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Biomedical subjects

C R Howard

Publications and source records attributed to C R Howard.

At least 37 records · Page 2Linked to original sources
PubMed1999

Drugs and breastfeeding.

Breastfeeding provides important benefits to mother and infant and should be strongly encouraged as the optimal infant feeding choice for most infants. In assessing the impact of maternal medication on breastfeeding, the clinician must always weigh the many benefits of breastfeeding for the mother and infant against the risk of exposing the infant to the drug as it appears in breast milk. With regard to the vast majority of medications, continued breastfeeding is advantageous to both mother and infant.

Breast Feeding↗
PubMed1999

Given the benefits of breastfeeding, are there any contraindications?

There are many benefits to the infant to be breastfed and to the mother to breastfeed. There are, however, a few conditions where the tremendous benefit may be outweighed by maternal infection, disease, drugs, or contaminants as these are rare. HIV is the only infection that is an absolute contraindication in developed countries. Galactosemia is the only infant disease and there are a few medications that are contraindicated.

Breast Feeding↗
PubMed1999

Physiologic stability of newborns during cup- and bottle-feeding.

BACKGROUND: To prevent breastfeeding problems, cup-feeding has been recommended as a method of providing medically necessary supplemental feedings to breastfed infants. OBJECTIVES: To compare amounts ingested, administration time, and infant physiologic stability during cup-, bottle-, and breastfeeding. DESIGN/METHODS: A total of 98 term, healthy newborns were randomized to either cup-feeding (n = 51) or bottle-feeding (n = 47). The heart (HR), respiratory (RR), and oxygen (O(2)) saturation rates were monitored on these infants and 25 breastfed newborns during 1 feeding. Differences in amounts ingested and administration times were evaluated with t tests and physiologic data with repeat measures analysis of variance. RESULTS: There were no significant differences in administration time, amounts ingested or overall HR, RR, and (O(2)) saturation rates, between cup and bottle groups. Breastfed infants had longer administration times and lower overall HR, RR, and higher O(2) saturation as compared with cup- and bottle-fed infants. CONCLUSIONS: Administration times, amounts ingested, and infant physiologic stability do not differ with cup- and bottle-feeding. Breastfeeding takes longer than cup- or bottle-feeding, but infants experience less physiologic variability. These data support cup-feeding as an alternative to bottle-feeding for supplying supplements to breastfed infants.

Bottle Feeding↗
PubMed1998

Determinants of rotavirus host range restriction--a heterologous bovine NSP1 gene does not affect replication kinetics in the pig.

The genetic basis of rotavirus host range restriction (host species specificity) is unknown but the NSP1 (fifth) gene has been implicated in some studies. We studied the replication kinetics in vivo of a NSP1 gene monoreassortant, E11, to assess the influence of a heterologous NSP1 gene on the ability to replicate in pigs. The monoreassortant possessed 10 genes from the porcine parent rotavirus SW20/21, which replicated productively in pigs, and the NSP1 gene from the bovine rotavirus UK which produced an abortive infection in pigs. Groups of up to four pigs were inoculated orally with 10(5) to 10(6) TCID50 of the monoreassortant, the porcine parent rotavirus, or the bovine parent rotavirus or were sham inoculated. The monoreassortant replicated productively in pigs with replication kinetics almost identical to the porcine parent rotavirus. During a 9-day observation period after inoculation, the number of days with virus in the faeces, the onset and duration of virus excretion, and peak titres in faeces were similar for the monoreassortant and the parent porcine rotavirus. The genetic composition of the viruses excreted in the faeces was confirmed as that of the inocula by PAGE. Thus possession of a heterologous NSP1 gene from a bovine rotavirus which failed to replicate in pigs did not produce an abortive infection or affect the replication kinetics in vivo. The genetic basis of host range restriction between porcine and bovine rotaviruses remains to be established.

Animals↗
PubMed1998

Breast-feeding and drug exposure.

