Biomedical subjects
Publications and source records attributed to J Goldfarb.
We describe a patient with granulomatous mastitis due to Mycobacterium abscessus that presented as a mass lesion and was associated with a pierced nipple. To our knowledge, this is the first reported case of mastitis due to M. abscessus and the first association of this organism with body piercing.
Mycobacterium triplex was first named in 1996 as an acid-fast bacillus with features that most resemble Mycobacterium simiae and Mycobacterium avium-intracellulare complex but which possesses a distinct mycolic acid pattern as well as a distinctive 16S rRNA hypervariable region. It has been isolated from lymph node, sputum, and cerebrospinal fluid specimens, but to date only rare clinical cases of this organism have been reported in the literature. The following is a case report of M. triplex that was isolated from the pericardial and peritoneal fluid of a 13-year-old female liver transplant patient.
OBJECTIVES: To identify the causes of mortality in children with vertically transmitted human immunodeficiency virus (HIV) infection and to study age-related mortality trends. METHODS: In the multicenter P(2)C(2) HIV Study, 816 children born to HIV-infected mothers were followed for a median of 3.6 years. Two hundred five study participants with HIV infection were enrolled at a median age of 23 months; 611 were enrolled either prenatally or in the neonatal period before their HIV infection status was known. There were 121 deaths in study patients. The cause of death for all patients, its relationship to HIV infection, and pulmonary or cardiac involvement were determined. Age trends in disease-specific mortality were summarized for the HIV-related deaths. RESULTS: Ninety-three children died of HIV-related conditions. Infection was the most prevalent cause of death for children under 6 years of age with 32.3% caused by pulmonary infection and another 16.9% caused by nonpulmonary infection. The frequency of pulmonary disease as the underlying cause of death decreased significantly with increasing age: 5/9 (55.6%) by age 1, 1/12 (8.3%) after age 10 years. The frequency of chronic cardiac disease as the underlying cause increased with age-0% by age 1 year, 3/12 (25.0%) after age 10 years, as did the frequency of wasting syndrome with disseminated Mycobacterium avium complex-0% by age 1 year, 6/12 (50.0%) after age 10 years. CONCLUSIONS: Children with HIV who survive longer are less likely to die of pulmonary disease or infection and more likely to die of cardiac causes or with wasting syndrome.pediatric acquired immunodeficiency syndrome, mortality, human immunodeficiency virus.
Cortical perfusion with GABA agonists and antagonists modulates the spontaneous release of cortical acetylcholine and GABA in freely moving rats. Twenty-four hours after implantation of a dialysis fibre, cerebral cortex spontaneously released acetylcholine (3.8 +/- 0.2 pmol/10 min) and GABA (6.6 +/- 0.4 pmol/10 min) at a stable rate. Local administration of GABA (1 or 5 mM) or the GABAA agonist muscimol (25 or 50 microM) had no effect on the spontaneous release of acetylcholine. However, bicuculline (1-25 microM), a GABAA antagonist, added to the dialysis perfusate, elicited a concentration-dependent increase of acetylcholine release to approximately double that of control. This effect of bicuculline (25 microM) was completely prevented by coperfusion with muscimol (50 microM). Local administration of the GABAB receptor agonist baclofen (10 or 50 microM) elicited a concentration-dependent increase in spontaneous acetylcholine release with a maximal increase of about 60%. Intracortical administration of baclofen also decreased the spontaneous release of GABA. The GABAB receptor antagonist CGP 35348 (1 mM), administered alone for 20 min through the dialysis fibre, was without effect on spontaneous acetylcholine release; however, it completely blocked both the baclofen-induced increase in acetylcholine release and the decrease in GABA release. These results suggest that cortically released GABA exerts a tonic influence on cholinergic activity.
