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Purpose Clinicians and researchers must contextualize a patient’s genetic variants against population-based references with detailed phenotyping. We sought to establish globally scalable technology, policy, and procedures for sharing biosamples and associated genomic and phenotypic data on broadly consented cohorts, across sites of care. Methods Three of the nation’s leading children’s hospitals launched the Genomic Research and Innovation Network (GRIN), with federated information technology infrastructure, harmonized biobanking protocols, and material transfer agreements. Pilot studies in epilepsy and short stature were completed to design and test the collaboration model. Results Harmonized, broadly consented institutional review board (IRB) protocols were approved and used for biobank enrollment, creating ever-expanding, compatible biobanks. An open source federated query infrastructure was established over genotype–phenotype databases at the three hospitals. Investigators securely access the GRIN platform for prep to research queries, receiving aggregate counts of patients with particular phenotypes or genotypes in each biobank. With proper approvals, de-identified data is exported to a shared analytic workspace. Investigators at all sites enthusiastically collaborated on the pilot studies, resulting in multiple publications. Investigators have also begun to successfully utilize the infrastructure for grant applications. Conclusions The GRIN collaboration establishes the technology, policy, and procedures for a scalable genomic research network.

* Abbreviation: USC — : University of Southern California The following is an address given by the author in receipt of the Joseph W. St Geme, Jr Leadership Award, presented by the Federation of Pediatric Organizations at the Pediatric Academic Societies meeting on April 30, 2021. It is difficult to describe the feeling of receiving the Joseph W. St Geme, Jr Leadership Award, established in honor of my dad. The award has enormous meaning to me, as is likely obvious. My dad died on October 11, 1986, nearly 35 years ago, at the age of 55. If he were still alive today, he would be 90 years old, born in April 1931. Accordingly, some members of the pediatric community knew my dad as a colleague, some knew him as a teacher or mentor, and some may have known him as an examiner for the American Board of Pediatrics, but most never had the good fortune to know him. So I want to tell people about him and what I learned from him. My dad was born in Los Angeles, the first of 2 sons to my grandfather Joseph William Sr and my grandmother Malvina Pozzo. By the time I knew him, he was a big man, 6 ft 2 in tall, with broad shoulders and an athletic physique. He filled a room in every sense possible. Although he made no effort to dominate conversation or assume center stage, he naturally captured the attention of others, and when he spoke, people listened. He was gregarious, filled with interesting stories and pithy messages and a knack for word choice that made people smile. He took an interest in others, and he had a special gift for making people feel important. Consistent with his physique, he was an athlete, and he often used examples from sports to express his points. I learned … Address correspondence to Joseph W. St Geme, III, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104. E-mail: stgemeiiij{at}email.chop.edu

Background Septic arthritis is a serious infection, but the results of blood and joint fluid cultures are often negative in children. We describe here the clinical features and management of culture-negative septic arthritis in children at our hospital and their outcomes. Methods We performed a retrospective review of a cohort of children with septic arthritis who were hospitalized at Children’s Hospital of Philadelphia between January 2002 and December 2014. Culture-negative septic arthritis was defined as a joint white blood cell count of >50000/μL with associated symptoms, a clinical diagnosis of septic arthritis, and a negative culture result. Children with pretreatment, an intensive case unit admission, Lyme arthritis, immunodeficiency, or surgical hardware were excluded. Treatment failure included a change in antibiotics, surgery, and/or reevaluation because of a lack of improvement/worsening. Results We identified 157 children with septic arthritis. The patients with concurrent osteomyelitis (n = 28) had higher inflammatory marker levels at presentation, had a longer duration of symptoms (median, 4.5 vs 3 days, respectively; P < .001), and more often had bacteremia (46.4% vs 6.2%, respectively; P < .001). Among children with septic arthritis without associated osteomyelitis, 69% (89 of 129) had negative culture results. These children had lower C-reactive protein levels (median, 4.0 vs 7.3 mg/dL, respectively; P = .001) and erythrocyte sedimentation rates (median, 39 vs 51 mm/hour, respectively; P = .01) at admission and less often had foot/ankle involvement (P = .02). Among the children with culture-negative septic arthritis, the inpatient treatment failure rate was 9.1%, and treatment failure was more common in boys than in girls (17.1% vs 3.8%, respectively; P = .03). We found no association between treatment failure and empiric antibiotics or patient age. No outpatient treatment failures occurred during the 6-month follow-up period, although 17% of the children discharged with a peripherally inserted central catheter line experienced complications, including 3 with bacteremia. Conclusions The majority of septic arthritis infections at our institution were culture negative. Among patients with culture-negative infection, empiric antibiotics failed for 9% and necessitated a change in therapy. More sensitive diagnostic testing should be implemented to elucidate the causes of culture-negative septic arthritis in children.

