Chaunocephalosis in a wild population of Asian open-billed storks in Thailand. The most common trematode collected from Asian open-billed storks (Anastomus oscitans) was Chaunocephalus ferox (80% prevalence). The trematode was paired in granulomas in the intestinal wall. Based on histological examination of these capsules, there was degeneration and necrosis of muscle cells in the tunica muscularis. Granulation tissue with hetrophil and lymphocyte infiltration appeared in the granulomas. Intestinal villi were shorter and wider in infected areas than in non-infected areas. Some intestinal glands were dilated. Storks with high intensity of C. ferox appeared ill. The death of storks infected with C. ferox may result from malnutrition due to the loss of absorptive function of the intestine and from the effect of granuloma formation which might interfere with the intestinal peristalsis.


Clinostomum complanatum (Trematoda: Clinostomatidae) in five new fish hosts in Japan. Metacercariae of Clinostomum complanatum were found in six species of natural freshwater fishes collected at Koyama Pond in Tottori City of Tottori Prefecture, Japan. Five of these fish species are reported here as new records for second intermediate hosts of C. complanatum in Japan: the silver crucian carp (Carassius gibelio langsdorfi), the deepbodied crucian carp (Carassius cuvieri), the carp (Cyprinus carpio), the topmouth gudgeon (Pseudorasbora parva) and the rose bitterling (Rhodeus ocelatus).


Natural infections of Clinostomum complanatum (Trematoda: Clinostomatidae) in wild herons and egrets, Tottori Prefecture, Japan. Nycticorax nycticorax, Ardea cinerea, Egretta garzetta, and Egretta intermedia were naturally infected with Clinostomum complanatum (Trematoda: Clinostomatidae) among fourteen wild herons, seven wild egrets and one wild bittern evaluated at the Veterinary Hospital of Tottori University, Tottori, Japan. The latter three species of heron and egrets are reported for the first time as definitive hosts of this parasite in Japan.


Experimental evaluation of mink and Apodemus speciosus in the Echinococcus multilocularis life-cycle in Hokkaido, Japan. The epizootiological status of mink (Mustela vison) as definitive hosts and Apodemus speciosus as intermediate hosts in the transmission of Echinococcus multilocularis in Hokkaido, Japan, were evaluated by orally inoculating mink with protoscoleces, and A. speciosus with eggs of the cestode, respectively. No tapeworms were recovered from the alimentary tract of the mink, and no hydatid cysts were recovered from the viscera of the egg-inoculated A. speciosus. We conclude that mink and A. speciosus cannot serve as definitive hosts and intermediate hosts of E. multilocularis, respectively, in Hokkaido.


Prevalence of Trichinella spiralis in black bears (Ursus americanus) from Newfoundland and Labrador, Canada. Tongue and diaphragm samples from 158 black bears (Ursus americanus) from Newfoundland and Labrador were examined for Trichinella spiralis. No larvae were detected in samples from the island of Newfoundland but one animal from the Labrador samples was infected. The results of this and other studies suggest a lack of involvement of the black bear in a sylvatic cycle of T. spiralis in eastern Canada.


Insects feeding on desert bighorn sheep, domestic rabbits, and Japanese quail in the Santa Rosa mountains of southern California. Desert bighorn sheep (Ovis canadensis cremnobates), a domestic rabbit (Oryctolagus cuniculus), and Japanese quail (Coturnix japonica) were used as bait animals to collect blood-feeding flies in an area of active blue-tongue and epizootic hemorrhagic disease virus transmission. Precipitin tests were used to confirm the blood source where feasible. Eight species of Culicoides, members of the Leptoconops kerteszi group, Simulium spp., Anopheles franciscanus, and Stomoxys calcitrans were collected from the bighorn sheep. Feeding on the bighorn sheep by Culicoides brookmani (n = 25), C. variipennis (n = 6), C. cacticola (n = 1), and Simulium spp. (n = 3) was confirmed by precipitin testing. Primary species attacking the rabbit were C. brookmani, C. variipennis, and the L. kerteszi group. The quail were attacked primarily by members of the C. copiosus group and the L. kerteszi group.


Ectoparasites of the blackbuck antelope (Antilope cervicapra). Fifty-two free-ranging blackbuck antelope (Antilope cervicapra) from Texas were examined for ectoparasites. Two species of sucking lice (Anoplura), one species of chewing louse (Mallophaga), one species of louse fly (Diptera), and three species of ticks (Acari) were found. This is the first report of the anoplurans Linognathus cervicaprae and L. pithodes from the Western Hemisphere. The southern deer ked (Lipoptena mazamae), the winter tick (Dermacentor albipictus), and the rabbit tick (Haemaphysalis leporispalustris) are reported from blackbuck for the first time. The lone star tick (Amblyomma americanum) and the mallophagan (Damalinia cornuta cornuta) were reported previously from blackbuck in Texas, the latter species under the name Tricholipeurus balanicus balanicus.


Parasites and condition of coexisting populations of white-tailed and exotic deer in south-central Texas. We examined the parasites and physical condition of coexisting white-tailed deer (Odocoileus virginianus), axis deer (Axis axis), fallow deer (Dama dama), and sika deer (Cervus nippon) on the YO Ranch (Kerr County, Texas, USA) during December 1982 to January 1984. White-tailed deer harbored 12 species of parasites. Exotic deer were infected with nine species of parasites. All parasites recovered from exotic deer and white-tailed deer have been reported from white-tailed deer. Exotic deer had higher condition ratings than white-tailed deer.


A case of cleft palate in a Kuril seal (Phoca vitulina stejnegeri), from Hokkaido, Japan. A male pup Kuril seal (Phoca vitulina stejnegeri) from Hokkaido, Japan, was observed with a unilateral and total cleft of the primary palate. Complications included a supernumerary tooth, hypoplasia and asymmetry of the face, and deformation of the eyeball and external auditory meatus. An accompanying pneumonia may have resulted from water flowing into the respiratory system due to imperfect closure of the nostril by the cleft. No other abnormalities were found.


Freemartinism in a captive herd of Rocky Mountain bighorn sheep (Ovis canadensis). Freemartinism in two animals from a captive herd of Rocky Mountain bighorn sheep (Ovis canadensis) at the Denver Zoological Gardens (Denver, Colorado, USA) is described. A young ewe had female external genitalia, a masculine appearance, and demonstrated male behavior as she matured. Another ewe with female external genitalia died as a yearling. Necropsy revealed a non-patent vagina and internal male genitalia. Both females were chimeric with karyotypes containing XX and XY sex chromosomes.


Immobilization of giant Chacoan peccaries (Catagonus wagneri) with a tiletamine hydrochloride/zolazepam hydrochloride combination. A tiletamine/zolazepam combination was used to immobilize 24 captive giant Chacoan peccaries (Catagonus wagneri) at a mean dosage rate of 2.18 mg/kg (SD = 0.46) of body weight, given intramuscularly. The mean induction time (the time from injection until recumbency) was 7.6 min (SD = 2.1). Standing time (the time from injection until the peccary stood without stimulation or assistance) ranged from 90 to 240 min. Tiletamine/zolazepam in combination was an effective and safe immunobilizing agent for giant Chacoan peccaries.


Effects of capture on hematological values and plasma cortisol levels of free-range koalas (Phascolarctos cinereus). Eight free-range koalas (Phascolarctos cinereus) were captured on Kangaroo Island (South Australia) and later transported to the Adelaide Zoological Gardens. Blood samples were collected at the time of capture and at 6 hr, 24 hr and 7 days later. Routine hematological analyses were performed and plasma cortisol levels determined. Significant differences were observed between sampling times for erythrocyte numbers, hemoglobin concentrations, packed cell volumes, mean cell volumes, mean cell hemoglobin concentrations, numbers of leukocytes, neutrophils, lymphocytes and lymphocyte:neutrophil ratio (P less than 0.05). No significant differences were detected between sampling periods in the numbers of monocytes (P = 0.707), eosinophils (P = 0.174) or plasma cortisol levels (P = 0.192).


Xylazine hydrochloride-ketamine hydrochloride immobilization of free-living red foxes (Vulpes vulpes) in Spain. A combination of xylazine hydrochloride-ketamine hydrochloride was used to immobilize 83 wild red foxes (Vulpes vulpes) (15 pups and 68 adults) at Doñana National Park (Spain). Mean ketamine hydrochloride doses were 17.1 mg/kg (SE = 1.53) and 12.3 mg/kg (SE = 0.4) for pups and adults, respectively, and mean xylazine hydrochloride doses for the same groups were 6.2 mg/kg (SE = 0.63) and 4.7 mg/kg (SE = 0.14), respectively. Mean induction times and first reaction times were 1.6 minutes and 22.5 minutes for pups and 3.8 minutes and 39.4 minutes for adults, respectively. Recommended doses for wild adult foxes of unknown weight are 75 mg of ketamine hydrochloride and 20 mg of xylazine hydrochloride.


The exclusion of the elderly and women from clinical trials in acute myocardial infarction. To determine the extent to which the elderly have been excluded from trials of drug therapies used in the treatment of acute myocardial infarction, to identify factors associated with such exclusions, and to explore the relationship between the exclusion of elderly and the representation of women. We conducted a systematic search of the English-language literature from January 1960 through September 1991 to identify all relevant studies of specific pharmacotherapies employed in the treatment of acute myocardial infarction. To accomplish this, we searched MEDLINE, major cardiology textbooks, meta-analyses, reviews, editorials, and the bibliographies of all identified articles. Only trials in which patients were randomly allocated to receive a specific therapeutic regimen or a placebo or nonplacebo control regimen were included for review. Studies were abstracted for year of publication, source of support, performance location, drug therapies to which patients were randomized, use of invasive diagnostic tests or therapeutic procedures, exclusion criteria, size and demographic characteristics of the randomized study population, and principal outcome measures. A total of 214 trials met inclusion criteria, involving 150,920 study subjects. Over 60% of trials excluded persons over the age of 75 years. Studies published after 1980 were more likely to have age-based exclusions compared with studies published before 1980 (adjusted odds ratio, 4.92; 95% confidence interval, 2.33 to 10.54). Trials of thrombolytic therapy involving an invasive procedure were more likely to exclude elderly patients compared with other studies (adjusted odds ratio, 2.45; 95% confidence interval, 1.10 to 5.47). Studies with age-based exclusions had a smaller percentage of women compared with those without such exclusions (18% vs 23%; P = .0002), with the mean age of the study population significantly associated with the proportion of women participants (P = .0001, R2 = .29). Age-based exclusions are frequently used in clinical trials of medications used in the treatment of acute myocardial infarction. Such exclusions limit the ability to generalize study findings to the patient population that experiences the most morbidity and mortality from acute myocardial infarction.


