Clinical evaluation of newly developed oral ampicillin prodrug lenampicillin (LAPC, KBT-1585) applied to patients with superficial purulent infection at a dosage of 750-1,500mg daily was conducted. Additionally, as part of the basic study, transition of the compound to the human skin tissue was observed.
1. With regard to transition to human skin tissue in 11 presurgery dermatitis cases, 250mg or 500mg of LAPC was administered to 2-3 hours before surgery. Comparison was made between concentrations in serum and in skin tissue. Results in the case of 250mg application showed serum concentration to be 1.28-3.32 μg/ml, and in skin tissue, 0.13-0.82μg/g. At 500mg, serum concentration was found to be 2.23-10.05μg/ml, with skin tissue concentration at 0.45-1.34μg/g.
2. Rate of clinical efficacy in the treatment of the 183 cases of superficial purulent infection was 79.2%. By grouping of the infections (Table 3), high efficacy rates were obtained in the second group, at 85.7%; in the third at 88.9%; and in the fourth group at 96.4%. Evaluation of usefulness from the standpoint of safety was 77.6%. Good results were obtained in the third group with 88.9%; and in the fourth group with 96.4%.
3. LAPC's efficacy rates against individual strains of bacteria in simple infection are as follows: Staphylococcus aureus, 74.6%; Staphylococcus epidermidis, 76.3%; GPC, 100%; anaerobes, 87.5%. In polymicrobial infections the rate was 84.6%. The rate of efficacy against all strains of bacteria was 76.0%.
4. Adverse reactions were found in 13 cases (14 incidences) out of 193. The rate of incidence was 7.3%, with allergic response accounting for 5 cases, digestive tract disorders, 7 cases, and mouth odor, 1 case. There were 5 cases (6 incidences) of abnormal deviation of laboratory findings. In all cases, abnormal deviations were mild and their relation to the drug was unclear.

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1. Clinical efficacies of newly developed synthetic oral ampicillin prodrug lenampicillin (LAPC, KBT-1585) applied to 109 cases of oral infection were studied. There were 7 dropout cases. The results as determined on a point system are as follow: Remarkably effective, 26 cases; effective, 63 cases; and not effective, 13 cases, for an efficacy rate of 87.3%. When rated by the subjective judgement of the doctors in charge, these figures are as follow: remarkably effective, 21 cases, effective, 67 cases; slightly effective, 10 cases; and not effective, 4 cases. The rate of efficacy in this way being 86.3%. In either way, the results obtained were favorable.
2. Among 102 cases in this study, pus was aspirated with sterile needle from obstructed abscesses in 65 cases, with the result that 161 strains of bacteria were isolated and identified. Most of infections were found mixed type by aerobic Gram-positive cocci and anaerobes. Especially, cases caused by α-Streptococcus were observed in 48 out of 55 mixed infective cases.
3. LAPC's MIC distribution against the detected bacteria showed strong antibacterial effect as follows: against Gram-positive cocci, less than 0.39μg/ml; against Gram-negative bacteria (excluding some insusceptible strains), less than 3.13μg/ml. Thus, LAPC demonstrated a superiority when compared to CEX by 4-128-fold, and when compared to AMPC by about 2-fold.
4. Adverse reactions among the 109 cases consisted of 6 cases of gastro-intestinal disorders including 3 cases of diarrhea.
5. Recognized cases of abnormal laboratory findings were 3 cases out of 76 (3.9%), but none were serious.

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Penetration of aspoxicillin (ASPC), a new semisynthetic penicillin of broad spectrum, into normal and cancer tissue and wound exudate were examined in breast cancer. ASPC was administered by single injection of 1 or 2g.
The concentration of ASPC in the resected skin, normal mammary gland and cancer were similar to their serum levels, when ASPC was administered before radical mastectomy. ASPC concentration in the wound exudate which was collected from the inserted drains into the resected area reached the maximum at 3-4 hours after the injection at the levels of 19.4μg/ml (1g) and 35.1μg/ml (2g). The level decreased gradually by maintained still high at 3.7μg/ml (1g) and 11.4μg/ml (2g) even 8 hours after the injection. From these results it may be expected that ASPC is a useful penicillin in the breast surgery.

