Sonographic approach to diagnosing pulmonary consolidation.

Thirty-nine consecutive patients with consolidated lung confirmed radiologically underwent sonography, and their sonograms were compared with results for 100 healthy subjects. The hyperechoic line of normal aerated lung and its air artifacts showed respiratory motions ("gliding sign," n = 100). Patients with pneumonia demonstrated distinct sonographic patterns. Strong linear echoes with characteristic air artifacts (air bronchogram) and anechoic tubular structures (fluid bronchogram) were visualized in 36 of 39 patients (92.30%). The superficial lung showed a homogeneous hypoechoic band termed "superficial fluid alveolograms" (n = 39) with respiratory motions in 35 of 39 patients. We conclude that sonography can evaluate pulmonary consolidation and may provide additional roentgenographic information, especially when fluid bronchograms are visualized.


Improved growth and disease activity after intermittent administration of a defined formula diet in children with Crohn's disease.

Growth failure is the most common extraintestinal manifestation of Crohn's disease in childhood, occurring in up to 50% to 88% of affected patients. Previous studies have shown malnutrition to be the most likely cause of the decrease in height and weight velocities in these children. The purpose of this study was to determine the effect of an intermittent defined formula diet on growth and disease activity in children with Crohn's disease and growth failure. Six Tanner stage I-II patients, mean age 13.6 years with height less than the 5th percentile or height velocity less than the 3rd percentile were enrolled in a 1-year prospective study. An isotonic, hydrolyzed whey, medium-chain triglyceride formula was given by nocturnal nasogastric infusion at a caloric equivalent of 50th percentile for age, as the exclusive nutrient source 1 out of 4 months during a 1-year period. A 2-week exclusion diet and a 2-week low-residue diet followed the defined formula diet before resuming the regular diet for 2 months. Patients served as their individual control based on observations of at least 1 year before the study. Height and weight velocity significantly increased. Prednisone intake significantly decreased, and significant improvement was seen in disease activity, albumin, and somatomedin C. The results indicate that an intermittent defined formula diet can improve growth failure and significantly decrease disease activity in children with Crohn's disease.


Ornithine alpha-ketoglutarate and glutamine supplementation during refeeding of food-deprived rats.

The aim of this study was to compare the efficiency of ornithine alpha-ketoglutarate (OKG) and glutamine supplementation in an experimental model of denutrition that provides well-characterized disturbances of amino acid patterns. Male Wistar rats (187 +/- 11 g; five in each group) were starved for 3 days and then refed for 7 days with an oral diet (192 kcal kg-1.day-1 and 2.25 g of nitrogen kg-1.day-1), supplemented with 0.19 g of nitrogen kg-1.day-1 in the form of OKG, glutamine, or casein (control group). Food deprivation induced a fall in most tissue amino acids, with the notable exception of muscle leucine and liver glutamate, which increased by 43% (p < .01), and 11% (p < .05), respectively. The main effect of OKG was seen in the viscera, with a normalization of most amino acid pools (including proline and branched-chain amino acids) in the small bowel and liver. The main effect of glutamine was observed in the muscle, with a normalization of the glutamine and leucine pools. We conclude that, in this model and with the doses used, OKG and glutamine act in different target tissues, ie, splanchnic areas and muscle, respectively.


Substrate efficacy in early nutrition support of critically ill multiple trauma victims.

The metabolic consequences of excessive nutrition support in patients have been increasingly recognized in recent years. Time-dependent optimal nutrition support is desired for an early and uncomplicated recovery after severe injury or illness. Metabolic effects of adding balanced amino acids to glucose infusion during total parenteral nutrition were investigated in 18 patients after major trauma (injury severity score 32 +/- 2). Two studies were conducted on each subject, one in the early "flow" phase of injury (40-60 hours postinjury) in the basal state without any dietary intake and then after 4 to 6 days of intravenous nutrition provided solely as glucose (24 +/- 2 kcal/kg per day, 80% resting energy expenditure, n = 8) or isocaloric glucose (28 +/- 3 kcal/kg per day) with amino acids (275 +/- 28 mg of nitrogen per kilogram per day, n = 10). Whole-body fuel substrate kinetics were studied for energy metabolism (indirect calorimetry), protein kinetics (primed-constant infusion of 15N glycine), and lipid mobilization (two-stage infusion of 10% glycerol). Injury-induced hypoaminoacidemia was equally modulated whether the glucose-based nutrition had amino acids or not. The negative nitrogen balance is reduced similarly in both groups. Protein breakdown rate is significantly (p = .025) decreased in both groups and it is more so (30% vs 18%) in patients receiving total parenteral nutrition. Intravenous nutrition could not stimulate protein synthesis. Whole-body lipolysis rate as well as net fat oxidation rate are suppressed more when glucose alone is given, and this also results in less reesterification. Provision of intravenous glucose alone, not to exceed the resting energy expenditure, seems to be superior to isocaloric glucose with amino acids during this early catabolic flow phase of injury because the injured body could not assimilate this exogenous amino acid.


Continuous compared with intermittent tube feeding in the elderly.

The methods of continuous (C) and intermittent (I) nasogastric tube feedings in 60 patients, 54 men and 6 women, with a mean age of 72 +/- 9 years were compared in terms of number of complications, staff time used, and caloric intake. Patients were randomly assigned between these two methods and followed for 7 days. Diarrhea, aspiration pneumonia, clogged tubes, and self-extubation were observed in both groups. Diarrhea was significantly more frequent (96% of 30 patients) in the I group than the C group (66% of 30 patients) (p < .008). Furthermore, diarrhea was more prolonged (4 days or more) in 64% of 30 patients in the I group than the C group (4 days or more) in 58% of 30 patients (p < .02). However, clogged tubes occurred 3 times more often in the C group (p < .01). Self-extubation and aspiration pneumonia tend to be more frequent in the I group but the difference was not significant. The average time used by staff nurses in the maintenance of NGT feedings was not significantly longer in the I group (48.45 +/- 11 min/patient per day) than the C group (46.46 +/- 11 min/patient per day). In the C group the mean calories recommended were 2248 +/- 36 kcal/day but the actual caloric intake was only 1465 +/- 281 kcal/day, a deficiency of 783 +/- 291 kcal/day. The recommended calorie count for the I group was 2021 +/- 5 kcal/day but the amount delivered was only 1226 +/- 254 kcal/day, which resulted in a deficit of 795 +/- 259 kcal/day.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of excess xylitol on nitrogen and glucose metabolism in parenterally fed rats.

The objectives of this study were to investigate the effects of an excess of xylitol on nitrogen balance and glucose metabolism in parenterally fed rats. Female Sprague-Dawley rats (200-250 g, n = 17) were catheterized for total parenteral nutrition and then randomized into two groups based on subsequent diet. The two diets used were isonitrogenous (1.5 g of nitrogen per kilogram per day) and isocaloric, with half the calories (125 kcal/kg per day) being derived from lipid (125 kcal/kg per day) and the other half from either glucose or xylitol (125 kcal/kg per day). The rats were fed a half-strength total parenteral nutrition diet for the day after surgery and a full-strength total parenteral nutrition diet for the following 4 days. Urines were collected daily for the determination of nitrogen balance. On day 5, the rats were given a 7- to 8-hour infusion of 6.6-d2 glucose (6 mg/h and 2-d1 glucose (12 mg/h). At the conclusion of the isotope infusion period, the rats were killed and blood was collected. Urine output was increased by 22% per day in the xylitol-treated rats, and they excreted 46.5 mmol of xylitol per liter per kilogram per day (7.1 g/kg per day, approximately 22.7% of dose). The xylitol group lost weight, had poorer nitrogen balance (341 +/- 31 vs 83 +/- 29 mg/kg per day [mean +/- standard error of the mean], p < .05), and developed fatty livers. Analysis of the liver fat distribution pattern indicated that the source of the excess hepatic lipid was dietary fat.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of a single oat bran cereal breakfast on serum cholesterol, lipoproteins, and apolipoproteins in patients with hyperlipoproteinemia type IIa.

Serum cholesterol-lowering effects of oat bran-enriched diets have been indicated in several studies in which oat bran was given several times a day. Concomitant changes in the daily diet, ie, a diminished energy intake or changes in the composition of fats in the diet, also have been reported and used to explain the hypocholesterolemic effect of oats. The present study was designed to replace only the conventional continental breakfast by a single oat bran cereal muesli containing 60 g of oat bran and to measure the effects of this dietetic modification on serum lipids in 13 patients with hypercholesterolemia type IIa. Compared with a 3-week baseline period, total serum cholesterol (7.38 +/- 0.35 mmol/L, mean +/- SEM) was reduced by 10.9, 8.4, and 9.7% in the first, second, and third week of oat bran ingestion (p < .01). High-density lipoprotein and low-density lipoprotein cholesterol as well as apolipoprotein A1 decreased to the same extent (8 to 11%; p < .05) during the oat bran period, whereas a pronounced reduction of 25.8% was seen for apolipoprotein B100 (p < .01), which is a major component of low-density lipoprotein. Dietary data obtained by 3-day food records at baseline, oat bran, and follow-up period did not show any differences between the study periods except for dietary fiber, which was increased from 21.9 g/day to 42.4 g/day (p < .002) during the test period because of the daily oat bran intake.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of different lipid sources in total parenteral nutrition on whole body protein kinetics and tumor growth.

This study examined the short-term effects of three total parenteral nutrition solutions, each containing a different lipid source, on host and tumor protein metabolism in a rat cancer model. Each diet contained 220 kcal/kg per day, including 2 g of nitrogen/kg per day and 50% of nonprotein calories as either a structured lipid of medium-chain triglycerides and fish oil, a physical mix of medium-chain triglycerides and fish oil, or Liposyn II, a long-chain triglyceride. A 3-day intravenous feeding infusion began on day 7 after tumor implantation. Tumor growth rate, nitrogen balance, energy expenditure, and plasma albumin, glucose, and free fatty acids were measured, and whole body protein kinetics and fractional synthetic rates in liver, muscle, and tumor tissues were assessed using a constant infusion of 14C-leucine. The results revealed that tumor growth rate was slowed in structured lipid-fed animals (p = .06, one-way analysis of variance) with significant increases in rates of tumor protein synthesis and tumor protein breakdown (p < .001, one-way analysis of variance). Although muscle fractional synthetic rates were significantly decreased in tumor-bearing animals (p < .05, two-way analysis of variance), the rates in structured lipid-fed animals were restored. Nitrogen balance improved significantly in structured lipid-fed animals. The results demonstrate that the source of lipid in total parenteral nutrition solutions can influence tumor and host protein metabolism, and that a structured lipid composed of medium-chain triglycerides and fish oil seems to improve protein metabolism in host tissue without stimulating tumor growth.


