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Anticipatory guidance is acknowledged as an important aspect of pediatric practice, and research shows that parents expect and value the information and advice they receive from their pediatric health care providers. This study surveyed 373 parents (88% mothers) of infants in waiting rooms of diverse pediatric practices in Memphis,Tennessee, about their recall of anticipatory guidance received, unmet needs for anticipatory guidance, preferences for sources of information, and activities to promote healthy development. Most parents recalled specific guidance received (diet, communication, and discipline being the most common), and unmet needs (discipline and development being among the most common). Disadvantaged parents reported the fewest unmet needs. Most parents readily named specific activities they engage in to promote development, including reading, educational toys, and nurturing.

Objectives: To determine the relative role that academic hospitals (AHs) play in providing neonatal care for low-birth-weight infants within a single state and to determine if there are variations in inpatient costs for neonatal services among AHs., Design: Retrospective analysis of hospital costs for low-birth-weight infants., Setting: Cases were identified using 2003-2005 data from the Tennessee Hospital Discharge Data System. A specific focus was discharge data from the 5 AHs that support obstetrical residencies and have a neonatal intensive care unit., Participants: Cases included all discharged infants with a birth weight of <2500 grams., Results: The 5 AHs discharged 18% of the total normal-birth-weight infants and 30% of the low-birth-weight infants for the entire state. AHs had higher costs associated with these infants than did other hospitals, with a single exception The difference in costs at this hospital was consistent with the finding of lower utilization rates of hospital services, a shorter average length of stay, and lower costs for infants insured by the state Medicaid program., Conclusion: Academic obstetrical hospitals discharged a disproportionately high percentage of low-birth-weight infants compared with other Tennessee hospitals. The lower costs observed in the Shelby County hospital indicates that other hospitals could potentially lower their costs for the care of low-birth-weight infants.

Background: Potentially avoidable pediatric hospitalizations (PAPH) can now be identified using an analytical tool developed by the federal Agency for Healthcare Research and Quality (AHRQ). We apply this new tool to Tennessee inpatient discharge records for 2005 to determine the prevalence of PAPH and analyze the variation patterns of PAPH across racial, gender, and insurance status lines., Methods: Retrospective analysis of administrative data based on the UB-92 claims forms submitted by all short-term acute-care hospitals in Tennessee for 2005., Results: Tennessee had higher prevalence rates of PAPH than seen in the nation overall for four of the five Ambulatory-Care Sensitive Conditions (ACSC), identified by AHRQ as those hospitalizations which can potentially be avoided. Variations of the rates of PAPH across racial, gender and insurance subgroups were found to mirror those found for pediatric hospitalizations for all conditions. However, when PAPH were grouped according to whether they were chronic or acute in terms of their primary admitting condition, Black children were over-represented in PAPH for chronic conditions such as asthma and diabetes. In addition, Black children's average costs are significantly higher than those for White children irrespective of whether the admitting condition was chronic or acute., Conclusions: The high rates of PAPH reported in this study imply a weakness in Tennessee's primary care for children. These high rates also point out opportunities for reducing expensive hospitalizations associated with poorly controlled diabetes, asthma exacerbations, and dehydration due to gastroenteritis.

Because passive smoke exposure has not been previously linked to diarrhea diseases in children, it was hypothesized that very young children exposed to environmental tobacco smoke (ETS) exposure at home would also be more likely to develop infectious gastroenteritis (GE) than their unexposed counterparts. During 1-year period, 260 children 36 months and younger were prospectively followed up in a private pediatric practice in a southern community in the United States. Multiple logistic regression analysis showed that ETS was strongly predictive of acute GE in the univariate analysis (P = .003). Even after controlling for the various confounders, ETS exposure was still significantly associated with acute GE (relative risk = 2.55; 95% CI = 1.26-5.18). It is speculated that, similar to acute respiratory infections, the same mechanisms may explain why ETS may also be associated with acute infectious GE.

This study was conducted to determine if the Agency for Healthcare Research and Quality's newly established pediatric quality monitors, which measure potentially avoidable hospitalizations, are useful in detecting disparities in health care delivery. Data for all hospital discharges in Tennessee in 2002 were evaluated for the 5 pediatric discharge monitors identified by the Agency for Healthcare Research and Quality. These diagnoses were asthma, short-term complications of diabetes, gastroenteritis, urinary tract infection, and perforated appendix. Black children were more likely to be discharged with the diagnoses of asthma and short-term diabetes complications. Publicly insured children were more likely than commercially insured children to be discharged with each of the 5 potentially avoidable hospitalizations. The results show that black children and children insured by public programs have significantly different discharge rates for pediatric potentially avoidable hospitalizations than do white children or commercially insured children. This could be the result of less access to high-quality ambulatory care.

