Experimental infections of Eimeria alpacae and Eimeria punoensis in llamas (Lama glama).

Four llamas (Lama glama) ranging in age from 1.5 yr to 7 yr each were inoculated orally with 10,000 (n = 2) or 50,000 (n = 2) sporulated oocysts of Eimeria alpacae (25%) and Eimeria punoensis (75%). The prepatent period for E. aplacae was 16-18 days, and it was 10 days for E. punoensis. Patent periods for E. alpacae and E. punoensis were approximately 9 days and 24 days, respectively. Although large numbers of oocysts were present in feces, no clinical sign of coccidiosis was observed. Based on ths experiment, E. alpacae and E. punoensis at the numbers given are not likely pathogenic in healthy llamas older than 1 yr.


Equine protozoal myelitis in Panamanian horses and isolation of Sarcocystis neurona.

Schizonts of Sarcocystis neurona were identified microscopically in hematoxylin-eosin-stained spinal cord sections from 2 native Panamanian horses that exhibited clinical signs of equine protozoal myelitis (EPM). Spinal cord homogenate from a third Panamanian horse with EPM was inoculated onto monolayers of cultured bovine monocytes (M617). Intracytoplasmic schizonts containing merozoites arranged in rosette forms surrounding a central residual body first were observed 13 wk postinoculation. Parasites divided by endopolygeny and lacked rhoptries. Schizonts from each horse reacted with Sarcocystis cruzi antiserum in an immunohistochemical test.


Infections of Gyrodactylus bullatarudis and Gyrodactylus turnbulli on guppies (Poecilia reticulata) in Trinidad.

Gyrodactylus bullatarudis Turnbull, 1956, and Gyrodactylus turnbulli Harris, 1986, are recorded from guppies (Poecilia reticulata) from the northern mountains of Trinidad. Mixed infections of the 2 species were found at 9 localities. Gyrodactylus turnbulli had a predominantly posterior distribution on the fishes, whereas G. bullatarudis was more anteriorly distributed. This is the first record of these species from guppies collected from within their original range.


A possible genetic factor influencing protection from infection with Ascaris lumbricoides in Nigerian children.

An epidemiological study of Ascaris lumbricoides infections was carried out in primary school children aged 5-16 yr from Ile-Ife, Nigeria. Intensity of infection was assessed directly by means of counting worms passed during a 48-hr period after chemotherapy. Reinfection patterns of A. lumbricoides were assessed at 2 6-mo intervals and statistical evidence of predisposition to infection status was obtained. An investigation of 3 groups of children who were judged to be predisposed not to be infected, to be lightly infected, and to be heavily infected was undertaken. Assignment to the groups was based upon the mean worm burden plus 1 SD above the mean, measured at 2 6-mo intervals. The distribution of class I human leucocyte antigens among the 3 groups of children was described. None of the children who were predisposed to remain uninfected was found to possess the A30/31 antigens in contrast to those children who remained infected.


Secretion of metalloproteases by living infective larvae of Necator americanus.

Fresh living third-stage larvae of Necator americanus released a significant amount of label within 2 hr of their incubation on 125I-labeled gelatin-coated polystyrene plastic plates. This protease activity was primarily susceptible to o-phenanthroline, which identifies the activity as predominantly metalloprotease.


Twinning in metacestodes of Taenia solium.

Two cysticerci containing 2 scolices were found among several thousand Taenia solium metacestodes dissected from swine. Microscopic study of tissue sections revealed that both worms were equally well developed in 1 bladder worm, whereas 1 member of the other pair was incompletely formed.


The U.S. National Parasite Collection--a century of service.

The U.S. National Parasite Collection will complete its first century of service to the field of animal parasitology in 1992. A brief history of the collection and a description of current policies on deposit and loan of specimens are provided. The collection, started in 1892 by Charles Wardell Stiles and Albert Hassall, now includes several constituent collections: The USNM Helminthological Collection, The USDA Parasite Collection, The Hoffman-Bangham Collection of Parasites of Freshwater Fish, and The Southeastern Cooperative Wildlife Diseases Study Collection of Parasites of White-tailed Deer. Major personal collections have been donated by F. W. Douvres, J. H. Fischthal, A. O. Foster, A. Goldberg, E. P. Hoberg, R. Honess, R. A. Knight, D. C. Kritsky, R. E. Kuntz, G. L. LaRue, D. R. Lincicome, E. Linton, G. A. MacCallum, J. H. Sandground, L. Schultz, and H. J. Van Cleave. In addition to Stiles and Hassall, the collection has been curated by B. H. Ransom, M. C. Hall, A. McIntosh, W. W. Becklund, M. B. Chitwood, and the authors of this report. Other USDA researchers closely associated with the collection over the years include B. G. Chitwood, E. B. Cram, G. Dikmans, J. T. Lucker, E. W. Price, and E. E. Wehr. The collection includes about 90,000 lots of specimens, mostly helminths, but also significant numbers of ticks, mites, protozoans, and other miscellaneous parasites. Annually about 600-1,000 lots are accessioned and 300-400 lots are loaned to researchers around the world.


1 beta-hydroxylated bile acids in the urine of healthy neonates.

In order to clarify the metabolism of bile acids in neonates, 1 beta-hydroxylated bile acids in the urine of healthy newborns were examined by gas chromatography-mass spectrometry. The results showed that the percentage of total 1 beta-hydroxylated bile acids, 3 beta, 12 alpha-dihydroxy-5-cholenoic acid and hyocholic acid in neonates was significantly higher than in older children. The ratio of 1 beta-hydroxylated bile acids to their comparable primary bile acids was also higher in neonates than in older children. These results suggest that 1 beta- and 6 alpha-hydroxylation of bile acids are the predominant pathways of bile acid metabolism in neonates.


Abnormal gut blood flow velocities in neonates at risk of necrotising enterocolitis.