A controlled evaluation of continuous passive motion in patients undergoing total knee arthroplasty. To evaluate the efficacy of continuous passive motion (CPM) in the postoperative management of patients undergoing total knee arthroplasty. A randomized controlled single-blind trial of CPM plus standardized rehabilitation vs standard rehabilitation alone. A referral hospital for arthritis and musculoskeletal care. Consecutive patients with end-stage osteoarthritis or rheumatoid arthritis undergoing primary total knee arthroplasty who had at least 90 degrees of passive knee flexion. One hundred fifty-four patients were eligible and 102 patients agreed to participate and were randomized. Ninety-three patients completed the study protocol. Continuous passive motion machines programmed for rate and specified arc of motion within 24 hours of surgery with range increased daily as tolerated with standardized rehabilitation program compared with standardized rehabilitation program alone. Primary outcomes were pain, active and passive knee range of motion, swelling (or circumference), quadriceps strength at postoperative day 7, as well as complications, length of stay, and active and passive range of motion and function at 6 weeks. Use of CPM increased active flexion and decreased swelling and the need for manipulations but did not significantly affect pain, active and passive extension, quadriceps strength, or length of hospital stay. At 6 weeks there were no differences between the two groups in either range of motion or function. In this series, use of CPM resulted in a net savings of $6764 over conventional rehabilitation in achieving these results. For the average patient undergoing total knee arthroplasty, CPM is more effective in improving range of motion, decreasing swelling, and reducing the need for manipulation than is conventional therapy and lowers cost.


Changes in sequential coronary arteriograms and subsequent coronary events. Surgical Control of the Hyperlipidemias (POSCH) Group. Assessment of the relationship between changes in sequential coronary arteriograms and subsequent clinical coronary events. The Program on the Surgical Control of the Hyperlipidemias, a randomized secondary atherosclerosis intervention trial, obtained coronary arteriograms at baseline, 3, 5, and 7 or 10 years of follow-up. Assessments of changes between pairs of coronary arteriograms were made by two-member panels blinded to the patients' assigned treatment and to the temporal sequence of the films. The relationship of changes between the baseline and the 3-year follow-up arteriograms and subsequent clinical coronary events was examined. Three university hospitals and one private primary care facility. A total of 838 patients, with 417 patients randomized to the control group and 421 to the intervention group. Of all patients, 695 had baseline and 3-year arteriograms. The control group received American Heart Association Phase II diet instruction and the intervention group received identical dietary instruction plus a partial ileal bypass operation. The use of arteriographic changes as a predictor of subsequent clinical coronary events. Changes between the baseline and the 3-year coronary arteriographic overall disease assessment were significantly associated with subsequent overall and atherosclerotic coronary heart disease mortality (P less than .01). For the combined end point of atherosclerotic coronary heart disease mortality or confirmed nonfatal myocardial infarction, a significant relationship between the overall disease assessment and subsequent clinical events was found in the control group (P less than .0001) and in the surgery group (P = .04). For this combined end point, however, the control and the surgery groups were different with respect to clinical coronary events after 3 years, stratified by the baseline to 3-year overall disease assessment (P less than .001, unadjusted; P = .06, adjusted for 3-year clinical covariates). Coronary arteriographic changes can be used in atherosclerosis intervention trials as a limited surrogate end point for certain clinical coronary events. This relationship is statistically compelling for overall mortality and atherosclerotic coronary heart disease mortality. For an individual patient, changes in the severity of coronary atherosclerosis seen on sequential coronary arteriograms can serve as prognostic indicators for subsequent overall or atherosclerotic coronary heart disease mortality.


Access to recombinant erythropoietin by Medicare-entitled dialysis patients in the first year after FDA approval. Examine access to recombinant human erythropoietin (rHuEPO) by dialysis-dependent end-stage renal disease (ESRD) patients during the first year after FDA approval for use in clinical practice and Medicare coverage. Longitudinal and cross-sectional claims data analyses. All US providers of outpatient dialysis treatment. 126,201 Medicare-entitled dialysis patients (approximately 93% of all US dialysis patients). Percentage of patients who received rHuEPO, odds of receiving rHuEPO according to patient characteristics, and cost of rHuEPO to Medicare. One year after FDA approval, 52% of all dialysis and 60% of in-center hemodialysis patients who regularly had Medicare-paid dialysis services received rHuEPO at a monthly cost to Medicare of $19 million (18% of Medicare ESRD outpatient expenditures and 6% of all ESRD program expenditures). Blacks were less likely than whites to receive rHuEPO (odds ratio, 0.88; 95% confidence interval, 0.86 to 0.91). Home peritoneal and hemodialysis patients were less likely than in-center hemodialysis patients to receive rHuEPO (odds ratios, 0.17 and 0.22, respectively; 95% confidence intervals, 0.16 to 0.17 and 0.20 to 0.24, respectively). Use of rHuEPO varied across geographic regions. The odds of receiving rHuEPO were lower for patients of male vs female sex, of ages 35 through 64 years vs less than 35 years and greater than 65 years, with a longer history of ESRD, with polycystic kidney disease vs other causes of ESRD, and receiving care in nonprofit vs for-profit facilities. First-month hematocrits were slightly higher (1.2 percentage points) for patients starting rHuEPO in the 12th month than in the first month after FDA approval. With prompt insurance coverage, the majority of Medicare-entitled dialysis patients received rHuEPO following widespread availability. Factors that may not be related to clinical need (race, setting of care, and geography) possibly influenced early patient access. More attention should be paid to monitoring the appropriate use of high-cost biotechnologic therapy.


Increased incidence of silent ischemia after acute myocardial infarction. To determine the incidence of angina pectoris during induced myocardial ischemia in patients who have had thrombolytic therapy for acute myocardial infarction in comparison with patients with angina pectoris. During percutaneous transluminal coronary angioplasty, both study groups had coronary artery occlusion by the balloon dilatation catheter for 5 minutes. A tertiary, cardiology referral center. Twenty-five patients with angina pectoris who were undergoing angioplasty were compared with 30 patients having angioplasty 2 days after thrombolytic therapy for acute myocardial infarction. Development of angina pectoris during balloon occlusion of the coronary artery was the primary end point; the ischemic response and muscle viability were assessed using both surface and intracoronary electrocardiograms and pulmonary artery wedge pressure. During balloon occlusion 16 (64%) of 25 patients in the angina pectoris group developed angina. In contrast, nine (30%) of 30 patients in the thrombolysis group had angina pectoris during balloon occlusion of the infarct artery (P less than .01). The electrocardiographic response to ischemia and changes in pulmonary wedge pressure were similar in the two study groups. After thrombolytic therapy for myocardial infarction, silent ischemia may be the rule rather than the exception.


The effect of levofloxacin, an optically-active isomer of ofloxacin, on fecal microflora in human volunteers. Following oral administration of levofloxacin (LVFX, (S)-(-)-Ofloxacin; formerly designated as DR-3355) at 200 mg per dose 3 times a day for 7 days to 6 healthy male volunteers, degrees of disturbance of the fecal microflora and fecal drug concentrations were examined. The total viable count remained unchanged during the study period due to the minimal change in the number of members of the family Bacteroidaceae, the most predominant organisms. Most of the aerobes including facultative anaerobes were suppressed by LVFX with only a slight increase in yeasts. In particular, the members of the family Enterobacteriaceae were reduced to below the detection limit on and after day 3 through the time of discontinuation of the drug in all subjects but one. Among the obligate anaerobes, peptostreptococci and bifidobacteria decreased or disappeared in some volunteers, but no significant changes were observed in other anaerobes. Neither Clostridium difficile nor its toxin D-1 was detected in any of the volunteers. No side effects attributable to the drug were observed. During administration, LVFX was detected in the feces at high concentrations which correlated well with the decrease of susceptible members of flora as well as to their detection rate.


[A study on the concentrations of levofloxacin in the gallbladder tissue and bile of patients]. Concentrations of levofloxacin (LVFX, DR-3355), optically active (-)-ofloxacin, in the gall-bladder tissue and bile were determined in patients, and the results were as follows: 1. A single dose of LVFX (100 mg) was administered orally to 6 patients with cholelithiasis about 2 to 3 hours before operation. The range in the gallbladder tissues was 0.34 to 1.59 micrograms/g, while the range in sera was 0.20 to 1.05 micrograms/ml. The ranges in the adipose tissues, gallbladder bile, and common duct bile were 0.07 to 0.26 micrograms/g, 1.8 to 12.2 micrograms/ml, and 1.4 to 5.8 micrograms/ml, respectively. 2. A single dose of LVFX (100 mg) was administered orally to 5 patients with indwelling T-tube. Concentrations of LVFX in excreted bile samples were 1.2 to 2.4 micrograms/ml, 1.3 to 3.5 micrograms/ml, and 1.3 to 2.4 micrograms/ml at 2 to 4, 4 to 6, and 6 to 12 hours after administration, respectively. Therefore, it appears that LVFX may be effective in biliary tract infections, because of its sustained high concentrations in biliary system.


Efficacy of a new quinolone, levofloxacin in patients with surgical infections. The pharmacokinetics and clinical efficacy of levofloxacin (LVFX, DR-3355), an optically pure S(-)-enantiomer of ofloxacin, were studied in patients after surgery. In the pharmacokinetic study, 4 patients undergoing bile drainage were given 2 100-mg tablets by mouth. Peak levels of LVFX were from 2.22 to 4.02 micrograms/ml of plasma at 2-4 hours after the oral administration, and from 7.5 to 11.3 micrograms/ml of bile at 2-6 hours. Forty-three patients with surgical infections, including 16 skin and soft-tissue infections and 12 wound infections, were treated with LVFX. Twenty-eight (70%) of the 40 patients whose results could be evaluated had excellent or good results; 42 (93%) of the 45 causative organisms identified were eradicated. An episode of diarrhea with chills and fever occurred in a 38-year-old man. The results suggested that LVFX has satisfactory antimicrobial effects in surgical infections.


[Fundamental study on levofloxacin in the field of obstetrics and gynecology]. We performed a fundamental study on levofloxacin (LVFX, DR-3355), a new synthetic antimicrobial agent, in the field of obstetrics and gynecology. Concentrations in serum and intrapelvic genital organs (various regions in the uterus, ovary and oviduct) were determined following single oral administration. The transport of LVFX into genital tissues was found to be good, with the tissue levels of 0.64-2.13 micrograms/g after oral administration of 100 mg and 0.77-4.86 micrograms/g after administration of 200 mg. These tissue levels of LVFX were higher than those in serum and exceeded the MIC90 values against most causative organisms isolated from the lesions of obstetric and gynecological infections. These data indicate that LVFX should be useful in the field of obstetrics and gynecology.


[Pharmacokinetic and clinical evaluation of levofloxacin in obstetrics and gynecology]. Levofloxacin (LVFX, DR-3355), a new synthetic quinolone derivative antibacterial agent, was evaluated for its pharmacokinetics and clinical efficacy in obstetric and gynecological infections, and the following results were obtained. Concentrations of LVFX in serum and intrapelvic genital organs such as uterine and adnexal tissues were determined following oral administration of 100 mg. Tissue penetration of LVFX was found to be good, with its tissue levels (Cmax) of 1.17-2.16 micrograms/ml or g after inhalation anaesthesia and 1.15-2.17 micrograms/ml or g after lumbar spinal anaesthesia. LVFX was given to 22 cases of obstetric and gynecological infections with a daily dose of 200-600 mg for 3-14 days and its clinical efficacy was 95% and bacteriological response was 100%. No side effect was observed. From these findings, we consider that LVFX will be a useful antibacterial agent against obstetric and gynecological infections.


