Toxic shock-like syndrome with flu-like prodrome: a possible role of 'enhancing tissue focus' for streptococcal toxic shock.

We describe three patients with invasive group A streptococcal infection, admitted during the 3 months between November 1996 and February 1997. All patients were previously healthy Japanese women who developed a profound shock, with a rapidly fatal outcome, after experiencing flu-like symptoms. All cases conformed to the case definition of toxic shock-like syndrome (TSLS).Currently, the pathogenic mechanism of TSLS remains unclear. Known microbial virulence factors can not sufficiently explain the occurrence of TSLS, and it has been generally considered that host factors may be contributory. On pathological examination, each patient had one organ or tissue that was most severely involved: Case 1 a non-penetrating trauma; Case 2 a pregnant uterus; and Case 3 a pulmonary lesion reminiscent of lymphocytic interstitial pneumonia. On the basis of clinicopathological features of these cases, we propose that the coexistence of 'enhancing tissue focus' may be one of host factors for the progression of TSLS in patients infected with non-invasive GAS.

Degradation of human brain natriuretic peptide (BNP) by contact activation of blood coagulation system.

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were added to venous blood samples from healthy volunteers, and incubated in tubes made of various materials. The residual immunoreactivity was measured with radioimmunoassay for BNP and ANP. In blood samples stored in glass tubes, immunoreactivity of ANP was more stable than that of BNP. In siliconized glass or PET tubes, however, BNP immunoreactivity was more stable than ANP. The activation of blood coagulation factors was evaluated from the kallikrein activity in plasma. Kallikrein activity was increased in plasma stored in glass tube while it was negligible in plasma stored in siliconized glass or PET tubes. In kaolin-activated plasma, more rapid BNP degradation and higher kallikrein activity were observed. Our results indicated that the blood coagulation factors, especially kallikrein, played an important role in digestion of BNP.

Stability of brain natriuretic peptide (BNP) in human blood samples.

Stability of immunoreactivity of human brain natriuretic peptide (BNP) in blood samples was investigated. After storage of the whole blood samples in the blood collecting tubes made of glass or polyethylene terephthalate (PET), residual immunoreactivity of BNP in the plasma was measured by sandwich radioimmunoassay for human BNP. BNP in the blood samples collected in the PET tubes were kept more stable than that in the glass tubes. The results suggested that commercially available PET tubes would enable more accurate BNP values and this would also help to simplify the sample preparation.

Isoflurane inhibits neuronal Ca2+ channels through enhancement of current inactivation.

To help clarify the mechanisms by which volatile anaesthetics act on neuronal Ca2+ channel currents (IBa), the effects of isoflurane were studied on IBa in rat dorsal root ganglion (DRG) cells. Voltage-dependent IBa were pharmacologically subdivided into L-, N- and P/Q-types, and toxin-resistant IBa. At clinically relevant concentrations, isoflurane inhibited the L-, N- and P/Q-types, but not toxin-resistant IBa. The IC50 values for the L-, N- and P/Q-types were 0.7%, 1.3% and 3.0%, respectively (concentrations equivalent to 0.35, 0.68 and 1.46 mmol litre-1 in the aqueous phase). Isoflurane also produced initial transient augmentation of the N-type IBa. Isoflurane shifted the mid-point of the steady-state inactivation curve for the L-, N- and P/Q-type IBa towards negative potentials, and prolonged the time constant of current reactivation. We conclude that isoflurane inhibited L-, N- and P/Q-type IBa in rat DRG neurones by enhancing current inactivation and prolonging recovery time after inactivation. Transient augmentation of the N-type IBa may also form part of the overall actions of isoflurane in DRG neurones.

Low-dose intramuscular polymyxin B improves survival of septic rats.