Duplex pulsed Doppler ultrasound was used to determine blood flow velocities in the coeliac axis and superior mesenteric artery in three groups of neonates: a group at high risk of developing necrotising enterocolitis (n = 27) and two control groups, i.e., a nonasphyxiated, appropriately grown group of preterm infants (n = 18) and a group of nonasphyxiated term infants (n = 14). Subjects were studied on the first, second, and fourth days of life. The median peak systolic velocities in the superior mesenteric artery were between 20 and 51% lower in the at-risk group than in the term control group on all 3 days of measurement (p less than 0.05-p less than 0.002). The ratio of peak systolic velocity in the coeliac axis to that in superior mesenteric artery, an index of relative downstream vascular resistance in the superior mesenteric artery, was 42-65% greater in the at-risk group compared with the other two groups on days 1 and 2 (p less than 0.05-p less than 0.001) and significantly greater than the term group on day 4 (73%, p less than 0.002). These data demonstrate that neonates at risk of developing necrotising enterocolitis have abnormal gut blood flow velocities. Furthermore, they provide evidence that an alteration in the splanchnic circulation may be an important factor in the final common pathway that links diverse risk factors for necrotising enterocolitis with clinical disease.


Milk-stimulated PGE2 production by isolated gastric cells: a possible role in the inhibition of histamine-induced acid secretion.

The effects of a milk diet on gastric acid secretion of rats fed raw bovine milk for 4 days were examined using dispersed gastric cells. Parietal cell acid secretion was estimated by the accumulation of 14C-aminopyrine (AP), an index of secretory function. Basal AP accumulation was significantly increased (60%) by the milk diet. There was a marked upward shift in the dose-response curve of histamine (HA; 10(-8) to 10(-3) M) in milk-fed rats, indicating enhanced sensitivity of parietal cell-H2 receptor to exogenous HA. In contrast, the dose-dependent inhibition of HA-induced AP accumulation by prostaglandin (PG) E2 was significantly reduced, indicating that the parietal cells of milk-fed rats were less sensitive to exogenous PGE2. The PGE2 content of bovine milk was low (less than 20 pg/ml), but the production of endogenous PGE2 by the gastric cells was dramatically increased by the milk diet and exhibited maximal control production rate in the presence of 10 microM arachidonic acid. The increased responsiveness to histamine and the decreased responsiveness to PGE2 indicated that the milk diet induced low histamine and high PGE2 availability in the vicinity of the parietal cell basolateral membrane. This regulation, which involves stimulation of PGE2 production in the gastric mucosa, may underly the inhibition of acid secretion observed in vivo in chronically milk-fed adult rats.


Solubility and digestibility of milk proteins in infant formulas exposed to different heat treatments.

There are presently several fundamentally different technologies to produce infant formulas (IF), such as sterilization, spray-drying, and treatment at ultrahigh temperature (UHT). The effects of heat treatment on milk proteins in IF were analyzed by column chromatography, gel electrophoresis, and Kjeldahl analysis, revealing strong protein-protein and protein-lipid interactions in processed milk. These interactions were more pronounced in conventionally (in-can) sterilized than in spray-dried (powdered) and UHT products confirming their temperature dependency. Analysis of raw materials, intermediate and end products of IF processing revealed that after homogenization the first indications of protein denaturation occurred, but that in-can sterilization as the final heat treatment caused irreversible denaturation of proteins and strong protein-lipid interactions. Lowering of the pH to 4-5, which is physiological for the stomach of young infants, enhanced the interactions. Support for an impairment of protein digestibility was given by in vitro analysis of protein digestibility, demonstrating significantly lower digestibility of in-can sterilized IF compared to their spray-dried and UHT counterparts. To investigate the effect of heat treatment on chemical reactions, i.e., occurrence of Maillard products, we showed by a fluorimetric assay that the amount of "available" lysine is lower in sterilized than in powdered IF. Our findings suggest that a more differentiated view regarding the protein quality of IF is needed.


Comparison of two preterm formulas with or without addition of medium-chain triglycerides (MCTs). I: Effects on nitrogen and fat balance and body composition changes.

Medium-chain triglycerides (MCTs) are included in the fat blend of several preterm formulas because of their complete absorption and rapid oxidation. The effects of two different fat blend compositions on nitrogen and fat balances and macronutrient oxidation were investigated in 28 healthy very-low-birth weight infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT blend containing 38% MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk more, containing 6% MCTs (LCT group). There were no differences in nitrogen absorption or in excretion. Median nitrogen retention was 74% (MCT) vs. 71% (LCT) of intake. Fat absorption was higher (p less than 0.05) in the MCT group (88%) vs. 79% in the LCT group (median values). MCTs did not stimulate fat oxidation as measured by indirect calorimetry, so fat deposition was also higher on the MCT formula. As weight gain was not different between groups, the percentage of weight gain consisting of fat accretion was significantly (p less than 0.005) higher with the MCT formula (24% vs. 21%). On the other hand, there was no increase in percent protein accretion (both 15% of weight gain). We conclude that the existence of a slightly lower fat absorption in the healthy growing neonate fed a LCT formula compared with a MCT formula does not impair growth or nitrogen retention, but merely induces a slight decrease in the high relative fat accretion encountered in the preterm neonate.


Comparison of two preterm formulas with or without addition of medium-chain triglycerides (MCTs). II: Effects on mineral balance.

Medium-chain triglycerides (MCTs) are included in the fat blend of several preterm formulas because of their complete absorption and rapid oxidation. The effects of two different fat blend compositions on calcium (Ca), phosphorus (P), and magnesium (Mg) balances and plasma levels and on plasma levels of parathyroid hormone (PTH), alkaline phosphatase (AP), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] were investigated in 28 healthy very-low-birth weight infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT blend containing 38% MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk more, containing 6% MCTs (LCT group). There was a higher absorption of Ca in the MCT group (73% vs. 60%. p less than 0.005), and an equal absorption of P (both 92%). The excretion of Ca correlated with the excretion of fat (p less than 0.00005). The LCT group showed a higher median PTH level (MCT: 2.1 pmol/L, LCT: 4.7 pmol/L, p less than 0.01) and a higher urinary P excretion (p less than 0.001). Mg absorption was also lower with LCT, but retention of Mg exceeded intrauterine values in both groups. Mineral plasma levels were in the normal range in both groups. AP was not different between groups and in the upper part of the reference range, whereas 1,25-(OH)2D levels were above the normal range and also not different between groups. We conclude that with the LCT formula, Ca absorption is slightly lower than with the MCT formula, whereas P absorption is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)


Basal and meal-stimulated pepsinogen secretion in preterm infants: a longitudinal study.

