Feasibility of transperineal minimal invasive surgery when performing sacrectomy for advanced primary and recurrent pelvic malignancies.

BACKGROUND: This study aimed to clarify the efficacy and safety of minimally invasive transabdominal surgery (MIS) with transperineal minimal invasive surgery (tpMIS) for sacrectomy in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of MIS with tpMIS for sacrectomies. Surgery was performed between February 2019 and May 2023. The median follow-up period was 27 months (5-46 months). RESULTS: Fifteen consecutive patients were included in this analysis. The diagnoses were as follows: recurrent rectal cancer, n = 11 (73%); primary rectal cancer, n = 3 (20%); and recurrent ovarian cancer, n = 1 (7%). Seven patients (47%) underwent pelvic exenteration with sacrectomy, six patients (40%) underwent abdominoperineal resection (APR) with sacrectomy, and two patients (13%) underwent tumor resection with sacrectomy. The median intraoperative blood loss was 235 ml (range 45-1320 ml). The postoperative complications (Clavien-Dindo grade ≥ 3a) were graded as follows: 3a, n = 6 (40%); 3b, n = 1 (7%); and ≥ 4, n = 0 (0%). Pathological examinations demonstrated that R0 was achieved in 13 patients (87%). During the follow-up period, two patients (13%) developed local re-recurrence due to recurrent cancer. The remaining 13 patients (87%) had no local disease. Fourteen patients (93%) survived. CONCLUSIONS: Although the patient cohort in this study is heterogeneous, MIS with tpMIS was associated with a very small amount of blood loss, a low incidence of severe postoperative complications, and an acceptable R0 resection rate. Further studies are needed to clarify the long-term oncological feasibility.

Feasibility of transanal minimally invasive surgery for total pelvic exenteration for advanced primary and recurrent pelvic malignancies.

BACKGROUND: The purpose of this study was to clarify the efficacy and safety of transanal minimally invasive surgery (TAMIS) for total pelvic exenteration (TPE) in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of TAMIS for TPE. Surgery was performed between September 2019 and April 2023. The median follow-up period was 22 months (2-45 months). RESULTS: Fifteen consecutive patients were included in this analysis M:F = 14:1 and median (range) age was 63 (36-74). Their diagnoses were as follows: primary rectal cancer (n = 5; 33%), recurrent rectal cancer (n = 4; 27%), primary anorectal cancer (n = 5; 33%), and gastrointestinal stromal tumor (n = 1; 7%). Bladder-sparing TPE was selected for two patients (13%). In nine of 15 patients (60%) the anal sphincter could be successfully preserved, five patients (33%) required combined resection of the internal iliac vessels, and two (13%) required rectus muscle flap reconstruction. The median operative time was 723 min (561-1082), and the median intraoperative blood loss was 195 ml (30-1520). The Clavien-Dindo classifications of the postoperative complications were as follows: grade 0-2 (n = 11; 73%); 3a (n = 3; 20%); 3b (n = 1; 7%); and ≥ 4 (n = 0; 0%). No cases of conversion to laparotomy or mortality were observed. The pathological results demonstrated that R0 was achieved in 14 patients (93%). CONCLUSIONS: The short-term outcomes of this initial experience proved that this novel approach is feasible for TPE, with low blood loss, acceptable postoperative complications, and a satisfactory R0 resection rate.

Defining stakeholder involvement in participatory design processes.

A participatory approach could be used to implement work place or organizational improvements. However, the question is which participants should be involved and how. In this paper the theoretical involvement in different steps of a linear stepwise approach is described and compared with the latest projects of 300 practitioners. From a theoretical point of view ergonomists and employees play an essential role in the improvement process and are involved in most stages of a change process. Designers play an important role in idea generation and prototyping. Top management and middle management are important in the first step to set goals that are consistent with the strategy of the enterprise. Middle management is also needed in the steps where improvements are selected. This theoretical prediction is affirmed. However, middle management appeared to be also involved in implementation. The role of ergonomists is in practice limited in later stages in implementation, which is not preferred by the ergonomists.

