Middle-ear pressure variations during total intravenous anesthesia with propofol, fentanyl, and ketamine

Purpose As the middle-ear cavity is one of the noncompliant gas-filled cavities, an increase in middle-ear pressure (MEP) instead of volume expansion is observed with inhalation of nitrous oxide (N₂O). Changes in MEP cause many complications, such as ear pain, temporary hearing impairment, and postoperative emesis. Therefore, we investigated changes in MEP during total intravenous anesthesia (TIVA) with propofol, fentanyl, and ketamine (PFK) and inhalation of N₂O. Methods Twelve patients were anesthetized with PFK until 60 min after the induction of anesthesia, and then N₂O (60%) inhalation was started. MEP was measured by impedance audiometry (ranging from −300 daPa to +200 daPa) at 10-min intervals during PFK, and at 2-min intervals after the inhalation of N₂O. Results MEP gradually but significantly increased from the preanesthetic value of 16±8 to 34±12 (SEM) daPa 50 min after the induction of PFK. However, MEP did not exceed the normal limit. The values of MEP in all patients were more than 200 daPa within 36 min after the start of inhalation of N₂O in oxygen. Conclusion PFK had a minimal effect on MEP, whereas addition of N₂O to PFK increased MEP dramatically. Therefore, TIVA, or at least PFK, would be a better choice for patients with middle-ear or upper-airway diseases.     

Clinical studies on the measurement of urinary tissue polypeptide antigen (TPA) levels using Prolifigen TPA kit "Daiichi"-II in urothelial cancers

We have investigated the clinical significance of urinary tissue polypeptide antigen (TPA) as a tumor marker for urothelial cancers. Urinary TPA levels were determined by the immunoradiometric assay of Prolifigen TPA Kit "Daiichi"-II in 486 healthy controls and 1835 patients with various diseases including 526 with urothelial cancers and 140 with prostatic cancer. The mean value of urinary TPA was 199 +/- 213 (1SD)U/1 in 486 healthy controls. 95% of them having a level below 600 U/l. Therefore, 600 U/l was applied as a cut-off level. Positive rates of urothelial cancers and reactivated prostatic cancer were 57.6% (148 of 248 cases) and 45.5% (5 of 11 cases) respectively. On the other hand, the false positive rate of most urological benign diseases was only about 20% except for the acute stage of urinary tract infections and upper urinary tract stones with hydronephrosis. There was no significant difference in the positive rate between urinary TPA level and urinary cytology in urothelial cancers. The combination of both tests raised the positive rate to 73.1%. Therefore, urinary TPA may be useful in the monitoring of urothelial cancers, and the combination of urinary TPA and urinary cytology may increase the diagnostic accuracy.     

Correlation between vibration-induced white finger and symptoms of upper and lower extremities in vibration syndrome

Summary The correlation was investigated between the frequency of attacks of vibration-induced white finger (VWF) and numbness or coldness of the fingers and legs in patients with vibration syndrome. Some 1687 patients with vibration syndrome were examined and of these 342 chain-saw operators and 277 rock-drill operators had no disease other than vibration snydrome. Then subjects were matched by age and period of treatment within three years. In the last analysis, 20 in the VWF almost everyday group or in the never group, and 40 in the occasionally group were selected from the chain-saw operators, and from the rock-drill operators 32 in the VWF everyday or the never group and 64 in the occasionally group. The present study showed that, with the frequency of VWF attacks, patients had a higher prevalence of coldness not only in the fingers but also in the legs. These findings suggest a correlation between the severity of circulatory disturbances of the upper extremities and that of the lower ones in patients with vibration syndrome. Further studies on circulatory disturbances in the leg are required.     

Role of P-Selectin in the Migration of Neutrophils to Chemoattractant-Induced Cutaneous Inflammation in Mice

The role of P-selectin in the accumulation of neutrophils at acute dermal inflammatory sites induced by chemoattractants, LTB4 and IL-8 was investigated in the mouse. A mouse P-selectin-human IgG chimera bound to mouse neutrophils in vitro in a calcium-dependent manner, as detected by flow cytometry. A rat monoclonal antibody (mAb) against mouse P-selectin, RB40.34 abolished P-selectin-IgG chimera binding to mouse neutrophils, but a control antibody did not. Intradermal injection of LTB4 at a dose of 100 ng/site caused neutrophil accumulation to increase by 3-4 fold, as detected by measuring myeloperoxidase activity. Neutrophil extravasation to perivascular tissue was detected by histochemical observation. The intravenous injection of RB40.34 or the specific LTB4 antagonist, SM-15178, at doses at 5 mg/kg attenuated the accumulation of neutrophils by 55.6% and 70.3%, respectively, but a control antibody showed no effect. Similarly, intradermal administration of IL-8 at a dose of 5 g/site induced significant neutrophil migration into the interstitial tissue of the skin, as followed by measuring myeloperoxidase activity and histopathologic analysis. The intravenous injection of RB40.34 at a dose of 5 mg/kg reduced the neutrophil accumulation by 59.2%; in contrast, a control antibody showed no effect. To our knowledge, this is the first direct demonstration that P-selectin plays a substantial role in LTB4and IL-8-induced neutrophil accumulation in mouse skin.     