In order to establish longitudinal normal values for basal and meal-stimulated pepsinogen secretory function in preterm infants, we studied 44 preterm infants with gestational ages of 28-36 weeks during the period of nasogastric tube feeding. Three age groups were evaluated: gestational ages of 28-30, 31-33, and 34-36 weeks. Basal pepsinogen did not change with postnatal age in any of the groups. Significant meal-stimulated pepsinogen secretion appeared during the third postnatal week in infants of 28-30 weeks of gestation. In the groups of infants of 31-33 and 34-36 weeks of gestation, significant meal-stimulated pepsinogen secretion was apparent in the first postnatal week. This study suggests that maturation of pepsinogen secretion appears at 31 weeks of gestation, independent of early feeding.


Doppler assessment of human neonatal gut blood flow velocities: postnatal adaptation and response to feeds.

Duplex pulsed Doppler ultrasound was used to study changes in gut blood flow velocities during the first week of life in a group of 14 term babies. There was a significant increase in fasting peak systolic velocity in the superior mesenteric artery between days 1 and 2 with a further upward trend until day 5; no such changes were seen in the coeliac axis. Fasting velocities were 20% lower in breast-fed babies than bottle-fed babies. Following feeds, there was a significant increase in velocity in the superior mesenteric artery that was 35% greater in the bottle-fed than breast-fed babies. Changes in the coeliac axis were qualitatively similar but substantially smaller. The peak velocity in both vessels occurred 50 min after a feed. We conclude that Doppler ultrasound can be readily used to measure gut blood flow velocities in the human newborn. It provides a noninvasive technique for investigating adaptive postnatal changes in the splanchnic circulation, and, in particular, the response to feeds.


Esophagitis of likely traumatic origin in newborns.

We describe 17 full-term newborns presenting with vague symptoms related to the upper gastrointestinal tract (anorexia, poor feeding, retching, regurgitation, and incessant crying) during their stay in the maternity unit. After an esophagogastroduodenoscopy performed between days 2 and 5 of life, the babies could clearly be divided into two groups. Twelve babies (group 1) had an extremely severe esophagitis (circular ulcerations), without gastroduodenitis. In the remaining five babies (group 2), the upper gastrointestinal tract was unaffected. Allergic, infectious, metabolic, and toxic etiologies were excluded. Esophageal pH monitoring data were within normal ranges in all. All babies of group 1 were treated as follows: prone anti-Trendelenburg position, cisapride, and cimetidine syrup. Symptoms and lesions disappeared within 48-72 h. Reendoscopy after 72 h showed an almost normal esophagus with greatly improved histology. These observations highlight four points of interest: (a) the existence of an extremely severe ulcerative esophagitis in apparently healthy newborns, (b) the very rapid clinical and histological recovery, (c) the difficulties in predicting esophagitis on clinical grounds, and (d) the mysterious origin despite thorough assessment. The distribution of the lesions (more severe in the upper esophagus), the early onset (almost at birth), the very rapid healing, and the absence of gastric and duodenal lesions are in favor of a possible "traumatic" origin (pharyngeal, esophageal, and gastric suction at birth). Finally, because the condition described is transient, questions arise regarding the necessity of treatment, and we currently do not recommend overtreating newborns presenting with similar symptoms and/or endoscopic findings.


Midazolam as a sedative in esophageal manometry: a study of the effect on esophageal motility.

Midazolam 0.5 mg/kg was given intravenously as a sedative to 19 infants and children undergoing esophageal manometry after oral choral hydrate treatment. The lower esophageal sphincter pressure and motility were measured by manometry before and after midazolam injection. Midazolam did not change the lower esophageal sphincter pressure, blood pressure and respiratory rate of the subjects (p greater than 0.18), and the motility patterns. However, the mean heart rate increased by 5 beats/min after midazolam injection (p less than 0.05). One infant developed transient apnea, reversed promptly by intravenous flumazenil. Sedation occurred within 1 min after intravenous injection of the drug. No other side effects were noted. Midazolam is a relatively safe and effective sedative for accurate lower esophageal sphincter pressure measurement and esophageal manometry when a mild sedative such as choral hydrate does not work.


BUN/Cr ratio as an index of gastrointestinal bleeding mass in children.

Determining the site and severity of blood loss is important in the management of children with gastrointestinal (GI) bleeding. Blood urea nitrogen (BUN) and serum creatinine (Cr) were measured on the day of hospitalization and the ratio of BUN/Cr was calculated in 11 children with 16 episodes of upper GI bleeding and 49 with lower GI bleeding. There was a significant difference between the two GI bleeding groups with regard to BUN/Cr ratio (p less than 0.001). When the ratio was 30 or above, the specificity of upper GI bleeding was 98% with a sensitivity of 68.8%. A linear relationship was found between the BUN/Cr ratio and delta Hb (delta Hb = 0.08 x BUN/Cr +/- 0.8 g/dl) for bleeding originating from the upper GI tract. This study confirms that measurement of the BUN/Cr ratio is useful for localizing the source of bleeding to the upper GI tract and also demonstrates its usefulness as an estimation of the severity of blood loss from the upper GI tract.


Congenital sodium diarrhea with a partial defect in jejunal brush border membrane sodium transport, normal rectal transport, and resolving diarrhea.

Defective jejunal sodium/proton exchange causes severe, congenital secretory diarrhea. We report a boy who presented typically in utero, but in whom diarrhea resolved during the first year of life. Pregnancy was complicated by polyhydramnios, and an ultrasound at 31 weeks showed a distended fetal small intestine. The abdomen was grossly distended at birth, and profuse secretory diarrhea began immediately. He subsequently thrived on breast milk and electrolyte supplements. Studies of jejunal brush border sodium/proton exchange at 6 months showed a partial defect. Nonequilibrium rectal dialysis showed rectal sodium and potassium transport to be intact. Diarrhea lessened after 9 months, and the patient subsequently required occasional laxatives. These observations suggest that there is a spectrum of congenital abnormality in this exchanger, and that in children with incomplete defects normal colonic sodium salvage can subsequently mask net small intestinal secretion.


Efficacy of massive dose oral gentamicin therapy in nonbloody persistent diarrhea with associated malnutrition.