Polymyxin B reduces total parenteral nutrition-associated hepatic steatosis by its antibacterial activity and by blocking deleterious effects of lipopolysaccharide.

Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements. Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production. In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN-associated hepatic steatosis. Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels. Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group. The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin. We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN.


Microbial contamination of enteral feeding tubes occurring during nutritional treatment.

Enteral nutrition is an effective treatment for catabolic patients with normal intestinal absorption. However, tube-fed patients are at risk from superinfection. Our study is the first to evaluate in vivo the microbial contamination of solutions staying in the nasogastric tube of cancer patients receiving nutritional preparations. After daily feeding, the tube was rinsed with nonsterile tap water. Tap water staying overnight in the tube was considered as tube-rinsing solution. Microbial burden of nutritional preparations was determined on the fifth day of enteral nutrition, from opening the first container and throughout feeding. The next day, a sample of the tube-rinsing solution was cultured. All bacterial species were identified and antibiotic susceptibility pattern was assessed. Thirty-one cancer patients were included, 12 on the hospital's preparations and 19 on commercial feeding. Seven of the hospital--and none of the commercial--preparations were contaminated. Among the 48 samples collected during feeding, 16 were contaminated, including 10 hospital and 6 commercial preparations. All the 31 tube-rinsing solutions were contaminated and 102 strains cultured. Their median concentration was 10(6) colony-forming units/mL (range 10-10(10)). The strains were 48 Enterobacteriaceae, 20 group D streptococci, 9 Candida albicans, 9 Pseudomonas aeruginosa, and 16 others. Multiple antibiotic resistance was present in 12 of the 102 strains. Lower resistance was present in 33. The predominant microorganism of the tube-rinsing solution caused a bacterial colonization for three febrile patients. In conclusion, the feeding tube is an important reservoir for multiple antibiotic-resistant bacteria.


Variability of the Harris-Benedict equation in recently published textbooks.

The Harris-Benedict equation, as cited in a selection of textbooks of medicine, surgery, and nutrition, was compared with the original monograph published by the Carnegie Foundation. A significant amount of variation was found in published versions of this equation. Of 24 published versions, eight were sufficiently variant to produce errors of 7% to 55% in calculations of nutrition requirements. The error is usually in the constant term for one of the two Harris-Benedict equations. Either the constant term for men is increased to a value approximately the same as for women, or the constant term for women is reduced to be approximately equal to that for men. The primary reason appears to be the lack of availability in medical libraries of the original Carnegie Foundation publication by Harris and Benedict.


The role of protein and calorie restriction in outcome from Salmonella infection in mice.

We studied the separate effects of protein and calorie restriction in mice challenged with Salmonella typhimurium, an intracellular pathogen eliminated by cell-mediated immunity. Female A/J mice (n = 73) were placed on one of eight solid diets for 3 weeks. Animals were weighed at the beginning and the end of the feeding period. Diets were adjusted by two factors. The total amount of protein in the diet was 1%, 5%, 20%, or 40% by weight. The diets were fed to half the mice in quantities of 3 g and to the other half at 1.5 g per mouse per day. At the end of 3 weeks, mice were injected intraperitoneally with bacteria and mortality was observed for 2 weeks. Mortality was related to protein intake and was significantly higher in the 1% and 5% groups (chi 2: p = .0021). However, mortality was lower in the calorie-restricted groups (chi 2: p = .0242). Although caloric intake did not affect cell-mediated immunity, the response to 2,4-dinitrofluorobenzene was greater in the low protein groups. Lymphoproliferative responses in the mixed lymphocyte response were not affected by either caloric or protein intake. Lymphoproliferative responses to both lipopolysaccharide and phytohemagglutinin were affected by dietary protein but not by caloric intake; proliferative responses were higher in the low-protein groups. We conclude that protein restriction can increase mortality in this model. On the other hand, short-term calorie restriction can improve survival.


How amino acids get into cells: mechanisms, models, menus, and mediators.

The bloodstream provides a readily available pool of amino acids, which can be taken up by all cells of the body to support the myriad of biochemical reactions that are essential for life. The transport of amino acids into the cytoplasm occurs via functionally and biochemically distinct amino acid transport systems that have been defined on the basis of their amino acid selectivities and physico-chemical properties. Each system presumably relates to a discrete putative membrane-bound transporter protein that resides within the cell membrane and functions to translocate the amino acid from the extracellular environment into the cytoplasm. Many of these transporters require sodium for maximal activity. The sodium-dependent model presented is consistent with "preferred random" kinetics, with sodium binding preferentially before the amino acid. The transporter acts as an enzyme that catalyzes the movement of its bound amino acid (and sodium) into the cell. In this review, the authors provide a conceptual view of the mechanism of carrier-mediated amino acid transport as well as an overview of the various models that can be used in the laboratory to study this process. In addition, the known agencies that accomplish transport and their regulation by nutrition, hormones, and other mediators of critical illness are discussed.


Acute phosphate intoxication in seven infants under parenteral nutrition.

After major surgery, seven infants aged 4 to 29 weeks, under parenteral nutrition, received monosodium phosphate (4.2 to 14.3 mEq/kg body weight) instead of prescribed calcium gluconate. The wrong solution was perfused during 16 hours. At the 15th hour, blood samples showed hyperphosphatemia in all (8.0 to 14.4 mg/100 mL) and hypocalcemia in four infants (6.1 to 8.0 mg/100 mL), but all were asymptomatic. Under a perfusion of glucose in water, calcemia and phosphatemia returned to normal within 24 hours. In a review of the pediatric literature, we found 11 subjects with symptomatic acute phosphate intoxication, who also presented with hypocalcemia and hyperphosphatemia. The differences were that they received high bolus doses of phosphate orally or rectally and showed symptomatic features. Normalization of the calcemia occurred only when hyperphosphatemia was corrected throughout intravenous hydration.


Prevention of catheter-related sepsis during parenteral nutrition: effect of a new connection device.

A prospective study was carried out to determine the clinical effect of a newly devised catheter connection method (I system) and piggyback access system. Previous studies have demonstrated that the I system avoided bacterial contamination in vitro during tubing change that Luer-Lock connectors did not. The purpose of this study was to investigate the ability of this device coupled with a new closed-system piggyback technique for multipurpose access to reduce catheter-related sepsis in clinical practice. Two hundred and thirty patients receiving total parenteral nutrition were divided into two groups. Group I (n = 106) used the I system connector and group L (n = 124) used a Luer-Lock connector. Catheters in both groups were used for multipurpose access for infusion and blood sampling. In group L, a three-way stopcock and/or pig-gyback system was used for multiple access. In group I, a newly designed closed-system piggyback was used. The incidence of catheter-related sepsis was significantly lower in group I (1.89%/catheter) than in group L (12.10%/catheter) (p < .01, chi 2 analysis), and the average duration of use of each catheter was significantly longer in group I than in Group L (p < .01 by generalized Wilcoxon test). The results of this clinical study suggest that the newly designed connection method and piggyback access system are able to reduce catheter-related sepsis.


Placement of a duodenal feeding tube via gastrostoma with fiberoptic bronchoscope.

We report a case of esophageal disruption that required a duodenal feeding tube. Because of collapse of the gastric outlet secondary to severe emaciation, several attempts to place a tube into the duodenum via gastrostoma had ended in failure. We finally were able to accomplish it with the aid of a fiberoptic bronchoscope and a Swan-Ganz catheter. The procedure is described and discussed.


[Antimicrobial activities of ceftazidime on fresh clinical isolates].

Antimicrobial activity of ceftazidime (CAZ) was compared with those of other cephem antibiotics against clinically isolated strains sent to us by medical institutions throughout Japan in 1989 and 1991. Those strains separated and identified from samples collected from patients with various infections were also examined, and the following results were obtained. 1. The results suggested that, compared with reports of studies conducted with clinical isolates in early 1980's, MIC90 of CAZ in 1991 were markedly higher against Staphylococcus spp., Streptococcus pneumoniae, Escherichia coli, Enterobacter spp., Serratia marcescens, Proteus vulgaris, Morganella morganii, and Pseudomonas aeruginosa. Also, among other bacteria such as Providencia rettgeri, Providencia stuartii, Xanthomonas maltophilia, and Bacteroides fragilis group, strains resistant to CAZ were observed in high proportions. However, large time-course changes were not observed in microbial activities of CAZ on Streptococcus pyogenes, Klebsiella spp, Proteus mirabilis, Pseudomonas cepacia, Acinetobacter calcoaceticus, Haemophilus influenzae and Anaerobic GPC (Gram-positive cocci). 2. Among the strains used in the study, methicillin-resistant Staphylococcus aureus (MRSA), Benzylpenicillin (PCG)-insensitive S. pneumoniae (PISP), cephamycin and oxime type cephem-resistant Gram-negative bacilli of Enterobacteriaceae and new quinolone-resistant organisms were observed in high proportions. It appears therefore, that CAZ failed to exert sufficient antimicrobial activities to these strains because of combination of resistance in these strains. 3. Antimicrobial activities of CAZ on recent clinical isolates showed problems as mentioned above. However, it was also demonstrated that CAZ maintained effective antimicrobial activities against most of the clinical isolates which could be causative organisms of infectious diseases in the clinical practice. When it is additionally taken into account that CAZ is one of those limited drugs with activity against P. aeruginosa, and it has excellent permeability through outer membrane, it is concluded that CAZ still is one of the clinically useful cephem drugs in 1990's.


[Antimicrobial activity of cefetamet against clinically isolated microbial strains collected from urban RTI patients].

The authors studied antimicrobial activities of cefetamet (CFMT) and other leading oral antimicrobials of beta-lactam class against clinically isolated strains from urban respiratory tract infection (RTI) patients from January to March, 1992. 1. CFMT showed potent antimicrobial activities against "3 primary pathogens" of RTIs i.e., Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, but the drug had a slightly higher MIC than those of a few oxime-type cephems already on the market. 2. CFMT was as stable as cefixime to beta-lactamase, generated by Moraxella subgenus Branhamella catarrhalis, which reduces the antimicrobial activity of cephems. 3. Blood concentrations of CFMT after administering cefetamet pivoxil (CFMT-PI), an oral form of the drug, exceeded the MIC80 against the "3 primary pathogens" as well as M. (B) catarrhalis and Klebsiella pneumoniae, for a duration of approximately 9 and 11 hours, respectively, after single doses of 250 and 500 mg. This suggests that CFMT could remain above the MICs for a sufficient time period with twice daily dosages of normal dose levels. 4. It is concluded that CFMT-PI will be useful for treating urban RTIs.


