[Clinical efficacy of levofloxacin (LVFX) single-dose therapy in female acute uncomplicated cystitis].

Treatment of infections by the use of antimicrobial agents should be made essentially in a dose close to the minimally required dose. Acute uncomplicated cystitis in female fits as the subject for a single-dose therapy since it is an infection reactive relatively easily to antimicrobial agents. Accordingly, an assessment has been made regarding the therapeutic results of the single-dose therapy in 76 female cases of acute uncomplicated cystitis by the use of LVFX 200 mg which is a new quinolone. The urinary concentration more than MIC90 to Escherichia coli is sustained for about 3 days by this single-dose therapy. As a result of judging the therapeutic results from the reactions of the three clinical findings of pain on micturition, pyuria and bacteriuria, excellent therapeutic results were obtained with effective rates being 100% (76/76) on the day 3, 93.9% (46/49) on the day 7 and 94.4% (34/36) on the day 14. The rate of cystitic symptoms which recurred posed no problem, being 12.5% (5/40) up to three months, as investigated by a questionnaire. As a result of performing close urological examinations such as cystoscopy on six cases with insufficient results or recurrence, we could detect mild underlying conditions which are considered to be intractable factors in the bladder in three cases. From the above results, the single-dose therapy of acute uncomplicated cystitis in the female by LVFX which is a new quinolone was considered to be an excellent therapeutic drug from its characteristics such as its therapeutic results being the same as the conventional therapy by daily administration, excellent drug compliance, low cost, hard selectiveness of resistant strains, less side effects and furthermore it gives the opportunity of detecting a latent and mild underlying condition.


[An isolation procedure of Chlamydia pneumoniae and Chlamydia trachomatis].

The author devised a method which permits simultaneous isolation and identification of Chlamydia using a slide chamber with 8 wells. Contaminating bacteria were eliminated by filtration with the membrane filter. The procedure allowed isolation of Chlamydia pneumoniae and Chlamydia trachomatis from 11 (10.1%) out of 109 and 10 (9.2%) out of 109 otolaryngologic clinical specimens, respectively. The use of HL cells together with Hela-229 cells had been considered essential to isolate Chlamydia from specimens in this field. The conditions for isolating Chlamydia pneumoniae were similar to those for Chlamydia trachomatis. The slide chamber procedure with membrane filter treated specimens was suitable for simultaneous isolation and culture of various species of Chlamydia and allowed easy differentiation of Chlamydia pneumoniae from Chlamydia trachomatis with identification by the indirect fluorescent-antibody technique. Routine examination of clinical specimens using this procedure should be required in the future in order to better understand chlamydial infections.


[Effect of erythromycin on intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide].

Recently, "low dose and long term" erythromycin (EM) treatment has been reported as effective on chronic lower respiratory tract disease, including diffuse panbronchiolitis (DPB). However the effective mechanism of EM is still obscure. In this study, we investigated the effect of EM on intrapulmonary influx of neutrophils by intratracheal injection of lipopolysaccharide (LPS), and the following results were obtained. 1) The intrapulmonary influx of neutrophils was significantly suppressed (p less than 0.001) in mice intraperitoneally injected with EM at 5 mg per animal 2 hr before intratracheal injection of LPS (control group: 6.5 +/- 0.8 x 10(5) vs EM-treated group: 1.7 +/- 0.3 x 10(5)), but not 10 hr before lung challenge. This inhibition was observed at 6 hr after lung challenge, and became maximum with 84% suppression at 24 hr. 2) The intrapulmonary influx of neutrophils was not affected when EM was injected intraperitoneally daily for 3, 7, or 14 days, and lung challenge was performed 24 hr after the final administration of EM. 3) The number of neutrophils in the peripheral blood was not affected by EM. These results suggest that EM treatment impairs the capacity for pulmonary inflammation by reducing, at least in part, the migration of neutrophils to inflammatory sites.


[Spotted fever group rickettsiosis in Chiba Prefecture].

In Chiba Prefecture, the first patient of infection with spotted fever group Rickettsia was found in 1987, thereafter nine patients were detected serologically by the end of 1990. Patients were found in the villages of Amatsukominato, Katsuura and Ootaki, which were located in southern part of Chiba Prefecture. The illness occurred from June to October. On the other hand, patients with Rickettsia tsutsugamushi were seen from October to September. Difference of prevalent seasons of these two types of rickettsiosis is important to make a clinical diagnosis and serological identification of this spotted fever group rickettsiosis. Antibody of the patients showed the highest titer to YH strain of Rickettsia and showed high cross-reactivity to other spotted fever group rickettsiae. For the diagnosis of the patient serologically, it was confirmed that any strain of spotted fever group Rickettsia were useful.


[Evaluation of aerosol therapy of streptomycin for tracheobronchial and pulmonary tuberculosis].

The clinical features of tracheobronchial tuberculosis are distinct from those of pulmonary tuberculosis in some aspects. Streptomycin (SM) is claimed by some investigators that it has a tendency to promote the development of bronchial stenosis due to scarred healing of the involved endobronchial mucosa, and, for that reason, they recommend not to use it in treatment of bronchial tuberculosis. In some patients with pulmonary tuberculosis, who have renal or hearing disturbance, SM avoided. Yet unless SM is used improvement of tuberculosis could be delayed. It is the purpose of the present investigation to point out that aerosol therapy of SM is useful for patients with respiratory tuberculosis. Furthermore, we wish to demonstrate that we can safely treat the patients with respiratory tuberculosis who suffer from renal function or hearing disorder by use of aerosol therapy of SM. Prior to clinical application of the inhalation therapy, we confirmed that the therapy was not harmful. Serum concentration of SM, when inhaled, was measured in 9 volunteers. Before and after administration of SM aerosol, spirograms were examined in 4 volunteers, nevertheless, no special abnormality was recognized. It seemed that serum concentration of SM after the administration was two low to evoke adverse reactions (less than 3.0 gamma). In 6 patients with pulmonary tuberculosis, blood gases were measured and no obvious change was observed. As a result, it was demonstrated that the endobronchial tuberculous lesions improved faster when treated by inhalation of aerosolized SM as compared with the conventional injection therapy, without evoking any apparent adverse reactions. In some of the patients with pulmonary tuberculosis, it seemed that the therapy was useful.(ABSTRACT TRUNCATED AT 250 WORDS)


[Asporogenic anaerobic thoracic empyema--an experimental model for anaerobic thoracic empyema in rabbits].

Sterile pleural effusion was induced by intrapleural administration of turpentine, and empyema was induced by direct intrapleural inoculation of bacteria in rabbits. Experimental models of anaerobic thoracic empyema were successfully made in this study, using Escherichia coli, Peptostreptococcus asaccharolyticus, Bacteroides fragilis, using the following methods; (1) a single bacterium inoculation of, a) E. coli, b) P. asaccharolyticus, c) B. fragilis, (2) simultaneous inoculations with an aerobe and an anaerobe, a) E. coli + P. asaccharolyticus, b) E. coli + B. fragilis. (3) an anaerobic inoculation 5 days after an aerobic inoculation, a) P. asaccharolyticus inoculation 5 days after E. coli inoculation, b) B. fragilis inoculation 5 days after E. coli inoculation. The developments of several parameters (sialic acid levels, glucose levels, oxidation-reduction potential levels, bacterial counts and WBC counts in the pleural fluid and so on) were measured in each group. There was little difference of the rate of incidence of empyema between each group. Empyema was highly induced even by a single anaerobe inoculation. The following tendencies were observed in development of parameters: (1) sialic acid levels and oxidation-reduction potential levels were decreased only in the conditions being associated by B. fragilis infections. (2) in mixed infections of E. coli and anaerobes, bacterial counts of E. coli increased in number in the late phases of the infections probably by the influences of anaerobes. The experiments of groups (2) and (3) were designed for demonstrations of biphasic infections between aerobes and anaerobes, but it turned out that quite unexpected results were seen in these models.


[Clinicobacteriological study of Pasteurella multocida as a zoonosis (1). Condition of dog and cat carriers of Pasteurella, and the influence for human carrier rate by kiss with the pets].

Pasteurella multocida is a gram-negative short rod-shaped bacteria, which is a part of the indigenous flora of the oral cavity of many animals other than man. The number of reports on cases of infections with this bacterium due to animal bites and/or scratches, bacterial infections of the respiratory tract, sepsis due to this organism and death caused by the bacteria have been increasing in recent years. We investigated P. multocida in the hair and oral cavity of 3 dogs and 29 cats according to the classification of Mutters et al.. We also studied the relationship between the carrier rate for Pasteurella in the oral cavity and kissing of pets in 24 pet owners (3 dogs and 11 cats). No P. multocida was isolated from the hair of neither dogs nor cats. One strain of P. multocida subsp. multocida and two strains of P. stomatis, were isolated from the oral cavity of dogs, and 35 strains of Pasteurella were isolated from the oral cavity of cats. Two strains of P. multocida subsp. multocida, whose biochemical properties were different, were detected in the oral cavity of one cat. In three cats, Pasteurella other than P. multocida subsp. multocida was isolated from the same oral cavity. No Pasteurella was detected in the oral cavity of 19 pet owners who had not kissed their cats, whereas P. stomatis was isolated from the oral cavity of one of 2 pet owners who had kissed their cats and in 2 of 3 pet owners who had kissed their dogs (the same bacteria was isolated from a dog that was being kept by some of these positive pet owners).(ABSTRACT TRUNCATED AT 250 WORDS)


[Detection of polymeric IgA antibody to herpes simplex virus by pretreatment of sera with Streptococcus pyogenes--its application to diagnosis of primary infection].

In 17 patients of genital herpes virus infections, herpes simplex virus (HSV)-specific IgA antibody responses were analyzed using an enzyme-linked immunosorbent assay (ELISA) and the absorption of sera with Streptococcus pyogenes, AW43 and AR1, which bind monomeric IgA (m-IgA) and IgG antibodies, respectively. The ratio of polymeric IgA (p-IgA) to total IgA was calculated from the formula, the p-IgA index = IgA activity after absorption/IgA activity before absorption. In early-convalescent-phase sera from primary cases, the p-IgA indices were 0.5-0.9, whereas in recurrent or provoked cases, they were lower than 0.2. There results indicate that the p-IgA index may be useful for rapid and simple differentiation of primary from non-primary HSV infections.


[The first report of human chronic sinusitis by Pasteurella multocida subsp. multocida in Japan].