Overgrowth of aerobic and anaerobic bacteria in the upper small intestine is a common finding in persistent diarrhea. We hypothesized that a large dose of broad spectrum, nonabsorbable oral antibiotic would hasten recovery from persistent diarrhea by eradicating aerobic bacterial overgrowth. Sixty-eight patients were randomly assigned to treatment with either oral gentamicin (n = 33) or placebo (n = 35) for a period of 6 days. The two groups were comparable in their clinical features, stool weights, duodenal and fecal microflora, during an initial 24 h observation period before randomization. The proportion of patients recovering within 6 days post-treatment was similar in the antibiotic (45.2%) and placebo (50%) groups. The stool weights in the two groups during 24-72, 72-120, and 120-168 h of the study did not differ significantly. The percent mean weight gain (g) at 168 h post-treatment in the antibiotic (1.0 +/- 5.1) and placebo (1.4 +/- 5.3) groups also did not differ significantly (p = 0.8). A similar proportion of antibiotic- (61.3%) and placebo- (60.7%) treated patients had started to gain weight by the last day of the study. We conclude that oral gentamicin was no more effective than placebo in reducing purge rates, in achieving earlier recovery from diarrhea, and in promoting the earlier onset of weight gain in this study.


Cardiac, respiratory, and arousal responses to an esophageal acid infusion test in near-term infants during active sleep.

This study was designed to determine the cardiac, respiratory, and arousal responses to an esophageal acid infusion test in near-term infants free from neurological, gastroesophageal, and cardiopulmonary disease at time of testing during active sleep. Eight infants (gestational age 28-37.5 weeks, postconceptional age 36-40 weeks) were tested. Using standardized procedures and timing, we compared the cardiac, respiratory and arousal responses during a control period and during distal esophageal saline and acid infusion periods. The duration of each of these periods was 5 min. The pH of the acid infusion was 2.2. We found that this mild distal esophageal acid infusion test induced significant prolongation of the interval between successive electrocardiogram R waves compared with control and saline infusion periods (806.5 +/- 145.7 ms, 478.8 +/- 49.4 ms, and 468.8 +/- 37.2 ms, respectively; p less than 0.01) and of the duration of the respiratory cycle (2.9 +/- 0.7 s, 1.5 +/- 0.3 s, and 1.5 +/- 0.2 s, respectively; p less than 0.01). Esophageal acid infusion elicited significant electroencephalogram (EEG) arousal responses. The number of the EEG arousals was significantly increased during the acid period as compared with control and saline infusion periods (2.9 +/- 1.4, 0.5 +/- 0.5, and 0.4 +/- 0.5, respectively; p less than 0.01). Total arousal duration was significantly increased during acid as compared with control and saline infusion periods (42 +/- 17.5 s, 4.5 +/- 5.1 s, and 3.5 +/- 5.0 s, respectively; p less than 0.01). We conclude that distal esophageal acid stimulation elicits significant cardiac, respiratory, and EEG arousal responses in near-term infants during active sleep.


Nutritional rehabilitation in cystic fibrosis: a 5 year follow-up study.

Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV1 and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p less than 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short- and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study.


Short-chain fatty acid absorption in patients with cystic fibrosis.

Patients with cystic fibrosis (CF) often exhibit malabsorption despite the use of supplemental pancreatic enzymes. Unabsorbed carbohydrates and amino acids can serve as substrates for large intestine anaerobic fermentation, thus increasing excretion of short-chain fatty acids (SCFA) in the feces. Nine patients with CF on regular pancreatic enzyme supplementations in the age range of 5-11 years and one older patient were studied. Three-day stool samples were collected, as were 72-h food records. Stools were analyzed for gross energy, total nitrogen, fat content, and SCFA concentration. A significant difference was found between CF and normal controls in total caloric excretion due to fat malabsorption. No significant difference was found between CF and normal controls in protein or SCFA excretion. Fat excretion as percentage of fat intake was significantly increased in CF patients: 35.3 +/- 10.2% versus 8.0 +/- 3.0%, respectively. These data suggest that carbohydrate supplementation could be more widely used to increase caloric intake in CF patients without causing secondary osmotic diarrhea.


Gliadin-specific and cow's milk protein-specific IgA in human milk.

The presence of gliadin-specific IgA and IgG antibodies in colostrum and serum of 140 newly delivered mothers was assessed by enzyme-linked immunosorbent assay. In addition, cow's milk protein (CMP)-specific IgA was determined in the colostrum samples. From 14 of the mothers longitudinal milk samples were obtained after 1 and 2 months of lactation and from 12 mothers after 3 months. Gliadin-specific IgA was found in 97.1% and gliadin-specific IgG in 9.3% of the colostrum samples. Gliadin-specific IgA was detected in mature samples but at significantly lower levels after 1, 2, and 3 months of lactation (p less than 0.01) as compared with colostrum. Gliadin-specific IgA was found in 2.8% of the serum samples and gliadin-specific IgG in 40%; however, the levels of both isotypes were low. CMP-specific IgA was found in 78.1% of the colostrum samples. It is concluded that IgA antibodies to two common food proteins are frequently found in human milk and that food-specific IgA present in milk may play a role in adapting the infant's immune reactions to food antigens in the gut.


Gastrointestinal priming prior to full enteral nutrition in very low birth weight infants.

Priming of the gastrointestinal (GI) tract with low-volume feedings before giving full enteral feedings to very premature, high-risk infants is a controversial practice. We designed a study of infants weighing less than 1,250 g and receiving total parenteral nutrition to determine whether GI priming would hasten weight gain, improve tolerance of subsequent feedings, enhance nutritional status, and increase serum concentration of gastrin, a hormone trophic for intestinal growth. Infants were randomly assigned to receive total parenteral nutrition (TPN) alone (N = 21) or GI priming plus TPN (N = 19) for 12 days beginning on day 3 of life. Full-strength premature infant formula was used for priming. Both groups received the same total nutrition. Beginning on day 15, feedings in both groups were increased daily to a maximum of 120 kcal/kg/day on day 20, where they were maintained until day 30. After day 30, the feedings were modified according to the infants' condition. The groups did not differ in birth weight, gestational age, or 5-min Apgar scores. GI-primed infants had improved feeding tolerance after day 20 and a faster rise in serum gastrin during the initial phase of the study. There was no significant difference in weight gain. GI priming improves tolerance of feedings, accelerates rate of rise of serum gastrin during the first weeks of life, and does not increase the risk of feeding complications when compared to TPN alone. This may lead to more rapid maturation of the GI tract in primed infants.