Differential effect of LFA703, pravastatin, and fluvastatin on production of IL-18 and expression of ICAM-1 and CD40 in human monocytes

A novel, proinflammatory cytokine, interleukin (IL)-18 production was detected in the medium of human monocytes treated with 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, pravastatin, and fluvastatin (0.1 and 1 muM) but not with the statin-derived lymphocyte function-associated antigen-1 (LFA-1) inhibitor LFA703, which did not inhibit HMG-CoA reductase. Pravastatin and fluvastatin also induced the production of IL-18, tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in human peripheral blood mononuclear cells (PBMC) in contrast to LFA703. IL-18 production by PBMC is located upstream of the cytokine cascade activated by these statins. The IL-18-induced cytokine production was demonstrated to be dependent on adhesion molecule expression on monocytes. In the absence and presence of lower concentrations (0.1 and 1 ng/ml) of IL-18, pravastatin and fluvastatin inhibited the expression of intercellular adhesion molecule (ICAM)-1 and induced the expression of CD40, whereas LFA703 had no effect. In the presence of higher concentrations (5, 10, and 100 ng/ml) of IL-18, pravastatin, fluvastatin, and LFA703 similarly inhibited the expression of ICAM-1 and CD40 as well as the production of IL-12, TNF-alpha, and IFN-gamma in PBMC. The effects of pravastatin and fluvastatin but not LFA703 were abolished by the addition of mevalonate, indicating the involvement of HMG-CoA reductase in the action of pravastatin and fluvastatin. Thus, the effects of LFA703 were distinct from those of pravastatin and fluvastatin in the presence of lower concentrations of IL-18. It was concluded that LFA703 has the inhibitory effect on an IL-18-initiated immune response without any activation on monocytes.     

Importance of a biofouling-resistant phospholipid polymer to create a heparinized blood-compatible surface

Heparinization is believed to be one of the methods to suppress thrombus formation on blood-contacting surfaces. However, this study hypothesizes that heparinization alone might not be sufficient to provide a blood-compatible surface; that is, a surface property that resists biofouling is necessary to obtain an effective heparin-modified surface. 2-Methacryloyloxyethyl phosphorylcholine (MPC) polymers with 2-aminoethyl methacrylate (AEMA) were synthesized to immobilize heparin through ionic bonding. The primary amino groups of AEMA were considered to be the polymer surface because the zeta-potential of the surface was positive when the mole fraction of the AEMA units was above 0.2. The antithrombogenic character of the polymer surface modified with heparin was evaluated by both Lee-White and microsphere column methods. The coagulation period of human whole blood in the absence of anticoagulant in glass tubing coated with the MPC polymer was longer than that in the original glass tube. Cell adhesion was completely inhibited on the MPC polymer surface after contact with human whole blood without anticoagulant. However, many adherent blood cells were observed on poly(2-ethylhexyl methacrylate-co-AEMA) (no MPC unit) even after heparinization. These results strongly indicate that the MPC polymer is a useful substrate where the heparin works well and that the heparin-immobilized MPC polymer has superior blood compatibility to the simple MPC polymer.     

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.     

Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes.

BACKGROUND. Disruption of an atherosclerotic plaque in a coronary artery followed by the formation of a thrombus is believed to be the cause of both unstable angina and acute myocardial infarction. Although thrombolytic therapy is efficacious in patients with acute myocardial infarction, for unknown reasons it is far less effective in patients with unstable angina. We postulated that there might be differences in the composition of the coronary-artery thrombi in unstable angina and acute myocardial infarction. METHODS. To investigate the appearance of coronary-artery thrombi, we performed percutaneous transluminal coronary angioscopy in 15 patients with unstable angina and 16 with acute myocardial infarction. Angioscopy was performed within 48 hours after an episode of pain at rest in the patients with unstable angina and within 8 hours of onset in those with acute myocardial infarction. RESULTS. Angioscopy revealed coronary thrombi in all but two patients (one in each group). Of the 29 patients with thrombi, those with unstable angina were frequently observed to have grayish-white thrombi (10 of 14, 71 percent), but none were seen in the 15 patients with acute myocardial infarction (P less than 0.01). By contrast, reddish thrombi were observed in all 15 patients with acute myocardial infarction who had thrombi, but in only 4 of the 14 patients with unstable angina and thrombi (P less than 0.01). As assessed by coronary angiography, occlusive thrombi occurred frequently in patients with acute myocardial infarction (13 of 16 patients) but were not seen in any of the 15 patients with unstable angina (P less than 0.01). CONCLUSIONS. Coronary-artery thrombi play an important part in the pathogenesis of unstable angina and acute myocardial infarction. However, the appearance of the thrombi is different in the two conditions, possibly reflecting differences in the composition of age of the thrombi or the presence or absence of blood flow in the artery. This difference may account for the contrasting results of thrombolytic therapy.