Puridication and properties of an intracellular ribonuclease from Candida lipolytica.

1. A ribonuclease (RNAase CL) (EC 3.1.4.23, ribonucleate 3'-oligonucleotide hydrolase) was extracted by EDTA/acetate buffer, pH 5.6 from acetonedried cells of Candida lipolytica and purified 1350-fold by acetone and (NH4)2SO4 fractionation, DEAE-cellulose and DEAE-Sephadex chromatography. 2. RNAase CL is an acidic protein having an isoelectric point of 4.2, and an approximate molecular weight of 32 000. 3. Optimal pH and temperature for the enzyme were 6.0 and 60 degrees C, respectively. It is stable at neutral pH up to 50 degrees C. At 64 degrees C for 30 min, 95, 49 and 64% inactivation of the enzyme occurred at pH values 4.2, 6.6 and 10.0, respectively. 4. RNAase CL inhibited by Zn2+ and Cu2+, sulfhydryl reactants and by high concentration of salts, but not by chelating agents. 5. RNAase CL degraded ribosomal RNA, transfer RNA, polyadenylic acid, polycytidylic acid and polyuridylic acid into acid-soluble nucleotides. Among the synthetic homopolymers, polycytidylic acid was most rapidly degraded. Polyguanylic acid and duplexes of synthetic homopolymers were less sensitive. DNA was not attacked. Specificity studies showed that RNAase CL preferentially cleaves pC-purine bonds. 6. Digestion of poly (C) by RNAase CL resulted in the liberation of cyclic 2',3'-CPM from the start of the reaction with no observable formation of intermediate oligonucleotides. This suggests that the enzyme depolymerizes by an exonucleolytic mechanism.

Comparison between in vivo and in vitro chemokine production in Helicobacter pylori infection.

BACKGROUND: Enhanced gastric mucosal chemokine activity has been demonstrated in patients with Helicobacter pylori infection. However, little is known about the mechanisms involved in this phenomenon. AIM: To examine whether in vivo chemokine activity is similar to in vitro response of gastric epithelial cells infected by H. pylori. PATIENTS AND METHODS: Antral biopsy specimens were obtained from patients with H. pylori infection for organ culture, isolation of H. pylori and histological examination. RESULTS: In organ cultures of mucosal tissues, the levels of interleukin-8 and growth-related gene product a were elevated in patients with peptic ulcer disease compared with those with erosive gastritis or endoscopically normal mucosa. However, there were no significant differences in in vitro cultures of MKN45 or KATO III cells that were infected with H. pylori isolated from these same patients. These in vivo and in vitro alpha-chemokine levels showed no significant association with the presence of cagA gene and CagA protein, ureB genotype, or binding capacity to MKN45 or KATO III cells in individual H. pylori isolates. In contrast, in vivo mucosal alpha-chemokine activity correlated with H. pylori colonization density. CONCLUSION: Mucosal chemokine profiles and inflammatory responses in H. pylori infection may be associated more closely with host factors, including those determining bacterial adhesiveness, than with differences in H. pylori strains.

Clarithromycin increases the release of heat shock protein B from Helicobacter pylori.