In children, hematogenous osteomyelitis is an infection that primarily affects the most vascularized regions of the growing skeleton. The disease has increased in frequency, virulence, and degree of soft-tissue involvement. The change in clinical manifestations and management over the past 2 decades should be reflected in the current imaging approach to the disease. Imaging of infection must depict the location of a single focus or of multiple foci of involvement and the presence of drainable collections. This review provides an overview of the imaging implications directed by the changing epidemiology, the newer insights of anatomy and pathophysiology, the imaging characteristics with emphasis on specific locations and disease complications, and the differential diagnosis considerations. In addition, basic imaging guidelines for appropriate extent of area to image based on patient age are provided. © RSNA, 2017.

Haemophilus influenzae is a rare cause of soft tissue infection. In this report, we present a case of multifocal necrotizing fasciitis in a healthy adult patient, secondary to Haemophilus influenzae serotype f infection, and we review literature on this rare cause of necrotizing fasciitis.

* Abbreviations: ABP — : American Board of Pediatrics ABMS — : American Board of Medical Specialties ACGME — : Accreditation Council for Graduate Medical Education CBME — : competency-based medical education EPA — : entrustable professional activity FOPO — : Federation of Pediatric Organizations MOC — : Maintenance of Certification SCTC — : Subspecialty Clinical Training and Certification The American Board of Pediatrics (ABP) certifies general pediatricians and pediatric subspecialists based on standards of excellence that lead to high-quality health care during infancy, childhood, adolescence, and the transition into adulthood. Thus, central to the ABP’s mission is assurance to the public that a general pediatrician or pediatric subspecialist has successfully completed accredited training and fulfills the continuous evaluation requirements that encompass the 6 core competencies of the Accreditation Council for Graduate Medical Education (ACGME) and the American Board of Medical Specialties (ABMS). The ABP’s quest for excellence is evident in its rigorous evaluation process and in new initiatives undertaken that not only continually improve the standards of its certification but also advance the science, education, study, and practice of pediatrics. The ABP’s responsibilities and authorities in standard setting and evaluation overlap through interest and influence the responsibilities and authorities assumed by the ACGME through its Pediatric Review Committee in the area of training, as well as those of the American Academy of Pediatrics and the subspecialty societies with respect to advocacy and education. Although the respective organizations have distinct missions and roles, they often work in collaboration and synergy regarding training and advocacy. Nonetheless, standard setting, evaluation, and certification remain the sole purview of the ABP. Because of the centrality of accredited training to certification, a decision by the ABP to offer a subspecialty certificate leads to a petition to the ACGME to accredit training programs. The ABP provides substantial input to the development of initial subspecialty program requirements and periodic revisions through its respective subboards, and the ABP standards for certification heavily influence the content of program requirements. In the late 1990s, the ACGME and ABMS introduced the concept of competency-based medical education (CBME) with the establishment of 6 domains of competence: patient care, medical knowledge, practice-based … Address correspondence to David K. Stevenson, MD, Harold K. Faber Professor of Pediatrics, Stanford University School of Medicine, Medical School Office Building, 1265 Welch Rd, X157, Stanford, CA 94305. E-mail: dstevenson{at}stanford.edu

Over the past 20 years, hospitalists have emerged as a distinct group of pediatric practitioners. In August of 2014, the American Board of Pediatrics (ABP) received a petition to consider recommending that pediatric hospital medicine (PHM) be recognized as a distinct new subspecialty. PHM as a formal subspecialty raises important considerations related to: (1) quality, cost, and access to pediatric health care; (2) current pediatric residency training; (3) the evolving body of knowledge in pediatrics; and (4) the impact on both primary care generalists and existing subspecialists. After a comprehensive and iterative review process, the ABP recommended that the American Board of Medical Specialties approve PHM as a new subspecialty. This article describes the broad array of challenges and certain unique opportunities that were considered by the ABP in supporting PHM as a new pediatric subspecialty.