[Therapeutic effects of cefuzonam against severe infections in patients with hematopoietic disorders. Hanshin Infection Study Group].

Cefuzonam (CZON) was used to treat severe infections in 151 patients with hematopoietic disorders, and its efficacy and safety were assessed. The drug was given in doses of 2.0 to 6.0 g a day, divided into 2 or 3, intravenously by injection or infusion. The clinical effects were excellent in 34 cases, good in 40 cases, fair in 5 cases, and poor in 57 cases. Therefore, the results were excellent or good in 54.4% of the patients treated. The efficacy rates were 43.8 and 35.9% for groups of patients whose neutrophil counts were 500/microliters or less and 100/microliters or less, respectively. It was excellent or good in 70.6% of patients in whom causative agents were identified, and in 66.7 and 80.0% of patients infected with Gram-negative and -positive bacilli, respectively. The efficacy rate for patients infected with unidentified agents was 52.1%. The rate for patients who had received other antibiotics previously was 41.5%. The rate for patients having received only one antibiotic for the preceding treatment was 50.0%. Six (3.9%) of the treated patients experienced adverse effects including changes in laboratory test results observed in 4.


[Pharmacokinetics of cefprozil in infant and adult beagle dogs].

The Pharmacokinetics of cefprozil was studied upon oral administration of 25 mg/kg to fasted infant and adult Beagle dogs. When the pharmacokinetic parameters between infant and adult dogs were compared, the mean peak concentration (Cmax) in infant dogs (21.2 micrograms/ml) was significantly (P < 0.01) lower than that of adult dogs (27.8 micrograms/ml). But significant differences were not found in the areas under the concentration-time curve (AUC, in infant dogs: 121 micrograms.hr/ml, in adult dogs: 130 micrograms.hr/ml), half-lives (T 1/2, in infant dogs: 4.7 hours, in adult dogs: 4.7 hours) or urinary recovery rates (UR, in infant dogs: 36.3%, in adult dogs: 34.7%) between the 2 groups. These results suggest the distribution volumes of infant dogs are larger than those of adult dogs, and the absorption rates of infant dogs are slower than those of adult dogs, whereas the absorption quantities are similar.


[The influence of cefprozil on intestinal bacterial flora].

Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin antibiotic, was studied for its effect on the intestinal bacterial flora in pediatric patients. The subjects were children admitted for infections (2 males and 2 females, 9 months to 6 years 3 months old, weighed 4.3 to 19.0 kg). CFPZ granule was orally administered at a dose between 10.0 to 11.6 mg/kg, 3 doses daily, over 4 to 14 days. The feces from these children were collected before, during and after administration, and bacteria were identified and counted. CFPZ concentration, beta-lactamase activity were also assayed. Bacterial flora in feces during CFPZ administration showed some variance, but no significant change was observed in main aerobes and anaerobes. And in no case, glucose nonfermentative Gram-negative bacilli or fungi were found dominant. beta-Lactamase activity was positive in the feces in all cases. CFPZ concentrations were not detectable in feces before, during and after administration. The above results suggest that CFPZ is a drug with little influence on the intestinal bacterial flora in children.


[Pharmacokinetic study on oral antibiotics in pediatrics. III. A pharmacokinetic study on cefprozil in pediatrics].

The absorption and excretion were studied in the field of pediatrics, and pharmacokinetic analyses were performed. 1. Influence of food: Cefprozil (CFPZ, BMY-28100) was given to 6 school children in a before and after meal cross over design. With before meal administration, Tmax was 1.11 +/- 0.08 hours, Cmax was 5.08 +/- 0.27 micrograms/ml, T 1/2 was 0.77 +/- 0.09 hour, and urinary recovery rate (0-8 hours) was 55.2 +/- 4.7%. With after meal administration, these values were 1.31 +/- 0.04 hours, 3.98 +/- 0.38 micrograms/ml, 0.72 +/- 0.03 hour and 46.3 +/- 9.0%, respectively. A shorter Tmax value was, obtained higher Cmax and more or less higher urinary recovery rate when the drug was administered before meal, hence the food was considered to influence the absorption of the drug. 2. Dose effect: CFPZ was given on empty stomach to 6 school children in doses of 7.5 mg/kg and 15.0 mg/kg in the cross over design. With the lower dose Cmax was 6.19 +/- 0.36 micrograms/ml and AUC was 14.90 +/- 1.02 micrograms.hr/ml, and with the higher dose they were 12.38 +/- 1.29 micrograms/ml and 28.56 +/- 1.79 micrograms.hr/ml. Dose effects appeared to exist for CFPZ. A higher urinary recovery rate was obtained at the dosage of 7.5 mg/kg (82.1 +/- 6.4%) compared to the dosage of 15.0 mg/kg (51.1 +/- 7.1%). 3. Influence of age: CFPZ was given on empty stomach to 17 school children, 19 younger children and 5 infants. Tmax were 1.07 +/- 0.09, 1.06 +/- 0.07, and 1.40 +/- 0.09 hours, respectively for the 3 groups, hence significantly longer Tmax was observed in infants. Cmax were higher in older children and they were 5.62 +/- 0.38, 4.72 +/- 0.53 and 4.05 +/- 0.33 micrograms/ml, in the 3 age groups, respectively. T 1/2 were 0.73 +/- 0.04, 0.78 +/- 0.09 and 0.98 +/- 0.12 hour, respectively, it was longer in infants. The AUCs were not different among the 3 groups, but different urinary recovery rates were obtained with higher recovery in school children, with values of 64.1 +/- 4.3, 44.3 +/- 3.8 and 51.6 +/- 3.3%, respectively.


[Clinical evaluation of a new oral cephem, cefprozil in children].

Cefprozil (CFPZ, BMY-28100) was evaluated for its efficacy, safety and pharmacokinetics in children. CFPZ was effective against streptococcal pharyngitis, pneumococcal lower respiratory tract infections, staphylococcal skin infections and Escherichia coli urinary tract infections, but was less effective against lower respiratory tract infections and otitis media due to Haemophilus influenzae. No adverse reactions were encountered in 46 cases treated with CFPZ. With a premeal administration of 7.5 mg/kg, the Cmax was approximately 3.2 micrograms/ml and the T 1/2 beta was 1.4 hours. From the present study, CFPZ appears to be safe and effective against community-acquired childhood infections.


[Clinical studies on cefprozil granules in pediatrics].

Cefprozil (CFPZ, BMY-28100) granules was administered to a group of pediatric patients. The new oral cephalosporin, CFPZ, was evaluated clinically in 42 pediatric patients, and a pharmacokinetic study was performed in 6 patients. Serum and urinary concentrations of CFPZ were determined in 6 patients who were given single dose of 7.5 or 15.0 mg/kg. Serum concentrations were determined at 1, 2, 3, 4 and 6 hours after dosing. Urinary concentrations were measured for periods of 0-6 hours after dosing. With oral administrations of 7.5 mg/kg and 15.0 mg/kg, peak serum concentrations were 2.13 micrograms/ml and 6.22 micrograms/ml, respectively, at 2 hours, and biological half-lives were 1.06 hours and 1.36 hours, respectively. Urinary recovery rates were 44.8% and 56.1%. The clinical evaluation was conducted in 41 patients including 16 patients with acute tonsillitis, 8 patients with lacunar tonsillitis, 4 patients with scarlet fever, 3 patients with acute bronchitis, 1 patient each with pertussis, furuncle, impetigo and lymphadenitis, and 6 patients with urinary tract infections. The ages of the patients were 10 month to 11 years 1 month, and they were treated with CFPZ at doses ranging 9.0-45.0 mg/kg daily for 3-14 days, the overall clinical efficacy rate was 92.7%. An eradication rate of 79.2% was achieved for 28 strains of 8 species identified in the patients. No side effects were observed. Abnormal laboratory test results obtained were eosinophilia in 2 patients.


[Laboratory and clinical studies on cefprozil granules in pediatrics].

Fundamental and clinical effects of cefprozil (CFPZ, BMY-28100) granules, a new oral cephalosporin antibiotic, in pediatric field were investigated. The result obtained were summarized as follows. 1. CFPZ (10% granules) was given to 1 child in a single dose of 7.5 mg/kg. The peak serum concentration of CFPZ was 4.51 micrograms/ml at 2 hours after administration. Half-life and AUC values were 0.98 hour and 20.7 micrograms.hr/ml. The mean peak urinary concentrations of CFPZ and 6 hours recovery rates were over 200 micrograms/ml at 2-6 hours and 27.6%, respectively. 2. Clinical efficacy of CFPZ was investigated in a total of 41 children, including 14 with upper respiratory tract infections, 6 with acute bronchitis and pneumonia, 2 with acute otitis media, 3 with skin and soft tissue infections and 16 with urinary tract infections. The clinical efficacy rate was 95.1%. The bacteriological eradication rate was 84.6%. 3. Two patients showed abnormal laboratory test results. One had elevations of both GOT and GPT, and another had eosinophilia which were attributed to this antibiotic as side effects.


[Clinical study on cefprozil in pediatrics].

Clinical efficacy and safety of cefprozil (CFPZ, BMY-28100), a newly developed oral cephalosporin, were studied in our pediatric department. Clinical effectiveness, bacteriological effectiveness and side effects were studied in 116 pediatric patients with ages ranging 4 months to 11 years. CFPZ was given 4.6-14.1 mg/kg daily in 3 times for 3-10 days. Clinical efficacies were evaluated in 112 patients, and the therapeutic effectiveness were excellent in 1 and good in 6 for 7 patients with acute pharyngitis, excellent in 24 and good in 26 for acute purulent tonsillitis, excellent in 3, good in 8 and fair in 1 for acute bronchitis, excellent in 21, good in 7, fair in 1 and poor in 1 for acute pneumonia, excellent in 1 acute purulent parotitis, excellent in 2 and good in 7 for acute UTI, good in 1 impetigo, fair in 1 periproctal abscess and good in 1 acute enteritis. The effectiveness rate was 96.4%. Bacteriologically, 4 strains of Staphylococcus aureus (beta-lactamase producing strains), 1 strain of Staphylococcus epidermidis (beta-lactamase producing strain), 2 strains of Streptococcus pneumoniae, 2 strains of Streptococcus agalactiae, 4 strains of beta-Streptococcus, 1 strain of Klebsiella pneumoniae (beta-lactamase producing strain) and 1 strain of Salmonella C2 were all disappeared, and of 22 strains of Streptococcus pyogenes, 20 strains were disappeared, 1 was decreased and 1 was unknown, of 5 strains of Escherichia coli (3 beta-lactamase producing strains), 4 were disappeared and 1 was decreased, of 29 strains of Haemophilus influenzae (14 beta-lactamase producing strains), 14 were disappeared, 11 were decreased, 3 persisted and 1 was unknown and of 2 strains of Haemophilus parainfluenzae (1 beta-lactamase producing strain), 1 was disappeared and 1 persisted. The bacteriological eradication rates for Gram-positive bacteria and Gram-negative bacteria were 97.1% and 56.8%, respectively, and the drug was especially effective against Gram-positive bacteria. No side effects nor refusal of ingestion were observed. As abnormalities in laboratory test results, 3 cases of elevation of eosinophil counts and 1 of elevation of platelet counts were observed. In conclusion, CFPZ was considered to be a safe and highly effective antibiotic in pediatric infections.


