Left adrenal aldosteronism coexisting with left paraaortic paraganglioma presenting as bilateral adrenal and left paraaortic tumors- comprehensive adrenal evaluation aiding perfect management: a case report.

BACKGROUND: Coexistence of a catecholamine-secreting tumor and an adrenal cortical tumor is quite rare which makes both diagnosis and management challenging. The purpose of this article is to describe the presence of this condition, share a stepwise approach for preoperative evaluation, and review the related literature. CASE PRESENTATION: A 44-year-old male patient had a history of hypertension and aggravating hypokalemia for years. Abdominal computed tomography incidentally found concomitant bilateral adrenal and left para-aortic tumors. Comprehensive adrenal hormone tests revealed a high aldosterone renin ratio and mildly elevated 24-h urine vanillylmandelic acid and norepinephrine levels. Subsequently, a metaiodobenzylguanidine scan showed uptake over the left para-aortic tumor, and NP-59 adrenal scintigraphy showed uptake over the left adrenal tumor. Further confirmatory tests, including captopril suppression, irbesartan suppression, and saline infusion, all confirmed the diagnosis of hyperaldosteronism. Adrenal venous sampling following 2 months of preparation with an alpha blocker demonstrated a left aldosterone-producing adrenal adenoma. Combining hormonal analysis, imaging studies, and adrenal venous sampling, the patient was diagnosed with left adrenal aldosteronoma, right adrenal nonfunctional tumor, and left para-aortic paraganglioma (PGL). Accordingly, laparoscopic left adrenalectomy and left PGL excision were performed smoothly under alpha blocker maintenance. The pathology report confirmed left adrenal cortical adenoma and left para-aortic PGL. Postoperatively, the blood pressure, biochemical tests, and adrenal hormone assays returned to normal, and related symptoms disappeared and were relatively stable during the follow-up period of two years. CONCLUSIONS: This is the first case of left para-aortic PGL coexisting with an ipsilateral aldosterone-producing adenoma presenting as a left para-aortic tumor associated with bilateral adrenal tumors. Awareness of the rarity of this coexistence can avoid unexpected disasters during the process of evaluation and management.

Chimeric Anterolateral Thigh Flap for One-stage Reconstruction after Cervical Exenteration with Anterior Mediastinal Tracheostomy.

Cervical exenteration with anterior mediastinal tracheostomy is rarely performed for extensive cervicothoracic malignancies. Although it provides effective palliation and occasional cure, reconstruction remains a formidable challenge owing to its complexity and high mortality. The resultant defects usually require an intestinal flap or tubed skin flap to restore the alimentary tract, soft-tissue interposition to separate the relocated trachea from the innominate artery, and another tubed or fenestrated skin flap to create a tension-free tracheocutaneous anastomosis and provide coverage for the exposed vessels, hopefully in one stage. We report a case involving a 60-year-old woman with recurrent medullary thyroid cancer who developed dyspnea and dysphagia. Salvage cervical exenteration and anterior mediastinal tracheostomy were complicated by tissue fibrosis caused by previous surgical and radiation therapies, resulting in complex defects with segmental loss of the esophagus, a short stump of trachea incapable of tracheocutaneous anastomosis, and great-vessel exposure. We used a chimeric anterolateral thigh flap consisting of a tubed skin flap for pharyngoesophageal reconstruction, a fenestrated skin flap for tracheostomy and neck coverage, and a vastus lateralis muscle bulk to separate the innominate artery from the relocated trachea. To our knowledge, this is the first report describing the reconstruction of such a complex defect with a single skin flap in a single stage.

Anaplastic Thyroid Cancer Successfully Treated With Radiation and Immunotherapy: A Case Report.