A 53-year-old male visited our hospital due to nasal obstruction persisting for 6 months and constant rhinorrhea. Pasteurella multocida subsp. multocida was isolated from his nasal discharge and lavage fluid of the maxillary sinus, and also from the oral cavity of the dog he kept. The bacterial strains isolated from the patient and dog were identical in terms of biochemical properties, and drug sensitivity. Although serotype was different, the strain from the patient showed (A:6) and that from his dog showed (A:5). The microorganism is not present in the general environment. The patient had contact with his dog such as he kissed it frequently, gave it food with his chopsticks et al.. From the mouth of the people who kiss one's dog, we detected Pasteurella of the same character of bacteria as from the mouth of the dog. We detected two Pasteurella multocida of different character from only one mouth of a cat. Pasteurella multocida was checked in only one colony for sero type. Sero type A is the popular type for dogs and cats. The above suggest that their was a high possibility that the Pasteurella multocida subsp. multocida found in the patient was from his dog. In Japan, the incidence of Pasteurella multocida subsp. multocida infection has been increasing. In 1969, the Japanese Ministry of Health and Welfare officially communicated this infection as a zoonosis to related institutions. At both medical and surgical departments, wither the patient keeps a pet should be confirmed during interview, and guidance of pet keeping methods is important in some cases from the aspect of clinical bacteriology.(ABSTRACT TRUNCATED AT 250 WORDS)


[Detection of Neisseria gonorrhoeae from male patients with urethritis by polymerase chain reaction].

A polymerase chain reaction (PCR) procedure was developed for detection of Neisseria gonorrhoeae. Two oligonucleotides based on sequences within a 16S ribosomal RNA gene from N. gonorrhoeae were used as extension primers for the PCR. A single DNA fragment of 206 bp was amplified, when N. gonorrhoeae DNA was template for the PCR. No amplified product was detected in Chlamydia trachomatis DNA, Ureaplasma urealyticum DNA or other bacterial DNAs. The DNA fragment of 206 bp was detected on agarose gel electrophoresis, when DNA of greater than or equal to 6.5 N. gonorrhoeae per PCR was used as template DNA for the PCR. The culture and the PCR were carried out for detection of N. gonorrhoeae in 67 urethral swabs obtained from male patients with urethritis. In 27 of 28 specimens in which N. gonorrhoeae was isolated and identified by the culture, 206 bp DNA fragment was amplified by the PCR, but in one specimen no DNA fragment was detected. In 2 of 39 culture-negative specimens, 206 pb DNA fragment was detected and in the remaining specimens, PCR was negative for N. gonorrhoeae. The overall detection coincidence rate between the culture and the PCR was 95.5% (64/67). Thus, the PCR procedure developed in this study was sensitive and specific for detection of N. gonorrhoeae and could be applied for diagnosis of gonococcal urethritis.


[The long-term chemotherapy with erythromycin (EM) in chronic lower respiratory tract infections--third report: clinical study of cases administered EM over 3 years].

An investigation was made of the use of EM therapy which began in 1986 or earlier in 31 cases with chronic lower respiratory tract infections. 1) Of the 20 cases in which EM (Erythromycin stearate) administration (600-1200 mg/day) was continued for 3 years or more and its usefulness could be evaluated, treatment with this agent was judged markedly effective in three, effective in 14, somewhat effective in two, and ineffective in one. This amounted to an effectiveness rate (effective or better) of 85%. 2) Improved QOL was observed in 15 of the 20 cases. 3) In the Pseudomonas infected cases, a discrepancy was seen between the effectiveness rate of 87.5% and the disappearance rate of the organism (12.5%), while in the Haemophilus cases no such discrepancy was found (75%). 4) EM administration was stopped in 11 cases because of side effects in two (stomatitis, gastrointestinal disorder) death in five, desire of the patient in three, and transfer to another hospital in one. The cause of death cases had no connection with administration of EM. 5) In the three patients who stopped EM on their own, the agent was again administered because of exacerbation of symptoms, although this readministration proved ineffective in two of the cases. The above results suggest that long term EM therapy is useful and that its continued administration is important.


[The role of TNF in septic ARDS].

This study was performed to demonstrate the role of TNF in septic ARDS. The interaction with neutrophil and TNF was examined in both in vitro and in rat experimental observation. The results obtained are as follows: Serum level of natural TNF was significantly increased immediately after the endotoxin injection into the rat vein. In in vitro observation, TNF activated neutrophil and enhanced super oxide production and elastase was released from neutrophil. On the other hand, TNF was inactivated by contact with elastase released from activated PMNs both in dose and in time dependently. Also, in the in vivo study, the serum level of natural TNF that was enhanced by endotoxin injection was continued for a longer period in neutropenic rats than in the normal rat. The lung tissue injury such as cell infiltration, capillary congestion and increased intrapulmonary fluid in morphometric determination were observed only when the extremely high dose of TNF was injected. These findings were more significantly observed in the neutropenic rats than in the normal neutrophil rat. The weaker interaction of PMNs elastase to TNF is suspected in such neutropenic animals. From the above, the role of TNF in septic ARDS may be explained as follows: By endotoxin injection, TNF is released from stimulated macrophages. The released TNF activates neutrophil which plays the main role of septic ARDS. In the usual system, lung tissue damage induced by TNF is inhibited, because TNF is inactivated by elastase released from activated PMNs. However, in neutropenic state, PMNs elastase is not enough to inhibit the TNF action, then the tissue damage is directly induced by TNF. As my conclusion, the role of TNF in septic ARDS is to provide two different ways by the host is condition. One is to activate neutrophils in the usual condition and the another is to introduce direct damage of lung tissue in the neutropenic state.


[An effective concentration method for human immunodeficiency virus type 1 (HIV-1)].

We designed an effective virus concentration method to prevent the infection with human immunodeficiency virus type 1 (HIV-1) in laboratories. The absorbent of Minicon concentrators (Amicon Division, M.R. Grace & Co.-Conn.) was changed to chitin, a mucopolysaccharide extracted from the shells of Japanese pink crab. HIV-1 in the supernatant of HIV-1 infected Molt-4 cells was concentrated by Minicon and the new concentrators. The new concentrator showed good concentration rate and equality of concentration speed.


[Relation of bacterial flora between upper and lower respiratory tracts in patients with long-term tracheostomy].

Throat secretions (TS) and bronchial secretions aspirated from tracheostomy (TSTA) were cultured at the same time in 9 subjects with long term tracheostomy every two weeks from January, 1990 to December, 1990. Total number of each examination in TS and TSTA were 200 times. Mean number of bacteria isolated by single culture were 2.9 strains in TS and 1.8 strains in TSTA. Isolated bacteria were mainly alpha-Streptococcus (84.8%) and Neisseria (69%) in TS, and Pseudomonas aeruginosa (53.5%) and Serratia marcescens (30%) in TSTA. Only 20% of P. aeruginosa or S. marcescens in TSTA were isolated from TS. In 8 cases of 9, P. aeruginosa in TSTA were isolated with every time or long term. There were 14 episodes of respiratory infections in 6 cases. P. aeruginosa were causative organisms in 7 episodes. It suggests that P. aeruginosa tended to colonize in lower respiratory tracts of the patients with long term tracheostomy and to become causative organisms in respiratory infections.


[Protective activity of tea and catechins against Bordetella pertussis].

We examined the bactericidal activity of tea and catechins against Bordetella pertussis. Green tea, black tea and coffee showed marked bactericidal activity at their concentrations in beverages, while pu-erh tea killed the bacteria in a moderate way. (-) Epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) showed also marked bactericidal activity. Green tea and black tea also effectively blocked the adhesion of B. pertussis to HeLa and CHO cells, whereas ECGg and TF3 could not. EGCg and TF3 markedly inactivated leuco-lymphocytosis promoting activity of pertussis toxin. Black tea showed slight but significant inactivation of the activity, whereas green tea showed no inactivation. These results suggest that green tea, black tea, EGCg and TF3 might act as prophylactic agents against pertussis infection.


[Antimicrobial and microbicidal activities of tea and catechins against Mycoplasma].

We examined tea extracts, (-) epigallocatechin gallate (EGCg) and theaflavin digallate (TF3) for their antimicrobial and microbicidal activities against Mycoplasma. Green tea and black tea showed antimicrobial activities against M. pneumoniae. At a concentration of 0.2% green tea and black tea showed microbicidal activities against M. pneumoniae and M. orale but not against M. salivarium. Extracts of pu-erh tea showed a slight microbicidal activity against M. pneumoniae and M. orale. EGCg purified from green tea and TF3 from black tea markedly showed microbicidal activities against M. pneumoniae. M. orale and M. salivarium. These results suggest that tea and catechins can be used as prophylactic agents against Mycoplasma pneumoniae infection.


[Analysis of 84 cases with fungemia].

Eighty-four patients with fungemia were analyzed. Fungi had been isolated by culture of blood samples, including blood from the catheter for intravenous hyperalimentation, between 1986-1990. Candida albicans (39.3%), Candida parapsilosis (20.2%), Candida tropicalis (11.9%), Candida glabrata (10.7%), Candida guilliermondii (4.8%) and Trichosporon beigelii (4.8%) were the most frequently isolated fungal pathogens. Four patients' blood yielded two different fungal species. Fifty-nine cases were male, and 25 cases were female. Forty-six of the 84 patients died (54.8%), but there were no differences in the overall mortality rate as a function of the fungal species or sex. All patients had underlying diseases: solid cancer, 37 cases; cardiovascular diseases, 9 cases; gastrointestinal diseases excluding gastrointestinal cancer, 8 cases; central nervous system diseases, 7 cases; premature infants and congenital abnormality, 7 cases; leukemia, 6 cases and miscellaneous, 10 cases. Twenty-four of the 46 dead cases were autopsied, and eight cases showed systemic fungal lesions. However, in one case of pulmonary cryptococcosis and one case of pulmonary penicilliosis, there was no correlation between the isolation of C. glabrata by blood culture and the pathological findings. A fungus-positive blood culture was surmised to be a result of contamination of the sample in 33 cases, and the mortality rate for those cases was 72.2% (24 cases). For 6 of the corpses, fungal lesions observed at autopsy were compatible with the types of lesions found by the fungi which had been isolated before death. Removal of the catheter reduced the mortality rate to 41.7%. Fungal endophthalmitis was diagnosed in six cases.(ABSTRACT TRUNCATED AT 250 WORDS)


[A clinical study of bacteremia in the last fifteen years].