[Pharmacokinetic and clinical evaluation of levofloxacin in obstetrical and gynecological field]. Levofloxacin (LVFX, DR-3355) a new synthetic antibacterial agent, was evaluated pharmacokinetic and clinically in the field of obstetrics and gynecology and the following results were obtained. 1. The transport of LVFX into genital tissues (various regions in the uterus, ovary and oviduct) after a single oral administration of 200 mg was found to be good. 2. Sixteen patients with genital infections (endometritis, salpingitis, cervicitis, mastitis) were treated with LVFX at daily doses of 200-300 mg for 5-15 days. The efficacy rate was 100% and no side effect was observed.


[Pharmacokinetic, bacteriological, and clinical studies on panipenem/betamipron in children]. Pharmacokinetic, bacteriological and clinical studies were performed on panipenem/betamipron (PAPM/BP) in children. The results are summarized as follow: 1. Twelve patients with various bacterial infectious diseases were treated with PAPM/BP. Each dose was 20 mg/20 mg/kg, administered 3 times daily, in 30-minute intravenous drip infusion. Treatments were continued for 5-22 days. Clinical efficacies of PAPM/BP in 12 patients with bacterial infections (1 with suspected sepsis, 5 with pneumonia, 1 with acute maxillary sinusitis, 2 with acute otitis media, 1 with cervical abscess and 2 with urinary tract infection complexed type) were evaluated as excellent in 7, good in 4 and fair in 1, with an efficacy rate of 91.7%. Seventeen causative organisms found in 10 patients (Haemophilus influenzae in 4, Branhamella catarrhalis in 3, Streptococcus pneumoniae in 2, Pseudomonas aeruginosa in 2, Staphylococcus aureus in 1, alpha-Streptococcus in 1, Corynebacterium sp. in 1, Peptostreptococcus micros in 1 and Klebsiella pneumoniae in 2) were eradicated except 2 strains (S. aureus and P. aeruginosa) from 1 patient (patient No. 2). No adverse reactions were observed in any of the 12 patients. 2. MICs of PAPM were examined against 22 clinical isolates (H. influenzae 5, B. catarrhalis 3, alpha-Streptococcus 3, S. pneumoniae 2, Corynebacterium sp. 2, S. aureus 1, P. aeruginosa 1, P. micros 1, Enterobacter cloacae 1, Escherichia coli 1, Group D Streptococcus 1 and Staphylococcus epidermidis 1) from children with bacterial infections. PAPM showed a good antibacterial activity comparable to the activity of cefoperazone (CPZ) against S. pneumoniae strains relatively tolerant to penicillins. However, the activity of PAPM against H. influenzae was somewhat weaker than that of CPZ. 3. Pharmacokinetic studies.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical evaluation of panipenem/betamipron in children]. Panipenem/betamipron (PAPM/BP), a new injectable carbapenem antibiotic, was evaluated for its safety and efficacy in children. Ninety three percentage (14 in 15 cases) of various infections were cured with PAPM/BP therapy. Transient skin rash occurred in 1 case, probably due to the histamine-like effect of PAPM/BP. The plasma half life of panipenem was 0.85 +/- 0.07 hours. PAPM/BP was evaluated to be a less-epileptogenic carbapenem antibiotic.


[Studies on panipenem/betamipron in the pediatric field]. Pharmacokinetic and clinical evaluations of panipenem/betamipron (PAPM/BP) were carried out in pediatric patients. The following results were obtained: 1. Upon 30-minute intravenous drip infusion at a dose of 20 mg/kg, plasma concentrations of PAPM/BP reached their peaks at the end of drip infusion with average values of 62.94/47.32 micrograms/ml, and their plasma half-lives were 1.00/0.51 hour in the beta-phase. Upon 30-minute intravenous drip infusion at a dose of 10 mg/kg, peak plasma concentrations were 32.10/23.76 micrograms/ml and plasma half-lives were 0.93/0.59 hour. 2. The urinary excretion rates of PAPM/BP after 30-minute intravenous infusion at doses of 20 and 10 mg/kg were 25.09/81.04% and 32.14/84.66%, respectively. 3. PAPM/BP was administered to 18 cases (upper and lower respiratory tract infections, pneumonia and urinary tract infections) at daily doses of 30-88.9 mg/kg/day divided into 3 dosages using 30-minute intravenous drip infusion. Clinical responses were "excellent" in 12 patients, "good" in 5, and "poor" in 1, hence an efficacy rate of 94.4% was obtained. 4. Bacteria identified from various diseases involved 11 strains of 6 species, and the eradication rate was 90.9%. 5. No side effect was recognized in any patient. Laboratory test results showed abnormalities in including 1 case with leukopenia, and in 2 cases with elevation of GOT and GPT.


[Bacteriological and clinical studies of panipenem/betamipron in pediatrics]. We carried out bacteriological and clinical studies of panipenem/betamipron (PAPM/BP), a newly-developed carbapenem antibiotic, in pediatrics, and the following results were obtained: 1. When antibacterial activities of panipenem (PAPM) were determined, it was found that MICs against such Gram-positive cocci as Staphylococcus aureus and Streptococcus pneumoniae and against such Gram-negative rods as Escherichia coli, Haemophilus influenzae, Pseudomonas aeruginosa, and Branhamella catarrhalis were all sufficiently low. 2. PAPM showed better MIC-correlated antibacterial activities against 215 subcultured strains of methicillin-resistant S. aureus (MRSA) than imipenem. 3. Clinical efficacies were evaluated to be excellent in 23 of 34 patients treated with PAPM/BP, excluding 3 patients from the efficacy evaluation. In addition, good responses were obtained in 10 patients but poor response in one, showing the overall efficacy rate of 97.1%. As for bacteriological efficacies, the eradication rate was also determined to be high, 92.6%. 4. As for side effects, rash appeared in 2 patients, and soft stool and diarrhea occurred in one each. The overall incidence of side effects was calculated to be 10.8%. As for abnormal laboratory findings, increases of eosinophiles in 4 patients, thrombocytes in 2, total bilirubin in 1, and GOT in 1 were observed. From these results, PAPM/BP was thought to be a highly useful drug in pediatrics.


[Pharmacokinetic and clinical studies on panipenem/betamipron in the pediatric field]. Panipenem/betamipron (PAPM/BP), one of the carbapenems, was studied for its absorption and excretion, and clinical efficacy. The following is a summary of the results: 1. Absorption and excretion: Fourteen patients with their ages between 2 years and 14 years were administered with PAPM/BP 10 mg/kg, 20 mg/kg or 30 mg/kg, in 30-minute intravenous drip infusion. Maximum serum levels of PAPM, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg of PAPM/BP, were 27.37 micrograms/ml, 59.3 micrograms/ml, 91.7 micrograms/ml, respectively, at the end of infusion. The half-lives of the 3 dose levels were all within 0.90-0.96 hour. Mean peak serum levels of BP, at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 21.77 micrograms/ml, 35.29 micrograms/ml, 50.08 micrograms/ml, respectively, with half-lives of 0.55-0.63 hour. Urinary recovery rates of PAPM in the first 8 hours after administration at dose levels of 10 mg/10 mg/kg, 20 mg/20 mg/kg and 30 mg/30 mg/kg, were 15.9-31.1%, 15.3-36.9%, 11.0-40.5%, respectively, and those of BP during the same time were 33.1-79.1%, 41.3-93.4%, 12.9-94.4%, respectively. 2. Thirty-nine patients, including 2 with purulent meningitis, 1 with septicemia (suspect), 18 with acute pneumonia, 5 with bronchiolitis, 2 with tonsillitis (unable to receive oral antibiotics), 3 with cervical purulent lymphadenitis, 2 with bacterial enteritis, 6 with urinary tract infections were treated with PAPM/BP at dose levels of 30-100 mg/kg/day. Clinical responses in the patients were excellent or good. Even 2 patients with purulent meningitis were treated with PAPM/BP at dose levels of no less than 20 mg/kg x 3 and 33 mg/kg x 3. Most of respiratory and urinary tract infection cases of moderate severities were treated at dose levels of 30-60 mg/kg/day, i.e., 10 mg/kg x 3 or 20 mg/kg x 3. No adverse reaction was observed. One patient suffered from frequent watery diarrhea but the drug was continued to be administered and the patient recovered quickly. Abnormal laboratory findings were noted, in 2 cases with elevation of platelet, in 1 case with elevation of GOT, in 1 case with elevation of monocyte, in 1 with eosinophilia, in 1 with eosinophilia and decrease in platelet count, in 1 with eosinophilia and elevation of GOT and in 2 with elevation of GOT and GPT, but these abnormalities in the 9 cases were slight and transient.


[A study on the disc sensitivity test for cefodizime]. Susceptibilities of 289 strains of 34 bacterial species to cefodizime (CDZM) were determined using the 2-fold agar dilution method in parallel with the measurement of inhibition zone diameters in the single-disc method under the experimental conditions established by Kanazawa. The experiments demonstrated a significant correlation between MIC by the dilution method and diameter of inhibition zone in each of the conventional, overnight assay (about 16 hours incubation), thus the applicability of the single-disc assay for CDZM was established. Analysis of the data obtained using discs containing 30 micrograms of CDZM/disc revealed that the primary regression equation was in the form: D (Diameter, mm) = 32.3-13.5 log MIC (micrograms/ml) in the conventional assay for staphylococci, Enterococcus group and glucose-non-fermentative Gram-negative rods. For other bacteria, the primary regression equation was in the form: D (diameter, mm) = 24.1-8.4 log MIC (micrograms/ml) in the conventional assay. The range of variations in MICs estimated from diameters of inhibition zones in the disc test was then calculated in comparison with that in MIC determined by the 2-fold agar dilution test to estimate experimental errors which may be involved in the determination of MICs of CDZM using the single-disc assay.


[Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. III. Synergistic action with gentamicin]. An in vitro investigation was done on antimicrobial activities of cefodizime (CDZM) in combination with gentamicin (GM) against clinically isolated Gram-negative rods. The results are summarized as follows. 1. Combined antimicrobial activities were dependent on antimicrobial activities of GM, similar to the CDZM + sisomicin (SISO) combination. The combined activities were concentration dependent, and they were more strongly dependent on GM concentrations than on CDZM concentrations. The obtained results suggested that synergistic or cooperative antimicrobial activities of the combination would be expected when GM concentrations in blood are at or somewhat lower than 1 MIC, and clinical activities would be exerted regardless of the presence of CDZM resistant organisms, similarly to CDZM+SISO combination. 2. It seems possible that, with regard to combinations of beta-lactam antibiotics and aminoglycoside antibiotics, there exist universal rules that combined activities are dependent on activities of aminoglycoside antibiotics, and that stronger concentration dependencies on aminoglycosides would be observed than those on beta-lactams.


[Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. IV. Synergistic action with dibekacin]. Antimicrobial activities of cefodizime (CDZM) in combination with dibekacin (DKB) were studied in vitro against clinically isolated Gram-negative rods. The results obtained are summarized as follows. 1. Similarly to combinations of CDZM+sisomicin (SISO) and CDZM+gentamicin (GM), combined activities of CDZM and DKB were dependent on antimicrobial activities of DKB, and the combined activities were more strongly dependent on DKB concentrations than on CDZM concentrations. The obtained results suggested that synergistic or cooperative antimicrobial activities of the combination would be expected when DKB concentrations in blood are at or somewhat lower than 1 MIC, and that clinical activities would be exerted regardless of the presence of CDZM resistant organisms, similarly to CDZM+GM combination. 2. As we have suggested previously, it seems possible that, with regard to combinations of beta-lactam antibiotics and aminoglycoside antibiotics, there exist universal rules that combined activities are dependent on activities of aminoglycoside antibiotics, and that stronger concentration dependencies on aminoglycosides would be observed than those on beta-lactams.


[Clinical laboratory approach to evaluate efficacy of amikacin. Reevaluation of in vitro MIC break points in disc susceptibility test]. Antimicrobial activities of amikacin (AMK) against 269 strains of various clinical isolates obtained in 1989 were determined and the reliability of the AMK disc susceptibility test in estimating approximate values of MICs was studied. In addition, clinical significance of various systems for the interpretation of the disc tests was evaluated to determine more useful method in the evaluation of clinical efficacy of AMK. Included in the study were a 3 category system of NCCLS, a 4 category system used in Japan, and the system proposed by the British Society for Antimicrobial chemotherapy. In this study, MICs were determined using the Mueller-Hinton agar containing 50 mg/L of Ca and 25 mg/L of Mg at an inoculum level of 10(3-4) CFU/ml. MIC80 values of AMK against Staphylococcus aureus and Staphylococcus epidermidis were 6.25 and 25 micrograms/ml, respectively. Those against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Enterobactor aerogenes, and Citrobacter spp. were less than 3.13 micrograms/ml. MIC values against Pseudomonas aeruginosa and Serratia marcescens were both less than or equal to 12.5 micrograms/ml. The disc susceptibility test was carried out according to the instruction in the Showa disc manual. Inhibition zones obtained with the disc method were compared with MIC values. The results of AMK disc susceptibility test obtained either with 30 micrograms discs or 10 micrograms discs were well correlated with MICs, indicating that the disc method was reliable in estimating approximate values of MICs (r = -0.807 to -0.897, P less than 0.01 in both instances). In the 4 category classification system currently used in Japan, the break points in MIC values of AMK proposed are (+3) MIC less than or equal to 3 micrograms/ml, (+2) MIC greater than 3-15 micrograms/ml, and (+) MIC greater than 15-60 micrograms/ml. The results obtained with Showa 30 micrograms discs and 30 micrograms discs prepared in this laboratory showed false positive results in 13% and 10.8% of the samples, and false negative results in 1.5% and 3.3%, respectively. In the 3 category classification system of NCCLS, the MIC break points proposed are defined sensitive (S) for MIC less than or equal to 16 micrograms/ml and resistant (R) for MIC greater than or equal to 32 micrograms/ml. In this study, the 30 micrograms disc tests using the above-mentioned 2 different types of discs resulted in false positive responses in 6.3% and 5.2% of the samples tested and false negative results in 1.1% and 1.9% of the samples, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)


[Therapeutic efficacy of norfloxacin for experimental osteomyelitis in rabbits]. Norfloxacin (NFLX), a new quinolone antibiotic agent, was evaluated for its efficacy in experimental osteomyelitis in rabbits. Osteomyelitis was induced in male rabbits by the inoculation of 10(7) CFU/ml (0.1 ml) of Staphylococcus aureus (MIC for NFLX: 0.78 micrograms/ml) with 0.4 ml of 3% sodium tetradecyl sulphate into the medullary cavity of the proximal tibia. The rabbits were divided into 3 different groups of 4 animals each. The animals in 2 groups were orally administered with NFLX; 100 mg/kg once-daily (group 2) and 50 mg/kg twice-daily (group 3) for 7 days from the 6th hour after inoculation. Group 1 was established as a control without administration of NFLX. All animals were sacrificed on the 7th day after inoculation. Acute osteomyelitic changes were found microscopically in all animals in group 1. In each of the 2 therapeutic groups, incidence of microscopic changes was 50% associated with remission of S-sialic acid value. Thus, NFLX may be considered a useful antimicrobial agent for the treatment of suppurative osteomyelitis.


[Pharmacokinetics and clinical efficacy of ciprofloxacin in aged patients with chronic respiratory diseases]. Pharmacokinetics and clinical efficacy of ciprofloxacin (CPFX) were investigated in aged patients with chronic respiratory diseases. Serum and sputum concentrations of CPFX were determined upon oral administration of 200 mg CPFX in 6 aged patients with chronic respiratory diseases (mean age = 78.8 +/- 3.2 years, 2 cases diagnosed chronic obstructive pulmonary disease with pneumonia, 3 cases were diagnosed bronchiectasis with acute exacerbation, and 1 case diagnosed chronic lung abscess). Maximal serum concentrations in these patients were 0.88-1.29 micrograms/ml (mean = 1.08 micrograms/ml). Thus, maximal serum concentrations of CPFX after oral administration in these aged patients were slightly lower than those in young subjects. However, peak sputum levels of CPFX following oral administration of 200 mg CPFX ranged from 0.53 to 1.47 micrograms/ml at 1-4 hours. These sputum concentrations of the 6 patients were sufficiently high for the inhibition of most infecting organisms in vitro. Clinical responses to CPFX in these 6 patients were good in 5, fair in 1, with an efficacy rate of 100%. Upon administration of CPFX, these 6 patients did not show any adverse reactions. These results suggest that oral administration of CPFX may keep effective levels in serum and sputum over 3 hours in aged patients with chronic respiratory diseases, and good clinical responses should be obtained without side effects in such patients.


[Therapeutic effects of cefclidin against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group]. One hundred thirty-eight patients with severe infections associated with hematopoietic disorders were treated with cefclidin (CFCL), and the efficacy and the safety of the drug were evaluated. The results obtained are summarized below. 1. Of the 126 patients in whom the efficacies were evaluable, 22 (17.5%) responded markedly well and 48 (38.1%) moderately, and the overall efficacy rate was 55.6%. 2. Efficacy rates for different infections were: 20.0% in septicemia, 61.2% in suspected septicemia, 46.7% in respiratory tract infection and 25.0% in others. 3. Significantly different efficacy ratings were observed between a group of patients with neutrophil counts of less than 100/mm3 and that with neutrophil counts of higher than 501/mm3. 4. Out of 138 patients in whom the safety was evaluable, side effects were observed in 5 patients (3.6%) and abnormal laboratory test values in 9 (6.5%). None was serious, however.


[Clinical evaluation of ceftazidime monotherapy for infections complicated with hematological disorders]. Fifty patients with infections associated with hematological disorders were treated with ceftazidime (CAZ). Among them 44 cases were evaluable, including 21 with acute leukemia, 17 with malignant lymphoma, and 6 with other hematological disorders. Excellent responses were observed in 15 patients (34.1%) and good responses in 15 (34.1%), with an overall efficacy rate of 68.2%. The efficacy rate among sepsis and suspected sepsis cases was 67.6%. This treatment was also effective in 7 of 10 cases in which neutrophil counts were less than 500/mm3 through the course of administration. Laboratory abnormalities included mild eosinophilia in 1 case, slight elevation of GOT in 1 case and slight elevation of GPT in 1 case. These results suggest that CAZ is an effective and safe antibiotics for the treatment of infections in patients with hematological disorders.


[Clinical pharmacology and efficacy of levofloxacin in elderly patients]. We studied a newly developed oral quinolone antimicrobial agent, levofloxacin (LVFX, DR-3355), and obtained the following results. 1. Serum and urine levels of LVFX were determined after oral administration of LVFX 100 mg to 11 elderly patients with various degrees of renal function insufficiencies. The patients were classified according to creatinine clearance (Ccr) values into Group I (n = 1, Ccr greater than or equal to 70 ml/min), Group II (n = 4, 40 less than or equal to Ccr less than 70 ml/min), and Group III (n = 6, Ccr less than 40 ml/min). The peak levels of LVFX did not differ greatly among the 3 groups, but in patients with severely impaired renal functions, serum concentrations decreased more slowly than in those with slightly and moderately impaired renal functions, and high serum levels were maintained over a long period. Urinary excretion of LVFX diminished in relation to degrees of renal failure. 2. LVFX was administered to treat 13 elderly patients with respiratory tract infections. Clinical responses were good in all patients with a high efficacy rate of 100%. Laboratory tests revealed eosinophilia in 1 case. The symptom was mild, however, and no severe side effects due to the drug were observed.


[Sputum penetration of levofloxacin and its clinical efficacy in patients with chronic lower respiratory tract infections]. Sputum penetration of levofloxacin (LVFX) was evaluated after a single oral dose of 100 mg or 200 mg to 4 patients with copious purulent sputa. The sputum concentration of LVFX reached maximum levels of 1.27 and 4.36 micrograms/ml at 4 hours, and still remained at concentrations of 0.32 and 1.68 micrograms/ml at 8 hours after administration of 100 mg and 200 mg, respectively. The AUC ratio of sputum/serum was 0.9-1.0, indicating good sputum penetration of LVFX in these patients. The clinical efficacy and the safety of LVFX were also evaluated in a total of 13 patients with respiratory tract infections associated with bronchiectasis, diffuse panbronchiolitis, etc. LVFX was administered orally at a daily dose of 200 mg once a day, 100 mg t.i.d. or 200 mg t.i.d. for 7-28 days (mean 14.7 days). The clinical response to the drug was rated as excellent in 1 case, good in 5, fair in 3, and poor in 2 cases in 11 evaluable cases, thus the efficacy rate was 54.5%. All the 3 strains of Haemophilus influenzae were eradicated. Of the 3 strains of Pseudomonas aeruginosa, eradication, decrease, and unchange was observed for 1 strain each. One strain of Streptococcus pneumoniae remained unchanged. No adverse reaction was observed except for 1 case with slight and temporary increase of eosinophils. The above results suggested that LVFX would be clinically useful in the treatment of chronic lower respiratory tract infections.