OBJECTIVE: Anaplastic thyroid cancer (ATC) is a rare thyroid cancer subtype with a devastating prognosis. Novel treatment strategies are under investigation to improve the survival of patients with ATC. METHODS: We present a case of recurrent ATC treated with a combination of radiation therapy (RT) and pembrolizumab, a programmed death-1 inhibitor, with a durable complete response. RESULTS: A 63-year-old woman underwent total thyroidectomy and left neck lymph node dissection and was diagnosed with papillary carcinoma in December, 2017. She received radioiodine in April, 2018. However, a left neck mass was noted in April, 2018 with biopsy demonstrating ATC with 95% positivity for programmed death-ligand 1 immunostaining. Positron emission tomography showed fluorodeoxyglucose uptake in the left thyroid bed and multiple lymph nodes in the left retropharyngeal, left neck, and right upper paratracheal areas. Hypofractionated RT for the recurrent areas was initiated in August,2018, and concomitant pembrolizumab was given 2 days after RT. A total of 10 cycles of pembrolizumab (2 mg/kg) were given every 3 weeks. The computed tomography scan after completion of RT and 3 cycles of pembrolizumab showed shrinkage of the neck lymph nodes. The serial follow-up computed tomography scans showed further shrinkage of the lymph nodes, and there was no recurrence of ATC as of October, 2020. CONCLUSION: We describe an ATC case successfully treated with a combination of RT and pembrolizumab with a durable response of 26 months and acceptable toxicities. This result warrants further investigation of this combination regimen in the treatment of ATC.

Application of Tissue Aspirate Parathyroid Hormone Assay for Imaging Suspicious Neck Lesions in Patients with Complicated Recurrent or Persistent Renal Hyperparathyroidism.

BACKGROUND: Comprehensive pre-reoperative localization is essential in complicated persistent or recurrent renal hyperparathyroidism. The widely used imaging studies sometimes lead to ambiguous results. Our study aimed to clarify the role of tissue aspirate parathyroid hormone (PTH) assay with a new positive assay definition for imaging suspicious neck lesions in these challenging scenarios. METHODS: All patients with complicated recurrent or persistent renal hyperparathyroidism underwent parathyroid sonography and scintigraphy. Echo-guided tissue aspirate PTH assay was performed in suspicious lesions revealed by localization imaging studies. The tissue aspirate PTH level was determined by an immunoradiometric assay. We proposed a newly-developed definition for positive assay as a washout level higher than one-thirtieth of the serum PTH level obtained at the same time. The final diagnosis after re-operation was confirmed by the pathologists. RESULTS: In total, 50 tissue aspirate PTH assays were performed in 32 patients with imaging suspicious neck lesions, including discrepant results between scintigraphy and sonography in 47 lesions (94%), unusual locations in 19 lesions (38%), multiple foci in 28 lesions (56%), and locations over previously explored areas in 31 lesions (62%). Among 39 assay-positive lesions, 13 lesions (33.3%) were not identified by parathyroid scintigraphy, and 28 lesions (71.8%) had uncertain parathyroid sonography findings. The final pathology in patients who underwent re-operative surgery proved the tissue aspirate PTH assays had a 100% positive predictive value. CONCLUSIONS: Our findings suggest tissue aspirate PTH assay with this new positive assay definition is beneficial to clarify the nature of imaging suspicious lesions in patients with complicated persistent or recurrent renal hyperparathyroidism.

Experience of sorafenib treatment in differentiated thyroid cancer from Taiwan.

BACKGROUND: Sorafenib has been shown to prolong the progression free survival (PFS) of advanced radioiodine (RAI) refractory differentiated thyroid cancer (DTC) and has been approved by the FDA as the result of the phase III DECISION trial. Sorafenib has been reimbursed for the treatment of RAI refractory DTC in Taiwan since Jan 2017. High percentage of adverse events (AE) was noted in DECISION trial. We conducted a study to show the real-world experience of sorafenib in Taiwan. METHODS: We retrospectively collected the clinical data, including dose, AE, and PFS of sorafenib, of the DTC patients who received sorafenib treatment in National Cheng Kung University Hospital and China Medical University Hospital by chart review from 2012 to 2018. RESULTS: Thirty-six advanced DTC patients with progression were included in this study. The starting dose of sorafenib in most patients was 200 mg twice daily and the mean daily maintenance dose was 433 mg. Five patients had partial response (13.9%) and 28 patients had stable disease (77.8%). The median PFS was 17.3 months (95% confidence interval: 11.9-33.6 months). Daily maintenance dose ≥ 600 mg was associated with better PFS (median PFS, not reached). The most common toxicity of sorafenib was hand foot skin reaction (69%), followed by diarrhea (42%), and skin rash (33%). Most of the toxicities were grade I/II. CONCLUSION: Higher maintenance dose of sorafenib is associated with longer PFS while starting from half dose is feasible to minimize the incidence of high grade toxicities in the real-world use of sorafenib.

