Single-blind randomized clinical trial of transinguinal preperitoneal repair using self-expanding mesh patch vs. Lichtenstein repair for adult male patients with primary unilateral inguinal hernia.

PURPOSE: The aim of the study was to compare proportions of chronic postoperative inguinal pain (CPIP) and other surgical outcomes between transinguinal preperitoneal repair with modified Kugel patch (MK) and Lichtenstein repair (LR). METHODS: Two-hundred adult male patients with primary unilateral inguinal hernia were randomized into MK or LR groups. The primary endpoint was CPIP, pain at 6 months after surgery. Secondary outcomes included recurrence rate, incidence of postoperative complications, time until return to activities, inguinal pain and sensory disturbances assessed at 1 week, 1 month, 3, 6, and 12 months after the operation using an 11-point numerical rating scale (NRS). The study was an intention-to-treat analysis. RESULTS: In comparison of MK (n = 100) and LR (n = 100) with similar backgrounds, proportions of CPIP were similar (7.2 vs. 11.1%, p = 0.3452). Favorable outcomes for MK were duration of operation (32 vs. 40 min, p < 0.0001), NRS of foreign body sensation at 1 year (0 [0-1] vs. 0 [0-2], p = 0.0067), and NRS of numbness at 1 month (0 [0-1] vs. 0 [0-3], p = 0.0078) after the operation. CONCLUSIONS: In regard to CPIP, the short-term results of MK and LR were similar.

Modified Kugel herniorrhaphy using standardized dissection technique of the preperitoneal space: long-term operative outcome in consecutive 340 patients with inguinal hernia.

PURPOSE: The aim of this study was to evaluate the outcome, with a special reference to recurrence and postoperative chronic pain, of the modified Kugel herniorrhaphy (MKH) using standardized dissection of the preperitoneal space. PATIENTS AND METHODS: Operative results were examined based on medical records and questionnaire surveys in 340 consecutive cases of MKH performed at a single institution. The operation was performed with an original 3-stage dissection of the preperitoneal space only via the internal inguinal ring. RESULTS: The mean follow-up period was 50.5 ± 24.3 months. The mean operating time was 42.2 ± 13.1 min, and by Nyhus classification, significant difference was observed between types IIIA and IIIB (39.5 ± 10.8 vs. 45.6 ± 15.6 min, P = 0.0279). Eight surgeons performed 10 or more operations, and no significant difference was found in their operating time. Thirty-one patients used additional analgesics postoperatively (9.1 %) and the length of postoperative stay was 1.2 ± 0.7 days. Seven patients (2.1 %) developed complications related to the hernia operation, but none of them required re-operation. The period required to return to normal daily activities was 3 ± 3.2 days. Questionnaire forms were returned from 77.7 % of all the patients, in which 12 patients reported chronic pain (4.7 %). Visual analog scale for patients with chronic pain scored 3.8 ± 2.4, with no patient indicating restrictions on daily life. Recurrence was observed in only one case (0.3 %). CONCLUSION: MKH using standardized dissection of the preperitoneal space is a highly reproducible procedure with acceptable rate of postoperative chronic pain and recurrence.

Arteriovenous fistula in a nerve root of the cauda equina fed by a proximal radiculo-medullary artery: a report of two cases.

While there have been a few reports on cases of intradural spinal arteriovenous fistula located on the filum terminale, no cases of its location in a nerve root of the cauda equina have been reported to date.We describe two such cases and describe the intraoperative findings. A 40-year-old man presented weakness of his left leg. Another 62-year-old man presented paraparesis dominantly in his left leg with urinary hesitation. In both cases, spinal T2-weighted magnetic resonance images showed edema of the spinal cord, indicating a flow void around it. Digital subtraction angiography disclosed an anterior radicular artery branching from the anterior spinal artery on the surface of the conus medullaris and a turnaround vein running in the opposite direction within the cauda equina. In the first patient, while the feeding artery running along a nerve root was detected, the draining vein and the fistula were not identified at first sight. An incision into the respective nerve root exposed their location within it. In the second patient, unlike the first case, the feeding artery and the fistula were buried in a nerve root, while the draining vein was running along the nerve's surface. In both cases, permanent clips were applied to the draining vein closest to the fistula. The recognition of a hidden fistulous point in a nerve root of the cauda equina is essential for successful obliteration of the fistula.

