol, and an additional 13 centers (14.4%) reported their usual follow-up patterns. Protocols ranged from no formal follow-up to visits every few weeks in the early postoperative period followed by evaluation every 6 months. Evaluation beyond 12 months is typically on an as-needed basis. Personal psychosocial support services after donation were unusual and included regular phone calls from the coordinator (5 centers), quality-of-life instruments (3 centers), scheduled follow-up with the psychologist (1 center), or a satisfaction survey (1 center). Several centers provided newsletters, combined donor-recipient support groups, recognitions parties, and certificates. There is significant variability in the long-term care of donors. Formal psychosocial support after donation is rare.
Relationship between portal venous flow and liver regeneration in patients after living donor right-lobe liver transplantation
Authors: Eguchi Susumu , Yanaga Katsuhiko , Sugiyama Nozomu , Okudaira Sadayuki , Furui Junichiro , Kanematsu Takashi
Published: June 2003

The purpose of this study is to evaluate the relationship between portal venous (PV) velocity and degree of liver regeneration in humans after living donor liver transplantation (LDLT). Between July 1997 and September 2002, a total of 15 adult-to-adult LDLTs with right-lobe grafts were performed, and 13 of these patients were enrolled in this study. Postoperative PV dynamics differed according to the primary liver disease; therefore, patients were divided into two groups: a fulminant hepatic failure (FHF) group (n = 4) and a liver cirrhosis (LC) group (n = 9). Right-lobe donors (n = 13; D group) were used as controls. Doppler ultrasound was used to measured changes in PV velocity preoperatively; postoperative days (PODs) 1, 3, 7, 14, and 28; and 3 months after LDLT. To assess hepatic regeneration, the increase in liver volume ratio (postoperative liver volume to standard liver volume [SLV]) was measured. PV velocity after LDLT in the LC group increased sharply until POD 7, whereas those in the FHF and D groups were constant. In the first 3 months after LDLT, mean PV velocity was greater in the LC group than the other groups, reflecting the persistent hyperdynamic state in chronic end-stage liver disease. Liver regeneration also was more rapid in the LC group than the FHF and D groups and reached 100% as early as 2 weeks posttransplantation, whereas both the FHF and D livers reached approximately 80% of SLV at 3 months. PV velocity POD 7 correlated significantly with regeneration of the partial-liver allograft at 1 month (r = 0.84; P = .0091). In conclusion, the PV persistent hyperdynamic state in the LC group could directly trigger early liver regeneration in partial-liver allografts after LDLT.
Biliary reconstructions and complications encountered in 50 consecutive right-lobe living donor liver transplantations
Authors: Icoz Gokhan , Kilic Murat , Zeytunlu Murat , Celebi Arzu , Ersoz Galip , Killi Refik , Memis Ahmet , Karasu Zeki , Yuzer Yildiray , Tokat Yaman
Published: June 2003

Biliary complications appear to be the leading cause of postoperative complications after living donor liver transplantation (LDLT). The aim of this study is to analyze the complications, treatment modalities, and outcomes of biliary anastomoses in a series of 50 consecutive right-lobe LDLTs. Median patient age was 45 years, and median right-lobe graft volume was 740 g. Graft-recipient weight ratio was 0.69 to 1.80. Median follow-up time was 15 months (range, 2 to 38 months). Eleven of 50 patients died, resulting in an overall allograft and patient survival rate of 78%. In biliary reconstruction, a duct-to-duct (D-D) anastomosis or a standard Roux-en-Y (R-Y) anastomosis was performed. Twenty-nine grafts (58%) had a single duct for anastomosis. Seventeen grafts (34%) had two bile duct orifices, and four grafts (8%) had three bile duct orifices. A D-D anastomosis was performed in 36 cases (72%), whereas R-Y reconstruction was preferred in 14 cases (28%). The overall incidence of biliary anastomotic complications was 30% in this series. Five patients developed biliary leaks, presumably from the cut surface, and all of them healed spontaneously. Two bilomas were drained percutaneously. Anastomotic strictures occurred in 8 patients (16%) and were significantly greater than in the R-Y group (P = .03). Although strictures seemed to develop more frequently in allografts with multiple bile ducts, this did not reach statistical significance (P = .05). All strictures were managed by nonsurgical measures initially. Restenosis occurred in 2 patients, both of whom had an R-Y anastomotic stricture. These anastomoses were revised surgically, giving a reoperation rate of 4% for biliary problems. No graft or patient was lost because of biliary problems. Our data suggest that D-D anastomosis is a safe and feasible method of biliary reconstruction in LDLT by preserving physiological bilioenteric continuity and allowing easy access through endoscopic techniques.
Evaluation of the Harmonic Scalpel for Laparoscopic Bilateral Ovariectomy in Standing Horses
Authors: Düsterdieck Katja F. , Pleasant R. Scott , Lanz Otto I. , Saunders Geoffrey , Howard Rick D.
Published: June 2003

Objective—To evaluate use of the Harmonic Scalpel (Ethicon Endo‐Surgery Inc., Cincinnati, OH) for performing laparoscopic bilateral ovariectomy in standing horses.