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Aspoxicillin (ASPC), a semisynthetic penicillin has a broad spectrum of antibacterial activities against Gram-positive and Gram-negative anaerobic bacteria. Its in vitro antibacterial activity was less than those of cefoxitin against Peptostreptococcus and Veilonella, but was significantly high against Bacteroides fragilis, one of the most clinically important anaerobe. The therapeutic and/or protective effect of ASPC in experimental subcutaneous abscess or experimental intraabdominal mixed infection due to β-lactamase producing B. fragilis and non-producing Escherichia coli were much stronger than those of ticarcillin.
In order to account the superiority of ASPC in vivo, the effects of ASPC and other β-lactams on B. fragilis were compared and the results were analyzed in relation to their in vitro bactericidal activities, stability against the β-lactamase, binding properties with penicillin-binding proteins and pharmacokinetic properties. Interestingly, administration of ASPC did not increase the bacterial counts of Clostridium difficile in caecal contents, but piperacillin, ticalcillin, carbenicillin, ampicillin and cefotaxime increased the counts.

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Clinically pathogenic Pseudomonas aeruginosa and Escherichia coli were subjected to test in vitro combination effect of mezlocillin (MZPC) and sisomicin (SISO).
The chequer board titration method, using brain heart infusion broth (BHIB, Difco), demonstrated the combination effect of MZPC and SISO on the both isolates. The bactericidal combination effects (MBCs) were clearly higher than the bacteriostatic combination effects (MICs).
The bactericidal activities of combination with MZPC and SISO were tested on both P. aeruginosa and E. coli. The MZPC plus SISO of low concentrations showed the synergistic effects on both isolates.

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The efficacy, safety and utility of sisomicin (SISO) followed intravenous infusion were evaluated in 35 cases with various respiratory infections.
For many cases, SISO was given at a daily dosage of 100mg, and a single dose was infused over about 1 hour.
Clinical efficacy was evaluable in 28 cases including pneumonia (14 cases), bronchitis (8 cases), bronchiectasis (4 cases), pulmonary suppuration (1 case) and pulmonary abscess plus pyothorax (1 case). Almost cases had diagnosis of serious infection associated with various diseases.
Clinical efficacy was evaluated as “excellent” in 2 cases, “good” in 15 cases, “fair” in 5 cases and “poor” in 6 cases, and efficacy rate in total case was 60.7%. Efficacy rate stratified by disease was calculated as 57.1% in pneumonia, 87.5% in bronchitis, 50.0% in bronchiectasis. Responses against pulmonary suppuration or pulmonary abscess with pyothorax were little or not.
Bacteriologically, organisms isolated from sputum cleared in 7 out of 15 evaluable cases, thus the responses rate was 46.7%.
Adverse reaction probably due to treatment observed in 2 cases with hepatic dysfunction.
Blood levels of SISO at the end of infusion were ranged from 2.1 to 6.4μg/ml, and no tendency of accumulation in blood after repeated infusion was showed.

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SISO in doses of 1.0 to 1.8mg/kg was administered by a 30-minute intravenous infusion every 12 hours to 10 patients with infections, 9 of whom had underlying diseases including malignant diseases, diabetes mellitus, and diabetes insipidus with indwelling FOLLEY catheter. The serum concentration of SISO was around 6.75 & mu;g/ml in the end of infusion, and less than 1.0 & mu;g/ml at 8 to 12 hours after infusion. SISO was given to the patients as a single agent for at least 3 to 5 days and all patients experienced an excellent to good response clinically, and causative organisms which showed a minimal inhibitory concentration of less than 1.56 & mu;g/ml disappeared after the treatment associated with clinical improvement. There were no untoward effects noted in this study.

