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.     

Effectiveness of tonsillectomy in adult sleep apnea syndrome

Abstract Tonsillectomy was performed on 10 adult sleep apnea patients (five males, five females; average age, 39 years old; average body mass index, 24.8 kg/m²). Tonsillectomy alone was indicated if tonsillar hypertrophy was moderate to severe and the length of the soft palate was less than 35 mm according to cephalometry. Remarkable improvements were observed in all cases following surgery. The average weight of the resected tonsils was 11 g. The patients demonstrated a preoperative apnea + hypopnea index (AHI) of 14.4/h. This decreased to 2.9/h postoperatively. The intraesophageal pressure change improved from -36.6 to -15.7 cmH₂O following surgery. A significant correlation between preoperative AHI and the degree of obesity ( r = 0.684, P < 0.05) was found. Although uvulopalatopharyngoplasty has been used extensively to treat sleep apnea, the present results suggests that certain subjects can be effectively treated through only tonsillectomy.     

Epidural air associated with spontaneous pneumomediastinum in children: Uncommon complication?

BACKGROUND: The purpose of the present study was to evaluate the incidence of epidural air associated with spontaneous pneumomediastinum in children. METHODS: The subjects consisted of 25 boys and 17 girls with an age range of 3-14 years (mean age: 8.5 years) who underwent chest computed tomography (CT) for evaluation of spontaneous pneumomediastinum. The CT scans and medical records were reviewed retrospectively. RESULTS: Of the 42 patients, four (9.5%) had intraspinal air on CT. The air was interpreted as epidural in every patient. The small number of patients with epidural air meant that there was no significant difference in age, gender, or clinical manifestations between groups with and without epidural air. Subcutaneous emphysema was identified in all four patients with epidural air versus 18 out of 38 patients (47%) without epidural air. The patients with epidural air did not have any neurologic symptoms. Irrespective of the presence or absence of epidural air, every patient had a favorable outcome without any serious complications. CONCLUSION: In patients with spontaneous pneumomediastinum, epidural air may be more common than was previously realized. It is suggested that an air leak may spread from the mediastinum into the epidural space via the cervical fascial planes and neural foramina.     

A quantitative assessment of serum chylomicron by light scattering intensity: Application to the intestinal fat absorption test

A novel fat absorption test to clarify the malabsorption syndrome was developed using a micronephelometric technique and compared with the classic conventional technique using ¹³¹I-triolein. An integrity of time-sequential light scattered from chylomicron-related turbidity in serum was determined between 0 and 300 min after butter fat load, being expressed in terms of the light scattering intensity (LSI). A good correlation was obtained between LSI and the serum level of chylomicron-triglyceride determined by an ultracentrifugation technique (r=0.819, P < 0.001). The maximal LSI was consistently observed at 180 min after administration of a test meal in the normal group (n= 39), whereas the malabsorption syndrome group (n= 35) was distinctly different and could be further classified according to four patterns of LSI changes. In addition, an inverse correlation was found between this fat absorption test and the ¹³¹I-triolein absorption test. It was concluded that the micronephelometric technique which does not use a radionuclide is advantageous in its simple and safe evaluation of fat malabsorption syndrome.     

Radio-frequency ablation of renal cell carcinoma in patients who were at significant risk

OBJECTIVE: Although radio-frequency ablation (RFA) has been recently applied as a minimally invasive treatment option for renal cell carcinoma (RCC), indication of this modality remains a critical issue due to the lack of complete tumor destruction as well as the uncertainty of its long-term efficacy. We report the efficacy of RFA for nine carefully selected patients with RCC who had significant reason to avoid invasive surgical treatment under general anesthesia. METHODS: Radio-frequency ablation was performed under epidural or local anesthesia by ultrasound or computed tomography (CT) guidance in nine patients with biopsy proven RCC (mean diameter, 38 mm; range, 20-53 mm), who were at significant operative or anesthetic risk for invasive surgery. Follow-up enhanced CT scans or magnetic resonance images were evaluated every 3-6 months and an evaluation of metastasis was performed every 6 months. RESULTS: At a mean follow-up of 17 months, seven (78%) of the nine patients with renal tumor showed no tumor enhancement. The renal function of all patients was well preserved. All patients were able to continue undergoing their respective treatments for active diseases in other organs in parallel to the RFA treatment. No distant metastasis, urine leakage were reported and one case of temporary hematuria and one case of peri-renal hemorrhage not requiring blood transfusion were encountered. Intra-operative ultrasonography was useful in the real-time monitoring of the minimally excessive extension of ablation into the normal parenchyma. CONCLUSION: Radio-frequency ablation appears to be an effective and safe minimally invasive therapeutic option for selected patients with RCC who have reason to avoid invasive surgery under general anesthesia.     

Case Report: Interferon induced coma in Sheehan's syndrome

A 54-year-old woman who was being treated with 10 million units (mu) of natural interferon (IFN)-α per day for chronic active hepatitis C at a local clinic, developed coma on the fourth day of treatment. On admission to Yamagata University Hospital, she was still in a state of semicoma with severe hyponatraemia (122 mEq/L) and hypochloraemia (89 mEq/L). After the administration of electrolytes, her condition improved remarkably. Endocrinological loading tests showed a hypofunction of the anterior pituitary gland. In consideration of these results, and her past experiences of haemorrhage during childbirth and subsequent amenorrhoea, we diagnosed her illness as a coma as a result of Sheehan's syndrome which had become overt during IFN therapy. She recovered completely after treatment with hydrocortisone and 1-thyroxine.     

Hepatotoxicity of Agents That Enhance Formation of Focal Hepatocellular Proliferative Lesions (Putative Preneoplastic Foci) in a Rapid Rat Liver Bioassay

Hepatotoxicity of Agents That Enhance Formation of Focal HepatocellularProliferative Lesions (Putative Preneoplastic Foci) in a RapidRat Liver Bioassay. WARD, J. M., TSUDA, H., TATEMATSU, M., HAGIWARA,A., AND ITO, N. (1989). Fundam Appl Toxicol. 12., 163–171.The histopathology of hepatic toxicity for 58 chemicals previouslytested in a rapid rat liver bioassay for demonstrating potentialhepatocellular carcinogens and/or tumor promoters was reviewed.Rats received the test diet for 1 week prior to partial hepatectomyand for an additional 5 weeks thereafter at doses near the estimatedmaximally tolerated dose. These rats served as controls forothers receiving initiation by N-nitrosodiethylamine (DEN) andthe test diets. Twenty-two of these chemicals were previouslyfound to enhance the formation of glutathione S-transferase,placental form (GST-P)-positive putative preneoplastic hepatocellularfoci (promoters) following DEN initiation in this rapid bioassay,whereas 36 chemicals did not. Of the agents that promoted GST-P-positivefoci, 14/22 (63.6%) produced toxic hepatocyte lesions whileonly 4/36(11.1%) of the nonpromoters did so at the doses used.Biliary toxicity was found for 7/22 (31.8%) of the promotersand 6/36 (16.7%) of the nonpromoters. Only 2/13 (15%) chemicalsthat inhibited GST-P-positive foci produced hepatic toxicity.Thus, agents that were presumed hepatic tumor promoters characteristicallywere hepatotoxins while nonpromoters of carcinogenesis werenot hepatotoxins in this rapid rat liver bioassay.