BACKGROUND: Clarithromycin (CAM) may have certain indirect effects on Helicobacter pylori (H. pylori) other than its inhibitory activity on bacterial growth, as indicated in other infections with Gram-negative micro-organisms. In the present study, we examined the effects of lower concentrations of CAM on the release of heat shock protein B (HspB), one of the major antigenic proteins from H. pylori cells, as well as the changes in humoral immune response and histological degree of antral gastritis in patients who received eradication therapy with CAM. METHODS: The H. pylori strain 26695 and three CAM-resistant clinical isolates were cultured in broth with and without CAM (2-500 ng/mL). Expression of H. pylori proteins was examined by two-dimensional (2D)-electrophoresis followed by N-terminal amino acid sequencing. Changes in host immune response and histological degree of antral gastritis were monitored in patients with peptic ulcer disease who received H. pylori eradication therapy. RESULTS: 2D electrophoresis showed 26 spots in extracellularly released proteins with different profiles from those in cytoplasmic proteins. The release of HspB increased after incubation with CAM (30-500 ng/mL) in all three H. pylori clinical isolates tested. Patients with failed H. pylori eradication after triple therapy with CAM, but not those with failed eradication after dual therapy without CAM, showed an increase in serum IgG1 and IgG2 antibodies against HspB along with a decrease in the degree of neutrophil and H. pylori colonization density in tissue sections. CONCLUSIONS: CAM may induce a humoral immune response against H. pylori and a decrease in gastric mucosal inflammation through up-regulation of the release of HspB from the bacteria in infected patients.

Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome. Kansai-FGS-Apheresis Treatment (K-FLAT) Study Group.

BACKGROUND: The pathogenic role of hyperlipidemia in long-standing nephrotic syndrome (NS) is known to be responsible for both the progression of glomerulosclerosis and tubulointerstitial injury, especially in focal segmental glomerulosclerosis (FGS). METHODS: Aggressive lipid lowering treatment by low density lipoprotein (LDL) apheresis (LDL-A) using a dextran sulfate cellulose column to treat patients with steroid-resistant or frequently recurrent severe NS was performed first without fixing the protocol in eight patients with FGS and one with minimal change nephrotic syndrome (MCNS). The period of NS before LDL-A, number and average intervals of LDL-A until the end of the therapy, and the prognosis were investigated. Next, a multicenter study with a fixed protocol of LDL-A treatment was designed in combination with steroid therapy for treatment twice a week for three weeks and weekly for six weeks, and was performed in 17 patients with FGS. The effects on the state of NS in addition to the change of urinary eicosanoid metabolites and remission rates were evaluated. RESULTS: In the preliminary study, along with a rapid improvement of hyperlipidemia, a high incidence of remission was achieved by LDL-A performed at relatively short intervals. In the multicenter study with a fixed protocol, there was a significant decrease of urinary protein (P < 0.001) and increase of serum albumin (P < 0.02) as well as a decrease of thromboxane B2 (TXB2) excretion (P < 0.05) after the treatment. Urinary excretion of TXB2 was significantly reduced after LDL-A (P < 0.05). The rate of entering into complete or incomplete remission was 71% with a relatively short duration of nephrotic-range proteinuria using the LDL-A therapy in comparison with steroid therapy alone. CONCLUSION: The rapid improvement of hypercholesterolemia with LDL-A treatment may provide a new approach for a high rate of improvement in the degree of NS in steroid-resistant NS of FGS and MCNS.

Neuronal changes of hypokalemic myopathy. A light- and electron-microscopic study on muscle biopsy.

Hypokalemic myopathy has been observed in various clinical conditions. There are many studies of the pathomorphological changes of muscle fibers but alterations in intramuscular nerves and motor end-plates are seldom mentioned. The present authors observed biopsied muscle from a 51-year-old housewife who had suffered from gradually increasing muscle weakness. Laboratory examinations revealed a severe hypokalemia of 1.5 mEq/1, 18304 U/1 of CPK, 1300 U/1 of LDH, 343 U/1 of SGOT and 297 IU/1 of adolase. Light-microscopic examination showed changes previously described, including twin-peaked distribution in the histogram of type I, IIA and IIB fibers, ballooning and thickening of terminal axon, and 2 or 3 end-plates closely spaced along the length of muscle fibers. The electron-microscopic examination revealed empty folds of basement membrane in end-plate regions, reduced secondary synaptic clefts, interposition of Schwann cell processes between nerve ending and primary synaptic cleft, and an increase of disarranged microtubules and neurofilaments in terminal axons. The findings suggest that severe hypokalemia primarily produces structural alterations of intramuscular peripheral nerves and motor end-plates as well as of muscle fibers.