Traction Injury of Recurrent Laryngeal Nerve During Thyroidectomy.

BACKGROUND: Loss of the neuromonitoring signal (LOS) during thyroidectomy signifies recurrent laryngeal nerve (RLN) injury, which is one of the common complications, especially by traction injury. Transient intraoperative LOS means spontaneous recovery of nerve function during surgery or within 6-month post-surgery. Few articles discuss intraoperative recovery time and transient LOS, and there is no consensus on the risk factors for RLN traction injury and its recovery course; thus, we wanted to determine the maximum intraoperative recovery time. MATERIALS AND METHODS: This retrospective study included patients who had undergone thyroidectomies at Tainan National Cheng Kung University Hospital between January 2015 and August 2018. A total of 775 patients (with 1000 nerves at risk) who underwent intermittent intraoperative neuromonitoring during thyroidectomy were included in this study. The LOS nerves were divided into 4 groups based on the LOS subtype and the intraoperative status of the recovery. The postoperative vocal cord function was determined by thyroid ultrasound and/or laryngoscope. All the patients would be followed up postoperatively in 2-3 days, 1 week, 2 weeks, and 4-6 weeks. RESULTS: LOS occurred in 67 of 775 (8.6%) patients and in 70 of 1000 nerves at risk (7.0%). There were 2 in 70 nerves (2.9%) with LOS type 1 (segmental nerve traction injury) with intraoperative recovery (Group 1), 5 (7.1%) with LOS type 1 without intraoperative recovery (Group 2), 47 (67.1%) with LOS type 2 (global injury) with intraoperative recovery (Group 3), and 16 (22.8%) with LOS type 2 without intraoperative recovery (Group 4). All LOS type 1 (segmental nerve injury) nerves had pathologic lesions near the RLN or vagus nerve, but none had invaded the nerves (p < 0.05). The resolving time intraoperatively in the 2 patients in Group 1 was 5 min and 10 min, respectively. The resolving time intraoperatively in Group 3 was 1-20 min, and the average time was 4.8 min. In Group 2, 3 injured nerves recovered within 6 weeks postoperatively, and 2 nerves in 12 weeks. In Group 4, all the 16 injured nerves recovered within 6 weeks postoperatively. CONCLUSION: Applying intermittent intraoperative neuromonitoring during thyroidectomy, traction recurrent laryngeal nerve injury still happened in 7.0%. 70% of the injured nerves recovered the function intraoperatively after releasing the traction, and the longest duration of recovery is 20 min.

Is Partial or Total Thyroidectomy Associated with Risk of Long-Term Osteoporosis: A Nationwide Population-Based Study.

BACKGROUND: Whether thyroidectomy contributes to osteoporosis (OP) and osteoporotic fracture (OF) is a subject of debate. This study aimed to determine the effect of thyroidectomy on the risk of OP and OF. METHODS: This retrospective cohort study is based on patient data between January 2000 to December 2005 from the National Health Insurance Research Database. Patients who underwent thyroidectomy were enrolled in the thyroidectomy cohort, and the control cohort was selected by propensity score matching at a ratio of 1:4. Incident OP and OF cases were identified until the end of 2013. The thyroidectomy cohort to control cohort adjusted hazard ratio (aHR) for OP/OF was assessed through multivariable Cox proportional hazard regression analysis. RESULTS: Totals of 1426 and 5704 patients were included in the thyroidectomy and control cohorts, respectively. The incidence density of OP was higher in the thyroidectomy cohort (7.91/1000 person-years) than in the control cohort (5.98/1000 person-years), with an aHR of 1.43 (95% CI 1.16-1.77, p < 0.05). Younger patients, women, and patients with comorbidities were at a higher risk. The risks of postoperative OP/OF were significantly increased in patients who received thyroxine treatment for more than 1 year, both in the partial thyroidectomy group and in the total and subtotal thyroidectomy group (aHR: 2.47, 95% CI: 1.42-2.31 vs. aHR: 1.84, 95% CI: 1.22-2.76). CONCLUSION: Thyroidectomy significantly increased the long-term risk of OP. Younger patients, women, patients with comorbidities, and patients receiving chronic thyroxin treatment should be monitored for changes in postoperative bone density.