[Laboratory and clinical studies on cefprozil in the field of pediatrics].

Laboratory and clinical studies on cefprozil (CFPZ, BMY-28100), a new cephem antibiotic, were carried out in the field of pediatrics. The results obtained are summarized as follows: 1. Serum concentrations, urinary concentrations and urinary recovery rates of CFPZ were determined upon oral administration of CFPZ after meal at doses of 4 mg/kg granules in a case, 7.5 mg/kg granules in 2 cases and 15 mg/kg granules in one. Peak serum levels of CFPZ were obtained at an hour in 3 cases and at 2 hours in 1 case after administration of the drug with a range of 2.7-8.6 micrograms/ml with half-lives of 0.69-0.95 hours. Urinary recovery rates in the first 6 hours after administration ranged from 59.4-71.3%. 2. MICs of CFPZ against 36 clinical isolates (Staphylococcus aureus 4 strains, Streptococcus pneumoniae 5, Streptococcus pyogenes 5, Escherichia coli 5, Haemophilus influenzae 12, Haemophilus parainfluenzae 4, and Branhamella catarrhalis 1) were compared with those of cefaclor (CCL) and ampicillin (ABPC). The antibacterial activity of CFPZ was superior to those of CCL against Gram-positive cocci, and to those of ABPC against E. coli, and was equal to those of CCL and inferior to those of ABPC against H. influenzae. 3. Thirty-seven pediatric patients with acute infectious diseases (pharyngitis/tonsillitis 17, bronchitis 7, pneumonia 3, skin and soft tissue infection 2, and urinary tract infection 8) were treated with CFPZ at daily doses of 10-47 mg/kg t.i.d. as a rule. The efficacy rates were 100% clinically and 56% bacteriologically. 4. Side effects or abnormal laboratory test values were not observed except for an increased platelet count in 1 case and elevated GOT, GPT values in 2 cases.


[Pharmacokinetic, bacteriological and clinical studies on cefprozil in pediatric patients].

Cefprozil (CFPZ, BMY-28100), a new oral cephem antibiotic, was studied for its antibacterial activities, absorption and excretion upon administration. Its clinical efficacies were also studied in pediatric patients with infections. A study on antibacterial activities of CFPZ against 11 clinical isolates including 6 species found that its activities against Staphylococcus aureus, alpha-hemolytic Streptococcus, Escherichia coli and Haemophilus influenzae were equal or superior to those of CCL. When CFPZ was given to patients orally at 15 mg/kg, maximum serum concentration was obtained between 1 to 2 hours after administration and urinary excretion rate in the first 6 hours was 33.8 +/- 17.6%. Clinical evaluation was done in a total of 25 patients with various infections. Responses were excellent in 15 cases and good in 10 cases, hence the efficacy rate was 100%. As side effect, soft stool was found in 1 case, and eosinophilia in 2 cases and elevation of GOT and GPT in 1 case were found as abnormal laboratory test results, but none of them was serious. It appears that CFPZ is an effective and safe antibiotic in the field of pediatrics.


[Laboratory and clinical studies of cefprozil in pediatric field].

Laboratory and clinical studies were done on cefprozil (CFPZ, BMY-28100). The results are summarized as follows. CFPZ was administered through the oral route to 2 children at a single dose of 7.5 mg/kg. After administration, peak serum levels of CFPZ obtained in the 2 cases were 6.71 micrograms/ml at 1 hour and 6.45 micrograms/ml at 2 hours, respectively and half-lives were 1.28 hours and 0.92 hour, respectively. The urinary excretion rates of CFPZ were 58.9% and 59.4%, respectively. Treatment with CFPZ was made in 37 cases of pediatric bacterial infections: 1 case of pharyngitis, 16 cases of tonsillitis, 16 cases of scarlet fever, 3 cases of impetigo, 1 case of UTI. Results obtained were excellent in 24 cases, good in 13 cases. No significant side effects due to the drug were observed, except 1 case of loose stool, 3 cases of eosinophilia, and 1 case each of elevated GOT and GPT.


[Overall clinical evaluation of cefprozil against infections in pediatric fields. Pediatric Study Group for Cefprozil].

Cefprozil (CFPZ, BMY-28100) granule preparation was studied for pharmacokinetic, bacteriological and clinical aspects in the pediatric infections. The results obtained are summarized as follows: 1. Serum concentrations and urinary excretion. The pharmacokinetics of CFPZ in pediatrics was investigated by single oral administration of fine granules at doses of 4.0, 7.5 and 15.0 mg/kg. Peak blood levels of CFPZ were 3.06, 4.62 and 9.65 micrograms/ml, respectively, at 1.00-1.30 hours after each dose and AUCs were 7.44, 12.50 and 27.01 micrograms.hr/ml, respectively. These data showed that Cmax and AUC depended on dose levels. T 1/2 (beta) at these dose levels were 1.03, 0.94 and 1.01 hours, respectively. There were no differences related to dose. Urinary recovery rates in the first 6 hours after administration were 51.5-57.1%. The pharmacokinetics of CFPZ before or after meals were also investigated at a dose of 7.5 mg/kg. Peak blood levels were 4.88 micrograms/ml at 1.17 hours after administration in the fasting state, and 4.30 micrograms/ml at 1.54 hours after administration in the non-fasting state. Delay of Tmax and slight decrease of Cmax were observed in the non-fasting state, but T 1/2 and AUC were 0.91 hour and 12.96 micrograms.hr/ml, respectively, in the non-fasting state, and were similar to those in the fasting state, 0.93 hour and 12.82 micrograms.hr/ml, respectively. Urinary recovery rates in the first 6 hours after administration were 63.8% in the fasting state and 50.7% in the non-fasting state. 2. Clinical results. Clinical efficacies of CFPZ granules in various infectious diseases were studied in 804 cases. Twenty nine cases, mostly viral or mycoplasmal infections, were excluded from the statistical analysis. The clinical efficacy rate in 527 cases with causative bacteria isolated was 97.2%; and in 248 cases from whom no significant isolate had been obtained was 96.0%. The clinical efficacy rate in 475 cases with monobacterial infections (proven by culture of isolates) was 97.3%, and that in 52 case with polybacterial infections was 96.2%. Haemophilus influenzae was isolated mostly from acute respiratory infections. In 88 cases from whom H. influenzae was isolated, clinical efficacy rate was 95.5%. In cases from whom H. influenzae was found concomitant by with Staphylococcus aureus, Streptococcus pyogenes or Streptococcus pneumoniae, the clinical efficacy rates were also high. The bacteriological eradication rate in cases with 582 strains was 83.3%; the eradication rate for Gram-positive organisms was 95.8%; and for Gram-negative organisms, it was 64.2%.(ABSTRACT TRUNCATED AT 400 WORDS)


[Changes in DNA synthesis in lymphocytes induced by carbachol via muscarinic acetylcholine receptor in relation to aging and Alzheimer's disease in females].

To investigate whether cellular DNA synthesis in lymphocytes can be induced by carbachol, we studied the effect of carbachol in cultures of peripheral lymphocytes. Three age groups of healthy female adults were examined: 40-49 (N = 10), 51-59 (N = 8), and 61-69 years old (N = 8). Moreover, we studied lymphocytes from 14 female patients (47-69 years old) with probable Alzheimer's disease. Lymphocytes were incubated for 72 hrs at 37 degrees C, with or without 5 mM carbachol. The effects of carbachol on the initiation of DNA synthesis in lymphocytes were determined by 24 hr-pulse-labeling with [3H]-thymidine ([3H]-dT). Stimulation indexes (S.I.) were defined as the ratios of DNA synthesis induced with or without carbachol. In 37 out of 40 subjects, carbachol elicited an increase in [3H]-dT incorporation. Furthermore, carbachol induction of DNA synthesis was blocked by muscarinic antagonist, atropine. These data show that carbachol induces DNA synthesis in peripheral lymphocytes are well as the central nervous system, indicating that the proliferation is mediated by the muscarinic acetylcholine receptor. For healthy controls (age range 40-69 years old, N = 26), a negative correlation (r = -0.505, p < 0.01) was found between age and S.I. The regression equation was: Y = -0.575X + 142.1 where, X and Y designate the age of individuals and S.I., respectively. However, there were significant differences (p < 0.05) with S.I. between age groups 40-49 and 61-69 years old. For patients with Alzheimer's disease, no correlation was obtained between age and S.I.(ABSTRACT TRUNCATED AT 250 WORDS)


[The relationship between dietary ascorbic acid intake and serum lipid concentration in the aged].

The aim of this study was to investigate the relationship between dietary ascorbic acid intake and serum lipid concentration in the aged. The amount of dairy food intake for three consecutive days were measured and the serum levels of total-cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDLC) were determined 279 subjects (135 males and 135 females), 65 years and over living in one community. The LDL-cholesterol (LDLC) was calculated by (TC-HDLC)-TG x 0.2. Dietary ascorbic acid intake showed no significantly difference between males and females, but had a significantly positive correlation with HDLC, the intake of carbohydrates and protein and total fat. However it had a significantly negative correlation with LDLC and LDLC/HDLC. Multiple regression analysis showed that dietary ascorbic acid intake had a statistically significant relationship with HDLC, LDLC and LDLC/HDLC. Since HDLC, which is known to be an anti-atherogenic, was related to increase in the dietary ascorbic acid intake, and LDLC, which is known to be an atherogenic, was related to its decrease, it was suggested that dietary ascorbic acid intake might have an important effect on the genesis and prevention of atherogenic diseases.


[Changes in blood pressure and pulse rate during visit to a doctor's office].