Researchers often face dilemmas about authorship. When the researchers are graduate students, fellows, or junior faculty, the dilemmas might involve discussions about fair criteria for more senior faculty to be acknowledged as key contributors or authors on manuscripts. This “Ethics Rounds” presents a case in which a fellow faced such a dilemma. We review current journal guidelines for authorship and some ethical considerations that should help make this process more streamlined.

BACKGROUND AND OBJECTIVE: The diversifying US population of children necessitates assessing the diversity of the pediatric academic workforce and its level of cultural competency training. Such data are essential for workforce and educational policies. METHODS: An 8-question survey was sent to 131 US pediatric chairs to assess plans for diversity, targeted groups, departmental diversity, diversity measures, perceived success in diversity, and presence and type of cultural competency training. RESULTS: In all, 49.6% of chairs responded, and three-quarters of them reported having a plan for diversity, which targeted racial; ethnic; gender; lesbian, gay, bisexual, and transgender; disabled; and social class groups. Of the residents, 75% were women, as compared with 54% of faculty and 26% of chairs. Racial and ethnic diversity was limited among trainees, faculty, and leaders; CONCLUSIONS: Pipeline issues for minorities are ongoing challenges. Pediatric leadership needs more representation of racial and ethnic minorities, women, and LGBT. Suggestions for workforce and educational policies are made.

Objectives. National recommendations are to use high-dose amoxicillin (80–90 mg/kg per day) to treat uncomplicated acute otitis media (AOM) in children who are at high risk for infection with nonsusceptible Streptococcus pneumoniae (NSSP). However, high-dose treatment may not be necessary if the local prevalence of NSSP is low. The objective of this study was to estimate the local prevalence of NSSP in children with acute upper respiratory illnesses and to develop community-specific recommendations for first-line empiric treatment of AOM. Methods. We conducted a cross-sectional prevalence study in the offices of 7 community pediatricians in St Louis, Missouri. S pneumoniae was isolated from nasopharyngeal swabs collected from children who were younger than 7 years and had AOM, nonspecific upper respiratory infection, cough, acute sinusitis, or pharyngitis. Children were excluded from the study when they had received an antibiotic in the previous 4-week period. Parents and providers completed a brief questionnaire to assess risk factors for carriage of NSSP. On the basis of National Clinical Chemistry Laboratory Standards, isolates with a penicillin minimum inhibitory concentration ≥0.12 μg/mL were considered to be nonsusceptible to penicillin (NSSP), and isolates with a penicillin minimum inhibitory concentration >2 μg/mL were categorized as nonsusceptible to standard-dose amoxicillin (35–45 mg/kg per day; NSSP-A). Results. S pneumoniae was isolated from the nasopharynx of 85 (40%) of 212 study patients (95% confidence interval [CI]: 33%–47%); 41 (48%) of 85 isolates were NSSP (95% CI: 37%–59%), and 6 (7%) were NSSP-A (95% CI: 1.5%–13%). Among the 212 study patients, the prevalence of NSSP was 19% (95% CI: 14%–25%), and the prevalence of NSSP-A was 3% (95% CI: 0.6%–5%). Carriage of NSSP was increased in child care attendees compared with nonattendees (29% vs 14%; odds ratio: 2.6; 95% CI: 1.3–5.2). Conclusions. In our community, although the prevalence of NSSP among isolates of S pneumoniae identified from the nasopharynx of symptomatic children is high (48%), the probability of NSSP-A infection among symptomatic children is

A 33-month-old girl presented with 3 days of fever and 1 day of multiple paroxysmal episodes of screaming with apparent unresponsiveness, flexed lower extremities, clenched hands, and upward eye deviation. These events lasted seconds to a minute at a time and occurred only during sleep. She slept peacefully between episodes and was easily awakened. She had a history of mild speech delay and mild intermittent asthma but was otherwise healthy. She was tired-appearing and fussy on examination with dry mucous membranes, but her examination was otherwise normal. A complete blood count with differential and serum levels of sodium, potassium, chloride, and calcium were normal, but her bicarbonate level was 12 mmol/L. Her fingerstick glucose level was 69 mg/dL. Urine dipstick was notable for large ketones, and a urine drug screen was normal. Cerebrospinal fluid examination yielded 2 white blood cells and 1040 red blood cells/mm3 with normal chemistries. A computed tomography (CT) scan of her head was unremarkable, and an abdominal ultrasound demonstrated no evidence of intussusception. Over the course of her hospitalization, these paroxysmal episodes persisted, and she subsequently developed mutism, right-sided weakness, and difficulty swallowing liquids. Here we present her case, diagnostic evaluation, and ultimate diagnosis.

