Medium-term results of percutaneous transluminal balloon aortic valvuloplasty with Inoue balloon catheter for congenital aortic stenosis

Although percutaneous transluminal balloon aortic valvuloplasty (PTAV) has been performed for congenital aortic stenosis in infants and children for several years, its efficacy and the associated aortic regurgitation (AR) have not been widely discussed. Percutaneous transluminal balloon aortic valvuloplasty using an Inoue balloon catheter was performed for congenital aortic stenosis in 12 patients (4–16 years old) in this study. The systolic aortic valve pressure gradient ranged from 42 to 111 mmHg before PTAV and became < 50 mmHg immediately after PTAV in 10 cases (83%). Eight of these 10 patients had no increase in the gradient during subsequent observation for a period of 9–40 months. Aortic regurgitation increased immediately after PTAV in nine cases (75%). It increased from grade 1 to grade 2 in eight cases and from grade 1 to grade 3 in one patient; no significant enlargement of the left ventricular end-diastolic diameter and no significant change in the left ventricular end-diastolic pressure (LVEDP) or the cardiac index was observed during follow-up in these patients. There was a correlation between the diameter of the balloon and efficacy; an appropriate diameter was considered to be about 90% of the aortic annular diameter. Changes in the hemodynamic parameter after PTAV with an Inoue balloon were small in most patients and this procedure is considered to be a treatment that should be attempted prior to surgery for congenital aortic stenosis.     

Oral Sustained-release Cisplatin Preparation for Rats and Mice

A new oral sustained-release solid-dispersion preparation of cisplatin (cis-diamminedichloroplatinum(II); cisplatin) has been developed for administration to small experimental animals such as mice. This preparation was obtained by formulating cisplatin with the water-insoluble polymer ethylcellulose and with stearic acid in different ratios. In-vitro dissolution studies showed that cisplatin release characteristics were zero-order for the formulation cisplatin–ethylcellulose–stearic acid (1:10:5) and levels equilibrated 7 h after the start of the experiment. The availability of cisplatin from this preparation was evaluated both in rats and mice. The cisplatin preparation (20 mg kg^?1) was administered orally to rats and the resulting curve of serum cisplatin levels against time was compared with that obtained after intravenous infusion (20 mg kg^?1) to rats. By comparing the areas under serum concentration-time curves (AUCs), the bioavailability of cisplatin was estimated to be 31%. The mean residence time (MRT) of cisplatin solid dispersion was 6.13 ± 0.43 h, whereas the MRT of cisplatin administered by intravenous infusion was 3.89 ± 0.05 h. Serum cisplatin levels were maintained above 0.3 mg mL^?1 (believed from our clinical studies to be the minimum effective concentration) for 24 h. The curve of serum cisplatin level against time suggested that cisplatin was released from the solid dispersion preparation in a sustained-release fashion. Similar levels were also maintained in mice for 24 h. The MRT of the cisplatin preparation was 10–16 h in mice, which is longer than that obtained after oral administration of the physical mixture. The serum free-cisplatin concentration was determined to be 0.10 mg mL^?1 in mice serum in which the total cisplatin concentration was 0.30 mg mL^?1. The free fraction of cisplatin in mice serum was the same as that in human patient serum. Pathological examination showed that this new sustained-release oral cisplatin preparation did not have any side effects on the gastrointestinal tract. These results suggest usefulness of this new solid-dispersion preparation for oral cisplatin therapy in lung cancer patients.     

GENETIC DIFFERENCES IN THE EFFECTS OF VOLUNTARY ETHANOL CONSUMPTION ON BRAIN MONOAMINE LEVELS IN INBRED STRAINS OF MICE, C57BL/6J, C3H/He AND DBA/2Cr

This study was carried out to determine whether concentrationsof the brain monoamines noradrenaline (NA), dopamine (DA), and5-hydroxytryptamine or serotonin (5-HT) are different in threeinbred strains of mice (C57BL/6J, C3H/He and DBA/2Cr) knownto differ in their preference to alcohol, when they were givena free choice of 10% (v/v) ethanol and tap water to drink for4 weeks. Mice of these three strains showed mean ethanol intakesof 4.41, 1.76 and 0.77 g/kg/day respectively. Levels of theabove brain monoamines did not change in the alcohol-preferringC57BL/6J mice, but in those with less preference for alcohol,C3H/He and DBA/2Cr, there were significant increases in DA and5-HT levels respectively during the 4-week experiment. Thesefindings suggest that inbred strains of mice show genetic differencesof susceptibility to ethanol and that the strains with a lowpreference for alcohol undergo neurochemical changes after exposureto 10% ethanol and water even by free choice.     

