Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells.

Exploiting the lytic life cycle of viruses has gained recent attention as an anticancer strategy (oncolysis). To explore the utility of adenovirus (Ad)-mediated oncolysis for rhabdomyosarcoma (RMS), we tested RMS cell lines for Ad gene transduction and infection. RMS cells were variably transduced by Ad. Compared with control cells, RMS cells were less sensitive or even resistant to oncolysis by wild-type virus. RMS cells expressed the Ad internalization receptors, alpha(v) integrins, but had low or undetectable expression of the major attachment receptor, coxsackievirus-Ad receptor (CAR). Mutant Ads with ablated CAR binding exhibited only 5-20% of transgene expression in RMS cells seen with a wild-type vector, suggesting that residual or heterogeneous CAR expression mediated the little transduction that was detectable. Immunohistochemical analysis of archived clinical specimens showed little detectable CAR expression in five embryonal and eight alveolar RMS tumors. Stable transduction of the cDNA for CAR enabled both efficient Ad gene transfer and oncolysis for otherwise resistant RMS cells, suggesting that poor CAR expression is the limiting feature. Gene transfer to RMS cells was increased >2 logs using Ads engineered with modified fiber knobs containing either an integrin-binding RGD peptide or a polylysine peptide in the exposed HI loop. The RGD modification enabled increased oncolysis for RMS cells by a conditionally replicative Ad, Ad delta24RGD, harboring a retinoblastoma-binding mutation in the E1A gene. Thus, the development of replication-competent vectors targeted to cell surface receptors other than CAR is critical to advance the use of Ad for treating RMS.

From pedialyte to popsicles: a look at oral rehydration therapy used in the United States and Canada.

To obtain information on the attitudes and practices concerning oral rehydration therapy in the United States and Canada, a questionnaire was sent to the chairmen of departments of pediatrics of 142 medical colleges. Some form of oral fluid therapy for treatment of diarrheal dehydration is used by the institutions of all 128 survey respondents. The most commonly used fluids, commercial sugar-electrolyte solutions (89%), clear liquids (78%), and fruit juices (58%) have very different compositions and concentrations of ingredients. Oral therapy is based on a specific written protocol at 30% of the institutions and is used most frequently to treat outpatients with mild dehydration. To determine a uniform and optimal approach to oral fluid treatment for diarrhea, comparative clinical trials are needed to assess which fluid compositions and concentrations are most effective in preventing dehydration and in treating dehydration once it has occurred.

Dietary risk factors associated with acute and persistent diarrhea in children in Karachi, Pakistan.

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.

Human Yersinia enterocolitica infections in Wisconsin. Clinical, laboratory and epidemiologic features.

Yersinia enterocolitica has been sought in stool and blood culture specimens by the Wisconsin State Laboratory of Hygiene (SLH) since 1973. Clinical information on symptoms, duration of illness, and use of antibiotics for 41 persons with Y. enterocolitica infections from January 1, 1979, to September 30, 1980, was obtained by telephone interviews. Diarrhea and abdominal pain were the most common symptoms of the ill persons; extraintestinal symptoms were infrequently reported. Ten infected persons (24 percent) had no illness. Review of a 10 percent sample of all stool specimens cultured at the SLH from June 20, 1977, to June 20, 1979, revealed that Salmonella was the most commonly isolated enteric pathogen (15.4 percent) followed by Shigella (2.0 percent) and Y. enterocolitica (0.7 percent). Several different biotypes and serotypes of Y. enterocolitica were associated with illness. Y. enterocolitica isolates were uniformly susceptible to a wide variety of antibiotics, and most isolates were resistant to ampicillin. Epidemiologic studies showed that persons with Y. enterocolitica infections were more likely to live in rural counties than were all persons sending stool samples or those having Salmonella infections; underlying illness was identified as a risk factor for infection.

Use and misuse of oral therapy for diarrhea: comparison of US practices with American Academy of Pediatrics recommendations.

