Evidence for the role of neutrophils in reperfusion injury after cold cardioplegic ischemia in neonatal lambs.

The role of neutrophils in reperfusion injury after hypothermic, cardioplegia-protected ischemia is incompletely understood but may involve neutrophil-endothelial interactions. We examined 33 isolated blood-perfused neonatal lamb hearts arrested for 2 hours with 15 degrees C potassium cardioplegic solution and reperfused with unmodified blood (group C, n = 9), with neutrophil-depleted (Sepacell filter) blood (group ND, n = 9), with the addition of CV-3988, a platelet-activating factor antagonist, to the perfusate (group NA, n = 9), and with neutrophil-depleted blood plus CV-3988 (group ND/NA, n = 6). The percent recovery of isovolumic left ventricular developed pressure at a fixed balloon volume at 30 minutes after reperfusion in groups ND (84.8% +/- 11.8%, mean +/- standard deviation), NA (89.9% +/- 11.5%), and ND/NA (87.8% +/- 6.4%) were higher than in group C (73.1% +/- 7.9%) (p less than 0.05). Groups NA (105.5% +/- 13.7%) and ND/NA (108.0% +/- 11.2%) achieved higher percent recovery of coronary blood flow than group C (84.4% +/- 10.4%) (p less than 0.05). In each heart, we also tested coronary vascular resistance response to infusion of acetylcholine 10(-6) mol/L to assess endothelial function. Percent recovery of coronary vascular resistance response to acetylcholine was higher in groups ND (56.8% +/- 31.4%), NA (56.3% +/- 17.3%), and ND/NA (58.7% +/- 24.8%) than in group C (13.3% +/- 38.3%) (p less than 0.05). These results show that, after ischemia/reperfusion, groups ND, NA, and ND/NA had better recovery of both mechanical and endothelial function than group C. The parallel changes in recovery of mechanical and endothelial function suggest that neutrophil-endothelial interactions may be a significant factor in reperfusion injury.

Staged operation for pulmonary atresia and ventricular septal defect with major aortopulmonary collateral arteries. New technique for complete unifocalization.

A new staged operation for total correction of pulmonary atresia and ventricular septal defect with major aortopulmonary collateral arteries has been developed. In first-stage repair (complete unifocalization), intrapulmonary arteries were unified at the hilum with equine pericardial conduits (intrapulmonary bridges). In case of absent or severely hypoplastic central pulmonary arteries, new central pulmonary arteries were created. Finally, the unifocalization was completed by modified Blalock-Taussig shunts with the ligation of collateral arteries. In second-stage repair, right ventricular-pulmonary arterial continuity was established with a trileaflet pericardial conduit and closure of the ventricular septal defect. From January 1982 through July 1988, 34 patients, whose ages ranged from 1 month to 24 years (mean 6.6 years), underwent first-stage repair with two resultant late deaths (mortality rate 5.9%). Second-stage repair has been completed in 16 patients. There were two early deaths (mortality rate 12%) from bacterial infection. Postoperative right ventricular/left ventricular systolic pressure ratios ranged from 0.36 to 1.0 (mean 0.72). In four patients in whom the ratio was 1.0, the ventricular septal defect had been closed with a perforated patch. By complete unifocalization with the intrapulmonary bridge technique and the creation of new central pulmonary arteries, the majority of patients with major aortopulmonary collateral arteries can have successful repair.

Growth of composite conduits utilizing longitudinal arterial autograft in growing lambs.