[Laboratory and clinical studies on levofloxacin]. A newly developed broad-spectrum fluoroquinolone, levofloxacin (LVFX, DR-3355), was evaluated in vitro and in vivo in comparison with ciprofloxacin (CPFX), ofloxacin (OFLX) and norfloxacin (NFLX). The results were as follows. 1. Antimicrobial activity Minimal inhibitory concentrations (MICs) against 480 clinical isolates including 16 different species were determined using the microbroth dilution method. LVFX showed excellent antimicrobial activities against Gram-positive and -negative bacteria. The MIC values of LVFX for Gram-positive bacteria were superior to those of the other quinolones tested. The MIC values of LVFX for Gram-negative bacteria were comparable to those of CPFX and superior to those of OFLX and NFLX. 2. LVFX concentrations in serum and sputum LVFX was orally administered in a single dose of 200 mg to 2 patients with chronic lower respiratory tract infections, and its concentrations in serum and sputum were measured at intervals using bioassay. The peak concentrations of LVFX in serum were 1.52 and 1.24 micrograms/ml, and 84-95% of serum level were detected in sputum. From these data, it appeared that LVFX penetrate well into the lung. 3. Clinical efficacy and adverse reactions Fifteen patients with respiratory tract infections were treated with LVFX, and the overall efficacy rate was 78.6% (excellent in 3 cases, good in 8, fair in 3, poor in 0). As adverse reactions, anorexia was observed in 2 cases, diarrhea in 1 case and tremor of finger in 1 case. Although an elevation of total bilirubin in serum was observed in a case as an abnormal laboratory finding, it was mild, transient and improved rapidly after the completion of LVFX treatment.


[Chemotherapy of biliary tract infections (XXXVII). Excretion into bile and gallbladder tissue levels of levofloxacin and its clinical effect in biliary tract infections]. Evaluations were made on biliary excretion and penetration into the gallbladder tissue of levofloxacin (LVFX, DR-3355), a new quinolone antibacterial agent, and its clinical efficacy in biliary tract infections. 1. Gallbladder tissue concentrations and biliary concentrations of LVFX at 2-6 hours at oral administration of 100 mg were 0.58-1.99 micrograms/g and 0.49-5.63 micrograms/ml, respectively. These tissue and biliary levels are almost equal or somewhat higher than the serum levels (0.55-1.63 micrograms/ml) of the compound. 2. The concentrations of LVFX and optical isomer DR-3354 in the serum, gallbladder tissue, and bile were determined after a single or a concomitant administration of LVFX 100 mg and/or ofloxacin (OFLX) 100 to 200 mg. The concentration ratio of LVFX to DR-3354 paralleled with the ratio of the 2 compounds administrated. 3. At a dose of 100 mg, the glucuronide of LVFX in the common duct bile was detected at proportions between 0.9 and 36.0%. 4. A total of 11 patients with biliary tract infections, including 6 cholecystitis 3 cholangitis, and 1 each of cholecystocholangitis and liver abscess was treated with LVFX at 100-200 mg t.i.d. for 3-14 days. Clinical results were excellent or good in 8 cases and fair in 3 cases, resulting in an efficacy rate of 72.7%. 5. A side effect and an abnormal change in laboratory findings were observed in both 1 case each and they were both mild. It was concluded that LVFX showed good penetration to the biliary tract as does OFLX, and that it would be a useful oral agent for the treatment of biliary tract infections.


[Penetration of levofloxacin in bile].

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


[Levofloxacin in the field of dermatology]. 1. Minimum inhibitory concentrations (MICs) of levofloxacin (LVFX, DR-3355), ofloxacin (OFLX), tosufloxacin (TFLX), norfloxacin (NFLX) were determined, with an inoculum size of 10(6) cfu/ml, against 122 strains of Staphylococcus aureus isolated from lesions of skin infections. LVFX showed most frequent MIC values of 0.20 micrograms/ml. OFLX, TFLX, and NFLX showed most frequent MIC values of 0.39 micrograms/ml, less than or equal to 0.05 micrograms/ml and 0.78 micrograms/ml, respectively. 2. Serum and skin levels of LVFX after oral administration (10 mg/kg, fasting) were determined in rats. Serum levels were 1.79, 1.29, 0.60, 0.43 and 0.18 micrograms/ml, and corresponding skin levels were 1.63, 1.77, 1.04, 0.87 and 0.64 micrograms/g (wet weight) at 0.5, 1, 2, 4 and 8 hours after administration (n = 5), respectively. 3. LVFX was used clinically in 43 cases at doses of 200-300 mg divided into 2 or 3 doses, and evaluated for final overall clinical efficacy in 41 cases. Cure was observed in 21 cases, remarkable improvement in 13 cases, improvement in 4 cases, unchanged in 1 case, aggravation in 1 case, and remarkable aggravation in 1 case. Diarrhea was observed in 2 cases, diffuse erythema with feverishness in 1 case and slight dyspnea in 1 case. Transient slight eosinophilia, elevation of Al-P, anemia and leukopenia were observed.


[Levofloxacin in obstetrics and gynecology]. We investigated the clinical efficacy and the safety of levofloxacin (LVFX, DR-3355) in obstetrical and gynecological infections and the following results were obtained. 1. Clinical efficacies were evaluated as excellent in 2 and good in 9 cases, hence the efficacy rate was 100%. 2. Bacteriologically, the eradication rate was 16/17 (94.1%). 3. No Side effects nor abnormal changes in laboratory test results were observed. These results indicated that LVFX was highly useful in the treatment of obstetrical and gynecological infections.


[A study of comparison between Technicon THMS H-2 and Hematrak 590]. Using 655 peripheral blood samples from normal individuals and patients, we evaluated the relationship between the measurements of red blood cell (RBC) and white blood cell (WBC) through the Hematrak 590 (Hematrak) and the generated flag systems in the Technicon H-2 (H-2). 1) Among the 12 VAR (Variation) flag positive samples in H-2, 10 samples were obtained from the patients receiving blood transfusions. The samples with high values of HDW (Hemoglobin distribution width) in H-2 seemed to have hypochromatic and polychromatic changes in RBC. 2) Hematrak is likely to be more sensitive than H-2 in discovering atypical lymphocytes (AL). When AL counts in Hematrak were over 5 or 6% of WBC, these results were coincident with ATYP flag positive in H-2. 3) In our examinations, when %Blast in H-2 was over 4%, BLASTS flag always generated positively. We think that H-2 is a tool with high reproducibility for the detection of the blast-like abnormal cells. 4) We evaluated the results of WBC differential count by the three methods of H-2, Hematrak and manual procedures in the peripheral blood samples from normal individuals. We recognized close correlations in neutrophils, lymphocytes and eosinophils (coefficients of correlation = 0.826-0.911), and relatively close ones in monocytes (r = 0.280-0.562), but no correlations in basophils (r = 0.106-0.281). To comprehend the pathophysiological states of the various diseases hematologically, it is necessary to understand the characteristics of the different measurement principles between the two instruments (H-2 and Hematrak).


[Studies on the efficient application by STKS and 8200]. We examined the usefulness of differential leukocyte counts provided by the automated STKS (Coulter) using the VCS method, the cell analyzer 8200 (Hitachi) using the image analysing as compared with that of the traditional manual method. In the STKS, about 8000 leukocytes can be counted within one minute and 5 part differential counts (neutrophils, eosinophils, monocytes, lymphocytes) are provided. The STKS may provided adequate identification of patients who have significant leukocyte abnormalities that require further study. Potential deficiencies of this system included an inability to detect abnormal lymphocytes such as ATL cells. In addition, low numbers of erythroblasts were missed, although these cells could be warned by a flagging system. In the cell analyzer 8200, the differential leukocyte count is done by the microscopic examination of stained blood films which is prepared by automatic device. Results from counts performed with this system correlated well with those obtained by the manual method. This system also missed low numbers of erythroblasts and ATL cells. Another potential deficiencies of the system is that number of cells observed within one minute were limited to about 100. When a prescribed set of cut-off limits, carefully chosen qualitatively, is introduced into these systems, automated leukocyte differential counts, with combination of STKS, 8200 and the manual method, clearly improve turn around time for laboratory blood assessments and this help to reduce unnecessary differential leukocyte counts by the manual method.


[The clinicopathological evaluation of automated cytochemical hematology system (Technicon H1) in patients with leukemia and myelodysplastic syndrome]. To determine the usefulness of the H1 system, we applied it to 14 patients with acute leukemia and 19 patients with myelodysplastic syndrome (MDS). We revealed interesting cytogram patterns in several patients with acute leukemia, ALL (L2), ALL (L3), and AML (M7). In the basophil and lobularity cytogram, their blast cells were clustered mainly in the blast box. However, a small cluster appeared in the basophil area and was expressed as pseudo-basophilia of 4.4%, 9.6%, and 21%, respectively. We speculated that not only normal basophils but also some type of leukemic blasts could be resistant to rupture of the cell membrane induced by a surfuctant at a low pH. Characteristics of H1 cytogram and histogram pattern have hardly been reported in patients with MDS. From the analysis of H1 pattern of 19 cases, we found that the (1) the values of RDW and HDW were high in comparison to those for aplastic anemia and normal controls and (2) the MPXI (mean peroxidase activity index) was significantly low at the time of diagnosis. MPXI had declined at the terminal stage in cases of death with bone marrow failure. These characteristics were concluded to be useful in clinicopathological diagnosis using the H1 automatic hematological system.


[The correlation between hematopoietic status of the bone marrow and peripheral or marrow reticulocyte classification by using the automated reticulocyte analyzer Sysmex R-3000]. In this study peripheral and marrow reticulocytes were counted by using the automated reticulocyte analyzer Sysmex R-3000 with the quick and accurate function of reticulocyte classification dependent on reticulocyte maturation. The correlation of reticulocyte count of the R-3000 to that of visual reticulocyte counting method was r = 0.926, y = 0.88x + 0.305 and r = 0.933, y = 1.32x + 0.328 for peripheral blood and bone marrow, respectively. The hematopoietic status of the bone marrow was reflected in peripheral reticulocytes better than in leukocytes or platelets. Moreover, at recovery stage from bone marrow suppression after chemotherapy, the ratio of immature type (HFR fraction) in peripheral reticulocytes increased to precede in several days increasing total reticulocytes. The relative reticulocyte counts in bone marrow was about 3 times higher than peripheral blood to be drawn at the same time higher and the patients suffering from megaloblastic anemia, MDS or DIC tended to have a much higher reticulocyte count in bone marrow than in peripheral blood.


[Clinical application of data measured by automated blood cell counter]. Rapid progress has been made in automated blood cell counting techniques using several kinds of apparatuses based on different mechanisms of measurement. We report a method of clinical application of the measurements made by an automated blood cell counter in the diagnosis and treatment of diseases, and discuss its usefulness, and its weaknesses that require improvement.