To determine how closely US pediatricians follow the 1985 American Academy of Pediatrics Committee on Nutrition's recommendations on oral therapy for acute diarrhea, a questionnaire was administered to four groups: New England private practitioners, pediatricians from 27 states attending a postgraduate course, representatives of departments of pediatrics at US schools of medicine, and housestaff at Boston Children's and Massachusetts General hospitals. The responses from departments of pediatrics and housestaff were not significantly different from those of community practitioners in most categories. The reported rate of use of glucose-electrolyte solutions recommended by the American Academy of Pediatrics was not different from the use of nonphysiologic, high-osmolar, low-salt solutions such as sodas and juices. The usage rate for glucose-electrolyte solutions meeting the American Academy of Pediatrics-recommended carbohydrate-to-sodium ratio of less than 2:1 was less than 30%. Other findings included the general lack of agreement on the use of a single type of therapy and the common use of oral therapy only for mild or no dehydration. Although the American Academy of Pediatrics recommends that feeding be reintroduced in the first 24 hours of a diarrheal episode, the majority of respondents withhold feeding until the second day or later. These findings indicate that educational programs on oral therapy during acute diarrhea are needed in the United States.

Dietary management of persistent diarrhea: comparison of a traditional rice-lentil based diet with soy formula.

Recent studies have indicated that enteral diets can play an important role in the treatment of persistent diarrhea. Khitchri, a local weaning food in Pakistan, is composed of rice and lentils, which have previously been shown to be well tolerated in many children with acute diarrhea. The effectiveness of a khitchri and yogurt (KY) diet, which is inexpensive and widely available in Pakistan, was studied. One hundred two weaned boys (6 to 36 months old) with persistent diarrhea were randomly assigned to receive either soy formula (group A) or the KY diet (group B) for 14 days. Group A also received the KY diet in addition to formula for days 8 through 14. Twenty-nine children did not complete the study because of severe infection (13) or their family's decision to leave the study early (9 in group A and 7 in group B). Sixty-six children successfully completed the study protocol; there were five clinical failures in group A and two in group B. On a comparable caloric intake, there was a significantly lower stool volume (group B: 38 +/- 16 [mean +/- SD] vs group A: 64 +/- 75 g/kg per day, P less than .05) and frequency (B: 4.4 +/- 2.0 vs. A: 6.6 +/- 4.2 stools per day, P less than .005) in children fed KY during the first week of therapy. Group B children also had a significantly greater weight gain than children in group A during the first week (B: 468 +/- 373 g/wk vs A: 68 +/- 286 g/wk, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Growth failure and inflammatory bowel disease: approach to treatment of a complicated adolescent problem.

Severe retardation of linear growth occurs in a minority of children with Crohn's disease. It appears to be associated with increased disease activity and decreased caloric intake. Why some children are affected and others are not is unknown, but some degree of growth retardation is probably more prevalent than is generally appreciated. The use of somatomedin-C levels may be of some future value in predicting which children will be affected. Growth failure is often difficult to treat and requires vigorous medical and nutritional support. No current treatment is without attendant problems. Proper and frequent assessment of growth and development will help ensure intervention while growth potential still exists in these children. Large cooperative studies are needed to compare the effects of various treatment plans on the growth velocity and ultimate stature of children with Crohn's disease-related growth retardation.

Is anemia an accurate predictor of vitamin A status in Pakistani children?

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)

Prevalence of residual paralysis from paralytic poliomyelitis in a rural population of Bangladesh.

