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A coagulation defect, characterised mainly by a prolongation of the thrombin time, the prothrombin time and the partial thromboplastin times was discovered in a patient with severe liver damage. As the reptilase time was also prolonged and a discrepancy was found between fibrinogen determinations in plasma with different methods the presence of an abnormal fibrinogen was postulated. After purification of fibrinogen from the plasma, a delayed aggregation of fibrin monomers was confirmed. Histological examination of the liver at autopsy revealed the existence of a primary hepatoma, suggesting the acquired nature of the abnormal molecule.

Safety margins and variability in the composition of glucose and maize-based oral rehydration therapy (ORT) prepared by mothers in a rural district of Western Kenya, are reported here. In a 2-year longitudinal field study, packets containing glucose ORS and a home solution made with maize and table salts, were provided to the mothers of 6180 children in Kakamega District in two separate sub-locations. Experienced and trained field workers supported by community registered nurses provided training for the preparation and use of ORT during weekly visits to every household. On four occasions separated by 4-6 months, a 5 per cent random sampling was done of the home-prepared solutions actually used for the treatment of children with diarrhoea. The water used for preparing ORT was also sampled. Samples of 174 glucose-based ORT, 148 maize-salt ORT, and 201 samples of water were analysed. Only 2 per cent of the maize-based ORT were above 120 meq/1 sodium (i.e., the safe range of sodium concentration) compared to 17.8 per cent for glucose solutions (p < 0.001). Home water samples contained substantial amounts of salt, which could unpredictably affect the final composition of the ORT solutions. We conclude that maize-salt ORT had a better margin of safety than glucose-based ORS.

Objectives: Both clinical and subclinical vitamin A deficiency has substantial impact on the mortality and morbidity of infectious diseases among children. We prospectively studied the serum retinol level in 200 neonates and their mothers at the Al-Adan Hospital in Kuwait. Methods: Five millilitres each of cord blood and maternal venous blood were collected at the time of delivery. Serum was separated and transported under specified conditions to the laboratory. Serum retinol was estimated using high performance liquid chromatography. Results: Mean serum retinol levels of both babies and mothers were found to be adequate, being 48 and 57 µg/dl, respectively. Significant correlation (p < 0.01) was obtained between serum retinol levels for the babies and their mothers. Conclusion: The results of this study demonstrate that vitamin A deficiency is not present among the neonates and their mothers studied. A larger population survey is recommended in some high risk areas of Kuwait.

We prospectively studied clinical outcome and nutrition absorption in male children (6-36 months of age) with persistent diarrhea (PD) and severe protein-energy malnutrition (mean z score for age, -4.2 +/- 0.8). Fifty-one children were randomly allocated to receive a combination of khitchri, a rice-lentil mixture, yogurt, and half-strength buffalo milk (group A; n = 26) or full-strength soy formula (group B; n = 25) for 14 days. The initial caloric intake (p < 0.02) and mean weight gain (p < 0.02) were greater in the group B patients. The mean stool volume and frequency were comparable between the two groups. Seven children in group A were considered clinical failures by criteria of weight loss and PD, compared to three in group B. The coefficients of absorption (COA) for protein were similar between the two groups, but group B patients had higher values of COA for energy and fat (p < 0.05) in the second week of nutritional rehabilitation. The majority (63%) of the children improved on the khichri-yogurt-milk diet but the nutritional outcome was not as good as with the soy formula. These data indicate that a traditional diet can be successfully used in the dietary management of PD and severe malnutrition but that a more optimal composition, yielding a higher success rate, should be sought.

Serum retinol and hemoglobin levels were determined in 532 children aged 6-60 months living in urban slums of Karachi, Pakistan. Overall 67% (358 of 532) of children had hemoglobin levels of less than 11 g/dl, the World Health Organization definition of anemia for this age group. Estimations for red blood cell indices (hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and red blood cell count) were done on a sample of 391 children to classify anemia morphologically. A similar percentage (69.8% [273 of 391 children]) of anemia was found in this group. The anemia was predominantly microcytic and hypochromic. Normocytic normochromic anemia was present in only 16.5%. Serum retinol levels were significantly correlated with hemoglobin (P < 0.002), hematocrit (P < 0.01), and red blood cell (P < 0.001) levels. However, anemia was found to be a poor predictor (positive predictive value [PPV] = 2.5%) for the presence of vitamin A deficiency (retinol < 10 micrograms/dl). The PPV increased to 54% if 20 micrograms/dl, which is an indicator of marginal vitamin A status, was used as the cutoff point. The sensitivity of the hemoglobin test was found to be 75% in correctly identifying vitamin A deficiency when retinol levels of 10 micrograms/dl and 20 micrograms/dl were both used as the cutoff points for deficiency. The specificity for the hemoglobin test varied from 33% to 40% when levels of 10 micrograms/dl and 20 micrograms/dl were used as the cutoff points for vitamin A deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