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The safety and pharmacokinetics of micronomicin (MCR) by intravenous drip infusion were evaluated and the intravenous drip infusion of MCR was carried out on several cases on which the blood levels and clinical usefulness of MCR were investigated.
Five healthy adult male volunteers received by crossover method 1 hour intravenous drip infusion of MCR in doses of 60 and 120mg and intramuscular injection in a dose of 120mg. The mean highest serum level was 6.3μg/ml by intravenous drip infusion of 60mg, 10.7μg/ml by intravenous drip infusion of 120mg, and 10.3μg/ml by intramuscular injection of 120mg. Serum levels of MCR were similar for intravenous drip infusion and intramuscular injection of 120mg of MCR. The biological serum half-lives of MCR were 2.15 hours by 1 hour intravenous drip infusion of 60mg, 2.54 hours by 1 hour intravenous drip infusion of 120mg, and 1.59 hours by intramuscular injection of 120mg. The mean urinary recovery rates within 24 hours after administration were 74.3% by 1 hour intravenous drip infusion of 60mg, 59.6% by 1 hour intravenous drip infusion of 120mg, and 64.9% by intramuscular injection of 120mg, the results being nearly consistent. In all treatment groups, MCR could be safely administered.
Intravenous drip infusion of MCR in a dose of 60 or 120mg once or twice a day was conducted on a total of 6 cases consisting of 2 cases of pneumonia and 4 cases of urinary tract infections. It was concluded that intravenous drip infusion of MCR is of clinically high usefulness. The highest serum levels ranged from 3.0 to 9.5μg/ml, this being a favorable level from views of both effectiveness and risk of adverse reactions.
The above evaluation demonstrated high effectiveness and safety as well as clinical usefulness of intravenous drip infusion of MCR.

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Cefotiam (CTM) was administered through 1 hour intravenous drip infusion for the patients performed biliary tract surgery. The concentration of CTM in serum, gallbladder tissue and the excretion in bile of the choledochus were measured.
1. Twenty-one patients performed cholecystectomy were followed the concentration of CTM in the gallbladder tissue and the results were studied with pharmacokinetic analysis. The simulation curve, which was described by computer system in two-compartment open model, showed the maximal concentration of CTM in the serum was 60.3μg/ml at 1 hour after infusion and that in the gallbladder tissue was 27.1μg/g at 1.07 hours. The concentration of CTM in the gallbladder tissue was presumed to be in proportion to that of CTM in the serum.
2. Six patients performed bile drainage were followed the concentration of CTM in bile of the choledochus for 6 hours after infusion. The maximal concentration was 215.2 ± 62.7μg/ml at 3 hours after injection, and the mean biliary recovery was 1.66 ± 0.55% through 6 hours.
3. Neither any side effects nor any abnormal values in the laboratory analysis of samples were observed for CTM.

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Cefotiam dihydrochloride (CTM) in a dose of 2g was given by intravenous bolus injection to 15 patients operated upon for acute or subacute abdominal organs. They were included to 5 cases of acute localized peritonitis due to perforative appendicitis, 3 of diffuse peritonitis due to perforative duodenal ulcer, 1 of diffuse peritonitis with intestinal obstruction, 1 of perforative sigmoid colon cancer, 2 of gastric cancer or polyp with cholelithiasis, and 3 of cholangitis with cholecyst-choledocholithiasis. The materials of exudate from drain were taken at intervals by sterilized paper disc and determined by paper disc bioassay method with Proteus rettgeri ATCC 9250 or Proteus mirabilis ATCC 21100 as the test organisms to CTM concentrations.
CTM concentrations in purulent exudate from drain of patients with acute peritonitis, they were increased quickly after intravenous bolus injection, and reached higher levels at early time after injection in cases 2 or 3 days after operation. CTM concentration in purulent exudate from drain was tended to increase in proportion to the severity of the inflammation.
The CTM levels in infected exudate were higher than the MICs against clinically isolated organisms for a long time after administration. Therefore, CTM was very useful drug when used for chemotherapy of postoperative peritonitis.

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In vitro activity of antimicrobial agents such as ABPC, SBPC, MPC, CEZ, CTM, CMZ, CTX, CMX, CZX, LMOX, CPZ, CFS and GM against major clinical isolates, S. aureus, S. pyogenes, E. coli, K. pneumoniae, P. mirabilis, C. freundii, Enterobacter spp., S. marcescens, P. vulgaris and P. aeruginosa, was examined.
In this paper, we will report the susceptibility of S. aureus, S. pyogenes, E. coli, K. pneumoniae and P. mirabilis during a three-year period, 1981-4983.
1. CEZ-and GM-resistant S. aureus has markedly increased and occupied 24% and 18%, respectively, in 1983. CMZ and CFS have showed potent activity against CEZ-resistant S. aureus. It seems that the abuse of third generation-cephems and new oral cephalosporins is closely related with the increase of cephemsresistant S. aureus.
2. The penicillin-and cephem-resistant strains of S. pyogenes could not be found in our study.
3. Quite a few strains of E. coil, K. pneumoniae and P. mirabilis are resistant to penicillins, and also there is no appreciable change in susceptibility. Some strains of E. coli, K. pneumoniae and P. mirabilis showed low susceptibility to CPZ, but all strains showed high susceptibility and no change in susceptibility to third generations, and these strains showed no tendency to decrease in susceptibility to GM.

