Megacystis and megacolon in an infant with Ehlers-Danlos syndrome

We report a 14 month old male infant with Ehlers-Danlos syndrome who became ‘anuric’ due to an acutely dilated urinary bladder. Although the patient was also found to have megacolon, no diverticulum was seen in his gastrointestinal tract or urinary bladder. In order to decompress the urinary bladder and colonic wall, we put an indwelling urinary catheter in place for 2 months, and carried out daily glycerin enema for 3 months. All urological and gastrointestinal symptoms subsided with this intensive medical treatment. The diagnosis of megacystis and megacolon was made very early in life for this patient. This may indicate that the striking extension of gastrointestinal and bladder wall may lead to the development of diverticula of gastrointestinal and urinary tracts in later life.     

Expression of the Plasmodium berghei ookinete protein Pbs21 in a baculovirus-insect cell system produces an efficient transmission blocking immunogen

A surface protein of Plasmodium berghei ookinetes, Pbs21, was expressed in a baculovirus-insect cell system in cell culture and in Heliothis virescens larvae. Groups of BALB/c mice received two intraperitoneal inoculations of either i) Tris-buffer or homogenized H. virescens larvae infected with wild-type baculovirus; ii) enriched, homogenized ookinetes, or Hi) homogenizedH. virescens larvae expressing recombinant Pbs21 (rPbs21). All animals immunized with ookinetes or with rPbs21 had high litres of antibodies (IgG isotype) that bound to native Pbs21. The large majority of antibodies in immune sera of both groups recognized the antigen under non-reducing but not under reducing conditions. The predominant IgG-sub-classes in mice immunized with ookinetes was IgGl and in mice immunized with rPbs21, the subclasses were IgGl and IgG2a. Immunization with rPbs21 reduced the infec-tivity of P. berghei to mosquitoes by 91% compared to a 99% reduction following immunization with ookinetes. This preliminary data indicate that rPbs21 expressed in this eukaryotic system induces a transmission-blocking immunity which is more effective than that achieved using rPbsll expressed in Escherichia coli (Matsuoka et al. 1994).     

Detection of hepatocellular carcinoma after interferon therapy for chronic hepatitis C: Clinical study of 26 cases

The clinical findings in 26 patients in whom hepatocellular carcinoma (HCC) was detected after the start of interferon (IFN) therapy for chronic hepatitis C were analysed. Histological study before IFN therapy showed that 34.6% of patients were categorized as stage 3 (septal fibrosis with architectural distortion; the 0–4 scale) and 80.8% demonstrated at least some evidence of septal fibrosis or more advanced features. The AFP levels examined before IFN therapy were more than 20 ng/mL in 13 patients (84.6% of those studied). One of 26 patients had a complete response to IFN therapy, while six of 26 patients had only a partial response. HCC was detected within 1 year after the start of IFN therapy in 76.9% of patients. Thus, the possibility of the early occurrence of HCC or its existence at the time of therapy should be seriously considered when IFN therapy is contemplated. Patients with stage 3 or 3–4 histology may already have a small undetectable HCC before IFN therapy. Thus, for this reason, every patient treated with IFN should be examined at short regular intervals for the development of HCC during and after IFN therapy.     

Deficiency of endogenous prostanoids in gastric and duodenal ulcer diseases

The levels of prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F₁α (PGF₁α) and thromboxane B₂ (TXB₂) in endoscopic biopsy specimens from the gastric and duodenal mucosa of healthy volunteers and ulcer patients were measured by radio-immunoassay. The PGE₂ and PGF₁α levels in the mucosa of the corpus of the stomach were lower and the TXB₂ level was higher in 10 patients with gastric ulcer in the corpus than in the 16 healthy subjects. The PGE₂ level in the antral mucosa of 14 patients with gastric ulcer in the antrum was lower than in the controls. In 18 patients with duodenal ulcer, PGE₂ deficiency was more widespread in the entire gastric and duodenal mucosa while the reduced PGF₁α level was limited in the gastric corpus. Lower levels of PGE₂ in patients with antral or duodenal ulcer and of PGE₂ and PGF₁α in patients with corpus ulcer in the anatomical mucosal area including the ulcer site may predispose the mucosa to ulceration.     

Sequential changes of [3H]cyclic AMP binding in the gerbil brain following transient cerebral ischaemia

Abstract— Sequential alterations in the binding of [³H]cyclic AMP (cAMP) as an indicator of cAMP-dependent protein kinase (cAMP-DPK) binding activity following transient cerebral ischaemia were studied in the gerbil brain using receptor autoradiography. Transient ischaemia was induced for 10 min. [³H]cAMP binding in the stratum oriens and pyramidale of the hippocampal CA1 sector significantly decreased in the early post-ischaemic stage and showed severe reduction 7 days and 1 month after recirculation. By contrast, [³H]cAMP binding showed no significant alterations in the stratum radiatum of the hippocampal CA1 sector and the stratum pyramidale of the hippocampal CA3 sector up to 48 h after ischaemia. However, the binding in these areas significantly decreased 7 days and 1 month after ischaemia. The stratum lacunosum-moleculare of the hippocampal CA1 sector and dentate gyrus showed no significant changes in [³H]cAMP binding throughout the recirculation period. However, in the dorsolateral part of the striatum, where severe neuronal damage was seen morphologically, [³H]cAMP binding was significantly reduced only one month after ischaemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 sector, but not in the striatum. Furthermore, our autoradiographic data suggest that post-ischaemic alteration in [³H]cAMP binding between the hippocampal CA1 sector and striatum may be produced by different mechanisms.     

