[Parental responses to children's pain : Analysis of the parental responses to their child's pain in the German general population]. / Elterliche Reaktionen auf kindlichen Schmerz : Analyse der elterlichen Reaktionen auf die Schmerzen ihres Kindes in der deutschen Allgemeinbevölkerung.

BACKGROUND: Parental reactions to their child's pain can comprise cognitive-affective and behavioral responses. Dysfunctional responses like parental catastrophizing may lead to an aggravation of the child's pain. OBJECTIVES: Aims of the online-based study were (1) to psychometrically evaluate existing questionnaires into cognitive-affective (Pain Catastrophizing Scale for Parents; PCS-P) and behavioral responses (Inventar zum schmerzbezogenen Elternverhalten; ISEV-E) within a sample of 105 healthy parents, and (2) to compare their responses to existing (inter)national clinical samples and to the reactions of 80 parents with self-reported chronic pain from the general population. METHODS: The assessment of parental pain-related reactions was online-based. RESULTS: While the factor structure of the ISEV-E could not be replicated, the three factors of the PCS-P could be replicated. Parental catastrophizing of the healthy parents was lower compared to clinical samples. Healthy parents did not differ from parents with chronic pain from the general population. CONCLUSION: The results offer a basis to grade parental catastrophizing, so that risk-groups can be identified.

[Pain-related parental behavior : Maternal and paternal responses to chronic pain of their child and modifications following inpatient interdisciplinary pain treatment]. / Schmerzbezogenes Elternverhalten : Mütterliche und väterliche Reaktionen auf die chronischen Schmerzen ihres Kindes und deren Veränderung nach stationärer interdisziplinärer Schmerztherapie.

BACKGROUND: There is a dearth of research studies regarding the pain-related behavior of parents with children suffering from chronic pain. This study examined the pain-related reactions of mothers and fathers, analyzed changes in these reactions following the child's inpatient interdisciplinary pain treatment and identified predictors for these changes. METHOD: Using validated questionnaires 40 mothers and 40 fathers of children suffering from chronic pain reported their pain-related responses and cognitive distortions at treatment commencement, immediately following therapy as well as at follow-up after 6 and 12 months. RESULTS: At treatment commencement there were neither differences between maternal and paternal behavior nor in their reactions towards the sons and daughters. Immediately after treatment both parents showed increased distracting behavior and decreased solicitous behavior. Only the change in solicitous behavior showed long-term stability. The study identified the extent of parental catastrophizing at treatment commencement as well as changes in this reaction during treatment as predictors for reduction in solicitous behavior. The more parents reported catastrophizing thoughts at treatment commencement, the less they changed their solicitous behavior and strong changes in catastrophizing during treatment correlated with strong changes in solicitous reactions. CONCLUSION: Pain-related solicitous behavior can be modified by the interdisciplinary inpatient treatment of chronic pain in children and changes in solicitous behavior seem to be closely related to parental catastrophizing. This association should be considered when dealing with parents of children with chronic pain and also within the framework of future research projects.

[The need to monitor risk factors relating to patients on antipsychotics]. / Monitoring van risicofactoren bij het gebruik van antipsychotica.

BACKGROUND: The use of antipsychotics can lead to the development of obesity, dyslipidemia, hypertension and hyperglycemia, risk factors for diabetes mellitus type 2 and cardiovascular diseases. AIM: To find out whether patients suffering from psychoses and schizophrenia and taking antipsychotics should be monitored systematically and periodically for the risk factors for and complications of the above-mentioned diseases. METHOD: A written survey was conducted among the relatives of users of antipsychotics, relatives being members of the Ypsilon association in the Limburg region. RESULTS: Seventy-eight relatives (27%) returned the forms. Compared to the Dutch population, the risk factor for high blood pressure was remarkably common in the 20-30 age group. In the group of persons aged 30-40 obesity occurred surprisingly frequently; remarkably frequent too was diabetes in the 40-50 age group. At each monitoring session 27% of the users were checked on all parameters. Only 59% of the users were checked periodically. CONCLUSION: Apparently, systematic and regular monitoring of risk factors and somatic complications is currently inadequate. The regional survey therefore needs to be extended so that it covers the entire country.

Identification of novel dyslexia candidate genes through the analysis of a chromosomal deletion.

Dyslexia is the most common childhood learning disorder and it is a significantly heritable trait. At least nine chromosomal loci have been linked to dyslexia, and additional susceptibility loci on other chromosomes have been suggested. Within two of these loci, DYX1C1 (15q21) and ROBO1 (3p12) have recently been proposed as dyslexia candidate genes through the molecular analysis of translocation breakpoints in dyslexic individuals carrying balanced chromosomal translocations. Moreover, genetic association studies have indicated a cluster of five dyslexia candidate genes in another linkage region on chromosome 6p22, although there is currently no consensus about which of these five genes contributes to the genetic susceptibility for dyslexia. In this article, we report the identification of four new dyslexia candidate genes (PCNT, DIP2A, S100B, and PRMT2) on chromosome region 21q22.3 by FISH and SNP microarray analyses of a very small deletion in this region, which cosegregates with dyslexia in a father and his three sons.