BACKGROUND: Peripheral blood CD4(+) and CD8(+) T cells, CD19(+)/20(+) B cells, and serum Igs are known to be altered by the progression of pediatric HIV-1 infection, but their evaluation as predictors of survival needs further definition. OBJECTIVE: To determine the natural history of these immune factors and their importance in predicting survival, we studied 298 HIV-1 vertically infected (HIV-1(+)) children over a 5-year period. METHODS: These immune factors and serum HIV-1 RNA levels were measured in two groups: (1) a birth cohort of children enrolled up to age 28 days postnatally, including 93 HIV-1(+) and 463 HIV-1 uninfected infants (HIV-1(-)), and (2) an older cohort of 205 HIV-1(+) children enrolled after the age of 28 days, who were classified as survivors or nonsurvivors. RESULTS: In the birth cohort HIV-1(+) children had significantly lower CD4(+) T-cell counts, higher CD8(+) T-cell counts, and lower CD19(+)/20(+) B-cell counts and higher IgG, IgA, and IgM levels than HIV-1(-) children. In the older cohort survivors had significantly higher CD4(+) and CD8(+) T-cell and CD19(+)/CD20(+) B-cell counts and higher IgG, lower IgA, and lower IgM levels than did nonsurvivors. In univariable analysis factors affecting survival in the older cohort were baseline CD4(+) and CD8(+) T-cell and CD19(+)/20(+) B-cell counts and IgG and HIV-1 RNA levels (all P <.05). In multivariable analysis high baseline CD4(+) T-cell count and low baseline HIV-1 RNA load remained important. CONCLUSION: The longitudinal mean profiles of CD4 and CD8 T-cell and CD19/20 B-cell counts and serum IgG levels helped to describe the natural progression of HIV-1 disease in children. However, only baseline CD4 T-cell count independently predicted survival.
The objective of this study was to assess the influence of specific factors on post-thaw development of mouse cryopreserved morulae. Thawed morulae (n = 206) were randomly distributed between 10 treatment groups: medium alone control (CT), Vero (VR) cells, leukaemia inhibitory factor (1 ng/ml), interleukin-6 (1 ng/ml), transforming growth factor (TGF) alpha (2 ng/ml), epidermal growth factor (EGF) (4 ng/ml), platelet-derived growth factor (1 ng/ml), insulin-like growth factor (IGF)-I (30 ng/ml), IGF-II (1 ng/ml) and TGFbeta (2 ng/ml). At 4, 8, 20, 30 and 48 h, a digitized image of each thawed embryo was captured and stored for later analysis. The following parameters were examined: blastocoel formation, blastocyst expansion, zona thickness and hatching. At termination of the experiment, cell number per embryo was determined by bisbenzimide staining. When contrasted to the medium alone control, co-culture consistently accelerated the development of frozen-thawed morulae to the hatched blastocyst stage, allowing embryos to recover rapidly from any damage sustained during the cryopreservation process. While no single growth factor/cytokine was able to completely mimic the results achieved with co-culture, all of the growth factors impacted positively on at least one of the morphological parameters studied. Cell proliferation was significantly stimulated by just 48 h exposure to growth factors, either through co-culture or by direct media supplementation. Co-culture again yielded the best results with a mean cell count of 217 +/- 76 cells per blastocyst as compared with 131 +/- 36 in control medium alone. Amongst the factors tested, IGF-I, IGF-II and EGF had the greatest impact, with mean cell counts of 172 +/- 50, 168 +/- 50 and 179 +/- 55 respectively. Whereas only 5% of CT embryos developed to blastocysts with > 200 cells, 51% of thawed embryos placed on co-culture monolayers and 25-32% of embryos cultured with IGF-I, IGF-II or EGF had > 200 cells. This study for the first time systematically describes the effect of culture regimen and growth factor additives on the post-thaw development of cryopreserved embryos.
