Domino hepatic transplantation using the liver from a patient with familial amyloid polyneuropathy

BACKGROUND: In transplantation, novel methods are required to augment the supply of donor organs. We report the first domino liver transplant in which a patient with familial amyloid polyneuropathy (FAP) received an orthotopic split liver graft, and her explanted liver was donated to another patient. Three successful liver transplants were thus achieved from the one cadaver liver. PATIENTS AND METHODS: A cadaveric donor liver was split and the left lobe was grafted into a child with biliary atresia. The right lobe was transplanted into a woman with FAP associated with the transthyretin Met30 variant. Her own otherwise healthy liver was donated to a patient with cirrhosis and hepatocellular carcinoma. RESULTS: Fifteen months after transplantation, all three recipients are well with normal liver function. The domino recipient developed inferior vena cava stricturing at the level of anastomosis after surgery with resultant ascites, requiring dilatation and LeVeen shunt insertion. Serum amyloid P component scintigraphy showed amyloid regression in the domino donor and to date has not identified any amyloid deposits in the recipient, who also remains free of tumor recurrence. CONCLUSIONS: Domino transplantation using the livers from patients with FAP may be justified for patients whose disease condition precludes a long spell on the waiting list, including those with hepatic malignancies and those for whom palliation rather than long-term cure is the aim.     

Serum amyloid P component scintigraphy and turnover studies for diagnosis and quantitative monitoring of AA amyloidosis in juvenile rheumatoid arthritis

OBJECTIVE: To evaluate aspects of the natural history of AA amyloidosis complicating juvenile rheumatoid arthritis (JRA), and its response to therapy with chlorambucil. METHODS: Scintigraphy and 7-day turnover studies were performed in JRA patients with histologically proven (n = 35) or clinically suspected (n = 30) AA amyloidosis, following intravenous injection of 123I and 125I-labeled serum amyloid P component (SAP). Prospective monitoring studies were performed over 2-3 years in 20 patients with amyloidosis. All but 2 amyloidosis patients were treated with chlorambucil. RESULTS: Positive scanning results were obtained in all patients in whom imaging was performed within 12 years of positive biopsy findings of amyloid and in 5 patients with clinically suspected amyloidosis. Negative scanning results with normal SAP metabolism, indicating regression of amyloid, were obtained in 4 patients whose amyloidosis had been in full clinical remission for more than 12 years. Prospective monitoring studies in patients whose JRA-associated inflammatory activity was in remission demonstrated regression of amyloid in 8 patients and no substantial changes in 8 others; however, in 4 further patients with active inflammation, there was accumulation of amyloid. There was a very poor correlation between the amount of amyloid present at a particular site and the resultant organ dysfunction. CONCLUSION: Radiolabeled SAP scintigraphy and turnover studies are useful complementary tools in the diagnosis, screening, and quantitative monitoring of type AA amyloidosis in JRA. The amyloid deposits may progress and/or regress at different rates in different anatomic sites over short periods.     

Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis

Extracellular deposition of amyloid fibrils is responsible for the pathology in the systemic amyloidoses and probably also in Alzheimer disease [Haass, C. & Selkoe, D. J. (1993) Cell 75, 1039-1042] and type II diabetes mellitus [Lorenzo, A., Razzaboni, B., Weir, G. C. & Yankner, B. A. (1994) Nature (London) 368, 756-760]. The fibrils themselves are relatively resistant to proteolysis in vitro but amyloid deposits do regress in vivo, usually with clinical benefit, if new amyloid fibril formation can be halted. Serum amyloid P component (SAP) binds to all types of amyloid fibrils and is a universal constituent of amyloid deposits, including the plaques, amorphous amyloid beta protein deposits and neurofibrillary tangles of Alzheimer disease [Coria, F., Castano, E., Prelli, F., Larrondo-Lillo, M., van Duinen, S., Shelanski, M. L. & Frangione, B. (1988) Lab. Invest. 58, 454-458; Duong, T., Pommier, E. C. & Scheibel, A. B. (1989) Acta Neuropathol. 78, 429-437]. Here we show that SAP prevents proteolysis of the amyloid fibrils of Alzheimer disease, of systemic amyloid A amyloidosis and of systemic monoclonal light chain amyloidosis and may thereby contribute to their persistence in vivo. SAP is not an enzyme inhibitor and is protective only when bound to the fibrils. Interference with binding of SAP to amyloid fibrils in vivo is thus an attractive therapeutic objective, achievement of which should promote regression of the deposits.     

Case of familial amyloid polyneuropathy discovered at the development of hematemesis

In a retrospective study we analyzed clinical features and their prognostic significance in 72 patients with onset of multiple sclerosis by the age of 21 years. In juvenile multiple sclerosis disease progression does not depend on age of onset, severity of neurologic involvement, or polysymptomatic or monosymptomatic involvement at presentation.     