Bleeding time prolonged by daily low-dose aspirin is shortened by one medium dose aspirin.

BACKGROUND: In planning surgery, a low-dose aspirin regimen for prevention of thrombotic events is often discontinued in order to avoid the risk of excessive bleeding during surgery. However, this procedure increases the risk from adverse thrombotic events. We propose a different method, which may normalize the prolonged bleeding time caused by low-dose aspirin. We verified the effectiveness of this method in healthy volunteers. METHODS: Volunteers with bleeding time prolonged by taking 81 mg of aspirin a day for a period of 1 week were randomly divided into two groups. The test group of 18 volunteers received a dose of 660 mg of aspirin, while the control group of 16 received placebo. Bleeding time and maximum platelet activity were then evaluated. RESULTS: Before 660 mg of aspirin or placebo, bleeding time was prolonged: in the aspirin group from 3.1 +/- 0.7 to 6.1 +/- 1.4 min (n=18), and in the placebo group from 2.9 +/- 0.9 to 6.1 +/- 1.5 min (n=16). This prolongation was significant in both groups at the P<0.01 level. In the test group, bleeding time was shortened to 4.5 +/- 1.3 min (P<0.01), which is in the normal range, while it remained prolonged in the control group (6.0 +/- 1.2 min). Platelet activity, on the other hand, was suppressed in both groups. CONCLUSION: We conclude that 660 mg of aspirin effectively shortens the bleeding time prolonged by daily low-dose (81 mg) aspirin.

Cadmium(II) complexes of (arylazo)imidazoles: synthesis, structure, photochromism, and density functional theory calculation.

Reaction between CdX2 and 1-alkyl-2-(phenylazo)imidazole (RaaiR') has isolated complexes of composition Cd(RaaiR')2X2 in MeOH or MeCN. Crystallization of Cd(RaaiR')2I2 from N,N-dimethylformamide (DMF) has separated [Cd(RaaiR')I2.DMF], while Cd(RaaiR')2X2 (X = Cl and Br) remains unchanged in its composition upon crystallization under identical conditions. The structure has been established by spectral (UV-vis and 1H NMR) data and confirmation in the latter case by a single-crystal X-ray diffraction study of [Cd(TaiMe)I2.DMF] [where TaiMe = 1-methyl-2-(p-tolylazo)imidazole]. UV-light irradiation in a MeCN solution of Cd(RaaiR')2I2 and [Cd(RaaiR')I2.DMF] shows trans-to-cis isomerization of coordinated azoimidazole. The reverse transformation, cis-to-trans, is very slow with visible light irradiation. Quantum yields (phit-->c) of trans-to-cis isomerization are calculated, and the free ligand shows higher phi values than their cadmium(II) iodo complexes. The cis-to-trans isomerization is a thermally induced process. The activation energy (Ea) of cis-to-trans isomerization is calculated by a controlled-temperature experiment. The effects of the anions (Cl-, Br-, I-, and ClO4-) and the number of coordinated azoimidazoles (RaaiR') [Cd(RaaiR') or Cd(RaaiR')2] on the rate and quantum yields of photochromism are established in this work. A slow rate of photoisomerization of [Cd(RaaiR')4](ClO4)2 compared to Cd(RaaiR')I2 or Cd(RaaiR')2X2 may be associated with the increased mass and rotor volume of the complexes. The rate of isomerization is also dependent on the nature of X and follows the sequence Cd(RaaiR')2Cl2 < Cd(RaaiR')2Br2 < Cd(RaaiR')2I2. It may be related to the size and electronegativity of halide, which reduces the effective molar association in the order of I < Br < Cl and hence the rate. Gaussian 03 calculations of representative complexes and free ligands are used to explain the difference in the rates and quantum yields of photoisomerization.