Between 1976 and 1990, 208 cases of bacteremia in our department were studied. Community acquired bacteremias were only 18 (8.7%) cases. Bacteremias, particularly caused by Gram positive organisms, increased significantly after 1981, compared with the first five years. It was related to the marked increase in cases of venous access devices and less sensitivity of the Gram positive organisms to the new cephem antibiotics. In the study, 144 (69.2%) cases were eradicated. Severe underlying diseases or complication of pneumonia influenced the eradication rate of bacteremia. Bacteremia caused by methicillin resistant Staphylococcus aureus or Pseudomonas aeruginosa showed poor prognosis. The average duration from onset to death, was 5.1 days. Forty cases (62.5%) died within 3 days. Among the 201 cases, leukocytosis (WBC greater than 10,000/mm3) was present in 38.3%, while leukopenia (WBC less than 1000/mm3) in 25.3%. Eradication rate between the two groups was not significant. CRP was elevated (greater than 8.5 mg/dl) in 63.5%. The prognosis of this group was significantly poor. Elevation of serum bilirubin was also related with increase of mortality. According to these results, empiric therapy before the isolation of organisms is the most important strategy for treatment of bacteremia.


[Studies on motile-Aeromonas infection 3). Phage typing of motile Aeromonas isolated from patients with diarrhea].

Phage types were determined for 102 strains of motile Aeromonas isolated from patients with diarrhea at four metropolitan hospitals in Tokyo. The following results were obtained. 1) Of the 102 strains examined, 52 (51.0%) were divided into 28 phage types. This rate was considerably higher, compared to our previous results, namely, 21.7% for strains isolated from natural environments and 25% for those isolated from meats. By bacterial species, phage types could be determined for 33 (52.4%) of 63 strains of A. hydrophila, for 16 (45.7%) of 35 strains of A. sobria, 2 (50.0%) of 4 strains of A. caviae and 1 (100%) strain of Aeromonas spp. 2) Of the 52 strains for which the phage types could be determined, the greatest number (16 strains, 30.8%) were identified as belonging to Type I group. These are followed by 5 strains (9.6%) which were identified as Type I/III group and 2 strains (3.4%) each identified as Type I/II, I/II/V, IV, V and VI groups. The remaining 21 strains were identified as belonging to one of the other phage type groups. Thirty-five (67.3%) of the strains for which the phage types were identified, were found to belong either to Type I group or to combinations with Type I. This demonstrated that 34.0% of the isolates from patients with diarrhea were related to Type I.


[Morphology and immunotyping of AC-43 strain of Chlamydia pneumoniae isolated from a Japanese child].

A strain of Chlamydia pneumoniae (C. pneumoniae) which had been isolated from a Japanese child (AC-43) was examined morphologically and serologically using micro-immunofluorescent (micro-IF) test. Inclusions of AC-43 were stained by an indirect immunofluorescent method using C. pneumoniae specific monoclonal antibody. They were dense round inclusions which had been reported as a characteristic figure for C. pneumoniae. An elementary body (EB) of AC-43 was pear-shaped by electron micrograph, which was the same as previous reports for C. pneumoniae. We produced monoclonal antibodies using purified EB of AC-43 as antigen. Culture fluids of these clones reacted with C. pneumoniae antigens, but did not react with C. trachomatis or C. psittaci antigens by micro-IF tests. There was no difference in morphological and serological findings among standard strains and Japanese isolate of C. pneumoniae.


[Isolation of Chlamydia pneumoniae from a patient with acute bronchitis].

Chlamydia was isolated from the throat of a 15-year-old male patient with acute bronchitis. The Chlamydia isolate, YK-41, was stained with FITC-conjugated monoclonal antibodies specific to C. pneumoniae and the genus Chlamydia, whereas staining of monoclonal antibody specific to C. trachomatis was negative. These results indicated that the strain YK-41 could be identified as C. pneumoniae. Serum IgM antibody against C. pneumoniae was detected in high titer in the patient in the acute phase using the microimmunofluorescence (MIF) test, serum IgG antibody against C. pneumoniae demonstrated a fourfold antibody titer rise between acute and convalescent serum using MIF test. Thus, our patient almost certainly contracted acute bronchitis caused by C. pneumoniae.


[A case of empyema with subphrenic abscess].

A 75-year-old female was admitted to our hospital with complaints of fever, cough and left hypochondralgia. She had been operated for cholecystectomy ten years ago. Chest roentgenogram indicated bilateral pleural effusion. Tube drainage was done to the left thorax and empyema was caused by Bacteroides fragilis and Escherichia coli (E. coli). Though antibiotic therapy was already being conducted, the left hypochondralgia persisted. A CT scan and MRI demonstrated local subphrenic abscess around the spleen due to E. coli. Tube drainage was conducted to the subphrenic abscess under ultrasound control and and the symptoms disappeared rapidly. The present results show that examination of the abdomen is necessary for empyema with complication of compromised host. The past history of abdominal surgery and disturbance in the biliary tract should also be considered.


[A case of mediastinitis and bilateral pyothorax, following acute epiglottitis with concurrent Aspergillus infection].

Life threatening mediastinitis as a complication of acute epiglottitis is very rare. A 38-year-old male in previously good health was admitted to our hospital in a state of unconsciousness. Seven days prior to admission he had complained of a sore throat, dysphagia, high fever and dyspnea. A chest X-ray on admission showed widening of the mediastinum, mediastinal emphysema, subcutaneous emphysema and left pleural effusion. Bronchoscopy showed the swelling of supraglottic structures. He was diagnosed as having acute mediastinitis and pyothorax as a complication of acute epiglottitis, but pathogens were not identified. The blood was hyperglycemic and insulin therapy was started. Though he gradually improved by massive antibiotic therapy, steroid therapy, tracheotomy and surgical drainage of both the left thoracic cavity and the mediastinum, he died suddenly of massive hemoptysis. Autopsy revealed that the acute mediastinitis had healed, but that the Aspergillus infection was present in both lungs and the pericardium. The Aspergillus infection was not lethal in the present case, and it seemed that death had resulted from arterial hemorrhage caused by erosion of the trachea. The present case suggests the need for antifungal therapy even in non-immunocompromised patients in particular when massive doses of antibiotics and steroids are administered.


[A case of Vibrio cholerae non-O1 septicemia with liver cirrhosis].

A case of Vibrio cholerae non-O1 septicemia is described in this paper. A 45-year-old male with a three year history of liver cirrhosis, was admitted to our division with hematemesis, abdominal pain, high fever and a loss of consciousness. Three days before onset of symptoms, he traveled to Ishigaki Island and ate a raw lobster. Two days after, his temperature rose to 39.7 degrees C and the blood pressure dropped to 36/- mmHg. By endoscopic examination, an ulcer was found in the stomach, and the bleeding was stopped by electrical coagulation. Blood culture showed growth of V. cholerae non-O1. The organism was found to be sensitive to OFLX, CZX, MINO, LMOX and CP. Although DIC, infections of fungus and MRSA occurred as complications, he recovered by adequate procedures. Subsequently, he left this division after eight weeks. There are various reports related to V. cholerae non-O1 septicemia in foreign countries, but few cases have been reported in Japan. And these cases had severe underlying diseases such as leukemia and liver cirrhosis.


[Characterization of Rickettsia tsutsugamushi strains newly isolated in Ehime Prefecture, Japan].

Five strains of Rickettsia tsutsugamushi were isolated in Ehime Prefecture during December 1987 to January 1990. Of these, two strains, the Yamazaki and Noma-3, were isolated at Noma area of Imabari city and three strains, the Kakiwara-10, -11, -12, at Kakiwara area of Uwajima city. The Yamazaki strain was isolated from a patient of tsutsugamushi disease and the other strains from wild rodents (Apodemus speciosus). These strains showed virulence in euthymic mice. The calculated LD50 of the Yamazaki and Kakiwara-10 strains showed 10(-3.0) and 10(-1.8), respectively. The immunofluorescent antibody test using thirty monoclonal antibodies to six representative strains, the Gilliam, Karp, Kato, Irie, Hirano and Shimokoshi, revealed that two strains isolated at Noma area, the Yamazaki and Noma-3, were identified as the Karp type and three strains at Kakiwara area, the Kakiwara-10, -11, -12, were identified as the Kato type. It was clarified that the serotypic differences were present among the strains isolated in Ehime Prefecture. Moreover, these five strains isolated in Ehime Prefecture did not react with the serotype-specific monoclonal antibodies to the Irie, Hirano and Shimokoshi strains known as the representative strains of so-called new type of tsutsugamushi disease, showing antigenic differences.


Changing patterns of blood culture isolates from patients with acute leukemia: a review of twenty years' experience.

During the 20-year period, 1972-1991, 286 episodes of bacteremia occurred in 200 (45%) of 445 patients with acute leukemia in a hematology ward, giving an incidence of 482 episodes per 1,000 hospital admissions. The frequency of bacteremia was almost unchanged throughout the study period. The frequency of gram-negative bacilli decreased significantly, however, from 81% of all the isolates for the first half of the study period to 50% for the latter half. Despite the common use of ceftazidime and imipenem during the last 5-year period, Pseudomonas aeruginosa increased in frequency to be the most frequent organism. This was opposite to the decreased frequencies of Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae. The isolates of P. aeruginosa obtained during this period, all of which proved sensitive to ceftazidime and/or imipenem, were almost equally distributed among five serogroups, although a temporal preponderance of a limited number of serogroups was observed during the preceding 15-year period. On the other hand, the frequency of gram-positive cocci increased from 9% in the first decade to 35% in the latter decade. Staphylococcus epidermidis, Enterococcus species and, to a lesser extent, Staphylococcus aureus were ranked as major pathogens. Among the recent isolates of S. aureus, methicillin-resistant strains virtually replaced methicillin-sensitive ones. Therefore, until more effective means for control of P. aeruginosa bacteremia in particular become available, the occurrence of this infection will continue to limit the successful treatment of acute leukemia.


[Limulus test (factor G) and polysaccharides from fungus].

Picogram quantifies per ml of endotoxin showed a positive limulus test. The concentration more than ten pg/ml of curdlan ((1-3)-beta-D-glucan) was also positive to a conventional limulus test, which contains a factor G. One nanogram per ml of CM-curdlan was positive, but higher concentration of 10 pg/ml of CM-curdlan decreased its optical density of the conventional limulus test. More than one hundred ng/ml of mannan from Saccharomyces cerevisiae did not react with factor G. However, a culture supernatant of Saccharomyces cerevisiae activated factor G. This result suggested that beta-glucan activated factor G. In addition, culture supernatant of Aspergillus fumigatus, Rhodotorula rubra, Candida parapsilosis, Candida tropicalis, Candida krusei also activated factor G, but Cryptococcus neoformans did not activate it.


[Comparison of sensitivity of Hep-2 cells with that of HL cells against Chlamydia pneumoniae].