Effect of intragastric ammonia on gastrin-, somatostatin-and somatostatin receptor subtype 2 positive-cells in rat antral mucosa.

Somatostatin suppresses gastrin and somatostatin secretion via somatostatin receptors (SSTRs). Ammonia produced by Helicobacter pylori has been reported to modify gastric gastrin and somatostatin levels. We investigated the distribution of SSTR-subtype 2 (SSTR-2) in relation to gastrin- and somatostatin-containing cells and the effect of ammonia solution (0.01%-0.1%) administered orally for 2 to 4 weeks on these cells in rat antral mucosa by immunohistochemistry. The majority of SSTR-2 peptide [31-41]-positive cells were located in the basal third of the glands. Double staining experiments revealed that SSTR-2 peptide [31-41]-positive cells are co-localized in 85.0 +/- 2.2% of the gastrin-containing cells and in 34.4 +/- 4.8% of the somatostatin-containing cells. Ammonia solution significantly decreased the number of somatostatin-containing cells and increased the proportion of SSTR-2 peptide [31-41]-labeling in the somatostatin-containing cells in a duration-dependent manner. Maximum changes were observed in rats treated with ammonia solution at the lowest level of 0.01% accompanied by an increase in serum gastrin levels in the portal vein. Sodium hydroxide at the similar pH to 0.01% ammonia solution had no effect. These findings suggest that SSTR-2 are localized in antral endocrine cells and that ammonia solution mainly decreases somatostatin-containing cells without SSTR-2 expression, resulting in an increase in gastrin secretion into the portal vein.

C-19393 S2 and H2, new carbapenem antibiotics. III. Mode of action.

Biochemical activities of new carbapenem antibiotics, C-19393 H2(H2) and C-19393 S2(S2), were examined in comparison with those of mecillinam using Escherichia coli. H2 showed remarkably high affinity for penicillin-binding protein (PBP) 2, and high affinity for PBPs 1 and 3. S2 showed high affinity for PBP 2, moderate affinity for PBP 1 and low affinity for PBP 3. They induced ovoid cells at lower concentrations and cell lysis at higher concentrations. The inhibitory potency of H2 for peptidoglycan synthesis was similar to that of mecillinam at lower concentrations up to 0.1 micrograms/ml. At concentrations higher than 0.1 micrograms/ml, the inhibition rate by H2 gradually increased up to 100%, whereas that by mecillinam remained at 60% level. The MICs of H2, S2 and mecillinam corresponded to the lowest concentrations giving 60% of inhibition of peptidoglycan synthesis at which concentrations the function of PBP 2 seemed to be prevented completely. These findings indicate that the primary targets of H2 and S2 are PBP 2 involved in cell shape determination in E. coli.

Structure-activity relations of 5,6-cis carbapenem antibiotics and role of factors determining susceptibility of Escherichia coli to beta-lactam antibiotics.

The antibacterial activities of twelve 5,6-cis carbapenem antibiotics, including four semisynthetic derivatives of C-19393 H2 and S2, against 15 microorganisms were examined, and their structure-activity relations are discussed in relation to minimum inhibitory concentrations against Staphylococcus aureus and Escherichia coli as a Gram-positive and a Gram-negative standard strain, respectively. The contribution of chromosomal beta-lactamase (amp C), permeability barrier, and penicillin-binding protein (PBP) 1B to the resistance of E. coli to these carbapenem antibiotics was examined using mutants lacking each of these cellular components. The beta-lactamase was not involved in the resistance. These antibiotics easily permeated the outer membrane. A PBP 1B-defective mutant was supersensitive to these carbapenem antibiotics and to other types of beta-lactam antibiotics.

Isosulfazecin, a new beta-lactam antibiotic, produced by an acidophilic pseudomonad. Fermentation, isolation and characterization.