Hypoxemia in infants with biliary atresia: the role of airway obstruction.

Hypoxemia in liver cirrhosis has been attributed to increased pulmonary perfusion; lung function abnormalities have rarely been found in adults. In infants, however, smaller airways and the disproportion in size between the enlarged liver and abdominal cavity leading to lung compression by elevated diaphragms may well suggest that ventilation disturbances play an important role in the development of hypoxemia. We examined lung functions, ventilation-perfusion scans, chest radiographs, and blood gases in air and 80% oxygen in 19 infants with biliary atresia (mean age 14 months) and found maximum flows at functional residual capacity (VmaxFRC) markedly decreased [48% +/- 29% (mean +/- SD)] and thoracic gas volume (TGV) elevated (156% +/- 30.2%). PO2 was less than 9.3 kPa in seven of 19 patients, in whom TGV was higher compared with the other patients (182% vs. 141%, p less than 0.005). However, the decrease in PO2, was much more closely correlated to the amount of shunting (r = 0.62, p less than 0.05) than to the reduced airway patency (VmaxFRC/TGV, r = 0.41, p = 0.08). We conclude that airway narrowing probably by lung compression is present more frequently in infants than in adults with liver disease. We found some evidence that hyperinflation contributes to the observed low PO2 values, possibly aggravated by inadequate vasoconstriction to hypoxic stimuli. However, pulmonary shunting independent of ventilatory disturbances more readily explained hypoxemia already present in these infants.


In vitro stability of liposomes in the presence of polymers, trehalose and sodium taurocholate.

We report the influence of synthetic polymers, trehalose and sodium taurocholate on the stability of both MLVs* and SPLVs prepared from a range of lipids including synthetic polyhydroxyl lipids. In the absence of cryoprotective agents liposomes were found to release greater than 90 per cent of encapsulated marker when exposed to freeze-thawing or freeze-drying procedures. In the presence of polyvinylpalmitate a marginal enhancement of stability towards freeze-drying was observed, the effect being most marked with cholesterol-containing liposomes. Trehalose was also found to stabilize all preparations investigated towards freeze-drying. In particular SPLVS prepared from (C18:0, C14:0-GMG):EPC:C retained in greater than 90 per cent of the entrapped marker. Addition of polymers to trehalose-containing SPLVS did not further increase the stability. SPLVS prepared from lipids possessing a high transition temperature demonstrated enhanced stability in the presence of bile salts. This effect was most marked with SPLVs prepared from (C18:0, C22:0-GMG):C.


Dependence on pH of permeability towards electrolyte ions of poly(L-lysine-alt-terephthalic acid) microcapsule membranes.

Permeation of electrolyte ions through poly(L-lysine-alt-terephthalic acid) microcapsule membranes was studied as a function of the pH of the medium at different ionic strengths. When the pH of the medium was varied, the permeation rate for 5-sulphosalicylate anions, as well as phenyltrimethylammonium cations, was slow at pH values lower than 4, showed a sudden and large increase in the pH range between 4 and 6, and thereafter remained unchanged. This remarkable change in the permeation rate was found to be produced by an abrupt increase in the microcapsule size observed in the same pH range. Increase in the ionic strength of the medium at pH values higher than 6 increased the rate of anion permeation but decreased the rate of cation permeation due to increase in the screening effect of salt ions on the negative charges in the microcapsule membranes.


An investigation of internal phase losses during the microencapsulation of fragrances.

Prototype fragrances, prepared from common fragrance components, were extracted with water, recovered, and characterized by gas chromatography before and after the water treatment, revealing a significant loss of the more water-soluble components. Unextracted prototype fragrances were also microencapsulated by a gelatin/gum arabic coacervation process. The microencapsulated fragrance oils were recovered from the microcapsules, using pepsin enzyme to open up the capsules. Comparison of GC results of microencapsulated fragrance oil versus unencapsulated oil showed many of the changes could be ascribed to solubility losses of the more water-soluble components to the process water. Deliberate inclusion of toluene as a fragrance component in one of the prototype fragrances showed that some losses of highly volatile fragrance components can be expected during microencapsulation; but because most fragrance components do not approach the volatility of toluene, such losses are expected to be minimal. Chromatograms taken before and after microencapsulation of two commercial fragrances are discussed.


Drug encapsulation in alginate microspheres by emulsification.

A method based on an emulsification process was developed for the production of calcium alginate microspheres. Isopropyl alcohol and acetone, which are strong dehydrating agents, were used to aid in the hardening and drying of the microspheres. However, the amount of drug encapsulated was very low. This was due to the drug being soluble in the dehydrating solvents. In the absence of the solvents a high percentage of drug was encapsulated, and this was further increased by forming the microspheres by phase inversion. It was also found that a suspension of the drug particles was required for effective microencapsulation. The efficiency of drug encapsulation generally increased with the ratio of drug to encapsulating material. The microspheres produced were free-flowing and most of them were smaller than 150 microns.


Polymeric pseudolatices bearing pilocarpine for controlled ocular delivery.

The pseudolatex-based ocular formulations of pilocarpine were prepared using different combinations of Eudragit RS 100 and polyvinyl pyrrolidone for prolonged and controlled release of the drug. The designed system was essentially based on polymeric pseudolatex dispersion. The process variables that effect the latex particle size, drug loading and release profiles of drug were studied. Preparations were evaluated for their in vitro performance with regard to release profile and diffusion co-efficient. The designed system exhibited linear relationship between cumulative drug release (Q) and square root of time (t0.5). The products selected on the basis of in vitro characterization were studied for in vivo performance evaluation. It was observed that the preparations exhibited in vivo prolonged therapeutic efficacy. Thus polymer based pseudolatices hold promise for controlled pilocarpine ocular delivery.


In vivo distribution and antitumour activity of liposomal 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine.

