Effect of subarachnoid hemorrhage on serotonin uptake and metabolism in rabbit basilar artery.

The effects of subarachnoid hemorrhage (SAH) on neuronal uptake and metabolism of serotonin (5-HT) in the rabbit basilar artery were examined. Extracted 3H-amines from the isolated arteries after incubation with [3H]5-HT were separated by column chromatography. Radioactivity of 5-HT and 5-hydroxyindoleacetic acid was, respectively, 52.7 +/- 13.9 and 22.9 +/- 5.4 x 10(2) dpm/mg tissue in the control group (n = 8); 32 and 18% of control after denervation (n = 6); 99 and 12% of control after treatment with pargyline (n = 7); and 65 and 76% of control after SAH (n = 7). These results suggest that the neuronal uptake of 5-HT is impaired by SAH, although monoamine oxidase activity is relatively preserved.

Instability of F-actin in the absence of ATP: a small amount of myosin destabilizes F-actin.

The effects of the neutral salt concentration, pH, and coexistence of myosin on the denaturation of F-actin without ATP at low temperature were studied using the DNase I inhibition assay. The percent denaturation of F-actin gradually increased with a decrease in pH from 8.0 to 5.2, on incubation for 2 weeks in the presence of 50 mM KCl at 0 degrees C. This change was much faster in 0.5 M KCl and more than 75% of the F-actin became denatured on incubation for 1 week at pH 5.2. The buffer composition was found to exert a strong influence on the denaturation of F-actin. That is, there was a tendency for the denaturation of F-actin at pH 6.0 to be faster in MES[2-(N-morpholino)ethanesulfonic acid]-NaOH buffer than in sodium phosphate buffer, the critical concentrations of actin in 0.5 M KCl being 0.31 mg/ml for MES-NaOH buffer and 0.15 mg/ml for sodium phosphate buffer. A sigmoidal relationship was found between the percent denaturation of F-actin and the KCl concentration added, the greatest change occurring at KCl concentrations between 0.25 and 0.75 M. The time courses of the denaturation of F-actin showed that the percent denaturation rose at first and that in time the rate of the increase decreased. In the case of pH 8.0 and 0.5 M KCl, it took about 1 week for the denaturation rate to begin to drop. The pH of 6.0 further promoted the instability of F-actin exposed to high KCl concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of subarachnoid hemorrhage on serotonin uptake and release in the rabbit basilar artery.

This study analyzes the changes induced by subarachnoid hemorrhage (SAH) on the serotonin (5-hydroxytryptamine, 5-HT) uptake and release evoked in rabbit basilar arteries by tyramine. Rabbits were injected with 5 ml of autologous arterial blood into the cisterna magna to produce SAH. Tritium accumulation in basilar arteries was measured after 30 minutes of incubation with 10(-7) M [3H]5-HT and a subsequent 120-minute superfusion (1 ml/min) period. The uptake of 5-HT by arteries 1, 2, 3, and 7 days after SAH was found to be 109%, 69%, 57% (P less than 0.05), and 67% (P less than 0.05) (n = 4, 4, 9, and 6; P less than 0.05) of control (n = 13; 16.8 +/- 1.2 X 10(2) dpm/mg tissue), respectively. The neuronal (cocaine-sensitive) uptake of 5-HT in the arteries 3 days after SAH decreased to approximately 38% of control, whereas the extraneuronal (cocaine-insensitive) uptake of both groups had almost the same absolute value (n = 6 and 6; 4.4 +/- 0.4 and 4.8 +/- 0.4 X 10(2) dpm/mg). Autoradiographic study disclosed that dense clusters of silver grains in the adventitia were not observed after treatment with cocaine (3 X 10(-5) M), although a diffuse distribution of grains was present throughout the vascular wall. The labeled arteries were stimulated by superfusion of tyramine, which is known to replace amines in the sympathetic nerve ending. Tyramine (10(-6) and 10(-4) M)-induced 3H efflux was significantly potentiated by SAH (n = 6) and was suppressed by treatment with cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of bilirubin on rabbit cerebral arteries in vivo and in vitro.