Structural studies and photochromism of mercury(II)-iodo complexes of (arylazo)imidazoles.

Neat reaction between HgI2 and 1-methyl-2-(phenylazo)imidazole (Pai-Me) under microwave irradiation has isolated a novel compound whose structure shows intercalated HgI2 in the layers of Pai-Me. They exist independently in interpenetrated arrays. In a solution phase study, the same reaction has synthesized an iodo-bridged azoimidazole-Hg(II) complex, [Hg(RaaiR')(mu-I)(I)]2 (RaaiR' = 1-alkyl-2-(arylazo)imidazole). The structures have been characterized by X-ray diffraction studies. Chloro-bridged Hg(II) complexes of azoimidazoles, [Hg(RaaiR')(mu-Cl)(Cl)]2, are also known. These complexes upon irradiation with UV light show trans-to-cis isomerization. The reverse transformation, cis-to-trans isomerization, is very slow with visible light irradiation. Quantum yields (phi t-->c) of trans-to-cis isomerization are calculated, and the free ligand shows higher phi than their Hg(II) complexes. The cis-to-trans isomerization is a thermally induced process. The activation energy (Ea) of cis-to-trans isomerization is calculated by controlled temperature reaction. The Ea's of free ligands are much higher than that of halo-bridged Hg(II)-azoimidazole complexes. Chloro-bridged Hg(II) complexes show lower Ea's than those of iodo-bridged complexes. DFT calculation has been adopted to rationalize the experimental results.

An 8-cM interstitial deletion on 4q21-q22 in DNA from an infant with hepatoblastoma overlaps with a commonly deleted region in adult liver cancers.

We performed molecular analysis of a germline interstitial deletion of chromosome 4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early-onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated with a unique congenital syndrome including HBL, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mental retardation, and seizures. However, the patient did not exhibit a megalencephaly typical of 4q21-22 deletions. His HBL was associated with an increasing serum alpha-fetoprotein level and rapid growth. To define the chromosomal deletion at the molecular level in this child, we analyzed his lymphoblasts with fluorescence in situ hybridization, using as probes a panel of BAC/PAC genomic clones containing STS markers covering the 4q12-27 region. The analysis revealed that the affected chromosome had an 8-cM deletion within 4q21-q22, flanked by markers D4S2964 and D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21-q22 that was recently defined in adult hepatocellular carcinomas.

Analyzing the eye movement of dentists during their reading of CT images.

In order to evaluate the eye movements of dentists when they were interpreting radiographs, ten normal computed tomography (CT) images and ten images with pathologic lesions were shown to eight dentists, and the pattern of their eye movement was qualitatively analyzed. Six fixation point parameters were calculated, including the time required to discriminate between normal and pathologic images (X(1)), the total fixation point count (X(2)), the total travel distance between fixation points (X(3)), the average time spent on each fixation point (X(4)), the total gaze fixation time (X(5)), and the maximum gaze fixation time spent on each image (X(6)). When the subjects were interpreting pathologic images, X(2) and X(4) were shorter; however, when they were viewing normal images, time was spent on observing multiple fixation points before the completion of the interpretive process. While pathologic images were recognized through top-down processing, there was a tendency for normal images to be recognized through bottom-up processing. The results of discriminant analysis, using a linear discriminant function, indicated that the independent variables X(2) and X(4) and the dependent variable X(5) were the only variables that contributed significantly to differentiating between normal and pathologic images. The linear discriminant function was Z = 9.0 x 10(-2) x X(2) + 3.0 x X(4) - 2.1 (discriminant score: Z < 0, pathologic image; Z > or = 0, normal image). When the mean value of each individual's gaze fixation data was substituted into the discriminant formula, the hit rate for normal and pathologic images was discriminated at 94% (15 of 16).