Multiple early childhood intervention programs have been introduced to provide at-risk children with a better start in life. This is due to the recognition that early childhood experiences, both positive and negative, can affect the physical, mental, behavioral, and economic well-being of the child. A few of these programs have evaluated long-term outcomes and have demonstrated that the effects of interventions may still be apparent years after the intervention. Pediatricians need to become more aware of the information available about the impact of early childhood events and become more active in promoting proven best intervention practices at the local, state, and national level.

Background and Objectives: Use of health services in rural communities has not been well studied. We explored how black and white children used health services in a rural Mississippi community., Methods: Data were prospectively collected for 396 children attending a private practice to determine if race was associated with the use of health services in this community., Results: White children made more sick contacts than black children (P < 0.001). Black children (36%) were more likely to be treated in the emergency room than white children (24%; P = 0.013). There was no black-white difference in the hospitalization rates, although white children were more likely to undergo ear-nose-throat (ENT) surgery for pressure equalizing tube (PET) placement, and/or tonsillectomy and adenoidectomy (T and A; P < 0.001). Even after controlling for various confounders, the frequency of all physician sick contacts was twice as high for white children than for black children (RR = 2.17; 95% C.I. = 1.32-3.58)., Conclusion: Overall, black children used disproportionately fewer health services than their white counterparts, but used significantly higher emergency room services. Private insurance coverage was the single most significant variable that accounted for the black-white differential use of the emergency room.

Background and Objectives: Environmental tobacco smoke (ETS) exposure is probably one of the most important public health hazards in our community. Our aim with this article is to (1) review the prevalence of ETS exposure in the United States and how this prevalence is often measured in practice and (2) summarize current thinking concerning the mechanism by which this exposure may cause infections in young children., Methods: We conducted a Medline search to obtain data published mainly in peer-reviewed journals., Results: There is still a very high prevalence of ETS exposure among US children ranging from 35% to 80% depending on the method of measurement used and the population studied. The mechanism by which ETS may be related to these infections is not entirely clear but may be through suppression or modulation of the immune system, enhancement of bacterial adherence factors, or impairment of the mucociliary apparatus of the respiratory tract, or possibly through enhancement of toxicity of low levels of certain toxins that are not easily detected by conventional means., Conclusions: The prevalence of ETS exposure in the United States is still very high, and its role in causing infections in children is no longer in doubt even if still poorly understood. Research, therefore, should continue to focus on the various mechanisms of causation of these infections and how to best reduce the exposure levels.

Objectives: We attempted to determine the incidence, predictors, attitudes, and practices of breast-feeding initiation among women in a low-income rural Mississippi community., Methods: We interviewed 420 new mothers regarding breast-feeding., Results: Ninety-six women (24%) initiated breast-feeding. More whites (44%) than blacks (20%) initiated breast-feeding. Of those 96, 59% planned to breast-feed for <6 months and 38% for 6 to 12 months. Among women who breast-fed, 78% said they did so because it was healthier. Among those not breast-feeding, most (48%) specifically stated, "I have no reason," while 20% hated the idea and 19% lacked time. About 73% of all women had been encouraged to breast-feed by nonphysicians (83%). For both races, the most significant predictor was a breast-feeding friend or relative., Conclusion: Breast-feeding rates in the Mississippi Delta are low, especially among blacks. Effective education programs are needed to increase these rates, and such programs should include friends, spouses, relatives, and significant others.

Background: Children with recurrent infections significant enough to warrant referral to an immunologist frequently have mild abnormalities of the humoral immune system. Parents of these children are generally reassured that their child will outgrow the clinical problems that prompted their referral., Objective: This is a retrospective study with the objective being to evaluate changes in immune measurements and clinical status of children with recurrent infections followed in an immunology clinic., Methods: Forty-two patients (mean age 60 months) previously evaluated for recurrent infections were re-evaluated after at least 12 months (mean 37 months). Initial evaluation studies included quantitative immunoglobulins in all patients and IgG subclass determinations and pre- and postvaccination pneumococcal polysaccharide antibody titers in a subpopulation of patients., Results: Patients were assigned to one of two categories: those with initial laboratory abnormalities (27 patients) and those with normal initial studies (15 patients). Among the patients with initial abnormalities, partial IgA deficiency was most commonly seen (20/27). It persisted in 15. Only 6/27 patients had studies that were completely normal on follow-up. Among patients with no initial abnormality, 9/15 developed a partial deficiency of at least one immunoglobulin isotype or IgG subclass. Eighty-six percent of the patients were clinically improved at the time of their last follow-up visit regardless of their laboratory values., Conclusions: A high proportion of children with recurrent infection have persistent, partial immunoglobulin deficiencies lasting in some cases for years. Despite this finding almost all patients demonstrate clinical improvement with time.

