ABO-incompatible orthotopic liver allografting in urgent indications.

The influence of ABO-compatibility was reviewed in 70 emergency orthotopic hepatic transplantations (OHT) performed at our institution in 60 highly urgent recipients between February 1984 and March 1989. Thirty-eight were ABO-identical (Id); 16, compatible (Comp), and 16, incompatible (Inc) transplants, respectively. The three groups did not differ statistically with respect to the indications, the adult/child ratio and the proportions of first OHT and retransplantations. Graft survival rates of ABO-Id, ABO-Comp and ABO-Inc OHT at one year were 47, 38 and 19 per cent, respectively (p less than 0.02). Incidences of perioperative mortality, arterial thrombosis and irreversible rejection were slightly (although not significantly) higher in the ABO-Inc group. Retransplantation rates were 19, 7 and 36 per cent in the ABO-Id, Comp and Inc groups, respectively. Patient survival rates at one year were 59 per cent for the ABO-Id group versus 43 per cent for both ABO-Comp and Inc combinations (NS). The results of this series of highly urgent OHT confirm that graft survival is lower with ABO-Inc livers; their use should be strictly considered as a short term life-saving procedure. Improvement of patient survival after a first urgent ABO-Inc OHT may require an aggressive policy of retransplantation.     

Somatostatin receptor scintigraphy with 111In-DOTA-lanreotide and 111In-DOTA-Tyr3-octreotide in patients with stage IV melanoma: in-vitro and in-vivo results

The overexpression of somatostatin receptors (SST-Rs) on various tumour cells provides the molecular basis for the successful use of radiolabelled SST analogues in clinical oncology. The objective of the study was to evaluate the tumour binding of In-1,4,7,10-tetraazacyclo-dodecane-N,N',N',N'-tetraacetic acid-lanreotide (In-DOTA-LAN) and In-DOTA-tyrosine-octreotide (In-DOTA-Tyr-OCT) in patients with stage IV melanoma. In addition, we evaluated the potential antiproliferative effect of SST analogues, together with an assessment of the functionality of SST-Rs, on four melanoma cell lines. Twenty-three patients with advanced metastatic melanoma underwent scintigraphy. Thirty-eight of 61 lesions (62%) were positively imaged with In-DOTA-LAN, whereas 23 (37%) were negative. With In-DOTA-Tyr-OCT, 10 of the 23 documented lesions (43%) were positive and 13 (56%) were negative. In vitro, cell lines showed no growth inhibition in the presence of SST analogues and no influence on cell cycle distribution was found with the addition of SST analogues to cultured cells. In addition, no functional surface SST-Rs could be demonstrated on these cell lines. Taken together, our results demonstrate the visualization of metastatic melanoma in a high percentage of patients, probably due to binding of SST analogues to SST-Rs on tumour vessels or infiltrating immune cells. Judging from our data, however, there is no evidence of functional SST-R expression on melanoma cells.     

Altered expression of the hormone- and xenobiotic-metabolizing sulfotransferase enzymes 1A2 and 1C1 in malignant breast tissue

Cytosolic sulfotransferases (SULTs) catalyze the biotransformation of steroid hormones as well as drugs and environmental toxins. Mostly, sulfonation leads to an inactivation of parent compounds, although formation of more toxic and cancerogenic metabolites also occurs. To assess possible alterations in the SULT enzyme expression pattern between malignant and non-malignant tissue, we studied the presence of 9 SULT enzymes of family 1 and 2 by semi-quantitative RT-PCR. Forty-two specimens from ductal and lobular breast carcinomas, lymph node metastasis, mastopathy and normal breast tissue were derived from 29 patients. Substantial expression of SULT 1A1, 1A2, 1A3, 1B1, 1C1, 1E1, 2A1, 2B1a and 2B1b mRNAs was observed in malignant and non-malignant tissue, although the pattern of the individual SULTs varied between the patients, and SULT1C1 mRNA was present in a greater number of malignant than non-malignant tissues (p<0.05). A major finding was that unspliced SULT1A2 mRNA, containing the complete intron between exons 7 and 8, was found in 4 of 16 non-malignant specimens, but was undetectable in the 26 malignant samples investigated. Taken together, the presence of various SULT enzymes in normal, premalignant and malignant breast tissue suggests an important role of SULT-mediated biotransformation in the breast. While the increased expression of SULT1C1 in malignant tissue seems to reflect tumor dedifferentiation, our finding of unspliced SULT1A2 mRNA in non-malignant tissue offers additional aspects regarding the search for breast cancer risk factors.     

Wisconsin rural women's health study psychological factors and blood cholesterol level: difference between normal and overweight rural women

OBJECTIVE: The aim of the present study is to investigate the effects of psychological factors on plasma lipid levels among rural women of central Wisconsin and to compare the effects of these variables among normal-weight and overweight women. METHODS: Stratified sampling was used to select a random sample (n=1500) of farm and non-farm women aged 25 to 71 years from the Central Marshfield Epidemiologic Study Area. The baseline examination included measurements of blood pressure, skin folds, height, weight, and fasting blood lipids, glucose, and insulin. Framingham study questionnaires were employed to measure anger, anxiety, tension, and marital disagreement. The Spielberger Trait anger-reaction subscale was employed to assess proneness to anger. RESULTS: Among normal-weight women, a positive association was found between anger-reaction scores and cholesterol (b=0.008), ratio (b=0.014), triglycerides (b=0.02), and LDL (b=0.07). The odds of elevated cholesterol were highest among women with high scores on the Speilberger anger-reaction scale (OR=2.0) and anger discussion scale (OR=2.0), while the odds were less among women with high scores on the anger-out scale (OR=0.59). However, among overweight women, we found only scores on the Framingham anger-discussion scale as an important factor to determine the plasma lipid levels. CONCLUSION: Anger management may help to sever the link between psychological factors and CHD risk factors. Intervention intended to prevent cardiac events through the reduction of stress and modification of related psychological risk factors have successfully improved the CHD risk factors profile. Similar studies are needed to determine the efficacy of intervention for the primary prevention of CHD risk factors.     