UNLABELLED: Polymyxin B (PLB) is a cationic antibiotic that also stoichiometrically neutralizes the lipid A moiety of endotoxin. We examined effects of a small dose of PLB on the mortality of rats with cecal ligation and puncture, on LPS-stimulated nitric oxide (NO) production, and on tumor necrosis factor alpha (TNF alpha) production by isolated rat Kupffer cells. MATERIALS AND METHODS: In vivo studies: Cecal ligation and puncture (CLP) was performed under anesthesia in 28 rats. One hour after CLP, either 600 U/kg of PLB or saline was administered intramuscularly every 6 h (PLB group: n = 12; control group: n = 16). Plasma endotoxin was measured at 3 and 24 h after the CLP by the Endospecy test. This was compared with survival. IN VITRO STUDIES: Kupffer cells were isolated from the normal rat liver. The cells were incubated with LPS or LPS + PLB. After 24 h, NO and TNF alpha content were measured using the Griess and ELISA methods, respectively. RESULTS: Low dose PLB significantly decreased the endotoxin levels at both 3 and 24 h (5.5 +/- 2.1 pg/mL vs. 32.8 +/- 3.6 at 3 h; 26.1 +/- 6.1 vs. 49.1 +/- 5.6 at 24 h (p < .05) after CLP. PLB significantly improved survival of CLP rats (68.8% in the control group vs. 100% in the PLB treated group on 3 days after CLP, p < .001). PLB also attenuated NO and TNF alpha production from the Kupffer cells. CONCLUSION: Intramuscular PLB administered in low doses may improve the mortality of sepsis.

In vitro and in vivo expression of inducible nitric oxide synthase during experimental endotoxemia: involvement of other cytokines.

In this study, we investigated the expression of genes for inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) of Kupffer cells in the presence of lipopolysaccharide (LPS), and the tissue expression of iNOS in a rat liver after LPS injection at various time intervals. The effects of L-NG-nitroarginine-methyl-esther HCI (L-NAME), a NO inhibitor, also were examined. The mRNA transcripts of TNF-alpha, IL-1 beta, and IL-6 were rapidly detected no more than at 1 h after LPS stimulation, whereas the iNOS transcript was detectable from 3 h after LPS stimulation and maximally increased at 12 h. This fact suggested that these early induced cytokines were related to expression of iNOS. Using an anti-iNOS antiserum raised against recombinant iNOS protein, immunohistochemical analysis was made to reveal kinetics of NO producing cells. The cells immunoreactive for iNOS appeared at 6 h post-LPS injection in the sinusoids of the liver. By structural and immunohistochemical studies, almost all iNOS positive cells were identified as Kupffer cells and endothelial cells. The number of cells immunoreactive for iNOS increased until 12 h post-LPS injection. At 24 h after LPS injection, iNOS positive cells were restricted to the foci of spotty necrosis. Hepatic injury measured by released enzymes was increased by pretreatment of L-NAME before LPS injection.

Point mutations of the c-Ki-ras gene in carcinoma and atypical epithelium associated with congenital biliary dilation.

OBJECTIVES: Congenital biliary dilation (CBD) may be accompanied later by gallbladder carcinoma or bile duct carcinoma. These cancerous lesions are frequently associated with atypical epithelium that was suspected of being precancerous. To determine whether atypical epithelium may be precancerous, we examined the DNA sequence of the c-Ki-ras gene at codon 12 in nine cases of CBD concurrent with seven gallbladder carcinomas, one bile duct carcinoma, and one bile duct atypical epithelium. METHODS: Tumor specimens were surgically removed from nine patients with CBD at Nagoya University Hospital between 1979 and 1988. Tumor was isolated by microdissection, and DNA was amplified by a two-step polymerase chain reaction which then was directly sequenced. RESULTS: Four of seven gallbladder carcinomas and one bile duct carcinoma contained the c-Ki-ras point mutation at codon 12, and atypical epithelium associated with these carcinomas had the same mutation. One case of atypical bile duct epithelium also contained the mutation. CONCLUSIONS: These results indicate that the c-Ki-ras point mutation at codon 12 may be responsible for either cancer or atypical epithelia associated with CBD.

Establishment of a monoepoxide (leukotoxin and its isomer) producing system using a hydrogen peroxide-generating system.

We established an effective monoepoxide-generating system by combining cytochrome-c (Cyt-c) with a hydrogen peroxide (H2O2)-generating system comprising hypoxanthine (HX), xanthine oxidase (XO) and superoxide dismutase (SOD; HX-XO-SOD-Cyt-c system). Using this and the H2O2-Cyt-c system, we proved that monoepoxide production from linoleic acid was due to hydroxy radical formation by the reaction of Cyt-c with H2O2 and not to the formation of other active oxygen species.

pH dependent alterations of monoepoxides and monochlorohydrins of linoleic acid, and their existence in vivo.

