The change in zoster-associated pain treated with oral valaciclovir in immunocompetent patients with acute herpes zoster.

We have analysed zoster-associated pain treated with valaciclovir (VCV) in immunocompetent patients with acute herpes zoster over 6 months, and evaluated the safety of VCV. We know of no reports that evaluate postherpetic neuralgia (PHN) treated with VCV for 6 months. Predisposing factors that influence PHN were age (over 60 years), clustered vesicles, severity of eruption, sleep disturbance, and hypesthesia. Timing of the administration of VCV before or after the onset of rash did not influence the incidence of PHN. No serious adverse reactions were observed during the administration of VCV.

Interactions among mu- and delta-opioid receptors, especially putative delta1- and delta2-opioid receptors, promote dopamine release in the nucleus accumbens.

The effect of interactions among mu- and delta-opioid receptors, especially the putative delta(1)- and delta(2)-opioid receptors, in the nucleus accumbens on accumbal dopamine release was investigated in awake rats by in vivo brain microdialysis. In agreement with previous studies, perfusion of the nucleus accumbens with the mu-, delta(1)- and delta(2)-opioid receptor agonists [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), [D-Pen(2,5)]-enkephalin (DPDPE) and [D-Ser(2)]Leu-enkephalin-Thr(6), respectively, significantly enhanced the extracellular amount of accumbal dopamine in a dose-related manner (5.0 nmol and 50.0 nmol). However, the highest concentration tested (50.0 nmol) of DAMGO induced a biphasic effect, i.e. a rapid onset increase lasting for 75 min followed by a slower onset gradual and prolonged increase. The mu-opioid receptor antagonist D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Phe-Thr-NH(2) (0.15 nmol) primarily reduced the DAMGO-induced second component. The delta(1)-opioid receptor antagonist (E)-7-benzylidenenaltrexone (0.15 nmol) significantly reduced the first component and abolished the second component induced by DAMGO, while the delta(2)-opioid receptor antagonist naltriben (1.5 nmol) significantly reduced only the first component. The DPDPE (50.0 nmol)-induced dopamine increase was almost completely abolished by (E)-7-benzylidenenaltrexone, but only partially reduced by D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Phe-Thr-NH(2) and naltriben. The [D-Ser(2)]Leu-enkephalin-Thr(6) (50.0 nmol)-induced dopamine increase was almost completely abolished by naltriben, but not at all by D-Phe-Cys-Tyr-d-Trp-Orn-Thr-Phe-Thr-NH(2) and (E)-7-benzylidenenaltrexone. The non-selective opioid receptor antagonist naloxone (0.75 and 1.5 nmol) dose-dependently reduced the effects of DAMGO, DPDPE and [D-Ser(2)]Leu-enkephalin-Thr(6) but only to about 10-25% of the control values. Moreover, perfusion with the sodium channel blocker tetrodotoxin (0.1 nmol) reduced the DAMGO-induced dopamine increase by 75%, while it almost completely abolished the increase induced by DPDPE or [D-Ser(2)]Leu-enkephalin-Thr(6). The results show that stimulation of mu-opioid receptors or, to a lesser degree, delta(1)-opioid receptors results in a large naloxone-sensitive increase and a small naloxone-insensitive increase of extracellular dopamine. It is suggested that the naloxone-insensitive component is also tetrodotoxin-insensitive. Furthermore, it is hypothesized that stimulation of mu-opioid receptors activates delta(1)-receptors, which in turn activate delta(2)-opioid receptors, thereby giving rise to a rapid onset increase of extracellular dopamine. In addition, it is hypothesized that stimulation of another group of mu-opioid receptors activates a second group of delta(1)-opioid receptors that is not coupled to delta(2)-opioid receptors and mediates a slow onset increase of extracellular dopamine. Finally, it is suggested that stimulation of delta(1)- or delta(2)-opioid receptors inhibits mu-opioid receptors involved in the slow onset increase in extracellular dopamine, whereas stimulation of delta(1)-, but not delta(2)-, opioid receptors is suggested to activate mu-opioid receptors involved in the rapid increase in extracellular dopamine.

Clinical correlates of prolonged pain in Japanese patients with acute herpes zoster.

