Milo D. Hilty

Vidrabine therapy of varicella in immunosuppressed patients

In order to assess further the clinical usefulness of vidarabine therapy of chicken pox, a double-blind, placebo-controlled trial was performed in immunocompromised patients. Thirty-four patients entered the trial; 19 received vidarabine and 15 the placebo. All patients had disease less than or equal to 72 hours in duration and 23 had lymphoproliferative malignancies. Both patient populations were balanced for underlying disease, preceding chemotherapy, and duration of chicken pox. No patient received zoster immune globulin. Drug therapy accelerated cessation of new vesicle formation (P = 0.015) and decreased median daily lesion counts (P = 0.06 on days 2 and 3). Fever (greater than or equal to 37.8 degrees C orally) resolved more rapidly in the drug-treated group. By day five, 70% of drug-treated subjects were afebrile in contrast to 35% of placebo recipients (P = 0.066). One drug recipient developed mild pneumonitis during the study which resolved with therapy, whereas eight placebo recipients developed varicella-related complications which led to death in two patients (P less than 0.01). These results were achieved with minimal evidence of laboratory or clinical toxicity related to drug administration. The findings indicate that vidarabine has a good therapeutic index (efficacy/toxicity) for treatment of chicken pox in immunocompromised patients when given early in the course of the infection.

Glycerol: a review of its pharmacology, pharmacokinetics, adverse reactions, and clinical use.

Glycerol is a potent osmotic dehydrating agent with additional effects on brain metabolism. In doses of 0.25‐2.0 g/kg glycerol decreases intracranial pressure in numerous disease states, including Reyes syndrome, stroke, encephalitis, meningitis, pseudotumor cerebri, central nervous system tumor, and space occupying lesions. It is also effective in lowering intraocular pressure in glaucoma and shrinking the brain during neurosurgical procedures.

Human Milk Oligosaccharides

Human milk is a unique reservoir of oligosaccharides. The presence of many of these oligosaccharides is determined genetically and is related to the Lewis blood group and secretor antigen status of each donor. A method to quantitate neutral human milk oligosaccharides was developed. Sample preparation was based on a single centrifugation-filtration step that yields oligosaccharide extracts. These extracts first were fractionated to remove a significant portion of their lactose content and were analyzed using high-pH anion-exchange chromatography. Oligosaccharide profiles from 386 milk samples obtained in this fashion generated quantitative information on lactose, the neutral cores lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNneoT), and the key fucosylated oligosaccharides. Additionally, the profiles provided genetic footprints of the Lewis and secretor status of the donors. Furthermore, unusual profiles that could not have been predicted from known genotypes were found. For this reason, milk glycoproteins were studied using carbohydrate-binding

Identification of long chain dicarboxylic acids in the serum of two patients with Reye's syndrome

Sera from two patients with Reyes Syndrome were analysed by computerized capillary gas chromatography--mass spectrometry profiling techniques. The most striking abnormalities were the accumulation of long chain dicarboxylic acids. Four saturated dicarboxylic acids (dodecanedioic, tetradecanedioic, hexadecanedioic, and octadecanedioic), and six unsaturated long chain dicarboxylic acids (dodecenedioic, tetradecenedioic, tetradecadienedioic, hexadecenedioic, octadecadienedioic, and octadecenedioic) were identified. The C16 and C13 dicarboxylic acids have never been reported for Reyes Syndrome or any other dicarboxylic acidemias. The data might reflect marked increase of extramitochondrial omega-oxidation of long chain fatty acids or impaired metabolism of omega-dicarboxylic acids formed in Reyes patients.

Interactions among chloramphenicol, phenytoin, and phenobarbital in a pediatric patient

O N E of the important factors determining serum concentration of chloramphenicol is the rate of hepatic metabolism to inactive metabolites by the microsomal enzyme glucuronyl transferase. 1 Since both phenytoin and phenobarbital can induce hepatic microsomal enzymes, their use may increase the rate of chloramphenicol metabolism. 2 Because these drugs may be used with chloramphenicol in treating pediatric infections of the central nervous system, it is important to know how these drugs interact. We report a child with hydrocephalus who was treated with chloramphenicol for a ventriculojugular infection. Concomitant with the sequential addition of phenytoin and phenobarbital, there was a significantly lowered chloramphenicol serum concentration and an increased total body clearance of chloramphenicol relative to values reported in pediatric patients.