Social capital and transaction cost on co-creating IT value towards inter-organizational EMR exchange.

This study adopts social capital theory and transaction cost theory to explore the feasibility of an inter-organizational cross-hospital electronic medical records (EMR) exchange system, and the factors that affect its adoption. The concept of value co-creation is also used to assess such a system, and its influence on the performance of participating medical institutes. This research collected 330 valid paper-based questionnaires from the medical staff of various institutes. The results showed that social interaction ties and shared vision positively affected medical institutes' willingness to adopt the EMR exchange system, while asset specificity and uncertainty increased the related transaction costs. With a greater willingness to invest in relation-specific assets and to meet the related transaction costs, this behavior lead to an increase in medical IT value, as well as better results for the related medical institutes, medical staff, and patients. Therefore, this study suggests that such institutes encourage their medical staff to participate in seminars or reunions in order to develop their professional and social networks, and set up clear schedules and desire for expected effects when introducing the cross-hospital EMR exchange system.

Intramuscular and subcutaneous forearm parathyroid autograft hyperplasia in renal dialysis patients: A retrospective cohort study.

BACKGROUND: Intramuscular and subcutaneous forearm parathyroid autograft are proved to have compatible short-term outcome. However, long-term clinical courses have not been studied. METHODS: A single-surgeon retrospective cohort study of parathyroid autograft hyperplasia from August 1998 to January 2013 was performed. According to the location of their parathyroid autograft, patients were divided into an Intramuscular group and a Subcutaneous group. Clinical parameters were analyzed to assess the risk factors and clinical course of autograft hyperplasia. RESULTS: There were 888 consecutive patients who underwent total parathyroidectomy with forearm autotransplantation for renal hyperparathyroidism during the period. The median age at the time of total parathyroidectomy with forearm autotransplantation was 54.2 years (range, 12-86) and the median follow-up time was 4.0 years (range 0.1-16). Autograftectomy was performed on 29 of 888 patients. The incidence of autograftectomy was 15 of 65 in the Intramuscular group and 14 of 823 in the Subcutaneous group; the incidence of repeated autograftectomy was 4 of 65 in the Intramuscular group and 1 of 823 in the Subcutaneous group. The cumulative frequency of autograftectomy was greater in the Intramuscular group than that in the Subcutaneous group (11.6 vs 3.1% at 6 years, P < .001). The location of the autograft was the only significant factor affecting the autograftectomy frequency (P = .002). The Intramuscular group reoperation patients experienced a longer period between their first operation and the autograftectomy (6.6 vs 3.3 years, P = .003), longer operating times (79 vs 37 minutes, P = .002), and a greater level of pre-autograftectomy systemic intact parathyroid hormone (1,044 vs 559 ng/L, P = .014) than the Subcutaneous group. CONCLUSION: Intramuscular parathyroid autotransplantation results in a high incidence of autograftectomy, repeated autograftectomy, and a high cumulative frequency of autograftectomy.

Service quality and perceived value of technology-based service encounters: evaluation of clinical staff satisfaction in Taiwan.

Previous research has evaluated technology-based service encounters (TBSEs) in the delivery of health care by assessing patient satisfaction. This study examined service quality and perceived value of TBSEs used in health organisations from the perspective of clinical staff, with staff technology readiness as a moderator. A quantitative survey was conducted in Taiwan, across private and public healthcare organisations. Results showed that TBSEs had a direct effect on service quality and perceived value, which in turn had a direct effect on staff satisfaction in using TBSEs. However, service quality had no effect on perceived value when moderated by technology readiness. Theoretical and managerial implications of these findings are discussed.

Angiographic-CT-FDG-Pathologic Correlations of the Incidentally Discovered Adrenal Mass.