Analysis of amyloid deposition in a transgenic mouse model of homozygous familial amyloidotic polyneuropathy

Amyloid fibrils derived from the Japanese, Portuguese, and Swedish types of familial amyloidotic polyneuropathy all consist of a variant transthyretin (TTR) with a substitution of methionine for valine at position 30 (TTR Met 30). In an attempt to establish an animal model of TTR Met-30-associated homozygous familial amyloidotic polyneuropathy and to study the structural and functional properties of human TTR Met 30, we generated a mouse line carrying a null mutation at the endogenous ttr locus (ttr-/-) and the human mutant ttr gene (6.0-hMet 30) as a transgene. In these mice, human TTR Met-30-derived amyloid deposits were first observed in the esophagus and stomach when the mice were 11 months of age. With advancing age, amyloid deposits extended to various other tissues. Because no significant difference was detected in the onset, progression, and tissue distribution of amyloid deposition between the ttr-/- and ttr+/+ transgenic mice expressing 6.0-hMet 30, endogenous normal mouse TTR probably does not affect the deposition of human TTR Met-30-derived amyloid in mice. TTR is a tetramer composed of four identical subunits that binds thyroxine (T4) and plasma retinol-binding protein. The introduction of 6.0-hMet 30 into the ttr-/- mice significantly increased their depressed serum levels of T4 and retinol-binding protein, suggesting that human TTR Met 30 binds T4 and retinol-binding protein in vivo. The T4-binding ability of human TTR Met 30 was confirmed by the analysis of T4-binding proteins in the sera of ttr-/- transgenic mice expressing 6.0-hMet 30. The T4-binding studies also demonstrated the presence of hybrid tetramers between mouse and human TTR subunits in the ttr+/+ transgenic mice expressing 6.0-hMet 30.     

Comparison of amyloid deposition in two lines of transgenic mouse that model familial amyloidotic polyneuropathy, type I

Aortic disease frequently requires extended and multiple resections. Occasionally, resection of the entire aorta may be indicated. At our Institution, from 1982 to 1994, 34 patients were operated upon for extended and total simultaneous aortic replacement. In seven patients, the aorta was replaced from valve to bifurcation; in 27, the aortic valve was included. Operations were performed with circulatory arrest under profound hypothermia. As the first step, the aortic valve and ascending aorta are replaced and the coronary arteries are reconnected, following which the aortic arch is reconstructed. Meanwhile, a second surgical team proceeds to open the thoracoabdominal aorta and tie up the intercostal orifices. If circulatory arrest is likely to exceed 60 minutes, the aortic graft is clamped and upper body perfusion (1000 cc/min) is begun. Finally, the thoracoabdominal aorta is fully replaced. Cardiopulmonary bypass (CPB) with rewarming is resumed only after the operation has been completed. Thirty-four patients survived operation; five died within 1 month for an overall mortality of 14.7%. No mortality occurred in the most recent nine operations. No permanent spinal neurological deficits occurred. Total simultaneous aortic replacement for treatment of extended aortic disease may be reasonable using our approach.     

Recurrence of autoimmune hepatitis following liver transplantation

A patient with complaints of right foot pain and previous normal radiographs had an abnormal three-phase bone scan consistent with a second metatarsal stress fracture. Subsequent radiographs confirmed this diagnosis. Two months later, the patient developed pain in his left foot, and again initial radiographs were noncontributory. A later bone scan revealed a left second metatarsal stress fracture. The results in this case reemphasize the value of bone scintigraphy in patients with foot pain and no bone abnormalities on plain radiographs.     

Binding of human serum amyloid P component (hSAP) to human neutrophils

Human serum amyloid P component (hSAP) and human C-reactive protein (hCRP) are normal serum constituents related to the pentraxin family of plasma proteins. hSAP has morphological and immunochemical identity and extensive sequence similarity to the amyloid P (AP) component found in normal tissues and particularly in amyloid deposits. hCRP and its proteolytic products have been previously shown to bind and to interact with various types of human leukocytes. Binding-displacement experiments with 125I-labeled hSAP and hCRP show that both proteins have specific high-affinity binding sites on normal human polymorphonuclear leukocytes (PMN) and each can compete efficiently with the binding of the other. Scatchard analysis of hSAP-displacement curves reveals a heterogeneous population of hSAP-binding sites existing on the PMN cells, among them about 300,000 low-affinity binding sites with Kd < or = 5 x 10(-6) M and about 30,000 high-affinity binding sites with Kd < or = 5 x 10(-8) M. hAP was found to be degraded by enzymes from human neutrophils to yield a mixture of low-molecular-mass peptides, similarly to the case of CRP reported previously. The binding of hSAP can be efficiently inhibited by this peptide mixture. The results suggest that both hCRP and hSAP, together with related peptides, may participate in vivo in an unknown mechanism of regulation of human neutrophils.     

