Static properties of the passive pharynx in sleep apnea.

Complete paralysis under general anesthesia allowed separating anatomic factors from neural factors which influence pharyngeal patency. We compared static mechanical properties of the passive pharynx in normals and sleep apneics. The passive pharynx was narrower and more collapsible in sleep apneics than normal controls indicating significance of anatomic factors in the pathogenesis of obstructive sleep apnea.

Advancement of the mandible improves velopharyngeal airway patency.

The velopharynx is the most common site of obstruction in patients with obstructive sleep apnea (OSA). Advancement of the mandible effectively reverses the pharyngeal obstruction. Accordingly, we hypothesized that mandibular advancement increases cross-sectional area of several segments of the upper airway, including the velopharynx and the oropharynx. We examined the pressure-area properties of the pharyngeal airway in 13 patients with OSA. Under general anesthesia and total muscle paralysis, the pharynx was visualized with an endoscope connected to a video-recording system. During an experimentally induced apnea, we manipulated the nasal pressure from 20 cmH2O to the point of total closure at the velopharynx. The procedure was repeated after maximal forward displacement of the mandible. Measurements of the cross-sectional area at different levels of nasal pressure allowed construction of a static pressure-area relationship of the "passive pharynx," where active neuromuscular factors are suppressed. In 12 of 13 patients with OSA, advancement of the mandible stabilized the airway by reducing the closing pressure and increasing the area at any airway pressure. Thus the maneuver shifted the static pressure-area curve of the velopharynx and the oropharynx upward in these patients. We conclude that anterior movement of the mandible widens the retropalatal airway as well as that at the base of the tongue in the passive pharynx of OSA patients.

Anatomy of pharynx in patients with obstructive sleep apnea and in normal subjects.

Anatomic abnormalities of the pharynx are thought to play a role in the pathogenesis of obstructive sleep apnea (OSA), but their contribution has never been conclusively proven. The present study tested this anatomic hypothesis by comparing the mechanics of the paralyzed pharynx in OSA patients and in normal subjects. According to evaluation of sleep-disordered breathing (SDB) by nocturnal oximetry, subjects were divided into three groups: normal group (n = 17), SDB-1 (n = 18), and SDB-2 (n = 22). The static pressure-area relationship of the passive pharynx was quantified under general anesthesia with complete paralysis. Age and body mass index were matched among the three groups. The site of the primary closure was the velopharynx in 49 subjects and the oropharynx in only 8 subjects. Distribution of the location of the primary closure did not differ among the groups. Closing pressure (PC) of the velopharynx for SDB-1 and SDB-2 groups (0.90 +/- 1.34 and 2.78 +/- 2.78 cmH2O, respectively) was significantly higher than that for the normal group (-3.77 +/- 3.44 cmH2O; P < 0.01). Maximal velopharyngeal area for the normal group (2.10 +/- 0.85 cm2) was significantly greater than for SDB-1 and SDB-2 groups (1.15 +/- 0.46 and 1.06 +/- 0.75 cm2, respectively). The shape of the pressure-area curve for the velopharynx differed between normal subjects and patients with SDB, being steeper in slope near Pc in patients with SDB. Multivariate analysis of mechanical parameters and oxygen desaturation index (ODI) revealed that velopharyngeal Pc was the only variable highly correlated with ODI. Velopharyngeal Pc was associated with oropharyngeal Pc, suggesting mechanical interdependence of these segments. We conclude that the passive pharynx is more narrow and collapsible in sleep-apneic patients than in matched controls and that velopharyngeal Pc is the principal correlate of the frequency of nocturnal desaturations.

Hepatitis C virus RNA and anti-N14 antibody levels during interferon alpha therapy for chronic hepatitis C.

To investigate the markers useful for evaluating the long-term efficacy of interferon (IFN) therapy, the quantity of hepatitis C virus (HCV) RNA and two anti-HCV antibody titers (anti-N14 and anti-C-100-3 antibody) in 21 chronic hepatitis C patients were determined. In all complete responders, a sustained clearance of the virus and reductions in the anti-HCV antibody titers were observed during and after therapy. In most of the temporary responders, reductions in the HCV RNA levels and in both anti-HCV antibody titers were observed temporarily during the therapy, and relapse followed. In nonresponders, although the HCV RNA levels and anti-N14 antibody titer tended to remain unchanged or increased during and after therapy, the anti-C-100-3 antibody titers showed no tendency. These results demonstrate that the monitoring of the HCV RNA level and anti-N14 antibody titer is clinically useful for following the patient's response to IFN therapy for chronic hepatitis C.

[A case of tracheobronchopathia osteoplastica discovered incidentally by hypoxemia following the operation].