Revisiting liver transplant immunology: from the concept of immune engagement to the dualistic pathway paradigm.

Ever since the demonstration that allografts are rejected through immune reactions of the host, clinical therapies for organ allografts have relied on immune suppression to prevent these destructive events. A growing body of clinical and experimental data suggests that allografts elicit multiple, interactive immune responses. The result is not inevitably graft rejection, and "spontaneous" acceptance of fully allogeneic liver grafts occurs in rodents without immunosuppression. A spectrum of results range from spontaneous acceptance without immunosuppression to rejection with immunosuppression. The "dualistic pathway paradigm" aims to reconcile apparently conflicting observations in liver transplantation and proposes that: (1) immune engagement between the host and the allograft is instrumental in both rejection and acceptance; (2) there exist in all mammalian species congruent interactive pathways of immune activation whereby the fate of the allograft is determined by the quantitative results of these interactions; (3) the dualistic effect of immunosuppressive drugs on pathways of immune activation, conferring the capacity for favorable or unfavorable graft outcome should be investigated in experimental models in which organ allografts are spontaneously accepted. In conclusion the design of clinical strategies based on this research may contribute to protocols resulting in allograft acceptance without chronic immunosuppression.     

Benefit and risk of heparin for maintaining peripheral venous catheters in neonates: a placebo-controlled trial

OBJECTIVES: Heparin addition to infusion fluids is used to prolong catheter patency in newborns. Heparin may also induce adverse effects such as bleeding complications and immune-mediated heparin-induced thrombocytopenia (HIT). One objective was peripheral venous catheter patency with heparinization of continuous infusions (0.5 IU/mL). Secondary objectives were incidences of bleeding, clinically manifest HIT, HIT antibodies, and catheter-related complications. STUDY DESIGN: Inclusion criteria were anticipated need for intravenous peripheral infusion (>or=5 days for HIT-related endpoints) and postnatal age <28 days at study entry. Exclusion criteria were bodyweight <1000 g, congenital malformation, need for therapeutic anticoagulation or mechanical ventilation, and severe bleeding. HIT antibodies were assessed by enzyme-linked immunosorbent assay. RESULTS: A total of 145 infants received heparin, and 151 infants received saline. Patient characteristics, number of additional drugs, duration of treatment, and location and size of catheters did not differ. Patency of catheters was 7.4 hours longer in the heparin group (33.8 hours vs 26.4 hours, P<.0001), but the total numbers of catheters did not differ (565 vs 692, P=.3). No infant developed HIT antibodies. Incidences of bleeding complications and thrombocytopenia were comparable between groups. CONCLUSIONS: Balancing the benefits against the risks of heparin addition and the rare complication of HIT, we will not use 0.5 IU/mL heparin addition to parenteral fluids.     

Association of right ventricular dysfunction and Cheyne-Stokes respiration in patients with chronic heart failure

Cheyne-Stokes respiration (CSR) is present in up to 40% of patients with congestive heart failure (CHF) and is an independent risk factor for increased overall mortality. We examined whether CSR is associated with right ventricular (RV) dysfunction in CHF patients. Parameters of RV function were assessed by two-dimensional echocardiography and tissue velocity imaging in 42 patients (aged 23-75 years) with a left ventricular (LV) ejection fraction below 40%. Respiratory polygraphy revealed CSR with an central apnea-hypopnea index (CAHI) >10 h-1 in 13 of the 42 patients (31%). Demographic characteristics did not differ among the patient groups. The velocity of the tricuspid annular systolic motion (TASM), a parameter reflecting systolic RV function, was significantly reduced in CHF patients with CSR (10.5 +/- 2.3 cm s-1) compared with those without CSR (15.0 +/- 5.1 cm s-1, P = 0.004), and was inversely associated with the CAHI (y = 15.2-0.2x; r = 0.46, P = 0.003). The RV dimensions were significantly increased and the fractional RV area changes significantly reduced in CHF patients with CSR (33 +/- 17 versus 48 +/- 20%; P = 0.04). Doppler parameters of pulmonary artery flow indicate higher pulmonary artery pressures in CSR patients compared with patients without CSR, which is also reflected by an increased RV free-wall thickness in CSR patients (6.5 +/- 1.1 vs. 5.3 +/- 1.3 mm; P = 0.05). Parameters of systolic LV function, forced expiratory volume in 1 s (FEV1), and PaO2 and PaCO2 were not different among patients with or without CSR. In conclusion, CSR is associated with depressed systolic RV function and increased RV dimensions in CHF patients. Future studies will show whether optimized treatment of CSR will improve RV function.