Randomized clinical trial comparing lightweight or heavyweight mesh for mesh plug repair of primary inguinal hernia.

BACKGROUND: The aim of this study was to assess whether the application of a lightweight mesh for mesh plug repair (MPR) for primary inguinal hernia could reduce chronic pain or other symptoms associated with the insertion of the prosthesis. METHODS: Patients over 20 years of age with a unilateral primary inguinal hernia were eligible to participate in the study. The patients were randomly assigned to a lightweight mesh (LWM) or a heavyweight mesh (HWM) group. All the operations were performed under local anesthesia. The operative details, including the hernia type and the nerves that were identified, and the postoperative complications were recorded. All follow-up and outcome measures were obtained based on a physical examination and a questionnaire regarding pain and other symptoms at 1 week, 1, 3, 6, and 12 months after the surgery in a double-blinded manner. RESULTS: The use of LWM significantly reduced foreign body sensation after 12 months to one-third of the incidence reported for the use of HWM (5.8 vs. 17.9%; P = 0.013), while no significant differences were found in pain parameters, including the use of pain relief medications, between the groups throughout the study period. CONCLUSION: This study indicated that the use of LWM in the MPR decreases the incidence of foreign body sensation at 1 year after surgery for primary inguinal hernia. LWM may be preferable to MPR, similar to results described previously for Lichtenstein repair.

[Is delayed surgical repair admitted for the thrombosed aortic dissection?].

The initial treatment for the thrombosed aortic dissection is still controversial. Accordingly, we sought to evaluate the strategy of its surgical repair. Ninety-six (35 type A and 61 type B) acute thrombosed aortic dissection were studied retrospectively. Initially all of them were treated medically. The ratio of the false and the true lumen (F/T ratio) was calculated on the onset. The uncontrollable cardiac tamponade, recanalization, large ulcer-like projection (ULP) and enlargement of the dissected aorta had a delayed surgical repair during the follow-up period. Eighteen of the type A and 14 of the type B were surgically treated and showed good result. The 1- and 5-year survival rates and the event-free survival rates for the type A and the type B were almost equal with no statistical difference. The mean F/T ratio for the type A was 31% for the operative and 51% of the nonoperative cases (p = 0.007). The maximum size of the initial aorta of the operative cases was larger than that in the nonoperative for the type B. The conservative therapy for the thrombosed aortic dissection decreased the number of the unnecessary operation and the strategy of the delayed surgical repair was justified properly.

[Atrial fibrillation after isolated coronary bypass surgery].

Postoperative atrial fibrillation (Af) remains a significant source of morbidity after coronary artery bypass grafting (CABG). Prophylactic therapy with beta-adrenergic blockers or amiodarone hydrochloride is reported to reduce the incidence of Af. We studied the incidence of Af retrospectively and considered the risk factors for it. Ninety-three patients who underwent isolated CABG from April 2003 to March 2004 are included in this study. Postoperative Af was observed in 22 (25%) patients. Ten of them were operated on off-pump procedure, and 14 had any type of beta-adrenergic blockers preoperatively. The mean age of the group of postoperative Af is 69.7 +/- 9.2 years old (older than the non-Af group: 65.5 +/- 10 years old, p = 0.087). And the preoperative left atrial size was larger in the Af group than in the non-Af group (43.4 +/- 6.1 versus 40.6 +/- 5.4mm, p = 0.064) Major embolic complication occurred in only 1 (1.1%) patient of non-Af group. We observed postoperative Af in 25% of patients after CABG. Older age and larger left atrial size may relate to the incidence of Af, and appropriate anticoagulant therapy and medication of beta-blockers are important for the patients who have such risk factors.

[Early and long-term outcome for surgical treatment of aortic arch aneurysm].