The diagnosis and management of chronic sinusitis in children represents a difficult challenge for the clinician. Part of the problem stems from the fact that normal children have many upper respiratory infections and it is sometimes difficult to determine whether the upper respiratory symptoms a child experiences with these infections are consistent with a normal number of "routine" childhood infections or whether there is a more significant problem. The issue is complicated by the fact that sinus infections in children may not have the same clinical manifestations as similar infections in adults. This review focuses on the pathophysiology of persistent and chronic sinus infections in children. Particular emphasis is placed on the potential role for allergic and/or immunologic disorders in children with chronic sinus problems.

During a 30-month interval at LeBonheur Children's Medical Center, 394 patients had a blood or cerebrospinal fluid culture positive for Streptococcus pneumoniae. Sixteen of these episodes (4%) were repeated infections; 6 of these 16 patients had sickle cell disease. Six of the remaining 10 patients had immunologic evaluations of varying completeness; no immunodeficiency was identified by these tests or on follow-up. Nine of the ten previously healthy patients with repeated pneumococcal disease were less than 2 years of age. In our experience, repeated invasive pneumococcal infections in otherwise healthy young children were relatively common (10/394, or 2.5% of patients with invasive pneumococcal infections) and did not indicate the presence of an unsuspected immunodeficiency.

Background: Increasingly, antibody testing is being used to evaluate the status of humoral immunity in patients with recurrent infection and suspected immunodeficiency. In the past, we had been impressed that immunization with unconjugated Haemophilus influenzae b (uHib) vaccine provided useful information about the ability to produce antibody to polysaccharides and that the use of pneumococcal polysaccharide (PPS) vaccine frequently produced results that were difficult to interpret., Objective: The study was carried out to compare antibody responsiveness to vaccination with uHib with the response seen after PPS vaccination., Methods: Twenty children (ages, 2 to 13 years; 11 male) who were referred to our immunology clinic because of recurrent infections were immunized with both uHib vaccine and PPS vaccine. Nine children had previously received conjugated Hib vaccine., Results: All 20 children either responded with a twofold or greater increase in antibody titer after uHib vaccine or had preimmunization antibody concentrations of greater than 400 nanograms antibody nitrogen per milliliter (ng Ab N/ml). All of the children responded to PPS-3 with postimmunization antibody concentrations greater than 400 ng Ab N/ml. Three children had an increase in titer to PPS-7 of less than twofold, seven did not have a twofold increase in titer to PPS-9, and 15 had an increase in titer to PPS-14 of less than twofold., Conclusion: Unconjugated Hib vaccine is a potent immunogen in children over 2 years of age. Prior immunization with the conjugate vaccine did not prevent a response to unconjugated vaccine. Unconjugated Hib vaccine appears to be at least as immunogenic as PPS-3 when used as an assessment vaccine for evaluating antibody responsiveness.

In this brief review, only the most useful immunologic tests available for defining host defects that lead to susceptibility to infection have been emphasized. It should be pointed out that those evaluations and tests ordered by the physician will rule out the vast majority of the currently recognized defects. Finally, it is important that any patients identified as abnormal by these screening tests be characterized as fully as possible in centers specializing in these diseases before therapy is initiated, since what may appear to be a simple diagnosis on the surface may be an indicator of more complex underlying problems.