An 85-year-old woman was found to have tracheobronchopathia osteoplastica incidentally following an operation for left breast cancer. She entered the ICU because of impaired sputum expectoration and hypoxemia. For the purpose of bronchial toilet, bronchofiberscopy was performed under general anesthesia. Numerous nodular elevated lesions were found on all sides of trachea and lobar bronchi except at the membranous part. Transbronchial forceps biopsy showed squamous metaplasia of the mucosa and formation of lamellar bone in the submucosal tissue. The diagnosis was finally confirmed as tracheobronchopathia osteoplastica from these two findings. Although anesthesiologists rarely encounter this disease in their daily practice, it is necessary to keep tracheobronchopathia osteoplastica in their mind as an airway disease.

[Morphological study of carcinoma of the gallbladder: its differences between calculous and acalculous carcinoma].

The most characteristic phenomenon in patients with carcinoma of the gallbladder is frequent coexistence of gallstones. In this study, morphological differences of carcinoma of the gallbladder in between calculous and acalculous cases is investigated. This study involved fifty-three cases (eleven early carcinoma and forty-two advanced) that had been surgically treated at the Hamamatsu Medical Center Hospital during the past ten years. Nine of 11 early carcinomas were calculous and two, acalculous. All calculous carcinomas showed grossly superficial type and two acalculous, polypoid type. All of them were histologically differentiated adenocarcinoma. In advanced carcinoma, thirty-one of 42 cases were calculous and eleven, acalculous. Fifteen of 31 calculous cases showed polypoid type and sixteen, diffuse infiltrative type. In all cases with the latter type, the cystic duct was completely obstructed by impacted gallstones. All calculous carcinomas were histologically belonged to differentiated adenocarcinoma, mucinous carcinoma or adenosquamous carcinoma. On the other hand, six of 11 acalculous carcinomas revealed grossly polypoid type, and histologically differentiated adenocarcinoma or mucinous carcinoma. The remaining five were of diffuse infiltrative type, and of poorly-differentiated adenocarcinoma or signet-ring cell carcinoma. From these data, it may be highly suggestive that differentiated adenocarcinoma or adenosquamous carcinoma of histologic type irrespective of it's gross type is characteristic of calculous carcinoma, and poorly-differentiated adenocarcinoma or signet-ring cell carcinoma possessing primary diffuse infiltrative growth, of acalculous. The majority of the superficial type in early carcinoma and the diffuse infiltrative type in advanced are considered as a secondary modified gross appearance by direct or indirect effects of coexistent gallstones onto the main tumor.

Carcinoma with lymphoid stroma of the gallbladder--a case report.

A case of carcinoma with lymphoid stroma of the gallbladder is presented. Carcinoma of this type in the breast or the stomach is specified under the designation of carcinoma with lymphoid stroma or infiltration because of a relatively favorable prognosis. The characteristic morphological features are described and the significance of prognostic favorability is discussed together a short review of the literature. This seems to be the first documentation of such a case.

Quantitation of anti-hepatitic C virus antibodies in interferon-treated patients by S29-1/S4 ELISA.

In 23 patients with chronic hepatitis C who have undergone interferon (IFN) treatment, quantitation of anti-hepatitis C virus IgG antibodies by a second-generation assay S29-1/S4 ELISA [Sato et al. (1993): Microbiology and Immunology 37: 295-304]. (anti-S29-1/S4) was compared with that of anti-HCV core IgG antibodies (C22-3, anticore) and the presence of viral RNA confirmed by the reverse transcription-nested polymerase chain reaction (RT-nested PCR). In 12 complete responders with loss of HCV-RNA and normal alanine aminotransferase (ALT) levels at 6 months after therapy, IgG antibodies quantified by a second-generation assay have decreased significantly at the end of treatment (P < 0.05). Further significant reduction of anti-S29-1/S4 titers was observed at 6 months after therapy (P < 0.01) as well as anti-core antibodies (P < 0.01). On the other hand, in 11 non-responders with persistent or intermittent viremia at 6 months after therapy, no significant change in the level of anti-S29-1/S4 titers was observed, whereas anti-core titers have decreased at the end of therapy (P < 0.01). In contrast, both levels of anti-S29-1/S4 and anti-core have increased at 6 months after treatment (P < 0.05). It is concluded that, although it appears difficult to monitor the effect of virus clearance during IFN therapy, changes in anti-S29-1/S4 titers after IFN treatment correlate with virus clearance and with anti-core titers.

Pharyngeal patency in response to advancement of the mandible in obese anesthetized persons.

BACKGROUND: During anesthesia in humans, anterior displacement of the mandible is often helpful to relieve airway obstruction. However, it appears to be less useful in obese patients. The authors tested the possibility that obesity limits the effectiveness of the maneuver. METHODS: Total muscle paralysis was induced under general anesthesia in a group of obese persons (n = 9; body mass index, 32 +/- 3 kg[-2]) and in a group of nonobese persons (n = 9; body mas index, 21 +/- 2 kg[-2]). Nocturnal oximetry confirmed that none of them had sleep-disordered breathing. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. A static pressure-area plot allowed assessment of the mechanical properties of the pharynx. The influence of mandibular advancement on airway patency was assessed by comparing the static pressure-area relation with and without the maneuver in obese and nonobese persons. RESULTS: Mandibular advancement increased the retroglossal area at a given pharyngeal pressure, and mandibular advancement increased the retropalatal area in nonobese but not in obese persons at a given pharyngeal pressure. CONCLUSION: Mandibular advancement did not improve the retropalatal airway in obese persons.