We examined the growth potential of a longitudinal strip of autologous aortic wall incorporated in an autologous pericardial conduit in 10 lambs (mean age 26 days, mean weight 10.1 kg). A 15 mm length of descending thoracic aorta (diameter 11.5 +/- 7 mm) was excised and replaced with a composite autograft conduit of autologous pericardium with a longitudinally inserted aortic strip 5 mm in width taken from the excised aortic tissue. Radiopaque markers along all suture lines allowed determination of growth of the aortic strip relative to growth of the composite conduit and descending aorta, in addition to growth assessment by pathologic analysis. Plain x-ray films and aortograms were performed at 7 days (baseline) and at 3, 6, 9, and 12 months. No graft became stenotic or aneurysmal. The diameter of the descending aorta distal to the conduit increased from 11.7 +/- 1.3 mm to 18.7 +/- 2.1 mm. Appropriate growth of the autograft conduit was demonstrated by a minimal change in the diameter ratio of conduit to distal aorta from 1.00 to 1.02 during a period of 12 months. The aortic strip increased to 172% +/- 19%, 148% +/- 15%, and 256% +/- 31% of baseline width, length, and area, respectively (p less than 0.05). Histologic study confirmed the maintenance of normal architecture in the aortic strip and colonization of the pericardial tissue by aortic intimal and medial elements. A clinical implant with an autologous aortic strip in an aortic homograft in a 4-year-old child with tetralogy and pulmonary atresia has also grown, according to angiography, from 15 to 21 mm in diameter at 1 year's follow-up. This study confirms that the incorporation of a free autologous arterial patch graft as part of cardiovascular reconstructive procedures permits growth.

Mechanical durability of pulmonary allograft conduits at systemic pressure. Angiographic and histologic study in lambs.

We examined the mechanical durability of cryopreserved pulmonary allograft conduits at systemic pressure in lambs. Composite valveless tube grafts made of cryopreserved pulmonary allograft and a length of Dacron tube were implanted in the thoracic aortic position in 10 lambs (aged 1 month, mean weight 11.4 kg). The pulmonary allografts were harvested from similar-sized lambs (aged 1 month, mean weight 10.5 kg) at 0 to 48 hours postmortem and were cryopreserved. Recipient sheep were catheterized at 1 week (baseline) and at 1, 4, 6, 9, and 12 months postoperatively to allow changes in the diameters of the grafts to be followed up by angiography. Samples of the grafts were examined histologically at the time of harvest, at implantation after cryopreservation and thawing, and at the end of the study. At the postoperative baseline study, the pulmonary allografts had almost doubled (mean 21.1 mm) their implantation diameters (unpressurized mean 12.6 mm). During the 12-month study period, the allografts further increased their angiographic diameter by 36.2% compared with baseline (p < 0.01). One animal died at 3 1/2 months postoperatively and was found to have an aneurysm of the allograft. Five of the remaining eight lambs showed aneurysmal dilatation (more than 40% increase in diameter relative to pressurized baseline) at 12 months. Postmortem study revealed disruption at the suture line between allograft and Dacron in these five recipients. Histologic study showed much less calcification than was seen in our previous study of aortic allografts. There was loss of most of the smooth muscle, intimal and adventitial fibrous proliferation, and occasional dense lymphocytic infiltrates associated with foci of persistent smooth muscle cells. Time of harvest after donor death did not affect the histologic appearance after 12 months' implantation. Pulmonary allografts dilate substantially at systemic pressure. This characteristic has the benefit of allowing progressive enlargement with time as a recipient grows but also carries the risk of aneurysm formation, particularly pseudoaneurysm at the suture line when anastomosed with a noncompliant Dacron prosthesis.

Influence of initial reperfusion pressure after hypothermic cardioplegic ischemia on endothelial modulation of coronary tone in neonatal lambs. Impaired coronary vasodilator response to acetylcholine.

To examine the effect of initial coronary reperfusion pressure on endothelial function, we subjected 16 isolated perfused neonatal lamb hearts to 2 hours of ischemia with potassium cardioplegic solution followed by reperfusion for 1 hour. Before ischemia both acetylcholine, an endothelium-dependent vasodilator, and nitroglycerin, and endothelium-independent vasodilator, caused coronary vasodilation. After ischemia the response to acetylcholine was impaired in the eight hearts with high initial reperfusion pressure (60 mm Hg) but was intact in the eight hearts with low initial reperfusion pressure (20 mm Hg for 10 minutes, 40 mm Hg for 10 minutes, and then 60 mm Hg thereafter). The response to nitroglycerin, however, remained intact regardless of initial reperfusion pressure. Recovery of resting coronary flow and myocardial oxygen consumption was lower in the group with high pressure reperfusion than in the group with low pressure reperfusion. On reperfusion a transient burst of coronary flow was exhibited by the hearts reperfused at high pressure. These results suggest that high initial reperfusion pressure impairs the endothelial modulation of coronary tone; this may be related to the effects on the coronary vasculature of the "burst" of coronary flow associated with high intravascular pressure.