A novel beta-lactam antibiotic, isosulfazecin (iSZ), was found to be produced by an acidophilic pseudomonad, Pseudomonas mesoacidophila sp. nov. iSZ was produced in parallel with bacterial growth in nutrient broth containing glycerol and sodium thiosulfate under aerated conditions. iSZ was isolated by chromatography on activated charcoal and anion-exchangers and crystallized from 70% aqueous methanol. The molecular formula was determined to be C12H20N4O9S from physiochemical data. The IR and NMR spectra suggested that iSZ has a beta-lactam ring, methoxyl and sulfonate groups. On acid hydrolysis, it gave L-alanine and D-glutamic acid. iSZ is an epimeric isomer of sulfazecin. iSZ was weakly active against Gram-positive and -negative bacteria, and was strongly active against mutants hypersensitive to beta-lactam antibiotics.

C-19393 S2 and H2, new carbapenem antibiotics. IV. Inhibitory activity against beta-lactamases.

New carbapenem antibiotics, C-19393 S2 and H2, have been found to be potent and broad-spectrum inhibitors of beta-lactamases. Among 11 types of beta-lactamases tested, those from Escherichia coli (plasmid-bearing), Klebsiella pneumoniae, Proteus vulgaris, Serratia marcescens and Bacteroides fragilis were especially sensitive. They also inhibited cephalosporinases insensitive to clavulanic acid. The inhibition by C-19393 S2 and H2 was of progressive type, except for the inhibition of E. coli enzyme (plasmid-mediated type I) by C-19393 H2. The inhibition of E. coli beta-lactamase by C-19393 S2 was irreversible, while that by C-19393 H2 was reversible.

Isolation and characterization of bulgecins, new bacterial metabolites with bulge-inducing activity.

Bulgecins A, B and C, new bacterial metabolites which induce the formation of bulges by cooperation with beta-lactam antibiotics, were isolated from the culture broth of Pseudomonas mesoacidophila. The three components, separated by column chromatography on QAE-Sephadex A-25, are water-soluble acidic compounds containing a sulfate group in the molecule. Acid hydrolysis showed that D-glucosamine and a new proline derivative are common constituents of the three components. In addition, taurine and beta-alanine are constituents of bulgecins A and B, respectively.

Beta-lactamase inhibitory activities and synergistic effects of 5,6-cis-carbapenem antibiotics.

Twelve 5,6-cis-carbapenem antibiotics were examined for their beta-lactamase inhibitory activities, their types of inhibitions, and their synergistic activities with other beta-lactam antibiotics. All the carbapenems inhibited eight types of beta-lactamases including cephalosporinases which were insensitive to clavulanic acid and sulbactam. The sulfonyloxy ethyl carbapenems were the most active inhibitors; they inhibited all beta-lactamases in a progressive fashion, whereas some of the hydroxyl compounds exerted non-progressive inhibition against several beta-lactamases such as those of Escherichia coli TN713 and Proteus vulgaris GN4413. Several carbapenems were inactivated by the beta-lactamases of Citrobacter freundii GN1706, P. vulgaris GN4413, E. coli TN713, and Klebsiella pneumoniae TN1698. Most of the carbapenems potentiated the antibacterial activities of ampicillin and cefotiam against beta-lactamase-producing bacteria.

Studies on condensed-heterocyclic azolium cephalosporins. IV. Synthesis and antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)- alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl cephalosporins including SCE-2787.