Immune responses of blood donors to peptides of various lengths and those with genotypic sequence variations corresponding to the N-terminal portion of the core protein of hepatitis C virus.

Immune reactivities of blood donor sera with the peptides of various lengths (24, 30, 40 and 50 mer) and those with genotypic sequence variations in the N-terminal portion of the core protein of hepatitis C virus (HCV) were compared by enzyme-linked immunosorbent assays. It was found that a 40-mer oligopeptide (amino acids 2-41) was recognized more frequently than other peptides even in serum samples that did not react with the C22-3 (core) by the recombinant immunoblot assay (RIBA-II). On the other hand, a 30-mer peptide (amino acids 1-30) had good correlation with viremia as confirmed by the polymerase chain reaction (PCR). In addition, four individuals showed the obvious differences in the immune responses to 30-mer oligopeptides representing the 4 genotypic variations. As a result, some samples that were PCR-positive but nonreactive by a commercial assay were found to react with short synthetic peptides in the N-terminal portion of the core protein.

A sensitive serodiagnosis of hepatitis C virus (HCV) infection with two non-fused peptides: comparison of antibody responses detected with a newly developed assay and a commercial second-generation test.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of anti-HCV antibody. We assayed for antibodies against either oligopeptide (S29-1) deduced from the nucleocapsid gene or the product of nonstructural region (NS3) synthesized in a recombinant Escherichia coli (S4). To reduce false-positive results induced by non-specific binding of antibodies with a carrier protein and to increase the sensitivity of an immunoassay, non-fused S4 peptide was prepared by the recombinant DNA technique and site-specific proteolysis (by factor Xa). In 71 non-A, non-B hepatitis patients with chronic liver disease, 70 (98.5%) were positive by S29-1/S4 ELISA as well as by a second-generation test (Abbott II). On the other hand, of 40 serum samples from blood donors, in which anti-N14 (core) and C100-3 antibodies were not detected but hepatitis C virus (HCV) RNA was detectable by polymerase chain reaction (PCR), 24 (60%) were positive by S29-1/S4 ELISA, whereas only 18 (45%) were diagnosed by Abbott II. In addition, based on results in a small group of 92 blood donors, detection of anti-S29-1/S4 antibody correlated well with HCV viremia as confirmed by PCR. These results indicated that the preparation of nonfused protein (S4) by recombinant DNA technique and a combination of S29-1 and S4 as immobilized antigens in an ELISA provide a sensitive and specific diagnosis for HCV infection with good correlation with the presence of viral RNA as confirmed by PCR.

Preoperative nocturnal desaturations as a risk factor for late postoperative nocturnal desaturations.

Severe postoperative hypoxaemia during sleep may increase the risk of postoperative cardiovascular complications. We hypothesized that the severity of hypoxic episodes after surgery are related to the presence of preoperative sleep-disordered breathing (SDB). We tested this hypothesis in a multicentre study designed to elucidate the major risk factors for development of postoperative nocturnal desaturations. We performed overnight oximetry before operation and for one night between the second and fourth day after operation in 80 patients undergoing major surgery. We calculated oximetry variables such as oxygen desaturation index (ODI), defined as the number of oxygen desaturations exceeding 4% below baseline, percentage time spent at SpO2 < 90% (CT90, %) and lowest SpO2 value. After operation, although the change in ODI was not significant (P = 0.34), deterioration in CT90 and lowest SpO2 values were significant (P = 0.036 and P = 0.007, respectively). Multivariate analysis of possible risk factors for postoperative desaturations revealed that preoperative hypoxaemia and apnoea witnessed by others were highly correlated with postoperative hypoxaemia.

Effects of urinary metabolites of etodolac on diagnostic tests of bilirubin in urine.

Etodolac (CAS 41340-25-4) is a non-steroidal anti-inflammatory drug used clinically. The bilirubin levels in urine samples from patients treated with etodolac were determined with diagnostic tests (diazo and oxidized methods). The urine samples gave a positive reaction with a diazo method, but not with an oxidized method. The serum concentrations of bilirubin in the patients were also in the normal range. These results indicate that the positive reaction of the urine samples from patients treated with etodolac is false and caused by urinary metabolites of etodolac. To identify the false positive substance in the urine samples, the urinary metabolites of etodolac were extracted with ethyl acetate. The extract was injected into a high performance liquid chromatography (HPLC) column and the eluate was mixed with the diazo reagent. Three positive fractions were found. The retention times of the two metabolites in HPLC matched with those of the 6- and 7-hydroxylated metabolites of etodolac. In addition, authentic compounds of the 6- and 7-hydroxylated metabolites gave a positive reaction in the diazo methods. These results indicate that the 6- and 7-hydroxylated metabolites are mainly responsible for the false positive reactions of the urine sample from patients treated with etodolac.