Ventricular function after anatomic repair in patients with atrioventricular discordance.

Since June 1989, 18 patients with atrioventricular discordant anomalies under 15 years of age underwent anatomic correction, or double switch operation, with 2 hospital deaths (11%). Ages ranged from 1 year 4 months to 12 years (mean 7.2 years) and body weights ranged from 7.1 to 32.5 kg (mean 20.1 kg) at operation. Visceral situs was solitus in 12 and inversus in 6. Ventriculoarterial connection was discordant in 4 and double-outlet in 14. All had associated congenital cardiac anomalies consisting of ventricular septal defect in 17, atrial septal defect in 9, pulmonary atresia in 10, pulmonary stenosis in 6, systemic tricuspid regurgitation in 9, mitral regurgitation in 6, bilateral superior venae cavae in 6, patent ductus arteriosus in 6, Wolff-Parkinson-White syndrome in 2, and congenital atrioventricular block in 1. Previous palliation had been performed 19 times in 11 patients including systemic-pulmonary shunts in 10 patients and pulmonary banding in 1 patient. Anatomic correction consisted in the Mustard procedure in 12 or the Senning procedure in 6 at the atrial level and in external conduit repair in 14, arterial switch operations in 3, or direct anastomosis between the pulmonary artery and right ventricle in 1 at the ventriculoarterial level. The arterial switch operation was indicated in patients with a normal pulmonary valve, and external conduit repair was indicated for patients with pulmonic stenosis or atresia. Anatomic right ventricular end-diastolic volume showed significant reduction from 122.2% +/- 46.3% of normal to 78.8% +/- 24.0%, mainly owing to unloading of the ventricle after the operation (p < 0.0003). Right ventricular ejection fraction remained unchanged (56% +/- 8% to 56% +/- 6%). Anatomic left ventricular end-diastolic volume and left ventricular ejection fraction remained unchanged before and after the operation: volume 134.6% +/- 50.0% of normal to 127.3% +/- 32.8% and ejection fraction from 61% +/- 8% to 56% +/- 8%. Cardiac index averaged 3.1 +/- 0.5 L/min per square meter after the operation. The double switch operation is best indicated in patients with atrioventricular discordance associated with systemic tricuspid regurgitation and/or with poor systemic right ventricular function.

Septation and Fontan repair of univentricular atrioventricular connection.

From April 1986 to September 1988, 12 patients with double- or common-inlet left ventricle and left anterior rudimentary right ventricle underwent septation while 17 patients with double- or common-inlet left or right ventricle underwent the Fontan operation. In the septation group, three patients who had pressure gradients ranging from 10 to 85 mm Hg between the left ventricle and the aorta underwent enlargement of the outlet foramen, and all survived. One of the 12 patients had a common atrioventricular valve that was repaired by separating the atrioventricular valve by the procedure used for atrioventricular septal defect. One had complete heart block before septation and the other one had it after separation. One 17-year-old woman, who had the smallest left ventricle (168% of normal), died in the hospital (mortality, 8.3%). In the Fontan group, one patient who died in the hospital (5.9%) had high pulmonary resistance of 4.4 U/m2, and one late death (5.9%) occurred in a patient who had complete heart block and a high mean pulmonary arterial pressure of 20 mm Hg. Because of suprasystemic pressure in the pulmonary ventricle, two patients had immediate takedown of the septation repair and substitution of the Fontan repair. Although right atrial pressure was almost equal in both groups after operation, the cardiac index was significantly higher in the septation group than in the Fontan repair group (p less than 0.01). These data suggest that patients who are candidates for either septation or Fontan repair might fare better with septation.

Infundibular septum and coronary anatomy in Jatene operation.