Changes in blood pressure (BP) and pulse rate were measured during visits to a doctor's office by means of an non-invasive ambulatory BP monitoring device in 47 elderly hypertensive patients (mean age 73.0 years). Systolic BP increased from 140.5/85.4 mmHg to 157.9/85.7 mmHg immediately after entering the doctor's office and tended to return to the previous level at 5 minutes after entering although diastolic BP did not change during the visit. Pulse rate also increased slightly, but significantly on entering the office. The difference in BP between 25 minute before and just after entering an office was +17.4 mmHg in systolic. -0.1 mmHg in diastolic. If an increment in systolic BP more than 10 mmHg was defined as positive for white coat effect, they were observed in 59.6%. The frequency of white coat hypertension was 46.7% in the age of sixties, 65.2% in seventies and 66.7% in eighties but there was no significant difference among 3 groups. There was a tendency for white coat hypertensions to be more frequent in men compared than in women (p = 0.07).


[Cerebral infarctions in elderly patients with anemia].

The authors investigated the cause of cerebral infarctions in elderly patients with anemia. Among 411 patients with acute cerebral infarctions, eight patients showed anemia (Hb < 10 g/dl) at the time of stroke. Only 2 patients had strokes during hospitalization were aware of their anemias before stroke. They were classified into two groups. One was the sudden onset group (4 patients) of whom 3 had malignant tumors, and 2 showed disseminated intravascular coagulations (DIC). There were no patients with atrial fibrillation or cardiac disease. All patients showed cortical infarction, and two died soon after stroke. Autopsy revealed verruca formation of the mitral valve in one patient and thrombus in the right ventricle in another. We thought that non-bacterial thrombotic endocarditis (NBTE) was the major cause of cerebral infarctions in this group. The other group consisted of 4 cases of thrombotic stroke. Their neurological symptoms appeared to be progressive. They also showed cortical infarctions except for one case of pontine infarction. Severe stenosis of the cerebral arteries was revealed by angiography in two patients and by autopsy in one. We concluded that cerebral infarctions in elderly patients with anemia can be important signs of underlying malignant tumors in sudden onset strokes or cases of severe cerebral artery stenosis with thrombotic strokes.


[Psychosomatic state of centenarians].

A survey to investigate the psychiatric and physical characteristics of centenarians was conducted from 1987 to 1989 in the Tokyo metropolitan area with a team of psychiatrists and psychologists using a semi-structured interview form. In that 3-three period, out of 509 centenarians living in Tokyo, 294 persons and their caregivers (57.8%) including the 65 institutionalized centenarians were examined. Two hundred and fifteen centenarians were not able to be interviewed due to various reasons. Out of 294 centenarians, 76 persons (25.9%) were interviewed by telephone. Also out of these, 176 (59.8%) were living with their son's or daughter's family. Ten male centenarians (12.8%) were living with their wives, while no female was living with a spouse. Five men and four women were living alone. There was a marked difference of education in years between both sexes. Mean years of education were 10.2 in the male and 5.5 in the female. According to the Clinical Dementia Rating, 31.6% out of 218 centenarians interviewed were not demented and those with dementia were even distribution of mild, moderate and severe dementia. There were marked differences according to sex, similar to that found in ADL. Of 63 males, 46.0% were not demented, whereas 25.8% of 155 females were not demented. Only 3.2% of males were severely demented, but in females 27.1% showed severe dementia. HDS scores decreased in relation to the advance in severity of dementia. Approximately 27% of the cases had no previous physical histories; 21.8% for the male and 29.2% for the female.(ABSTRACT TRUNCATED AT 250 WORDS)


[Clinical characteristic of elderly patients with insulin-dependent diabetes mellitus].

The number of elderly patients with insulin-dependent diabetes mellitus (IDDM) is increasing because of the prolongation of life due to the improvement of diabetic control. For better management of elderly patients with IDDM, we investigated the clinical and genetic characteristic of older patients with IDDM in comparison with younger patients. The subjects studied consisted of 19 patients with IDDM treated at the Department of Geriatric Medicine, Osaka University Hospital. Among the 19 subjects, 7 patients (37%) were more than 50 years old, including 3 patients (16%) more than 65 years old. The clinical and genetic characteristics of these 7 patients (older patients group) were compared with those of 12 patients (younger patient group) whose age was less than 50 years old. The age at onset of IDDM was significantly higher in older patient group (46 +/- 13 years old; mean +/- SD) than in younger patient group (34 +/- 6 years old). There was no significant difference in the duration of IDDM between older and younger patients (13 +/- 6 and 12 +/- 8 years, respectively). There were no significant differences in daily insulin dose, glycemic control (fasting plasma glucose and HbA1c levels) and glycemic stability as measured by the standard deviation of 10 measured fasting plasma glucose levels between the two groups. The frequency of diabetic retinopathy and neuropathy in the older patients was slightly, but not significantly, higher than that in younger patients. The frequency of diabetic nephropathy was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)


[Role of neutrophil and T cell functions in host defense mechanisms of the elderly].

We studied neutrophil functions (phagocytosis, intracellular killing and chemotaxis with or without recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and T cell functions (lymphocyte proliferation and production of GM-CSF in response to phytohemagglutin (PHA)) to clarify host defense mechanisms in the elderly. There was no significant difference in phagocytic activity of neutrophils between the elderly and control young adults. rhGM-CSF enhanced phagocytosis by neutrophils, and a similar degree of enhancement was obtained in both groups. Killing activity of neutrophils evaluated by the new Nitroblue tetrazolium reduction test in the elderly was significantly lower than that in young adults (p < 0.001), however, pretreatment of neutrophils with rhGM-CSF resulted in an increase of killing activity in the elderly, raising their response to a level comparable to that of young adults pretreated with rhGM-CSF. There was no significant difference between the elderly and young adults in chemotaxis of neutrophils. rhGM-CSF alone did not prime chemotaxis, but primed chemotaxis in response to chemoattractant (N-formyl-methionyl-leucyl-phenylalanin) in both individuals. Lymphocyte proliferation and production of GM-CSF in response to PHA in the elderly were significantly lower than those in the young adults (p < 0.001, p < 0.05, respectively). These results indicated that impaired T cell functions may contribute, at least in part, to susceptibility to bacterial infection in the elderly.


[The relationship between fecal kinetics and body temperature in elderly people].

The relationship between fecal kinetics and body temperature was examined in elderly people. The subjects consisted of 34 hospitalized patients over 65 years of age (11 males aged 66-82 years, with a mean age of 70.3 years; and 23 females aged 65-84 years, with a mean age of 72.1 years). Then mean age of all subjects was 71.5 years. The subjects were divided into two groups: the non-constipation (NCP) group (patients who had been evacuating at least once daily) and the constipation (CP) group (patients who had not evacuated for 3 days or more). In the CP group, we analyzed the lowest and highest body temperature during two consecutive days (the day of evacuation and the previous day) and the lowest body temperature during another two days (the day of evacuation and the following day). In the NCP group, 3 consecutive days were selected at random for analyzing the lowest body temperature on the first day, the highest body temperature on the second day and the lowest body temperature on the third day. In the CP group, the body temperature before evacuation was 37.3 degrees C or more in 6 of the 28 patients (21.4%). In the NCP group, the highest body temperature before evacuation averaged 36.39 degrees C and the lowest body temperature after evacuation averaged 36.0 degrees C, with a temperature difference of 0.39 degrees C between the pre- and post-evacuation periods.(ABSTRACT TRUNCATED AT 250 WORDS)


[Prediction of nocturnal desaturation in elderly patients with chronic respiratory disease].

Previous reports suggest that nocturnal disorders of sleep and breathing have increased prevalence among the elderly, and episodic nocturnal oxygen desaturation (NOD) has an increased incidence in patients with chronic respiratory disease. Current Japanese criteria for home low flow oxygen therapy (LFOT), recommend LFOT for patients with daytime PaO2 < 55 torr or with daytime PaO2 < or = 60 torr who have significant NOD. Strict adherence to these LFOT criteria requries full overnight monitoring of arterial oxygen saturation (SaO2) in all patients with daytime PaO2 < or = 60 torr. Since widespread nocturnal oximetry involves significant expenditure of time and resources, it is important among patients with chronic respiratory diseases to predict those who will have significant NOD. The aim of the present study was to formulate criteria for identification of patients who are most likely to demonstrate significant NOD based upon daytime respiratory function data. Subjects included 34 elderly patients with daytime PaO2 > or = 55 torr, who had stable severe chronic respiratory disease (15 chronic emphysema, 6 chronic bronchitis, 12 post-tuberculosis, and 1 kyphoscoliosis). Study data included medical history, assessment of dyspnea by Hugh-Jones classification, and measurement of daytime, awake arterial blood gases and spirometry. Each subject underwent full overnight oximetry monitoring. The percentage of total sleep time recorded with SaO2 < or = 85% was noted (DST85), and NOD was defined as DST85 > or = 1%. Of the 34 patients, 11 were identified as NOD, and 23 as non-NOD patients. Duration and severity of dyspnea were not different between NOD and non-NOD patients.(ABSTRACT TRUNCATED AT 250 WORDS)


[Two cases of adult onset of Still's disease in the elderly].

Two cases of adult onset of Still's disease is in a 83-year-old and a 61-year-old women. Both cases complained of high fever, arthralgia, sore throat and maculae. Examinations on admission revealed leukocytosis and negative antinuclear antibody. Administration of prednisolone resulted in improvement of the clinical symptoms and laboratory data. In general, the onset of this disease is usually in early adulthood, but in these two cases the onset was at an advanced age. These results suggest that Still's disease of adult onset should be included in the differential diagnosis of fever of unknown origin, if the patient is elderly. In the treatment of the disease, proper attention to side effects of prednisolone and complications can be important.


[Improvement of respiratory function with weight reduction in obese elderly].

The patient was a 74-year-old woman who had been obese since age 18. Her obesity was refractory to dietary manipulation. She had been suffering from increasing dyspnea for several months and eventually could not even move. She was admitted to a hospital and diagnosed as having heart failure. Although her cardiac function recovered with medical treatment, her symptoms did not improve. The patient was then sent to our hospital. On admission, her height and weight were 149 cm and 81.9 kg, respectively, yielding a body mass index (BMI) of 36.6 kg/m2. Arterial blood gas analysis in room air revealed hypoxemia and an apnea index of 27 per hour. She was given a daily 500-1000 kcal diet. After four months of treatment, her weight decreased to 65 kg with a BMI of 29.3 kg/m2. Weight reduction together with the usage of progesterone-derivatives resulted in marked improvement of sleep apnea. The apnea index decreased to 3/h and arterial blood gas values normalized. This patient seemed to have suffered from both obesity hypoventilation syndrome and sleep apnea syndrome. Improvement of respiratory function was achieved through relief of airway obstruction and weight reduction, with activation of the respiratory center due to progesterone treatment.