3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine (FUdR-dipalmitate), a lipophilic prodrug of 5-fluoro-2'-deoxyuridine (FUdR), was incorporated in different types of liposomes. The in vivo distribution and intrahepatic deacylation of liposomal FUdR-dipalmitate was found to be strongly dependent on liposome composition and on drug to lipid ratio. The use of fluid-type liposomes (egg PC/PS/CHOL) rendered FUdR-dipalmitate more susceptible to enzymatic breakdown than solid-type liposomes (DSPC/DPPG/CHOL). A decrease of the retention of the drug in the body was also obtained when FUdR-dipalmitate was incorporated in solid-type liposomes with high drug to lipid ratio (1:10) than with low ratio (1:50). In spite of these substantial differences in the rates at which FUdR was liberated from liposomes with different fluidity, size, or drug to lipid ratio, only minor differences in therapeutic effect were observed in a number of murine tumour models (P388 leukaemia, Lewis Lung carcinoma, B16 melanoma and a C26 adenocarcinoma liver metastasis model). The lipophilic prodrug of FUdR exhibited antitumour activity at 100-600 times lower doses than the free drug. However, at these therapeutic doses FUdR-dipalmitate was also far more toxic. This prohibited the use of higher doses to increase antitumour activity.


Preparation and physical evaluation of microcapsules of hydrophilic drug-cyclodextrin complexes.

An emulsion-solvent evaporation method for preparation of microcapsules containing water-soluble 2-hydroxypropyl-beta-cyclodextrin complex of a lipophilic water-insoluble drug, hydrocortisone, is described. The release of the drug from the microcapsules was determined in simulated gastric fluid. The drug release rate from the microcapsules could be controlled by addition of a plasticizer and it was sustained over extended time. Addition of solubilizing compounds to the dissolution medium did not affect the drug release rate.


Preparation and evaluation of abietic acid microcapsules by a solvent evaporation technique.

Abietic acid was isolated from rosin N Grade (ISI) by a simple process and the product was further standardized. Sulphadiazine microcapsules were prepared by the solvent evaporation technique, using abietic acid as a wall-forming material. Discrete, spherical and free-flowing microcapsules were obtained by phase separation induced by solvent evaporation using bentonite as a solid emulsifier. The prepared microcapsules were evaluated for drug content, wall thickness, flow properties, size distribution, density and in vitro dissolution studies in gastric fluid. The effect of various process variables such as agitation speed, coat-core ratio, etc., on the micromeritic and release characteristics has been described.


Erythrocyte based delivery system of primaquine: in vitro characterization.

Primaquine phosphate, an antimalarial drug, was loaded in erythrocytes by the process of endocytosis. The encapsulation of 0.1-0.15 mg of drug ml-1 of packed erythrocytes was achieved. The loaded cells attained spherical shape and exhibited higher osmotic fragility and lower resistance to turbulence shock as compared with normal cells. Glutaraldehyde treatment stabilized the cells which were noted to be resistant to the osmotic and turbulence shocks. In vitro release of drug and haemoglobin was also retarded upon treatment of loaded erythrocytes with glutaraldehyde. The studies suggest the potentiality of primaquine-loaded, glutaraldehyde-treated erythrocytes as an intravenous drug delivery system for casual prophylaxis and radical cure of malaria.


Sirenomelia: case of the surviving mermaid.

This report describes a neonate with sirenomelia who was recently treated at British Columbia Children's Hospital. Prenatal diagnosis was made at 29 weeks' gestation. Survival was not anticipated. Cesarean-section at term showed a live 2,375-g infant with excellent Apgar scores. Anomalies noted were fused lower extremities, imperforate anus, colon atresia, bilateral fused pelvic kidneys with renal dysplasia, pelvic and sacral dysplasia, and genital abnormalities. Laparotomy and colostomy were performed. All other anomalies are compatible with life and she is neurologically normal. Eventual separation of the lower extremities is planned. This is the second reported case of survival in a patient born with sirenomelia.


Pseudomembranous colitis following resection for Hirschsprung's disease.

Enterocolitis is the most common cause of significant morbidity and death in Hirschsprung's disease. Although most cases respond to nasogastric decompression, antibiotics, and colonic evacuation, some children have an unusually fulminant or protracted clinical course. Four cases are reported of pseudomembranous colitis (PMC) that developed 1 to 18 months (mean, 8 months) after definitive surgery for Hirschsprung's disease (Soave endorectal pull-though, 2; Duhamel procedure, 2). While all children presented with fever, abdominal distention, and diarrhea, indistinguishable from typical Hirschsprung's enterocolitis, the clinical course was fulminant in two cases, both of whom died of septic shock. Postmortem examination in both showed extensive colonic pseudomembranes despite identification of Clostridium difficile toxin and subsequent vancomycin therapy (initiated late in the clinical course). Two children in the series had protracted hospitalizations and eventually required diverting enterostomy despite recognition of C difficile toxin and treatment with enteral vancomycin, in one child necessitating multiple courses of antibiotic therapy. Awareness of the virulence of PMC associated with Hirschsprung's disease (even after definitive resection) should prompt submission of stool specimens from any child who presents with enterocolitis for both C difficile culture and toxin levels. On the basis of our experience it is our policy to initiate a prompt course of vancomycin by rectal lavage or nasogastric tube in all children with Hirschsprung's enterocolitis, pending culture results, in view of the significant morbidity and mortality exemplified by cases in this review.


The bowel management tube: an effective means for controlling fecal incontinence.

Regular bowel washout enemas have been used as a method of management of fecal incontinence. The effective administration of a washout enema to a child with weak anal sphincters is often a problem. Using a new silastic balloon-tipped enema catheter (bowel management tube [BMT]) of our design, we prospectively studied its effectiveness in a group of children who suffered fecal incontinence. Thirty-one children were studied over a 1-year period. Their diagnoses included meningomyelocele (19), postoperative Hirschsprung's disease or imperforate anus (10), and other (2). Before and after starting the BMT enema system, clinical assessment and a diary, which graded the degree of fecal incontinence and satisfaction with the system, were completed. Five patients failed to benefit because of noncompliance (3) or balloon extrusion (2). Three more patients discontinued the use of the tube system. Twenty-three patients achieved successful results with this system as evidenced by a significant amelioration in their fecal incontinence and their unwillingness to give up the use of the BMT. We conclude that the use of a regular washout enemas with BMT can be an effective method for control of fecal incontinence in children.