The zygomycetes are saprophytic fungi that rarely cause disease in the normal human host. In immunocompromised individuals, these organisms can cause invasive infections, collectively called mucormycosis. Mucormycosis is associated with a high mortality rate, especially in organ transplant recipients. In this report, we describe the first case of successfully treated mucormycosis involving a pulmonary allograft. Treatment consisted of surgical excision of the affected lobe and chest wall and lipid-complex amphotericin B. The lipid complex formulation permitted a prolonged course of therapy that was likely critical to eradication of the infection.

* Abbreviations: ABP — : American Board of Pediatrics SOC — : Scholarship Oversight Committee What is the goal of pediatric subspecialty training, how long should the training period be, and what is the value of a scholarly activity? A committee of the American Board of Pediatrics (ABP) grappled with these and other questions from 2000 to 2003. Previously the ABP supported the view of the Federation of Pediatric Organizations that “the principal goal of fellowship training should be to develop future academic pediatricians”1 and required all applicants for subspecialty certification to have evidence of “meaningful accomplishment in research,” usually a peer-reviewed publication. A number of concerns spawned the 2000 to 2003 ABP review, including subspecialty workforce shortages, decreasing numbers of pediatric physician–scientists, and trends toward nonacademic careers among subspecialty fellowship graduates, concerns that persist today. Based on the committee’s recommendations, in 2004 the ABP issued new fellowship training requirements providing greater curricular flexibility to better prepare subspecialists with varied career aspirations.2 In place of “meaningful accomplishment in research,” the ABP embraced a variety of scholarly activities that could be tailored to individual career goals. Furthermore, fellows were to be mentored by a Scholarship Oversight Committee (SOC) that approved their scholarship work product. Examples of scholarship offered by the ABP included basic, clinical, translational, and health … Address correspondence to F. Bruder Stapleton, MD, Department of Pediatrics, Seattle Children’s Hospital, 4800 Sand Point Way NE, RB2:401, Seattle, WA 98105. E-mail: bruder.stapleton{at}seattlechildrens.org

Coagulase-negative staphylococci represent the most common cause of serious nosocomial infection in many intensive care nurseries. However, these organisms are also common blood culture contaminants. To determine the value of quantitative blood cultures in distinguishing sepsis from culture contamination, we reviewed records of all infants in our nurseries who had peripheral blood isolates of coagulase-negative staphylococci during a 3-year period. Twenty-three episodes of sepsis were identified in 21 infants, and 10 infants had blood culture contamination. Colony counts from the initial peripheral blood culture were significantly different for the two study groups (P < .001). In 9 of 23 episodes of sepsis, the initial peripheral blood culture grew >100 colony-forming units (cfu) per mL. In the other 14 episodes, the initial culture yielded ≤50 cfu/mL. All 10 infants with culture contamination had colony counts of