Displacement of the infundibular septum and coronary anatomy was studied in 40 patients with variable transposition of the great arteries who underwent the Jatene operation between August, 1982, and May, The perioperative mortality was 12.5%. Fourteen of the 16 patients (87.5%) with intact ventricular septum (Group I), eight of the 12 patients (67%) with aligned infundibular septum and perimembranous trabecular defect (Group II-A), and four of the 12 patients (33%) with anteriorly displaced infundibular septum, malaligned defect, overriding of the pulmonary valve, and severe pulmonary hypertension (Group hypertension (Group II-B) has Shaher type 1 coronary anatomy. In this type of coronary anatomy, the left coronary artery courses in front of the pulmonary artery. However, two patients (12.5%) from Group I, four (33%) from Group II-A, and eight (67%) from Group II-B had various unusual coronary patterns, such as Shaher types 2,3,4,7, and 9. All patients had a left or circumflex coronary artery coursing behind the pulmonary artery. These data suggest that the displacement of the infundibular septum not only determines the type of the defect and hemodynamics, but also often relates to the coronary anatomy Removal of a whole, scallop-shaped sinus of Valsalva and minimal dissection of the coronary artery are preferable, particularly for translocation of such unusual coronary anatomy.

Recovery of cerebral blood flow and energy state in piglets after hypothermic circulatory arrest versus recovery after low-flow bypass.

A miniature piglet model that replicates clinical hypothermic (14 degrees C nasopharyngeal) circulatory arrest and low-flow (50 ml/kg per minute) bypass was used to study carotid blood flow with electromagnetic flow probe, cerebral blood flow by microsphere injection, cerebral metabolic rate by arteriovenous oxygen and glucose extractions, lactate production by cerebral arteriovenous difference, and cerebral edema. Data from five animals that underwent circulatory arrest and five animals that underwent low-flow bypass (aged 28.8 +/- 0.4 [mean +/- standard error of the mean] days) were analyzed. The duration of circulatory arrest and low-flow bypass was 1 hour. In a parallel study with the same animal model, phosphorus 31 magnetic resonance spectroscopy was used to assess cerebral phosphocreatine, nucleoside triphosphate (adenosine triphosphate), and intracellular pH. Five animals (aged 31.8 +/- 1.1 days) underwent circulatory arrest, and five underwent low-flow bypass. A brief phase of hyperemic carotid blood flow was seen immediately after the onset of reperfusion in the circulatory arrest group but not in the low-flow group. In the circulatory arrest and low-flow bypass groups, cerebral blood flow (percentage of baseline 71.2% +/- 8.3% and 69.1% +/- 5.8%, respectively), cerebral oxygen consumption (45.6% +/- 10.0%, 44.5% +/- 7.6%), and cerebral glucose consumption (31.5% +/- 30.7%, 83.5% +/- 24.2%) remained depressed after 45 minutes of reperfusion and rewarming to normothermia. However, after 3 more hours of pulsatile normothermic reperfusion, cerebral oxygen consumption and cerebral glucose consumption had returned to baseline. Phosphocreatine, adenosine triphosphate, and pH were maintained at or above baseline levels throughout low-flow bypass and throughout 3 hours of normothermic reperfusion. In contrast, both phosphocreatine and adenosine triphosphate became undetectable 32 +/- 3.7 minutes after onset of circulatory arrest. During and early after circulatory arrest, pH decreased to a minimum of 6.506 +/- 0.129 at 40 minutes after reperfusion. After 3 hours of normothermic reperfusion, phosphocreatine and adenosine triphosphate recovered to 98.6% +/- 9.0% and 90.1% +/- 13.5% of baseline, respectively, and pH was 7.087 +/- 0.051, similar to baseline (7.1755 +/- 0.041). In the low-flow bypass group, the disparity between the depressed level of cerebral oxygen consumption and normal high-energy phosphate levels may reflect incomplete cerebral rewarming or decreased energy consumption. In the circulatory arrest group, the parallel recovery of oxygen consumption and high-energy phosphates eventually achieving baseline levels suggests that the degree of hypothermia used provides adequate protection for acute cerebral recovery after 1 hour of circulatory arrest.(ABSTRACT TRUNCATED AT 400 WORDS)

Induction of neonatal immunologic tolerance to heart transplantation by intrathymic myocardial cell inoculation in rats.

