[A questionnaire survey on the theory of postoperative infection prophylaxis in gynecology].

A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among gynecologists in Japan in the period from April to July 2000. Fifty-six of the 83 gynecologists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., Escherichia coli and Bacteroides fragilis group. Use an AMP agent that archives a bactericidal concentrations in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. The newer agents should be considered as a therapeutics for postoperative infections. The therapeutic antimicrobial agents having no cross-resistance to the AMP agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for clean operations are cefazolin (CEZ), followed by cefotiam (CTM) and cefmetazole (CMZ). The most commonly used agent for clean-contaminated operations where low grade level of bacterial invasion expected is CTM, followed by CEZ and CMZ, where as operations where mild grade level of bacterial invasion expected is flomxef (FMOX), followed by CTM and other cephalosporins.

[A questionnaire survey on the theory of postoperative infection prophylaxis in orthopedics].

A questionnaire survey on the theory of postoperative infection prophylaxis was conducted to obtain the consensus on perioperative antimicrobial use among orthopedists in Japan in the period from April to September 2000. Fifty of the 91 orthopedists replied, and the following consensus was obtained. An antimicrobial prophylaxis (AMP) agent should be chosen based on their efficacy against the pathogens expected to be contaminants, such as Staphylococcus spp., and Streptococcus spp., Use an AMP agent that achieves a bactericidal concentration in both the serum and operating site. Use an AMP agent that has little unfavourable side effects. Use an AMP agent that affects minimally the normal bacterial flora. The most commonly used agents are the penicillins and first and second generation cephalosporins. The optimal strategy for most commonly used agents entails infusion of the first dose between approximately 30 minutes pre and post-skin incision and the therapeutic levels should be maintained throughout the operation. The AMP agents having no cross-resistance to the prophylactic agents should be used, if postoperative infection is suspected or developed. The most commonly used agent for both clean operations with or without foreign implants and dirty operations is cefazolin (CEZ), followed by cefotiam (CTM) and flomoxef (FMOX).

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1998 and March 1999].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in Japan since July 1982. This paper describes the results obtained in fiscal 1998 (from April 1998 to March 1999). The number of cases investigated as objectives was 225 for one year. A total of 429 strains (121 strains from primary infections and 308 strains from postoperative infections) were isolated from 183 cases (81.3% of total cases). In primary infections, the isolation rates of anaerobes and Escherichia coli were higher than in postoperative infections, while in postoperative infections, those of Gram-positive aerobes and Pseudomonas aeruginosa were higher than in primary infections. On the whole, among Gram-positive aerobes, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus with high frequency in isolation from postoperative infections. Among Gram-positive anaerobes, Peptostreptococcus spp. and Streptococcus spp. were predominantly isolated. Among Gram-negative aerobes, E. coli, P. aeruginosa, Klebsiella pneumoniae and Enterobacter cloacae were frequently isolated. Among Gram-negative anaerobes, Bacteroides fragilis group was the majority of isolates. In primary infections, the percentage of Gram-negative aerobes has gradually increased since fiscal 1995 or 1996 with these years as the turning point, while those of Gram-positive and Gram-negative anaerobes have gradually declined. In postoperative infections, the percentage of Gram-negative anaerobes has increased continuously since the mid-1980s. The percentage of MRSA among S. aureus rose to 89.7%, which was the highest level since the beginning of this study. The susceptibilities of B. fragilis, which did not show apparent changes, were recognized to have decreased against cephems in fiscal 1998. Among other bacteria in B. fragilis group, development of resistance to cephems has continued on a long-term basis since the mid-1980s. E. coli and K. pneuminiae have obviously not changed in susceptibilities, however, the susceptibilities of isolated strains in fiscal 1998 against high-generation cephems, oxacephems and monobactams have declined. We found neither vancomycin-resistant nor teicoplanin-resistant strains of S. aureus and Enterococcus spp.