Bispectral analysis of the electroencephalogram does not predict responsiveness to verbal command in patients emerging from xenon anaesthesia.

The bispectral index (BIS) is derived empirically from the electroencephalogram database of patients receiving common anaesthetics, but it may not be valid for uncommon agents. Therefore, we investigated how xenon affects the BIS. Nine and 11 patients were anaesthetized with 0.8 of the minimal alveolar concentration (MAC) of isoflurane (0.92%) and xenon (56%), respectively. After the end of operation, these concentrations were decreased in decrements of 0.1 MAC (isoflurane 0.12% or xenon 7%) and each new concentration was maintained for 15 min. This was repeated until the patient first opened her eyes or squeezed the investigator's hand on command. Isoflurane and xenon at 0.8 MAC reduced the BIS to a median of 40 (range 36-53) and 36 (30-61), respectively. With decreasing concentrations of isoflurane, the BIS increased progressively and it reached a median of 96 (90-98) when the patients awoke. In contrast, four patients receiving xenon responded to verbal command while the BIS was below 50 [median 45 (range 41-49)]. The remaining seven patients in the xenon group awoke when their BIS was greater than 80 [median 96 (range 82-98)], but in four of them the BIS was no greater than 50 when the xenon concentration was only 0.1 MAC (7%) higher than that associated with awakening. We conclude that low BIS values (< 50) do not guarantee adequate hypnosis during xenon anaesthesia.

Correlations of elevated levels of hexacosanoate in erythrocyte membranes with risk factors for atherosclerosis.

We analyzed erythrocyte membrane C26:0 from 504 volunteers by high-performance liquid chromatography. The associations between the elevated levels of erythrocyte membrane C26:0 (0.20 or greater than 0.20%) and sex, obesity (body mass index> or =26.4), smoking (> or =20 cigarettes per day), present illnesses and past diseases were examined with the chi(2) test. The correlations among age and the levels of erythrocyte membrane C26:0, plasma total cholesterol, triglycerides, LDL cholesterol and HDL cholesterol were analyzed using Spearman's correlation coefficient. Moreover, the frequencies of high levels of erythrocyte membrane C26:0 were examined in male and female subjects divided into seven age groups. The elevated levels of erythrocyte membrane C26:0 were significantly more frequent in male subjects than in females, and were closely associated with obesity, smoking, and atherosclerosis-related diseases of present illnesses. The levels of erythrocyte membrane C26:0 were highly correlated with age and the levels of plasma total cholesterol, triglycerides and LDL cholesterol, and inversely with those of HDL cholesterol. The frequency of high levels of erythrocyte membrane C26:0 in male subjects was greater than that in female subjects in all of the seven age groups. Elevated levels of erythrocyte membrane C26:0 may be closely related with atherosclerosis.

Minimum alveolar concentration-awake of Xenon alone and in combination with isoflurane or sevoflurane.