Rice based oral rehydration therapy (ORT) solutions have been shown to be superior to glucose oral rehydration salts (World Health Organisation (WHO) ORS) in reducing stool volume and duration of diarrhoea in children and adults. Rice based ORT has been used only sparingly in young infants, however, because of theoretical concerns about digestibility. A randomised controlled trial of rice based ORT (50 g rice and electrolytes identical to WHO ORS) and WHO ORS was carried out in 52 male infants less than 6 months old with moderately severe acute diarrhoea to evaluate efficacy and digestibility. Nineteen (70%) of 27 children who received rice based ORT and 18 (72%) of 25 children who received WHO ORS were treated successfully. The mean (SD) diarrhoeal stool output for the first 24 hours of treatment was significantly lower in the infants receiving the rice based ORT than in those receiving WHO ORS (101.0 (60.5) v 137.1 (74.6) g/kg). The stool output was also significantly less in the rice based ORT group in the second 24 hours. Infants in the rice based ORT group drank significantly less rehydration solution than infants in the WHO ORS group (mean (SD) 165.4 (77.4) v 217.9 (86.1) during the first 24 hours of treatment. There was no difference in the duration of diarrhoea between the groups. The volume of breast and formula feeding was similar in the two groups. No difference was seen in the frequency of finding reducing substances or acid pH in the stools of either group of children. The results suggest that rice based ORT is as effective as WHO ORS in infants with moderately severe diarrhoea and that rice based ORT is as well tolerated as WHO ORS in infants.

We assessed the vitamin A status of 532 children with an age range of 6-60 months who were living in slum areas of Karachi, Pakistan, using three methodologies: clinical eye examination, dietary vitamin A intake, and serum retinol level. No definite clinical signs of xerophthalmia were observed in any of these children. The mean +/- SD vitamin A intake estimated from a food frequency questionnaire for the group with inadequate (low and deficient) serum retinol levels (20 micrograms/dl) was 362 +/- 332 retinol equivalents (RE) compared with 431 +/- 332) RE in the group with adequate serum levels (P0.005). Deficient serum retinol levels (10 micrograms/dl) were present in 12 children (2%); two of these had a healed corneal scar. Low serum retinol levels (10-19 micrograms/dl) were present in 46%, while 51% children had adequate levels (or = 20 micrograms/dl). The mean +/- SD serum retinol level for the inadequate (20 micrograms/dl) and adequate groups were 15.3 +/- 2.8 and 26.6 +/- 6.7 micrograms/dl, respectively. These results suggest that a significant number of children in these communities have low vitamin A levels and thus may constitute an at risk group. These results also suggest that the dietary intake method may be a simple and inexpensive screening tool for assessment of vitamin A status in communities.

Feeding practices may have an important impact on diarrheal diseases in developing countries. This study evaluated feeding practices in three groups of male children aged 6-36 mo: 100 with persistent diarrhea (PD), 79 with acute diarrhea (AD), and 86 in a comparison group (CG). The children came from comparably poor socioeconomic settings in Karachi, Pakistan, except that the literacy rates were higher in mothers of the CG (P = 0.0001). Although greater than 95% of all infants were breast-fed, delayed initiation of breast-feeding was more common in the diarrhea groups. Children with diarrhea were also more likely to receive supplemental milk (PD = 92%, AD = 87%) than were children in the CG (69%, P less than 0.05). Feedings were not withheld during diarrhea but changes were made in the nature of foods given. These results indicate that several feeding practices may be important risk factors for diarrhea in Pakistan.

With the discovery of oral rehydration therapy, mortality in acute diarrhea due to dehydration has decreased. But the nutritional effect of diarrhea in turn makes the child more vulnerable to other infectious diseases, including severe episodes of diarrhea. This remains an important hindrance towards improved child health especially in the developing countries. It is now essential to focus more attention on the nutritional aspect of diarrhea rather than rehydration alone. In 1924 Park advocated the nutritional benefit of the child rather than the frequency of the stool as being more important [1]. The same was elegantly shown by Chung and his co-workers in 1948 [2]. Recently, the value of this concept has been amply rediscovered both in the developed and the developing countries [3–5]. However, the main principles for the treatment of diarrhea in the west as well as in many of the developing countries are still rehydration and the modification or withholding of the pre-diarrheal diet along with a variable period of starvation. All these are aimed at reducing the malabsorption of nutrients and thereby inducing early recovery from diarrhea.

