Effect of (2"R)-4'-O-tetrahydropyranyladriamycin, a new antitumor antibiotic, on the cardiac function of hamsters

Cardiovascular effects of (2'R)-4'-O-tetrahydropylanyladriamycin X HCl (THP) and doxorubicin (adriamycin, ADM) were studied in hamsters. In experiments to observe acute effects, THP was administered intravenously at a dose of 12.5, 25.0 or 50.0 mg/kg, and ADM at 1.56, 3.13 or 6.25 mg/kg was given to different subjects. The THP caused slight ECG alterations at a dose of 12.5 mg/kg. At a dose of 25.0 mg/kg or 50.0 mg/kg, THP caused moderate to remarkable alterations in ECG like a widening of PR and PRc interval, A-V block, ST segment depression and T wave flattening. The ADM caused moderate to remarkable alterations in ECG at a dose of 3.13 mg/kg or 6.25 mg/kg, including arrhythmia, bradycardia, A-V block, ST segment changes and T wave flattening. These changes caused by THP and ADM recovered within 5 approximately 10 minutes after injection. Alterations in the ultrastructure of the myocardium caused by THP at a dose of 50.0 mg/kg included some cells with slight changes like swelling of mitochondria, focal intracellular edema, and enlargement of myofibrils. The ADM, at a dose of 3.13 mg/kg, induced severer swelling of mitochondria than THP, dilatation of sarcoplasmic reticulum, intracellular edema, and disorganization of myofilaments. At a dose of 6.25 mg/kg of ADM, these changes became more pronounced. In experiments to observe subacute effects, hamsters were treated with THP or ADM by daily intraperitoneal injections for 15 consecutive days, and then allowed to be recovered for 15 days. Dose levels of THP or ADM were 0.125, 0.25, 0.5 and 1.0 mg/kg. General toxicity, ECG, hematological and blood biochemical analysis, and electron microscopic examination were studied. In the ECG study, THP-treated hamsters showed a reversible elevation of R wave amplitude at a daily dose of 0.5 mg/kg. Widening of PR and PRc interval, elevation of R and S wave amplitude, and reduction of T wave amplitude were observed at a daily dose of 1.0 mg/kg of THP. Hamsters treated with ADM showed increase of heart rate, reduction of T wave amplitude, and shortening of PR and PRc interval at a daily dose of 0.5 mg/kg. Severe changes were observed at a daily dose of 1.0 mg/kg of ADM including an increase of heart rate, elevation of R wave amplitude, reduction of S and T wave amplitude, and shortening of QT interval. The electron microscopic examination revealed that THP-treated hamsters showed separation of intercalated discs, formation of myelin structure, and dilatation of T-tubules at a daily dose of 1.0 mg/kg. Similar changes were caused by ADM at a daily dose of 0.25 to 1.0 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)     

A case of autoimmune hepatitis needed to be differentiated from EBV hepatitis, in that the histology of liver biopsy specimen was useful for diagnosis]

A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted to our hospital because of cholestasis and elevation of liver enzymes for 2 months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA, hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth muscle antibody. The histology of her liver biopsy specimen revealed interface hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis. She was treated firstly with methylprednisolone pulses, then will prednisolone p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced because of her abnormal immune pathology. All abnormal laboratory parameters improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC became negative after 4 months. The histology of liver biopsy specimen was useful for the diagnosis of AIH in such a difficult case needed to be differentiated from EBV hepatitis.     

The Japan Morning Surge-1 (JMS-1) study: protocol description.

Morning blood pressure is reported to be more closely related to hypertensive organ damages such as left ventricular mass index, microalbuminuria and silent cerebral infarcts, than blood pressure at other times of the day. Morning blood pressure may play an important role in the pathogenesis of hypertensive target organ damage. Increased sympathetic nerve activity is reported to be one of the mechanisms of morning hypertension; however, there are no available data that show whether strict home blood pressure control, especially in the morning period, can reduce target organ damage. The Japan Morning Surge-1 (JMS-1) study includes hypertensive outpatients with elevated morning systolic blood pressure (>or=135 mmHg) as assessed by self-measured blood pressure monitoring at home. All enrolled patients are under stable antihypertensive medication status. Exclusion criteria are arrhythmia, chronic inflammatory disease, and taking alpha-blockers or beta-blockers. The target number of patients to be enrolled in the JMS-1 study is 600, and the aim is to evaluate differences in the markers of hypertensive target organ damage, such as brain natriuretic peptide and the urinary albumin excretion/creatinine ratio. All of the patients are randomized to an experimental group or a control group, with randomization to be carried out by telephone interviews with the patients' physicians. In the experimental group, patients begin taking additional antihypertensive medication just before going to bed. This consists of doxazosin 1 mg/day, which then is increased to 2 mg/day and 4 mg/day, with a beta-blocker added after a 1-month interval until the morning systolic blood pressure is controlled to less than 135 mmHg. Patients in the control group continue the treatment they are receiving at the enrollment for 6 months. Blood pressure levels, adverse effects, and hypertensive target organ damage before and after the study are evaluated. In the JMS-1 study, we will evaluate whether strict morning blood pressure control by sympathetic nervous system blockade using an alpha-blocker, doxazosin, and with the addition of a beta-blocker if needed, can reduce hypertensive target organ damage.     