During abdominal ultrasonography of a 37-year-old man a 3.2 cm hypoechoic mass in the right hepatic lobe was found incidentally. This prompted an abdominal CT, an FDG PET/CT, and an angiography to evaluate the nature of the mass. Laboratory data showed positive anti-HBs/anti-HBe, and negative HCV antibody. The alfa-fetoprotein and liver function tests were within normal limits. Contrast-enhanced CT found an enhanced hepatic tumor and primary hepatocellular carcinoma was suspected. PET/CT revealed no abnormal FDG accumulation in the right hepatic mass. The digital subtraction angiographies of the right inferior phrenic artery and right renal artery revealed a hypervascular tumor in the right adrenal gland. Therefore, a diagnosis of a right adrenal tumor was made. Serum aldosterone, serum cortisol, and urine vanillylmandelic acid, and catecholamine were all within normal limits. Laparoscopic right adrenalectomy was performed and adrenal cortical adenoma was diagnosed on a histological study.

Development of laparoscopic donor nephrectomy: a strategy to increase living kidney donation incentive and maintain equivalent donor/recipient outcome.

BACKGROUND/PURPOSE: Laparoscopic donor nephrectomy (LDN) has emerged as the preferred technique worldwide, and has contributed to a dramatic increase in living kidney donation during the past decade. We adopted LDN in 2002 with the intention of increasing living kidney donation incentive and maintaining equivalent donor/recipient outcome. METHODS: Forty-five LDNs were performed between September 2002 and November 2007. Donor demographics, operative characteristics, perioperative complications and donor/recipient outcome were reviewed retrospectively. The LDN series was divided into earlier and later groups for comparison. To confirm the safety and efficacy of LDN, we compared the results with those of previous series and our open donor nephrectomy (ODN) series. RESULTS: All 45 LDN kidneys were procured and transplanted successfully. Mean donor operation time was 327.7+/-10.2 minutes, blood loss was 286.0+/-48.3 mL, and warm ischemia time was 233.9+/-19.6 seconds. Two (4.4%) open conversions happened in the earlier group. There was a significant decrease in warm ischemia time and donor intraoperative complications in the later group. There was no donor mortality and there were no repeat surgical procedures. Delayed graft function occurred in 8.9% of cases and three (6.7%) recipients developed ureteral complications. All but one recipient was discharged with adequate renal function. Graft function continued in 41 of the 43 harvested kidneys (95.3%). Compared with ODN, there was a significant decrease in donor postoperative stay in the LDN series (p=0.00). There was no difference between the series with regard to donor safety, donor outcome, and immediate and long-term recipient outcome. CONCLUSION: The number of living kidney donations increased significantly after adopting LDN in our series. The equivalent donor/recipient outcome of the LDN series compared with that of previous and ODN series was achieved with increasing experience.

Pancreaticoduodenectomy for pancreatic head cancer: PPPD versus Whipple procedure.

BACKGROUND/AIMS: Resectable carcinoma of the head of the pancreas can be treated with either standard (the Whipple) or pylorus-preserving pancreaticoduodenectomy (PPPD). Only a few reports compared the differences between these two procedures. METHODOLOGY: From July 1994 to Oct 2002, a prospective randomized comparison between the Whipple procedure and PPPD done by the same surgeon for the patients with carcinoma of the head of the pancreas was conducted. Thirty-six patients diagnosed as pancreatic head adenocarcinoma were randomized to receive either the Whipple procedure or a PPPD. Three patients initially randomized to have a PPPD were converted to the Whipple procedure due to gross duodenal involvement. Finally, 19 patients received the Whipple procedure, 14 patients underwent PPPD and three patients had conversion. RESULTS: Two perioperative deaths in the Whipple group and one perioperative death in PPPD resulted in an 8 percent mortality rate in the 36 patients. Median duration of the Whipple operation was 265 (range 203-475) min with a median blood loss of 570 (50-8540) mL. In the patients who had PPPD, median operating time was 232 (range 165-270) min, and median blood loss was 375 (range 100-1300) mL. There was one minor leak from the pancreaticojejunostomy in each group, resulting in a 5.5 percent minor leak in 36 patients. These outcomes were not significantly different. Delayed gastric emptying was observed more frequently after PPPD (six of 14 patients) than after the Whipple procedure (none of 19 patients) (P < 0.05). There was no significant difference between the Whipple procedure and PPPD in terms of median survival and 5-year survival rate. The median survival time was 16.0 months and 5-year survival rate was 9.4 percent in the 36 patients. Blood loss during operation influenced the prognosis. CONCLUSIONS: There was no significant difference between the Whipple procedure and PPPD for the treatment of pancreatic head cancer in terms of operating time, blood loss, operative mortality and long-term survival. But delayed gastric emptying was more frequently encountered in PPPD than in the Whipple procedure.