Objectives: The purposes of this study were to determine the accuracy of the immunization histories of hospitalized preschool children, assess the sociodemographic factors associated with delayed immunizations, and interview parents or guardians concerning their views on ways of improving immunization delivery., Methods: The immunization status of 215 preschool children admitted to a pediatric hospital was determined by interviewing parents or guardians regarding their children's immunization histories. The patient's immunization records were subsequently reviewed for confirmation. The admitting physician's history also was reviewed to determine whether the patient's immunization status had been noted. Finally, parents or guardians of all children studied were interviewed to assess their views on ways of improving the delivery of immunization services., Results: Only 44% of the 215 preschoolers evaluated were adequately immunized. Among those between 2 and 5 years of age, 52% were fully immunized. Only 17% of those who were inadequately immunized could have been completely updated if given an immunization at discharge. The admitting physician failed to document the immunization status of 22% of the patients. Thirty percent of the parents gave inaccurate information concerning the immunization status of their children. Most parents felt that the provision of transport (30%) or formal remainders (21%) would enhance immunization rates. Multiple regression analysis showed that a history of missed opportunity to immunize, male gender, lack of transportation, and lack of day care attendance were significant predictors of delayed immunization., Conclusions: Resident physicians should be more stringent in documenting the immunization status of all admitted preschoolers so that those found to be delayed could be updated before discharge. A hospital policy of updating underimmunized children at discharge and reporting the immunization status of all discharged patients to their primary care provider could help improve the immunization coverage in this population. Transportation for routine health maintenance and telephone or mailed remainders might further improve the immunization status of inner-city children.

Objective: To evaluate the cell-mediated immune status of children with recurrent respiratory tract infections., Design: We evaluated the cell-mediated immune status of 76 patients referred because of recurrent infection. Patients were divided into those with serologic abnormalities and those without such findings. Twenty-three healthy children served as control subjects. Studies of lymphocyte phenotype included CD4+ CD29+ cells (an immunologically mature phenotype), lymphocyte proliferation studies, cytokine production including interleukin-2 (IL-2), IL-4, IL-6, and interferon gamma), and measurement of in vitro IgM and IgG synthesis., Results: Lymphocyte proliferation and T-cell phenotype were similar in both patient groups as well as in control subjects. The proportions of CD4+ CD29+ cells at different ages were similar in all groups. Patients with serologic abnormalities (e.g., partial IgA deficiency, partial IgG subclass deficiency) produced more IL-2 and IL-4 than did other patients. The control population had greater spontaneous IgM and IgG synthesis than the patient groups., Conclusion: Routine studies of T-cell function of patients with recurrent infection provide little information useful in making clinical decisions.

Although intravenous immunoglobulin (IVIG) has primarily been recognized as useful in patients with antibody deficiencies, it continues to be used for an ever-expanding list of conditions. In addition to antibody replacement, IVIG may act as an immune modulator in certain autoimmune and inflammatory conditions. Its use should be carefully weighed against the high cost of the product. In conditions where it appears to be useful, controlled studies are necessary to prove its efficacy and its cost benefits.

Background: We have cared for an unusual patient with serum IgE concentrations of up to 150,000 IU/mL who did not have the hyper-IgE syndrome., Objective: Our objective in this study was to compare the regulation of in vitro IgE synthesis in this patient with results reported for in vitro IgE production by patients with the hyper-IgE syndrome., Methods: We utilized an enzyme-linked immunosorbent assay to measure in vitro IgE production under varying conditions. In vitro cytokine production including IL-2, IL-4, IL-6, and interferon-gamma also was evaluated as was expression of the IgE receptor molecule CD23., Results: B cells from this patient produced high concentrations of IgE. The patient was found to produce very high levels of interleukin-4 (IL-4) in vitro, to have high levels of soluble CD23 in his serum, and to have cells that were inconsistently responsive to the effect of IL-4 on IgE synthesis., Conclusions: Patients with elevated production of IL-4 may have increased serum IgE concentrations without having the hyper-IgE syndrome syndrome.

Recent studies show that most patients with X-linked hyper IgM syndrome have defects in the gene for CD40 ligand. We evaluated 17 unrelated males suspected of having X-linked hyper IgM syndrome. Activated T cells from 13 of the 17 patients failed to bind a soluble CD40 construct. In these patients, the sequence of CD40 ligand demonstrated mutations. By contrast, T cells from the remaining four patients exhibited normal binding to the CD40 construct. Sequencing of the cDNA for CD40 ligand from these patients did not show mutations. The possibility that hyper IgM syndrome in these four patients was due to abnormalities in the B cell response to CD40-mediated signals was examined. Peripheral blood lymphocytes were stimulated with anti-CD40 alone, IL4 alone or anti-CD40 plus IL4. In comparison with B cells from controls or patients with hyper IgM syndrome and mutant CD40 ligand, B cells from the patients with hyper IgM syndrome and normal CD40 ligand were defective in their ability to secrete IgE (P < 0.02) or express activation markers, CD25 and CD23 (P < 0.02) in response to stimulation with anti-CD40. The failure of these B cells to respond to CD40-mediated activation could not be attributed to a generalized deficiency in B cell activation because IL4 induced normal up-regulation of CD23 and CD25 expression. These findings indicate that hyper IgM syndrome may result from defects in expression of CD40 ligand by activated T cells or defects in CD40-mediated signal transduction in B cells.