Release kinetics of fluphenazine from biodegradable microspheres.

Fluphenazine-loaded microspheres were prepared using biodegradable lactide and lactide-co-glycolide polymers. Sustained release of fluphenazine was achieved with fluphenazine loadings of up to 30 per cent in both the lactide and lactide-co-glycolide polymers. Fluphenazine release from microspheres was found to increase with increasing drug loading and was most rapid from the poly-L-lactide-co-glycolide microspheres. The release profiles showed a 'lag' period followed by an accelerating release phase and in some cases a decay period, i.e. the release profiles were sigmoidal and fitted the Prout-Tomkins equation (Prout and Tompkins 1944). Consequently it was considered that polymer degradation, the primary rate-determining step controlling drug release, occurred by a mechanism involving propagation of active sites, drug release reflecting the spread of this degradation throughout the polymer.


Preparation and in vitro evaluation of slow release ketoprofen microcapsules formulated into tablets and capsules.

Ketoprofen powder was encapsulated with Eudragit RL/RS polymer solutions in isopropanol-acetone 1:1, using a simple and rapid method. Microcapsules were prepared using Eudragit solutions with different RL/RS ratios. The encapsulation process produces free-flowing microcapsules with good drug content and marked decrease in dissolution rate. The retardation in release profile of ketoprofen from microcapsules was a function of the polymer ratio employed in the encapsulation process. In vitro release of ketoprofen from microcapsules either filled in gelatin capsules or compressed into tablets, using calcium sulphate as diluent, confirmed the efficiency of the encapsulation process for preparing prolonged release medication. A capsule formulation with optimum sustained-release profile was suggested.


Motility and sensation of the rectosigmoid and the rectum in patients with anorectal malformations.

Motility of the rectosigmoid and rectum and reservoir function of the rectum after surgery for anorectal malformations were investigated in 32 patients (17 with high type, 6 with intermediate type, and 9 with low type anomaly) aged 5 to 16 years. All 32 patients were examined manometrically as well as with a newly devised myoelectrical method. Manometry showed that the values of maximum anal pressure and anorectal pressure difference in the high type were significantly lower than those in the low type. However, the incidence of contractile activity of the rectosigmoid was not significantly different between these two groups. The threshold sensation pressure and the maximum tolerable pressure in the high type were significantly higher than those in the low type, and the rectal compliance in the high type was significantly lower than that in the low type. Electromyography was recorded at 8 cm and 5 cm from the anal verge. Two types of slow waves were observed, a faster rhythm and a slower rhythm. Their frequency was similar in the three groups. However, the numbers of spike bursts in the high type and intermediate type were significantly higher than those in the low type. These results indicate that in addition to an inadequate anal resting pressure a loss of optimal rectal sensation or rectal reservoir function might be associated with fecal incontinence in the high type and that increased spike bursts might play some role in rectal motility.


Congenital urethral fistula with normal anus: a report of two cases.

Congenital rectourethral or anourethral fistulae without imperforate anus in males are rare, representing less than 1% of anorectal malformations. We report our experience with two males with "N type" urethral fistulae. One, a 5-year-old boy, presented with recurrent urinary tract infections (UTIs) and passage of urine per anus. Investigations included a voiding cystourethrogram (VCUG), which demonstrated a fistula from the urethra to the anus. On physical examination, a small perianal opening was noted just outside the anus, which drained a small amount of urine after voiding. The fistula was excised via a perineal approach. The second patient is a 5-year-old boy with a long history of recurrent UTI requiring multiple hospitalizations since the newborn period. Chronic renal failure developed as a complication of repeated urinary tract infections. Investigations showed a single hydronephrotic pelvic kidney and a small bladder. He underwent numerous diagnostic and reconstructive procedures including cystoscopy and augmentation cystoplasty. Recurrent infections continued and an N type anourethral fistula was eventually diagnosed. The fistula was located between the anal canal and the membranous urethra. An anterior perineal approach was also used. Both fistulae were easily located, and reconstructive surgery of the urethra was not required. Postoperative VCUGs in both patients were normal. They have been free of infection with normal urinary continence since resection of the fistula. Congenital N type anourethral fistulae are rare, but should be considered in cases of recurrent urinary tract infections. The diagnosis may be missed by endoscopic procedures, but VCUG should demonstrate the fistulous tract.


Poly(4-vinylpyridine)-coated liposomes: stability studies and release of acetylsalicylic acid.

Liposomes of dimyristoylphosphatidylcholine (DMPC) and dicetylphosphate (DCP) reacted with 4-vinylpyridine (4-VP) to form a salt and, subsequently, autopolymerized for form poly(4-vinylpyridine) (poly(4-VP))-coated liposomes. The conditions for optimization of polymer coating have been determined; also, the effects of polymer coating on liposome stability, the encapsulation of ASA and its release kinetics have been measured. The coating efficiency was maximum at a DMPC:DCP 1:1 mole ratio, at pH 4.0 in acetate buffer, and a polymerization time of 40 min. The polymer-coated liposomes were stable in 2 mM sodium cholate and 4 per cent isopropanol solutions, as determined from turbidity measurements, versus a 20-25% decrease in stability of uncoated liposomes. The encapsulation efficiency of ASA reached a maximum of 9 per cent at DMPC:DCP 1:1 mole ratio. The release of ASA at 37 degrees C, pH 7.0 was characterized by an initial fast release (85 and 63 per cent in 20 min from uncoated and polymer-coated liposomes, respectively) followed by a slow, constant release rate up to 140 min. Thus, autopolymerization of a polymerizable monomer at liposome surfaces represents a potentially feasible stabilization approach for liposomes exposed to sodium cholate solutions with greater retention of solute than uncoated liposomes.


Release kinetics of salbutamol sulphate from wax coated microcapsules and tableted microcapsules.

Microcapsules of salbutamol sulphate were prepared using beeswax and carnauba wax as coating materials. In vitro release kinetics were studied following the zero order, first order and Higuchi equations. Beeswax alone was not effective but beeswax and carnauba wax combinations were suitable in controlling the in vitro release of the drug. Microcapsules were compressed into tablets to get a controlled release oral dosage form. Release from tableted microcapsules was significantly more prolonged than the respective batches of the microcapsules. Best data fit with the highest correlation coefficient for the tableted microcapsules was obtained for first order.