Successful Radiofrequency Current Catheter Ablation of Sustained Ventricular Tachycardia

We performed radiofrequency current catheter ablation in two patients with nonischemic sustained ventricular tachycardia (VT). In one patient, two morphologically distinct VTs were induced by electrical stimulation. One showed right bundle branch block pattern and the other left bundle branch block pattern. The earliest site of activation during each VT was determined at the septum of the right ventricle. However, these two sites were close to the His-bundle elecfrogram recording area. In the other patient, a VT with a left bundle branch block pattern occurred spontaneously after the administration of isoproterenol. The earliest site of activation during VT was determined at the outflow tract of the right ventricle. During tachycardia, radiofrequency current ablation (40 W ± 30 sec) was delivered to the earliest site of activation, A few seconds after fulguration, each VT was terminated and additional radio-frequency currents were given near these sites. After the ablation, VT could not be induced by the electrical stimulations, nor did it recur. No side effects were observed and the atrioventricular conduction remained intact. We feel that nonischemic VTs could possibly be treated by using radiofrequency current catheter ablation.     

Electrophysiological Characteristics of Localized Reentrant Atrial Tachycardia Occurring After Catheter Ablation of Long-Lasting Persistent Atrial Fibrillation

Background: Mapping of recurrent atrial tachycardia (AT) after extensive ablation for long-lasting persistent atrial fibrillation (AF) is complex. We sought to describe the electrophysiological characteristics of localized reentry occurring after ablation of long-lasting persistent AF.
Methods: Out of 70 patients undergoing catheter ablation of long-lasting persistent AF, 9 patients (13%, 55 ± 8 years, 8 males) in whom localized reentry was demonstrated in a repeat ablation were studied. Localized reentry was defined as reentry in which the circuit was localized to a small area and did not have a central obstacle. The mechanism of AT was determined by electroanatomical and entrainment mapping.
Results: Nine localized reentries with cycle length of 243 ± 41 ms were mapped in 9 patients. The location of AT was the left atrial appendage in 4 patients, anterior left atrium in 2, left septum in 2, and mitral isthmus in 1. In all ATs, a critical isthmus of <10 mm in width was identified in the vicinity of the prior linear lesions or ostia of isolated pulmonary veins. Ablation of the critical isthmus, which was characterized by continuous low-voltage activity (median voltage: 0.15 mV, mean duration: 117 ± 31 ms), terminated AT and rendered it noninducible. Additionally, ablation was performed for all of inducible ATs. At 11 ± 7 months after the procedure, 8 of 9 patients (89%) were free from any arrhythmias.
Conclusions: After ablation of long-lasting persistent AF, localized reentry may arise from a site in the vicinity of the prior ablation lesions. Ablation of the critical isthmus eliminates the arrhythmia.     

Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia

Congenital amegakaryocytic thrombocytopenia (CAMT) is an uncommon disorder in newborns and infants, characterized by isolated thrombocytopenia and megakaryocytopenia in the first year without physical anomalies. The defect of thrombopoiesis is not well understood. Recently, thrombopoietin (TPO), the ligand for the c-mpl receptor, was cloned. Accumulating evidence from in vitro and in vivo studies indicate that TPO plays a key role in the regulation of megakaryocytopoiesis. In this study we examined the effect of TPO on megakaryocyte colony formation from a patient with CAMT using a plasma-containing methylcellulose clonal culture. The in vitro results demonstrated a defective response to TPO in megakaryocyte colony formation from bone marrow mononuclear cells (MNC) of the patient, although interleukin-3 (IL-3) but not stem cell factor (SCF) induced only a small number of megakaryocyte colonies. These findings indicated that thrombocytopenia in CAMT could not be corrected by administration of TPO in vitro. Additionally, clonal cultures containing SCF, IL-3, IL-6 and erythropoietin showed decreased numbers of erythroid and myelocytic progenitors in the bone marrow of the patient. The serum TPO level measured by enzyme-linked immunosorbent assay was significantly higher than that in healthy controls. By PCR, marrow MNC from healthy children and from a patient with essential thrombocytosis expressed c-mpl mRNA, whereas no c-mpl mRNA was detected in marrow MNC from the patient with CAMT. There was no difference in the CD34 expression and c-kit mRNA between the CAMT patient and healthy children. The results of this study suggest that the pathophysiology in CAMT may be a defective response to TPO in haemopoietic cells through impaired expression of c-mpl mRNA.