Peripheral blood CD4+ and CD8+ T cells, CD19+/20+ B cells, and serum immunoglobulins (Igs) have been implicated as survival factors for pediatric HIV-1 infection. To determine which of these immune factors might be important in predicting survival, we studied HIV-1 vertically infected (HIV-1+) children over a 5-year period. Peripheral blood lymphocytes and Igs were measured in 298 HIV-1+ children, who were classified as survivors or nonsurvivors, and in 463 HIV-1 vertically exposed and noninfected (HIV-1-) children. Measurements of other possible survival factors were included in this study: albumin, hemoglobin, lactic dehydrogenase (LDH), and HIV-1 RNA levels. Survivors had significantly higher CD4+ T-cell, CD8+ T-cell, and CD19+/CD20+ B-cell counts and serum IgG levels, but lower serum IgA and IgM levels than nonsurvivors. Serum albumin and blood hemoglobin levels were higher, but serum LDH and HIV-1 RNA levels were lower in the survivors compared to nonsurvivors. In univariable analysis, factors affecting survival were baseline CD4+ T-cell and CD8+ T-cell counts, IgG, albumin, hemoglobin, LDH, and HIV-1 RNA (all p < 0.001). In multivariable analysis, high baseline CD4+ T-cell count, IgG and albumin levels, and low baseline HIV-1 RNA load remained important factors for survival. Serum IgG level has been identified as an immune factor that independently predicts survival, in addition to the already established CD4+ T-cell count. The HIV-1 RNA and serum albumin levels also predicted survival.
PURPOSE: To test the feasibility of captopril magnetic resonance (MR) renography and to validate the technique in an animal model of renal arterial stenosis. MATERIALS AND METHODS: Seven pigs with induced renal arterial stenosis were studied. MR renography was performed with a T1-weighted approach by using three-dimensional fast imaging with steady-state precession, or FISP, sequences after administration of a bolus of 0.1 mmol of gadopentetate dimeglumine per kilogram of body weight. Captopril was administered to improve the specificity. RESULTS: The results demonstrate that differences in renographic curves and indices are observed only if an anatomically substantial stenosis, typically a diameter reduction of more than 70%, is present and captopril is administered. CONCLUSION: In this preliminary experience in an animal model, captopril MR renography provided data consistent with expectations based on conventional renographic results.
OBJECTIVE: Infants with human immunodeficiency virus type 1 (HIV-1) can be divided into rapid progressors (RPs) and non-rapid progressors (non-RPs) based on symptoms and immunologic status, but detailed information about cardiac and pulmonary function in RP and non-RP children needs to be adequately described. METHODOLOGY: Cardiac, pulmonary, and immunologic data and HIV-1 RNA burden were periodically measured in 3 groups: group I, 205 vertically infected children enrolled from 1990 to 1994 and followed through 1996; group II, a prospectively studied cohort enrolled at birth that included 93 infected (group IIa); and 463 noninfected infants (group IIb). RESULTS: Mean respiratory rates were generally higher in group IIa RP than non-RP children throughout the period of follow-up, achieving statistical signifance at 1 month, 12 months, 24 months, 30 months, and 48 months of follow-up. Non-RP and group IIb (HIV-uninfected children) had similar mean respiratory rates from birth to 5 years of age. Significant differences in mean respiratory rates were found between group I RP and non-RP at 7 age intervals over the first 6 years of life. Mean respiratory rates were higher in RP than in non-RP at <1 year, 2.0 years, 2.5 years, 3.0 years, 3. 5 years, 4.0 years, and 6.0 years of age. Mean heart rates in group IIa RP, non-RP, and group IIb differed at every age. Rapid progressors had higher mean heart rates than non-RP at all ages through 24 months. Mean heart rates at 30 months through 60 months of age were similar for RP and non-RP children. Non-RP children had higher mean heart rates than did group IIb at 8 months, 24 months, 36 months, 42 months, 48 months, 54 months, and 60 months of age. In group I, RP had higher mean heart rates than non-RP at 2.0 years, 2.5 years, 3.0 years, and 4.0 years of age. After 4 years of age, the non-RP and RP had similar mean heart rates. Mean fractional shortening differed between