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1997 and March 1998].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 19 facilities in Japan since July 1982. This paper describes the results obtained during the period from April 1997 to March 1998. The number of cases investigated as objectives was 215 for one year. A total of 420 strains (170 strains from primary infections and 250 strains from postoperative infections) were isolated from 174 cases (80.9% of total cases). In primary infections, the isolation rate of anaerobic bacteria was higher than in postoperative infections, while in postoperative infections, those of aerobic Gram-positive bacteria and Pseudomonas aeruginosa were higher than in primary infections. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus, which was frequently isolated from postoperative infections. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by P. aeruginosa, Klebsiella pneumoniae in this order, and from postoperative infections, P. aeruginosa was most predominantly isolated, followed by E. coli and K. pneumoniae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. We found neither vancomycin nor arbekacin resistant strains of S. aureus, and found no vancomycin resistant strains of Enterococcus spp. The susceptibility of P. aeruginosa against carbapenems did not decline in the year 1997, while resistance of B. fragilis group against cephems advanced increasingly.

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents: special references to bacteria isolated between July 1996 and June 1997].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 20 facilities in Japan since July 1982. This paper describes the results obtained during period from July 1996 to June 1997. The number of cases investigated as objectives was 217 for one year. A total of 406 strains were isolated from 177 cases (81.6% of total cases). From primary infections 162 strains were isolated, and from postoperative infections 244 strains were isolated, respectively. From primary infections, anaerobic bacteria were predominant, while from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus spp. was the highest. In postoperative infections, the majority of them were Enterococcus faecalis, while in primary infections, many of them were Enterococcus avium. The isolation rate of Staphylococcus spp., especially from postoperative infections, followed that of Enterococcus spp. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by E. coli and Enterobacter cloacae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. The isolation rate of aerobic Gram-negative bacillus has decreased with time, while those of anaerobes like B. fragilis group and of aerobic Gram-positive bacteria have gradually increased in both types of infections. We found vancomycin-resistant strains of neither Staphylacoccus aureus nor Enterococcus spp.; however, the MIC of arbekacin for one of strains of S. aureus was 100 micrograms/ml. Both the MIC90's of meropenem and imipenem/cilastatin against P. aeruginosa isolated in this term were 25 micrograms/ml, which were higher than those against the strains isolated in the previous years. Compared with the isolated strains in the year 1995, progress of resistance against carbapenem antibiotics was confirmed.

[Isolation rate of Enterococcus spp. from surgical infections and their susceptibilities].

Enterococcus spp. isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of Enterococcus faecalis and other Enterococcus spp. were not high from primary infections, and from postoperative infections the isolation rate of other Enterococcus spp. was also low, the isolation rate of E. faecalis was highest from postoperative infections after 1993. 2. Vancomycin (VCM) showed strongest activity against E. faecalis, and followed by those of ampicillin (ABPC), imipenem. levofloxacin (LVFX) and meropenem in this order. Against other Enterococcus spp., VCM showed strongest activity, and followed by those of ABPC and LVFX. There were no resistant strains against VCM.

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1995 and June 1996].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated in a multicenter study in Japan, and the following results were obtained. One hundred and sixty-four strains were isolated from primary infections, and 202 strains were isolated from postoperative infections. From primary infections, anaerobic Gram-positive bacteria were predominant, while from post operative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by that of Staphylococcus aureus from postoperative infections. Among anaerobic Gram-positive bacteria, the isolation rate of Peptostreptococcus spp. was the highest from both types of infections. Among anaerobic Gram-negative, Escherichia coli was the most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order, and from postoperative infections, P. aeruginosa was the most predominantly isolated, followed by Enterobacter spp. and Klebsiella spp. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We noticed that MICs of cefazolin against three out of 23 strains of E. coli were higher than 100 micrograms/ml. Among anaerobic bacteria, there were many resistant strains against penicillins and cephems with MICs higher than 100 micrograms/ml, and the same trend was observed among other Bacteroides spp. and Prevotella spp.

[Bacteria isolated from surgical infections and its susceptibilities to antimicrobial agents. Special references to bacteria isolated between July 1994 and June 1995].