Calcium-dependent and -independent binding of the pentraxin serum amyloid P component to glycosaminoglycans and amyloid proteins: enhanced binding at slightly acid pH

It has been found that sphingosine and sphingosylphosphorylcholine (amphiphilic cations) have a stimulatory, and cholesterol 3-sulfate (an amphiphilic anion), an inhibitory, effect on [14C]serine incorporation into phosphatidylserine in glioma C6 and rat liver microsomes. In glioma intact cells sphingosine stimulates phosphatidylserine synthesis in a process independent of protein kinase C, but suppressed by thapsigargin. We suggest that the stimulation of the enzyme occurs by the interaction of amphiphilic cations with the membrane cosubstrate phospholipids, leading to a charge redistribution on their phosphate groups, and hence facilitating the enzyme action. A new hypothesis concerning the mechanism of the serine base exchange reaction is discussed.     

Differing haemodynamic and catecholamine responses to exercise in three groups with peripheralautonomic dysfunction: insulin-dependent diabetes mellitus, familial amyloid polyneuropathy and pure autonomic failure

BACKGROUND: The nosological status of postpartum psychoses has remained controversial because of their often 'atypical' symptomatology. A polydiagnostic approach may further clarify this issue. METHODS: In a retrospective study, we applied the ICD-10 and Leonhard's classification to 39 patients with severe postpartum psychiatric disorders. The patients were personally reexamined on average 12.5 years (6-26 years) after the onset of the illness. RESULTS: An acute onset and a polymorphous psychotic symptomatology with rapid changes characterized the majority of our cases. Unipolar depressive disorders (28%) and acute polymorphous psychotic disorders (21%) represented the largest proportions within the ICD-10-classification. Applying Leonhard's classification, over half the patients (54%) suffered from a cycloid psychosis. Among cycloid psychoses, motility psychoses clearly predominated. Schizophrenias occurred rarely (10%) according to both classifications. LIMITATIONS: Due to the unknown prevalence of the various diagnoses among women of child-bearing age, it is impossible to statistically infer a specific association between childbirth and a distinct diagnosis from our data. CONCLUSIONS: Our findings suggest that cycloid psychoses, in particular motility psychoses, account for the majority of postpartum psychoses, and do not support the hypothesis of a nosological independence of postpartum psychoses.     

The radiological management of biliary complications following liver transplantation

PURPOSE: Biliary complications contribute significantly to morbidity and mortality in the liver transplant recipient. Surgery has been the mainstay of therapy, but interventional radiological techniques have made significant progress. METHODS: Diagnostic percutaneous transhepatic cholangiography (PTC) was performed in 12 patients; percutaneous transhepatic drainage (PTD) was performed in 10 patients. Additional interventional procedures included laser lithotripsy, biopsy, dilatation, and stent implantation. RESULTS: In 6 patients PTC revealed anastomotic, and in 6 patients nonanastomotic biliary strictures. Four patients had intrahepatic stones. Biliary strictures were treated by implantation of Palmaz stents in 5 of 6 patients with anastomotic strictures, and in 3 of 6 patients with nonanastomotic strictures. The intrahepatic stones were fragmented with dye laser lithotripsy under cholangioscopic control in 3 of 4 patients. One spontaneous stent migration after 24 months and one stent occlusion were observed; the remaining stents are still patent. Patients with anastomotic strictures had a more favorable outcome: 5 of 6 of these patients are still alive and symptom-free after an average of 27.4 months, but only 3 of 6 patients with nonanastomotic strictures are alive after an average of 9.8 months. CONCLUSION: The different outcomes in patients with anastomotic versus nonanastomotic strictures may be explained by the different causes of these types of stricture.     

Meal patterns prior to and following liver transplantation in rats

As the second part of a community based educational campaign to convey the risk of HIV/AIDS to commercial sex workers in Jakarta, from May-July 1995, a total of 253 male transvestites (WARIA) were questioned about their sexual behavior patterns and their knowledge and attitude toward HIV/AIDS. In the previous report, 1991-1993, there was one out of 830 WARIA found HIV positive in November 1993. In this study, 1995, a total of two out of 253 WARIA were confirmed of HIV infection in July 1995. Most of them still have incorrect knowledge on HIV/AIDS transmission mode, they are still practicing high risk sexual attitudes such as an exchange partner rate of 5 men per three weeks, low condom use (1.2 out of the last 5 sexual contacts). The reasons for not using condoms were forgetfulness 35.3% and partner does not like condom 38.2% Most of WARIA know about condoms (94.5%), but it is difficult to access condom use from small shops around them. Therefore, to prevent further spread of HIV/AIDS in WARIA, condom should be used constantly and properly. It has been shown from another study, that more information, better availability and better promotion of condoms can increase condom use. Thus, attention should be placed on various ways of distributing condoms for WARIA in Jakarta, especially community-based distribution by peer leaders, social marketing and commercial sales.