the 3 group II subsets (RP, non-RP, and IIb) at 4, 8, 12, 16, and 20 months of age. Although mean fractional shortening was lower in RP than in non-RP in group II at all time points between 1 and 20 months, the mean fractional shortening was significantly lower in RP only at 8 months when restricting the statistical comparisons to the 2 HIV-infected groups (RP and non-RP). Mean fractional shortening increased in the first 8 months of life followed by a gradual decline through 5 years of age among group IIb children. No significant differences among the 3 groups in mean fractional shortening were detected after 20 months of age. In group I, differences between RP and non-RP in mean fractional shortening were detected at 1.5, 2.0, 2.5, and 3.0 years of age. After 3 years of age, group means for fractional shortening in RP and non-RP did not differ. Because of the limited data from the first months of the group I patients, it could not be determined whether this group experienced the gradual early rise in mean fractional shortening seen in the group II infants. In group IIa, RP had more clinical (eg, oxygen saturation <96%) and chest radiographic abnormalities (eg, cardiomegaly) at 18 months of life. RP also had significantly higher 5-year cumulative mortality than non-RP, higher HIV-1 viral burdens than non-RP, and lower CD8(+) T-cell counts. CONCLUSIONS: Rapid disease progression in HIV-1- infected infants is associated with significant alterations in heart and lung function: increased respiratory rate, increased heart rate, and decreased fractional shortening. The same children exhibited the anticipated significantly increased 5-year cumulative mortality, increased serum HIV-1 RNA load, and decreased CD8(+) (cytotoxic) T-cell counts. Measurements of cardiopulmonary function in HIV-1-infected children seem to be useful in the total assessment of HIV-1 disease progression.
Infections caused by human parvovirus B19 can result in a wide spectrum of manifestations, which are usually influenced by the patient's immunologic and hematologic status. In the normal host, parvovirus infection can be asymptomatic or can result in erythema infectiosum or arthropathy. Patients with underlying hematologic and immunologic disorders who become infected with this virus are at risk for aplastic anemia. Hydrops fetalis and fetal death are complications of intrauterine parvovirus B19 infection.
BACKGROUND AND METHODS: Cytomegalovirus (CMV) has been implicated as a cofactor in the progression of human immunodeficiency virus type 1 (HIV-1) disease. We assessed 440 infants (75 of whom were HIV-1-infected and 365 of whom were not) who had known CMV status and were born to HIV-1-infected women and who were followed prospectively. HIV-1 disease progression was defined as the presence of class C symptoms (according to the criteria of the Centers for Disease Control and Prevention [CDC]) or CD4 counts of less than 750 cells per cubic millimeter by 1 year of age and less than 500 cells per cubic millimeter by 18 months of age. RESULTS: At birth the frequency of CMV infection was similar in the HIV-1-infected and HIV-1-uninfected infants (4.3 percent and 4.5 percent, respectively), but the HIV-1-infected infants had a higher rate of CMV infection at six months of age (39.9 percent vs. 15.3 percent, P=0.001) and continued to have a higher rate of CMV infection through four years of age (P=0.04). By 18 months of age, the infants with both infections had higher rates of HIV-1 disease progression (70.0 percent vs. 30.4 percent, P=0.001), CDC class C symptoms or death (52.5 percent vs. 21.7 percent, P=0.008), and impaired brain growth or progressive motor deficits (35.6 percent vs. 8.7 percent, P=0.005) than infants infected only with HIV-1. In a Cox regression analysis, CMV infection was associated with an increased risk of HIV-1 disease progression (relative risk, 2.59; 95 percent confidence interval, 1.13 to 5.95). Among children infected with HIV-1 alone, but not among those infected with both viruses, children with rapid progression of HIV-1 disease had higher mean levels of HIV-1 RNA than those with slower or no progression of disease. CONCLUSIONS: HIV-1-infected infants who acquire CMV infection in the first 18 months of life have a significantly higher rate of disease progression and central nervous system disease than those infected with HIV-1 alone.