Isolated bacteria from infections in general surgery during the period from July 1994 to June 1995 were investigated by a multicenter study in Japan, and the following results were obtained. One hundred and fifty-three strains were isolated from primary infections, and 143 strains were isolated from postoperative infections. From primary infections, both anaerobic Gram-positive and-negative bacteria were predominant, and from postoperative infections, aerobic Gram-positive bacteria were predominant. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was highest, followed by that of Staphylococcus aureus from both types of infections. Among anaerobic Gram-positive bacteria, the isolation rate of Streptococcus intermedius was highest from primary infections, but from postoperative infections anaerobic Gram-positive bacteria was uncommon. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa in this order. From postoperative infections, P. aeruginosa was most predominantly isolated, followed by Serratia marcescens and E. coli. Among anaerobic Gram-negative bacteria, the isolation rate of Bacteroides fragilis group was the highest from both types of infections. We have noticed that resistant strains against imipenem and ofloxacin were increasing among P. aeruginosa and resistant strains against cefazolin were increasing among E. coli. MICs of cefazolin against four out of 30 strains of E. coli were higher than 100 micrograms/ml, and MICs of imipenem was higher than 50 micrograms/ml against 5 out of 22 strains of P. aeruginosa.

[Isolation rate of Pseudomonas aeruginosa from surgical infections and their susceptibilities].

Pseudomonas aeruginosa isolated from surgical infections during the period from July 1982 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Though the isolation rate of P. aeruginosa was not high from primary infections, it was more frequently isolated from postoperative infections throughout the study period. Enterococcus spp., P. aeruginosa and Staphylococcus aureus including MRSA were predominant among postoperative infections. From the postoperative cases that had previous antibiotic treatment, Enterococcus spp., MRSA and P. aeruginosa were more predominantly isolated than from those without previous treatments with antibiotics. 2. Cefozopran, ceftazidime, cefsulodin, aztreonam, carumonam, gentamicin, amikacin and ofloxacin had strong activities against P. aeruginosa. We recognize recently that antibiotic-resistant strains of P. aeruginosa against imipenem and ofloxacin have been increasing year by year.

[Isolation rate of E. coli from surgical infections and their susceptibilities].

Escherichia coli isolated from surgical infections during the period from July 1983 to June 1995 were investigated in a multicenter study involving 19 hospitals in Japan, and the following results were obtained. 1. Although the isolation rate of E. coli was not high from postoperative infections, it was most frequently isolated from primary infections throughout the study period. E. coli, Klebsiella spp. and anaerobic bacteria were predominant from fresh infections. From the cases that had previous antibiotics treatment, Enterococcus spp. were the most predominant isolates followed by MRSA and Pseudomonas spp. in this order. 2. Against E. coli, cefozopran, carumonam and aztreonam had the strongest activity, followed by cefmenoxime, imipenem, latamoxef, gentamicin and ofloxacin. Recently, we have noticed that antibiotic resistant E. coli strains particularly against cefazolin are increasing year by year.

[Bacteriological and clinical evaluation tazobactam/piperacillin in infectious diseases in surgical field].