Quantification of alpha 1-fetoprotein mRNA in peripheral blood and bone marrow: a tool for perioperative evaluation of patients with hepatocellular carcinoma.

BACKGROUND/AIMS: Quantification of alpha 1-fetoprotein (AFP) mRNA in the blood using reverse transcriptase polymerase chain reaction (RT-PCR) could be a useful tool in monitoring the dynamics of minimal residual disease in patients with hepatocellular carcinoma (HCC). Since all available assays do not take into account the efficiency of cell separation, RNA extraction and reverse transcription, a competitive RT-PCR assay for quantification of AFP mRNA in relation to the housekeeping gene glyceraldehyde phosphate dehydrogenase (GAPDH) was established. PATIENTS AND METHODS: Peripheral blood of 22 patients and bone marrow aspirates of 11 patients with hepatocellular carcinoma was monitored perioperatively. Eighteen patients with other hepatic tumours or non-malignant hepatic diseases and 26 healthy blood donors served as controls. Messenger RNA contents were calculated relative to the content of GAPDH mRNA as an indicator of total cell count. RESULTS: Among HCC patients, 6 of 22 (26%) were positive for AFP mRNA before operation with values ranging from 2 ag/100 fg to 36 ag/100 fg GAPDH mRNA (mean 14). Among bone marrow samples, AFP mRNA was detectable in 5 of 11 (45%) cases, with 4 ag/100 fg to 23 ag/100 fg GAPDH (mean 9). However, AFP mRNA was also detectable in 3 of 18 (17%) control patients and in 2 of 26 (8%) healthy blood donors. Perioperative findings were highly variable. CONCLUSION: AFP mRNA is not a specific marker for circulating malignant hepatocytes. Whether definition of a cut-off level or the use of a multimarker-PCR will provide more useful data remains to be established.

Isolated hyperthermic liver perfusion with high dose tumor necrosis factor alpha in pigs: an experimental study in preparation of clinical Use.

Isolated hyperthermic perfusion of the liver was performed for 45 min in 27 pigs via hepatic artery and portal vein at mean inflow temperatures between 40.7 and 41.2 degrees C. In two study groups B and C (n = 9 pigs each) 50 microg recombinant human tumor necrosis factor-alpha (rhTNFalpha) per kg body weight were added to the perfusate, whereas in a control group A liver perfusion was done without rhTNFalpha. Before reperfusion the livers were washed out with Ringer's solution in all groups followed by a protein solution in group C. At 30 and 60 min after reperfusion the maximum systemic rhTNFalpha concentrations were significantly higher in group B with 68 and 61 ng/ml compared to 14.5 and 14.9 ng/ml in group C (p < 0. 05). Mean systemic porcine TNFalpha concentration was significantly higher in group B (217 pg/ml) compared to group C (50 pg/ml) 30 min after reperfusion (p = 0.012). Survival was 7/9 in group A and C and only 2/9 in group B with 6/7 pigs dying due to severe cardiopulmonary failure within 12 h after operation. In surviving pigs of group A and C only mild and transient hepatotoxicity was registered. The presented study underlines the feasibility of high dose rhTNFalpha application in an isolated hyperthermic liver perfusion system. Washout of the liver with a protein solution before reperfusion reduces systemic TNFalpha levels as well as associated lethal cardiocirculatory and hepatotoxic side effects.

Long-term outcomes in pediatric liver recipients: comparison between cyclosporin A and tacrolimus.