To determine which risk factors are relevant to the occurrence of post-herpetic neuralgia in Japanese patients with acute herpes zoster, correlations between the prolongation of pain and various disease factors were examined in 263 adult patients presenting within 10 days of the onset of rash at 17 institutions in the Hyogo region of Japan. All patients in whom pain persisted for more than 3 months were over 60 years of age. The pain also tended to be more prolonged in those with clustered vesicles, disturbed sleep and hypanaesthesia. Other factors such as underlying disease states, critically involved regions, scar tissue, generalized rash and allodynia were not relevant to the duration of pain. Although decreased pain persistence was observed in patients in whom acyclovir therapy was initiated within 72 h of the onset of symptoms in comparison with those in whom it was initiated after this time, the difference between the two groups of patients was not statistically significant. Our results suggest that advanced age, the presence of clustered vesicles, and disturbed sleep and hypanaesthesia influence the prolongation of herpes zoster pain.

[Acute exacerbations due to Streptococcus pneumoniae in chronic lower respiratory tract infections during long-term macrolide therapy].

In Japan, long-term 14-membered macrolide administration is chosen as a first line therapy against chronic lower respiratory tract infections (CLRTIs) such as diffuse panbronchiolitis, bronchiectasis and chronic bronchitis. However, sometimes acute exacerbations occur in these cases, even if therapy is effective. We investigated 18 episodes of CLRTIs exacerbations that were caused by Streptococcus pneumoniae during long-term macrolides therapy from 1991 to 1999 to clarify the clinical features and prevalence of antimicrobial resistance in S. pneumoniae. Exacerbations did not occur only in winter season, but also in other seasons. Among 18 episodes of exacerbation, only 7 episodes (39%) revealed infiltration in chest roentogenogram and few episodes revealed marked elevations of inflammation markers in laboratory data. Intermediate resistance or resistance rates of S. pneumoniae isolated from sputum or transtracheal aspiration were 100% to erythromycin, 67% to clindamycin or minocycline, 11% to ampicillin, and 0% to cephazoline or imipenem. Coresistance to erythromycin, clindamycin and minocycline was seen in a half of the episodes. Resistance was not correlated with the duration of macrolides administration. All episodes were mainly treated with beta-lactam agents or fluoroquinolones and cured successfully. These findings suggest that acute exacerbations in CLRTIs caused by S. pneumoniae during long-term macrolides therapy do not reveal severe clinical aspects and can be treated successfully at present, but attention should be paid to the trend of antibiotic susceptibility in S. pneumoniae.

[Low dose intrathecal morphine and postoperative pain relief in elderly patients].

Patient (ASA PS I-III, mean age 68 +/- 14 yr) who had undergone lower extremity surgery under spinal anesthesia were studied to determine the effect of intrathecal administration of morphine 0.1 mg on intra- and postoperative pain relief and its side effects. They were randomly divided into control (C) and intrathecal morphine (M) groups (n = 25, respectively) and received 10 mg tetracaine in 4 ml of a quarter saline with 7.5 micrograms epinephrine. Incidence of intraoperative tourniquet pain was significantly lower in M group (36.8%) than in C group (64.3%). Postoperative pain was examined in terms of the duration until the first supplemental analgesic within 24 hr. The mean duration was 7.0 +/- 4.3 hr in the control group, but 11 patients in the M group needed it within 24 hr (18.1 +/- 6.8 hr, excluding 6 patients who did not receive analgesic). Although incidences of postoperative nausea, vomiting, and itching were higher in M group than in C group, none required antiemetic or naloxone. Both groups showed no difference in postoperative respiratory depression measured by apnea monitor (Eden Trace II, Mallinkrodt Japan, Tokyo). The results suggest that a low dose of intrathecal morphine is effective on postoperative 24 hr pain relief in elderly patients and that its side effects are negligible.

A novel missense mutation in human lactate dehydrogenase B-subunit gene.

Reduced activity of serum lactate dehydrogenase (LDH; EC 1.1.1.27) was found in a male medical student during practical examinations of his own blood. Serum LDH isoenzyme pattern showed reductions in activities of the isoenzymes with lower subunit A/B ratios such as LDH1 and LDH2. These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting. Polymerase chain reaction (PCR)-based DNA sequence analysis of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B subunit gene that resulted in a glycine to glutamic acid substitution (G69E). The mutation was confirmed by PCR-restriction fragment length polymorphism (RFLP) analysis using a mismatched primer to introduce a new NcoI restriction site. The same heterozygous mutation was found in his mother but not in other family members. This mutation involves a residue belonging to alphaC helix in LDH-B subunit protein molecule that functions as an interface for other subunits.