Some monoepoxides of linoleic acid (LA) were converted to monochlorohydrins in low-pH solutions containing chloride ions (Cl-). Conversely, monochlorohydrins of LA were converted to monoepoxides in high-pH solutions. We attempted to determine whether these monochlorohydrins and monoepoxides were produced from LA by the cytochrome-c-H2O2-and/or myeloperoxidase-H2O2-system. The existence of monoepoxides and monochlorohydrins of LA in leukocytes was confirmed by high-performance liquid chromatography (HPLC). Furthermore, leukotoxin in human leukemia cells (THP-1) was stained immunohistochemically by a monoclonal anti-leukotoxin antibody.

Kupffer cells cytotoxicity against hepatoma cells is related to nitric oxide.

We have previously demonstrated that rat resting macrophages have cytotoxicity against tumor cells. In the current study we have performed an in vitro experiment to explore the mechanism of Kupffer cells-mediated cytotoxicity against hepatomas. The coculture of tumor cells with Kupffer cells (derived from rat livers) stimulated syngeneic and allogeneic Kupffer cells to produce nitric oxide. Kupffer cell-mediated cytotoxicity was paralleled to the amount of nitric oxide and was abolished by the addition of NG-monomethyl-L-arginine. The ability to stimulate Kupffer cells to produce nitric oxide resided on the membranous fragment of tumor cells.

Blood pressure, heart rate and catecholamine response during fiberoptic nasotracheal intubation under general anesthesia.

Arterial blood pressure (ABP) and heart rate were recorded at one-minute intervals during several stages of intubation in the fiberscope group and the laryngoscope group, to determine if fiberoptic nasotracheal intubation would result in fewer hemodynamic and catecholamine responses than when intubation was performed with a Macintosh laryngoscope. Blood samples were also taken to measure plasma catecholamine concentration immediately after intubation with the fiberscope. The mean ABP in the laryngoscope group was slightly greater than that of the fiberscope group for 4 min after intubation. Heart rates at 2 min and 4 min after intubation in the laryngoscope group were significantly greater than those for the fiberscope group. Even immediately after intubation, the mean plasma levels of epinephrine and norepinephrine were unchanged in the fiberscope group. Arterial oxygen saturation (Sp(O)(2)) was maintained within normal range during both of intubation procedures, although the time required for intubation was longer than in the laryngoscope group. Other cardiovascular complications were more common in the laryngoscope group than in the fiberscope group. These results suggest that fiberoptic intubation results in less severe stress than does laryngoscopic intubation. Fiberoptic intubation should therefore be used not only in patients with difficult airway, hypertension, ischemic heart disease, or cerebrovascular atherosclerosis, but also it is recommended for all patients for whom nasotracheal intubation is indicated.

A case of coronary artery spasm during oral surgery under general anesthesia.

A case of coronary artery spasm during oral surgery under general anesthesia is reported. The patient, aged 44 years, 160 cm in height, and 55 kg in weight, was scheduled for radical surgery for right maxillary sinusitis and was healthy except for the disease requiring surgery. Just before the start of the surgery, severe and persistent hypotension with tachycardia after local injection of 3% propitocaine with 0.03 IU/mL felypressin (Citanest-Octapressin) was followed by sudden ST elevations in the ECG. Immediate continuous intravenous injection of nitroglycerin was thought to be effective. The patient recovered without any sequelae.

A case of middle lobe syndrome occurring in two sisters.

We report herein a rare case of middle lobe syndrome, occurring in two sisters. Since selective aspirations of sputum under bronchoscopic guidance proved ineffective, a middle lobectomy was performed in both cases. Histological findings of the resected specimens showed overgrowth of the bronchial glands, lymphocytic infiltration around the alveoli and glandular metaplasia of the alveoli in both cases. Based on the allergic diathesis, we suggest that in these 2 sisters, middle lobe syndrome was caused by chronic inflammation.