High concentrations of circulating macrophage migration inhibitory factor in patients with severe blunt trauma: Is serum macrophage migration inhibitory factor concentration a valuable prognostic factor?

OBJECTIVE: To determine serum concentrations of macrophage migration inhibitory factor and other cytokines in severe blunt trauma patients in critical settings and to evaluate their association with patient outcome. DESIGN: Prospective, observational study. SETTING: Emergency department and surgical intensive care unit of a university hospital. PATIENTS: Fifty-four severe blunt trauma patients with systemic inflammatory response syndrome requiring intensive care, emergency surgical intervention, or both were enrolled in the study. Forty-four patients with minor injuries were the controls. INTERVENTIONS: Serum macrophage migration inhibitory factor concentrations were measured in the emergency department <4 hrs postinjury (day 1) and the surgical intensive care unit 24 hrs later (day 2). Blood samples for determination of tumor necrosis factor-alpha, interleukin-6, interleukin-8, and interleukin-10 were measured both in patients with severe blunt trauma and in controls. The Acute Physiology and Chronic Health Evaluation II, Injury Severity Score, Revised Trauma Score, and Trauma Revised Injury Severity Score were used for clinical evaluation of trauma severity. MEASUREMENTS AND MAIN RESULTS: Serum macrophage migration inhibitory factor concentrations were higher in severe blunt trauma patients than in controls; were significantly correlated with Acute Physiology and Chronic Health Evaluation II, Revised Trauma Score, and Trauma Revised Injury Severity Score scores in severe blunt trauma patients but not in controls; and were higher in nonsurvivors than in survivors. CONCLUSIONS: Our data suggest that the serum macrophage migration inhibitory factor concentration is higher in severe blunt trauma and that it reflects the severity of trauma. The serum macrophage migration inhibitory factor concentration might be a valuable predictor for the outcome of severe blunt trauma.

Variability of clinical presentations in three cases of parathyroid carcinoma.

Parathyroid carcinoma accounts for 0.5 to 4.0% of cases of primary hyperparathyroidism. The prognosis depends largely on the extent of successful resection at the time of initial operation. Therefore, early diagnosis before surgery is important. We report 3 cases of primary hyperparathyroidism. The first patient, a 20-year-old uremic female, had refractory hypercalcemia after 5 years of hemodialysis treatment. Hypercalcemia persisted despite repeated parathyroidectomy. Pathology revealed diffuse hyperplasia of the parathyroid glands with focal adenomatous changes. Multiple pulmonary metastases were found later. The second patient, a 45-year-old female with history of nephrolithiasis, presented with severe osteoporosis. She underwent repeated parathyroidectomy for local recurrence. Pathology disclosed typical features of parathyroid carcinoma with adjacent lymph node metastasis. The third patient, a 34-year-old male, had recurrent episodes of extremity fracture and hypercalcemia with palpable neck mass. He underwent resection of the parathyroid tumor. Vascular and capsular invasions were noted microscopically. All three patients were relatively young and had extremely high intact parathyroid hormone (iPTH) level (15 to 31 times the upper limit of normal). The first patient died of hypercalcemia and respiratory failure and the other 2 were treated successfully with surgical excision and, in case 2, combined chemotherapy and radiotherapy. The latter 2 patients had no recurrence during 18 months and 14 months of follow-up, respectively. Our experience with these cases suggests that the combination of the following characteristics are highly suggestive of parathyroid carcinoma: young age, palpable neck mass, concomitant renal and skeletal disease, and extremely high iPTH level in patients with PTH-dependent hypercalcemia.

All chronic rejection failures of kidney transplants were preceded by the development of HLA antibodies.