To induce immunologic tolerance, intrathymic inoculation of myocardial cells in rats was performed during the neonatal period. Isolated myocardial cells from Wistar-Lewis (LEW/Crj) rat hearts were inoculated into the thymi of incompatible neonatal Wistar-King (WKAH/HKm) rats without use of immunosuppressants. Ten weeks later the heart from the LEW donor was transplanted heterotropically to the pretreated male WKAH rat (group 1, n = 14). As controls (groups 2 through 4), heart transplantation was performed in each of 10-week-old rats as follows: (1) The syngeneic heart was transplanted (group 2, n = 4); (2) the allogeneic heart was transplanted without use of immunosuppressants (group 2, n = 12); and (3) the allogeneic heart was transplanted with use of immunosuppressants (cyclosporine, 20 mg/kg/day, for 10 days after transplantation, (group 4, n = 5). In groups 1 through 3, four rats with heart transplants in each group were killed on the seventh day after transplantation and were histopathologically examined. No early rejection was seen in group 1. Hematoxylin-eosin staining of the thymus from the inoculated recipient revealed that donor myocardial cells continued to survive in the thymic tissue. The remaining rats in groups 1, 3, and 4 were saved for study of graft survival time. The longest proven graft survival in group 1 was 390 days, whereas it was only 7 days in group 3. These results indicated that intrathymic inoculation of donor myocardial cells in rats into incompatible neonatal recipients induced donor-specific tolerance for subsequent heart transplantation.

Surgical management of tricuspid malinsertion in the Rastelli operation: conal flap method.

From June 1986 to May 1994, 25 patients underwent the Rastelli operation for complete transposition of the great arteries with ventricular septal defect and pulmonary stenosis or atresia. Fourteen patients whose tricuspid valve chordae were normal underwent the conventional Rastelli procedure (conventional group), whereas 11 patients who had tricuspid malinsertion into the infundibular septum underwent the Rastelli operation concomitant with mobilization of the infundibular septal flap, with the tricuspid valve chordae, to the right ventricular side of the intraventricular conduit (conal flap method) (conal flap group). In relation to the mobilization of the tricuspid valve chordae, right heart function and tricuspid regurgitation were compared between the two groups. There was one early death after the conventional Rastelli procedure and no early death after the Rastelli operation with a conal flap. There was one late death in the conventional group and two late deaths in the conal flap group. The mean follow-up was 50.8 +/- 5.1 months in the conventional group and 54.9 +/- 7.5 months in the conal flap group (p = 0.43). Reoperation was necessary for 1 patient in the conal flap group during follow-up. At the most recent follow-up, all patients in both groups were in New York Heart Association functional class I. Tricuspid regurgitation was estimated from the echocardiograms. Mild to moderate regurgitation was noted in 6 patients in the conventional group and 8 in the conal flap group. However, postoperative right heart catheterization data did not show any significant differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Endovascular therapeutic occlusion following bilateral carotid artery bypass for radiation-induced carotid artery blowout: case report.

A patient with breast cancer received radiation therapy to the upper chest wall. Twenty-two years later, she presented with repeated severe bleeding through a left lower neck ulcer. She was taken to surgery for hemostasis, which was not successful because the carotid artery was surgically inaccessible. To manage for explosive carotid blowout, we performed common carotid artery ligation and endovascular coil embolization after contralateral-external-carotid to ipsilateral-common-carotid artery bypass with a polytetrafluoroethylene (PTFE) graft. The patient has experienced no ischemic events or bleeding since this treatment.

Speciation of vanadium(IV) and vanadium(V) using ion-exchange chromatography and ICP-AES.

A speciation method for vanadium(IV) and vanadium(V) is presented that uses a combination of HPLC and ICP-AES. In this method, 1 mM HNO3 solution and 100 mM HNO3 solution were applied in sequence as eluent. A vanadium(IV) and vanadium(V) mixture was injected into a HPLC anion-exchange column; and vanadium(IV) cation was then eluted by 1 mM HNO3, while vanadium(V) oxoacid anion was trapped on the column. After this separation, vanadium(V) was eluted as a cation from the column by 100 mM HNO3. Vanadium was detected by ICP-AES. In this separation, about 15% of vanadium(V) interfered with vanadium(IV), and trace vanadium(IV) interfered with vanadium(V). This interference could be estimated by simple calculation based on standard observations, and the speciation of vanadium(IV) and vanadium(V) was performed. The lower determination limit was 1 microgram/mL, which is insufficient to speciate vanadium sampled by conventional sampling methods in a working environment. However, impurity of the other valent vanadium species in a vanadium(V) reagent can be determined by the present method, which should be valuable in precisely assessing the toxicities of vanadium species.

