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Biomedical subjects

S J Holmes

Publications and source records attributed to S J Holmes.

18 recordsLinked to original sources

Exocrine pancreatic function in mediastinal teratomata: an aid to preoperative diagnosis?

The diagnosis of teratoma may be made by demonstration of high amylase content in fluid aspirated from anterior mediastinal lesions. In 2 cases of mediastinal teratoma proteolytic enzyme activity was evident at the time of operation. A diagnosis of mediastinal teratoma was aided in 2 subsequent cases by demonstration of elevated amylase activity in the aspirated fluid before definitive operation.

Adolescent

Familial intussusception.

We report a father and two sons who each suffered from recurrent acute ileocolic intussusception in childhood, suggesting that there may in some cases be a genetic predisposition to the condition. This might have an anatomical basis.

Adult

Differences in the immunogenicity of three Haemophilus influenzae type b conjugate vaccines in infants.

OBJECTIVE: To compare the immunogenicity of three Haemophilus influenzae type b (Hib) conjugate vaccines in infants residing in different geographic areas. DESIGN: A multicenter, randomized immunogenicity trial with sera assayed in one laboratory without knowledge of vaccine brand status. In Minneapolis and Dallas, infants were vaccinated at 2, 4, and 6 months of age; in St. Louis, infants were vaccinated at 2 and 4 months of age. SUBJECTS: A convenience sample of 458 infants recruited largely from private pediatric practices. MEASUREMENTS AND RESULTS: At each of the study sites, the respective trends between the anticapsular antibody responses of the infants assigned to the different conjugate vaccine groups were similar. After one or two doses, Hib polysaccharide conjugated to outer membrane protein complex of Neisseria meningitidis (PRP-OMP) was more immunogenic than Hib polysaccharide-tetanus toxoid conjugate (PRP-T), or Hib oligomers conjugated to the mutant diphtheria toxin CRM197 (HbOC) (p less than 0.001). After two doses, PRP-T was more immunogenic than HbOC (p less than or equal to 0.001). After three doses there was no significant difference in the geometric mean antibody concentrations of the three groups, and 88% to 97% of the infants had greater than 1.0 microgram/ml of antibody. The HbOC vaccine elicited a 10-fold lower antibody response after two doses (0.45 micrograms/ml vs 5.9 micrograms/ml) and a threefold lower antibody response after three doses (6.3 micrograms/ml vs 22.9 micrograms/ml) than observed by us previously with a prelicensure lot of this vaccine (p less than 0.001). Because of these low responses, the infants in St. Louis who received two doses of HbOC were revaccinated with unconjugated PRP at a mean age of 8.9 months. This group was immunologically primed, as evidenced by a 10-fold increase in geometric mean antibody concentration after vaccination at an age when unprimed infants do not normally respond to this vaccine. CONCLUSIONS: In infants in three geographic regions, PRP-OMP elicited earlier acquisition of serum antibody than the other two conjugate vaccines; however, after three doses the antibody concentrations of the three groups were not significantly different. The reason for the markedly lower immunogenicity of HbOC vaccine than reported previously is unknown.

Age Factors

The biology of Haemophilus influenzae type b vaccination failure.

Vaccination with unconjugated polysaccharide vaccine against Haemophilus influenzae type b (Hib) disease at a median age of 25 months was not effective in a group of children who developed Hib disease at a median age of 35 months. This group had normal serum immunoglobulin concentrations but impaired anticapsular antibody responses to Hib infection and to reimmunization with unconjugated polysaccharide. Another group vaccinated with conjugated polysaccharide vaccine at a median age of 18 months developed Hib disease at a median age of 24 months. Of this group, 40% had subnormal immunoglobulin concentrations, particularly IgG2, and showed impaired antibody responses to Hib infection, whereas those with normal immunoglobulin concentrations showed high antibody responses to Hib infection. In both vaccination failure groups, low antibody responders to infection responded to revaccination with Hib conjugate, and most children expressed the idiotype HibId-1 in convalescent or postrevaccination sera. The presence of this idiotype implies that vaccination failure did not result from an inability to use the V kappa II A2 variable region gene, which is used in the anticapsular antibody response of most healthy children.