We compared the growth of Chlamydia pneumoniae, reference strain TW183 and an isolate from a Japanese infant, AC43 in HeLa229, HL and Hep-2 cells. The mean number of inclusion-forming units was significantly higher on HL cells than HeLa229 cells, when the cells were not pretreated with DEAE-dextran. When the cells were not pretreated with DEAE-dextran, Hep-2 cells had a higher mean number of inclusion-forming units and a higher yield than other cell lines. Iscove's modified Dulbecco medium enhanced growth of strain TW183 in HeLa229 cells but had a low yield of strain AC43 in Hep-2 cells.


[Clinical studies on pediatric purulent meningitis--clinical symptoms and prognosis].

In 149 patients with purulent meningitis we encountered in the period of 20 years from 1970 to 1990, their clinical symptoms and prognosis were investigated. Death or sequela was noted in many of the patients having loss of consciousness, stiffness of the members and/or cyanosis as primary clinical symptoms, or having hypoalbuminemia (less than 2.5 g/dl) and/or thrombocytopenia as abnormal laboratory findings, or having excessive protein levels and/or excessively low sugar levels in cerebro-spinal fluid. Early initiation of adequate antibiotic therapy, as well as symptomatic treatment using transfusion, steroids and anticonvulsants, are important.


[Clinical studies on pediatric purulent meningitis--statistical analysis of etiology and therapy].

In a total of 149 children with purulent meningitis we encountered in our institute in the last 20 years, the causatives, the changes in therapeutic management and the prognosis were investigated. The causatives could be detected in 109 patients (73%): H. influenzae; 30 patients (20%), S. pneumoniae; 18 patients (12%), E. coli; 13 patients (9%), GBS; 7 patients (5%) and S. aureus; 6 patients (4%). These five causatives were detected in 49% of the total patients, or 67% of the patients in whom causatives could be detected. Of these five causatives, E. coli were detected the most frequently in the first half of 1970's, but, in recent years, the detection of GBS, S. pneumoniae and H. influenzae has been remarkably increasing. In spite of progress in antibiotics, the prognosis of the disease due to S. pneumoniae, GBS and S. aureus was poor. In the majority of the patients who died, the death came within five days after hospitalization due to loss of consciousness, convulsion etc. It is therefore necessary not only to initiate strong antibiotic treatment as soon as possible after early diagnosis, but also to take symptomatic measures such as steroidal treatment, treatment of shock etc.


[Role of capsular polysaccharide and lipopolysaccharide of Klebsiella pneumoniae in experimental mice pneumonia model].

In this study, role of capsular polysaccharide (CPS) and lipopolysaccharide (LPS) of Klebsiella pneumoniae was investigated in experimental mice pneumonia model. Inoculation with K. pneumoniae mucoid strain DT-S into mice lung induced expansive, voluminous lethal pneumonia characterized with thickening of the alveolar septa caused by infiltration of inflammatory cell and packing of bacteria within alveolar spaces. On the other hand, mice lung inoculated with K. pneumoniae DT-X, which was non-mucoid mutant isolated from DT-S during natural passage, showed infiltration of inflammatory cell into alveolar spaces but there was no death of mice during the course of this pneumonia. Inoculation of CPS 100 micrograms of DT-S strain into mice lung induced lesser extent of accumulation of inflammatory cell than that of LPS 4 micrograms of this strain. Stimulation of alveolar and peritoneal macrophage with CPS, even at a concentration of 100 micrograms/ml, induced weaker Interleukin-1 (IL-1) activity than stimulation with LPS 4 micrograms/ml. These results suggest that since CPS of K. pneumoniae DT-S encapsulate bacteria including LPS, CPS may inhibit chemotaxis of inflammatory cell and IL-1 production of macrophage to be induced by LPS during course of pneumonia. It is speculated that existence of CPS have important role in modulating host response to bacterial LPS, and this effect of CPS may be related with difference of pathological findings of lung and lethality between K. pneumoniae DT-S and DT-X.


[Studies on the giardiasis as the zoonosis. III. Prevalence of Giardia among the dogs and the owners in Japan].

To obtain the basic data on the route of Giardia infection as zoonosis, of many regions in Japan, the feces from 2218 dogs were examined for detection of Giardia cysts. Giardia cysts were detected in 239 of the 2218 dogs (10.9%), which was the same as previous reports from America. None were found from the owners of 51 dogs in which Giardia cysts were detected. The detection rates of each facilities were, 68 of 366 (18.6%) from the breeder's kennels, 169 of 1811 (9.3%) in individual houses, 2 of 42 (4.9%) from research institutes. The detection rate of the breeder's kennels was higher than the other two facilities (p less than 0.05, p less than 0.001). The detection rates of Kanagawa and Shizuoka prefectures among 17 regions in Japan were higher than the others (p less than 0.001, p less than 0.05). Especially in Shizuoka, the rate of the individual houses was higher than from breeder's kennels. In kanagawa the rates of the individual houses and the breeders kennels were higher than the mean in Japan (p less than 0.001). Therefore one must instruct the breeders when teaching health education to included zoonosis, and that the detection rate of the age groups of less than 3 years old was high-221 of 1276 (17.3%). Since the detection rates of Giardia cysts in the dogs were low, the possibility that human infection acquired from dogs was low. However, some of patients with giardiasis we encountered had never been abroad, and it is not yet clear whether Giardia is strictly host specific or not, so attention should be paid to the possibility of cross-infection between man and animals.


[Studies on genetic differentiation of Salmonella enteritidis isolates by plasmid profile].

Since 1989, the number of salmonellosis cases caused by S. Enteritidis has increased considerably in Japan. Genetic differentiation of 385 strains isolated from January 1982 to December 1988 and January 1989 to April 1991 were used for plasmid profiles. Plasmids were found in 377 out of 385 strains; therefore, only 8 strains carried no plasmid. Among 377 strains, 15 different plasmid profile types (OP-1 to OP-15) were classified. The most common plasmid profile types from 1982 to 1988 were OP-7 (70 kbp) and OP-8 (70 kbp and 2 kbp). On the other hand, the most common plasmid profile types from 1989 to 1991 were OP-1 (60 kbp) and OP-2 (60 kbp and 54 kbp). Serovar-specific virulence 60 kbp plasmids of S. Enteritidis were identified in 7 plasmid profile types (A total of 200 strains). In the other plasmid profile types, 70 kbp plasmids were found in 5 plasmid profile types (A total of 173 strains). In restriction enzyme analysis of 70 kbp plasmid DNAs obtained from 5 plasmid profile types of S. Enteritidis, we found that these plasmid DNAs shared both 60 kbp and 10 kbp fragments. These results indicate that these plasmid profile types also carried serovar-specific virulence plasmids of S. Enteritidis. The strains of plasmid profile type OP-2 were SA (sulfisoxazole) and SM (streptomycin) resistance, and the 54 kbp plasmids in the strains of OP-2 were transferred by bacterial conjugation into the E. coli strains. All transconjugants acquired SM resistance.


[Microtiter enzyme-linked immunosorbent assay for rubella antibodies in human sera--analysis by parallel line assay method].

Antibodies against rubella virus in human sera were measured by ELISA and antibody titers were calculated by the parallel line assay method. The dose response regression curves of standard sera and test sera containing IgG antibody calculated by the parallel line assay method showed linearity, and were parallel to one another. However, the regression lines of sera positive for IgM antibody against rubella virus were not parallel to one another in the low dilution region, but parallel in the higher dilution region. A good correlation was observed between the rubella IgG antibody titers measured by the hemagglutination-inhibition (HI) test and those calculated by the parallel line assay method. The coefficient of the correlation was 0.781. Time-course studies of IgG or IgM antibody titers against rubella virus in rubella patients or in vaccines with MMR vaccine indicated that the ELISA was more precise and specific method than the HI test. Thus, the parallel line assay method using ELISA is considered to be a more useful method for the detection and quantification of antibodies to rubella than the conventional HI test.


[Detection of Legionella pneumophila using a nested polymerase chain reaction].

We evaluated the usefulness of a Nested PCR method for detecting Legionella pneumophila. This method resulted in L. pneumophila specific detection as far as we evaluated. The first and second step PCR achieved the sensitivity as small as 10 pg and 10 fg of the target DNA, respectively. In the detection from Legionella seeded sputa, the method could detect 0.1 cfu/ml of the bacteria, and it took about 12 hours to detect the target DNA. We demonstrated that the Nested PCR method was superior in sensitivity and rapidity for isolation of the bacteria to the conventional using low pH treatment and selective media for Legionella.


[Incidence of Mobiluncus spp. from the patients with clinical bacterial vaginosis].

Aerobic and anaerobic cultures as well as a Gram stain and wet mount preparations were made of vaginal swabs in twenty patients with clinical bacterial vaginosis. Mobiluncus spp. were detected in 7 cases (35%). Cultures appeared to indicate that mixed abnormal flora between aerobic and anaerobic bacteria are found in bacterial vaginosis, and that Mobiluncus spp. may play a role in bacterial vaginosis.


[Evaluation of the alkaline-phosphatase labeled DNA probes for Mycobacterium tuberculosis and Mycobacterium avium complex].

Non-radioisotopic, alkaline phosphatase-labeled DNA (AP-DNA) probe tests for the identification of Mycobacterium tuberculosis complex (Mtb) and Mycobacterium avium complex (MAC) were evaluated. The overall agreement, sensitivity and specificity of the AP-DNA probes for Mtb and MAC were 100% respectively compared with the conventional biochemical method. Because the procedure is rapid (it can be completed approximately 120 min), safe (it does not use radioisotopes) and convenient (it does not need the special equipment to be performed), it can be easily performed in any clinical laboratory.


[Long-term chemotherapy using erythromycin (EM) for chronic lower airway infection: effectiveness of clarithromycin in EM ineffective cases--the fourth report].

The effectiveness of long-term chemotherapy using Erythromycin (EM) for chronic lower airway infection has been practically proved. However, there still exist some ineffective cases, or cases in which the clinical effect was scarcely seen. In the present study was administered Clarithromycin (CAM) to such cases and found that CAM was effective in alleviating symptoms in some of them. The results were presented along with clinical findings and other basic studies. The subjects were 4 cases in which EM was either ineffective or low in its clinical effect. The subjects consisted of 1 case of DPB and 3 cases of bronchiectasis. EM was clinically ineffective in 2 cases and slightly effective in the two others. The pathogen was Pseudomonas aeruginosa in all cases. The dosage of EM was 200-1200 mg/day. The period of administration ranged from 2 years to 6 years 9 months. CAM was given orally after meals at a dose of either 200 or 400 mg/day. Chemotherapy had continued for 3-8 months at the time of final observation (Feb. 1992). Clinical effectiveness was evaluated on the basis of sputum volume and PaO2 examination, as well as evaluation by the patients themselves. As a result, in all 4 cases, reduction in sputum volume and improvement of PaO2 were observed. All subjects evaluated CAM therapy as being more effective than EM therapy. Moreover, it was found that CAM inhibited both the elastase and leucocidin produced in one of the ineffective cases by P. aeruginosa, whereas EM didnt.(ABSTRACT TRUNCATED AT 250 WORDS)


[Quantitative analyses of the normal throat flora of children with upper respiratory tract infections].