[Pathogenetic study on bronchopulmonary infections in 1,416 patients by transtracheal aspiration method].

We have performed transtracheal aspiration (TTA) in 1,416 patients, who were suspected to have bronchopulmonary infection, in order to collect non-contaminated specimens directly from the lower airway. The overall isolation rates in 1,416 TTA were 68.7% for any microorganisms. Aerobes had a high incidence but many kinds of microorganisms were associated with bronchopulmonary infections. Haemophilus influenzae was the major pathogen in patients with acute bronchitis. Streptococcus pneumoniae was the most important pathogen and mycoplasma was often isolated in patients with community-acquired pneumonia. Major pathogens of nosocomial pneumonia consisted of alpha-streptococcus spp., anaerobes and Pseudomonas aeruginosa. Anaerobes were isolated from transtracheal aspirates in 20 of 33 episodes of lung abscesses. H. influenzae and P. aeruginosa were the main persistent pathogens and H. influenzae, S. pneumoniae and anaerobes were important exacerbated pathogens in patients with chronic lower respiratory tract infection. S. pneumoniae was isolated more from TTA than expectorated sputa. Oropharyngeal flora bacteria were easily isolated in the culture of expectorated sputa. We assessed the final diagnosis or causative factor in 443 patients whom no microorganism was isolated from transtracheal aspirates. The final diagnosis was infectious diseases in 52 patients (11.7%) and non-infectious diseases in 80 patients (18.1%), respectively. The causative factor was unsuited TTA sample in 81 patients (18.3%), preceding antimicrobial chemotherapy in 95 patients (21.4%) and unknown in 135 patients (30.5%), respectively. The pathogenesis of bronchopulmonary infections is complex and various microorganisms are associated with pathogens of bronchopulmonary infections. Therefore, we should accurately diagnose the pathogens in patients with bronchopulmonary infections. TTA is one of the useful methods that we can accurately detect the respiratory pathogens.

Effects of protein binding on the placental transfer of propofol in the human dually perfused cotyledon in vitro.

The placental transfer of propofol was investigated using the in vitro dually perfused cotyledon model of the human placenta, and the effects of protein binding in the foetal perfusate were examined. Both maternal and foetal circulations were perfused in a single-pass mode and > 30 min of stabilization was allowed before adding propofol and antipyrine to the maternal perfusate. The placental clearances of propofol were significantly increased by the augmented albumin concentrations in the foetal perfusate (1.68 (SD 0.68), 3.08 (1.55), 4.79 (1.76), 5.75 (1.89) and 7.03 (1.46) ml h-1 g-1 at the albumin concentrations of 4.4, 11, 22, 33 and 44 g litre-1, respectively). Although the total propofol concentration in the foetal vein increased significantly with increasing albumin concentration, the concentration of free propofol remained unchanged. These results indicate that binding to foetal albumin is a determining feature in the control of the placental transfer of propofol, and that the pharmacological effects of propofol on the foetus can be expected to be fairly constant and predictable from the maternal propofol concentration.

Increased expression of cyclooxygenase-2 protein in rat lung tumors induced by N-nitrosobis(2-hydroxypropyl)amine.

Expression of cyclooxygenase (COX)-2 protein in preneoplastic and neoplastic lung lesions induced by the administration of 2000 ppm of N-nitrosobis(2-hydroxypropyl)amine (BHP) in the drinking water to Wistar male rats, was examined immunohistochemically. The majority of alveolar/bronchiolar adenomas (ADs) and all adenocarcinomas (ADCs) examined, stained positive or strongly positive for COX-2. In contrast, only a minority of alveolar/bronchiolar hyperplasias demonstrated immunoreactivity and half of the squamous cell carcinomas examined, were only weakly positive. Western blotting analysis also revealed expression of COX-2 protein in the resected ADs and ADCs. These results clearly indicate up-regulated expression of COX-2 in lung neoplastic lesions, particularly ADs and ADCs, induced by BHP in rats.