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This report presents data concerning in vitro activity of antimicrobial agents against Citrobacter freundii, Enterobacter spp., Serratia marcescens and Proteus vulgalis isolated from patients with complicated urinary tract infections and against Pseudomonas aeruginosa isolated from surgical wounds with postoperative infection and exudate from superficial abscesses.
1. There was a marked increase of resistant strains of C. freundii, Enterobacter spp. and S. marcescens to penicillins, CEPs or GM. The isolates of these species obtained in 1983 showed MIC values of 100μg/ml or more for the so-called new CEPs (CTX, CMX, CZX, LMOX and CPZ).
2. The P. vulgalis isolates exhibited an increasing incidence of strains resistant to penicillins, and data on P. vulgalis isolates in 1983 indicated increase of strains resistant to CEPs. GM-resistant organisms were also noted to be increasing among the isolate of this species.
3. The analysis did not reveal any appreciable change with calendar years among P. aeruginosa in respect of frequency of strains resistant to SBPC or CEPs (except CPZ). The data obtained in 1983, however, showed an indication of increasing incidence of organisms resistant to CPZ and GM.
4. The increasing tendency of emergence of organisms resistant to new CEPs designed to expand activity against C. freundii, Enterobacter spp., S. marcescens and P. vulgalis, observed among the isolates of these species is considered probably to be the consequence of bacterial selective acquisition of R plasmid that carry drug resistant genes against CEPs. These are exactly reflected in the present data obtained in studies initiated in 1981 when the new CEPs became commonly prescribed in the daily clinics. It is concluded, accordingly, that organisms of these species resistant to CEPs have been increasing throughout the country.

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Sixty-three infectious episodes in 61 patients with hematological disorders were treated with cefminox (CMNX, MT-141), a new antibiotics in the cephamycin group. CMNX was given by 1 hour infusion every 8 to 12 hours in a dose of 4-6g per day for 3 to 12 days, not being combined with other antibiotics. CMNX was effective in 45% of total cases. In 24 cases, the number of granulocytes at the start of CMNX were less than 500/mm³, and 11 cases (46%) of them responded to CMNX.
Thus, CMNX was found effective in severe infections in patients with hematological disorders. No serious side effects attributable to CMNX were noted.

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This clinical trial was designed to evaluate the efficacy, safety and patient tolerance of cefoxitin (CFS) in 46 patients who were admitted to the hospitals from June 1983 to April 1984. The daily doses of CFX for 34 patients (ages ranged from 6 to 75 years old) were 2 to 8g to prevent the infections and for 12 patients (ages ranged from 55 to 81 years old) were 2 to 6g to treat the infections by intravenous drip infusion 1 or 3 times a day in divided doses.
The following results were obtained.
1. All of 34 patients with intracranial operation who received CFX for prevention of postoperative infections showed good results.
2. Of 12 patients with postoperative pneumonia, infections of urinary tract and late meningitis, 11 patients showed good results. One patient was discontinued on the 3 days because of the drug eruption which improved 3 days after.
3. The side effect was noted in only 1 patient. This was eruption which improved 3 days after the stop of the administration. The influences to the laboratory data due to CFX were not recognized.
The results of this study demonstrated that CFX was an excellent drug for the prevention and treatment of the postoperative infections in the neurosurgical field because of high efficacy rate and safety.

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In 11 patients with respiratory tract infections, the concentrations of cefmenoxime (CMX) in serum and sputum after 1 hour intravenous administration of 2 g of CMX were investigated.
The peak serum level of CMX was 102.2±11.4 μg/ml after 1 hour drip infusion, then declined and was 3.5±10.55 μg/ml after 5 hours.
Sputum level of CMX was lower than serum level but it was able to cover enough for MIC of Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, Streptococcus pneumoniae and the peak sputum level of CMX was 0.77±0.17 μg/g after from 2 hours to 4 hours.
Among the 11 patients with respiratory tract infections, 2 patients showed excellent, 6 patients good, 3 patients poor results (isolated organisms of sputum were normal flora) and no side effects observed.