[Anti-C100-3 antibody titration using 4-parameter logistic curve (results in its application to hepatitis C cases treated with interferon]. We evaluated titers of C100-3 antibody by ELISA using a 4-parameter logistic fitting curve and examined the transition of the values in the cases of interferon treatment. The 4-parameter logistic fitting curve produced a standard curve in a wider range using a micro plate reader than the logarithmic curve. The values of C100-3 antibody during and after the treatments of interferon were changed in parallel with the alterations of ALT. The anti-C100-3 antibody titers assayed in the complete or partial responders were significantly reduced at the end of interferon therapy. These findings suggest the clinical usefulness of the evaluation of anti C100-3 antibody titers.


[Detection of Campylobacter species by using polymerase chain reaction and nonradioactive labeled DNA probe]. We have detected Campylobacter species which are now recognized as major pathogens of acute diarrheal disease in humans using polymerase chain reaction (PCR) and a nonradioactive labeled DNA probe. Diagnosis of Campylobacter enteritis without doing culture from stool samples is of great benefit in the laboratory. Two oligonucleotide primers (20 mer) complementary to a unique sequence of the DNA encoding ribosomal RNA (rRNA) of Campylobacter jejuni for PCR were synthesized by solid-phase phosphoamidite method. Amplified target DNA of 275 base pairs could be resolved on ethidium bromide-stained gels, and hybridized with an oligodeoxynucleotide probe (28 mer) conjugated to alkaline phosphatase. In identification experiments, it was shown that the nonradioactive probe was hybridized to clinical strains of C. jejuni (104), C. coli (5), C. laridis (5), C. hyointestinalis (1) and C. fetus subsp. fetus (1) with an accuracy of 99-100%, while it was not for Helicobacter pylori. Further, there was no evidence of amplification in strains of K. pneumoniae, S. marcescens and E. coli. Using direct detection to stool specimens, this method could be performed in C. jejuni in 39 of 43 culture-positive specimens (91%), and in 19 of 141 culture-negative specimens (13.5%), respectively. The results of this comparative study suggested that the DNA probe assay became a rapid and reliable technique to confirm culture of Campylobacter species.


[Further evaluation of GPIb binding domain of vWf by synthetic peptides]. We have already demonstrated that the GPIb binding domain of vWf resided at the regions corresponding to residues 474-488(G10) and 694-708(D5). Moreover, conformational change of vWf was suggested to be important for binding to GPIb. The effect of newly synthetized peptide combining G10 and D5 with lysin(G10-D5) on vWf binding to GPIb and platelet aggregation was studied. All synthetic peptides inhibited both vWf binding to GPIb, ristocetin-induced platelet aggregation and asialo vWf-induced platelet aggregation. G10-D5 possessed the most potent inhibitory activity in the interaction of vWf with GPIb. Only G10-D5 reacted with NMC-4 which recognized the epitope in appropriate conformation of vWf. These results indicate that G10-D5 retains some conformational structure and might be a good tool for anti-thrombotic agent.


[Automated assay method for protein C anticoagulant activity]. We developed an automated assay method for protein C anticoagulant activity to prolong the APTT measured with automated coagulation apparatus. The automated assay method required following three reagents. One was 0.025 mol/l calcium chloride solution. The other two were a protein C deficient plasma and a phospholipid plus protein C activator both of which constituted a recomposed protein C assay kit (BMY). 0-50% activities of protein C and clotting times were regressed on normal linear curve, while 25-150% activities and clotting times were regressed on logarithmic curve. The coefficients of variation were 2.9-3.4% (intra-assay) and 3.6-3.9% (inter-assay). A correlation of protein C activities between measured by automated assay method and by ordinary manual method was good (r = 0.954). Our data suggest that this automated assay is a useful method for measuring the protein C anticoagulant activities utilizing a coagulation apparatus.


[Use of heart rate variability and pulse wave velocity for diagnosing cardiovascular autonomic neuropathy]. Heart rate (HR) and arterial pulse wave velocity (PWV) were used for the evaluation of cardiovascular autonomic neuropathy. Data were analyzed from 30 patients with diabetes mellitus (aged from 13 to 75 years). Twenty healthy male subjects (aged from 22 to 44 years) were analyzed for computing normal values as well. After 15 minutes rest, electrocardiogram (ECG) of lead II and plethysmogram of finger tip were simultaneously recorded for each subject. The recording was first done in supine position for 120 seconds and subsequently in upright position for 40 seconds. HR was computed on the basis of consecutive pairs of R wave of the ECG. PWV was estimated by transit time from R wave peak to initial rise of pulse wave. Mean and coefficient of variation (CV) were obtained from the HR in the supine and upright positions respectively, and also from the PWVs. The influence of changing the position was evaluated by percentage of the difference (increasing rate). All the parameters were statistically tested for the difference between the patients with neuropathy and those without neuropathy. As the result, two parameters, that is, the CV of HR in the supine position and the increasing rate of PWV were found to be useful for diagnosing the cardiovascular autonomic neuropathy (p less than 0.05).


[A case of C5 deficiency with polyarthritis]. A 27-year-old female with polyarthritis was found to lack serum complement activity. Her serum CH50 was less than 1.9 U/ml. C5 protein in her serum was less than 2 mg/dl and its activity was not detected. The serum level of the other proteins of complement system examined were within the normal range. At 17 years old, she was diagnosed as rheumatic fever and was admitted to our hospital. She was treated with aminobenzylpenicillin and predonisolone for two months, and she was discharged from our hospital without any abnormalities. But she had no other episode of repeated infections. Family studies of this patient revealed that an elder sister of this patient was also homozygous deficiency of C5 and her parents were considered to be heterozygous deficiency of C5. From these results, the patient was considered to be inherited deficiency of C5.


[Renal and neurologic symptoms due to cryoglobulinemia complicated with rheumatoid arthritis and Sjögren's syndrome]. A 55-year-old woman with rheumatoid arthritis and Sjögren's syndrome developed complications of acute renal failure and symmetrical polyneuropathy. Laboratory examination revealed macroglobulinemia, positive cryoglobulin, and low complement levels. Kidney biopsy specimen revealed "thrombi" in glomerular capillary loops that were positive for PAS stain and negative for Congo red stain. Sural nerve biopsy specimens showed axonal degeneration and subsequent myelin loss due to vasculitis. We, therefore, diagnosed renal failure and polyneuropathy due to cryoglobulinemia, and treated the patient with double filtration plasmapheresis. Moreover, lymph node biopsy specimen revealed malignant lymphoma of the follicular, small-cell lymphoplasmocytic type which seemed to be related to the macroglobulinemia. The complication of cryoglobulinemia must be taken into consideration in patients with autoimmune disease or lymphoproliferative disorder complicated with renal or neurologic symptoms.


[The clinical usefulness of the molar ratio of branched-chain amino acids to tyrosine (BTR) in discriminating stage of chronic liver diseases]. We determined the molar ratio of branched-chain amino acids to tyrosine (BTR) in plasma and in serum by enzymatic method and compared it with Fischer ratio (the molar ratio of branched-chain amino acids to tyrosine and phenylalanine) in plasma obtained by conventional HPLC method. BTR in plasma and in serum was well correlated with plasma Fischer ratio. The normal range (mean +/- 2SD) of BTR was determined to be 4.41-10.05 in 210 normal subjects. In addition, we investigated the distribution of BTR values in patients with various liver diseases. BTR value decreased according to the severity of liver disease. We evaluated the clinical usefulness of BTR in patients with chronic liver diseases by cumulative distribution analysis (CDA) graph and receiver operating characteristic curve (ROC) analysis. The area under the curve for BTR analyzed by ROC for CH versus LC.HCC group was the highest (86.3%) of any for various concurrently-measured liver function tests, and was significantly higher than AST/ALT, ALT, AST, gamma-GT (each, p less than 0.001) and ALB (p less than 0.05). These diagnostic results showed that BTR is a superior indicator in discriminating between liver cirrhosis and chronic hepatitis.


[Microheterogeneity of serum glycoproteins in alcoholic liver disease]. It has been reported that microheterogeneity (M-HT) of serum glycoproteins including transferrin is found in alcoholic liver disease (ALD). In the present study, M-HT of serum glycoproteins in ALD patients was analyzed using the Western blotting technique after isoelectric focusing. M-HT was found in serum alpha 1-antitrypsin, alpha 2-macroglobulin, ceruloplasmin, alpha 1-acid glycoprotein and hemopexin as well as transferrin, but not in serum prealbumin. M-HT disappeared following treatment with sialidase in one group of glycoproteins, but not in another group of glycoproteins. In hemopexin, M-HT was recognized only after treatment with sialidase. These results suggest that mechanisms of the appearance of M-HT of serum glycoproteins in ALD may differ. One mechanism is the interference of glycosylation of glycoproteins in the Golgi apparatus, and another is the decrease of asialo-protein receptors in hepatocytes.


[Studies on the glucose tolerance and the endocrine function of the pancreas in primary sclerosing cholangitis]. The responses of serum IRI, serum IRG, and blood sugar levels to 75 g oral glucose and serum IRI to glucagon injection were investigated in 26 chronic hepatitis, 20 liver cirrhosis, 5 primary sclerosing cholangitis (PSC) and 8 healthy volunteers served as controls. The results obtained herein were as follow: 1) The frequency of the glucose intolerance in PSC was higher than the other liver diseases. The mean values of the insulinogenic index (delta IRI/delta BS 30 min) in PSC was lower than control subjects. No suppression of IRG by glucose was observed in PSC. 2) The maximum IRI value (max delta IRI) in PSC during glucagon test was lower than that in control subjects. 3) In one case of 5 PSC ICSA was founded to be positive. These data suggest that we should pay much attention to suffering from diabetes mellitus in natural history of PSC.


[Comparative study of extracorporeal shock wave lithotripsy (ESWL) between spark gap system and piezoelectric system]. We have analyzed the results of the treatment given on 170 cases of cholecystolithiasis, using two different systems of ESWL: Spark Gap System (hereinafter SGS) and Piezoelectric System (hereinafter PES). 1) In the total cases, there were no significant differences in the fragmentation rate between the two systems. PES was, however, superior to SGS in terms of the complete stone free rate. On the other hand, SGS was superior to PES in terms of the average fragmentation rate. 2) We have classified cholecystolithiasis into 4 groups, combining CT and US. PES showed superiority in the ESWL Group 1 (seeming Pure Cholesterol Stone) and Group 2 (seemingly Mixed Stone) in terms of stone free rate. SGS showed superiority in ESWL Group 3 (seemingly Combination Stone) and Group 4 (seemingly Pigment Stone) in terms of fragmentation effect. 3) We have gained good results from both of the system according to Munich Criteria Modified. 4) Concerning the failures of fragmentation and insufficient stone free, further study shall be required to determine whether fragmentation should be repeated, the case should be handled as "beyond adaptability", or the two-system-combined therapy should be applied.