The effect of bilirubin on vasoreactivity was examined in the exposed rabbit basilar artery (diameter, 1045 +/- 17 microns; n = 18) and its cortical branches (diameter, 265 +/- 11 microns; n = 43) in vivo. Vasoconstriction induced by uridine triphosphate (UTP; 10(-5) to 10(-3) mol/L) was observed in vivo before and after a 60-minute application of supersaturated bilirubin (10(-4) mol/L). Bilirubin was dissolved in modified artificial cerebrospinal fluid (pH 7.4) or in physiological salt solution (pH 7.6). The latter was spectrophotometrically estimated to contain a higher concentration of free bilirubin because of the formation of less colloid. After treatment with bilirubin in artificial cerebrospinal fluid, the effect was minimal in the basilar arteries (n = 7), whereas the diameter of the branches was reduced by 9.6 +/- 1.5% (n = 23) and UTP-induced vasoconstriction was potentiated. After application of bilirubin in physiological salt solution, the basilar arteries contracted slightly (-2.1 +/- 0.9%; n = 6) and the UTP-induced vasoconstriction in the branches was attenuated (n = 12). After a 60-minute incubation of basilar artery with bilirubin in physiological salt solution in vitro, isometric tension recordings showed a diminution in KCl- and UTP-induced vasoconstrictions. Acetylcholine- and sodium nitroprusside-induced relaxations were also attenuated. It is suggested that bilirubin may exert different effects depending on the size of arteries and the concentration of free bilirubin. The constrictor and potentiating effects of bilirubin could be caused by the impairment of the relaxation mechanism. When the toxic effect of bilirubin becomes severe, the constrictor mechanism is also damaged.

The effect of hemoglobin on vasodilatory effect of calcium antagonists in the isolated rabbit basilar artery.

The effect of hemoglobin on the vasodilatory effect of calcium antagonists was studied in isolated rabbit basilar arteries using an isometric tension measurement method. The ability of nimodipine to relax or inhibit contractions elicited by high K+ depolarization or serotonin (5-hydroxytryptamine, 5-HT) was investigated in control arterial rings and rings pretreated by hemoglobin. Hemoglobin (10(-6) and 10(-5) M) reduced the relaxation induced by nimodipine (10(-10) to 10(-8) M) in the rings contracted by 40 mM KCl. This reduction in relaxation was also observed with 3 x 10(-10) to 3 x 10(-9) M nicardipine, 3 x 10(-8) to 3 x 10(-7) M verapamil, and 10(-7) to 10(-6) M diltiazem. On the other hand, the effect of nimodipine was not influenced by endothelial removal or by pretreatment with 10(-5) M albumin or 10(-6) M prostaglandin F2 alpha. Hemoglobin restored the 10(-10) and 10(-9) M nimodipine-induced inhibition of the contraction elicited by CaCl2 (0.3 to 20 mM) in a K(+)-rich, Ca(++)-free solution. This restoration was greater at higher concentrations of CaCl2. Hemoglobin enhanced both the nimodipine-sensitive tonic phase and the less sensitive phasic phase of contractions produced by 10(-6) M of 5-HT. It abolished the inhibitory effect of 10(-8) and 10(-7) M nimodipine on the phasic contraction. Endothelial removal also enhanced both phases of the contraction, but did not abolish the effect of nimodipine. This study showed that the vasodilatory effect of calcium antagonists, especially nimodipine, on the vasoconstriction induced by other vasoactive substances decreased in the presence of hemoglobin.

Neuronal and glial proteins in medulloblastomas. I. Immunohistochemical study.