Antibiotic resistance among bacteria that are commonly encountered in the pediatric emergency department is a fact of nature. New antibiotics will provide some help, but probably only temporarily. Vaccine strategies seem to provide the best answer to resistance, and many physicians eagerly await the conjugated pneumococcal vaccines, which we can only hope to be as successful as the H. influenzae type b vaccines. Vaccines against other resistant organisms are likely further off. At this point, a major goal must be to limit the prevalence of antibiotic resistance. In considering this goal, two complementary strategies are key. The first is to avoid antibiotics in situations in which they are unlikely to provide benefit, such as for colds, URIs, and bronchitis. The second is to use narrow-spectrum antibiotics as much as possible to minimize selective pressure. Emerging evidence shows that these strategies can be effective. In a day-care center in Omaha, Nebraska, Boken et al showed that nasopharyngeal carriage of highly resistant S. pneumoniae decreased dramatically among attendees when antibiotic use decreased. In Iceland, a nationwide campaign that resulted in decreased antibiotic use was followed by a decrease in the incidence of penicillin-resistant pneumococcal infections from 20.0% to 16.9% and a decrease in the rate of carriage of resistant pneumococci among day-care-center attendees from 49% to 15%. In Finland, erythromycin resistance in Group A streptococci recovered from pharyngeal and pus samples had reached 13% in 1990. National guidelines that recommended a reduction in the use of erythromycin and other macrolide antibiotics in the treatment of outpatients with respiratory and skin infections were instituted, and by 1996, macrolide antibiotic consumption had decreased by 50%, with a similar 50% decrease in frequency of erythromycin-resistant isolates. In the absence of such national strategies, it is incumbent on physicians treating infections on a daily basis in the emergency department to consider carefully the judicious use of antibiotics.

To the Editor: Acute lymphangitis is caused most often by Streptococcus pyogenes and occasionally by a range of other bacteria.1 We describe a patient in whom acute lymphangitis developed, with no evidence of infection. The patient was a 27-year-old medical student who was working in the laboratory and was resuspending membranes isolated from lysed Escherichia coli when he accidentally stabbed his left index finger with a contaminated needle. Within an hour, he noted pain and swelling in his left hand. Over the next several hours, tenderness in his left arm and axilla developed, and then red streaks extending from the . . .

Thirteen children 4 to 15 years of age were selected from an allergy clinic as representative of patients who might be expected to demonstrate interferon production in response to commonly employed inhalant allergen injections. Six were studied because of definite or possible untoward reactions with the thought that lymphocyte activation and interferon production might accompany such reactions. All subjects were receiving subcutaneous hyposensitization with aqueous allergen extracts containing multiple allergens at the time the test was done. Nine were receiving maximally tolerated maintenance doses ranging from 188 to 7,500 total protein nitrogen units (PNU) per injection. The remaining four were receiving early increasing extract doses ranging from 0.5 to 94 total PNU per injection. Samples were obtained before injection and at 2, 24, 48, and 168 hours after injection. A positive control consisting of a WHO human interferon standard (40 U. per milliliter) was tested simultaneously. All serum samples were found to be negative. Since the patients were receiving widely varying total extract doses and some experienced significant reactions to the injections, the study suggests that hyposensitization injections employing inhalant allergens in doses commonly used by allergists seldom result in interferon production.

Emergency medical systems are being developed throughout the United States primarily to deal with myocardial infarction and trauma. These programs often fail to recognize the special needs of the critically ill child. Data collected in Los Angeles County from the LA County Trauma Surveys, Mobile Intensive Care Unit Rescue Reports, and Base Station Hospitals demonstrate that children represent approximately 10% of the paramedic calls. The calls are for medical problems as well as trauma. These data suggest that children have a higher death rate in the field than adults, and deaths occur more commonly in areas where there are no pediatric centers. Children are often secondarily transferred from emergency departments to other centers for definitive care. This study suggests that the needs of children in the prehospital setting are not being met.

To follow the emergence of surface colonization with coagulase-negative staphylococci in neonates, we sampled four surface sites (axilla, ear, nasopharynx, and rectum) in 18 premature infants during the first 4 weeks of life. Swabs were obtained on the first day of life, twice weekly for 2 weeks, and weekly thereafter. Isolates were characterized by species, biotype, antibiotic susceptibility patterns, and slime production. Over 4 weeks the percentage of infants with Staphylococcus epidermidis as the only surface coagulase-negative staphylococci rose from 11% to 100%. Predominance of a single S. epidermidis biotype increased from none to 89%. Multiple antibiotic resistance rose from 32% to 82% of isolates, and the prevalence of slime production increased from 68% to 95%. This microbiologic pattern was established by the end of the first week of life and persisted throughout the month of study. In three infants, S. epidermidis sepsis developed with organisms identical to their predominant surface isolate. We conclude that species, multiple antibiotic resistance, and slime production appear to confer a selective advantage for the surface colonization of premature newborn infants in the intensive care nursery environment. Infants so colonized may be at greater risk for subsequent infection with these strains of coagulase-negative staphylococci.