Breast-feeding provides important benefits to mother and infant and should be strongly encouraged as the optimal feeding choice for most infants. In the mother with an ongoing illicit drug abuse problem, the risks posed to the infant are substantial and outweigh the benefits of breast-feeding in most cases. Moderate use of alcohol, cigarettes, or caffeine is compatible with breast-feeding.

Breast Feeding↗
PubMed1998

Neonatal circumcision and pain relief: current training practices.

OBJECTIVE: We conducted a national survey of pediatric, family practice, and obstetrics and gynecology residency program directors to determine the curriculum content and predominant practices in US training programs with regard to neonatal circumcision and anesthesia/analgesia for the procedure. METHODS: Residency directors of accredited programs were surveyed in two mailings of a forced response and short answer survey (response rate: 680/914, 74%; pediatrics 83%; family practice 72%; obstetrics 71%). RESULTS: Pediatric residents were less likely than family practice [odds ratio (OR), 0.04; 95% confidence interval (CI), 0.02-0.08] or obstetrical (OR, 0.14; 95% CI, 0.08-0.23) residents to be taught circumcision. Training and local custom were rated as important determinants of medical responsibility for neonatal circumcision. Pediatric residents training in programs in which community pediatricians perform circumcisions were more likely to learn circumcision (OR, 39.0; 95% CI, 14.3-110.6) as were obstetric residents (OR, 79.0; 95% CI, 22.4-306.4) training in programs in which community obstetricians perform circumcision. In programs that teach circumcision, pediatric (84%; OR, 3.4; 95% CI, 1.7-7.1) and family practice (80%; OR, 2.7; 95% CI, 1.7-4.2) programs were more likely than obstetric programs (60%) to teach analgesia/anesthesia techniques to relieve procedural pain. Overall, 26% of programs that taught circumcision failed to provide instruction in anesthesia/analgesia for the procedure. Significant regional variations in training in circumcision and analgesia/anesthesia techniques were noted within and across medical specialties. CONCLUSIONS: Residency training standards are not consistent for pediatric, family practice, and obstetrical residents with regard to neonatal circumcision or instruction in analgesia/anesthesia for the procedure. Training with regard to pain relief is clearly inadequate for what remains a common surgical procedure in the United States. Given the overwhelming evidence that neonatal circumcision is painful and the existence of safe and effective anesthesia/analgesia methods, residency training in neonatal circumcision should include instruction in pain relief techniques.

Analgesia↗
PubMed1998

Nucleic acid vaccines against hepatitis viruses.

Direct DNA intramuscular or intradermal injection of plasmids containing viral genes under the control of viral promoters is an efficient means of stimulating both class I and class II-mediated antiviral responses. Viral hepatitis B and C are suitable candidates for this approach, particularly as therapeutic immunogens for chronically infected individuals. Several groups have shown that the S gene of HBV is expressed in murine muscle and stimulates a high titre and long-lasting anti-HBs response. Uniquely, CD8+ CTL responses are also induced to HBsAg. No vaccine exists for HCV. Therefore the structural genes (C + E1 + E2) have been cloned as a 2,831 bp fragment from a genotype la isolate into the vector pcDNA3. The resulting plasmid DNA was injected directly into the quadriceps muscle of three-week-old BALB/c mice. Intracellular-expressed E1 and E2 proteins thus represent the complete spectrum of native structural epitopes, including those dependent on glycosylation and protein folding. Mouse antisera were tested for reactivity against conserved sequences using overlapping 7-mer peptides. Two conserved, overlapping epitopes were identified in E2 spanning residues 581-591 and 590-603. This domain represents one of seven major E2 antigenic domains recognized by HCV human antibodies, one of three with antigenic homologies to related flavivirus proteins. Thus antigen is presented with high efficiency following DNA injection and offers the potential of high rates of seroconversion and virus clearance in those predisposed to virus-induced chronic liver disease.

Animals↗
PubMed1997

Definition of the primary structure of hepatitis B virus (HBV) pre-S hepatocyte binding domain using random peptide libraries.