Neuronal and glial specific proteins were studied in 35 cases of medulloblastomas, using immunohistochemical methods and antibodies to neurofilament triplet proteins (NF68Kd, NF160Kd, NF210Kd), gamma-enolase, GFAP, S-100 protein, and myelin basic protein. NF160Kd positive cells were observed in 12 of the 35 cases. NF160Kd positive cells were noted in 2, but NF210Kd positive cells were not detected. Gamma-enolase positive cells were observed in 23 cases. GFAP and S-100 protein positive cells were seen in 25 and 28 cases respectively; many of these cells were reactive astrocytes. The myelin basic protein positive cells could not be identified. The expression of neuronal and glial proteins had no relation to the postoperative survival of patients with medulloblastoma, but gamma-enolase may be one factor for evaluating prognosis.

Parvovirus infection and generalized edema in adults.

We describe the clinical and laboratory findings of 7 adult patients with serological evidence of recent human parvovirus B19 (HPV) infection who presented with generalized edema. Six of the 7 patients had household contact with children with erythema infectiosum and had flu-like symptoms before visiting hospital. The interval between the flu-like episode and the development of edema ranged from 4 to 13 days (mean 7.0). In all 7 patients, there was serological confirmation of recent HPV infection, and all showed the development of edema following HPV infection without urine abnormalities or anemia. Two patients presented hypocomplementemia, and two patients showed signs of congestive heart failure. HPV may be considered a causative agent of generalized edema not only in the fetus but also in adults and HPV infection should be included in the differential diagnosis of generalized edema formation.

Severe chest pain due to gastric anisakiasis.

We treated two cases of gastric anisakiasis presenting with severe chest pain. In both cases, there was a history of prior ingestion of raw saltwater fish. After endoscopic removal of larvae, the chest pain disappeared and never recurred. Other diseases causing chest pain were ruled out by symptoms, signs, blood tests, electrocardiography, chest radiograph, and ultrasonic examination of the heart and abdomen. Thus the chest pain was considered to be caused by gastric anisakiasis. Gastric anisakiasis should be included in the differential diagnosis of acute chest pain.

Adult-onset Still's disease with submassive hepatic necrosis.

We present a 74-year old woman who was hospitalized because of typical spiking fever, evanescent rash, polyarthralgia, lymphadenopathy, and marked elevation of serum transaminases and lactate dehydrogenase (LDH) due to adult-onset Still's disease (AOSD) with submassive hepatic necrosis. All of the symptoms and abnormal laboratory findings were dramatically improved after treatment with prednisolone. The clinical course of this patient indicates that AOSD with severe hepatic necrosis can successfully be treated with early administration of corticosteroid, although it remains unknown whether the disease can remain in remission with no or minimal treatment.

Severe hypercalcemia and polyuria in a near-drowning victim.

A 73-year-old man was admitted because of near-drowning in a hot springs bath. Transient severe hypercalcemia and polyuria were seen during the first hospital day. It seemed that the hypercalcemia was due to acute intoxication from calcium contained in the water of the spring absorbed mainly through the alveoli. To our knowledge, this is the first case of acute hypercalcemia complicating a near-drowning in a hot spring. Analysis of serum and urine electrolytes during the polyuric phase revealed saline diuresis, which was probably due to interference by the hypercalcemia of the reabsorption of sodium and free water.

[Pseudomonas aeruginosa bacteremia associated with hematologic disorders [I]. Predisposing factors and clinical manifestations].