The synthesis and in vitro antibacterial activity of 7 beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetami do] cephalosporins bearing various condensed-heterocyclic azolium groups at the 3 position in the cephalosporin nucleus are described. The thiadiazolyl cephalosporins showed good antibacterial activity against both Gram-positive and Gram-negative bacteria and the MICs of the thiadiazolyl cephalosporins against Pseudomonas aeruginosa was more potent than that of the corresponding 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]-3- (condensed-heterocyclic azolium)methyl cephalosporins. Also, the thiadiazolyl cephalosporins bearing (imidazo[1,2-b]-pyridazinium-1-yl)methyl groups at the 3 position showed antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Among the cephalosporins tested, 7 beta-[2-(5- amino-1,2,4-thiadiazol-3-yl)-2(Z)-methoxyiminoacetamido]-3-(imidaz o[1,2- b]pyridazinium-1-yl)methyl-3- cephem-4-carboxylate (4, SCE-2787) which exhibited the most potent antibacterial activity and the broadest antibacterial spectrum was selected as a parenteral cephalosporin candidate for further biological evaluation.

C-19393 S2 and H2, new carbapenem antibiotics. I. Taxonomy of the producing strain, fermentation and antibacterial properties.

C-19393 S2 and H2 are new carbapenem antibiotics produced by a streptomycete. The producing strain was taxonomically studied and named Streptomyces griseus subsp. cryophilus. Cobaltous compounds were necessary for production of the antibiotics. C-19393 S2 and H2 showed a broad spectrum of antibacterial activities with C-19393 H2 being 8 approximately 120 times more active than C-19393 S2. They also exhibited beta-lactamase-inhibiting activities and acted synergistically with ampicillin and cefotiam against clinical isolates resistant to beta-lactam antibiotics.

Carriomycin, a new polyether antibiotic produced by Streptomyces hygroscopicus.

Carriomycin, a new polyether antibiotic, was isolated from culture broth of Streptomyces hygroscopicus strain T-42082. It is active against Gram-positive bacteria, several fungi, yeasts and mycoplasma. It is also coccidiostatic. The free acid of carriomycin occurs as colorless prisms having the molecular formula C47H80O15 (M.W. 885.15), m.p. 120 approximately 122 degrees C and [alpha]25D -0.5 in methanol. It has no characteristic absorption maxima in the ultraviolet spectrum. The presence of one carboxyl and three methoxy groups was observed from its infrared, PMR and CMR spectra.

Relevance of in vitro antibacterial activities and pharmacokinetic properties of antipseudomonal beta-lactam antibiotics to their therapeutic effects on urinary tract infection caused by Pseudomonas aeruginosa P 9 in mice.

The therapeutic effects of seven antipseudomonal beta-lactam antibiotics on experimental urinary tract infection caused by Pseudomonas aeruginosa P 9 in mice were compared, and the results were analyzed in relation to their in vitro antibacterial activities and pharmacokinetic properties. The CD50 values were (mg/kg): cefsulodin, 6.19; cefoperazone, 162; sulbenicillin, 167; ticarcillin, 184; azlocillin, 121; mezlocillin, 390; and piperacillin, 227. Cefsulodin was more active than the other antibiotics not only in therapeutic effects but also in in vitro antibacterial effects evaluated according to growth inhibitory, bactericidal, and bacteriolytic activities. It also penetrated and persisted well in the kidney of mice. The therapeutic effects of cefoperazone, azlocillin, and piperacillin were much less than expected from their in vitro antibacterial activities; the CD50 values were more than 18-fold as large as that of cefsulodin, whereas the differences of their MIC values were less than four-fold.

Pneumatosis cystoides intestinalis treated with hyperbaric oxygen therapy: usefulness of an endoscopic ultrasonic catheter probe for diagnosis.

A 67-year-old woman was admitted to our hospital with a complaint of abdominal pain. Barium enema examination and colonoscopy showed numerous round polypoid lesions covered with normal mucosa in the area from the ascending colon to the splenic flexure. Endoscopic ultrasound examination with an ultrasonic catheter probe revealed a strong echo with distal acoustic shadowing in the third layer of the diseased colonic wall, which suggested the presence of gas in the submucosa. The gaseous cysts disappeared completely after hyberbaric oxygen therapy at 2 to 3 atmospheres absolute (60 minutes, twice a day) for 30 consecutive days.