93 boys ages 5 or under who had diarrhea due to Vibrio cholerae were randomly assigned to treatment with glucose oral rehydration salt (ORS) or rice-based ORS. For the 1st 24 hours ORS only was given to all the patients. During the next 24 hour period ORS and normal food were given. The efficacy of the 2 types of ORS was compared in terms of ORS intake stool output change in hematocrit reading serum specific gravity and increase in body weight. At the end of the 1st 24 hours of treatment a 50% reduction in ORS intake and stool output was observed in the 47 patients randomly assigned to receive rice ORS as compared with the 46 patients who received glucose ORS. During the 2nd 24 hours of treatment a significant reduction in the stool output was noticed in the glucose ORS group making the efficacy of the glucose ORS equal to that of rice ORS. The study suggests that normal food can impart some of the superiority of "super" ORS to standard glucose ORS with regard to reduction of stool volume. (authors)

Agglutination inhibition immunoassays using antifibrinogen antiserum measure an antigenic determinant of fibrinogen which is located on the fragment D parts of this molecule. This antigenic determinant of fragment D, in contrast to others, does not form an immune precipitate with antifibrinogen antiserum. Upon very extensive hydrolysis by plasmin, this antigenic determinant has a reduced affinity for its antibody.

Exocrine pancreatic function was assessed by means of the Lundh test in 14 patients with acute cholera and 18 patients with acute infectious non-cholera diarrhoea within the first 24 h of their admission. Mean tryptic activity amounted to 39.8 +/- 4.8 microEq/min/ml in the cholera group and to 64.4 +/- 11.0 microEq/min/ml in the non-cholera group. None of these patients shared a value below the lower limit of normal. In fact, the mean tryptic activity per 2 h was significantly higher than that reported previously in a control group from the Bengal area. It is therefore concluded that the exocrine pancreatic function is preserved and responds to food stimulation in various types of acute infectious diarrhoea, including cholera. These findings provide the pathophysiological background for the recent observation that oral rehydration solutions containing high-molecular-weight nutrients such as rice powder are at least as efficient or even more potent than the WHO-recommended glucose-electrolyte formula in acute diarrhoea.

Highly purified human plasminogen with NH2-terminal glutamic acid was prepared from Cohn fraction III by a combination of affinity, molecular sieving and ion-exchange chromatography. Incubation of this material with plasmin in a molar ratio of 20:1 at 37°C for 30 minutes resulted in the conversion to equally active plasminogen with NH2-terminal lysine or valine, consisting of a single polypeptide chain with slower anodic mobility, lower molecular weight and fewer antigenic determinants. In the peptide material two major fragments with apparent molecular weights of 6,200 and 3,100 were distinguished by Sephadex G-50 molecular sieving chromatography. These two fragments had NH2-terminal glutamic acid. Thus NH2-terminal lysine or valine plasminogen can be derived from NH2-terminal glutamic acid plasminogen by plasmin digestion.

Somatostatin has been shown to inhibit intestinal secretion induced by a variety of secretagogues. The ability of somatostatin to reduce stool output in patients with cholera was therefore investigated in a double-blind randomized controlled trial. Twenty-two patients with severe purging due to infection with Vibrio cholerae (≤ 12.5 ml/kg · h) received either somatostatin at a dose of 250 μg/h in saline (n = 12) or placebo (n = 10). The study drug was given for 12 h followed by a control period of the same duration. No difference in stool output was apparent between somatostatin- and placebo-treated groups. No side effects of somatostatin were observed. It is concluded that somatostatin is ineffective as an antidiarrheal agent in Asiatic cholera in humans.

124 patients with acute diarrhoea due to Vibrio cholerae or Escherichia coli were treated with either the standard sucrose-electrolyte solution or a cereal-based electrolyte solution, containing 30 g rice powder per litre and electrolytes as recommended by the World Health Organisation. The treatments were compared by measuring the rate of purging, change in body weight, serum specific gravity, urine output, and post-hydrolysis sugar content in the stool. The proportions of successfully treated patients in the rice-powder group were 80% for cholera patients and 88% for E. coli patients--no different from those in patients receiving the sucrose-electrolyte solution. Failure was due to rates of purging that exceeded the patient's ability to drink enough replacement solution. This study suggests that a rice-powder electrolyte solution is efficient and safe to use as a rehydrating oral fluid in acute diarrhoea.