The objective was to describe the epidemiologic, clinical, bacteriologic and therapeutic features of seven infants who developed sternal wound and mediastinal infections following palliation and/or repair procedures for congenital heart disease. A retrospective chart review was used. All infants with sternal wound and mediastinal infections were < 30 days of age at the initial operative procedure. Six of the infants had hypoplastic left heart syndrome, and one had complete transposition. Two infants required delayed closure of their chest wound. Three infants had superficial sternal infections and presented at a mean of 12 days postoperatively. Four infants had infection of the deep mediastinal structures: they were all asymptomatic and had purulent collections in their mediastinum at their second palliative operation, which was performed at a mean of 120 days after the initial surgery. Staphylococcus aureus, or coagulase-negative Staphylococcus, was isolated from the wound and/or blood of six infants. All infants with mediastinal infections were managed with operative debridement. Infants with superficial infections underwent local debridement. All infants received long-term intravenous antibiotics. Mediastinal infections in infants undergoing palliative staged procedures for congenital heart lesions may be chronic and indolent, resulting in delayed repair of congenital heart lesions.
Extracellular matrices and their associated growth factors can modulate the in-vitro growth of cells. In this study, the effects of culture substrata and the cytokine interleukin-6 (IL-6) on embryonic development were investigated. In-vitro fertilized mouse oocytes were pooled and randomly distributed amongst treatment groups. The test treatments were: (i) IL-6, at either 500 or 1000 pg/ml; (ii) human extracellular matrix (HECM) applied to organ culture dishes at either 5.0 or 10.0 microg/ml; and (iii) HECM and IL-6 combined. A total of 1285 embryos was evaluated. The effect of IL-6 on embryos was dose dependent. Treated embryos exhibited higher blastulation and hatching rates than untreated control embryos. Culture of embryos on human matrix proteins versus standard culture surfaces significantly improved in-vitro hatching. The combination of both of these treatments was superior to the medium alone control, and the mean cell count per blastocyst was higher (131.7 +/- 29.7 versus 82. 5 +/- 14.3 in control embryos; P < 0.0001). In a pilot study with human triploid embryos, the HECM/IL-6 culture system appeared to support embryonic compaction, blastulation and hatching. This work suggests that extracellular matrix components in combination with growth factors/cytokines may be another avenue for formulating more physiological culture systems.
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INTRODUCTION: A high incidence of sudden, unexplained deaths in infants born to HIV-infected mothers has been noted in several epidemiologic studies. During the course of a prospective study of heart and lung disease in children born to HIV-infected mothers, we noted that of 5 unexpected non-HIV-related deaths, 4 were attributed to traumatic events. METHODS: The Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection (P2C2) study is a multicenter, prospective investigation of the incidence of heart and lung disease in HIV-infected children. A total of 805 children were enrolled and followed for 5 to 7 years with serial immunologic, pulmonary and cardiac function studies. During the study, a multidisciplinary committee was formed to review the cause of death for those patients who died. The committee used results of pulmonary, cardiac, and laboratory tests, hospital summaries, as well as autopsy and coroners' reports. The committee formed a consensus about the underlying and contributing causes of death for each subject using the definitions from the 1989 US Standard Certificate of Death. RESULTS: A total of 121 deaths occurred during the course of the P2C2 study. Of the 121 deaths, 5 were traumatic or sudden and unexpected and judged by the Mortality Review Committee to be unrelated to HIV infection. The median age at the time of death was 1.3 months and ranged from 1.2 to 37.8 months. Two infants died of trauma: a skull fracture and subdural hematoma in 1 infant and multiple skeletal fractures consistent with battered child syndrome in the other infant. The third infant died of accidental suffocation at home at 1.2 months of age. The fourth infant died suddenly and unexpectedly at home at 1.3 months of age. The autopsy showed no sign of HIV or other infection and was consistent with sudden unexpected death or SIDS. One non-HIV-related death occurred when a 38-month-old child died together with the mother in an unwitnessed drowning. The cumulative mortality rate attributable to trauma and sudden death at 4 months of age was 0.95% (95% CI: 0.02-1. 