Antibodies, Bacterial

G2m(23) immunoglobulin allotype and immunity to Haemophilus influenzae type b.

G2m(23), an allotype on IgG2 molecules, is detected in sera of about two of three Caucasians. Adults who are homozygous for G2m(23) have IgG2 antibody responses to types 14 and 18C pneumococcal polysaccharides fourfold higher than those of homozygous-negative subjects. Adults homozygous for G2m(23) also show higher IgG2 antibody responses to vaccination with Haemophilus influenzae type b (Hib) polysaccharide. Furthermore, adults heterozygous for G2m(23) show IgG2 antibody responses intermediate between responses of those homozygous-positive and homozygous-negative. In contrast, the magnitude of the IgG1 antibody responses of adults to Hib polysaccharide was similar irrespective of G2m(23) genotype status. The magnitude of the IgG antibody responses of children vaccinated with Hib polysaccharide is not affected by G2m(23) status, in part because the IgG subclass responses of children to this antigen are restricted to IgG1. Also, children show no consistent associations between G2m(23) allotype status and the risk of acquiring Hib disease or the risk of Hib vaccination failure.

Bacterial Capsules

Immunoglobulin deficiency and idiotype expression in children developing Haemophilus influenzae type b disease after vaccination with conjugate vaccine. The Collaborative Study Group.

OBJECTIVE: --Haemophilus influenzae type b (Hib) conjugate vaccines are effective in preventing Haemophilus disease in most children. The reasons why the vaccination fails in some children are unknown. This study investigated host factors in children who developed the disease despite conjugate vaccination. DESIGN, PATIENTS, OUTCOME MEASURES:--A convenience sample of 23 patients in whom Hib disease developed 14 days or more after conjugate vaccination was investigated for the presence of subnormal serum immunoglobulin concentrations and anticapsular antibody responses to Hib disease. We also investigated expression of the Hib idiotype 1 (Hibld-1), a serological marker of a VKII chain that comprises a major portion of the normal variable region repertoire of the antibody response to Hib polysaccharide. The results were compared with those of 149 patients in whom the unconjugated Hib polysaccharide vaccine failed and of 90 unvaccinated patients who developed the disease. RESULTS: --Compared with children in whom the unconjugated polysaccharide vaccination failed, the relative risk of a subnormal serum concentration of IgM, IgA, IgG, and/or IgG2 in the children in whom the conjugate vaccination failed was 4.9 (95% confidence interval [CI], 1.8 to 14; P less than .003) and of IgG2 was 22 (95% CI, 3.5 to 146; P less than .001). With the exception of the children with subnormal serum immunoglobulin concentrations, most of the children with conjugate vaccination failure showed normal or high anticapsular antibody responses to the disease, whereas the children with polysaccharide vaccination failure showed impaired responses. The Hibld-1 was expressed by the majority of the children in both vaccination failure groups and of the unvaccinated patients. CONCLUSIONS: --In most patients, vaccination failure is not attributable to lack of expression of the variable region gene encoding Hibld-1. However, children in whom conjugate vaccination has failed frequently have subnormal serum immunoglobulin concentrations and should be evaluated for immunodeficiency.

Antibodies, Bacterial

Comparative immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugate vaccines.

There are only minor differences in the immunogenicity of the three Haemophilus b polysaccharide-protein conjugate vaccines licensed in the US when tested in children 17 to 19 months of age. In contrast, there are much greater differences in immunogenicity in 2-month-old infants. At this age, a single dose of PRP-OMPC evokes a strong primary antibody response, whereas repeated doses of HbOC or PRP-D are required to evoke an antibody response. These differences in immunogenicity are noteworthy, but they are not necessarily correlated with differences in the ability of different conjugate vaccines to confer protection against disease. Vaccination with all three of the conjugate vaccines primes infants for the ability to make a booster antibody response to reimmunization with unconjugated PRP vaccine and, possibly, to exposure to the encapsulated bacteria. Although unproven, this priming may be sufficient to confer protection against disease even in the absence of a 'protective' level of serum antibody.