Publisher Summary This chapter describes the impact of acute diarrhea of different aetiologies on food intake in children. In a study reviewed in the chapter, 68 children aged between 1 and 5 years, suffering from acute diarrhea because of known aetiological agents and having moderate to severe dehydration, were included. Any child showing signs of systemic infection or third degree malnutrition on admission or during the study was excluded from the study. After initial rehydration using intravenous fluid a nonabsorbable charcoal marker was fed to the patients, followed by a familiar Bangladeshi home diet of known composition. In children who were breast-fed, the breast milk intake was determined by test weighing. Experience has shown that in spite of encouragement or even forced feeding it is difficult to enhance the intake of a child who is suffering from diarrhea, however, one have shown that it is relatively easy quite early in the recovery phase to make up the loss sustained during the acute phase of diarrhea. This finding gives a clear pointer in developing strategies for the reduction in morbidity in children during and after diarrhea.

Whole gut transit time (TT) was measured in 68 children aged up to 5 years (29 cholera, 17 rotavirus, 13 enterotoxigenic Escherichia coli, and 9 Shigella) during acute stages of diarrhoea and 2 weeks after recovery. Absorption of calories, fat, protein, and carbohydrates contained in a normal Bangladeshi diet was studied for 72 h after the first appearance of a charcoal marker in the stool, both during acute diarrhoea and 2 weeks after recovery. Mean TT varied from 5.5 to 7.3 h during the acute stage and from 14.1 to 15.5 h during the recovery period of diarrhoea of all aetiologies; the increase in the TT was significant as expected (P less than 0.001). Correlation coefficients were calculated between TT and the coefficients for absorption of fat, nitrogen, calories, and carbohydrates in the acute and recovery stages of cholera, rotavirus, E. coli, and Shigella. No significant relation was found between TT and absorption of nutrients in any stage of diarrhoea of any aetiology. The results of this study suggest that the mechanism for absorption of nutrients is independent of the whole-gut transit time. Further studies are necessary to identify the role of transit of a meal and its absorption along the whole gut.

Les taux seriques de vitamine A, de proteine de liaison du retinol et de prealbumine ont ete doses chez 13 enfants de 3 a 9 ans, 4 heures apres une dose orale de vitamine A hydrosoluble au cours d'une diarrhee aigue et 2 semaines apres la guerison. Les resultats confirment que l'administration rapide de vitamine A est hautement souhaitable et efficace pour la prevention de la cecite dans les regions en voie de developpement ou diarrhees et malnutrition sont predominants

Published work suggests that the “nutritional status” of a child may represent as much the effect of infection as of dietary intake.1,2 A study by Mata and co-workers3 showed that the nutritional status of the children in rural Guatemala was more related to infections than to the availability of food. The same may be true for many other developing countries. That the nutritional consequences of diarrhea are protein-energy malnutrition and growth retardation has been established.4,5 Several factors are involved in this process, among which partial anorexia or loss of appetite, cultural taboos, maternal behavior during diarrhea resulting in withholding of food as a measure to control it, and increased catabolic processes that compound direct loss due to malabsorption are important.

Total and individual duodenal bile salt concentrations measured during digestion of an amino acid-based test feed are compared with dietary fat absorption in 50 children. Thirty-six were newborn infants, of whom 21 were fed evaporated milk (group 1), and 15 a modified formula (group 2); 16 were older children who served as ‘controls’ (group 3). Total bile salt levels in resting duodenal contents were similar in all the groups, but in groups 1 and 2 these were significantly lower following the feed (P

Pancreatic lipase and trypsin have been measured autotitrigraphically in duodenal aspirate both before and for 3 hours after an oral test feed. These studies concern 12 normal newborns, gestational maturity 34±2 weeks (M±SD), at approximately 2 weeks of age, and 14 apparently normal children aged 3–72 months. A consistent pattern of enzyme activity was found, with higher activity in the resting samples and in the third hour compared to very low activity during the first post-prandial hour. There was a significantly higher mean lipase activity in children compared with that in newborns (P=0.001) which was not so for mean trypsin. An estimate oftotal enzyme secretion by the pancreas was devised using determinations of polyethylene glycol in test feed and duodenal contents; this also allowed intergroup comparison since there was a significant difference between the groups in the degree to which test feed diluted enzyme activity (P