We experienced 57 episodes of Pseudomonas aeruginosa bacteremia in 55 patients with hematologic disorders in a 16-year period. Ninety-five percent of the patients had hematologic malignancies such as acute leukemia. All but one patient received cytotoxic or immunosuppressive therapy at or prior to the onset of bacteremia. Seventy-seven percent of the episodes occurred during profound granulocytopenia of below 100/mm3. All the patients acquired their infection in the hospital, and 96% had received antibiotic therapy during the preceding two weeks. Periodontal, anorectal, lower respiratory tract, and urogenital infections were the sources of bacteremia in about three-quarters of the episodes. Periodontal infection tended to progress to cellulitis of the face or the floor of the mouth, often resulting in bacteremia of the unimicrobial type, while anorectal infection predisposed to abscess formation, frequently leading to bacteremia of the polymicrobial type. Cellulitis at onset was seen in 35% of the episodes. Most sites of infection did not become apparent until one to three days after the onset of fever, probably because of depressed inflammatory response associated with severe granulocytopenia. The majority of patients complained of gastrointestinal symptoms such as nausea and vomiting, abdominal pain, diarrhea, and abdominal fullness at the onset of bacteremia. Major complications included bacteremic shock (63%), impaired consciousness (25%), ecthyma gangrenosum or hemorrhagic gangrenous cellulitis (18%), and jaundice (12%). Furthermore, there were one case each of endocarditis and disseminated intravascular coagulation. It was thus suggested that the clinical picture of P. aeruginosa bacteremia complicating hematologic disorders is influenced by the predisposing conditions associated with the underlying diseases and their treatment.

[Pseudomonas aeruginosa bacteremia associated with hematologic disorders [II]. Blood culture isolates and surveillance cultures].

We experienced 57 episodes of Pseudomonas aeruginosa bacteremia in 55 patients with hematologic disorders such as acute leukemia over a 16-year period. All the patients were treated on the same hospital ward. A total of 57 blood culture isolates of P. aeruginosa were divided into nine serogroups. Seventy-four percent of the isolates belonged to four serogroups, which became preponderant one after the other. Surveillance throat and/or stool cultures grew the organisms identical to the isolates from the blood at or prior to the onset of bacteremia in 75% of the episodes. Only 11% of the patients had had P. aeruginosa cultured at admission. The acquisition of the organism was closely associated with antibiotic therapy for other presumed or proved infection. On the other hand, 60% of the episodes occurred during the administration of at least one in vitro effective antibiotic. In five episodes, the patients had received an antipseudomonal penicillin and an aminoglycoside in combination, both of which proved effective in vitro against the infecting organism, when bacteremia occurred. In managing P. aeruginosa bacteremia complicating hematologic disorders, it was thus suggested that surveillance cultures should be regularly carried out, and that attention should be drawn to the occurrence of "breakthrough" bacteremia.

[Pseudomonas aeruginosa bacteremia associated with hematologic disorders [III]. Prognostic factors].

We reviewed 57 episodes of Pseudomonas aeruginosa bacteremia in 55 patients with hematologic disorders such as acute leukemia during a 16-year period, focusing especially on the prognosis. Survival at one week after onset was observed in only 39% of the episodes. Prognosis was significantly better in patients with unimicrobial bacteremia than in those with polymicrobial bacteremia (21/42 vs 1/15, p less than 0.01), in patients without shock than in those with shock (13/21 vs 9/36, p less than 0.02), in patients with granulocyte count at onset of at least 100/mm3 than in those with more marked granulocytopenia (10/13 vs 12/44, p less than 0.01), in patients with an increase in granulocyte count by at least 100/mm3 during their infection than in those without any subsequent increase (18/18 vs 4/13, p less than 0.001), and in patients with total serum protein level at onset of at least 6.0 g/dl than in those with hypoproteinemia (18/32 vs 4/25, p less than 0.01). Patients with bacteremia secondary to urogenital infection tended to have a higher one-week survival rate than those with pneumonia followed by bacteremia (4/8, 50% vs 2/9, 22%). With regard to the antibiotic treatment of unimicrobial bacteremia, 14 (70%) of 20 patients receiving therapy with one or two anti-pseudomonal beta-lactam antibiotics and an aminoglycoside in combination that were effective in vitro against the infecting organism survived, and so did only seven (32%) of 22 patients receiving therapy with either one in vitro effective beta-lactam or aminoglycoside or inadequate drugs (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Changing patterns of blood culture isolates from patients with acute leukemia: a review of twenty years' experience.