Relationship between the normal throat flora and pathogenic bacteria recovered from the throat in 139 children with upper respiratory tract infections in winter were studied using quantitative analyses. Pathogenic bacteria examined include S. pyogenes, H. influenzae, S. aureus, and S. pneumoniae, and the normal floras include alpha-streptococci, gamma-streptococci, Neisseria species, and Micrococci. Children with S. pyogenes in their throats (S. pyogenes group) were examined with anti-streptococcal antibodies such as anti-streptolysin O, anti-streptokinase, and anti-deoxyribonuclease B. Eighty seven pathogenic bacteria were recovered from 72 children (51.8%) out of 139. S. pyogenes and S. pneumoniae groups showed significantly lower alpha-streptococci and gamma-streptococci in incidence of appearance when compared with children with the no pathogenic bacteria in their throats (no bacteria group). H. influenzae group showed significantly lower gamma-streptococci and higher Neisseria sp. in incidence of appearance compared with the no bacteria group. Positive cases for anti-streptococcal antibodies showed a significantly lower alpha-streptococci in number compared with negative cases for antibodies and the no bacteria group, and a significantly lower gamma-streptococci in incidence of appearance compared with the no bacteria group. These data suggest that the normal throat flora may have a role in prevention of colonization by the pathogenic bacteria in vivo, as were shown in vitro by many authors, and that the quantitative analysis of the normal flora is useful because this methodology might reveal whether the bacteria recovered from the throat show the pathogenicity.


[Plasma beta-glucan levels in deep fungal infections accompanying hematological diseases and clinical efficacy of miconazole--a multi-institutional study].

Miconazole (400-1200 mg/day) was administered to patients with deep mycosis and suspected deep mycosis, and the efficacy evaluated. beta-Glucan was determined as the early diagnostic parameter of deep mycosis, and the relationships between the clinical efficacy of miconazole and the titers of beta-glucan were also evaluated. Forty-nine cases were evaluated, including 2 cases of deep mycosis and 47 cases of suspected deep mycosis. Most of the patients had hematological malignancies. The rate of efficacy was 100% (2/2) in deep mycosis, 66.0% (31/47) in suspected deep mycosis, and 67.3% (33/49) in total. beta-Glucan was determined in 39 cases before the administration of miconazole. The rate of beta-glucan positivity was 100% (1/1) in deep mycosis and 44.7% (17/38) in suspected deep mycosis. beta-Glucan was also determined before and after the administration of miconazole in 11 cases. The titers of beta-glucan became negative in 6 cases, decreased in 2 cases and increased in 3 cases. Thus, the beta-glucan titers became negative or decreased in 72.7% (8/11) of the cases. Efficacy of miconazole was 83.3% (5/6) in the cases in which beta-glucan became negative, 50.0% (1/2) in the cases in which the titers of beta-glucan decreased, and 33.3% (1/3) in the cases in which the titers of beta-glucan increased. Miconazole was effective in the treatment of deep mycosis, and the titers of beta-glucan correlated well with the clinical efficacy of miconazole. The determination of beta-glucan appears to be useful for the diagnosis of deep mycosis.


[A case of tracho-bronchial aspergillosis complicated with acute myeloblastic leukemia].

A 59-year-old male was admitted to our hospital in Jan. 1991 with complaints of general malaise and palpitation. Laboratory findings on admission showed anemia, thrombocytopenia and leukopenia consisted of 2.0% myeloblasts with Auerbodies. The bone marrow study showed granuloid hyperplasia with 45.5% myeloblasts. The diagnosis of acute myeloblastic leukemia (M1) was made. After BHAC-AMP therapy, he obtained complete remission. However, he complained of fever and cough, and his chest X ray film showed a focal infiltrative shadow in the right upper lung field. Antibiotics for bacteria and fungus were administered and the abnormal shadow improved in a week. However, as he had hemosputum, the bronchoscopic examination was performed, and multiple ulcers covered by yellow-white tissue were revealed on the wall of the trachea and bilateral main bronchi. Biopsy specimens obtained by transbronchial biopsy showed bronchial aspergillosis. Though intravenous infusion and inhalation of amphotericin B were effective for aspergillosis, he had a relapse of the leukemia and died in autumn, 1991.


[A case of Trichosporon beigelii peritonitis in CAPD].

Continuous ambulatory peritoneal dialysis (CAPD) was introduced to Japan ten years ago and was established as the treatment for end-stage renal disease along with HD. Although the incidence of peritonitis in CAPD has decreased by educating the patients and parents and the improvement of various devises of CAPD, peritonitis is still one of the major complications of CAPD. Fungus is a rare pathogen for peritonitis in CAPD, but it must be considered as a causative agent in cases of intractable peritonitis. This report describes the first case of Trichosporon beigelii (T. beigelii) peritonitis in CAPD in Japan. A nine year old boy with chronic renal failure due to bilateral vesicoureteral reflux was given CAPD treatment four years prior to admission. This patient had been admitted to our hospital frequently because of recurrent bacterial peritonitis. The peritonitis in CAPD was usually treated by changing the peritoneal fluid and antibiotic treatment. In this case T. beigelii was proved to be a pathogen of peritonitis by culture of CAPD fluid and also serum antibody titers. T. beigelii infection was successfully eradicated from the peritoneal cavity by administration of MCZ and by the removal of peritoneal catheter. The patient was switched from CAPD to HD. In the case of intractable peritonitis in CAPD, rare fungal pathogens such as T. beigelii must be considered as a causative agent.


Concurrent ferromagnetic hyperthermia and 125I brachytherapy in a rabbit choroidal melanoma model.

Ferromagnetic (FM) thermoseeds and radioactive (125I) seeds were combined in an episcleral plaque to give concurrent hyperthermia and irradiation for enhanced tumour destruction. A Greene melanoma cell line was utilized to study the interaction between these treatment modalities. We attached five FM thermoseeds (with an operating temperature of 48 degrees C) in parallel with alternating rows of 125I seeds onto the inner surface of each 14 mm Silastic plaque. Plaques were centred over a 3-6 mm (diameter) intraocular melanoma in each rabbit. Some rabbits were then placed within a heating coil, and their eye tumours were warmed rapidly to therapeutic temperatures (43.6 degrees C across the tumour base) while the temperature of normal conjunctiva across the globe did not exceed 38.5 degrees C. Analysis of 49 treated eye melanomas showed 50% local tumour control at 41.7 Gy for 125I alone, whereas only 9.5 Gy were needed to give the same local control rate after 125I with concurrent FM hyperthermia. Thus, a thermal enhancement ratio of 4.4 was obtained. Hyperthermia alone gave a 20% tumour response rate, but responses were only temporary. We conclude that FM thermoseeds can be used to deliver biologically effective hyperthermia concurrently with radiation, thereby reducing the dose of radiation needed for tumour control.


Intrinsic thermal response, thermotolerance development and stepdown heating in murine bone marrow progenitor cells.

Thermal response, thermotolerance development and stepdown heating (SDH) in the murine bone marrow granulocyte-macrophage (CFU-GM) progenitors were determined in vitro. Marrow was removed from femora and tibia, heated in McCoy's 5A medium plus 15% FBS and cultured in soft agar in the presence of three different sources of colony stimulating factor. D0's (+/- SE) for survival curves of CFU-GM heated in vitro were 147 +/- 13, 71 +/- 9, 37 +/- 2, 19 +/- 0.7, 11 +/- 1, and 4.3 +/- 0.3 min, for temperatures of 41.8, 42, 42.3, 42.5, 43 and 44 degrees C, respectively. Arrhenius analysis showed inactivation enthalpies of 812 +/- 9 KJoules/mole (193 +/- 2 Kcal/mole) above, and 2142 +/- 157 KJoules/mole (509 +/- 37 Kcal/mole) below, an inflection at 42.5 degrees C. Thermotolerance development was evident during prolonged hyperthermia exposure at temperatures below 42.5 degrees C (chronic hyperthermia) as a change in the slope of the survival curves after approximately 110 min of heating. Thermotolerance development at 37 degrees C after exposure to temperatures of 43 degrees C or greater (acute hyperthermia) was assessed by fractionated heat treatments consisting of an initial heat treatment (15 min at 44 degrees C) followed by incubation at 37 degrees C and challenge with 15 min or 25 min at 44 degrees C. Maximum thermotolerance occurred after 210 and 330 min at 37 degrees C, respectively. The half-time for maximum thermotolerance development was 36 min. Depending on the amount of heat damage and the maximum amount of thermotolerance development, the decay of thermotolerance was complete after approximately 48-72 h at 37 degrees C. An exposure of 10 min at 44 degrees C before incubation at 40 or 41 degrees C (stepdown heating) reduced the slope of the 40 or 41 degrees C survival curves by inhibiting thermotolerance development that would have otherwise occurred. D0's were 100 +/- 19 and 45 +/- 5 min for 40 and 41 degrees C incubation preceded by 10 min at 44 degrees C, respectively. These studies indicate that whole-body or regional hyperthermia protocols designed either to treat solid tumours or to purge leukemic stem cells from marrow ex vivo should avoid inadvertent temperature elevations to large volumes of marrow. Although, marrow progenitors are capable of thermotolerance development during exposure to temperatures up to 42.3 degrees C, results suggest that conditions of stepdown heating may prevent thermotolerance development.


Techniques for intraoperative hyperthermia with ultrasound: the Dartmouth experience with 19 patients.

Over the course of 3 years, tumours of 19 patients were heated with ultrasound in the operating room during surgical resection. Immediately following intraoperative radiation therapy, thermocouples were inserted into tumour and adjacent normal structures. Patients were then given a 60-min heat treatment with ultrasound after a 10-15-min heatup period. Temperatures were measured at a total of 133 fixed locations for the 19 patient series. Temperature mapping was done in the tumour volume when logistically feasible. Treatment sites included colorectal (n = 3), portahepatus (n = 1), pancreas (n = 7), liver (n = 1), pelvis (n = 3), sacrum (n = 2), and abdomen (n = 2). A sterile, constant-volume water circulating system was utilized to control surface temperatures. Three generations of completely immersible transducers were designed over the course of this study with a 4-cm height specification. Since the ultrasound transducer was assembled on the sterile field during surgery, a 1, 2 or 3 MHz ceramic element was placed in either a 6, 8 or 10 cm diameter aluminium housing to conform the acoustic field to the tumour size. Average of the maximum temperatures attained was 46.6 degrees C. Temperature with which 90% of all measured points equalled or exceeded (T90) was 39.2 degrees C. The T50 was 42.9 degrees C. This compared favourably with T90 and T50 of 38.8 and 41.9 degrees C, respectively, in our outpatient clinic series, in which superficial tumours were treated with a similar external applicator, and patient tolerance was often a treatment limitation.