IgG subclass deficiency has been noted in association with a variety of clinical conditions. It's relative importance as a contributing factor to these conditions is unclear. Despite reservations about the importance of partial IgG subclass deficiency, evidence is beginning to emerge that suggests that in select patients with recurrent infection and subclass deficiency, gamma globulin therapy may be beneficial.

Objective: This study tests the hypothesis that dehydroepiandrosterone or its metabolic products are immunomodulatory in postmenopausal women with relative adrenal androgen deficiency., Study Design: A prospective, randomized, double-blind, crossover study of 11 subjects with 3-week treatment arms separated by a 2-week washout period was performed. Immunologic evaluation at the beginning and end of the treatment arms consisted of flow cytometry to delineate T-cell populations, in vitro T-cell mitogenic response and cytokine production, and natural killer cell cytotoxicity. Statistical analysis was based on a split-plot design with analysis of variance with repeated measures., Results: Dehydroepiandrosterone supplementation decreased CD4+ (helper) T cells and increased CD8+/CD56+ (natural killer) cells. Although T-cell mitogenic and interleukin-6 responses were inhibited, natural killer cell cytotoxicity increased dramatically., Conclusions: These data provide the first in vivo evidence in human for an immunomodulatory effect of dehydroepiandrosterone. The salutary immune changes could account for clinical and experimental evidence of antioncogenic effects of this steroid. This study provides a strong rationale for further clinical studies on dehydroepiandrosterone supplementation in adrenal androgen-deficient states.

The authors have attempted to develop a hybrid organoid capable of supporting the engraftment of human pancreatic islet tissue transplants. In this report, they we report the histologic appearance of this organoid structure for implantation periods up to 16 days. Both pancreatic duct-like and glandular cells were present inside the organoid. Insulin positive cells were identified within the pancreatic tissue. Although polymorphonuclear (PMN) cells were seen in association with tissue necrosis, the authors observed no lymphocyte infiltration in the area of the xenografted human pancreatic islet tissue in the implanted organoid. Endothelial cell growth factor induced neovascularization inside the organoid sufficient to support the engraftment of transplanted pancreatic islet tissue. This organoid model may provide an alternative for clinical pancreatic transplantation.

Three cases are reported of the association of childhood onset of thoracic aortic calcification with mucocutaneous candidiasis, endocrine dysfunction and recurrent non-fungal pulmonary disease. The aortic calcification affects the thoracic aorta and the low lumbar aorta and common iliac arteries, sparing the mid-lumbar aorta and its major branches. Ischemic signs and symptoms of the head and neck and lower limbs are absent. This peculiar, slowly progressive vascular calcification, although unexplained to date, appears to be a non-random part of the more common candidiasis-endocrinopathy syndrome.

IgG subclasses have been recognized since the early 1960s. Four such subclasses, designated IgG1, IgG2, IgG3, and IgG4, are known to exist. Approximately 65 to 70% of the total circulating IgG in normal persons is of the IgG1 subclass. IgG2 constitutes 20 to 25% of circulating IgG, and IgG3 and IgG4 each represent less than 10%. Deficiencies in the various IgG subclasses have been detected in adults and children with common variable hypogammaglobulinemia as well as in those with relatively normal total IgG levels. An important issue facing clinicians today is to determine what, if any, therapeutic implications are associated with demonstration of an IgG subclass deficiency.