One hundred twenty children below 5 years of age with diarrhea caused by Vibrio cholerae , enterotoxigenic Escherichia coli , or rotavirus were studied for stool electrolyte composition and purging rates. The mean purging rate in cholera was 60.1 ml, in ETEC 39.2 ml, and inrotavirus infection 31.4 ml/kg/8 hour. The mean stool sodium concentration in cholera was 88.9 mMol/L, in ETEC 53.7 mMol/L, and in rotavirus infection 37.2 mMol/L. Stool potassium concentration did not show much variation. Mean CO 2 concentration in rotavirus infection was 6 mMol/L, significantly lower than in cholera and in ETEC diarrhea. In cholera, stool sidium concentration increased significantly with increase in puring rates; the same was not true in rotavirus and ETEC diarrhea. These differences are considered important factors in formulating replacement therapy in diarrhea.

The high prevalence rates, particularly among young children in most developing countries, make the influence of diarrhea on nutritional requirements of major concern. The multiple mechanisms whereby diarrhea of infectious origin can affect dietary requirements for calories and protein are listed in Table I. Estimation of the consequences for nutritional requirements is complicated by large quantitative and qualitative variations in the disease burden among different population and age groups. The effects depend on the type of diarrhea as well as on its frequency, severity, and duration. Moreover, available quantitative data are extremely limited. Those available under each of the categories indicated are examined separately in the text that follows.

The efficacy in acute childhood diarrhoea of oral rehydration therapy (ORT) based on staple foods (maize, millet, wheat, sorghum, rice, or potato) was compared with that of standard ORT based on glucose. 266 children aged 1-5 years, with a history of acute diarrhoea for 48 h or less, moderate to severe dehydration, and no complications, were assigned to treatment with one of the food-based oral rehydration salt solutions (ORS) or standard ORS. The mean stool output over the first 24 h of treatment in the group receiving standard ORS was significantly higher than that of any other treatment group, and the groups receiving food-based ORT showed substantial reductions in stool output compared with the standard ORT group. Abnormalities in electrolyte concentrations were corrected in all treatment groups with similar efficiency. The digestibility of the food-based ORS was assessed by the stool pH, glucose content before and after acid hydrolysis, and osmolality; there were no significant differences between the standard ORS and food-based ORS groups. Food-based ORT should be more acceptable to users in developing countries since the mixtures are similar to traditional weaning foods and since, unlike standard ORT, it reduces stool output substantially.The efficacy in acute childhood diarrhea of oral rehydration therapy (ORT) based on staple foods (maize, millet, wheat, sorghum, rice or potato) was compared with that of standard ORT based on glucose. 266 children aged 1-5 years, with a history of acute diarrhea for 48 hours in a Nigerian population or less, moderate to severe dehydration, and no complications, were assigned to treatment with one of the food-based oral rehydration salt solutions (ORS) or standard ORS. The mean stool output over the first 24 hours of treatment in the group receiving standard ORS was significantly higher than that of any other treatment group, and the groups receiving food-based ORT showed substantial reductions in stool output compared with the standard ORT group. Abnormalities in electrolyte concentrations were corrected in all treatment groups with similar efficiency. The digestibility of the food-based ORS was assessed by the stool pH, glucose content before and after acid hydrolysis, and osmolality; there were no significant differences between the standard ORS and food-based ORS groups. Food-based ORT should be more acceptable to users in developing countries since the mixtures are similar to traditional weaning foods since, unlike standard ORT, it reduces stool output substantially.

Diarrhoeal disease is one of the most important causes for the mortality of children under 5 years in the developing countries [1–3]. Studies from Gambia and Guatemala showed that growth faltering and associated malnutrition are the direct consequence of diarrhoeal diseases [4–6]. Other infectious diseases were also found to cause a reduction in dietary intake due to anorexia and withdrawel of food [6]. Loss of nutrients due to vomiting and malabsorption could occur during enteric infections [7]. A child with fever may go into negative nitrogen balance due to increased rate of catabolism and even mild infections could result in a catabolic state with increased nitrogen loss [8]. Since diarrhoeal diseases adversely affect the child’s growth [4, 6], the mechanism for this health hazard needs to be focused. Several of the following factors were considered to explain the mechanisms through which diarrhoeal diseases can affect children nutritionally: 1. reduced intake due to anorexia, withdrawel of food, as practiced by mothers to control diarrhoea, or feeding an altered diet for a prolonged period; 2. breakdown of body protein due to increased catabolism; 3. malabsorption of carbohydrates due to lactase deficiency [9].