Effect of intravenous flow rate and injection site on in vitro delivery of chloramphenicol succinate and in vivo kinetics

The delivery rates of chloramphenicol succinate from a standard pediatric intravenous infusion set were studied in vitro at varying flow rates and injection sites of the infusion set. The pharmacokinetic properties of CAPS and chloramphenicol were then studied in 15 children given intravenous injections of CAPS via the infusion set at the flashball and Buretrol sites in a crossover fashion on successive days. In vitro, the actual times required for 95% delivery of CAPS from the infusion set were two- to fourfold longer than the predicted infusion times at flow rates of 5, 15, and 29 ml/min and at all three available injection sites. In vivo, flashball injections vs Buretrol injections resulted in significantly higher mean peak serum concentrations of CAPS and CAP, with peaks occurring significantly sooner after the beginning of the intravenous infusion. These results suggest a need for considering characteristics of CAPS infusion when monitoring and interpreting serum concentration values.

ECHO virus type 3 infections in children: Clinical and laboratory studies+

ECHO virus type 3 was recovered from 29 children during the summer of 1970. Twenty-four children had aseptic meningitis which was similar to the same illness caused by other enteroviruses. Two children had undifferentiated febrile illnesses associated with a short generalized convulsion. ECHO virus type 3 was also recovered from three children with illnesses not previously associated with this virus: concomitant aseptic meningitis, pericarditis, and myocarditis, a severe generalized neonatal infection, and a fatal illness fulfilling the criteria for Reyes syndrome.

Antibody Response to Herpes Simplex Virus Type 1 Polypeptides and Glycoproteins in Primary and Recurrent Infection

Summary: Sequential sera from a patient with primary Herpes Simplex Virus type I (HSV-1) encephalitis and a patient with HSV-1 recurrent oral lesions were collected. Sera were analyzed quantitatively by radioimmunoassay and qualitatively by electrophoresis and autoradiography of immune precipitates to determine the sequence of antibody production to specific radiolabeled HSV-1 polypeptide and glycoprotein antigens. The major antibody response in both primary and recurrent sera was against HSV-1 envelope antigens and the major capsid polypeptide. Sequential sera showed a significant correlation between neutralizing antibody titers and quantitative antibody to HSV-1 glycoproteins. Qualitative electrophoretic analysis of primary infection sera showed sequential appearance of antibodies to increasing numbers of HSV-1 polypeptides by the fourteenth day of infection. A corresponding qualitative antibody response to glycoproteins was not seen. Sequential sera obtained before, during, or after a recurrent lip lesion in another patient showed no significant quantitative or qualitative changes in antibodies to either HSV-1 glycoproteins or polypeptides.Speculation: A qualitative variation in antibody response to Herpes Simplex Virus polypeptides develops following a primary infection. The lack of qualitative variation in antibody response to recurrent infection provides a means of distinguishing primary from recurrent Herpes Simplex Virus infections.

TOLERANCE AND FECAL COLONIZATION WITH Lactobacillus reuteri IN CHILDREN FED A BEVERAGE WITH A MIXTURE OF Lactobacillus spp . 1090

Introduction. Intake of probiotics has been shown to be effective in the treatment of diarrhea. L. reuteri, a common bacteria in the gastrointestinal tract of humans, produces an antimicrobial substance called reuterin that may contribute to the prevention of colonization by enteropathogens. Aim. To establish the tolerance and dose response of a probiotic mixture containing Lactobacillus reuteri. Methods. A blinded, controlled community-based pilot clinical study was conducted with 72 children, ages 12 to 36 months. Children were randomized into four groups to receive either the control study feeding with no probiotic or a low (106 CFU), medium (108 CFU), or high dose (1010 CFU) of a probiotic blend containing L. reuteri, L. acidophilus and B. infantis added to a liquid nutritional beverage (PediaSure®). The study consisted of an entry evaluation, a three-week study feeding and a post-feeding evaluation. Intake of beverage and tolerance were monitored daily. Weekly evaluation of stool characteristics, and total Lactobacillus and L. reuteri fecal counts were done. Results. Intake, incidence of vomiting, abdominal discomfort, gas and stool characteristics were not statistically different among groups. None of the subjects had L. reuteri detected in feces at entry. Table Conclusions. Intake of a probiotic mixture containing L. reuteri at all doses was well tolerated. Lactobacillus colonization is transient, and level of fecal colonization of subjects is directly related to dose. Supported by Ross Products Division, Abbott Laboratories.

Passive Immune Protection from Diarrhea Caused by Rotavirus or E. Coli: An Animal Model to Demonstrate and Quantitate Efficacy

Several studies have described the use of orally administered passive antibodies from heterologous species origin to control enteric disease caused by bacteria1–4, viruses5–13, and protozoa14. Both the therapeutic and prophylactic properties of passive antibodies have been evaluated. The therapeutic efficacy has been confined to suppressed pathogen shedding with limited effects reported on the acute clinical disease2,12. The reported lack of therapeutic effect on the course of the Escherichia coli and rotavirus diarrhea episodes may be attributed to the self-limiting nature of these diarrheas in healthy patients. Passive antibody is effective in treating Cryptosporidium infection14 and may also be effective in treating chronic diarrhea in immunocompromised patients.