Variation in heat sensitivity through the cell cycle of M10 and Burkitt P3HR-1 cells.

The cell-cycle age response to 44 or 45 degrees C hyperthermic treatment was studied in M10, a mutant of mouse L5178Y cells, and human Burkitt P3HR-1 cells synchronized by centrifugal elutriation. Survival response to 44 degrees C hyperthermia or radiation showed that Burkitt cells were relatively hyperthermic resistant and average in radiosensitivity, while M10 cells were relatively hyperthermic sensitive and substantially radiosensitive. A typical age-response to hyperthermia through the cell-cycle was observed in M10 cells, although no significant variation in the response to hyperthermia was demonstrated in Burkitt P3HR-1 cells. Combined effect of procaine with 44 degrees C 20-min treatment for Burkitt P3HR-1 cells showed a substantial enhancement of cytotoxicity in S phase cells. The probable implication of membrane composition, membrane changes due to heat and its modifying agents are discussed. Furthermore, when hyperthermia was combined with radiation in Burkitt P3HR-1 cells, cytotoxic enhancement was observed in G1/S boundary phase, not in S phase.


Potentiation of hyperthermia in a murine tumour by metabolic inhibitors rhodamine 123 and 2-deoxy-D-glucose or 5-thio-D-glucose.

Rhodamine 123 injected into mice on 3 days consecutively before a single hyperthermia treatment (45 degrees C for 15 min) potentiated hyperthermia as evidenced by an increased mean tumour growth delay of a transplantable murine mammary adenocarcinoma (MTG-B). Addition of three daily injections of either 2-deoxy-D-glucose, or 5-thio-D-glucose, coordinated with the rhodamine 123, and administered before hyperthermia, resulted in an additional tumour growth delay, but not large enough to suggest an additional significant interaction between the two drugs and heat. This effect was obtained using doses of the glucose analogues which did not potentiate therapeutically when combined with heat without rhodamine 123. On the third day of treatments, rhodamine 123 or 5-thio-D-glucose, or the two drugs together, 60 min before heating, produced a longer growth delay compared with each combination treatment with drugs administered 15 min before heating. However, this effect was not significant. Results of these experiments suggest that in this murine tumour thermopotentiation can be attained by combining these two classes of metabolic inhibitors with hyperthermia.


Differential thermal sensitivity of tumour and normal tissue microvascular response during hyperthermia.

The goal of this study was to investigate the heat sensitivity of the microcirculation in normal C3H murine leg muscle and a variety of transplanted tumour lines (KHT, SCC-VII, RIF-1, C3H mouse mammary carcinoma, two human mammary carcinomas MDA-468 and S5). Clearance rate of a radioactive tracer monitored following an intra-tissue injection was used as a measurement of microvascular integrity during heat treatment. Clearance rate in all tumours studied was significantly lower after 1 h of heating at 44 degrees C than the initial pretreatment clearance rate. Response of normal muscle differed from that of tumours in that the clearance rate after 1 h of heating at 44 degrees C was similar to the initial clearance rate. Vasculature in the KHT fibrosarcoma was more sensitive to heat treatment than that in other tumours. In response to a heat treatment at 43, 44, 45 and 46 degrees C the same level of microvascular damage occurred in half the time in KHT fibrosarcoma than in normal muscle. Furthermore, vascular damage in both muscle and KHT tumour followed the same relative isoeffect relationship, a 1 degree C change in temperature was equivalent to a change in heating time by a factor of two.


In vitro and in vivo responses of doxorubicin ion exchange microspheres to hyperthermia.

The utility of microspheres as targeted drug delivery agents is addressed with reference to using heat during formulation and to administration in combination with hyperthermia. It was demonstrated that rate of loading of the drug doxorubicin onto resin microspheres is enhanced under conditions of elevated temperature but this was shown to increase the incidence of microsphere aggregation. Total amount of drug loaded was related to time rather than temperature such that low temperature loading for up to 24 h produced optimum quality injectates. However, release of doxorubicin from microspheres was significantly increased during elevations of temperature to 43 degrees C. Thus, during hyperthermia doxorubicin release can be increased to provide periods of high drug availability targeted to tumour tissue for concomitant thermochemotherapy with microspheres. The therapeutic benefit derived from this combined therapy was assessed in 20 rabbits with VX2 carcinoma implanted in the liver. Hyperthermia was delivered by 2450 MHz microwave applicator to the exteriorized liver at 43 degrees C for 30 min, while chemotherapy was administered by intratumoural injection of doxorubicin microspheres (2.3 mg) into each tumour. Both hyperthermia and chemotherapy alone significantly reduced the size of tumours 10 days following treatment (p less than 0.01). However, in animals treated with both modalities, the size of tumours was significantly less than either treatment alone (p less than 0.05). These results provide a strong rationale for combining hyperthermia with targeted chemotherapy using microspheres.


Effect of hyperthermia and protein kinase C inhibitors on DNA synthesis and cell proliferation on Ehrlich ascites tumour cells in vitro.

Effect of hyperthermia and/or protein kinase inhibitors on DNA synthesis and cell proliferation was investigated in Ehrlich ascites tumour cells in vitro. Both H-7 and H-8, potent inhibitors of protein kinase C, suppressed DNA synthesis significantly, but HA1004, an inhibitor of cAMP- and cGMP-dependent protein kinase, did not. Hyperthermia increased greatly the suppressive activity of H-7 and H-8 but not that of HA1004. H-7 also inhibited cell growth. These results suggest that the inhibition of protein kinase C enhances the suppression of DNA synthesis and the proliferation of tumour cells by hyperthermia.


Three-dimensional theoretical SAR and temperature distributions created in brain tissue by 915 and 2450 MHz dipole antenna arrays with varying insertion depths.

Theoretical three-dimensional power deposition and temperature distributions were calculated for interstitial hyperthermia microwave antenna arrays driven at 915 and 2450 MHz in brain tissue. Four dipole antennas were assumed to be placed in a 2 x 2 cm array with varying insertion depths in cylindrical tumour models. The bioheat transfer equation was solved for the three-dimensional steady-state temperature distributions using a finite element method. Homogeneous and non-homogeneous blood flow models were considered. As a basis of comparison of the various temperature distributions, the volume of the tumour heated to greater than or equal to 43 degrees C was calculated. SAR distributions calculated for the 915 MHz antenna arrays in brain tissue were very similar to those calculated for muscle. The 2450 MHz arrays showed similar behaviour to the 915 MHz arrays; however, as the insertion depth increased from slightly less than a full-wavelength there was a single hotspot centred at the antenna junction. For the 2450 MHz arrays, the predicted therapeutic tumour volumes were relatively constant over the entire range of insertion depths considered, and in fact, for most insertion depths considered, the model predicted the 2450 MHz arrays would heat larger therapeutic volumes than the 915 MHz arrays. For the 915 MHz array, at insertion depths between 7.8 and 14.6 cm there was a sharp decrease in the predicted therapeutic volume due to a proximal secondary hotspot in the normal tissue causing overheating. However, when the same size tumour at the same insertion depth was heated with the 2450 MHz array, the hotspot was in the tumour, adding to the volume of tumour that was heated to therapeutic temperatures.


Optimum excitation of phases and amplitudes in a phased array hyperthermia system.

In order to achieve a desired temperature distribution inside and outside of malignant tissues, optimization techniques could be used in phased array hyperthermia systems to control effectively the amplitude and phase of the radiating elements. The optimization of a four-element phased array hyperthermia system operating at 432 MHz is examined theoretically. The proposed technique is based on a detailed physical model of the tissue medium to be heated in terms of both electromagnetic and thermal properties. A penalty function technique using a Newton method is applied to determine the optimum phases and amplitudes of the array. Several array geometries have been studied and numerical results are presented.


Automated mechanical thermometry probe mapping systems for hyperthermia.

In order to better assess temperature distribution patterns in patients, tissue equivalent phantoms, and experimental animals, mechanical devices and automated control systems for positioning temperature probes in implanted catheters and catheters laid on the skin surface have been developed. They employ stepper motor actuated roller and idler wheel drives to move the probes. Two devices incorporate positive positioners in addition to the drive rollers in order to obtain higher positioning accuracy where significant probe to catheter friction is present. Automated systems have been constructed which can simultaneously position, record and display data from up to 10 temperature sensors in a colour-coded position versus temperature format to produce a real time two-dimensional colour-coded pseudo isotherm display. These thermal mapping devices have been used for characterizing the power deposition patterns of several large area microwave applicators (on the surface and at depth within tissue equivalent phantoms), for intraorgan temperature mapping in experimental animals, and for surface and subcutaneous temperature mapping during clinical treatments.


Winner of the Lund Science Award 1992. Thermosensitization induced by step-down heating. A review on heat-induced sensitization to hyperthermia alone or hyperthermia combined with radiation.

A few minute's exposure to a high temperature (sensitizing treatment, ST) may substantially increase the cytotoxic and the radiosensitizing effect of a subsequent heating at a lower temperature (test treatment, TT). This phenomenon, which is known as step-down heating (SDH) or thermosensitization, has been observed both in cultured cells in vitro and in tumours and normal tissues in vivo. The effect of SDH increases with a lowering of TT temperature, but it is rapidly lost at temperatures very close to 37 degrees C. SDH-induced thermosensitization decays within a few hours, when an interval is inserted between ST and TT. In vitro results suggest an exponential decay of the SDH effect with half times ranging from 1.5- to 3.1 h. The effect of SDH increases with increasing ST time or temperature. For single heating, the Arrhenius plot is biphasic with activation energies of 500-800 and 1200-1700 kJ/mol above and below a break point temperature in the region 42.5-43.0 degrees C, respectively. For SDH, the Arrhenius plot gradually becomes monophasic with increasing severity of ST and it approaches asymptotically to an activation energy of about 400 kJ/mol. The reduction of the activation energy depends on cell survival after the priming ST and not on the specific ST heating time or temperature. SDH strongly enhances hyperthermic radiosensitization with a 5-6-fold reduction of the radiation dose required to achieve tumour control. The thermosensitizing and the radiosensitizing effects of SDH have several features in common. Both effects become more prominent when the TT temperature is decreased and when the ST heating time or temperature increases. In addition, the decay kinetics for both effects are comparable. For heat alone, the effect of SDH in tumour and normal tissue seems to be quantitatively similar. However, the therapeutic ratio may be increased by combining SDH with radiation. Biologically, the critical subcellular targets involved in the SDH effect have not been revealed. However, the ability of SDH to inhibit the clearance of heat-induced aggregation of proteins in the nucleus is interesting. Blockage of the nuclear function by proteins is a central theory in the present molecular biological models for both cell kill by heat and heat radiosensitization. Clinically, SDH may be an advantage since even a short exposure to high temperature increases the effect of an otherwise inadequate heat treatment. The disadvantages are that SDH complicates thermal dose calculations, and may cause unacceptable damage to normal tissue.