Inhibitory effects of combined administration of antibiotics and anti-inflammatory drugs on lung tumor development initiated by N-nitrosobis(2-hydroxypropyl)amine in rats.

The effects of antibiotics and anti-inflammatory drugs on the promotion stage of lung carcinogenesis initiated with N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats were investigated in two experiments with a similar protocol. In experiment 1, rats received tap water containing 2000 p.p.m. BHP for 12 weeks followed by basal diet or basal diet containing 0.02% erythromycin (EM), 0. 04% ampicillin (ABPC), 1.5% sho-saiko-to, 0.02% EM plus 1.5% sho-saiko-to or 0.04% ABPC plus 1.5% sho-saiko-to for 8 weeks after BHP administration. The development of adenocarcinomas (AC), squamous cell carcinomas (SqC) and adenosquamous carcinomas (ASqC) was completely inhibited in rats given ABPC plus sho-saiko-to and the numbers of lung lesions including alveolar hyperplasias, adenomas and carcinomas were decreased in rats given EM plus sho-saiko-to or ABPC plus sho-saiko-to. Neutrophil and macrophage infiltration into alveolar spaces of the lung were also markedly suppressed. In experiment 2, rats received BHP in the same manner as in experiment 1 and basal diet or basal diet containing 0.04% ABPC, 0.006% piroxicam, 0.04% ABPC plus 0.006% piroxicam and 0.04% ABPC plus 0.75% ougon for 8 weeks. The incidence and number of carcinomas, including ACs, SqCs and ASqCs were decreased in rats given ABPC plus piroxicam or ABPC plus ougon. Bacteria, mainly Escherichia coli, were detected in broncho-alveolar lavage of rats receiving BHP. The results suggest that chronic inflammation might be involved in the progression of lung carcinogenesis by BHP in rats and its suppression may therefore be useful as a chemopreventive strategy in lung cancer clinics.

[Enterococcus gallinarum septicemia in a patient with acute myeloid leukemia].

A 62-year-old male was admitted with complaints of fever and body weight loss. The patient was diagnosed as acute myeloid leukemia (M1) and chemotherapy was started. About 80 days after admission, the patient developed diarrhea with high fever. And E. gallinarum was isolated from the blood culture. We carried out PCR using primers for vanA, vanB and vanC in our E. gallinarum, and showed the existence of the vanC1. This organism should be considered as one of the possible pathogenes in the infectious complications of the immuno-compromized patient.

A case of pseudosarcoma associated with type 3 squamous cell carcinoma of the esophagus: report of a case.

A case of a primary esophageal pseudosarcoma associated with an independent type 3 tumor is described herein. A 60-year-old male presented with dysphagia and chest discomfort. A clinical evaluation revealed a type 3 tumor in the middle of the esophagus, which was diagnosed after a biopsy to be squamous cell carcinoma (SCC). A subsequent gross examination of the subtotally removed esophagus revealed a polypoid tumor adjacent to the type 3 tumor. Histologically, the polypoid mass was composed of SCC and mesenchymal components without a transitional zone. The tumor was thus classified as a pseudosarcoma of the esophagus, and was unique in that this appeared to have developed independently from the SCC.

[Clinical evaluation of anaerobic infections in patients with bronchopulmonary infections diagnosed by transtracheal aspiration].

We evaluated the clinical and bacteriologic features in the patients with bronchopulmonary infections isolated anaerobes from transtracheal aspirates between April 1990 and March 1998. Some anaerobe was isolated in 42 (10.9%) in 387 patients whom we performed transtracheal aspiration (TTA), in 42 (15.7%) of 268 in whom some organism was isolated from TTA, or in 42 (16.3%) of 257 patients in whom some bacterium excluding acid-fast bacteria, fungi or mycoplasma from TTA. The isolation rate of anaerobic bacteria was 93.3% in the patients with lung abscess, 22.7% in the patients with nosocomial pneumonia, 19.4% in the patients with community-acquired pneumonia, 26.7% in the patients with acute exacerbation of chronic lower respiratory tract infection (CLRTI), 1.6% in the patients with persistent infection of CLRTI, and 3.0% in the patients with acute bronchitis, respectively. The major anaerobes, isolated from TTA, were Peptostreptococcus micros and Prevotella melaninogenica. The aerobic bacteria were isolated with anaerobic bacteria in 32 of 42 patients at the same time. The quantitive grade of colonial growth of anaerobes was equal to or more than aerobes in the patients with lung abscess and pneumonia. We mostly administrated 3rd generation cephems or carbapenems with or without clindamycin for the treatment of anaerobic infections. Forty-one of 42 patients were cured only by the therapy of antimicrobial agents, but pneumonia patient with lung cancer died in spite of adequate antimicrobial therapy. These results suggest that the anaerobic infections are important in the bronchopulmonary infections.