In recent years, tacrolimus (FK506, TAC) has been increasingly utilized in liver transplantation. However, long-term risks and benefits as compared with conventional cyclosporin A (CsA) have not been fully elucidated. This retrospective study examined the potential outcome differences between TAC- and CsA-based immunosuppressive therapy in pediatric liver transplant recipients. From March 1988 to December 1996, 218 children (aged 0.1-17 yr) underwent 238 orthotopic liver transplantations; 58.7% (128/218) were under 2 yr of age at time of transplant. Initially, the maintenance immunosuppressive regimen consisted of CsA and prednisone, with antilymphocytic preparations (MALG, ATGAM, and OKT3) as induction therapy. Subsequently, TAC was used first as rescue therapy for steroid refractory rejection in CsA patients and then as maintenance immunosuppression. Fifty-seven out of the 147 CsA patients were converted to TAC for various reasons while 71 patients were placed on TAC as primary maintenance immunosuppression. 62.6 per cent (92/147) of liver recipients on CsA experienced at least one biopsy-proven acute rejection episode as compared to 50.7% (36/71) for TAC patients (p = 0.09); likewise, 34% (50/147) of CsA patients had more than one episode of rejection vs. 18.3% (13/71) for patients on TAC (p < 0.02). Rejection was the reason for conversion from CsA to TAC in 29 of 57 patients. Conversely, 19.0% (28/147) of CsA patients had to be switched to TAC for reasons not related to rejection (i.e. side-effects). The overall incidence of histologically proven chronic rejection was 7.8% (17/218). 10.9 per cent (16/147) of the children who were on CsA initially developed chronic rejection, which was significantly higher compared with one of 71 TAC recipients (p < 0.02). Of these 16 CsA patients with chronic rejection, 50.0% (8/16) underwent retransplantation for graft failure (mean interval from time of diagnosis of chronic rejection to re-transplant, 4.0 months; range 1-8 months), whereas the TAC patient has remained clinically stable with normal liver function tests after 23 months of follow-up. One year after liver transplantation, 72.8% (107/147) of CsA patients were still on steroids (mean dosage 0.20 mg/kg/d), as compared to 42.3% (30/71) of the TAC patients (mean dosage 0.14 mg/kg/d). The incidence of post-transplant lymphoproliferative disorder (PTLD) in Epstein-Barr virus (EBV)-infected patients was 2.2% (2/90), 7.0% (5/71) and 12.3% (7/57) for CsA, primary and TAC-converted groups, respectively. The overall incidence of PTLD was 6.9% (15/218). In summary, pediatric liver transplant recipients treated with TAC as primary maintenance immunosuppressive medication experienced significantly fewer episodes of rejection; especially chronic rejection, which lead to graft loss. However, the trade-off is a potential increased incidence of EBV-related PTLD in these patients.

Rescue hepatectomy for initial graft non-function after liver transplantation.

BACKGROUND: Early retransplantation is the therapy of choice in patients with initial graft nonfunction (INF). In rare cases the patients' conditions deteriorate dramatically with severe cardiovascular and/or pulmonary insufficiency while on the waiting list for retransplantation. In this life-threatening situation removal of the graft and temporary portocaval shunt before allocation of a new liver proved to be effective. Our experience with this two-stage hepatectomy and subsequent liver transplantation in patients with complicated INF is reported. METHODS: Hepatectomy was performed in 20 patients with INF associated with severe cardiovascular and pulmonary insufficiency while on the waiting list for emergency liver retransplantation. The mean age was 41.75+/-16.64 years. The time period between primary transplantation and hepatectomy was 2.80+/-2.84 days with a range from 1 to 9 days. RESULTS: Hepatectomy reduced the need for vasopressive agents and improved pulmonary function in the majority of patients. Four patients died before a liver was available due to brain death in one patient and multiorgan failure in three patients. In the remaining 16 patients liver transplantation could be performed after 19.82+/-15.34 hr (range 6.58 to 72.50 hr). Two of the 16 transplanted patients died on the first postoperative day due to multiorgan failure and pneumonia. The remaining 14 of 16 patients survived retransplantation, but 7 died between days 13 and 105 mostly due to sepsis. Seven patients were discharged from the hospital in good condition and show long-term survival. CONCLUSION: Hepatectomy was able to stabilize the cardiovascular and pulmonary function. This study confirms the beneficial effects of hepatectomy and subsequent liver transplantation as a life-saving procedure in patients with INF complicated by cardiovascular and/or pulmonary instability.

Benign schwannoma of the liver with cystic changes misinterpreted as hydatid disease.

The rare event of a benign mesenchymal tumor of the liver is described since its cystic transformation resembled hydatid disease through the presence of Echinococcus. Ultrasound and computerized tomography showed a cystic mass within the liver of a 57 year-old woman with upper abdominal pain. This was interpreted as hydatid disease and an evacuation procedure was performed. The histopathology of a minute specimen was interpreted as consistent with chronic inflammation in a cyst wall. Five years later, a recurrence of the parasite was suspected, and complete excision of the mass and resection of a bile fistula was performed. The histopathological examination revealed a large benign schwannoma with regressive cystic changes, proven by positive immunoreaction for the neurogenic marker S-100 protein. Revision of old paraffin blocks of tissue taken during the first operation was able to retrospectively confirm the identical tumor by the same markers. Occurrence of schwannomas in parenchymatous organs or the retroperitoneum is extremely rare and may lead to asymptomatic growth with cystic changes, causing considerable difficulties in imaging procedures. Overall, the primary complete excision of cystic masses within the liver seems to be the best approach in discovering their real nature and to ultimately cure them.