The pre-S-specific monoclonal antibody MA 18/7 has been shown to inhibit the binding of HBV to HepG2 cells and liver membranes. This antibody can thus be used to identify the critical residues of the pre-S region involved in the hepatocyte-binding domain. Using overlapping 7-mer peptides representing the pre-S region of HBV, the epitope recognized by MA 18/7 was shown to contain sequences from both the pre-S1 and pre-S2 regions, thus indicating that the hepatocyte-binding domain is conformationally dependent. To further characterize the primary structure of the hepatocyte-binding domain on the pre-S protein, a phage-displayed 15-mer peptide library and a 8-mer solid phase peptide library were used to analyze the fine specificity of the monoclonal antibody MA 18/7. Several mimotopes were identified with the phage-displayed peptide library, the majority of which possess a central motif with at least three identical residues present within the native pre-S1 sequence. No significant consensus sequences were found when these mimotopes were compared to the pre-S2 sequence. Mimotopes identified using the solid-phase peptide library also contained a similar motif. All phage mimotopes and a single mimotope from the solid-phase peptide library competed with recombinant HBsAg particles containing the pre-S1 region for binding to MA 18/7. Mouse antisera raised against four mimotopes from the phage display library reacted with HBsAg particles containing pre-S sequences. The data show that the structure of the pre-S molecule around the conserved DPAF motif in the pre-S region may have a functional role in binding HBV to cellular receptors, and that the central motif identified in mimotopes of this region may offer a novel strategy target for the improvement of existing hepatitis B vaccines which, at present, are mostly devoid of pre-S specificities.

Amino Acid Sequence↗
PubMed1997

Attitudes, practices, and recommendations by obstetricians about infant feeding.

BACKGROUND: Little information is available about the degree to which obstetricians promote breastfeeding through patient care practices and educational activities. The purpose of this study was to determine the attitudes, practices, and recommendations of obstetricians regarding infant feeding selection. METHODS: A written survey was mailed to 148 obstetrician/gynecologists in Monroe County, New York (78% response rate, n = 116). RESULTS: Of the 104 physicians in active obstetric practice, 86 percent conducted prenatal discussions about infant feeding with patients, 80 percent recommended breastfeeding, and 68 percent were commonly contacted postpartum by patients to address breastfeeding questions. Overall, 57 percent routinely incorporated these breastfeeding supportive practices into their prenatal and postpartum patient care. Attitudes about obstetric responsibility for infant feeding counselings and about the importance of counseling independently predicted the provision of these services. Infant feeding information was given to patients by 98 percent of obstetricians; 75 percent used written and 39 percent used videotaped materials. Formula company-produced infant feeding literature (41%), pregnancy literature (57%), and free formula offers (61%) were commonly used. Of those surveyed, 58 percent lacked training and 22 percent reported inadequate training in infant nutrition. CONCLUSIONS: Although most obstetricians in Monroe County provide infant feeding education and recommend breastfeeding, most report that their training about infant nutrition is inadequate, and they distribute infant formula company materials and offers to patients. Such discrepancies in patient care are inconsistent with promoting breastfeeding as optimal infant nutrition.

Breast Feeding↗
PubMed1995

The ligase chain reaction distinguishes hepatitis B virus S-gene variants.

A novel method for the identification of hepatitis B virus (HBV) variants was developed. The ligase chain reaction (LCR) distinguished the sequences of two isolates from the Gambia showing a change at nucleotide 421 within the region coding for the surface protein a antigenic determinant. One sequence was derived from a child previously immunized with HBV vaccine, while the other, reported here for the first time, was from a chronic carrier. Nucleotide variations within the target sequence at, or up to 3 bases from the point of ligation inhibited the reaction. The LCR recognised variations in as little as 0.9 fmol DNA and will permit the rapid detection of HBV variants in molecular epidemiological studies.

Base Sequence↗
PubMed1995

The structure of hepatitis B envelope and molecular variants of hepatitis B virus.