Antibodies, Bacterial

Immunogenicity of four Haemophilus influenzae type b conjugate vaccines in 17- to 19-month-old children.

OBJECTIVE: To compare the immunogenicity of four Haemophilus influenzae type b (Hib) conjugate vaccines in different populations of 17- to 19-month-old children in the United States. DESIGN: Four immunogenicity trials with sera were assayed in one laboratory. Trials 1 and 2 each compared one vaccine in two regions, and trials 3 and 4 were randomized comparisons of multiple vaccines within a region. SUBJECTS: A convenience sample of 313 healthy children recruited from pediatric practices in Minneapolis, Minn., Dallas and Houston, Tex., and Sellersville, Pa. MEASUREMENTS AND RESULTS: Children with prevaccination antibody greater than 0.15 microgram/ml showed higher antibody responses to vaccination than children with less than or equal to 0.15 microgram/ml (p less than 0.001). Among the former, there were no significant differences in antibody response to vaccination with the different conjugates within any of the trials. Among children with less than or equal to 0.15 microgram/ml of antibody before vaccination, there were no significant differences in the geometric mean antibody responses of children in trial 1 vaccinated with polyribosylribitol phosphate-diphtheria toxoid (PRP-D) in Dallas or in Minneapolis, or of children in trial 3 in Dallas randomly assigned to receive Hib oligosaccharide-CRM197 (HbOC) or PRP-D. In contrast, in trial 2, children given PRP-tetanus toxoid (PRP-T) in Pennsylvania had a significantly higher geometric mean antibody response than children given PRP-T in Houston (13.5 vs 3.0 micrograms/ml; p = 0.005). In trial 4 in Minneapolis, the geometric mean antibody response was highest in children randomly assigned to receive PRP-outer membrane protein (OMP) (9.3 micrograms/ml), followed by PRP-D (5.0 micrograms/ml) and HbOC (2.3 micrograms/ml) (PRP-OMP vs HbOC; p = 0.005). In all four trials, IgG1 responses predominated compared with IgG2 responses. CONCLUSIONS: All four conjugate vaccines are immunogenic in children 17 to 19 months of age. However, the magnitude of the anticapsular antibody response varied by vaccine type, the level of antibody in prevaccination sera, and geographic location.

Antibodies, Bacterial

Seizures and other neurologic sequelae of bacterial meningitis in children.

BACKGROUND: Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy. METHODS: We followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter. RESULTS: One month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001). CONCLUSIONS: After bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy.

Acute Disease

The Kasabach-Merritt syndrome: treatment with intermittent pneumatic compression.

A 6 week old infant presented with a giant angiomatous naevus of the leg complicated by chronic disseminated intravascular coagulation. The bleeding and laboratory abnormalities responded to intermittent pneumatic compression of the affected limb. This innocuous treatment should be considered in the Kasabach-Merritt syndrome.

Air

Subdural effusion and its relationship with neurologic sequelae of bacterial meningitis in infancy: a prospective study.

One hundred thirteen infants, aged 1 to 18 months, were screened systematically and serially using transillumination for the presence of subdural effusion during acute bacterial meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae, or Neisseria meningitidis. Effusion developed in 44 (39%) of the patients during the course of treatment. Young age, rapid onset of illness, low peripheral white blood cell count, and high cerebrospinal fluid levels of protein and bacterial antigen were associated with a higher likelihood of developing effusion. Although patients with effusion were more likely to have neurologic abnormalities both at the time of admission and at completion of therapy, and were more likely to have seizures during the course of treatment, there was no greater incidence of seizures, hearing loss, neurologic deficits, or developmental delay on longterm follow-up (median follow-up interval 5.5 years) in patients with effusion. Specific invasive therapy is not indicated in infants with meningitis and subdural effusion who are otherwise improving.

Cerebrospinal Fluid Proteins

Vascular access.