We carried out bacteriological and clinical studies on tazobactam/piperacillin (TAZ/PIPC), a combination drug of piperacillin with the new beta-lactamase inhibitor tazobactam, in various infectious diseases in surgical field such as intra-abdominal infections (peritonitis and intra-abdominal abscess), hepatobiliary infections (cholecystitis, cholangitis and hepatic abscess) and secondary infections in wound, etc. The total number of cases treated with the combination drug was 164. Of these cases, 141 cases were assessable for clinical responses including 60 cases with intra-abdominal infections, 38 cases with hepatobiliary infections, and 43 cases with secondary infections. Clinical efficacy rates of the drug were 83.3% in cases with intra-abdominal infections, 86.8% in cases with hepatobiliary infections, and 95.3% in those with secondary infections, hence the overall efficacy rate was 87.9%. In the cases from which beta-lactamase producing strains were isolated, clinical efficacy rates were 84.8% in cases with intra-abdominal infections, 84.6% in those with hepatobiliary infections, and 96.2% in those with secondary infections, hence the overall efficacy rate was 88.9%. Bacteriological efficacy rates were 92.9% in cases with Gram-positive bacterial infections, 64.3% in those with Gram-negative bacterial infections, and 100% in those with anaerobic bacterial infections. Bacteriological efficacy rates were 84.2% in cases with single bacterial infections and 56.5% in those with multi-bacterial infections, and the overall bacteriological efficacy rate was 69.0%. In the cases of infections with beta-lactamase producing strains, bacteriological efficacy rates were 80.0% in cases with Gram-positive bacterial infections, 75.0% in those with Gram-negative bacterial infections, and 100% in those with anaerobic bacterial infections. They were 82.6% in cases with single bacterial infections and 57.9% in those with multi-bacterial infections; the overall bacteriological efficacy rate was 67.2%. The bacterial eradication rate was 79.9% against all the isolates, and it was 79.2% against beta-lactamase producing isolates. In addition, we compared the sensitivity distribution of the isolates to TAZ/PIPC with those to control drugs piperacillin (PIPC), cefotiam (CTM), ceftazidime (CAZ), sulbactam/cefoperazone (SBT/CPZ). The MIC50 and MIC90 values of TAZ/PIPC against all strains were 3.13 micrograms/ml and 50 micrograms/ml, respectively. MIC50 values show that TAZ/PIPC was two times less effective than CAZ and SBT/CPZ but four times more effective than CTM; furthermore, from the MIC90 values, TAZ/PIPC was four times more effective than PIPC, CTM and CAZ. The MIC50 and MIC90 values of TAZ/PIPC against beta-lactamase producing strains were 3.13 micrograms/ml and 50 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

[Bacteria isolated from intraabdominal infection and their susceptibilities to antimicrobial agents].

Bacteria isolated from intraabdominal infections during the period from July 1982 to June 1993 were investigated with regard to their classifications according to a joint research by 9 university hospitals in Japan. The following results were obtained. 1. A total of 971 strains were isolated from 684 out of 597 patients with peritonitis, and 287 strains out of 971 were isolated from postoperative peritonitis. 2. The most predominant organism isolated from patients with acute peritonitis was Escherichia coli (28%), followed by Bacteroides fragilis group (17%), Gram-positive anaerobic cocci (16%), Enterococcus spp. (9%) and Klebsiella spp. (8%). 3. Against E. coli, cefmenoxime, cefuzonam, cefozopran, aztreonam and carumonam showed MIC50 less than 0.05 micrograms/ml. Against B. fragilis group, erthromycin, clindamycin, imipenem, lincomycin and latamoxef showed MIC50 less than 0.78 micrograms/ml. 4. The most predominant organism isolated from patients with postoperative peritonitis was Enterococcus spp. (20%) and followed by Pseudomonas spp. (14%), and Staphylococcus spp. (13%), E. coli (9%), Enterobacter spp. (8%) and Klebsiella spp. (8%). We suggest that cefazolin, cefmetazole, flomoxef, cefmenoxime, cefuzonam, and latamoxef are the first choice agents in empiric therapy for the treatment of acute peritonitis.

[Efficacy of arbekacin, a new aminoglycoside antibiotic, in surgical patients with MRSA infections].

The clinical efficacy of a new aminoglycoside antibiotic, arbekacin (ABK), was studied in surgical patients who had been infected with methicillin-resistant Staphylococcus aureus (MRSA). Six cases of pneumonia, 2 of wound infections and 2 of intra-abdominal infections were treated by ABK alone or ABK together with beta-lactam antibiotics such as imipenem/cilastatin or cefotiam. The overall clinical efficacies against these MRSA infections were excellent in one case, good in 6 and poor in 3. In six cases treated by ABK alone, good clinical responses were obtained in 4 cases. Among 4 cases that received combination therapy with ABK, good responses were obtained in 3 cases. No adverse reactions were found in ABK monotherapy or in combined therapy. These data suggested that ABK is an effective antibiotic on surgical infections caused by MRSA.

[Year to year changes in isolation frequencies of different bacteria from postoperative infections].