Increase in intracellular Ca2+ level and modulation of nerve growth factor action on pheochromocytoma PC12h cells by extracellular ATP.

Extracellular ATP increased the cytosolic Ca2+ level of pheochromocytoma PC12h cells, a subclonal line of PC12. This increase in Ca2+ was predominantly due to an increased Ca2+ influx rather than to intracellular mobilization of the ion. One half of the maximal increase in Ca2+ level was observed with an ATP concentration of approximately 1 microM. ADP also induced an increase in cytosolic Ca2+ but to a lesser extent than ATP, whereas neither AMP nor adenosine showed such effect. ATP also modulated the nerve growth factor (NGF) action on these cells: ATP enhanced the NGF-induced neurite outgrowth, although ATP alone did not cause neurite development. After 3-day treatment the average neurite length of the cells treated with both NGF and ATP was about 1.5-fold greater than that of the cells treated with NGF alone. ADP also showed similar effect as ATP, while AMP did not. The ATP concentration that gave one half of the maximal enhancement of the outgrowth was estimated to be 180 microM. Enhancement of NGF-induced neurite outgrowth by ATP was also observed in serum-free cultures. The enhancing effect on NGF-induced neurite outgrowth was also specific for ATP. These results thus indicate the presence and involvement of P2-type purinergic receptors on PC12h cells in the ATP effects, and suggest a novel function of extracellular ATP as a modulator of hormonal actions.

Elevation in metallothionein messenger RNA in rat tissues after exposure to X-irradiation.

Metallothionein (MT) mRNA levels in tissues were measured in rats following whole-body X-irradiation (2 and 20 Gy). When compared with control rats, the elevation in MT mRNA levels of liver, kidney, and thymus was observed in irradiated rats at 9 or 72 hr after irradiation. However, the elevation in MT mRNA levels was not observed in brain, spleen, lung, heart, and testis. When compared with other tissues, testicular MT mRNA levels in control rats were extremely high, and treatment with X-irradiation produced a slight decrease of testicular MT mRNA levels. Time-course experiments indicated that hepatic and renal MT mRNA reached a maximum at 6 hr after irradiation. In low-dose (2 Gy) irradiated rat, these values were returned to control values by 4 days after irradiation. However, in high-dose (20 Gy) irradiated rat, the values were not decreased to control values. These data indicate that treatment with X-irradiation produces an elevation in MT mRNA in rat tissues.

[Determination of the desirable epinephrine concentration containing in dental local anesthetics. Comparison between two lidocaine solutions containing 1/80,000 and 1/200,000 epinephrine].

This study is a pilot study to determine the desirable epinephrine concentration containing in dental local anesthetics. Two percent lidocaine solution containing 1/80,000 and 1/200,000 epinephrine were compared in view points of onset and duration of anesthesia and hemodynamic responses after conduction and infiltration anesthesia in oral cavities of six voluntary dental students. Conduction anesthesia to the right inferior alveolar nerve, using 2% lidocaine solution containing 1/80,000 and 1/200,000 epinephrine showed no significant difference in onset and duration of anesthesia, changes in blood pressure and pulse rate. Duration of anesthesia determined by pin prick showed the longest in infiltration anesthesia, using 2% lidocaine solution containing 1/80,000 epinephrine, (103.4 +/- 18.5 min.), and followed by that containing 1/200,000 epinephrine (52.0 +/- 13.0 min.) and that excluding epinephrine (23.0 +/- 5.1 min.). These findings suggested that the desirable epinephrine concentration containing in dental local anesthetics may be 1/200,000, judging from the time of a dental practice.

[Arrhythmia during extraction of the third molars under intravenous sedation. A case report of postoperative tetralogy of Fallot].

Extraction of the third molars [formula: see text) was done under local anesthesia with intravenous sedation using diazepam in a 14 year-old girl. She had the history of radical operation for tetralogy of Fallot at 4 years of age. During extraction procedure, this patient showed many multifocal premature ventricular contraction in ECG. These arrhythmias were able to control with intravenous lidocaine. In this case, the preoperative evaluation of her cardiac function was not pertinent possibly due to the judgment by her ability of physical exercise in the past history. We reflect that inadequate preoperative evaluation of cardiac function may result in inadequate management.