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We investigated the concentrations of cefmenoxime (CMX) after administration of 2 g of CMX, in the tissues resected during operation 2 hours after the beginning of intravenous drip infusion, and in the exudates from abdominal or thoracic cavities in the postoperative period.
The results were as follows:
1. The highest tissue concentration of CMX was found in the liver (59.0±20.3 μg/g), and the lowest was in the pancreas (13.9±8.1 μg/g). The concentrations of CMX in the tissues were in order of liver>> colon=esophagus=stomach> pancreas.
2. The peak concentration of CMX in exudate from thoracic cavity was 15.6±10.1 μg/ml, and was observed 2 hours after the beginning of intravenous drip infusion, later than that in serum. Furthermore, the concentration of the exudate was maintained to a reasonable extent for 5 hours.
3. The concentrations of CMX in both tissues and exudates were enough to inhibit the growth of many kinds of bacteria isolated from abdominal infections.

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Cefmenoxime (1 g) was intravenously administered by one shot to investigate its pharmacokinetic profile with respect to transfer into the kidney, vesical wall and prostatic adenoma.
1. The concentration of cefmenoxime in the kidney reached a peak of 403 μg/g at 0.17 hour after administration. The biological half-life was 0.74 hour.
2. In the vesical wall, the level of cefmenoxime reached a peak of 28 μg/g at 0.67 hour after administration. The half-life was 2.30 hours.
3. The peak level of cefmenoxime in the prostatic adenoma was 22 μg/g at 0.39 hour after administration. The half-life was 2.90 hours.
The concentrations of cefmenoxime in these urogenital tissues were higher than its MIC₈₀ and MBC₈₀ against various Gram-negative organisms.

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A clinical study of cefoperazone (CPZ) in the surgery (on the prevention postoperative infections and transfer into pleural effusion) was conducted to obtain results as follows.
1. As for the blood concentration after a 30-minute drip infusion of CPZ 2 g, it was 115.6±19.88 μg/ml (Mean±S. E.) 1 hour after completion of the administration. The biological half-life was 2.16 hours.
2. The pleural effusion concentration of CPZ showed 33.3±7.86 μg/ml 2 hours after completion of the administration, which was enough to inhibit the growth of bacteria isolated from sputum and pleural effusion. The excretion was very slow.
3. As for the effectiveness of CPZ for prevention of postoperative infection, CPZ proved effective in all of 8 cases. Specific side-effects were not observed. Thus, the usefulness of this preparation was confirmed.

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There are few clinical reports about the concentration of ceftizoxime (CZX) in lung tissues. At present, clinically, we report the concentration of the drug in serum and lung tissues on 26 cases of chest disease and an effect of the drug on prophylaxis of postoperative pulmonary infections. Our results are the following;
1. The peak concentration of CZX in serum is 54.7 μg/ml at 1 hour after starting drip infusion of CZX 1 g. The serum half-life of CZX (β phase) is 2.07 hours.
2. The concentration of CZX in lung tissues is from 43.6 to 78.7% of serum level.
3. CZX is useful to prophylaxis of postoperative infections after thoracotomy, especially in case of administration of CZX 1 g just before operation.
4. Eruption was found in 1 of 26 cases. However, no side effects of the drug are noticed in other 25 cases.

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Serum and renal tissue concentrations of ceftizoxime (CZX) after intravenous dosing with 1 g were determined in 15 patients with renal disease.
The highest serum concentration of CZX was 105 μg/ml 6 minutes after dosing and the lowest concentration was 10.5 μg/ml at 170 minutes. The highest renal tissue concentration was 155 μg/g and the lowest concentration was 7.46 μg/g. There were no correlation between the tissue concentrations and sampling time. Tissue to serum concentration ratios ranged from 0.28 to 5.73.
These patients were divided into 3 groups; hydrcnephrosis, normal kidneys and renal atrophy according to pyelographic findings. Their renal tissue concentrations were compared with serum concentrations in each group. The tissue concentrations were lower than the serum concentrations in the first group, and were almost the same or higher in the other groups.
CZX concentrations in the medulla and the cortex were determined in 5 patients; and were higher in the medulla in 4 of these patients.
Urinary tract infection due to E. coli, K. pneumoniae, P. mirabilis, S. pyogenes or S. epidermidis was present in 5 of the 25 patients. Intravenous injection of 1 g of CZX provided therapeuticaly effective concentrations against these urinary tract infections.