We studied humoral immune function in 267 children with recurrent respiratory infections referred to our immunology clinic to determine the most appropriate immunologic studies for evaluating recurrent infections in children. Of this highly selected population, 58% had a partial deficiency in one or more of the major immunoglobulin isotypes or IgG subclasses (defined as at least 2 SD below the normal age-adjusted mean). In none of the patients was there a total absence of an immunoglobulin isotype. The most common abnormality was partial IgA deficiency, which was found in one third of the patients. Twenty-six patients had only partial IgG subclass deficiencies, of which 20 were deficiencies of a single subclass. IgG1 was an isolated partial defect in three patients, IgG3 in five patients, and IgG2 and IgG4 were selective partial defects in six patients each. Tetanus toxoid and pneumopolysaccharide type 3 were the most immunogenic of the immunogens tested; hyporesponsiveness to pneumococcal polysaccharide types 7, 9, and 14 was common. Nineteen percent of the patients with normal immunoglobulin concentrations who were tested had lower-than-expected antibody titers; 42% of those tested with partial isotype deficiencies had deficient antibody responses. Of 25 patients with selective partial IgG subclass deficiencies or combined IgG subclass deficiencies, eight had antibody deficiencies. Our findings indicate that a high proportion of children referred to immunology clinics for recurrent infection have a demonstrable immunologic abnormality. Selective IgG subclass deficiency or a combined IgG subclass deficiency without an associated deficiency in a major immunoglobulin isotype is unusual. Identification of such patients is not predictive of the capacity to form antibodies to the antigens tested in this study and, in our opinion, adds little to the initial evaluation of immune function in such children.

The exact role of natural killer (NK) cells in host defense is unclear, but they may be important as an early response to certain infections. We evaluated NK cell phenotype and activity in premature very low birth weight infants (VLBWI) (n = 52) with an average gestational age of 29.3 wk (24-35 wk) and an average birth weight of 1124 g (537-1480 g). All patients initially were evaluated within 7 d of birth. Samples also were obtained at 2, 4, and 6 wk in some infants. The proportion of mononuclear cells expressing the phenotypic marker of NK cells (NKH-1; CD56) was significantly lower in VLBWI than in adults (2.5 +/- 1.4 versus, 12.5 +/- 7.8%, p less than 0.0001) or term infants (2.5 +/- 1.4 versus 9.5 +/- 7.1%, p less than 0.0001). VLBWI also had significantly diminished NK activity expressed as the percentage of specific lysis compared with adults (4.7 +/- 4.4 versus 32.3 +/- 14.5%, p less than 0.0001) or term infants (4.7 +/- 4.4 versus 15.5 +/- 10.8%, p less than 0.0001). Both the number of cells expressing the NK phenotype and the NK lytic activity in VLBWI increased in the 6 wk after birth. NK activity in VLBWI was enhanced by IL-2 and in most cases by interferon-gamma.

We have successfully developed a technique for culturing human islet cells obtained from the cadaveric pancreata of children. Within 24-48 h of in vitro culture, collagenase-digested human pancreatic tissue formed epithelioid monolayers. Scattered within these monolayers were insulin-positive cells, as detected by immunocytochemical and dithizone staining. Treatment of the beta cell-containing epithelioid-cell monolayers with EDTA resulted in the formation of spherical cellular clusters, i.e., pseudoislets. These pseudoislets differed from isolated islets of Langerhans in that they showed a more peripheral distribution of insulin-positive cells. Our studies have demonstrated that insulin-positive cells can be detected in monolayers obtained from human pancreata 3-4 weeks after culture. When exposed to varying concentrations of glucose, these cells secreted insulin. The development of this in vitro technique for culturing human pancreatic islet tissue could provide a model for systematically studying in vitro islet function.

Isolated islet allografts survive indefinitely in the abdominal testis of nonimmunosuppressed diabetic rats. The predominant feature of these testes is that the presence of Sertoli cells, but not Leydig cells, is required for extended survival of the islet allografts. Sertoli cells cultures were therefore established in vitro and we examined the effects of the conditioned media on Con A--stimulated spleen lymphocyte proliferation. These studies revealed that a product(s) secreted by Sertoli cells inhibits Con A-stimulated lymphocyte proliferation in a dose-dependent manner. The synthesis of this product is both temperature-dependent, occurring predominantly at 37 degrees C, and hormone-dependent, requiring the presence of follicle stimulating hormone, in the culture medium. We further examined the mechanism of inhibition of lymphocyte proliferation and showed that Sertoli cell-enriched media inhibit the production of IL-2 in a dose-dependent manner. Furthermore, the finding that the addition of exogenous IL-2 is not able to reverse this inhibition indicates that the Sertoli cell-enriched media inhibit both IL-2 production and IL-2 responsiveness of T lymphocytes.