The effect of early immunization, prior to discharge from the newborn nursery, on subsequent immunity as determined by enzyme-linked immunosorbent assay (ELISA) immunoglobulion (Ig) M and IgG antibody titers to filamentous hemagglutinin and lymphocytosis-promoting toxin (LPT) of Bordetella pertussis and by standard pertussis agglutinin titers was investigated. Eighteen infants received routine diphtheria-tetanus-pertussis (DTP) immunization at 2, 4,and 6 months of age; 17 other infants received routine immunization and an additional DTP immunization in the newborn nursery. Antibody was determined on samples of cord blood and whole blood obtained at 4,6, and 9 months of age. IgM anti-filamentus hemagglutinin was significantly higher at 4 and 6 months of age in the group that received early immunization (P < .05). There was no significant difference in IgM anti-LPT, IgG anti-filamentus hemagglutinin, IgG anti-LPT, or pertussis agglutinin antibodies Six control infants had high cord IgG anti-LPT titers. These six infants had significantly lower antibody titers to LPT at 6 and 9 months of age when compared with control with control infants with lower cord titers. Thirteen infants in the early immunization group with lower cord IgG anti-LPT titers achieved significantly lower titers at 9 months of age than the 12 comparable infants in the control group.

The biologic validity of cell-mediated immunity to mumps virus was evaluated in 395 children, adolescents and adults. The study protocol included the determination of cutaneous delayed hypersensitivity to viral and avian control antigens and in 79% of the subjects an essential double bleeding was performed before and after mumps virus skin test for assay of neutralizing antibody. Seven per cent of subjects expressed sufficient delayed hypersentitivity to the control antigen to erase an apparently positive mumps virus skin test. Anamnestic conversions from seronegativity to seropositivity, elicited by the mumps virus skin test, increased from 4% in children to 25% in adults, which suggests waning B-cell recognition of prior mumps virus infection in adults. Although pregnancy diminished the difference (p smaller than .001), adults showed greater cutaneous delayed hypersensitivity to mumps virus antigen than did children (p smaller than .001), suggesting that mumps virus reinfection or persistence induced the escalation of more sensitive T-cell recognition with increasing age. Humoral immunity, assessed by the double bleeding technique in the vast majority of individuals, rose form 16% (1-4 years), 45% (5-9 years) and 80% (10-14 years) to 94% in adolescents and adults. Ordinarily 75-95% in other age groups, the decline of correlation between mumps virus cellular and humoral immunity to 60% in school children may result from prior parainfluenza virus infection, inconsistent potency of the skin test antigen, concurrent immunosuppressive infection, and lagging induction of mumps virus cellular immunity in recently infected individuals. Immunologic study of a large colony of subhuman primates failed to establish an hierarchial antigenic interrelationship among mumps virus and two additional paramyxoviruses.

Rose Hong Dang Bui, M.D., Giuseppe A. Molinaro, M.D., James D. Kettering, Ph.D., Douglas C. Heiner, M.D., Ph.D., David T. Imagawa, Ph.D.,, and Joseph W. St, Geme, Jr., M.D. From the Departments of Pediatrics, Pathology, and Microbiology, Loma Linda University School of Medicine, Loma Linda, California, and the Departments of Pediatrics, Microbiology, and Immunology, Harbor-UCLA Medical Center, UCLA School of Medicine, Torrance, California

The administration of live attenuated mumps virus vaccine to 26 tuberculin-positive children evoked significant depression of the tuberculin reaction in 17 of the children. There was only suggestive greater suppression of tuberculin delayed hypersensitivity in the group of 17 seronegative, susceptible children in contrast to the group of 9 seropostive, immune children. Mumps virus may interact with the cytoplasmic membrane of the immunoreactive lymphocyte and disrupt its ability to respond to specific tuberculoprotein antigen. Another vaccine has been added to the enlarging list of biologicals which may interfere transiently with accurate evaluation of tuberculin sensitivity.

A multidisciplinary study of a small group of institutionalized children has failed to provide any evidence of virus neurotropism or of even subtle neurophysiologic dysfunction following inoculation with live, attenuated measles virus. This conclusion was based on the absence of evidence for (a) persistent alteration of circadian temperature rhythm, (b) a change in quantified encephalographic electrical output, (c) spinal fluid pleocytosis or elevation of protein content, (d) an altered hematoencephalic barrier, or (e) dissemination of virus to the central nervous system.