Polyacrylate resin microcapsules for taste masking of antibiotics.

Various microencapsulated dosage forms were prepared to limit the release of an antibiotic in solution for up to 3 days and in the oral cavity following per oral administration. An experimental antibiotic, clarithromycin (TE-031), was used in these studies. The drug was first encapsulated in gelatin followed in some cases by crosslinking with glutaraldehyde. The gelatin microcapsules were then coated with acrylic resins (Eudragit), whose solubility properties vary according to pH. A non-solvent coacervation technique was used to apply the Eudragit resins. It was found that crosslinking the gelatin retarded release of TE-031 somewhat relative to that from uncrosslinked gelatin microcapsules in a 72h release experiment conducted at room temperature. Coating the gelatin microcapsules with Eudragit resins L100, S100, or E100 slowed the release of TE-031 further still; less TE-031 was released over 72 h from the Eudragit-coated formulations prepared with crosslinked gelatin compared with formulations prepared with uncrosslinked gelatin. The Eudragit E100-coated crosslinked gelatin microcapsule formulation was most effective in preventing release of the TE-031 under simulated conditions of storage in an aqueous solution.


Blunt traumatic disruption of the thoracic aorta: a rare injury in children.

Rupture of the thoracic aorta secondary to blunt chest trauma is an exceedingly uncommon injury in pediatric patients. We present a case of blunt traumatic aortic disruption in a 10-year-old child who was successfully managed by primary aortic repair using partial cardiopulmonary bypass. The epidemiology and pathophysiology of this injury, with particular reference to children, is reviewed. The ongoing controversies regarding the diagnosis and operative management of this injury are summarized.


Adult-to-neonate lung transplantation: anatomic considerations.

Babies born with severe pulmonary hypoplasia are unsalvageable despite maximal therapy including extracorporeal membrane oxygenation (ECMO). Using ECMO as a bridge to transplantation, reduced-size lung grafts (pulmonary lobe or segment) could expand the pool of cadaver donors and may allow for HLA-matched living-related transplants. We tested this concept first in the piglet model and developed the technical maneuvers necessary to perform lobar and segmental lung transplants from adult pigs into neonatal piglets. Prior to clinical application, a systematic evaluation of anatomic considerations for reduced-size human lung transplantation was needed. A series of human adult and neonatal cadaver thoracic dissections were performed to determine the adult pulmonary lobe or segment with the proper size, orientation, and vascular and bronchial anatomy for use as a neonatal lung transplant. The adult right middle lobe (RML) is the best candidate for neonatal left lung replacement. The adult RML, once removed, can be rotated 180 degrees around its superior-inferior axis and the vessels and bronchus align well in the left chest of the neonate. The RML may require further reduction to fit into the neonatal left chest. Selective arterial perfusion of the RML showed the anterior segment to be a near-perfect match for fit and anatomy. This technique may eventually permit living-related lung transplantation.


Juvenile hemangiomas involving the thoracic trachea in children: report of two cases.

Two 3-month-old girls presented with posterior mediastinal juvenile hemangioma (JH), a benign tumor rarely found in the mediastinum. Incomplete resections were performed. Over 4 and 7 months, respectively, the hemangiomas recurred and grew through the tracheal wall into the tracheal lumina, reducing the airway by 90% in one case and 70% in the other. The recurrences were resected, including five tracheal rings in the first case and four in the second. In case 1 the tumor recurred in the trachea 2 months later. A tracheostomy was performed, and corticosteroids were administered for 6 months. The tumor involuted and the patient was decannulated after 18 months; she is doing well 7 years later. The patient in case 2 has been well in the 18 months since her second operation. Airway obstructions can be treated by tracheal resection when conservative management fails.


Peritoneal exudates from microencapsulated rat islets of Langerhans xenografted mice presenting characteristics of potentially cytotoxic non-specific inflammation.

Grafted polyacrylamide microencapsulated islets of Langerhans in the peritoneal cavity of mice did not survive more than a few days, perhaps owing to a non-specific inflammatory reaction or an immune rejection. To assess the two hypotheses, we used flow cytometry (FACS) to analyse cell populations of empty or islet-loaded microcapsules grafted in the peritoneal cavity of mice, and performed cytotoxic assays with proteases secreted by inflammatory cells. An immune rejection did not seem to occur, but the degree of inflammation could explain the short life of the grafts.


Improvement of a microencapsulation with aqueous core by factorial design.

Preparation of microcapsules with aqueous core and polyamide walls is influenced by several factors. We improved the stability of walls and size of capsules by simultaneous variation of four factors: total ratio of polymer, ratio of amines to acid chlorides, concentration of surfactant and speed of stirring. Use of factorial design minimizes the number of experiments and permits us to know the influence of these factors and of their interactions. By increasing the ratio of amines to acid chlorides and with a low concentration of total polymer, we obtained more stable capsules. Surfactant had a negative effect on the hardness of the polymer.


Bioadhesive polymer-grafted starch microspheres bearing isosorbide dinitrate for buccal administration.

A polymer-grafted mucoadhesive system bearing isosorbide dinitrate was prepared for buccal administration. Polymer grafting of starch microspheres modified drug release and surface characteristics of microspheres. Bioadhesion and factors affecting bioadhesion were studied. Process variables that could affect microsphere size, and as a result the release of the drug, were also studied. It was observed that compression of grafted starch microspheres modified drug release and extended drug action via slow release following buccal application. Prepared system(s) were characterized for drug release and in vivo performance and compared with conventional oral treatment. The systems were noted to be promising.


Microencapsulation of terbutaline sulphate by the solvent evaporation technique.

Terbutaline sulphate microcapsules were prepared by coacervation-phase separation (solvent evaporation) technique using ethyl cellulose as a coating material. Acetone, ethyl alcohol and isopropyl alcohol were employed as solvents for coating material. Microcapsules were evaluated for their drug content, particle size distribution (microscopic method), flow properties, bulk density, in vitro dissolution, drug release kinetics and surface characteristics (scanning electron microscopy).