Study Design—Experimental study.

Animals—Eight mares aged 2–20 years and weighing 410–540 kg.

Methods—Standing laparoscopic bilateral ovariectomy was performed in 8 mares with normal reproductive tract anatomy. The Harmonic Scalpel (an ultrasonically activated instrument) was used to simultaneously transect and obtain hemostasis of the ovarian pedicle. Necropsy was performed on 4 mares 3 days after surgery and 4 mares 30 days after surgery. Gross and histopathologic evaluation of the ovarian pedicles was performed to characterize tissue reaction.

Results—Complete hemostasis of the ovarian pedicles was obtained in all mares. Median transection time for the ovarian pedicle was 28 minutes. Postoperative complications included transient fever, moderate subcutaneous emphysema, and incisional seroma formation. On necropsy examination, there were no signs of generalized peritonitis, postoperative hemorrhage, or adhesion formation. Mild to moderate acute inflammation and scar formation with moderate chronic inflammation at the ovarian pedicle was found at 3 and 30 days. Median depth of coagulation necrosis at 3 days was 2.87 mm.

Conclusions—The Harmonic Scalpel appears to provide reliable hemostasis of the ovarian pedicle during elective laparoscopic ovariectomy in horses.

Clinical Relevance—The Harmonic Scalpel represents a safe alternative to other methods of hemostasis during elective laparoscopic ovariectomy in horses.
Histologic Changes in Ruptured Canine Cranial Cruciate Ligament
Authors: Hayashi Kei , Frank Joseph D. , Dubinsky Caron , Hao Zhengling , Markel Mark D. , Manley Paul A. , Muir Peter
Published: June 2003

Objectives—To determine changes to the cells and collagenous and amorphous extracellular matrix (ECM) structure in ruptured canine cranial cruciate ligaments (CCL).

Study Design—Prospective clinical study.

Animals—CCL specimens obtained from 29 dogs with ruptured CCL and 6 young dogs with intact CCL.

Methods—Ligament fibroblast number density and phenotype were determined in the core and epiligamentous regions. ECM birefringence and crimp structure in the core region were also studied.

Results—Loss of fibroblasts from the core region of ruptured CCL was seen (P< .001), whereas, in the epiligamentous region, cell number densities were similar in ruptured and intact CCL (P= .7). In ruptured CCL, numbers of typical ligament fibroblasts (fusiform and ovoid cells) were decreased, and numbers of cells exhibiting chondroid transformation (spheroid cells) were increased in the core region (P< .001). Expansion of the volume of the epiligamentous region was also seen, although bridging scar tissue was not seen between the ends of ruptured CCL. The structure of the ECM collagen in the core region was extensively disrupted in ruptured CCL. This was, in part, because of decreased birefringence and elongation of the crimp in the remaining collagen fibers when compared with intact CCL (P< .01).

Conclusions—Extensive alterations to the cell populations and collagenous ECM structure were seen in ruptured CCL. Although a proliferative epiligamentous repair response was seen in ruptured CCL, there was a lack of any bridging scar between the ruptured ends of the CCL.

Clinical Relevance—The cellular and ECM changes in ruptured CCL that we have described appear to result from the cumulative effects of remodeling and adaptation to mechanical loading and microinjury. Treatment of early cruciate disease in dogs will need to inhibit or reverse these progressive changes to CCL tissue, which are directly associated with partial or complete structural failure of the CCL under conditions of normal activity.
Elution of Metronidazole and Gentamicin from Polymethylmethacrylate Beads
Authors: Ramos Jose R. , Howard Rick D. , Pleasant R. Scott , Moll H. David , Blodgett Dennis J. , Magnin Geraldine , Inzana Thomas J.
Published: June 2003

Objective—To characterize the elution and bioactivity of metronidazole and gentamicin sulfate polymerized, individually and in combination, with polymethylmethacrylate (PMMA).

Study Design—In vitro experimental study.

Methods—PMMA beads containing metronidazole (3 concentrations), gentamicin sulfate, or metronidazole and gentamicin sulfate were immersed in 5 mL of phosphate‐buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 or 21 days, and antibiotic concentrations were measured by high‐performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or copolymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of AIPMMA beads containing metronidazole were evaluated.

Results—Antibiotic elution patterns were similar for all groups. Day 1 elution for groups containing metronidazole or gentamicin individually represented a mean 63%‐66% and 79%, respectively, of the 21‐day total. Approximately 50% of the day 1 elution occurred during the first hour. The elution of metronidazole was dose dependent. The elution of metronidazole (day 3–21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (P< .05). The addition of metronidazole delayed polymerization of PMMA. Neither polymerization nor copolymerization of metronidazole and gentamicin with PMMA, gas sterilization, or 2‐month storage of beads containing metronidazole significantly affected antimicrobial bioactivity.