To address the relationship between the gene (or genes) that causes the syndrome of X-linked hypogammaglobulinemia with isolated growth hormone deficiency and the gene responsible for typical X-linked agammaglobulinemia (XLA), we have used cytogenetics, examination of X chromosome inactivation patterns in potential carriers of the defect, and linkage analysis to study two unrelated families in which the affected males had isolated growth hormone deficiency and immunologic findings indistinguishable from those of typical XLA. A deletion could not be demonstrated in either family by G-banded karyotypes or flow cytometric analysis of metaphase chromosomes. Studies of X inactivation showed that mothers of affected boys from both families exhibited selective use of a single X chromosome as the active X chromosome in B cells but not T cells. This pattern is the same as that seen in obligate carriers of typical XLA. Linkage analysis demonstrated the most likely location for this gene (or genes) to be the midportion of the long arm of the X chromosome between DXS3 and DXS94. This segment of the X chromosome, which constitutes approximately 5% of the total X chromosome, encompasses the gene for XLA. These findings are consistent with the combination of XLA and growth hormone deficiency being caused by a small, contiguous, gene deletion syndrome involving the gene for XLA or an allelic variant of the gene for typical XLA.

Sixteen healthy very low birth weight infants (VLBWI) were studied in a serial fashion over a 3-week period. Subjects were evaluated for lymphocyte phenotype, phytohemagglutinin (PHA) response, and metabolic status including weight, blood urea nitrogen, creatinine, albumin, pH, calcium, phosphorus, and ammonia. Lymphocyte phenotype determination showed a decreased proportion of CD3+ cells (66.8 +/- 10.4 vs 75.9 +/- 6.1, P less than 0.02) in VLBWI. When subsets of the CD4+ population were examined, VLBWI had a lower proportion of CD4+/CD29+ cells (8.2 +/- 5.8% vs 23.5 +/- 8.0%, P less than 0.0001) than adults and a higher proportion of CD4+/CD45R+ cells (35.6 +/- 12.4% vs 22.2 +/- 7.4%, P less than 0.03). The CD4+ subsets in VLBWI were similar to those seen in term infants. The peak PHA response in VLBWI was greater than that of adults (P less than 0.01). There was little change in the immune measurements over the 3-week study period. There were no strong correlations between any of the immunological measurements and the metabolic measurements except that the proportion of CD8+ cells increased with birth weight. Our findings demonstrate that immune measurements in healthy VLBWI differ from values found in adults but are similar to those of full-term infants. Lower proportions of the CD4+/CD29+ cells (the helper/inducer subset for antibody production) may contribute to some of the differences in immune function reported in neonates.

The proposita presented at birth with multiple congenital anomalies including craniofacial anomalies, bilateral cleft lip and palate, abnormalities of the urogenital system, talipes equinovarus, and the DiGeorge sequence. Cytogenetic investigation showed a 46,XX,-22,+der(9)t(9;22)(q22;q11.2) karyotype. The mother, maternal uncle, and maternal grandmother of the infant are carriers of a reciprocal balanced translocation involving chromosomes 9 and 22 at regions q22 and q11.2, respectively. The unbalanced karyotype seen in the proposita arose due to an adjacent-2 disjunction of the quadrivalent in the mother. Prenatal diagnosis of the second pregnancy of this woman showed a similar karyotype. Review of the literature shows that adjacent-2 disjunction may occur preferentially when certain chromosomes are involved in translocations.

We reviewed the clinical course in 43 patients from eight medical centers who were given the diagnosis of chronic mucocutaneous candidiasis, a rare disorder of unknown cause that may occur in childhood. Recurrent or severe infections with organisms other than Candida were seen in 80% of the patients. There were nine cases of septicemia. Seven patients have died; six of these deaths were directly related to non-Candida infectious complications. Endocrine dysfunction, including Addison disease (11 patients) and hypothyroidism (9 patients), was seen in 19 of 43 patients. Immunologic studies failed to reveal a consistent abnormality, although two of five patients with reversed T4/T8 ratios are among those who have died. Ketoconazole was effective in controlling symptoms of candidiasis in most patients. The findings from this study indicate that non-Candida infections cause serious morbidity and may result in death in patients with chronic mucocutaneous candidiasis.

Seventeen hospitalized children with acute asthma, ages 7 to 15 years, were studied to determine the efficacy of simultaneous administration of atropine sulfate and isoetharine. Combination therapy was superior in 11/17 (65%) patients while isoetharine alone was superior in 4/17 (23%) patients (P = .037). We conclude that simultaneous administration of combination therapy is safe and beneficial in some children with acute asthma.