Early experience of a commercial scanned focused ultrasound hyperthermia system.

Preliminary experiences of the Sonotherm 6500 scanned focused ultrasound (SFUS) system in the hyperthermic treatment of bulky tumours in breast, superficial sites and within the pelvis in 22 patients are reported. Tumour volumes ranged from 235 to 603 cm3 (breast), 105 to 209 cm3 (superficial sites) and 24 to 905 cm3 (pelvis). Temperature distributions in 58 evaluable treatments were analysed in terms of temporal peak and time-averaged temperatures (highest and lowest temperatures, percentage of sensors exceeding index temperatures, etc.) achieved within scanned volumes. Mean number of sensors implanted into tumour was 14 in breast and superficial tumours and approximately 11 in pelvic tumours. Mean time-averaged maximum and minimum temperatures for the best treatments (i.e. for each patient, that with the highest percentage of sensors recording time averaged temperatures greater than or equal to 42 degrees C) administered to patients with tumours in the breast and superficial sites were 44.6 +/- 1.7 degrees C and 39.7 +/- 1.1 degrees C, respectively and the mean number of sensors exceeding 42 degrees C was 58 +/- 19%. In the case of pelvic tumours these figures were 41.6 +/- 0.9 degrees C, 40.0 +/- 0.6 degrees C and 8 +/- 12%, respectively. Patient tolerance to treatments was, in general, good. Areas where technical improvement of the system is appropriate and further research and development are required are identified; these should lead to a better realization of the potential of the SFUS technique, particularly for pelvic tumours.


Quantitative determination of SAR profiles from photographs of the light-emitting diode matrix.

The utility of the light-emitting diode (LED) matrix, i.e. the qualitative localization of maxima and minima in the patterns of the specific absorption rate (SAR), can be extended to quantitative measurements by a method described. With the LED dipoles on the matrix representing light sources of similar characteristics, the minimal field strength necessary to produce light is a criterion which can be easily determined. From the power levels necessary to fulfil this criterion, relative SAR values have been calculated. The attenuation of field strength by the LED matrix has been measured by an additional dipole antenna with fibre-optic read-out, so that the calculated SAR profiles could be corrected for the relatively smaller attenuation near the edges. This technique has been tested for several set-ups in a 'Coaxial TEM applicator' and the resulting SAR profiles along the major axis of the aperture midplane were compared with SAR profiles determined using a single dipole E-field probe. Results show that, from a set of photographs at different power levels, SAR profiles can be constructed with limited accuracy along lines in any direction in the whole aperture midplane and by this the complete two-dimensional SAR pattern can be obtained.


Risk of tumour growth along thermometry catheter trace: a case report.

A patient with recurrent rectal cancer was treated with the combination of radiotherapy plus hyperthermia. Intratumoral thermometry probes were introduced within closed-tip catheters, inserted through the buttocks under computed tomography (CT) control. Catheters were fixed to the skin to stay in place during the whole treatment series. At the end of the radiotherapy series, tumour progression was apparent. Seven months following treatment, tumour growth was visible at the insertion site of one of the catheters. This finding indicates that catheters should not be placed outside the treatment volume involved in any locally curative treatment.


The false localizing signs of increased intracranial pressure.

False localizing signs, although rare, indicate significant increased intracranial pressure with tissue shift, has occurred. A review of the historical perspective highlights the discovery of these false localizing signs, and exploration of the anatomic and physiologic causes provides important insight for neuroscience nurses. Critical thinking skills, and a world view paradigm for clinical practice are developed upon an in-depth understanding of neurologic dysfunction. Collaborative relationships are enhanced by an interdisciplinary approach to assessment of the critically ill neuroscience patient.


An unusual nursing challenge: Guillain-Barré syndrome following cranial surgery.

An 84 year-old white female developed Guillain Barré syndrome (GBS) following a craniotomy for resection of a meningioma. GBS is a rare, idiopathic disease which presents multiple nursing challenges. To effectively care for the patient with GBS, it is necessary to be familiar with symptomatology, incidence and pathology. Using this information, nursing assessment may be performed and interventions developed and individualized as needed.


Experimental thermoradiotherapy of human tumour xenografts in nude mice; design of the hyperthermia system.

An experimental thermoradiotherapy study was started in 1986. For this study a hyperthermia system was developed for heating human tumours xenotransplanted into nude mice. The treatment device was a four-channel computer-controlled hyperthermia system. Temperature was monitored by microwave radiometry at 3 GHz. Specifications of the radiometer were evaluated first under reference conditions. Subsequently, thermal dosimetry was studied using non-invasive measurement of brightness temperature, TOR. Hyperthermia treatments were simulated in phantom material with radiometric monitor values, TR, of 40 and 41. In conjunction with the parameters of TOR, surface temperature, T0, and water bolus temperature, TW, thermal modelling was performed. Influence of a perfused phantom also was studied on microwave thermometry.


Nasoduodenal feeding tubes: prevention of occlusion.

Blockage of nasoduodenal feeding tubes is costly in terms of materials and nursing time, and traumatic to the neuroscience patient. A laboratory experimental study explored ways to decrease obstruction of small bore nasoduodenal feeding tubes when medications are given concurrently with continuous tube feeding. The first part of the study examined type and form of 4 medications in relation to frequency and timing of tube blockage. Trimethoprim sulfamethoxazole (Septra) in dissolved pill form blocked tubes most frequently (F10,77 = 10.333, p < .001) and in the shortest time (F10,77 = 10.534, p < .001). The second part of the study examined different irrigation methods. Irrigation before and after administration of medication and irrigation after medication administration only were significantly better than no irrigation in preventing blockage, both in terms of number of occlusions (F2,87 = 5.486, p < .01) and time to occlusion (F2,87 = 4.556, p < .02). The fact the study was performed in vitro rather than in vivo was a limiting factor. However, results of the study suggest trimethoprim sulfamethoxazole forms occlusions, especially in dissolved form. Elixir of this medication should probably be used whenever available. This study also found that irrigating the tube before and after administration of medications was the most effective of the 3 options examined.


Lethal interaction between heat and methylene blue in Escherichia coli.

Hyperthermia treatment is shown to act synergistically with methylene blue (MB), from the end point of lethality in Gram-negative Escherichia coli bacteria. That this lethality is correlated to the damage produced in DNA by the dye is deduced from the fact that bacteria differing in capacity for repair are almost equally sensitive to heat, but differ considerably in sensitivity to concomitant heat and dye treatment. It is demonstrated that the damage is repairable by the excision-repair system. The role of temperature seems to be that of facilitating the incorporation of the dye, which enables the latter to intercalate into the DNA. Ability of the outer membrane of E. coli AB1157 bacteria to act as a barrier to the penetration of MB remains almost intact up to 46 degrees C, but above this temperature it seems to disrupt abruptly (but reversibly), leading to inactivation of the cells by the dye. Since hyperthermia is in current use for the treatment of cancer, it is suggested that if this synergism also exists in mammalian cells, MB could eventually be used independently of its photodynamic action as an adjuvant in cancer therapy.


Cryptococcal meningitis in patients with AIDS.

In the U.S., cryptococcal meningitis is the most common form of fungal meningitis and a major cause of morbidity and mortality among immuno-suppressed patients. In the AIDS patient, cryptococcal meningitis often presents with fever and headache and is best treated with intravenous amphotericin B and oral flucytosine, or fluconazole. However, toxic effects may result from the therapy. This disease frequently relapses necessitating life-long treatment to prevent reactivation. Essential management principles focusing upon health education are presented to promote comprehensive nursing care for patients testing positive for the human immunodeficiency virus who also have cryptococcal meningitis.


Effects on the expression of heat shock proteins by step-down heating and hypothermia in rat hepatoma cells with a different degree of heat sensitivity.

Thermosensitization induced by pretreatment at supra- and subnormal temperatures, rate of protein synthesis and expression of the major heat shock proteins under such conditions was investigated in relation to intrinsic heat sensitivity of rat hepatoma cells, i.e. Reuber H35 and HTC. The high degree of heat susceptibility of H35 cells was reflected by a high degree of thermosensitization after pretreatment by heat (step-down heating) at temperatures of 42-44 degrees C for 30 min or cold for 16 h at temperatures ranging from 0 to 25 degrees C. Sensitization under step-down heating conditions was found to be paralleled by a delayed recovery of protein synthesis. Despite an increased relative rate, enhancement of the absolute rate of synthesis of the major heat shock proteins, HSP28, HSP60, HSP68, HSP70, HSP84 and HSP100, was less pronounced during step-down exposure. Comparable results were obtained during recovery of sensitized H35 cells at 37 degrees C after exposure to heat following pretreatment at 0 degrees C. Furthermore, clear differences in the regulation of the specific HSP synthesis, depending on the particular treatment protocol, were observed.


Risk of acute hypotension following epidural analgesia during deep regional hyperthermia: a case report.

A potentially dangerous complication occurring during deep regional hyperthermia is described. A patient receiving epidural analgesics for pain caused by a large pelvic recurrent rectal tumour was treated by hyperthermia induced by electromagnetic radiation. The epidural infusion pump failed during heating and further analgesics were administered by bolus injections into the epidural space. Following the second bolus injection, a severe drop in arterial blood pressure was observed. The most likely multifactorial pathogenesis is discussed and measures to avoid such an event are recommended.


The transoral approach to the cervical spine.

The transoral surgical approach is useful for operating on structures at the base of the brain and the upper cervical spinal cord. For example, this route has been used for resecting spinal tumors and clipping vertebrobasilar aneurysms. In the past, this surgical approach was not advocated due to concerns about exposure and infection. However, the availability of the microscope, computed tomography, computed myelotomography, magnetic resonance imaging and intraoperative radiography as well as more effective techniques have improved the diagnosis of pathology of the craniovertebral junction and surgical performance. An understanding of the operative procedures involved with this approach assists the neuro-science nurse in preoperative teaching and anticipating potential postoperative complications.


Comparative study of thermoradiosensitization by misonidazole and metronidazole in vivo: antitumour effect and pharmacokinetics.