Accumulated evidence in recent years has shown that the variation of hepatitis B virus (HBV) genomes may have profound implications for our understanding of hepatitis B pathogenesis and prevention. Attention has focused on areas of the outer envelope coded by the S gene which are involved in the induction of a protective neutralising antibody response, and mutations which directly affect the production of C gene products, one of which is considered as a target for immune T cells involved in virus clearance. This review highlights recent experimental data which emphasizes the role of such mutations in the establishment and maintenance of chronic HBV infections and focuses attention on the significance of HBV variants with respect to the expanding use of HBV vaccines for mass immunization.

Amino Acid Sequence↗
PubMed1995

Protection against morbillivirus-induced encephalitis by immunization with a rationally designed synthetic peptide vaccine containing B- and T-cell epitopes from the fusion protein of measles virus.

Synthetic peptides representing T- and B-cell epitopes from the fusion (F) protein of measles virus (MV) were tested for their ability to induce a protective immune response against intracerebral challenge with neuroadapted strains of MV and canine distemper virus (CDV) in mice. Of the panel of peptides tested, only a chimeric peptide consisting of two copies of a promiscuous T-cell epitope (representing residues 288 to 302 of MV F protein) synthesized at the amino terminus of a B-cell epitope (representing residues 404 to 414 of MV F protein) was able to induce a protective response against challenge with MV and CDV in inbred mice. The protective response induced by this peptide (TTB) was associated with a significant reduction in mortality, histological absence of acute encephalitis, and greatly reduced titers of virus in the brains of TTB-immune mice following challenge compared with the results for nonimmunized controls. A chimeric peptide comprising one copy of the T-cell epitope and one copy of the B-cell epitope (TB) did not induce a protective response. A comparison of the antibody responses induced by the two chimeras suggested that differences in protective efficacy following immunization may be a result of the higher affinity of the antibody induced by the TTB peptide than that of the antibody induced by the TB peptide. In addition, differences in the immunoglobulin G subclass of the antipeptide antibody responses were observed, and these may play a role in the differences in protection observed. These results indicate that appropriately designed synthetic peptides have potential as vaccines for the induction of cross-reactive protection against morbilliviruses.

Amino Acid Sequence↗
PubMed1995

Hepatitis B surface antigen variation and protective immunity.

Hepatitis B surface antigen (HBsAg) particles consist predominantly of a glycoprotein of 226 amino acids which bears the B-cell epitopes important for the induction of protective antibody responses in humans. It has been clearly shown that the region between residues 120 and 150 of the S protein represents the a determinants common to all hepatitis B virus (HBV) isolates and is exposed on the surface of the HBV particle. Anti-a antibodies protect adults against the majority of infections irrespective of the subtype of the wild-type virus. Occasional examples of infection positive for anti-HBs antibodies have been associated with the emergence of HBV variants. In particular, asymptomatic infections have been described in vaccinated children, an observation which is associated with an amino acid change in a domain critical for anti-HBs binding. Variation in amino acid sequence is also found within the preS amino terminal extensions of the S protein, although these do not correlate with subtypic variations among the S-antigenic domains. There is no direct evidence that preS determinants per se may stimulate a protective immune response in humans, although the hepatocyte attachment domain is located in the preS1 region which is conserved between HBV isolates. The inclusion of preS specificities augments anti-HBs responses in an experimental animal; however, at the present time it is unclear as to how this may best be exploited in improving hepatitis B vaccines for human use. Variability in HBV envelope proteins has implications for the design of vaccination programmes and the diagnosis of HBV infections; however, the low frequency of HBV variants emerging in the face of increasing levels of herd immunity to hepatitis B at the present time means that the extension of immunization programmes using existing vaccines remains a priority.

Amino Acid Sequence↗
PubMed1994

A novel hepatitis B virus variant in the sera of immunized children.