[Elderly non-Hodgkin's lymphoma presenting with pulmonary squamous cell carcinoma as a complication of chemotherapy for malignant lymphoma].

The authors report a case of pulmonary squamous cell carcinoma which occurred after chemotherapy of non-Hodgkin's lymphoma (NHL). A 76-year-old man, who was admitted to our department because of swelling of cervical lymph nodes, was diagnosed as having NHL (follicular mixed cell lymphoma). He was treated with 11 courses of CHOP therapy. Thereafter, chemotherapy including ifosfamide was carried out for approximately three years. In June, 1991, he was readmitted to our department because of swelling and pain in his left thigh and an abnormal shadow on chest X-ray. Chest CT demonstrated a cavitated shadow (about 5 cm in diameter) with an irregular margin in right S1, which was suggested to be lung cancer or pulmonary infiltration of malignant lymphoma. Bronchoscopy, which was carried out on July 12, showed bloody sputa from the right B1 ramus and markedly reddened mucosa at the orifice of the right upper bronchus. Sputum cytology revealed no malignancy. ACVP-16 chemotherapy including ara-C, CBDCA and VP-16 was initiated on July 14 because of enlarged superficial lymph nodes. On July 18, he fell out of bed and fractured his left femur. He also suffered from respiratory failure. He died of pulmonary haemorrhage on July 26. Autopsy revealed pulmonary squamous cell carcinoma. The occurrence of pulmonary squamous cell carcinoma is rare after the chemotherapy of malignant lymphoma.


Oral motor control, posturing, and myofunctional variables in 8-year-olds.

One hundred thirty-three rural second graders were evaluated for diadochokinetic abilities and myofunctional variables. Single-syllable diadochokinetic rates were significantly correlated with open-mouth resting postures. Slow trisyllable diadochokinetic rates were significantly correlated with a dentalized resting tongue posture and dentalized swallow patterns. The implications of these relationships are discussed.


Glottal gap configurations in two age groups of women.

The purpose of this study was to gather data on glottal gap configurations in two age groups of women. Using videostroboscopy, glottal closure patterns of 20 women (10 young, 10 elderly) were observed across nine pitch/loudness conditions. While both young and elderly speakers displayed a high incidence of glottal gaps, the two groups differed markedly in the configuration of the gaps observed and in the phonatory conditions under which gaps were observed. Young speakers demonstrated posterior chink and incomplete closure significantly more frequently than elderly women, although rarely demonstrating anterior gap or spindle configuration. In contrast, anterior gap was the single most common type of gap in the elderly, with spindle also occurring significantly more frequently. Individual elderly speakers, overall, changed glottic configuration more frequently across phonatory conditions than did young speakers. Some individual elderly speakers tended to vary glottic configuration consistently with pitch level changes.


Gradations in a pattern of neuromuscular activity associated with stuttering.

EMGs were recorded from muscles of the lip, jaw, and neck during conversational speech of 17 stuttering subjects. Averaged power spectra and coherence between pairs of EMGs were computed. Results indicate that tremorlike oscillations in the range of 5-15 Hz and high amplitudes of EMGs occupy a common continuum of motor patterns that may occur in stuttering. In subjects whose results fell at the strong end of this continuum, stuttered speech was distinguished by widely distributed, high-amplitude oscillations and relatively high coherence at the frequency of oscillation. At the other extreme, neither oscillatory activity nor amplitude was greater for stuttered speech; in fact stuttered and fluent speech were often associated with approximately equal EMG amplitude. These results suggest that there is not a single set of physiological events that uniformly characterize stuttering in all individuals; rather, events such as the occurrence of high-amplitude oscillations occur at different strengths in different individuals.


Disfluencies in the conversations of young children who stutter: some answers about questions.

Parents of children who stutter are often advised to reduce the number of questions they ask their children. Implicit in this advice is the assumption that children who stutter will be more disfluent when answering questions. This study assessed parent-child conversational speech for 8 parent-child pairs to determine the relative amounts of disfluency in the child's responses to questions versus making assertions. Length and complexity of the children's utterances and the frequency of the parents' requests by level of demand were also evaluated. Results suggested that the responses made by the children to their parents' requests were significantly less likely to contain disfluencies than were their assertions. Also, longer and more complex utterances were more likely to contain disfluencies, regardless of their designation as assertions or responses. Parents were shown to favor request types of lower levels of demand in conversations. Requests posed with greater levels of demand were somewhat more likely to yield disfluent responses than were those at a lower demand level.


Tongue strength and endurance: relation to highly skilled movements.

Tongue strength and endurance (fatigue) were examined in subjects who have acquired high skill levels with their tongues (supranormal) and in subjects who use the tongue normally. The supranormal groups were trumpet players and high school debaters who were able to speak intelligibly at rates much faster than normal. Hand strength and fatigue were also assessed. Maximal strength was measured by recording how much pressure an individual could exert on an air-filled bulb. Endurance was measured by determining how long subjects could sustain 50% of their maximal pressure. Results showed that maximal strength of the tongue and hand did not differentiate the supranormal subjects from the normal subjects. Hand endurance did not differentiate the subjects either. However, the supranormal groups had significantly longer tongue endurance times than did the normal subjects.


Speech breathing in senescent and younger women during oral reading.

Breathing patterns in 20-30-year-old and 60-70-year-old women were recorded noninvasively during various nonspeech and oral reading tasks. On the nonspeech tasks, the only significant difference between groups was a smaller mean vital capacity for the older women. On oral reading, the older women had significantly greater means for absolute and relative inhalatory volumes, relative inhalatory airflow rates, absolute and relative volumes during nonphonatory exhalations, and relative exhalatory volumes. No significant mean differences between groups were found on absolute inhalatory airflow rates, absolute exhalatory volumes during speech, and absolute and relative exhalatory airflow rates. In both age groups, increases in sentence length were associated with significantly increased inhalatory and exhalatory volumes but mean airflow rates were not significantly affected by sentence length. Some differential effects of reading context on only the older group seemed to represent additional demands placed on their respiratory systems for speech breathing.


Speaking rates, response time latencies, and interrupting behaviors of young stutterers, nonstutterers, and their mothers.

The purpose of this study was to investigate the speaking rates, interrupting behaviors, and response time latencies (RTL) produced by stuttering and nonstuttering children and their mothers, and the relationship these three paralinguistic behaviors have to children's speech disfluencies. Subjects were 13 boys who stutter (mean age = 4:0) and their mothers and 13 nonstuttering boys (mean age = 4:0) and their mothers. No significant differences were found between the two groups of children or between the two groups of mothers for any of the three paralinguistic behaviors with the exception that the mothers of nonstuttering children exhibited significantly (p < 0.01) faster rates of speech than either group of children. A strong positive correlation (r = .84) was found between stuttering children's scores on the Stuttering Severity Instrument (Riley, 1980) and the durations of the overlapping portions of their mothers' interruptions (i.e., their simultalk). Findings of this study are taken to support a facilitative demands-capacities model of conversational interaction in which mothers adjust the demands of their speaking models in response to their children's demonstrated capacities for fluent speech production.


Modifications in sign under conditions of impeded visibility.

This study investigated the effects of reduced visibility on the distance of signing hands from the bodies of adult signers who are deaf and on their rates of sign production. Subjects were videotaped as they signed with partners in each of three experimental conditions: unimpeded, moderately impeded, and severely impeded visibility. Visual impedance was created by placing screens between signing partners. The distance of a hand from the body, in terms of lateral, vertical, and forward-depth dimensions, was determined from digitized measurements of single video frames randomly selected from those in which the subject was actively signing. Sign rate was calculated as the number of signs produced in a given segment of time. Signs produced in the severely impeded visibility condition were found to be made at a slower rate and with a mean hand position further forward and vertically higher than signs produced in the unimpeded visibility condition.


Communicative gestures in children with delayed onset of oral expressive vocabulary.

Use of communicative gestures in a group of children with delayed onset of expressive oral vocabulary (late talkers) was compared with such use among normal-language-matched controls and age-matched controls. Analyses revealed that late talkers used significantly more communicative gestures and for a greater variety of communicative functions than did language-matched controls. However, a 1-year follow-up revealed that 4 of the late talkers remained delayed (truly delayed late talkers) and 6 caught up (late bloomers). Reanalyses of Year 1 data based on these follow-up outcomes demonstrated that only late bloomers used more communicative gestures than did language-matched controls. Truly delayed late talkers did not differ from language-matched controls either for number of gestures, type of gestures (symbolic vs. nonsymbolic), or number of different functions for which gestures were used. Late bloomers also used more communicative gestures than did age-matched controls, suggesting that they (the late bloomers) were using gestures to compensate for their small oral expressive vocabulary. Results are discussed in the context of early predictors of risk for language impairment and relationships between language and cognition.


Evaluating memory wallets in conversations with persons with dementia.

The use of memory wallets to self-prompt factual information during prompted conversations with familiar partners was evaluated for 9 subjects with dementia. Memory wallets contained 30 pictures and sentences about familiar persons, places, and events that each participant had difficulty remembering. The amount of training by caregivers was the one component of the intervention package that varied among the nine attempts to replicate condition effects observed on introduction of the wallets. All subjects learned to use the memory wallets to improve their conversations by making more accurate factual statements. Even when caregiver training was not provided to 3 subjects, condition effects were still demonstrated, with only 1 subject requiring a brief orientation to his wallet. Long-term maintenance of condition effects was demonstrated for 3 subjects up to 30 months' postintervention. These results support the clinical utility of a memory wallet intervention package for persons with dementia and provide preliminary evidence that often little more than preparing memory wallets and providing a brief orientation are required to facilitate their use in improving conversations with familiar conversational partners.


The effects of auditory and visual interference on speech and sign.

Hearing adults produced signed and spoken monologues under conditions of quiet or 80 dB SPL of noise and with their vision unobstructed or obstructed. Their signs were videotaped and a random sample of 24 frames was analyzed in each condition through a computer program that determined the overall distance of the hand from a marker placed on the signer's torso. Vocal intensity was digitized from the tape recordings and analyzed by computer for 1 min of continuous speech in each condition. The visual obstruction had no effect either on the distance of the signs or on the vocal intensity of their speech. The subjects increased vocal intensity by about 55% when the noise was introduced (the usual Lombard effect), but the noise had no effect on the distance of the signs. Sign performance was not influenced by visual feedback, and sign and speech were independent communication systems, even in bilingual speaking and signing subjects.


