A case of acetaminophen-induced pneumonitis]

A 20-year-old woman took 1.2 g of acetaminophen for toothache. She subsequently developed a dry cough, pyrexia, and dyspnea. Chest X-ray revealed diffuse reticulo-nodular shadows in both lung fields. Broncho-alveolar lavage examination showed a marked increase in the total cell number and an increase in the percentage of eosinophils, neutrophils, and lymphocytes. Because drug-induced pneumonitis was suspected, all drugs were stopped and she was administered methylprednisolone. Consequently her symptoms resolved, and pulmonary function and chest X-ray findings improved remarkably. The lymphocyte stimulation test was positive for Norshin and its acetaminophen element. Based on these findings, the diagnosis of acetaminophen-induced pneumonitis was made. Acetaminophen intoxication is well-known, but to our knowledge this is the first reported case of acetaminophen-induced allergic pneumonitis in Japan.     

Correlation between genetic alterations and histopathological subtypes in bronchiolo-alveolar carcinoma and atypical adenomatous hyperplasia of the lung

Bronchiolo-alveolar carcinoma (BAC) is a type of lung adenocarcinoma characterized by growth along the alveolar wall. It is divided into two subtypes: sclerosing BAC (SBAC), which has central fibrosis, and non-sclerosing BAC (NSBAC), which lacks central fibrosis. We compared the genetic alterations in these two types of BAC with those in atypical adenomatous hyperplasia (AAH). There were 39 cases of SBAC, 19 of NSBAC and 20 of AAH. To detect the loss of heterozygosity (LOH) we used the microsatellite markers D3S1234 and D3S1300 on chromosome 3p, IFNA and D9S144 on 9p, and TP53 on 17p. We also used polymerase chain reaction-SSCP analysis and direct sequencing to examine a point mutation of the p53 gene at exons 5-8. At the TP53 locus, the frequencies of LOH showed a statistical rank-difference correlation among AAH, NSBAC and SBAC. On chromosomes 3p and 9p there were no statistical differences of LOH among AAH, NSBAC and SBAC. We detected a significant statistical rank-difference correlation in the p53 mutation among AAH, NSBAC and SBAC. These findings suggest that a process of multistep carcinogenesis from AAH through NSBAC to SBAC might occur in some cases of adenocarcinoma, and LOH of 3p and 9p might be an early event of carcinogenesis, while the p53 mutation might be a later event.     

Selection of scientific periodicals to monitor drug safety information using Excerpta Medica and Japicdoc in the post marketing surveillance of drugs

In order to select important journals to be monitored for efficient collection of literature information on drug safety, a retrospective search was made of the safety information in the Excerpta Medica (EM) database between 1979 and 1981. The search provided 54,005 references to drug safety, which were found in a total of 2,536 journals. Fifty percent of the references appeared in only 148 journals, or 6% of all journals surveyed. A similar search, carried out using the Japicdoc (JD) database, provided 9,268 references in 172 journals. To cover all the necessary information appearing in overseas journals, however, a retrospective search of a bibliographic database is required as a cost-effective means to improve the comprehensiveness of the collection of information. In domestic journals, because JD includes fewer journals than EM, all of the 172 journals can be monitored for the collection of drug safety information.     

Hypothermia attenuates the vasodilatory response of pial arterioles to hemorrhagic hypotension in the cat

We investigated the effect of hypothermia on the vasodilatory response of pial arterioles to hemorrhagic hypotension. The cranial window technique was combined with microscopic video recording in an experiment involving 20 cats anesthetized with pentobarbital. The animals were randomly assigned to either a normothermic or a hypothermic group (32 degrees C). Mean arterial pressure (MAP) was reduced in stepwise increments of 10 mm Hg (from 100 to 50 mm Hg) by blood withdrawal. The diameter of small (50-100 microm) and large (100-200 microm) pial arterioles was measured. In the normothermic group (n = 9), small and large arterioles dilated at a MAP of 60 and 50 mm Hg, and at a MAP of 70, 60, and 50 mm Hg, respectively, compared with baseline values obtained at a MAP of 100 mm Hg. In contrast, in the hypothermic group (n = 11), vasodilation of either small or large arterioles was absent. The percentage diameter of small and large arterioles (percentage of control) was significantly lower at a MAP of 70, 60, and 50 mm Hg in the hypothermic group than the normothermic group. Our in vivo study demonstrates that hypothermia impairs autoregulatory vasodilation of pial arterioles in response to hemorrhagic hypotension. IMPLICATIONS: Deliberate mild hypothermia has been proposed as a means of providing cerebral protection during neurosurgical procedures. Our results suggest that cerebral blood flow autoregulation in response to hemorrhagic hypotension may be impaired during hypothermic conditions, indicating the importance of maintaining perfusion pressure during hypothermic therapy to prevent cerebral ischemia.     

Differences in hemodynamic effects of amrinone, milrinone and olprinon after cardiopulmonary bypass in valvular cardiac surgery

The differences in hemodynamic effects of amrinone, milrinone and olprinone were evaluated in 46 patients for valvular cardiac surgery after cardiopulmonary bypass (CPB). Patients were randomly allocated to three groups; group A with amrinone infusion (17 patients); group M with milrinone infusion (15 patients); and group O with olprinone infusion (14 patients). Each drug was administrated as a single dose into the venous reservoir of the CPB circuit 15 min prior to the end of emergence from CPB, followed by continuous infusion. Hemodynamic parameters were measured at the time of preCPB (C0), just after the end of CPB (C1), one hour after the termination of CPB (C2) and after the chest closure (C3). Catecholamines were used in order of dopamine, norepinephrine and dobutamine. These doses were modulated to maintain the cardiac index > 3.0 l.min-1.m-2 by each anesthesiologist. Hemodynamic parameters (at C0, C1, C2 and C3) and the doses of cathecholamine (at C1, C2 and C3) were compared among the 3 drugs. The systolic blood pressure in group M was significantly higher than that of group A and group O after chest closure. In group M and A, the systolic blood pressure showed a significant increase after CPB. On the other hand, the systolic blood pressure showed no significant change in group O after CPB. Three drugs showed no significant difference in the dosages of catecholamines used.     

A case of unusual longevity of tetralogy of Fallot confirmed by cardiac catheterization.

We describe a 61-year-old woman with tetralogy of Fallot and dextrocardia with complete situs inversus. The functional status of this patient was New York Heart Association (NYHA) class II and the systemic blood pressure was 100/54 mmHg. The hematocrit was 54.4% and the arterial partial pressure of oxygen was 53 mmHg. On cardiac catheterization, both pulmonary valvular and infundibular stenoses were of equal severity and the aorta and main pulmonary artery were of equal size. We think that this patient has survived to this unusual age for tetralogy of Fallot because of unusually low systemic pressure and a proper balance between the ventricular septal defect and the pulmonary stenosis.