Liver transplantation in tyrosinaemia type 1: the dilemma of timing the operation

Four children with tyrosinaemia type 1 received liver transplants. The metabolic disorder was corrected and all four had normal liver function on an unrestricted diet. Two children, transplanted at age five and seven years, proved to have occult hepatocellular carcinoma and both subsequently developed pulmonary metastases. One child was well 32 months after removal of a single pulmonary metastasis but the other child died with multiple metastases. The two younger children, transplanted at age 19 and 21 months, were well 28 and 44 months after operation, one after a second liver transplant. Our experience confirms the high risk of hepatocellular carcinoma in this disease and the potential value of early liver transplantation.     

SMN2 and NAIP gene dosages in Vietnamese patients with spinal muscular atrophy

Background: The SMN1 gene is now recognized as a spinal muscular atrophy (SMA)-causing gene, while SMN2 and NAIP have been characterized as a modifying factor of the clinical severity of SMA. Gene dosage of SMN2 is associated with clinical severity of SMA. But the relationship between gene dosage of NAIP and clinical severity of SMA remains to be clarified, although complete deletion of NAIP is frequent in type I patients.
Methods: To evaluate the contribution of the SMN2 and NAIP gene dosages to SMA, quantitative real-time polymerase chain reaction was used to measure copy numbers of SMN2 and NAIP in 34 Vietnamese SMA patients lacking SMN1 (13 type I, 11 type II and 10 type III patients).
Results: The SMN2 copy number in type I patients was significantly lower than that in type II–III patients, which was compatible with the previous reports. In contrast, 25 out of 34 patients had only zero or one copy of NAIP , while 50 out of 52 controls had two or more copies. For NAIP (+) genotype, six out of 13 type I patients, eight out of 11 type II patients and six out of 10 type III patients carried one NAIP copy.
Conclusions: The SMN2 copy number was related to the clinical severity of SMA among Vietnamese patients. The presence of one NAIP copy, that is, heterozygous NAIP deletion, was common in Vietnamese SMA, regardless of clinical phenotype.     

Neurological crisis in hereditary tyrosinaemia and complete reversal after liver transplantation

A 19 month old Indian girl with tyrosinaemia developed a severe generalised neuropathy involving both phrenic nerves. Treatment with haemarginate failed to improve her condition. After liver transplantation the raised concentrations of the neurotoxin delta amino-laevulinic acid returned to normal and gradual but complete neurological recovery occurred over a period of 13 months.     

Left ventricular assist devices for the treatment of congestive heart failure

Optional statement The mainstay of heart failure therapy is aggressive medical management with consideration of resynchronization therapy and automatic implantable cardioverter-defibrillator. This is best done with the support of a multidisciplinary team. Transplantation, when possible, remains the therapy of choice for patients who are refractory to medical therapy. Other options short of left ventricular assist device (LVAD) that should be considered include revascularization, mitral valve repair, and left ventricular remodeling procedures. LVAD therapy as a bridge to transplantation should be considered in patients with heart failure who are clinically deteriorating while on the transplant waiting list. This should be initiated prior to the onset of irreversible end-organ damage. In nontransplant candidates, an LVAD can be considered as an alternative to transplantation (destination therapy). However, cost and the availability of expertise continue to limit this therapy to quaternary care and research institutions.     

The possible mechanisms by which phanoside stimulates insulin secretion from rat islets

We recently showed that phanoside, a gypenoside isolated from the plant Gynostemma pentaphyllum, stimulates insulin secretion from rat pancreatic islets. To study the mechanisms by which phanoside stimulates insulin secretion. Isolated pancreatic islets of normal Wistar (W) rats and spontaneously diabetic Goto-Kakizaki (GK) rats were batch incubated or perifused. At both 3 x 3 and 16 x 7 mM glucose, phanoside stimulated insulin secretion several fold in both W and diabetic GK rat islets. In perifusion of W islets, phanoside (75 and 150 microM) dose dependently increased insulin secretion that returned to basal levels when phanoside was omitted. When W rat islets were incubated at 3 x 3 mM glucose with 150 muM phanoside and 0 x 25 mM diazoxide to keep K-ATP channels open, insulin secretion was similar to that in islets incubated in 150 microM phanoside alone. At 16 x 7 mM glucose, phanoside-stimulated insulin secretion was reduced in the presence of 0 x 25 mM diazoxide (P<0 x 01). In W islets depolarized by 50 mM KCl and with diazoxide, phanoside stimulated insulin release twofold at 3 x 3 mM glucose but did not further increase the release at 16 x 7 mM glucose. When using nimodipine to block L-type Ca2+ channels in B-cells, phanoside-induced insulin secretion was unaffected at 3 x 3 mM glucose but decreased at 16 x 7 mM glucose (P<0 x 01). Pretreatment of islets with pertussis toxin to inhibit exocytotic Ge-protein did not affect insulin response to 150 microM phanoside. Phanoside stimulated insulin secretion from Wand GK rat islets. This effect seems to be exerted distal to K-ATP channels and L-type Ca2+ channels, which is on the exocytotic machinery of the B-cells.