A novel hepatitis B virus (HBV) variant was detected in the sera of two children in The Gambia, West Africa. The children had been immunized with plasma-derived vaccine and had developed antibody titres of 1448 international units x 10(-3) (mIU)/ml and 133 mIU/ml respectively against the hepatitis B surface antigen (HBsAg). Despite the protective levels of antibodies, HBV DNA was subsequently detected in both children. The complete surface (S) protein gene sequence demonstrated that this HBV isolate was closely related to the ayw4 subtype. However, five nucleotide changes were identified and two of these were unique to the Gambian isolate. One of these changes was within the region of the S gene coding for the immunodominant a determinant of the S protein. A unique nucleotide change from adenosine to guanosine at nucleotide 421 was found, resulting in an amino acid substitution at residue 141 from lysine to glutamic acid. Previous studies have shown that amino acids 141 to 146 are critical for binding to the protective anti-HBsAg antibodies. The presence of a variant HBV in these children suggests the emergence of a novel strain of HBV which can evade immune recognition. This has potential implications for HBV diagnosis and prophylaxis.

Amino Acid Sequence↗
PubMed1994

Infant formula distribution and advertising in pregnancy: a hospital survey.

A survey was conducted at a 526-bed community hospital in Rochester, New York, to determine the prevalence of formula advertising and distribution during pregnancy to 136 consecutive intrapartum patients. Women answered a questionnaire about their choice of infant feeding methods and prenatal exposure to formula advertising. Of those who received printed information on infant feeding, 78 percent reported that it was published by a formula company, and 65 percent recalled receiving offers for free formula during their pregnancy. The likelihood of having received such offers was the same in women who planned to breastfeed as in those who planned to formula feed. Thirty-eight percent of women obtained formula through a free offer before their infant's birth. Women who were privately cared for were more likely to have received offers for free formula (p < 0.001) than were women cared for in hospital-affiliated clinics. Ninety percent of women who received free formula prenatally reported their prenatal caregiver as a source of samples. Of samples that women obtained prenatally, 93 percent were from companies that advertise only indirectly through hospitals and physicians, whereas 7 percent were from companies that advertise directly to patients. The prevalence of formula company advertising during the prenatal care of women who deliver in this hospital is high. The continued participation of prenatal caregivers in promotion efforts of formula companies provides a negative or mixed message about the importance of breastfeeding and may be a barrier to its success.

Adult↗
PubMed1994

Acetaminophen analgesia in neonatal circumcision: the effect on pain.

OBJECTIVE: Recognizing the concerns about the use of local anesthesia in neonatal circumcision, a painful procedure usually performed without analgesia or anesthesia, we undertook a study of acetaminophen for pain management of this procedure. DESIGN: A prospective, randomized, double-blind, placebo-controlled, clinical trial of acetaminophen analgesia in 44 healthy full-term neonates undergoing circumcision was conducted. Beginning 2 hours before Gomco circumcision, neonates received either acetaminophen (15 mg/kg per dose, 0.15 mL/kg per dose) or placebo (0.15 mL/kg per dose) every 6 hours for 24 hours. Neonates were monitored intraoperatively for changes in heart rate, respiratory rate, and crying time. Postoperative pain was assessed at 30, 60, 90, 120, 360 minutes, and 24 hours using a standardized postoperative comfort scoring system. Feeding behavior was also assessed before and after circumcision by nursing observation. RESULTS: Neonates in both groups showed significant increases in heart rate, respiratory rate, and crying during circumcision with no clinically significant differences observed between the groups. Postoperative comfort scores showed no significant differences between the groups until the 360-minute postoperative assessment, at which time the acetaminophen group had significantly improved scores (P < .05). Feeding behavior deteriorated in breast- and bottle-fed neonates in both groups, and acetaminophen did not seem to influence this deterioration. CONCLUSIONS: This study confirms that circumcision of the newborn causes severe and persistent pain. Acetaminophen was not found to ameliorate either the intraoperative or the immediate postoperative pain of circumcision, although it seems that it may provide some benefit after the immediate postoperative period.

Acetaminophen↗