Conclusions—Metronidazole elution from PMMA was dose dependent. Copolymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intraoperative preparation of metronidazole‐impregnated PMMA beads is not practical, but sterilization and storage for 2 months should not affect efficacy.

Clinical Relevance—The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible.
Comparison of the Incidence of Residual Shunting Between Two Surgical Techniques Used for Ligation of Patent Ductus Arteriosus in the Dog
Authors: Stanley Bryden J. , Luis‐Fuentes Virginia , Darke Peter G. G.
Published: June 2003

Objective—To compare the incidence of residual patent ductus arteriosus (PDA) flow after ligation using 2 different dissection techniques: a standard dissection and a method described by Jackson and Henderson.

Study Design—A randomized, prospective study.

Animals—Thirty‐five dogs admitted for surgical correction of a left to right shunting PDA.

Methods—Dogs were randomly assigned: 19 to a standard dissection technique (group S) and 16 to the Jackson and Henderson dissection group (group JH).

Results—Gender ratio, age at surgery, and diameter of the ductus were not statistically different between groups. Breed distribution was also similar. Because 1 dog had fatal intraoperative hemorrhage, only 34 dogs were available for residual flow comparisons. Twenty‐one percent of group S dogs had residual flow compared with 53% in group JH. Whereas no intraoperative complications occurred in group S, 3 were encountered in group JH.

Conclusions—The incidence of residual flow was higher when the Jackson and Henderson dissection was used for PDA ligation compared with a standard method of dissection. This was probably because of entrapment of loose connective tissue within the medial aspect of the ligature, impeding complete closure of the ductus.

Clinical Relevance—Ideal PDA closure should result in no residual ductal flow to prevent possible adverse long‐term sequelae, such as recanalization and infective endocarditis.
Concurrent Use of a Medial Saphenous Fasciocutaneous Free Tissue Flap and External Skeletal Fixation for Treatment of a Distal Antebrachial Injury in a Dog
Authors: Sereda Colin W. , Lanz Otto I. , Cross Alan R. , Anderson Gregory M.
Published: June 2003

Objective— To report the surgical management of a traumatic distal antebrachial wound using a medial saphenous fasciocutaneous free tissue flap and a type I external skeletal fixator (ESF).

Study Design— Case report.

Animals— A 7‐year‐old spayed, female Labrador retriever.

Results— Wound coverage and pancarpal arthrodesis were accomplished during a single anesthetic episode using a medial saphenous fasciocutaneous free tissue flap and type I ESF. A second surgical procedure was performed to expedite healing of part of the original wound that was initially left to heal by second intention.

Conclusions— Free tissue transfer can be used in combination with an ESF for repair of distal antebrachial wounds, allowing orthopedic repair and soft tissue coverage in a single anesthetic episode.

Clinical Relevance— Concurrent use of free tissue transfer and carpal arthrodesis with an ESF could be used for repair of complex antebrachial wounds without need for multiple procedures, extended hospitalization, and increased cost.
Retrospective Analysis of Canine Miniature Total Hip Prostheses
Authors: Warnock Jennifer J. , Dyce Jonathan , Pooya Hooman , Schulz Kurt S.
Published: June 2003

Objective—To determine the practicality and clinical outcome of miniature total hip replacement (THR) in dogs.

Study Design—Retrospective study.

Sample Population—Seventeen client‐owned dogs that had miniature THR.

Methods—Patient data surveyed included signalment, body weight, diagnosis, implant size, surgical technique, and intraoperative and postoperative complications. Radiographic evaluation included angle of lateral opening of the acetabular component, implant positioning, cement mantle quality, and femoral displacement measurement and ratio. Client questionnaire and orthopedic examination were used to obtain long‐term follow‐up information.

Results—Miniature THR was performed to address hip dysplasia and secondary osteoarthritis. In 1 dog, a staged bilateral procedure was performed. Mean body weight was 19 kg (range, 12 to 25 kg). Penetration or fissure of the femoral cortex was the most common intraoperative complication and occurred in 3 dogs. In 3 dogs, there was excessive coxofemoral laxity after reduction of the prosthesis. This instability was addressed specifically in 2 dogs by capsulorrhaphy or capsular prosthesis. Postoperative convalescent complications (craniodorsal luxation, 2 dogs; acetabular cup displacement, 1 dog) were related to surgical errors. Aseptic loosening of the femoral implant was diagnosed in 1 dog at 18 months. Mean follow‐up time was 17 months (range, 4 to 42 months). Fifteen of 18 (83%) miniature THRs had good or excellent outcomes.

Conclusions—Miniature THR should be considered a satisfactory alternative to femoral head and neck ostectomy in medium‐size dogs affected by hip dysplasia and secondary osteoarthritis. The population of medium‐size dogs that might derive more benefit from THR than FHO has yet to be defined.

Clinical Relevance—Miniature THR is a viable treatment option in medium‐size dogs with hip dysplasia.