Increased urinary excretion of human cytomegalovirus in children with malignancy: Detection by polymerase chain reaction

Human cytomegalovirus (HCMV) is one of the most important agents causing opportunistic infections in immunocompromised hosts. In this study, we examined the urinary excretion of HCMV in children with malignancy using polymerase chain reaction (PCR). Urine samples were collected from on-therapy, off-therapy patients with malignancy, and healthy controls. A simple DNA extraction method using glass powder was employed, and inhibitory effect of urine on PCR was prevented. For PCR, a pair of primers from the HCMV major immediate early gene sequence was used. Among patients who received intensive chemotherapy, 52.0% had urinary HCMV excretion after the chemotherapy course. In contrast, off-therapy patients and healthy controls showed a lower incidence of urinary HCMV excretion (20.4 and 8.7%, respectively). The incidence of HCMV urinary excretion in the on-therapy group was significantly higher than healthy controls (P < 0.05). In the on-therapy group, the total white blood cell count of the virus excreters was lower than that of non-excreters. The incidence of HCMV excretion was high in on-therapy patients. Most of the virus excreters were seropositive, so their viruria was thought to be caused by reactivation. Repeated monitoring of virus excretion by this rapid and simple method may be useful to detect HCMV infection early and to control it in such patients.     

Charging for drugs in Africa: UNICEF'S 'Bamako Initiative'

Recession and economic adjustment policies have led to massiveresource shortages in government health systems in many lessdeveloped countries in Africa. There is growing evidence thatthe IMF- and World Bank-sponsored adjustment programmes areresponsible for negative effects on the health of the poor inthese countries. Calls for a New International Economic Orderand 'adjustment' in the industrialized countries have been ignoredand the resource flow from the poor to the rich countries continues.UNICEF is currently promoting ‘Adjustment with a humanface’ as a means of alleviating poverty and minimizingthe negative impact of adjustment on the poor. In the healthsector, this approach concentrates on the GOBI-FFF strategyand the supply of essential drugs to primary level health services.UNICEF is also in the process of launching the ‘BamakoInitiative’ which aims, by introducing drug/treatmentcharges and setting-up revolving drug funds at community level,to finance drg costs, the operational costs of the MCH programmeand the salaries of community health workers at primary level.Quite apart from the debatable long-term impact of the healthstrategy being advocated, the Bamako Initiative poses seriousquestions related to equity and the implementation of fee systemswhich must be answered.     

METHIMAZOLE-INDUCED AGRANULOCYTOSIS IN JAPANESE PATIENTS WITH GRAVES'' DISEASE

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.     

Decreased prostaglandin E2 synthesis by lung fibroblasts isolated from rats with bleomycin-induced lung fibrosis

In order to clarify the mechanism of pulmonary fibrosis, we examined the functional changes of lung fibroblasts in bleomycin (BLM)-induced pulmonary fibrosis. Lung fibroblastic cells were obtained from rat lungs after an intratracheal treatment of BLM or saline. The spontaneous proliferation of BLM-treated rat fibroblasts (BRF), which was estimated by 3H-TdR incorporation and direct cell counting, was significantly more rapid than that of normal saline-treated rat fibroblasts (NRF). Next, we investigated prostaglandin (PG) E2 synthesis by BRF and NRF, with or without stimulation by interleukin (IL)-1 alpha, and found that PGE2 production by BRF was significantly less than that by NRF. There was no significant difference in cyclooxygenase (COX) activity and COX-2 mRNA level between BRF and NRF, indicating that the change in PGE2 production was independent of COX, a rate-limiting enzyme for the production of PGE2. These results suggest that the proliferation of fibroblasts is down-regulated by PGE2 released from themselves in normal lungs in an autocrine fashion, thus the decreased PGE2 production observed in lung fibroblasts from rats with BLM-induced pulmonary fibrosis may result in the excessive fibroblast proliferation in this disorder. Overall, these findings throw some light on the mechanism of development of BLM-induced pulmonary fibrosis.     

Reutilization of DNA Breakdown Products from Lymphocytes in Lumen of Intestine

Migration of a very large number of lymphocytes (211.8 x 10⁶ per day)into the intestinal canal of rats, which weighed about 100 Gm., was found.Lymphocytes in the lumen of the intestine were 80.2 per cent small, 15.9 percent medium and 3.9 per cent large. Any recycling of instilling cells intothe intestine could not be observed. Lymphocytes labeled with H³-thymidine,obtained from both thymus and mesenteric lymph nodes of donor rats, werewashed and injected into the intestine of recipient rats. H³ activity of the bloodand thoracic duct lymph plasma after administration of labeled lymphocytesshowed that DNA breakdown products from the lymphocytes in the gut wereabsorbed and transferred by way of both the portal vein and the thoracic duct.Evidence that the activity was actually incorporated into the DNA of proliferating cells of the recipient was demonstrated by autoradiographic means.

Submitted on July 15, 1965 Accepted on October 8, 1966     

MONITORING OF ETHANOL LEVELS IN THE RAT NUCLEUS ACCUMBENS BY BRAIN MICRODIALYSIS

Brain microdialysis was used to measure nucleus accumbens (NAC)ethanol (EtOH) over several hours after intraperitoneal (i.p.)injection of EtOH. Levels of EtOH in NAC perfusates were assayedby gas chromatography Peak EtOH levels were observed 40 minafter the injection and the three doses of EtOH, 0.5, 1.0, and2.0 g/kg, resulted in peak perfusate levels of 5 mM, 18 mM,and 38 mM, respectively. Measurement of regional brain EtOHlevels may prove useful for studying the relationship betweenpatterns of alcohol consumption and the action of EtOH in thecentral nervous system.