Bacterial species isolated from postoperative infections during the period from July 1982 to June 1993 were studied regarding isolation frequencies of different species in different years in a joint research project involving nine (9) university hospitals in Japan. The obtained results are summarized as follows. (1) Altogether, 1,453 strains were isolated with 153 strains obtained during the most recent one year from July of 1992 through June of 1993. The most numerous source of isolation was postoperative intra-abdominal sepsis. (2) Gram-positive cocci were the most often isolated, among them methicillin-resistant Staphylococcus aureus was isolated in increasing frequencies until June, 1992. (3) In the last one year, Enterococcus spp. was isolated the most from postoperative infections followed by Staphylococcus spp. and Pseudomonas spp. Rates of isolation of anaerobic bacteria were relatively low with annual isolation frequencies ranging 8 to 15 per cent.

The inhibitory effect of noradrenaline on thyrotrophin-stimulated 3,5,3'-tri-iodothyronine and thyroxine release is mediated through a Ca(2+)-dependent process in the thyroid gland of the mouse.

We examined the effect of noradrenaline on the release of 3,5,3'-tri-iodothyronine (T3) and thyroxine (T4) from perifused mouse thyroid. Noradrenaline suppressed the thyrotrophin (TSH)-stimulated release of T3 and T4. The addition of prazosin, which is a specific alpha 1 antagonist, or the depletion of Ca2+ from the perifusion buffer completely abolished the inhibitory effect of noradrenaline on TSH-stimulated T3 and T4 release. Noradrenaline did not inhibit TSH-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) release in the presence of 3-isobutyl-1-methylxanthine (IBMX), which inhibits both cAMP-specific and calmodulin-sensitive phosphodiesterases. Noradrenaline significantly suppressed the TSH-stimulated release of T3 and T4 in the presence of IBMX. These results suggest that the inhibitory effect of noradrenaline on TSH-stimulated T3 and T4 release is not mediated through a cAMP-dependent process or the activation of a calmodulin-sensitive phosphodiesterase, and that this inhibition is mediated through a Ca(2+)-dependent process regulated by the alpha 1-adrenergic system in the mouse thyroid.

[Penetration of levofloxacin in bile].

The penetration into bile of a new pyridonecarboxylic acid derivative, levofloxacin (LVFX), was studied in a closs-over method with ofloxacin (OFLX) as the control drug in 6 post-operative patients. The lengths of time to the maximum concentrations in bile and the total areas under the curves were both almost the same for these 2 compounds, although the maximum bile concentration of LVFX was slightly lower than that of OFLX. A stability test for LVFX in human bile revealed that over 95.4% of the initial amount was recovered up to 24 hours after commencement of incubation at a room temperature, thus the stability in bile was similar to that in water. The penetration of LVFX which possesses twice as strong antibacterial activities as OFLX was similar to that of OFLX, suggesting that LVFX is useful against bile duct infections.

[Postoperative infection control in patients with hepatic, biliary tract, and pancreatic cancers].

Postoperative infection occurs more frequently in patients with malignant disease than in patients with benign disease. Postoperative infection control in patients with hepatic cancer, biliary tract cancer and pancreatic cancer is studied. Although in patients with jaundice due to malignancy the rate of positive bacterial culture of the bile collected at the time of PTCD was low, the rate of positive bile culture increased after 10 to 14 days of PTCD. The predominant strain was Enterococcus spp., followed by Klebsiella spp., Enterobacter spp. and E. coli in that order. These bacteria isolated from the bile were considered to be causative organisms of postoperative infection. Prophylactic antibiotics after the operation for jaundice due to malignancy should be chosen based on the results of bile culture. In patients undergoing hepatectomy, which is considered to be an aseptic operation, gram positive cocci such as S. aureus was the most frequently encountered organism. On the other hand, in patients undergoing hepatectomy and intestinal anastomosis, enteric bacteria were frequently isolated from the infectious foci. In this study there were 6 cases of methicillin-resistant S. aureus (MRSA) postoperative infection, 3 cases after pancreatoduodenectomy, and 3 cases after hepatectomy. Even after an aseptic operation, postoperative MRSA infection is likely to occur in patients undergoing a more invasive operation, so hospital infection control should be again emphasized.