Effects of speech output type, message length, and reauditorization on perceptions of the communicative competence of an adult AAC user.

The effects of speech output type, aided message length, and partner reauditorization on naive observers' perceptions of the communicative competence of an adult augmentative and alternative communication (AAC) system user were examined. Subjects consisted of 48 naive adults with minimal exposure to nonspeaking persons. Eight scripted videotaped conversational conditions involving an AAC user and a normal-speaking partner were employed in the manipulation of the three independent variables. A balanced incomplete block design was used. Following each viewing, subjects completed a questionnaire designed to assess the communicative competence of the AAC user. Results indicated a significant main effect for aided message length only. Ratings of the AAC user were higher in conditions with phrases than in conditions with single-word messages. Of interest was the finding that the use of digitized versus synthesized speech output had no effect on observer ratings. Clinical implications are discussed.


Then as an indicator of deictic discontinuity in adults' oral descriptions of a film.

An analysis of film descriptions of 20 normal-language adults revealed the adults' selective and systematic use of the word then. Then served to indicate an upcoming shift in discourse deixis. It occurred in clauses that told of a shift to a different discourse frame (conversation vs. story world of the film), to a new scene location, to a different character, and a shift in who was doing the viewing. The regularity in the use of then is taken to be evidence that speakers conceptualize their descriptions as being located in a variety of related frames, all having to do with the perspective taken on the current talk. A conceptual model underlying the speakers' use of then would need to include distinctions between the conversational and story world, the various scenes in the objective world of the story, and various subjective views that different observers can have when experiencing the described events. The results are taken as support for viewing discourse discontinuity as an important factor in discourse analysis.


Speech perception and production skills of students with impaired hearing from oral and total communication education settings.

This study examined the degree to which students with profoundly impaired hearing who had been educated in oral and total communication (TC) environments developed auditory and speech skills. The sample consisted of 227 16- and 17-year-old students with profoundly impaired hearing: 127 from TC programs (63 with normal-hearing parents and 64 with deaf parents) and 100 from oral programs. Subject groups were matched in terms of age, unaided residual hearing, and IQ. On average, students from oral programs acquired more intelligible speech and made significantly better use of their limited residual hearing than did the TC students. This finding held for all TC students--those with deaf parents as well as those with normal-hearing parents. Although results of this study indicate that auditory and speech production skills are comparatively well developed in students who have consistently used spoken language throughout the day as the primary means of communicating, other factors associated with this oral sample, such as early amplification, consistent hearing aid use, early education, and parental support, may also be necessary for the development of good spoken language skills.


Aging and the binaural advantage in reverberation and noise.

The consonant identification ability of younger normal-hearing adults and older adults with little or no peripheral hearing loss was assessed using monaural and binaural presentation in four listening conditions: quiet, noise, reverberation, and reverberation + noise. Performance was examined in terms of identification accuracy and amount of binaural advantage. Results suggest that the small amount of hearing loss in the older subjects limited their perception of distorted consonants. Neither age nor peripheral hearing loss was related strongly to the amount of benefit obtained from binaural presentation.


Sustained benefits of hearing aids.

This study was designed to evaluate long-term benefits of hearing aids in elderly individuals with hearing loss. A primary care cohort of 192 elderly, hearing-impaired veterans (mean age 72 +/- 6, 97% White, 94% retired) were assessed at baseline and at 4, 8, and 12 months after hearing aid fitting. Drop-out rates at 4, 8, and 12 months were 5%, 13%, and 16%, respectively. Outcome assessments included several quality-of-life scales: Hearing Handicap Inventory in the Elderly (HHIE), Quantified Denver Scale of Communication Function (QDS), Geriatric Depression Scale (GDS), and the Short Portable Mental Status Questionnaire (SPMSQ). All quality-of-life areas improved significantly from baseline to 4-month post-hearing aid fittings (p < 0.05). Social and emotional (HHIE), communication (QDS), and depression (GDS) benefits were sustained at 8 and 12 months, whereas cognitive changes (SPMSQ) reverted to baseline at 12 months. We conclude that hearing aids provide sustained benefits for at least a year in these elderly individuals with hearing impairment.


Contributions of the fundamental, resolved harmonics, and unresolved harmonics in tone-phoneme identification.

Researchers describe Mandarin Chinese tone phonemes by their fundamental frequency (Fo) contours. However, tone phonemes are also comprised of higher harmonics that also may cue tone phonemes. We measured identification thresholds of acoustically filtered tone phonemes and found that higher harmonics, including resolved harmonics above the Fo and unresolved harmonics, cued tone phonemes. Resolved harmonics cued tone phonemes at lower intensity levels suggesting they are more practical tone-phoneme cues in everyday speech. The clear implication is that researchers should use the Fo only as a benchmark when describing tone-phoneme contours, recognizing that higher harmonics also cue tone phonemes. These results also help explain why tone-language speakers can identify tone phonemes over a telephone that attenuates selective frequencies, and suggests that hearing-impaired tone-language speakers may still identify tone phonemes when their hearing loss attenuates selective frequencies.


Modulation detection, modulation masking, and speech understanding in noise in the elderly.

Temporal processing of suprathreshold sounds was examined in a group of young normal-hearing subjects (mean age of 26.0 years), and in three groups of older subjects (mean ages of 54.3, 64.8, and 72.2 years) with normal hearing or mild sensorineural hearing loss. Three experiments were performed. In the first experiment (modulation detection), subjects were asked to detect sinusoidal amplitude modulation (SAM) of a broadband noise, for modulation frequencies ranging from 2-1024 Hz. In the second experiment (modulation masking), the task was to detect a SAM signal (modulation frequency of 8 Hz) in the presence of a 100%-modulated SAM masker. Masker modulation frequency ranged from 2-64 Hz. In the final experiment, speech understanding was measured as a function of signal-to-noise ratio in both an unmodulated background noise and in a SAM background noise that had a modulation frequency of 8 Hz and a modulation depth of 100%. Except for a very modest correlation between age and modulation detection sensitivity at low modulation frequencies, there were no significant effects of age once the effect of hearing loss was taken into account. The results of the experiments suggest, however, that subjects with even a mild sensorineural hearing loss may have difficulty with a modulation masking task, and may not understand speech as well as normal-hearing subjects do in a modulated noise background.


Operant response in infants as a function of time interval following signal onset.

This study investigated the hypothesis that estimates of infant auditory threshold are lowered by extending the duration of individual test trials such that infants have more time to detect and respond to the acoustic signal. Forty 8- and 12-month-old infants were evaluated with an operant procedure to determine response latencies at four near-threshold levels. Resulting data were used to estimate the effect of trial duration on threshold by calculating the response performance that occurred at several intervals following signal onset. Findings indicate that most detection responses occurred in the initial 4 sec of the test trial, and use of an 8-sec trial interval yielded little gain in performance. The data reflect an insignificant shift (< 5.0 dB) in threshold as a function of extended trial intervals.


Hepatocyte function in a hollow fiber bioreactor: a potential bioartificial liver.

We have developed a novel hepatocyte loaded hollow fiber bioreactor as a potential bioartificial liver. Freshly harvested rat hepatocytes were entrapped in a three-dimensional gel matrix within hollow fibers in a perfused bioreactor. Gel entrapment allowed cells to be cultured at high density while maintaining tissue-specific function. Hepatocyte function was evaluated in 10 bioreactors, each containing approximately 5 x 10(7) cells. Oxygen consumption averaged 0.32 pmole/cell/hr, albumin appearance averaged 0.60 pg/cell/hr, and lidocaine clearance (a measure of the P-450 activity) averaged 0.74 pg/cell/hr. Function persisted for the 7 days of the study. Electron microscopy at 7 days showed the distinctive ultrastructure of viable, differentiated hepatocytes: bile canaliculi, intercellular junctions, peroxisomes, abundant mitochondria, and glycogen granules. Maintenance of tissue specific function and ultrastructure suggests that this bioreactor configuration has potential as a device to support patients in liver failure, as well as to study hepatocytes in vitro.


Inhibition of intimal hyperplasia by photodynamic therapy using photofrin.

Photodynamic therapy using photofrin and light energy inhibits human myofibroblast proliferation in cell culture. The purpose of this study is to evaluate its influence on intimal hyperplasia in vivo. Twenty New Zealand White rabbits underwent a standardized intimal injury to both common carotid arteries with a 2 Fr balloon catheter. One week later, half of the animals received photofrin (5 mg/kg) intravenously. The remaining 10 rabbits received no photofrin. Two days later, all neck incisions were reopened and a 1-cm segment of each of the 40 carotid arteries was exposed for 5 min to 80 mW of 630 nm light energy from a continuous wave tunable dye laser (fluence = 7.6 J/cm2). All vessels were harvested 5 weeks post-laser treatment following in vivo fixation with formalin. From each artery, separate cross-sections taken from both the lasered and non-lasered regions of each vessel were mounted and stained for histologic evaluation. Analyzed segments were then divided into four different treatment groups: group I segments consisted of arterial cross-sections which were taken from vessel regions that were injured but received neither photofrin nor laser treatment (group I, n = 20); group II segments also did not receive photofrin but were exposed to light energy (group II, n = 20); group III segments received photofrin but no light energy (group III, n = 20); and cross-sections in group IV were taken from those segments which received both photofrin and laser treatment. Using planimetry, the ratio of the area of intimal hyperplasia (IH) to the area enclosed by the internal elastic lamina (IEL) was measured for each specimen (IH/IEL).(ABSTRACT TRUNCATED AT 250 WORDS)


In vivo microscopy of rat skeletal muscle after ischemia using labelled neutrophils (PMN).

Neutrophils (PMN) have been implicated as mediators of the "no-reflow" phenomenon seen in skeletal muscle during reperfusion after ischemia. In order to evaluate the PMN contribution to the changes seen in the microcirculation of skeletal muscle after ischemia, we evaluated PMN velocity using in vivo microscopy in a rat model. After the induction of anesthesia, the right iliac and femoral arteries were isolated. The right anterior tibialis muscle was exposed in situ, covered with a plexiglass disc, and perfused with Kreb's solution. Fluorescein-labeled bovine albumin was given intravenously, which identified the capillaries under microscopic magnification as viewed on the video screen. Acridine orange was then administered intravenously, which selectively fluoresced the PMN. The right iliac and femoral arteries were clamped for ischemia intervals of 5, 10, 15, 20, 25, and 30 min. Acridine orange was given immediately after the arteries were unclamped, after 30 min of reperfusion and after 60 min of reperfusion. PMN velocity was determined by the distance traveled by the PMN over time using the videotape and frame-by-frame review. Results demonstrated no change in PMN velocity (mm/sec) after 5 min of ischemia. After 10, 15, and 20 min of ischemia, PMN velocity initially slowed and then recovered, which was not statistically significant. After 25 min of ischemia, PMN velocity decreased significantly, which persisted (P < 0.05 compared to 5-min ischemia by ANOVA). No flow was seen after 30 min of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)


Selective lipoxygenase inhibitor reduces bile acid-induced gastric mucosal injury.