BACKGROUND: The minimum alveolar concentration (MAC)-awake is a traditional index of hypnotic potency of an inhalational anesthetic. The MAC-awake of xenon, an inert gas with anesthetic properties (MAC = 71%), has not been determined. It is also unknown how xenon interacts with isoflurane or sevoflurane on the MAC-awake. METHODS: In the first part of the study, 90 female patients received xenon, nitrous oxide (N2O), isoflurane, or sevoflurane supplemented with epidural anesthesia (n = 36 for xenon and n = 18 per group for other anesthetics). In the second part, 72 additional patients received either xenon or N2O combined with the 0.5 times MAC-awake concentration of isoflurane or sevoflurane (0.2% and 0.3%, respectively, based on the results of the first part; n = 18 per group). During emergence, the concentration of an assigned anesthetic (xenon or N2O only in the second part) was decreased in 0. 1 MAC decrements every 15 min from 0.8 MAC or from 70% in the case of N2O until the patient followed the command to either open her eyes or to squeeze and release the investigator's hand. The concentration midway between the value permitting the first response to command and that just preventing it was defined as the MAC-awake. RESULTS: The MAC-awake were as follows: xenon, 32.6 +/- 6.1% (mean +/- SD) or 0.46 +/- 0.09 MAC; N2O, 63.3 +/- 7.1% (0.61 +/- 0.07 MAC); isoflurane, 0.40 +/- 0.07% (0.35 +/- 0.06 MAC); and sevoflurane, 0.59 +/- 0.10% (0.35 +/- 0.06 MAC). Addition of the 0.5 MAC-awake concentrations of isoflurane and sevoflurane reduced the MAC-awake of xenon to 0.50 +/- 0.15 and 0.51 +/- 0.16 times its MAC-awake as a sole agent, but that of N2O to the values significantly greater than 0.5 times its MAC-awake as a sole agent (0.68 +/- 0.12 and 0.66 +/- 0.14 times MAC-awake; P < 0.01, analysis of variance and Dunnett's test). CONCLUSIONS: The MAC-awake of xenon is 33% or 0.46 times its MAC. In terms of the MAC-fraction, this is smaller than that for N2O but greater than those for isoflurane and sevoflurane. Unlike N2O, xenon interacts additively with isoflurane and sevoflurane on MAC-awake.

Effect of combined leukotriene D(4) and thromboxane A(2) receptor antagonist on mediator-controlled resistance in guinea pigs.

The effects of YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesu lfonyl )propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate), a new dual antagonist for leukotriene D(4) and thromboxane A(2) receptors, on antigen-induced increases in airway resistance were investigated in mediator-controlled novel asthmatic models using actively sensitized guinea pigs. While the predominant mediator was thromboxane A(2), complete inhibition of cyclooxygenase induced mediation by cysteinyl-leukotrienes. About 1-mg/kg indomethacin induced a state where both mediators participated equally. YM158 inhibited increases in resistance whether only one or both mediators were involved. When leukotriene D(4) and thromboxane A(2) equally participated, ED(50) values for 4-oxo-8-[4-(4-phenylbutoxy)benzoylamino]-2-(tetrazol-5-yl)-4 H-1-benzo pyran hemihydrate (pranlukast; 3.9 mg/kg) and 7-(3,5,6-trimethyl-1, 4-benzoquinon-2-yl)-7-phenylheptanoic acid (seratrodast; 2.1 mg/kg) were similar to that for YM158 (8.3 mg/kg), although those effects on the corresponding mediator-induced reaction were 10 times stronger than those of YM158. Additionally, the maximum inhibition of YM158 was stronger than those of either single receptor antagonist. In conclusion, YM158 has a potentially greater efficacy in wider types of experimental asthmatic models than single receptor antagonists.

In vivo pharmacologic profile of YM158, a new dual antagonist for leukotriene D4 and thromboxane A2 receptors.

The antagonistic activity of oral YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesu lfonyl)propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate), a new dual antagonist for leukotriene (LT) D4 and thromboxane (TX) A2 receptors, was investigated. Oral YM158 caused dose-dependent inhibition of LTD4-induced increases in plasma leakage and LTD4- or U46619-induced increases in airway resistance, with ED50 values of 6.6, 8.6 and 14 mg/kg, respectively. The dose-range of YM158's inhibitions was almost the same for both LTD4 and TXA2 receptors, and repeated oral doses did not affect its efficacy. Furthermore, oral YM158 inhibited antigen-induced bronchoconstriction. Although the potency of pranlukast for LTD4 receptor antagonism (ED50 = 0.34 mg/kg) is greater than that of YM158 (ED50 = 8.6 mg/kg), the doses of both pranlukast and YM158 for significant inhibition of the antigen-evoked airway response were the same, indicating that the TXA2 receptor antagonism of YM158 plays an important role in its anti-asthmatic effects. In conclusion, YM158 promises to be a novel agent for treating bronchial asthma.