The evaluation of suspected humoral immunodeficiency includes quantitative immunoglobulin levels and specific antibody assays. The Schick test is a simple procedure for measurement of specific diphtheria antibodies that has been overlooked because the availability of Schick test materials has been limited in recent years. We assessed the efficacy of the Schick test in screening for antibody deficiency states in 23 children. Five had positive Schick test reactions. All five had clinical and immunologic findings consistent with a primary immunodeficiency disorder. Each of these patients had at least one other abnormality of antibody formation detected. The Schick test is a simple screening device helpful in the assessment of immunocompetence.

A 9-year-old white boy developed a fatal primary Epstein-Barr virus (EBV) infection while receiving chemotherapy for acute lymphoblastic leukemia in remission. Histopathological findings at the height of the proliferative phase of the illness were compatible with a virally induced hemophagocytic syndrome. The infection spontaneously converted to complete aplasia of the bone marrow and lymph nodes. Serological studies disclosed that the patient had no antibodies to EBV prior to the infection, but during the acute phase he showed a spectrum and titers of antibodies to EBV-specific antigens characteristic of a current primary EBV infection. A lymph node biopsy obtained 5 weeks after onset revealed Epstein-Barr nuclear antigen in approximately 50% of the cells. The boy's condition deteriorated rapidly, with disseminated candidiasis resulting in cardiorespiratory failure and death. Lymph nodes obtained at autopsy no longer contained Epstein-Barr nuclear antigen-positive cells.

The role of various mononuclear cell subpopulations necessary for T lymphocyte colony formation was investigated. Neither T cell-enriched nor T cell-depleted populations formed colonies as readily as did unfractionated cells. Addition of small numbers of the T cell-depleted pool greatly enhanced the capacity of the T cell-enriched pool to form colonies. Populations depleted of cells bearing the OKT4 phenotype were deficient in their colony-forming capacity. This assay may prove useful in evaluating patients with subtle abnormalities of mononuclear cell function.

Twenty-four patients with aplastic anemia (AA) were evaluated with immunologic studies. Patients with posthepatitis AA had decreased proportions of T4 cells, increased proportions of T8 cells, and decreased T4:T8 ratios. Patients with constitutional AA had varied immunologic findings. There were no significant abnormalities in lymphocyte subsets in patients with idiopathic AA. Of the 12 patients who were treated with antithymocyte globulin (ATG), six (50%) responded. Nine of these patients are living 3-27 months after treatment; three of the nine are transfusion dependent. T-cell subsets were not helpful in predicting the response to ATG. Measurements of other immunologic mediators may be more useful with regard to pathophysiology and prognosis in AA.

Ecto 5' nucleotidase (5' NT) activity and T lymphocyte colony formation (TLCF) are both reputed to be markers for lymphocyte maturation. In order to determine whether these two expressions of lymphocyte activity are related, we compared 5' NT activity with the TLC forming capacity of mononuclear cells from three study groups: normal adults, cord blood, and patients with immunodeficiencies. Despite individual examples of correlation between these two measurements, there was poor overall correlation in any of the groups studied. Although both measurements may reflect maturation of certain cellular activities, these are unlikely to be related.

Inhaled beclomethasone dipropionate aerosol is a topically active corticosteroid that has proved to be of great value in treating asthma. The authors have examined the effect of inhaled beclomethasone dipropionate aerosol on circulating leukocytes and on immunological measurements in normal adult subjects. Subjects inhaled either 400 micrograms or 1600 micrograms as a single dose. White blood cell counts, total neutrophil counts, total eosinophil counts and total lymphocyte counts were determined at 0, 2, 4 and 6 hours following an 8:00 a.m. inhalation. Among the 11 subjects who inhaled 400 micrograms, the total white blood cell count increased significantly at six hours (p less than 0.05). The total neutrophil count was increased significantly at 2, 4 and 6 hours (p less than 0.05). Total eosinophil counts and total lymphocyte counts were diminished but not significantly. Among the five subjects inhaling 1600 micrograms similar findings were observed. Seventeen volunteers inhaled 200 micrograms of beclomethasone dipropionate qid for 24 hours. In addition to the above studies, T and B cell numbers were determined and lymphocyte transformation studies were performed. Although trends similar to those observed with single larger dose inhalations were seen, the changes were not statistically significant. The results of these studies indicate that inhaled beclomethasone dipropionate does have the potential to affect circulating leukocytes.