This study was undertaken to determine the factors that influence the final outcome after the operation of aortic arch aneurysm. Sixty-six patients, the median age was 72 years (range 44 to 90), were operated at our hospital during the 16-year period between 1985 and 2001. Preoperative complications included cardiac in 6 and vascular in 21, ruptured in 13, myocardial ischemia in 21 and stroke in 14. The distal hemiarch (11) and total arch replacement with or without ascending aorta and descending aorta (46) and proximal hemiarch with or without valve operations (7) and other procedures were performed mainly using cardio-pulmonary bypass with moderate deep hypothermia and selective cerebral perfusion. The in-hospital mortality were 6 (9%) and 14 (23%) late deaths occurred. One out of 14 was aneurysm related death. The survival rates were 81% at 1 year and 59% at 5 years. The multivariably determined risk factors for early death and postoperative neurological dysfunction were as follows (p < 0.05) cardiac anoxic arrest time, intubation time and gender.

The trichothecene biosynthesis regulatory gene from the type B producer Fusarium strains: sequence of Tri6 and its expression in Escherichia coli.

A genomic DNA fragment containing Tri6, a transcription activator gene of trichothecene biosynthesis, was cloned by vectorette PCR from Fusarium graminearum F15, which produces type B trichothecene, deoxynivalenol. The nucleotide sequence of the gene showed 84% of identity to that of the type A trichothecene producer Fusarium sporotrichioides NRRL 3299, but the sequence around the initiation codon was not highly conserved between these producers. Based on the upstream and downstream sequences of the coding region of F. graminearum, Tri6 could be amplified by PCR from other type B trichothecene producers. Tri6 appeared to be expressed for only a limited period prior to the toxin production.

The mystery of the trichothecene 3-O-acetyltransferase gene. Analysis of the region around Tri101 and characterization of its homologue from Fusarium sporotrichioides.

The trichothecene 3-O-acetyltransferase gene, Tri101, plays a pivotal role for the well-being of the type B trichothecene producer Fusarium graminearum. We have analyzed the cosmids containing Tri101 and found that this resistance gene is not in the biosynthetic gene cluster reported so far. It was located between the UTP-ammonia ligase gene and the phosphate permease gene which are not related to trichothecene biosynthesis. These two 'house-keeping' genes were also linked in Fusarium species that do not produce trichothecenes. The result suggests that the isolated occurrence of Tri101 is attributed to horizontal gene transfer and not to the reciprocal translocation of the chromosome containing the gene cluster. Interestingly, 3-O-acetylation was not always a primary self-defensive strategy for all the t-type trichothecene producers; i.e. the type A trichothecene producer Fusarium sporotrichioides did not acetylate T-2 toxin in vivo although the fungus possessed a functional 3-O-acetyltransferase gene. Thus Tri101 appears to be a defense option which the producers have independently acquired in addition to their original resistance mechanisms.

Single-step purification and characterization of MBP (maltose binding protein)-DnaJ fusion protein and its utilization for structure-function analysis.

DnaJ is a molecular chaperone, which contains a zinc finger-like motif and cooperates with DnaK to mediate the folding of newly synthesized and denatured proteins. DnaJ was overproduced and purified using the maltose binding protein (MBP) fusion vector. The fusion protein (MBP-DnaJ) was expressed in a soluble form in Escherichia coli and purified to homogeneity using amylose resin in a single step. The UV-visible absorption spectrum of MBP-DnaJ showed peaks at 355 and 475 nm. Moreover, these absorption peaks disappeared upon treatment with ethylenediaminetetraacetic acid (EDTA) or p-hydroxymercuriphenylsulfonic acid (PMPS). Inductively coupled plasma (ICP) spectrometry demonstrated that MBP-DnaJ contains Fe ions as well as Zn ions. MBP-DnaJ mediated the replication of the lambda phage in vivo, stimulated the ATPase activity of DnaK and prevented the aggregation of denatured rhodanase, indicating that fusion of MBP to the N-terminal of DnaJ does not affect the functions of DnaJ. To study the roles of bound metal ions, metal-free MBP-DnaJ, and MBP-DnaJ containing 2 Zn ions were prepared. MBP-DnaJ containing Fe and Zn ions, and MBP-DnaJ containing 2 Zn ions stimulated the ATPase activity of DnaK, prevented the aggregation of denatured rhodanase and bound to DNA to similar extents. On the other hand, metal-free MBP-DnaJ showed much lower DNA-binding ability and lower ability to prevent rhodanese aggregation. Therefore, the bound metal species do not affect the function of the zinc finger-like motif of DnaJ, whereas removal of the metal ions from DnaJ diminishes its binding ability as to DNA and denatured proteins.