Relationships between chemical structures and mutagenicity: a preliminary survey for a database of mutagenicity test results of new work place chemicals.

A database of mutagenicity test results of new chemicals has been developed. Based on the amendment of the Industrial Safety and Health Law (ISHL) in 1979, manufacturers and importers in Japan are required to register any new work place chemicals with bacterial mutagenicity test results. At present more than ten thousand substances have been examined. We have surveyed correlations between 44 substructures and mutagenicity in 2,857 ISHL data as well as in 1,207 National Toxicology Program data as a preliminary analysis. The percentages of the mutagenic compounds were calculated. High percentages were found for electrophilic reagents such as epoxides (63%), aromatic nitro compounds (49%) and primary alkyl monohalides (46%). 71% of peroxides was found to be mutagenic. The results suggest that several types of reactions such as nucleophilic substitution reaction, nitrenium cation reaction and radical reaction are included in the process of the mutagenic alterations of DNA.

Lung lesions induced by intratracheal instillation of nickel fumes and nickeloxide powder in rats.

Acute and subacute lung toxicity of nickel fumes was examined by single and repeated intratracheal instillation of nickel fumes and Ni2O3 and NiO powders in the rat. LD50 of nickel fumes was estimated as 38.2 mg/kg body weight (b.w.) according to the method of Litchfield and Wilcoxon. Body weight gain was retarded as in the order of a single dose of 13.0 mg Ni2O3/kg > 14.3 mg nickel fumes/kg > 1.4 mg Ni2O3/kg > 13.0 mg NiO/kg b.w. compared to controls. The histopathological changes in the lungs of the 14.3 mg nickel fumes/kg-dosed rats were milder than those induced by administration of 13.0 mg Ni2O3/kg but severer than those induced by administration of 1.4 mg Ni2O3/kg b.w. A single administration of NiO powder did not produce any histopathological effects on the lungs. The repeated administration of nickel fumes produced persistent edema and proteinosis in the alveoli. The nickel fumes, which were chemically composed of 97% of NiO and 3% of Ni2O3, were very fine particles about 5-10 nm in diameter, partly aggregated into larger particles and spherical particles about 0.6 micron in diameter. Solubility in distilled water and saline was in the order of nickel fumes > Ni2O3 powder > > NiO powder. It was suggested that a toxic Ni2O3 component and very fine particles of nickel fumes are involved in the acute lung toxicity of nickel fumes. The epithelial injury induced by reactive oxygen and hydroxy radicals, which would be produced during the process of conversion of Ni(III) to Ni(II) and phagocytosis of nickel fumes by macrophages and polymorphonuclear cells, are presumed to be involved in the pathogenesis of nickel fumes-induced lung lesion.

Development of an inhalation system of high melting point metal fumes and its use for exposure of rats to chromium and nickel fumes.

An experimental inhalation system was developed for fumes generated from powders of high melting point metals such as chromium, nickel, manganese and iron. The system consisted of a plasma flame metal sprayer as a fume generator, a granular bed type fume collector, a fluidized bed aerosol generator, an exposure and a control chamber of a horizontal-flow type and inhalant monitoring and controlling units. Performance of the chambers was ensured by a distribution test using flyash as a test aerosol. Using this system, rats were exposed to chromium fumes for one week or to nickel fumes for two months. The exposure concentrations of the chromium and nickel fumes were 1.85 +/- 0.55 mg/m3 and 0.51 +/- 0.15 mg/m3 (mean +/- SD), near the target levels of 2 mg/m3 and 0.5 mg/m3, respectively. The mass median aerodynamic diameter and the geometric standard deviation of the chromium fumes were 2.1 microns and 2.00, respectively. Those of the nickel fumes were 3.7 microns and 1.74, respectively. Species analysis of these fume particles revealed that 26.4% of the total chromium was hexavalent and the residue was trivalent and that 1-3% of the total nickel was nickel(III) and the residue was nickel(II). Inhaled-metal concentrations in the lungs showed steady increases with the exposure periods and were within the normal range of variation. On the basis of these results, it is concluded that this system is useful for long-term inhalation experiments using high melting point metal fumes.