Individual and environmental characteristics related to influenza-like illness among children: a school-based case-control study. To investigate individual and environmental characteristics associated with the manifestation of influenza-like illness (ILI), a survey enrolling 509 schoolchildren was conducted after an epidemic peak in the 1988/89 season, and then a case-control study was designed according to the information concerning illness onset and usual life-style. Case series were defined as those with fever greater than or equal to 38 degrees C due to acute respiratory illness, subsequent absenteeism and medical consultation during the epidemic peak; mild-ILI (MILI; fever greater than or equal to 38 degrees C and less than 39 degrees C) and severe-ILI (SILI; fever greater than or equal to 39 degrees C). Control series were defined as those with no symptoms (NS) during the same period. An adjusted odds ratio (OR) was obtained using an unconditional logistic regression model for MILI (55) or SILI (33) and NS (204) groups among respondents (508). For MILI, increased risk was observed for easily inflamed tonsils (OR, 3.2; 95% CI, 1.6-6.4), with decreased risks for higher school grade (0.4, 0.2-0.8) and frequent intake of milk or dairy products (0.5, 0.3-1.0), but no significant association was determined for vaccination (0.6, 0.3-1.2). For SILI, there was an increased risk for easily inflamed tonsils (3.3, 1.4-7.9); and decreased risks for the higher grades (0.1, 0.1-0.3); use of a kerosene or gas heater with indoor exhaust (0.4, 0.2-0.9); and vaccination (0.3, 0.1-0.7). The OR of vaccinees for SILI constantly decreased regardless of grade and easily inflamed tonsils.


[Seasonal variation of mean birth weight and births in Nagano Prefecture]. Seasonal variation of mean birth weight in Nagano Prefecture was examined by a traditional time series analysis, which decomposes the variation in a series into trend, seasonal variation, other cyclic changes, and remaining irregular fluctuations, based on the data in Vital Statistics from January 1974 to December 1983. The seasonal index of mean birth weight showed a unimodal pattern with a peak in June for males, and a bimodal pattern with peaks in spring and autumn in females with statistical significance. Previous reports have revealed that gestational period is the most important factor associated with birth weight. Therefore, we carried out time series analysis for the mean gestational period and observed an apparent seasonal periodicity, which showed a unimodal pattern with a bottom in winter for both sexes and parities. According to the results of statistical testing of the degree of coincidence between two time series, the time series of mean birth weight and that of mean gestational periods showed statistically significant coincidences in their monthly variations for multiparae. On the other hand, mean birth weight at 40 gestational weeks, which reflects the intrauterine growth, did not show seasonality. These results suggest that seasonality in gestational periods might play an important role in creating seasonal variations of mean birth weight in Nagano Prefecture. The average daily number of births by month also showed apparent seasonalities both for primiparae and multiparae. Primiparae showed a bimodal pattern with peaks in February and August, while multiparae showed a unimodal pattern with a peak in May and a bottom in November. It has been said that the seasonality in marriage is one of important factors associated with seasonal variation in births.(ABSTRACT TRUNCATED AT 250 WORDS)


[The effects of long-term intake of a low concentration of sodium fluoride on bone loss in the growing senescence-accelerated mouse (SAM-P/6)]. The long-term effects of low concentrations of sodium fluoride (0, 1 and 5 mg/l) in drinking water on bone metabolism were examined in the growing senescence accelerated mouse (SAM-P/6) as a spontaneous experimental model of senile osteoporosis. In 4 and 8 months of age respectively, there were almost no differences in body weight, and serum calcium, phosphorus and alkaline phosphatase levels between controls and fluoride groups. Calcium contents per dry weight of femoral bone were higher in fluoride groups than in controls. The bone mass of the trabecular was not affected by the low-concentration sodium fluoride intake. However, sodium fluoride decreased the rate of bone mass loss associated with aging in the cortical bone in SAM-P/6 compared with the control. The results of this study suggest that, in growing SAM-P/6 mice, a long-term low-concentration sodium fluoride intake affects the skeletal metabolism.


[Effects of repeated phase shifts in light-dark cycles on lipid metabolism in stroke-prone spontaneously hypertensive rats (SHRSP)]. In the present paper, we employed the stroke-prone spontaneously hypertensive rat (SHRSP) as an animal model and the Kyo: Wistar rat (WKY) as a control, and studied on the effect of repeated phase shifts in light-dark cycles on lipid metabolism. First, we investigated diurnal rhythms of the lipid metabolism in SHRSP and WKY. In both strains, the activities of lipoprotein lipase (LPL) and hepatic microsomal cholesterol 7 alpha-hydroxylase in the dark period were significantly higher than those in the light period. In addition, in SHRSP, the serum apoA-IV level in the dark period was also higher than that in the light period. Next, we repeated the phase shifts in light-dark cycles twice a week with elongation of the light period for 4 weeks. LPL activity in the light period increased in response to the repeated phase shifts in both strains. This might be a defensive reaction to maintain homeostasis in the lipid metabolism in addition to energy production. Moreover, we performed repeated phase shifts in rats fed a high-fat and high-cholesterol diet containing 0.1% propylthiouracil to elucidate the effect on the development of hypercholesterolemia. The repeated phase shifts increased the levels of atherogenic lipoproteins and the atherogenic index (apoB/apoA-I). In particular, the effect was more marked in SHRSP. This deleterious effect could be due to the overproduction of very low density lipoprotein (VLDL, beta-VLDL) in the liver.


[Quantitative evaluation of stress using the Type A behavior pattern]. The problem of quantitative assessment of individual stress remains to be solved. The purpose of this study was to attempt to quantify the evaluation of stress using the Type A behavior pattern. A total of 1,101 factory workers, 602 male workers (aged 20-59) completed questionnaires regarding subjective symptoms, Type A behaviors, shift work, age, and lifestyles such as drinking habits and smoking habits. Using the results of our previous study, 3 component scores were calculated from the responses to 11 questions pertaining to the Type A behavior pattern. Stepwise logistic regression analysis of complaints of 8 stress-related subjective symptoms was performed, using shift work, age, drinking habits, and smoking habits as categorical independent variables, and 3 component scores as interval-scaled independent variables. The following conclusions were obtained. 1. The first component score, which represented overall irritability, was chosen as an independent variable for complaints of "hunger pains" and "tendency to have diarrhea." The first component score had a positive association with complaints of these stress-related subjective symptoms, and the association with "hunger pains" was statistically significant with P less than 0.05, though the association with "tendency to have diarrhea" was not significant. 2. The second component score, which represented relaxation, was chosen for complaints of "heartburn or gastric reflux" and "abnormal thirst." The second component score had a negative association with complaints of these stress-related subjective symptoms, and both associations were statistically significant with P less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)


[Investigation of a new method for separation of neutrophils from a small volume of human blood]. We have already reported a neutrophil separation method for the multiple simultaneous measurement of neutrophil chemiluminescence. However, when the reported separation method was used, at least 4 ml of venous blood was needed to collect enough neutrophils for chemiluminescent measurement. Because of this blood volume, there is a limitation on applications of the multiple simultaneous method for neonates, infants, and in some clinical situations. To expand the application of this neutrophil chemiluminescence measurement into clinical and health science areas, we have developed a new method for separation of neutrophils from a relatively small amount of blood (500 microliters). In addition, the influences of remaining red blood cells and hemoglobin levels in the neutrophil fraction on the chemiluminescence were examined to determine the necessity for elimination procedures. The new separation method used a capillary tube (length, 130 mm; outside diameter, 5 mm; thickness, 0.8 mm) with density gradient reagents (Histopaque 1077 and 1119). After centrifugal separation (500 g, 30 min), the neutrophil fraction was isolated with 93.1 +/- 4.7% purity and 60.6 +/- 11.1% yield. This purity and yield were comparable to or better than those with the previously reported method, while levels of remaining red blood cells and hemoglobin were about the same. Remaining red blood cells and hemoglobin in the neutrophil fraction acted on the chemiluminescence as a quencher. For the correct estimation of neutrophil chemiluminescence, elimination of remaining red blood cells and hemoglobin in the neutrophil fraction is necessary. This new neutrophil separation method is a very useful method, especially for cases in which available blood amounts are limited.


Survival rate and risk factors for patients with retinoblastoma in Japan. The Committee for the National Registry of Retinoblastoma. Clinical, pathological and follow-up data on the 1,147 cases of retinoblastoma registered in Japan from 1975 to 1982 were statistically analyzed. The cumulative survival rate of the total 1,147 cases was 93.0% at 5 years and 90.3% at 10 years, calculated by the Kaplan-Meier method. The survival rate for the 757 unilateral cases was 93.3% at 5 years and 92.3% at 10 years. For the 390 bilateral cases, however, the rate was 92.2% at 5 years and 86.7% at 10 years. The Cox multivariate analysis indicated that, among the various clinical and pathological findings in the patients, extraocular invasion by the tumor was the most significant risk factor which is predictive of death due to tumor. The survival rate for patients with extraocular invasion was significantly better in cases undergoing subsequent local radiation and/or systemic chemotherapy than in cases without such aftercare. The cumulative incidence rate of second neoplasms in 409 cases of hereditary retinoblastoma was 4.8% at 10 years, 9.8% at 15 years and 15.7% at 20 years. The occurrence of a second neoplasm was the main cause of death in the hereditary cases 10 years after the first onset.


Japanese family with blue cone monochromatism. The diagnosis of blue cone monochromatism (BCM) is based on severely affected color vision with preserved blue function, nearly nonrecordable photopic ERG, and a family pedigree compatible with X-linked inheritance. We have studied the color vision and ocular function of three members of a family with BCM and a female carrier in the same family. Two of the three affected family members, 9- and 7-year-old brothers, showed the unique features of BCM in their color vision and ERG. The third affected family member, a 43-year-old uncle, showed achromatic vision. He had diabetic retinopathy and moderate cataract which were thought to disturb his blue cone function, causing apparent rod monochromatism. The female carrier, the mother of the brothers, showed normal visual functions except for a slight reduction in photopic ERG amplitude. We believe that this is the first description of BCM in a Japanese family.


Vitreoretinal surgical technique for transplanting retinal pigment epithelium in rabbit retina. Transplantation of retinal pigment epithelial (RPE) cells has been proposed as a potential remedial procedure for previously untreatable retinal diseases. In this study, a vitreoretinal surgical technique was used to transplant pigmented RPE cells obtained from pigmented rabbits into the subretinal space of New Zealand White rabbits. At the time the animals were sacrificed, the retina was re-attached in all but 4 of the 24 experimental eyes. Histologically, by one week the transplanted RPE cells had formed a monolayer in patchy areas beneath the attached retina. By electron microscopy, RPE cells with prominent melanin granules were found attached to Bruch's membrane. Three weeks after transplantation, grafted RPE cells had formed apical microvilli and tight junctions with adjacent cells. The nucleus of the cells containing pigment had become oval, and their contact with Bruch's membrane appeared to be composed of bsal infoldings that were well formed. Our findings demonstrated the functional appearance of the transplanted RPE cells.