Effect of YM158, a dual lipid mediator antagonist, on immediate and late asthmatic responses, and on airway hyper-responsiveness in guinea pigs.

The effects of lipid mediator antagonists: the LTD4-receptor antagonist pranlukast, the TXA2-receptor antagonist seratrodast, and the novel dual LTD4- and TXA2-receptor antagonist YM158 (3-[(4-tert-butylthiazol-2-yl)methoxy]-5'-[3-(4-chlorobenzenesu lfonyl) propyl]-2'-(1H-tetrazol-5-ylmethoxy)benzanilide monosodium salt monohydrate) were investigated in animals exhibiting immediate asthmatic response (IAR), late asthmatic response (LAR) and airway hyper-responsiveness (AHR). Antigen-induced LAR and AfR are inhibited by orally administered pranlukast (30, 100 mg/kg) and seratrodast (3, 10 mg/kg). YM158 (30 mg/kg), orally administered before or after IAR induction, also inhibited both LAR and AHR. However, while the inhibitory effects of pranlukast and seratrodast on IAR were marginal, the effects of YM158 (3, 10, 30 mg/kg) were dose-dependent, probably due to its multiple sites of action. Additionally, orally administered YM158 (30 mg/kg) inhibited ozone-induced AHR in guinea pigs. Thus, an antagonist that inhibits several lipid mediators might exhibit greater efficacy in treating asthmatic responses than antagonists with a single site of action. Therefore, YM158 shows great promise as a drug that will be able to treat bronchial asthma and related disorders more potently than currently used single-pathway inhibitors.

Acute relapsing encephalopathy mimicking acute necrotizing encephalopathy in a 4-year-old boy.

A 4-year-old boy showed two episodes of encephalitis/encephalopathy involving disturbed consciousness, convulsion, and paresis associated with the elevated levels of protein and myelin basic protein of the cerebrospinal fluid. MRI studies of the brain revealed symmetrical lesions in the brain stem and thalami at the first episode, and additional lesions were found in the cerebellum involving both the gray and white matter in the second episode. The intensities of MRI lesions were low in T I and high in T2. These episodes were followed by an elevation of the anti-viral antibody titers, for influenza A virus during the first episode and for adenovirus during the second. In the second episode, intravenous methylprednisolone therapy resulted in rapid improvement of his neurological signs.

Effects of lipid mediator antagonists on predominant mediator-controlled asthmatic reactions in passively sensitized guinea pigs.

The role of cysteinyl leukotrienes (cys-LTs) and thromboxane A(2) (TXA(2)) in guinea pig models of aspects of bronchial asthma was investigated. In a novel antigen (BSA)-induced asthmatic model using passively sensitized guinea pigs, pretreatment with varying doses of indomethacin controlled the ratio of followed lipid mediators, LTC(4)/D(4)/E(4) and TXB(2), in lungs of challenged guinea pigs. The predominant mediator in indomethacin-untreated asthma was TXA(2), and complete inhibition of cyclooxygenase by i.v. injection of 5-mg/kg indomethacin-induced cys-LTs mainly mediated asthmatic response. Furthermore, a 1-mg/kg indomethacin dose induced an asthmatic state where both cys-LTs and TXA(2) equally participated. Either LTD(4) or TXA(2) receptor antagonists given alone inhibited the asthmatic response in conditions where the corresponding mediator plays a predominant role. The combination of LTD(4) and TXA(2) receptor antagonists exhibited significant effects irrespective of the condition used. Under conditions where both mediators equally participate, a combination of both receptor antagonists showed additive inhibition. YM158, a newly synthesized and orally active dual antagonist for LTD(4) and TXA(2) receptors, showed the same antiasthmatic effect as a combinated LTD(4) receptor antagonist and a TXA(2) receptor antagonist mixture. Therefore, broad-acting compounds such as YM158 are expected to have antiasthmatic efficacies in a broader class of asthmatic patients than single-acting drugs.