BACKGROUND: Recent studies show that almost all patients who have rejected a kidney transplant had human leukocyte antigen (HLA) antibodies. In this study, we sought to determine whether patients develop HLA antibodies before chronic rejection. METHODS: For the past 8 years, 139 patients who had undergone kidney transplantation were systematically examined, using an enzyme-linked immunosorbent assay-based method, for the development of class-I and class-II HLA antibodies 3 months, 6 months, and yearly after transplantation. Chronic rejection was diagnosed by biopsy. RESULTS: Among 29 patients with chronic rejection, 100% of the patients had HLA antibodies before rejection. Of these patients, 14 patients developed antibodies de novo. In contrast, among 110 patients with stable function, 27% of the patients developed HLA antibodies posttransplant (P<0.001). CONCLUSIONS: HLA antibodies were found in 29 consecutive cases of chronic rejection failures as much as one year before the loss of grafts. We conclude that HLA antibodies may be a prerequisite for chronic immunologic rejection.

Induction of antinociception and increased met-enkephalin plasma levels by cyclosporine and morphine in rats: implications of the combined use of cyclosporine and morphine and acute posttransplant neuropsychosis.

BACKGROUND: Cyclosporine A (CsA) and morphine have neurotoxic and psychiatric side effects, respectively. Endogenous opiatelike peptides can elicit a number of behavioral responses that mimic the symptoms of psychiatric illness. The purpose of this study was to quantitiate the changes of Met-enkephalin (ME) and beta-endorphin (BE) after administration of CsA and morphine in surgery and to assess the antinociceptive effect. PATIENTS AND MATERIALS: Pain sensitivity, an antinociceptive indicator in rats, was determined with the hotplate test. Plasma ME and BE levels were measured with radioimmunoassays. RESULTS: In normal unoperated rats, CsA induced a profound analgesic effect concomitant with an increased plasma ME level on day 1. Morphine produced an analgesic effect on days 1 and 2, with decreased ME levels on days 2 and 3. Coadministration of CsA and morphine prolonged the analgesia from days 1 to 4 and increased the plasma ME level on day 1. No change in plasma BE level was found. In surgically operated rats, CsA induced an analgesic effect and higher ME levels than those in unoperated rats. Interestingly, the combined use of CsA and morphine prolonged the analgesia and increased plasma ME levels from days 1 to 4, with no significant change in plasma BE levels. CONCLUSIONS: Our results showed that CsA can induce antinociception and increase plasma ME levels. This induction can be potentiated by the addition of morphine. Acute neuropsychiatric manifestations in the early posttransplant period might, therefore, be due to induction of ME after coadministration of CsA and morphine.

A role for chronic parvovirus B19 infection in liver dysfunction in renal transplant recipients?

BACKGROUND: Clinically, liver dysfunction in renal transplant recipients is related to hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The contribution of parvovirus B19 (B19) to liver disease in renal transplant recipients has not been studied. Here we present the association of liver dysfunction with or without the coinfection of B19, HBV, and HCV after renal transplantation. METHODS: We used enzyme-linked immunosorbent assay to identify B19, HBV, and HCV infections in serum samples taken from 144 renal transplant recipients before transplantation and at 12 and 24 months after transplantation. After each patient had fasted for 12 hr, blood was taken for measurement of aspartate aminotransferase and alanine aminotransferase monthly for at least 6 months. RESULTS: Liver dysfunction developed at the significantly higher incidence of 47% in the anti-HCV(+) patients compared with 6% in the noninfected group (P<0.0001). HBV infection had no impact on the incidence of liver dysfunction in renal transplant recipients. A higher incidence of liver dysfunction was found in 42% of B19 IgG(+)IgM(-) group patients compared with 13% of the B19 IgG(+)IgM(+) group (P=0.0051) and 9.5% of the B19 IgG(-)IgM(-) group (P=0.0003). A B19 polymerase chain reaction (PCR) assay revealed significantly higher liver dysfunction in 29% of B19 PCR(+) group patients compared with 13.6% of B19 PCR(-) patients (P=0.0419). Patients who were anti-HCV(+) and B19 PCR(+) had a significantly higher incidence of liver dysfunction than B19 PCR(-) patients (P=0.002). CONCLUSIONS: Chronic B19 infection and HCV infection, both separately and in combination, increase the incidence of liver dysfunction in renal transplant recipients. HBV infection does not seem to be independently or synergistically associated with liver dysfunction.