During the 20-year period, 1972-1991, 286 episodes of bacteremia occurred in 200 (45%) of 445 patients with acute leukemia in a hematology ward, giving an incidence of 482 episodes per 1,000 hospital admissions. The frequency of bacteremia was almost unchanged throughout the study period. The frequency of gram-negative bacilli decreased significantly, however, from 81% of all the isolates for the first half of the study period to 50% for the latter half. Despite the common use of ceftazidime and imipenem during the last 5-year period, Pseudomonas aeruginosa increased in frequency to be the most frequent organism. This was opposite to the decreased frequencies of Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. The isolates of P. aeruginosa obtained during this period, all of which proved sensitive to ceftazidime and/or imipenem, were almost equally distributed among five serogroups, although a temporal preponderance of a limited number of serogroups was observed during the preceding 15-year period. On the other hand, the frequency of gram-positive cocci increased from 9% in the first decade to 35% in the latter decade. Staphylococcus epidermidis, Enterococcus species and, to a lesser extent, Staphylococcus aureus were ranked as major pathogens. Among the recent isolates of S. aureus, methicillin-resistant strains virtually replaced methicillin-sensitive ones. Therefore, until more effective means for control of P. aeruginosa bacteremia in particular become available, the occurrence of this infection will continue to limit the successful treatment of acute leukemia.

Disseminated mycobacteriosis in patients with severe hematologic disorders.

During a 20-year period disseminated mycobacteriosis occurred in 11 (1.1%) of a total of 1006 patients with severe hematologic disorders, with the frequency remaining almost unchanged. The diagnosis in three patients (27%) was made only at autopsy. Tuberculosis accounted for 64% of all cases. Female preponderance was seen with a male-to-female ratio of 3:8. The major factors associated with dissemination included immunosuppression, weight loss, old age, and diabetes mellitus. Fever was the most common clinical symptom. Chest X-ray abnormalities, hypoproteinemia, liver dysfunction, and hypoxemia were noted in most cases. The prognosis of tuberculosis depended mainly on early diagnosis and treatment, while that for the nontuberculous variety was largely influenced by the underlying disease. Thus, our findings indicated that clinicians must suspect disseminated mycobacteriosis especially in any febrile patient with recent pulmonary pathology on chest X-ray, so that an adequate trial of therapy can be provided.

Staphylococcus aureus bacteremia in patients with hematologic disorders.

During the 20-year period, 1972-1991, 27 episodes of Staphylococcus aureus bacteremia, including 10 with methicillin-resistant strains (MRSA), were documented in 26 patients with hematologic disorders, mainly acute leukemia and malignant lymphoma, representing 6% of all 433 episodes of bacteremia in a hematology unit. MRSA replaced methicillin-sensitive strains (MSSA) in the last four years. The skin and upper respiratory tract were the two most common primary foci. Most episodes occurred during neutropenia. Pharyngeal colonization often preceded the development of bacteremia. Antibiotic therapy predisposed to MRSA acquisition during hospitalization, whereas MSSA was mostly detected in admission cultures. Among 22 patients with monomicrobial bacteremia, 19 (86%) survived longer than one week, including all four with MRSA bacteremia who received vancomycin. The survival rate did not differ materially between MRSA and MSSA bacteremias. Secondary foci, chiefly located in the lung, were found in 30% of all patients with S. aureus bacteremia. Prolonged antibiotic therapy, therefore, seems warranted in patients with evident metastatic lesions, although abbreviated therapy is proposed in neutropenic cancer patients.

Effect of recombinant human granulocyte colony-stimulating factor (G-CSF) in the treatment of Pseudomonas aeruginosa bacteremia complicating hematologic malignancy--a preliminary study.

The efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) in the treatment of Pseudomonas aeruginosa bacteremia in cancer patients receiving intensive chemotherapy was studied retrospectively. In 14 of the 24 episodes of P. aeruginosa bacteremia, which occurred in 23 severely neutropenic patients with hematologic malignancies during a three-year period, G-CSF was given subcutaneously or intravenously at daily doses of 75 micrograms/body to 200 micrograms/m2 of body surface. Overall, survival at one week after onset was observed in 13 patients (54%). Treatment with G-CSF, however, had no statistically significant association with one-week survival, although a favorable outcome was well correlated with an increase in the neutrophil count during therapy. On the other hand, septic shock and appropriate antibiotic therapy were the major prognostic factors. The frequency of shock was reduced by appropriate therapy, but not by G-CSF treatment. These preliminary findings thus suggested that G-CSF should not be effective in the treatment of neutropenic cancer patients with P. aeruginosa bacteremia. No adverse effects of G-CSF were observed.

Capnocytophaga sputigena bacteremia associated with acute leukemia.

During a three-year period, Capnocytophaga sputigena bacteremia occurred in three patients with acute leukemia receiving induction therapy on a hematology ward. Oral pathology such as periodontitis or severe mucositis was considered to be the most likely source of bacteremia. All three blood culture isolates were identified as that species by deoxyribonucleic acid (DNA) homology studies. Because of the phenotypical similarity of Capnocytophaga species, it is difficult to differentiate them by conventional bacteriological methods. All three isolates were susceptible to antibiotics active against most anaerobes. However, production of beta-lactamase was found in two isolates, one of which proved resistant to both piperacillin and ceftazidime. Therefore, the empiric use of imipenem or clindamycin may be justified in febrile granulocytopenic patients with cancer who develop significant oral lesions.

A clinical index for the timing of blood cultures in febrile patients with acute leukemia.

In an attempt to define a clinical index for the timing of blood cultures in febrile patients with acute leukemia, subjective symptoms at onset of bacteremia were investigated in a total of 109 consecutive episodes. General malaise, chills, and nausea and vomiting were most frequently observed (66%, 59%, and 50%, respectively). The gastrointestinal (GI) symptoms including nausea and vomiting, abdominal discomfort and fullness, abdominal pain, and diarrhea were encountered in 72% of all the episodes, forming the second largest group next to those closely associated with high fever. These GI symptoms were usually mild and of brief durations, and their occurrence had no relation to sites of infections or etiology of bacteremia. In some cases, nausea and vomiting were aggravated by intensive antileukemic chemotherapy or massive GI bleeding. It was thus suggested that GI symptoms, particularly nausea and vomiting, concomitant with a remarkable, sometimes abrupt rise in temperature during granulocytopenia may serve as a useful index for the timing for blood collection for culture to improve the probability of detection of bacteremia.

[Cat scratch disease showing clinical picture resembling tuberculous lymphadenitis: a case report].

On February 18th, 1997, a 61-year-old woman visited our hospital because of a left inguinal mass. On physical examination, the mass was soft without inflammatory sign. About one month later, the node was excised. Pathological examination revealed granulomas with caseous necrosis and Langhans giant cells, suggesting tuberculosis, although acid fast stain was negative. Thereafter, re-history taking in detail disclosed that a kitten had often scratched her. We reexamined the pathology and checked her for serum antibodies to Bartonella henselae, the etiological microbe of cat scratch disease (CSD), using enzyme immunoassay. Histopathological reexamination of the excised mass revealed suppurative granulomas in addition to caseous ones. The level of IgG (negative: < 12 units) to B. henselae was 78 units on March 25th, 138 units on April 19th, and 18 units on July 18th, while the level of IgM (negative: < 12 units) was negative at each determination. These serological results strongly suggested current infection of B. henselae. The diagnosis of CSD could be established based on the history and the laboratory findings. When one encounters a case of granulomatous lymphadenitis, CSD should be considered for the differential diagnosis, and in this regard, anamnesis about contact with cats should be asked.