Cytomegalovirus was not detected in the salivary glands by virological or histopathological techniques during autopsies performed upon 100 subjects. It is hypothesized that the susceptible host acquires cytomegalovirus exogenously rather than from a latent focus in the salivary glands.

Two neonates and four adults with herpes simplex virus (HSV) encephalitis were treated with cytosine arabinoside (Ara-C). A low dose of 40 to 160 mg per m 2 per day was given for 4 to 6 days by continuous intravenous infusion and, except in two cases, by intrathecal administration. In one patient, idoxuridine (IUdR) at the dose of 1 g every 4 h was also administered after 4 days of Ara-C therapy. Both neonates and two of four adults survived. Their clinical improvement was closely related in time to the onset of therapy with Ara-C (cases 1, 2, 3) and with IUdR (case 4). In one adult who died on the 27th day of illness of a massive pulmonary embolus, postmortem examination of the brain did not disclose viral inclusions, and viral culture was negative. In the other patient who died, however, brain culture postmortem was still positive for HSV despite 4 days of Ara-C therapy. Ara-C, in addition to IUdR, may be effective in HSV encephalitis treatment, but double-blind, controlled studies appear to be necessary with these agents.

The ability of live attenuated mumps virus to induce delayed hypersensitivity and humoral antibody was studied in a prospective fashion. Thirty-five children between 15 months and 5 years of age with no history of overt mumps in the past received the attenuated virus subcutaneously. At the beginning of the study there was complete correlation between delayed hypersensitivity and neutralizing antibody in 83% of the children (26 skin-test negative and seronegative, 3 skin-test positive and seropositive). In the group initially seronegative and skin-test negative, 88% developed mumps neutralizing antibody following attenuated virus infection, and 91% of these seroresponsive children developed a positive mumps skin test. Therefore, a positive mumps skin test can serve as a simple marker for vaccine-induced immunologic response. Application of the mumps virus and avian placebo antigens simultaneously is necessary for meaningful interpretation of the mumps skin test. Two patients developed delayed hypersensitivity following vaccination without developing detectable humoral antibody. The possible significance and explanation of this partial, dissociated immunologic response is discussed.

During the summer of 1968 ECHO virus type 31 was isolated from four infants in a neonatal intensive care unit. The index case was admitted from home in a comatose state and harbored ECHO 31 in his throat. Necropsy findings were inconclusive, and no virus was recovered from neural tissues. After the admission of this patient, two infants in the unit developed apneic spells and ECHO 31 was isolated from their CSF, throat, and stool samples. The virus was also isolated from the stool of an asymptomatic infant. ECHO 31 had not been recovered in newborn infants prior to its isolation in these cases. The isolation techniques currently used in many neonatal units may be inadequate to prevent viral dissemination. It is important to maintain a high index of suspicion of neonatal viral disease since careful virologic study will clarify the ecology of these nosocomial infections.

THIS familial syndrome of eczema, thrombocytopenia and recurrent infection was described by Wiskott1 in 1937, but it was not until 1954 that Aldrich, Steinberg and Campbell2 defined it as a sex-linked recessive disease. The majority of children afflicted with this baffling disorder have died as a result of overwhelming bacterial infection. Recently, however, visceral invasion by measles virus and cytomegalovirus has been described as an additional microbial complication.3 In our own hospital, within a period of two and a half years, we observed an alarming progression of primary herpetic gingivostomatitis in 3 boys with this syndrome. Two of these patients . . .

Forty-five women between the ages of 16 and 35 years, scheduled for therapeutic abortions, were screened for susceptibility to primary mumps-virus infection. Susceptibility was established by a negative mumps-virus skin test and the absence of mumps-virus neutralizing antibody in the serum at the time of skin testing and seven to 10 days later. Five women, three susceptible and two immune, received live, attenuated mumps-virus vaccine seven to 10 days before termination of pregnancy by the intra-amniotic infusion of hypertonic saline. Mumps virus was recovered from the placentas of two of the three seronegative women, but virus was not isolated from the fetal tissues of any of those vaccinated. Live, attenuated mumps-virus vaccine should be used with caution in the post-pubertal female. (N Engl J Med 290:710–712, 1974)