Features of Tri101, the trichothecene 3-O-acetyltransferase gene, related to the self-defense mechanism in Fusarium graminearum.

A structural gene of Tri101, which encodes trichothecene 3-O-acetyltransferase, was isolated as a 3-kb XhoI-XbaI fragment from the trichothecene producer Fusarium graminearum strain F15. The gene contained no introns, and the coding region was 0.7-kb downstream of a putative UTP-ammonia ligase gene which obviously is not related to the biosynthesis of trichothecenes. Tri101 was expressed when T-2 toxin was added, but this induction was not dependent on the expression level of Tri6, a transcription activator gene in the trichothecene biosynthetic and regulatory gene cluster.

Neocarzinostatin-induced mutations at the hprt locus in exponentially growing CHO cells, compared with spontaneous mutations.

Spontaneous mutations and neocarzinostatin-induced mutations were investigated in the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in exponentially growing Chinese hamster ovary cells. Neocarzinostatin (NCS) treatment caused an 4.5-fold increase in mutation frequency. Analysis by multiplex polymerase chain reaction and sequencing of hprt cDNA revealed that spontaneous mutations in this system were characterized by a relatively high rate of large deletions and double-base substitutions, and a low rate of splice mutations compared with data reported in fibroblastic cell lines. NCS hardly affected this spectrum of spontaneous mutations, which indicates the rare incidence of NCS-specific change in the exponential growth phase. This is in contrast to aprt gene mutations reported in plateau phase cells in which base substitutions occur preferentially at sites affected by NCS. These results suggest that differences in the loci assayed or in the processes involved in mammalian mutagenesis in the exponential growth phase and the plateau phase may be the source of the different results.

Characterization of a novel aldose reductase inhibitor, FR74366, and its effects on diabetic cataract and neuropathy in the rat.

FR74366 (FK366) ([3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4- tetrahydroquinazolin-1-yl] acetic acid) is a chemically novel aldose reductase (AR) inhibitor. It exhibited a highly potent, reversible, and mixed type inhibition of partially purified AR from the rat sciatic nerve (IC50 = 3.6 nmol/L) and rat lens (IC50 = 4.4 nmol/L). FR74366 inhibited sorbitol accumulation in the isolated human erythrocyte (IC50 = 1.6 mumol/L), rat lens (IC50 = 39 mumol/L), and rat sciatic nerve (IC50 = 17 mumol/L) incubated with high glucose concentrations. The oral administration of FR74366 to streptozotocin (STZ)-induced diabetic rats for 2 weeks decreased sorbitol levels (ED50 = 3.7 mg/kg for sciatic nerve, 23 mg/kg for lens, 52 mg/kg for retina, and 62 mg/kg for renal cortex). Administration of FR74366 to diabetic rats for 17 weeks delayed cataract formation and admixture of 0.028% FR74366 in the diet completely inhibited the cataract formation. Moreover, the recovery of reduced motor nerve conduction velocity by FR74366 in diabetic rats was demonstrated in prevention and reversal experiments. This recovery effect correlated well with reduction of accumulated sorbitol and fructose levels and normalization of decreased myoinositol levels. The duration and tissue specificity of inhibitory effects of FR74366 on sorbitol accumulation also correlated well with the levels of FR74366 in various tissues of diabetic rats. These data indicate that both decreases in tissue sorbitol levels and improvement of functional defects reflect FR74366 levels in tissue rather than plasma in diabetic rats. These results, taken together, suggest that FR74366, which is currently undergoing clinical trials in Japan and the United States, will be a useful therapeutic agent for diabetic complications.