[A case of MRSA sepsis treated by the sequential combination therapy netilmycin and minocycline].

A sixteen year old female was feverish from June 12, 1993. Methicillin-resistant Staphylococcus aureus was isolated from the blood, the diagnosis of MRSA sepsis was established. Vancomycin (2 g/day) was administered for eighteen days, but MRSA was not eradicated in the blood culture. Then she was administered a combination therapy of arbekacin (200 mg/day) and imipenem/cilastain (1 g/day) for seven days, but MRSA in the blood was cultured continuously. The sequential combination therapy of netilmycin (200 mg/day) and minocycline (200 mg/day) was started, MRSA was eradicated from the blood culture after four days. The sequential combination therapy netilmycin and minocycline was seemed to be effective for MRSA infection.

[An imported case of primary pulmonary coccidioidomycosis].

Coccidioides immitis is a causative agent of coccidioidomycosis, which is one of the most dreadful mycosis because of its infectious and pathogenic nature. The endemic areas are in the southwestern parts of the United States and other semi-arid regions throughout the Western Hemisphere. During the early 1990s, the incidence of coccidioidomycosis in California increased dramatically, resulting in recognition for this mycosis as a reemerging infectious disease in the United States. The patients included a large number of non-informed visitors from non-endemic countries. Our report is on an imported case of primary pulmonary coccidioidomycosis. A 35-year-old Japanese male, after living in the United States for nine months, suffered from a combination of headache and fever. He was given a serological examination, and a chest radiograph in Phoenix, Arizona in the United States and was diagnosed as coccidioidomycosis. A daily dosage of 400 mg of fluconazole was administered and he returned to Japan. His headache and skin rash persisted and he was admitted to our hospital to evaluate the severity of his disease. There were no fungi cultured from neither bronchoalveolar nor cerebrospinal fluid and he was discharged. The patient had been treated with fluconazole and his symptoms, high-resolution CT and serological antibody titer were monitored. After 18 months, his clinical and radiological evolution was favorable and his serological IgM titer was below its sensitivity medication was stopped and there were no relapses.

[Invasive pulmonary aspergillosis caused by aspiration of polluted water after nearly drowning].

A 21-year-old male nearly drowned in a reservoir by a traffic accident and he aspirated a large mount of polluted water containing Aspergillus fumigatus. On admission to our hospital, he was alert but cyanotic. Chest rentogenograms showed scatter infiltrative shadows in bilateral lung fields. We administered methylpredonizolon and antimicrobial agents immediately because of respiratory failure which was rapidly progressing. During the following six days, infiltrative shadows diminished but multiple nodular shadows in both lung fields appeared. The diagnosis of pulmonary aspergillosis was confirmed by serological and microbiological studies. Intravenous amphotericin B and oral itraconazol were administrated, and clinical improvement was observed.

[A study of virulence factors produced by MRSA strains isolated from blood samples].

Toxic shock syndrome toxin-1 (TSST-1) and enterotoxins are important virulence factors produced by Staphylococcus aureus. It is reported that these toxins are associated with septic shock and toxic shock syndrome. We investigated the toxin production and coagulase types of 701 MRSA strains isolated in Sasebo City General Hospital between 1994 and 1996 TSST-1 or/and enterotoxins were detected in 67% of all MRSA strains, and those were detected in 88% of MRSA strains isolated from blood samples. 45% of all MRSA strains produced both TSST-1 and enterotoxin C, and 70% of MRSA strains obtained from blood produced those toxins. Frequency of TSST-1 or/and enterotoxin production by MRSA strains isolated from blood samples was significantly higher than that by MRSA strains isolated from urine and pharynx (p < 0.05), and frequency of both TSST-1 and enterotoxin C production by MRSA isolates from blood was significantly higher than that by MRSA strains isolated from pharyngeal sample (p < 0.05). This study indicated that investigation of virulence factors produced by MRSA might give the useful information on prevention and treatment of MRSA infection.