[Usefulness of power Doppler sonography for the assessment of subpleural lesions].

We investigated the usefulness of color Doppler power mode imaging for the assessment of subpleural lesions in 48 patients (27 with pneumonia, 4 with pulmonary abscesses, 12 with primary lung cancer, and 5 with metastatic lung cancer). We classified the patterns obtained by color flow imaging of subpleural lesions into six groups: type 0, no color flow; type I, spotty color flow; type II, linear color flow; type III, branchy color flow; and type IV, tortuous color flow, with type IV-A, for partial tortuous flow and type IV-B, for general tortuous flow. The color Doppler power mode proved better than velocity mode in terms of ability to generate clear color flow patterns. Color flow patterns obtained in power mode on the patients with pneumonia differed significantly from the patterns obtained on the lung cancer patients. Although the color flow patterns observed in power mode differed significantly for the benign and malignant groups, no statistically significant differences were observed in velocity mode. These findings illustrated the usefulness of color Doppler power mode imaging as a means of diagnosing benign and malignant subpleural lesions.

Improved oxygen delivery to the fetus during cesarean section under sevoflurane anesthesia with 100% oxygen.

PURPOSE: To assess the potential benefits of sevoflurane with 100% oxygen in cesarean section in terms of oxygen delivery to the fetus, neonatal depression, and uterine contractility. METHODS: Thirty-six patients undergoing elective cesarean section were enrolled. After thiamylal induction, 0.7% sevoflurane-60% nitrous oxide-40% oxygen anesthesia was administered in group G1 (n = 9), and 1.7% sevoflurane-100% oxygen anesthesia was administered in group G2 (n = 9). Spinal anesthesia under oxygen nasal prong was used in group SP (n = 18). RESULTS: At delivery, the PO(2) values in the maternal artery and the umbilical vein and artery (MA, UV, UA) of group G2 (474 +/- 50, 43 +/- 9, 32 +/- 9 mmHg, respectively) were significantly greater than those in groups G1 (228 +/- 46, 31 +/- 4, 23 +/- 5 mmHg, respectively) and SP (147 +/- 21, 30 +/- 7, 18 +/- 7 mmHg, respectively). The SO(2) in the UA of group G2 (56 +/- 17 %) was also greater than that in groups G1 (34 +/- 10 %) and SP (32 +/- 10 %). The sevoflurane concentrations at delivery in the MA, UV, and UA in group G2 were almost threefold higher than those in group G1, whereas all the newborns in the three groups had Apgar scores of 8 or more at 5 min, and the intraoperative blood loss did not differ among the groups. CONCLUSION: Sevoflurane anesthesia with 100% oxygen in elective cesarean delivery improves oxygen delivery to the fetus without severe neonatal depression, prolonged uterine relaxation, or increased blood loss.

[Perioperative managements of the patients with cancer-pain receiving morphine].

In the patients receiving morphine preoperatively, it is preoperatively important to avoid withdrawal symptoms postoperatively and to suppress postoperative pain and to maintain an appropriate anesthetic depth during the operation. We experienced six patients who had been under preoperative pain control with oral and/or epidural morphine and undergone palliative operation for their cancer pain. Four of the patients were preoperatively administered with oral morphine ranging from 30 to 270 mg.day-1. One patient was given epidural morphine 10 mg.day-1. Another was with morphine 1800 mg.day-1 orally and 50 mg.day-1 epiduraly. In all cases, general anesthesia was maintained with inhalation anesthetics. Anesthetic supplementation and postoperative pain management were performed with continuous i.v. infusion of morphine (half dosage of daily oral dosage), or subcutaneous injection (one sixth dosage of daily oral morphine) while preoperative epidural morphine was continued throughout the perioperative period. We were able to manage these patients well and none of them developed withdrawal symptom or increased postoperative pain.