Postoperative subconjunctival 5-fluorouracil injections and success probability of trabeculectomy in Japanese: results of 5-year follow-up. The effects of postoperative subconjunctival 5-fluorouracil (5-FU) injections on the surgical outcome of trabeculectomy in the Japanese were studied in a total of 362 eyes of 263 glaucoma patients with the postoperative follow-up of 1-9 years. The probability of successful intraocular pressure (IOP) control at the 5-year point of the continuing follow-up was calculated by the life-table method of Kaplan-Meier. The eyes that had undergone trabeculectomy with postoperative injections of 5-FU (5-FU group) included 165 eyes with primary open-angle glaucoma (POAG), 38 eyes with secondary glaucoma (SG) and 60 eyes with refractory glaucoma. The eyes that had undergone trabeculectomy without postoperative 5-FU (control group) included 46 eyes with POAG, 31 eyes with SG and 22 eyes with refractory glaucoma. The surgical techniques and postoperative care were virtually identical between the two groups, except that the control group did not receive the postoperative 5-FU. The total amount of 5-FU given to each case averaged 36.5, 36.0 and 49.5 mg for POAG, SG and refractory glaucoma, respectively. At the 5-year follow-up point, the probability of maintaining IOP control below 21 mmHg with or without medication in the 5-FU group was 92.5% for POAG, 87.4% for SG and 57.5% for refractory glaucoma; while without medication the probability was 58.2, 54.8 and 27.8%, respectively. The probability of IOP control below 16 mmHg with or without medication in the 5-FU group was 77.9% for POAG, 66.8% for SG and 26.9% for refractory glaucoma; without medication the probability was 55.2, 49.8 and 24.5%, respectively. In the control group, the corresponding probability for each type of glaucoma was much lower than that in the 5-FU group, and the probability for IOP control below 16 mmHG was 0.12% at the 5-year follow-up point. In the 5-FU group, the mean postoperative IOP in successfully treated eyes remained at about 12 mmHg throughout the first 5 years of the follow-up period. There was no significant difference in incidence of postoperative complications between the 5-FU and control groups, except that corneal epithelial defect was noted in 38.8% of the eyes in the 5-FU group. No late complications related to the use of postoperative 5-FU were observed.(ABSTRACT TRUNCATED AT 400 WORDS)


Morphological and histochemical studies of goblet cells in developing human conjunctiva. This study deals with the development of the human conjunctival goblet cells. Fifty-six eyes of human embryos and fetuses ranging from 5 to 41 weeks of gestational stage were used. The distribution of glycosaminoglycans in the goblet cells was investigated with 1% alcian blue (pH 2.5) staining. For identifying the types of glycosaminoglycans, enzyme digestion methods were carried out with streptomyces hyaluronidase, chondroitinase AC, chondroitinase ABC, or sialidase (neuraminidase). At 9 weeks of gestational age, goblet cells appeared in the fornix region of the conjunctiva and extended toward the palpebral and bulbar regions. Histochemical studies with enzyme digestion methods revealed the existence of sialomucin in the goblet cells from 9 weeks. This finding suggested that the goblet cells first appeared in the fornix area, extending toward the palpebral region, then toward the bulbar region, and containing sialomucin from their early stage of development.


Phagocytosis and fibronectin of cells observed on intraocular lenses. The phagocytic activity and distribution of fibronectin in the cells adhering to implanted intraocular lenses (IOLs) were studied in rabbits. IOLs were explanted from the posterior chamber 7 days after implantation. Phagocytosis by the cells from the IOLs was studied by electron microscopy after incubation with polystyrene beads. The distribution of fibronectin was examined immunohistochemically using an anti-fibronectin antibody. Many presumed macrophages and giant cells which were thought to be of macrophagic origin were observed on the IOLs. Adherence of the beads to the surface of the cells, phagocytosis of these beads, and fibronectin immunoreactivity were prominent in these presumed macrophages, whereas giant cells displayed a reduction in these activities. These findings suggest that the adherence activities of the presumed macrophages are less after giant cells are formed, reflecting a reduced production of fibronectin.


Type of arteriovenous crossing at site of branch retinal vein occlusion. A retrospective study of 63 patients (64 eyes) with symptomatic branch retinal vein occlusion, 30 men and 33 women, was carried out in this study. The ages of the subjects ranged from 40 to 82 years. Systemic hypertension was present in 41 patients and diabetes mellitus in 19. The occlusion involved the superotemporal vein in 39 eyes, inferotemporal vein in 20, superonasal vein in 2 or macular vein in 3. The site of the occlusion could be examined in detail in 57 eyes, and an arterial overcrossing was involved in 53 of these eyes (93%). This incidence of arterial overcrossing was significantly higher in the branch retinal vein occlusion eyes than in control eyes (P less than 0.05).


Nonfamilial and unusual cases of Leber's hereditary optic neuropathy identified by mitochondrial DNA analysis. Peripheral blood mitochondrial DNA (mtDNA) samples from 11 patients with acute optic neuritis or insidious optic atrophy were examined for the mutation at nt 11778 and nt 3460 in polymerase chain reaction products. The mtDNA mutation at nt 11778 was evident in 8 cases, which led to a definite diagnosis of Leber's hereditary optic neuropathy (LHON); 4 of the cases were familial and the remaining 4 cases were nonfamilial. None of the 11 patients showed the nt 3460 mutation. The symptoms and signs were variable among the LHON cases with nt 11778 mutation. Assessment of mtDNA provides a useful diagnostic aid for clinically undefined, seemingly nonfamilial or atypical cases of Leber's hereditary optic neuropathy, particularly in bilateral, insidious optic nerve disease in early childhood.


Orbital extension of sinus lymphoma in AIDS patient. A case of a 27-year-old white male with acquired immunodeficiency syndrome (AIDS) who had a maxillary sinus tumor with secondary orbital involvement was reported. Marked proptosis and distortion of the globe were present. Biopsy by the Caldwell-Luc approach disclosed an immunoblastic lymphoma of B-cell origin. To the best of our knowledge, this is the first reported case of a maxillary sinus lymphoma extending into the orbit in a patient with AIDS.


A case of endogenous Enterococcus faecalis endophthalmitis. A case of successful treatment by vitrectomy and lensectomy of early-stage endogenous endophthalmitis caused by Enterococcus faecalis was reported. The case was a 50-year-old man with poorly controlled diabetes. Following T-tube drainage for a necrotic cholecystitis operation, he developed iridocyclitis in both eyes as well as fever. At the time of his first visit to our clinic, his right eye had already lost light perception. His left eye had visual acuity recognizing hand movement, marked uveitis, complicated cataract, and dense vitreous opacity. As gram-positive cocci were isolated from the aspirated vitreous, lensectomy and vitrectomy under irrigation with antibiotics were conducted. After the administration of systemic postoperative antibiotics and human immunoglobulin, the patient showed remarkable improvement in the state of his ocular fundus. By 60 days after the surgery, the visual acuity of his left eye recovered to 0.2. Endogenous Enterococcus faecalis endophthalmitis has rarely been reported in Japan. The diagnosis and treatment of this disease with reference to the above findings were discussed.


The process of subretinal strand formation. Surgically resected subretinal proliferative tissue (SRP) in proliferative vitreoretinopathy was examined by morphological and immunohistochemical methods. Membranous and strand-like SRPs were observed. Membranous SRP (4 cases) consisted of retinal pigment epithelial cells (RPEs) and a thin layer of extracellular materials. Strand-like SRP (14 cases) had a core, in which the proliferated cells were embedded among extracellular materials. RPEs and glial cells were found on the surface of the core. Immunohistochemical investigation revealed that the predominant cell components of the strand-like SRPs were RPEs and Müller cells, whereas membranous SRPs were composed mainly of RPEs. It was found that the majority of membranous and strand-like SRPs contained types I, III and IV collagens and fibronectin in the extracellular space. Based on the results of this study, a hypothetical process for the formation of SRP tissues was proposed.


Attenuation of dysfunction in the ischemia-reperfused liver by glycyrrhizin. The present study evaluated the effect of glycyrrhizin (GR) on an injury of the liver caused by ischemia-reperfusion in rats. In the liver ischemia-reperfusion model, levels of serum GOT, GPT and LDH activities and lipid peroxides in the liver tissue were significantly increased. On the contrary, total glutathione content in the liver tissue and NADPH cytochrome P-450 reductase activity of liver microsomes were decreased. Pretreatment with GR 20 mg/kg, i.v. 10 min before induction of ischemia resulted in significant decreases in serum GOT, GPT, LDH activities and the lipid peroxide level and a higher tissue glutathione content during the period of reperfusion. Electron microscopic studies revealed various hepatocellular damages with an almost intact sinusoidal endothelium in ischemia-reperfused livers. However, the degree of damage was less severe in the livers from the rats pretreated with 20 mg/kg GR. The results indicate that GR is able to provide partial protection against ischemia-reperfused damage.


Comparison of contractile mechanisms by carbachol and ATP in detrusor strips of rabbit urinary bladder. Contractile mechanisms by carbachol and ATP were compared in the detrusor strips of rabbit bladder. To exclude modulation of the agonists-induced responses by intramurally synthesized prostaglandins, all the experiments were done in the presence of the potent cyclooxygenase inhibitor flurbiprofen (1 microM). The concentration-response curves for carbachol and ATP were shifted to the right by 6- 10-fold by verapamil (10 microM), which abolished the K-induced contraction of the atropinized detrusor completely. A similar curve for carbachol was obtained in the absence of extracellular Ca [(Ca)o], but the contraction by ATP below 1 mM was more reduced by (Ca)o-depletion than by verapamil. Under Ca-free conditions, repeated applications of ATP resulted in no response, but those of carbachol induced reproducible contractions. These results suggest that carbachol and ATP induces Ca-influx through L-type Ca channels and releases Ca from the Ca stores. However, while carbachol might increase the sensitivity of contractile machinery to Ca on the one hand, ATP would open additional, verapamil-insensitive Ca channels.


Antagonism of platelet-activating factor-induced increase in cytosolic free calcium concentration in human endothelial cells. The effects of platelet-activating factor (PAF) antagonists on the agonist-induced increase in cytosolic free calcium concentration, [Ca2+]i, in human vascular endothelial cells grown in monolayer were investigated by a continuous superfusion technique using a calcium fluorescent probe, fura-2. PAF caused a small but dose-dependent increase in [Ca2+]i. Seven structurally dissimilar PAF antagonists dose-dependently suppressed the peak response, among which WEB 2086 was the most potent, followed by WEB 2170 greater than FR 900452 not equal to ONO 6240 greater than BN 52021 not equal to kadsurenone not equal to CV 3988. These antagonists except for CV 3988 were specific for PAF, since they had no effects on calcium mobilization induced by thrombin or histamine, while CV 3988 had a non-specific effect. PAF in the same range of concentration increased prostacyclin release from human endothelial cells. WEB 2086 also inhibited the PAF-induced prostacyclin release, while it had not effect on the release induced by histamine and thrombin. These results demonstrate the specificity and dose-response characteristics of PAF antagonists in cultured human endothelial cells and suggest that a PAF antagonist could be a valuable therapeutic agent in certain human diseases where PAF activation of endothelial cells may have a critical role.