To estimate the prevalence of residual paralysis from poliomyelitis in children in one area of rural Bangladesh, a survey of the amount and original cause of lameness was undertaken. The International Center for Diarrhoeal Disease Research, Bangladesh Matlab field area, which has been under demographic surveillance for 13 years, provided the study population of 25,000 children aged 5--14 years. The cause of the lameness identified for a child in the survey was based on criteria obtained from a health history questionnaire and a physical examination performed by a physician. The prevalence rate for residual paralysis of poliomyelitis estimated from the lameness survey was 0.84/1,000 children aged 5--14 years. Since lower extremity paralysis occurs in only about 80% of children with paralytic poliomyelitis, the prevalence rate for all cases of residual paralysis of poliomyelitis was calculated to be 1.05/1,000 children in this age group.

Outbreak of invasive Escherichia coli gastroenteritis on a cruise ship.

An invasive strain of Escherichia coli (ONT:NM) was isolated from stool specimens from 7 of 10 ill passengers who developed diarrhea during a 5-day ocean cruise. The ill passengers had shared no common exposures off the ship before or during the cruise. Three of the persons whose stools were cultured were part of a tour group of 219 persons, and a food consumption and health history questionnaire was completed by 190 members (87%) of this tour group. Forty-seven (25%) had had diarrhea during the cruise; other symptoms among those with diarrhea included nausea (72%), abdominal cramps (68%), headache (68%), chills (60%), dizziness (53%), myalgias (43%), subjective fever (36%), and vomiting (26%). The median duration of symptoms was 3 days. Eating at cold buffets on ship and eating potato salad, a buffet food item, were significantly associated with illness. No evidence of secondary spread of illness in household contacts of the ill person was found.

Vitamin A status of children in the urban slums of Karachi, Pakistan, assessed by clinical, dietary, and biochemical methods.

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 (P < 0.005). 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.

Cholera in Indonesia: epidemiologic studies of transmission in Aceh Province.

To determine the modes of transmission of cholera in the regency of Pidie, Indonesia, and to consider strategies for its control, we set up a laboratory to identify Vibrio cholerae 01 from patients with severe diarrhea in all government clinics in the regency and questioned culture-positive cases and neighborhood controls about possible exposures to V. cholerae 01. Between 12 July and 15 August 1982, 63 of 138 suspected cholera cases were confirmed by the laboratory; 53 of these patients were seen and followed up. We were unable to identify a single, indisputable mode of transmission for cholera which was amenable to immediate control. Nonetheless, a number of factors, including exposure to water from the Tiro-Sigli River and consumption of ice, were associated with disease. Other findings bring into question the value of current practices of chlorinating dugwells and disinfecting homes with Lysol during a cholera outbreak. The case-control approach to investigating the mode of transmission of cholera has distinct limitations when applied in endemic setting where there may not be a single predominant vehicle of transmission, or where the vehicle such as river water is used by all and is only periodically contaminated.

Home-administered oral therapy for diarrhoea: a laboratory study of safety and efficacy.

Serum electrolytes were measured for persons treated for diarrhoea at home with prepackaged or locally available sugar and salt oral rehydration therapy (ORT) solutions and for persons with diarrhoea who received no ORT but were treated according to local customs. No detrimental effect was found for persons treated with ORT at home; no significant difference was found in the frequency at which members of the groups had hypernatraemia. The rates of hyponatraemia and hypokalaemia were significantly lower for persons who took estimated appropriate volumes of ORT than for those who took less than appropriate volumes or for persons treated according to local customs without ORT. These laboratory results indicate that ORT administered in rural homes in Bangladesh was safe and effective under the conditions of our study.

PIP: As part of an oral rehydration therapy (ORT) field trial, the serum electrolytes of 3 groups with diarrhea were analyzed: 1) persons receiving premixed packet fluids, 2) those receiving locally available salt (labon) and sugar (gur) fluids, and 3) those receiving no ORT intervention and treated according to local custom. Village workers provided instruction and supervision in the preparation of ORT during bimonthly home visits. Questionnaires and serum electrolyte measurements were available from 81 persons in the packet villages and 75 persons from the labon-gur villages. 5 persons treated with packet ORT (6%) and 3 persons treated with labon-gur ORT (4%) had electrolyte abnormalities, but all of them were taking less than appropriate volumes of ORT. In addition, serum electrolytes were evaluated in 489 persons admitted to a medical center after home treatment for diarrhea. No cases who took an appropriate volume of either type of ORT had hyponatremia or hypokalemia. There was no indication that electrolyte abnormalities varied by season or pathogen. Although the close supervision given to study participants and small size limit extrapolation of these results, the study suggests that ORT can be made and safely administered by villagers and that ORT administered at home may be a beneficial effect in preventing hyponatremia and hypokalemia.