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The penetration of cefotaxime (CTX) into the cerebrospinal fluid (CSF) was monitored to evaluate the prophylactic efficacy of the drug against post-craniotomic infections. Doses ranged from 1 to 2 g were administered to patients with subarachnoid hemorrhage due to the rupture of cerebral aneurysm, traumatic cerebral contusion, or subdural edema accompanied by intracerebral hemorrage, by intravenous drip infusion over a period of 30 or 60 minutes. CTX readily entered the CSF with concentrations exceeding MICs against the major pathogens occurring after craniotomy. CTX proved to be effective in the prevention of post-craniotomic infections in noninflammatory situations, especially after surgery in the case of cerebral traumas or subarachnoid hemorrhage.

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In vitro susceptibilities of 73 strains of Haemophilus influenzae isolated from clinical specimens in 1983 to various antibiotics were studied. The following antibiotics were evaluated; ampicillin (ABPC), piperacillin (PIPC), cefotaxime (CTX), cefoperazone (CPZ), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX), tetracycline (TC), doxycycline (DOXY), minocycline (MINO), chloramphenicol (CP) and erythromycin (EM).
Susceptible strains to ABPC and PIPC with MICs less than 3μg/ml were 80.3 and 84.1%, respectively. With this break point of MIC, all strains showed susceptibility to CPZ, CZX, and CMX, but resistant strains were observed in 1.5% against CTX and LMOX. Susceptible strains to TC, DOXY and MINO at MICs less than 2μg/ml were 86.3, 80, and 87.7%, respectively. Those to CP at MICs≤4μg/ml and to EM at MICs≤1μg/ml were 86.2 and 71.9%.

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The antigenicity or immunological characteristics of T-2588, newly-developed ester type cephem antibiotic, was studied employing rabbits, guinea pigs and mice.
The results obtained were as follows:
1. Antibody production against T-2588 was not observed in rabbit immunized with the emulsion of T-2588 and FREUND'S complete adjuvant (FCA).
2. Hapten-specific antibody production against T-2525 was demonstrated by indirect hemagglutination test and 4hrs. PCA of guinea pigs, employing rabbit antiserum hyperimmunized with the emulsion of T-2525 coupled to rabbit serum albumin and FCA.
3. Hapten-specific antibody production against T-2525 was demonstrated by 48hrs. PCA of rats, employing mice immunized with the mixture of T-2525 coupled to keyhole limpet hemocyanin and alminium hydroxide gel.
4. Cross antigenicity of T-2525 was observed to be relatively strong against cefotaxime and ceftizoxime, and very weak against cephalothin (CET), cefazolin, cefoperazone (CPZ), cefmenoxime, cefotiam and benzylpenicillin (PCG).
5. Anaphylactic syndrome was not observed in guinea pigs actively sensitized with the emulsion of T-2588 or T-2525 and FCA.
6. The ability of T-2588 and T-2525 to give a positive reaction in COOMBS' test was rather weaker than that of CET, CPZ and PCG.

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With the cooperation of 13 medical institutions in the Tokyo area, the methods to determine the prophylactic effect on postoperative infections in gynecological surgery were evaluated. Two hundred and ninety-nine patients were enrolled for the study of postoperative infections, febrile morbidity and fever index following abdominal (275) and vaginal (24) hysterectomies. Prophylactic cefotiam (CTM) of 1 gram was intravenously administered twice a day postoperatively for 3 to 5 days.
The rates of postoperative infections were 5.1% (14/275) in abdominal hysterectomy and 4.2% (1/24) in vaginal hysterectomy. The febrile morbidity (57.1%=8/14) and fever index (52.3±41.1 degree hours) in the infection group were approximately about 4 times higher than those (12.3%=32/261, and 15.6±13.7 degree hours, respectively) in the non-infection group. No significant differences were observed in age, body weight, height of patients, period of operation and blood loss between these 2 groups.
These data suggested that febrile morbidity and fever index were able to indicate the prophylactic effect of antibiotics on patients undergoing abdominal and vaginal hysterectomies.

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