In a retrospective survey of vascular access by means of central venous catheters, those inserted via a tunnel lasted four times longer than those inserted directly into a vein. The latter were four times more likely to become infected. The general health of patients receiving chemotherapy resulted in frequent episodes of sepsis and one-third of all catheters were removed because of presumed infection. There were no complications relating to insertion, which was by direct exposure of a central vein, preferably the right internal jugular. Long-term atrial catheters were not associated with major venous thrombosis or cardiac complications. Safe vascular access is an important contribution to the management of children with malignant disease, notwithstanding the high infection rate. A specially trained nurse, working closely with experienced play leaders and social workers, minimises the technical and psychological problems associated with long-term central venous catheters.

Catheterization, Central Venous

The role of parental disciplinary practices in the development of depression and alcoholism.

Awareness of child abuse has been growing over the past several decades as more cases have come to the attention of medical personnel and school and police authorities. Information-gathering systems have become more effective, and the long-term deleterious effects of abusive treatment have been brought into focus (American Humane Association 1981; Strauss et al. 1980). Cases which come to the attention of the authorities probably represent only the most blatant and severe instances of abuse. However, since Kempke and colleagues (1962) originally described the "battered child syndrome," descriptions of child abuse have been broadened to include maltreatment other than physical abuse resulting in injury (Martinez-Roig et al. 1983; Smith and Hanson 1974; Wolff 1981). Indeed, Strauss and colleagues contend that even mild forms of physical punishment should be considered abusive because they would be illegal if directed toward adults or strangers. The current paper examines retrospectively the relationship between disciplinary practices experienced in childhood, both mild and severe, and the experience of major depressive episodes and alcoholism in adulthood in a general population sample, in whom disorder tends to be untreated and mild.

Adolescent

The influence of childhood disciplinary experience on the development of alcoholism and depression.

In this case-control study, respondents from the general population with a lifetime diagnosis of major depressive disorder, alcohol abuse and/or dependence, or the absence of any psychiatric disorder ascertained by the St. Louis Epidemiological Catchment Area Study were reinterviewed about their early home environments during the period when they were 6 to 13 years of age. Two discipline scales were developed through factor analysis, and logistic regression was used to build a model using all the predictors. Unfair, inconsistent and harsh discipline by parents predicted both alcohol and depressive disorders independently of the influence of parental psychiatric history, the respondent's sex, and childhood behavior problems.

Adolescent

Melittin lysis of red cells.

This paper describes experiments designed to explore interactions between human red blood cell membranes and melittin, the main component of bee venom. We found that melittin binds to human red cell membranes suspended in isotonic NaCl at room temperature, with an apparent dissociation constant of 3 X 10(-8) M and maximum binding capacity of 1.8 X 10(7) molecules/cell. When about 1% of the melittin binding sites are occupied, cell lysis can be observed, and progressive, further increases in the fraction of the total sites occupied lead to progressively greater lysis in a graded manner. 50% lysis occurs when there are about 2 X 10(6) molecules bound to the cell membrane. For any particular extent of melittin binding, lysis proceeds rapidly during the first few minutes but then slows and stops so that no further lysis occurs after one hour of exposure of cells to melittin. The graded lysis of erythrocytes by melittin is due to complete lysis of some of the cells, since both the density and the hemoglobin content of surviving, intact cells in a suspension that has undergone graded melittin lysis are similar to the values observed in the same cells prior to the addition of melittin. The cells surviving graded melittin lysis have an increased Na and reduced K, proportional to the extent of occupation of the melittin binding sites. Like lysis, Na accumulation and K loss proceed rapidly during the first few minutes of exposure to melittin but then stops so that Na, K and hemoglobin content of the cells remain constant after the first hour. These kinetic characteristics of both lysis and cation movements suggest that melittin modifies the permeability of the red cell membrane only for the first few minutes after the start of the interaction. Direct observation of cells by Nomarsky optics revealed that they crenate, become swollen and lyse within 10 to 30 sec after these changes in morphology are first seen. Taken together, these results are consistent with the idea that melittin produces lysis of human red cells at room temperature by a colloid osmotic mechanism.

Anions