87%) and the infant mortality rate was 9.5/1000 live births. Three children were born prematurely at 30, 33, and 36 weeks' gestational age, respectively, and 3 mothers admitted using recreational drugs before or during pregnancy. DISCUSSION: These traumatic and sudden non-HIV-related deaths accounted for 4.1% (5/121) of the deaths during the entire P2C2 study period and for 20% (4/20) of the deaths in the first year of life. Four deaths were attributable to accidental and nonaccidental trauma rather than to other common causes of infant death. One death was a sudden unexpected death, similar to SIDS, a leading cause of infant death in the United States. The majority of previously reported non-HIV-related deaths in infants born to HIV-infected mothers have been attributed to SIDS or to unexplained sudden death. In contrast with other reports, 4 of the 5 children in our series died of accidental or nonaccidental trauma and only 1 was a sudden unexplained death. It is unlikely that HIV exposure is related directly to the deaths described in this report; however, maternal HIV infection may be a marker for factors that place the child at risk for sudden or traumatic death. SUMMARY: This report suggests that children born to HIV-infected mothers may be at increased risk for traumatic or sudden, unexplained, non-HIV-related death. These children seem to be at risk regardless of their own HIV infection status. Furthermore, 4 of the deaths in our study occurred within the first few months of life, suggesting that this is a period of increased vulnerability. Studies to identify associated risk factors for non-HIV-related deaths are needed to identify these high-risk infants. Children born to HIV-infected mothers may be more vulnerable than was recognized previously and may be in need of increased social services, especially in early infancy.
The association of maternal and perinatal factors with mother-infant transmission of HIV-1 was examined in a prospective multicenter cohort of singleton live births to 508 HIV-1-infected women with children of known HIV-1 infection status (91 [18%] HIV-1-infected, 417 [82%] uninfected). From multivariate logistic regression, independent predictors of HIV-1 transmission included maternal CD4 percentage (CD4%) (odds ratio [OR] per 10% increase in CD4% = 0.70; p = .003), ruptured membranes <24 hours (OR = 3.15; p = .02), and maternal bleeding (OR = 2.90; p = .03), whereas maternal zidovudine (ZDV) use was marginally associated (OR = 0.60; p = .08). The associations of maternal urinary cytomegalovirus (CMV) shedding, oropharyngeal Epstein-Barr virus (EBV) shedding, and serology profiles during pregnancy with HIV-1 transmission were examined in the subset of mothers in whom the CMV and EBV measurements were available. Maternal EBV seropositivity, CMV shedding, and CMV seropositivity were 100% (279 of 279), 7% (16 of 229), and 92% (270 of 274), respectively. These rates did not differ between transmitting and nontransmitting mothers. In univariate analyses, maternal EBV shedding was higher among transmitting than nontransmitting mothers (40 of 49 [82%] compared with 154 of 226 [68%]; p = .06) and was independently associated with transmission in multivariate logistic analyses adjusting for CD4%, ruptured membranes, and ZDV use, with an OR of 2.45 (95% confidence interval (CI), 1.03-5.84; p = .04). This permits the conclusion that EBV shedding is associated with maternal-infant HIV-1 transmission, independent of CD4%.
There is now considerable evidence that a single receptor subtype can couple to multiple effector pathways within a cell. Recently, Kenakin proposed a new concept, termed "agonist-directed trafficking of receptor stimulus", that suggests that agonists may be able to selectively activate a subset of multiple signaling pathways coupled to a single receptor subtype. 5-HT2A and 5-HT2C receptors couple to phospholipase C-(PLC) mediated inositol phosphate (IP) accumulation and PLA2-mediated arachidonic acid (AA) release. Relative efficacies of agonists (referenced to 5-HT) differed depending upon whether IP accumulation or AA release was measured. For the 5-HT2C receptor system, some agonists (e.g. TFMPP) preferentially activated the PLC-IP pathway, whereas others (e.g. LSD) favored PLA2-AA. As expected, EC50's of agonists did not differ between pathways. For the 5-HT2A receptor system, all agonists tested had greater relative efficacy for PLA2-AA than for PLC-IP. In contrast, relative efficacies were not different for 5-HT2A agonists when sequential effects in a pathway were measured (IP accumulation vs. calcium mobilization). These data strongly support the agonist-directed trafficking hypothesis.