Leukotriene receptor blockade attenuates topical bile acid-induced gastric mucosal injury, suggesting that peptidyl-leukotrienes may be mediators of this injury. The purpose of this study was to test the hypothesis that a selective 5-lipoxygenase inhibitor protects against bile acid-induced gastric epithelial injury in the rat. Prior to injury with 10 and 20 mM acidified taurocholate (pH 1.2), rat stomachs were pretreated with either vehicle or WY50295K (selective 5-lipoxygenase inhibitor, 20 mg/kg). Injury was assessed by measuring net transmucosal hydrogen ion flux, luminal appearance of DNA, and gross mucosal injury. Topical 5-lipoxygenase inhibitor significantly reduced luminal H+ ion loss, surface epithelial cell loss (as measured by luminal accumulation of DNA), and gross mucosal injury in bile acid-injured stomachs compared to controls. This study lends further support to the hypothesis that leukotrienes may be mediators of bile acid-induced gastric mucosal injury.


Systemic and local toxicity in the rat of methyl tert-butyl ether: a gallstone dissolution agent.

Methyl tert-butyl ether (MTBE) is an organic solvent that has been used to dissolve gallstones via a percutaneous transhepatic catheter into the gallbladder. To test whether MTBE might cause serious tissue injury if accidentally infused outside the gallbladder, the effect of MTBE (0.2 ml/kg) injected into the hepatic parenchyma, or administered intravenously or intraperitoneally, was examined in the rat. The toxicity of isopropyl acetate (IPA), an organic solvent with a similar chemical structure, was examined similarly. Intracaval injection of MTBE caused the highest mortality (100%). Mortality was less (59%) after intrahepatic injection and still less (17%) after peripheral vein injection. Most animals died instantaneously from cardiorespiratory arrest. Almost all animals that were injected with MTBE intrahepatically or intravenously showed localized areas of congestion, hemorrhage, and interstitial edema in the lungs. These changes were more severe in rats which survived for 24 hr than in those which died sooner. In those rats receiving intrahepatic injections, most rats which survived for 24 hr had liver necrosis at the site of injection. Intraperitoneal injection of MTBE produced 100% survival with only 1/5 rats showing a mild pulmonary injury at autopsy. IPA had toxic effects similar to those evoked by MTBE. To test whether tumor necrosis factor was involved in organ injury, serum levels were measured; they remained unchanged. These experiments indicate that two organic solvents, MTBE and IPA, are cytotoxic to local tissues and cause severe, and often fatal, lung damage when infused into a central vein. Less toxicity occurred if solvents were given into a peripheral or portal vein or intraperitoneally.(ABSTRACT TRUNCATED AT 250 WORDS)


Collateral blood flow from skeletal muscle to normal myocardium.

Collateral blood vessels from skeletal muscle to myocardium might supplement intramyocardial collaterals during periods of acute myocardial ischemia. This study was conducted to verify the existence of such collaterals and to measure their contribution to collateral flow. In 12 male goats, the innate coronary collateral system to a moderate size myocardial risk area was defined with colored microspheres, and a latissimus dorsi pedicle flap was then apposed to the heart. After 3 weeks, skeletal muscle to myocardial collaterals were characterized by (a) creation of vascular casts (three animals); (b) estimation of skeletal muscle to myocardial collateral blood flow (three animals); and, (c) measurement of total collateral blood flow to the risk area (innate plus skeletal muscle to myocardial collateral flow). Under a dissecting microscope the vascular casts revealed direct communications from the skeletal muscle which penetrated deeply into the myocardium. With the coronary artery to the risk area open, the estimated myocardial collateral blood flow derived from the muscle flap was 0.01, 0.02, and 0.04 ml/min. With the coronary artery to the risk area closed, there was no significant increase in total coronary collateral blood flow. Although the quantity of blood flow delivered by skeletal muscle collaterals was small, this study demonstrates that clearly identified collateral blood vessels form between skeletal muscle and myocardium in a cardiomyoplasty model. This raises the possibility that, under conditions more favorable to their development, extramyocardial collaterals from skeletal muscle might be exploited to augment the intramyocardial collateral system.


The role of myoneural and luminal continuity in the coordination of canine gastroduodenal patterns of motility.

Our aim was to determine the role of intrinsic myoneural and enteric luminal continuity in the coordination of gastric and duodenal motility patterns. Three groups of dogs were prepared: five dogs with an intact gastrointestinal tract served as a Control group; four dogs had transection and reanastomosis of the duodenum 0.5 cm distal to the pylorus (Pyloric Transection group); and seven dogs had identical proximal duodenal transection, but with oversewing of duodenum and pylorojejunostomy to a Roux-en-Y limb (Roux-en-Y group). In the Control and Pyloric Transection groups, the gastric and intestinal MMCs were similar in appearance, the cycle durations (x +/- SEM) were not different (134 +/- 19 vs 111 +/- 26 min, respectively; P > 0.05), and the times between the start of gastric and duodenal Phase III (gastroduodenal latency) were similar (6 +/- 1 vs 10 +/- 3 min; P > 0.05). In the Roux-en-Y group, MMCs also occurred in six of seven dogs but tended to have a longer cycle duration (176 +/- 19 min) and a more variable gastroduodenal latency (23 +/- 15 min). Plasma motilin concentration, measured only in the Roux-en-Y group, was greater during Phase III in the stomach and duodenum than during Phases I or II (P < 0.05). Feeding inhibited the gastric and duodenal MMCs in all groups, but the duodenal MMC returned earlier in the Roux-en-Y group. The Roux-en-Y jejunal limb exhibited a postprandial pattern in only seven of 14 studies.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of homodimeric isoforms of platelet-derived growth factor (PDGF-AA and PDGF-BB) on wound healing in rat.

Platelet-derived growth factor (PDGF) has been suggested to have a significant role in wound healing. The present work was aimed at studying the effects of PDGF-AA and PDGF-BB homodimers on developing granulation tissue in rats. Subcutaneously implanted hollow cylindrical cellulose sponges were used as an inductive matrix for the ingrowth of granulation tissue. Fifty microliters of solutions containing 0, 5, 50, or 500 ng of PDGF-AA or PDGF-BB homodimers was injected daily into the sponges; 7 days after implantation the granulation tissue in the sponge cylinders was analyzed. Five hundred nanograms of PDGF-BB stimulated significantly the accumulation of collagen, indicated by the elevated hydroxyproline content of the sponge (+34%, P < 0.001). Similarly, the amounts of RNA-ribose, nitrogen, hexosamines, and uronic acids were significantly higher, reflecting a PDGF-BB-induced increase in the accumulation of RNA, protein, and glycosaminoglycans. Analyses of wound fluid showed no essential changes in the composition of different cell types after PDGF-BB-treatment. The PDGF-AA-treatment increased significantly the mean amount of RNA but there were no significant changes in other parameters. In vitro both PDGF-AA and PDGF-BB increased significantly the number of rat granulation tissue derived fibroblasts in culture at concentrations of 10 and 30 ng/ml. This proliferative effect resulted in a lowered level of protein synthesis per cell. To conclude, PDGF-BB accelerates granulation tissue formation both in vitro and in vivo, whereas PDGF-AA is effective in vitro but it is clearly less effective in vivo.


Regulatory effects of interleukin-4 on tumor-infiltrating lymphocytes derived from human renal cell carcinoma.

We have studied the effects of interleukin-4 (IL-4) on the expansion, proliferation, phenotype, and antitumor activity of tumor-infiltrating lymphocytes (TIL) derived from human renal cell carcinoma. Cultures were obtained from three primary renal tumors and one group of tumor-invaded, regional lymph nodes. IL-4 induced a significant increase in lymphocyte expansion and proliferation, but the response was dependent on the concurrent dose of IL-2 in culture. Increased growth activity was only observed in those cultures receiving low doses (20 U/ml) of IL-2 (average increase of fold expansion of 6.5, P < 0.01) with no changes in growth activity in the high dose (1000 U/ml) cultures. The combination of low dose IL-2 and IL-4 (200 U/ml) promoted lymphocyte growth significantly better than high dose IL-2 alone, the current standard growth regimen for in vitro expansion of TIL. TIL grown in the presence of IL-4 significantly reduced the level of non-specific, non-major histocompatibility complex-restricted antitumor activity (P < 0.01 for allogeneic renal, nonrenal, and NK-sensitive K562 cells), while exhibiting no effect on the level of autologous killing. This is in contrast to previous findings of significant enhancement of autologous antitumor activity using IL-4 on tumor-specific, melanoma-derived TIL. We also evaluated the effects of irradiated autologous tumor stimulation (TIL:tumor ratio, 10:1) on TIL cultures. Addition of autologous tumor cells increased expansion and proliferation of all cultures regardless of concurrent lymphokines present in the culture media (average increase fold expansion of 2.21, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Acute effects of a nucleoside analog dideoxyinosine (DDI) on the pancreas.

Dideoxyinosine (DDI, Videx) is a recently developed nucleoside analog with activity against the human immunodeficiency virus. A significant number of patients with AIDS or AIDS-related complex treated with DDI have developed acute pancreatitis. This study was performed to investigate the acute effects of DDI on the pancreas utilizing an isolated ex vivo perfused canine pancreas preparation. Control preparations remained normal throughout a 4-hr perfusion period. The addition of 12.5 mg of DDI to the perfusate (ca. 100 mumol/liter) did not induce any changes in the preparation. The addition of 62.5 mg of DDI to the perfusate (ca. 500 mumol/liter) did not induce changes in the gross appearance, weight gain, or amylase activity. However, the arterial pressure and the oxygen consumption of the preparation decreased significantly after the administration of DDI. The amount of zymogen in the acinar cells also decreased, as evaluated by electron microscopy. Protein secretion increased temporarily, probably as a result of acinar cell emptying (increased secretion without new synthesis). Water and bicarbonate secretion were also increased during the fourth perfusion hour.