[Identification and antibiotic prophylaxis of high-risk patients in biliary tract surgery].

A prospective randomized trial has compared 3 policies of antibiotic prophylaxis in biliary surgery. Patients considered to be high-risked against postoperative infection were randomly allocated to 2 groups: in group CTM-H, patients were given cefotiam; in group CMX-H, patients were given cefmenoxime. Patients free of risk factors (group CTM-L) were all given cefotiam. The high-risk factors adopted in this trial were; emergency surgery, presence of jaundice or cirrhosis, malignant disease, diabetes mellitus, age over 70, recent biliary tract infection, choledocholithiasis, and previous biliary surgery. Postoperative infection occurred in 2.1% (4/190) in the CTM-L group, which was lower compared to 15.5% (11/71) of the CMT-H group (p less than 0.01), and 11.3% (8/71) of the CTM-H group (p less than 0.01). The rates of bacterial isolation from intraoperative bile culture and wound swab were significantly high in the two high-risk groups compared to the low-risk group, but is was not different within the two high-risk groups. These findings suggest that while cefotiam is appropriate for prophylaxis for the low-risk patients, the utmost care should be taken in the high-risk patients to prevent intraoperative contamination along with prophylactic antibiotic therapy which covers the bacteria isolated from the bile.

The operative risk factors of cholelithiasis in the elderly.

A total 725 patients with cholelithiasis were divided into three groups according to age, and the risk factors and morbidity rates compared. Group 1 consisted of those aged younger than 49 years, group 2 of those aged between 50 to 69 years, and group 3 of those aged over 70 years. In group 3, the incidence of calculi in the common bile duct was significantly higher than in the other two groups (p less than 0.05), and therefore, choledochotomy accompanying cholecystectomy was performed more often in this group (p less than 0.01). The rate of complications related to calculi and the presence of underlying disease were also higher in this group than in the two younger groups (p less than 0.05), as were preoperative abnormal liver or renal function tests, anemia and hypoproteinemia (p less than 0.05). The rate of positive bile cultures in group 3 was 75.6 per cent which was again significantly higher than in groups 1 and 2 (p less than 0.01). Postoperative complications appeared in 14.3 per cent of the group 3 patients, which was not statistically higher than in group 2 (9.7 per cent), but the percentages of both groups 2 and 3 were high compared to the 4.3 per cent of group 1 (p less than 0.01). The rates of complications directly attributable to the surgical procedures were 2.0 per cent in group 1, 4.8 per cent in group 2, and 5.1 per cent in group 3 with no significant differences between the three groups. There was no increase in the technical problems associated with the surgical procedures performed on the elderly patients and thus, if the operative risks are precisely evaluated and treated cautiously elderly patients should tolerate surgery for cholelithiasis well.

Alpha 1-adrenergic regulation of thyrotropin-stimulated release of 3, 5, 3' -triiodothyronine and thyroxine from perifused mouse thyroid.

The effect of methoxamine, a specific alpha 1-adrenergic agonist, on the release of T3, T4 and cAMP from perifused mouse thyroid was studied to clarify the role of the alpha 1-adrenergic receptor in the regulation of thyroid hormone secretion. TSH-stimulated T3 and T4 release was inhibited significantly by methoxamine. With regard to cAMP release, methoxamine inhibited TSH-stimulated cAMP release in the presence of 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone but did not inhibit TSH-stimulated cAMP release in the presence of 3-isobutyl-1-methylxanthine. Methoxamine did significantly suppress TSH-stimulated release of T3 and T4 in the presence of each phosphodiesterase inhibitor. Depletion of Ca2+ in the perifusion buffer abolished completely the inhibitory effect of methoxamine on TSH-stimulated T3 and T4 release. The present study suggests that activation of the alpha 1-adrenergic receptor inhibits TSH-stimulated T3 and T4 secretion through a Ca(2+)-dependent mechanism in the mouse thyroid gland.