Novel diagnostic tests to detect Helicobacter pylori infection: A pediatric perspective.

Because of the widespread problem of Helicobacter pylori infections, there is an increased need for rapid, reliable and inexpensive diagnostic tests. Five recently developed tests that offer potential advantages because they are less invasive or permit easier acquisition of samples than available tests are assessed. The tests assessed are whole blood, saliva and urine assays that measure systemic antibody response to H pylori, stool tests that measure H pylori antigens and string tests that recover H pylori organisms.

Learning by teaching. A resident-taught oral therapy program for acute diarrhea.

An educational program on oral rehydration therapy (ORT) for diarrhea was instituted in our residents' continuity clinics to evaluate the impact that residents teaching parents would have on the knowledge and practices of both groups. Sixty-one residents and 287 parents answered the initial written questionnaire before the teaching program began, and 48 residents and 147 parents completed a second questionnaire at the end of the program. Nineteen residents in two clinics were told to participate frequently in teaching the parents, while 29 residents in three other clinics were given no such instructions. The parents were divided into three groups: 58 received teaching and an instructional handout on the management of diarrhea; 73 received only the instructional handout; and 16 received neither intervention. The 19 "teaching" residents had a significantly improved overall score compared with the "nonteaching" residents (p < .03). No improvement was found in the scores of the 58 parents who received teaching compared with those of the 89 parents who received either a handout or no educational intervention. We conclude that active teaching of ORT may improve the knowledge and practices of residents, but that single teaching encounters, whether or not accompanied by written instructions, may have little impact on parents.

Periodontal emergencies.

Discomfort manifesting in the gingival tissues prompts patients to seek emergency treatment. Several clinical entities should be included in the differential diagnosis. Accurate diagnosis and appropriate therapy is essential to resolving the problem.

Dietary protein sensitivity: is it an important risk factor for persistent diarrhea?

Although the causes of persistent diarrhea are largely unknown, dietary protein sensitivity has been identified as one possible mechanism. Since nutritional therapy appears to be an essential component of treatment for persistent diarrhea, a clearer understanding of the importance of dietary protein allergy is needed to provide optimal dietary recommendations. This paper reviews the current concepts of the pathophysiology, clinical features and criteria for diagnosis of dietary protein sensitivity. Evaluation of the results of several clinical studies indicates that dietary protein sensitivity does occur especially in young infants fed cows' milk but that it is an uncommon event, especially in older infants and children.

Nutritional management of persistent diarrhea: factors predicting clinical outcome.

In a prospective study we randomized 102 male children (age 6-36 months) with persistent diarrhea to receive a traditional rice-lentil (Khitchri) diet and yogurt (K-Y) or a soy formula (alone for seven days and then in combination with K-Y for seven days). Of 73 children satisfying the study criteria, 66 were successfully treated and there were 7 treatment failures. There was poor concordance between parental accounts of severity of diarrhea or vomiting and that observed after admission. Significant risk factors associated with treatment failure included younger age (p < 0.005) and vomiting at presentation (p < 0.02). The greatest number of risk factors associated with delayed recovery (> 10 days) were identified during an initial evaluation period (the first 8 h after admission). These included greater severity of watery diarrhoea (p < 0.01) and increased ORS intake (p < 0.02). Our data suggest that an initial evaluation period, including objective observations, may identify children with persistent diarrhea who are at greatest need of hospitalization.