Tumour control by local hyperthermia (43.5 degrees C, 30 min) and radiation (20 Gy) given in combination with misonidazole (MISO) or metronidazole (METRO) was studied using FSa-II murine fibrosarcoma. When MISO or METRO (5 mmol/kg) was given 30 min before heat and subsequently treated with radiation, tumour regression was observed for both agents. Radiation dose-response curves for MISO and METRO with heating at 43.5 degrees C for 30 min were identical. Mouse foot reaction was used to evaluate local toxicity following combined heat, a nitroimidazole and radiation treatment. MISO enhanced the magnitude of foot reaction and prolonged the recovery time compared with heat plus radiation controls. There were no observable differences of foot reaction between animals treated with heat plus radiation and those animals treated with heat, radiation and METRO. Pharmacokinetics of the nitroimidazoles heated at 43.5 degrees C for 30 min in FSa-II tumours were investigated as a possible mechanism of thermal sensitization. Local hyperthermia did not alter the pharmacokinetics of METRO. Tumour concentration and tumour/plasma ratio of MISO were slightly decreased during heating. Since the hypoxic metabolism of the nitroimidazoles did not increase significantly during the heat treatment, the thermal enhancement of MISO or METRO radiosensitization cannot be explained by the increase in hypoxic cytotoxicity of the nitroimidazoles at elevated temperature alone. The two nitroimidazoles also were not accumulated in the tumour after heating. Therefore, alternation of pharmacokinetics is not the major mechanism for the thermal enhancement of nitroimidazole radiosensitization. The METRO radiosensitization effect became identical to that of MISO at elevated temperatures is of particular importance in clinical radiosensitization. The very low local and systemic toxicity together with the high efficacy of METRO at elevated temperatures will make it an attractive candidate as a future clinical radiosensitizer.


Olfaction: the neglected sense.

Although olfactory complaints prompt an estimated 200,000 people each year to seek medical consultation in the U.S., there is a dearth of information available in the nursing literature. Recent research links olfaction to degenerative processes in Alzheimer's disease, Parkinson's disease and human immunodeficiency virus infection. This article reviews anatomy and physiology of the olfactory system, describes alterations in smell function and reviews assessment with the University of Pennsylvania Smell Identification Test and odor detection threshold testing. Nurses can advocate thorough assessment and prompt treatment of associated conditions, and educate the patient and family regarding ways to maximize current functioning when olfaction is impaired.


Tolerance of intraperitoneal chemohyperthermia with mitomycin C: in vivo study in dogs.

Tolerance of intraperitoneal chemohyperthermia (IPCH) with mitomycin C (2 mg/kg) by irrigation of the peritoneal cavity via a closed circuit system was evaluated in Beagle dogs for possible use in the management of human peritoneal carcinomatosis. Of dogs, 24 underwent three digestive anastomoses each. They were randomized into three groups: control (n = 6), intraperitoneal hyperthermia (n = 8) and IPCH (n = 10). Peritoneal temperatures were maintained between 41-43 degrees C for 60 min. Tolerance was evaluated through clinical follow-up, biological samples (serum electrolytes, blood counts and serum enzymes), histological examinations and post-mortem macro- and microscopic controls of anastomosis. Mortality and morbidity rates were not different in the three groups. No anastomotic leakage occurred. Evidence of biological toxicity was minimal. Histological examinations showed no definitive tissue damage. IPCH appears to be a safe and reliable device in dogs. Plans to combine IPCH with MMC in surgical resection of patients with peritoneal carcinomatosis are underway.


Implementing managed care and case management: the neuroscience experience.

The case management model for patient care in the neuroscience area was recently implemented in the neurosciences area at a tertiary care hospital. Understanding of the concepts of case management and managed care were essential to the implementation process. Clustering of case types and appointment of group leaders made the development of individual care maps a manageable task. Case management of 2 case types, Parkinson's disease and Guillain Barré syndrome are described, including the rationale for selection, care map development and education. The process of continuing education focused on operational issues regarding utilization of the map and professional issues such as health teaching responsibilities.


Effects of a second heating on rat liver blood flow.

Effects of a second heating on blood flow in the liver and cardiac output were studied in Fischer rats. Heating was done by an experimental capacitive heating device using 8 MHz radiofrequency. Thermometry was performed at seven points around the liver with thermocouples. Blood flow and cardiac output were measured with the radioactive microsphere method. The liver was preheated for 30 min at 41 or 43 degrees C, and then reheated 1-7 days later at 41 degrees C for 15 min. Hepatic arterial blood flow, portal venous blood flow and the cardiac output were measured immediately before and at the end of the reheating. Heating the liver at 41 degrees C for 15 min without preheating slightly increased the hepatic arterial blood flow, and reheating 1-7 days after the first heating caused a greater increase in the hepatic arterial blood flow. Increase in hepatic arterial blood flow caused by reheatings pointed to the development of thermotolerance or thermal adaptation in the hepatic artery. When the liver was heated at 41 degrees C for 15 min without preheating, the portal venous blood flow remained almost unchanged 1-7 days after the heating. On the other hand, a reheating at 41 degrees C for 15 min applied 1-7 days after the preheating reduced the portal venous blood flow. Reduction in portal venous blood flow was approximately parallel to reduction in cardiac output by reheating, pointing to the existence of a causal relationship. Reduction in portal venous blood flow by reheating may also be, in part, due to the decrease in the splanchnic blood flow resulting from a systemic adaptation to the heat stress.


Living with spina bifida.

Health care workers are normally the ones who surround family members as they first begin to cope with spina bifida. It is important to assess family stressors and work with family members to formulate a care plan which assists them to cope with this child. Helping these children grow in society, within our schools and in their jobs, shows that continual observations and interventions may be necessary to maintain optimal growth. I have had the opportunity here to share personal experiences. I can truly say that I look forward to the opportunities ahead and realize that success lies not in my job, but within me.


The neuroscience nurse as an expert witness.

Serving as an expert witness in cases alleging nursing negligence is an interesting, rewarding and stressful role. Having knowledge about qualifications of an expert, what is expected of the expert, how to assess adequacy of nursing care, and how to bill for services may lower the stress. If after careful consideration you choose to serve as an expert witness, you should experience satisfaction knowing you are fulfilling a professional responsibility to maintain standards of care and to protect nurses accused unjustly of negligence.


Ticlopidine hydrochloride.

Ticlopidine, a new prototype antiplatelet agent, offers a significant alternative in the primary and secondary prevention of atherothrombotic stroke. While 2 multicenter trials demonstrated benefits of ticlopidine, this drug is not without risks and limitations and more studies are indicated. The neuroscience nurse must apply current knowledge about ticlopidine in the care for patients receiving ticlopidine therapy.


[Surgical correction of atrioventricular discordance--results and follow-up].

Between January 1977 and October 1991, 47 consecutive patients with atrioventricular discordance, ventriculoarterial discordance, and two ventricles underwent intracardiac repair at the Heart Institute of Japan. Their ages at operation ranged from 2 months to 21 years (average 9.2 years) and period of follow-up ranged from 1 month to 168 months (average 65.1 months). There were five basic anatomic types according to the associated anomalies, grouped into (1) situs solitus, ventriculoarterial (V-A) discordance or double-outlet right ventricle (DORV), ventricular septal defect (VSD) and pulmonary outflow tract obstruction (POTO) (31 patients); (2) situs solitus, V-A discordance and VSD (6 patients); (3) situs solitus, V-A discordance and tricuspid regurgitation (TR) (2 patients); (4) situs inversus, V-A discordance or DORV, VSA and POTO (7 patients); (5) situs inversus, V-A discordance and VSD (1 patient). TR was evident preoperatively in 13 patients (28% of 47 patients), one of whom had Ebstein's anomaly. The conventional operation, which consisted of closure of VSD (34 patients), posterolateral pulmonary outflow enlargement (2 patients), tricuspid valvuloplasty (2 patients), and tricuspid replacement (1 patient) using the anatomical right ventricle as the systemic ventricle, was performed in 35 patients (RV group). The anatomic correction (so-called "double switch operation"), the new alternative operation using the anatomical left ventricle as the systemic ventricle, was achieved in 12 patients (LV group). Anatomic correction consisted of Senning and RV-PA ECR in 3, Mustard and RV-PA ECR in 4, Senning and arterial switch in 2, and Mustard and arterial switch in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)


[Analysis of lymph node metastatic pattern in relation to prognosis and recurrence in pN2 resected lung cancer patients].

Lymph node metastasis was analyzed quantitatively with 4 categories and relation to post surgical survival and recurrence pattern was studied in patients with pN2 primary lung cancer who underwent relatively curative or relatively noncurative resection of the tumors. There was no relation between metastatic coefficient and post surgical survival, however, better survival was observed when the metastatic ratio and metastatic frequency were low and metastatic mode was random or skip pattern rather than sequential pattern. Metastatic coefficient and metastatic frequency were higher in cases with recurrence in lymph nodes but the former was lower and the latter was higher in cases with recurrence in intra-pulmonary dissemination or metastasis. There was no relation between metastatic coefficient and distant metastasis but metastatic frequency was lower in cases with recurrence in distant metastasis. Cases with sequential lymph node metastasis showed a tendency of lymph node recurrence and intrapulmonary metastasis and those with random or skip metastasis of lymph nodes had a tendency of distant metastasis.


[Total repair for truncus arteriosus].

Total repair for truncus arteriosus using an external conduit was performed in 12 patients from 1978 through 1989. Six cases were infants (mean age: 3.4 months) and 6 were children (mean age; 1 years 9 months). Two cases had Collet-Edwards type II truncus and the other 10 cases had type I truncus. One of the infants was associated with an interruption of the aorta and another had a severe regurgitation of the truncal valve (TrV). For external conduits, we used a non-valved conduit in one infant, a composite valved conduit of Dacron containing a heterograft valve in 4 children and a valved pericardial roll made of an autologous or porcine pericardium in 5 infants and 2 children. One infant with a severe regurgitation of the TrV needed valve replacement along with enlargement of the annulus of the TrV. One infant who had replacement of the TrV died early postoperatively. Another infant died 10 months after total repair due to an infection of an external conduit. Cardiac catheterization was performed in all 10 survivors. The mean value for the systolic pulmonary/systemic pressure ratio decreased from 0.98 +/- 0.09 preoperatively to 0.36 +/- 0.09 postoperatively. Replacement of an external conduit was performed due to a conduit stenosis in 2 children and 1 infant, 10 years and 2 months, 7 years and 9 months, and 1 year and 8 months after the total repair, respectively. In one of these 2 children, replacement of the aortic valve was performed due to a severe aortic regurgitation. We conclude that our results of total repair for truncus arteriosus were satisfactory. However, it remains to be solved how to manage an infant with truncus arteriosus associated with a severe regurgitation of the TrV.