Immunological Detection and Quantitation of DNA Adducts Formed by 4-Aminoazobenzene Species in vivo

Antibodies to 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and 2-methoxy-4-aminoazobenzene (2-MeO-AAB) DNA adducts were raised in rabbits against in vitro-adducted DNA samples. The enzyme-linked immunosorbent assay (ELISA) was used to determine the sensitivity and specificity of these antibodies. They proved highly specific for the modified DNA used as the immunogen, but cross-reacted with each other. Moreover, they showed cross reactivity with DNA modified by 4-( o -tolylazo)- o -toluidine, but not by other carcinogens, such as 4-aminobiphenyl or 4-nitroquinoline 1-oxide. The 50% inhibition level of antibody binding in the competitive ELISA was at 10–20 fmol of modified base per assay (equivalent to 1–2 adducts per 10⁶ bases). Immunohistochemical staining indicated that these antibodies bind specifically to nuclear components of the liver in rats given either 3-MeO-AAB or 2-MeO-AAB at the dose of 50 mg/kg body weight.     

Tumor dissemination during laparoscopic cholecystectomy for gallbladder carcinoma

Surgical Endoscopy -     

Spontaneous mesenteric hemorrhage associated with ehlers-danlos syndrome

The vascular type of Ehlers-Danlos syndrome is a genetic disorder of connective tissue and is frequently associated with catastrophic arterial complications. Its surgical treatment is extremely difficult because of the fragility of vessels. This article describes three patients with vascular type of Ehlers-Danlos syndrome who developed mesenteric hemorrhage due to spontaneous arterial rupture. The clinical and molecular characteristics of the disease are briefly reviewed.     

The importance of carbohydrate counting in the treatment of children with diabetes

Abstract:  Carbohydrate (Carb) counting is a meal planning approach for patients with diabetes mellitus that focuses on carbohydrate as the primary nutrient affecting postprandial glycemic response. The concept of carb counting is not new. In the early 1990`s the Diabetes Control and Complications Trial (DCCT) used carb counting as one of its education tools. More recently, short acting insulin analogues and insulin pumps have made the role of carb counting important and popular. Carb counting can be used in conjunction with a meal plan to set carbohydrate targets at each meal and snack. It is also used, perhaps more commonly, to estimate carbohydrate intake and adjust insulin around mixed meals and snacks using insulin to carbohydrate ratio. This effectively addresses the variable eating habits of most children and adolescents. The method may be adapted for patients who use a conventional insulin regimen and may meet the needs of patients who use multiple daily injections (MDI) or an insulin pump. Carb counting can make food planning flexible and enjoyable for patients, and the meal planning approach is very important for the physical growth and psychological development of children with diabetes. This paper describes the importance of carb counting for childhood diabetes as well as some of the special aspects associated with it.     

A phase II study of epirubicin in acute leukemia: a cooperative group study

A new doxorubicin analogue, epirubicin (EPI), was evaluated in 41 patients with acute leukemia at 11 Japanese institutions participating in a phase II study between January 1983 and July 1985; during this period 35 patients were considered evaluable. There were 25 males and 10 females with a median age of 43 years (range, 19-71 years) and the median PS of 2 (range, 0-4). EPI was given to 25 patients who had previously been treated with intensive combination chemotherapy, of whom 22 had already received anthracyclines. Ten patients had not been treated previously. Two dose schedules were explored. The higher dose schedule (18 cases) consisted of the administration of 24 to 60 mg/m2 for 3 to 5 consecutive days, and the lower dose schedule (17 cases) consisted of 11 to 20 mg/m2 for 5 to 7 days. Remissions were obtained in 7 patients (20%), 2 of whom showed complete remission and 5 partial remission. The remission duration was 2, 2, 3, 5, 16, 16 and 29+ weeks, respectively. The expected myelosuppression was universal. Stomatitis occurred in 15 patients, of which 7 cases were severe. This stomatitis occurred frequently in the higher dose schedule, and was thought to be a dose-limiting factor. In others, alopecia, G.I. symptoms, and diarrhoea (4 patients) were seen. These results from a cooperative group study indicated that EPI was an effective drug for the treatment of acute leukemia.     

A comparative study of CHOP therapy and COP-BLAM therapy for non-Hodgkin's lymphoma in elderly patients]

Elderly patients (aged greater than or equal to 65 years) with non-Hodgkin's lymphoma were treated either with CHOP or COP-BLAM therapy, and the effectiveness and reverse effects of COP-BLAM therapy were compared with those of CHOP therapy. Thirty-three patients (aged greater than or equal to 65 years) with previously untreated non-Hodgkin's lymphoma were entered either on CHOP or COP-BLAM regimen between September, 1979 and February 1990. To CHOP therapy was performed in 15 patients (median age; 70 years). Eight of them had diffuse large cell type lymphoma (large), five had diffuse medium-sized cell type (medium) and two had diffuse mixed cell type (mixed). As to clinical stage, there were patients in stage II, 4 in stage III and 9 in stage IV in CHOP group. Of 18 patients (median age; 68 years), who were treated with COP-BLAM therapy, 8 had of large lymphoma and 10 medium lymphomas in histopathological classification. In terms of clinical stage, there were 5 patients in stage II, 4 in stage III and 9 in stage IV. CHOP therapy and COP-BLAM therapy were performed according to the method reported by McKelvey et al, and by Laurence et al., respectively, using the full doses of drugs without consideration the age. Complete remission (CR) was achieved in seven (46.7%) of 15 patients treated with CHOP therapy. In this group, five (38.5%) of 13 patients in advanced stages (stage III or IV) entered CR. Of 18 patients subjected to COP-BLAM therapy, 15 (83.3%) achieved CR. Among 13 patients in advanced stage treated with COP-BLAM therapy, CR was achieved in 11 (84.6%).(ABSTRACT TRUNCATED AT 250 WORDS)