Two-step procedure in Budd-Chiari syndrome with severe intrahepatic vena cava stenosis: vena cava stenting and portocaval shunt.

Budd-Chiari syndrome is characterized by hepatic venous outflow obstruction, which often leads to death as a result of portal hypertension and liver failure. Venous decompressive shunt surgery and liver transplantation represent efficient surgical treatments of Budd-Chiari syndrome. In the case presented here, severe intrahepatic compression of the inferior vena cava (IVC) was caused by the hypertrophic caudate lobe. A mere portocaval shunt was not feasible because of a large pressure gradient across the intrahepatic stenosis. A two-step procedure with preoperative radiological dilation and stenting of the intrahepatic IVC followed by a portocaval shunt was successfully performed. Consequently, liver transplantation and its subsequent immunosuppression could be avoided.

The surgical technique of isolated hyperthermic arterial liver perfusion in humans.

Various techniques of isolated liver perfusions have been described, using hepatic artery or both hepatic artery and portal vein. In this paper the technique of isolated arterial liver perfusion is presented. Twelve patients suffering from non-resectable liver tumors underwent this approach. All of them had been previously unsuccessfully treated by resection or systemic chemotherapy. The liver perfusions were performed without technical problems. No operative death occurred. The mean operating time was 413 +/- 29 min. Although the perfusion medium was oxygenated and the absolute anoxic period was shorter than 10 min in all cases the perfused livers showed a marked postoperative increase of liver enzyme levels. Further studies should be aimed at reducing this hepatic injury and simplifying the complex surgical procedure.

First experience and technical aspects of isolated liver perfusion for extensive liver metastasis.

BACKGROUND: New drugs and modalities for locoregional tumor treatment in recent years may offer new potential for isolated liver perfusion in patients with nonresectable liver tumors. The purpose of this study was to prove the feasibility of arterial isolated liver perfusion and to assess the tolerance of perfusion with high-dose tumor necrosis factor (TNF). METHODS: Twelve patients with extensive liver metastases previously treated unsuccessfully with systemic chemotherapy underwent isolated hyperthermic liver perfusion using a heart-lung machine. High doses of mitomycin were administered in the first six and a combination of TNF and melphalan in the last six patients. RESULTS: No operative death occurred and no direct postoperative liver failure was observed in any patient. In cases of variations of the arterial hepatic blood supply, the perfusion was done through the splenic artery or an angiography catheter. Histologic analysis of tumor biopsy specimens obtained on the first postoperative day revealed major tumor necrosis in 8 of 12 patients. CONCLUSIONS: Isolated arterial perfusion of the liver is a complex surgical procedure that is feasible in patients with anatomic variations of the hepatic artery. The remarkable histologic response to perfusion in several pretreated patients, especially after application of high-dose TNF and melphalan, suggests that this modality is very effective in tumor killing.

High-dose mitomycin C in isolated hyperthermic liver perfusion for unresectable liver metastases.

In order to reduce systemic side effects and increase intrahepatic mitomycin C (MMC) concentrations, isolated hyperthermic liver perfusion (IHLP) has been performed using MMC. This article describes the pharmacokinetics of MMC in IHLP and presents our clinical experience with its use in six patients suffering from unresectable liver metastases. Primary tumors consisted of colorectal carcinomas in three cases, breast cancer in two, and a choroidal melanoma in one. Dosages of MMC varied between 0.5 and 1.0 mg MMC/kg body weight. MMC was added as a bolus directly into the extracorporeal circuit. Intrahepatic temperature was elevated to 40.0-41.0 degrees C by hyperthermic perfusion. MMC concentrations were measured in peripheral blood (preperfusion, then at 5, 30, and 55 min during perfusion, and finally at 5 and 60 min and 6 and 24 h after perfusion) and in recirculating perfusate (5, 30, and 55 min). While markedly elevated MMC concentrations (maximum 6290 ng/mL) were found in the liver perfusate, systemic concentrations remained low (maximum 45 ng/mL), indicating no considerable leakage. MMC concentrations in the perfusate constantly decreased during perfusion. After rinsing with 1500 mL saline, a mean concentration of 52.5+/-33 ng MMC/mL was measured in the washout from 5 patients. In 1 patient with a colorectal carcinoma, MMC concentrations in the perfusion medium were 10-fold and in the plasma 2-fold higher than in the other patients. This high MMC concentration caused severe intrahepatic vascular damage and finally led to the patient's death. In conclusion, IHLP and intrahepatic perfusion with MMC resulted in a high response of hepatic tumors. Systemic exposure of MMC can be reduced effectively by isolated perfusion. However, hepatic toxicity of MMC must be considered.