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Biomedical subjects

J H Passwell

Publications and source records attributed to J H Passwell.

At least 19 recordsLinked to original sources
PubMed2002

Localized thigh swelling mimicking a neoplastic process: involvement of coxsackie virus type A21.

UNLABELLED: A 4-y-old girl was admitted because of a left leg limp with an isolated swollen upper thigh and normal muscle enzymes. A radioisotope scan showed increased uptake especially in the bone and soft tissue of the left thigh, while magnetic resonance imaging of that region demonstrated widespread oedema in striated muscle. On muscle biopsy perivascular infiltrates were demonstrated but muscle fibres were not shown to be affected. Sequence analysis of reverse transcription-polymerase chain reaction amplified fragments from the 5'-non-coding region of human enteroviruses identified a local strain of coxsackie virus A21 in the muscle. Clinical symptomatology subsided with oral steroids. CONCLUSION: Local swelling mimicking a neoplasm may be related to infestation of coxsackie virus in muscle tissue.

Base Sequence↗
PubMed2001

Extrahepatic synthesis of complement proteins in inflammation.

The demonstration of local complement protein synthesis leads to speculation as to the biological significance of this phenomenon. A narrative review is provided to illuminate several queries. It is difficult to establish a causal role for the locally produced complement because participation of systemic complement cannot be excluded. It is also difficult to discern whether local complement synthesis is a beneficial response to an inflammatory event or whether it promotes tissue damage. Finally, it remains to be seen if the roles of local and systemic complement differ in these respects. Extrahepatic expression of complement components of the activation pathways may provide a rapid response to microbial invasion. Once produced and activated, these proteins evoke a phlogistic response composed of cells and soluble mediators of inflammation. Many cells, not only synthesize complement proteins, but can also be stimulated via their complement receptors. This positive feedback may enhance local immune defense, especially in organs isolated from plasma components. In addition, local environmental factors in different organs may differentially regulate complement synthesis. These factors may include pro-inflammatory molecules and non-immune effectors, such as tissue ischemia/reoxygenation and drugs. Local complement dysregulation due to inhibition of activity of a complement regulatory component was shown to cause disease and restoration of the capacity to regulate the complement pathway restored health. Extrahepatic complement synthesis may also modulate local cellular responses, as to decrease detrimental damage of the inflammatory reaction. The demonstration that complement proteins play a significant role in the clearance of apoptotic cells suggests that local synthesis and activation of complement may contribute not only to tissue damage but also to tissue repair.

Arthritis↗
PubMed2001

Safety and immunogenicity of improved Shigella O-specific polysaccharide-protein conjugate vaccines in adults in Israel.

Data suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) of Shigella species is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigella species were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity of Shigella conjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates of Shigella sonnei and Shigella flexneri 2a bound to succinylated mutant Pseudomonas aeruginosa exotoxin A (rEPAsucc) or native or succinylated Corynebacterium diphtheriae toxin mutant (CRM9 or CRM9succ) was conducted in healthy adults. The conjugates were safe and immunogenic. S. sonnei-CRM9, S. sonnei-CRM9succ, and S. sonnei-rEPAsucc elicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P < 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P < 0.0001). GM IgG anti-LPS levels elicited by S. flexneri 2a-rEPAsucc were significantly higher than those elicited by S. flexneri 2a-rCRM9succ at all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P < 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these five Shigella conjugates elicited higher fold rises than similar conjugates (D. N. Taylor et al., Infect. Immun. 61:3678-3687, 1993). Based on these data, we chose S. sonnei-CRM9 and S. flexneri 2a-rEPAsucc for evaluation in children.

Adolescent↗
PubMed2000

In vivo modulation of the allogeneic immune response by human fetal kidneys: the role of cytokines, chemokines, and cytolytic effector molecules.

BACKGROUND: We have recently demonstrated that human fetal renal tissue, implanted under the kidney capsule of severe immunodeficient rats, escapes early destruction by intraperitoneal infusion of allogeneic human peripheral blood mononuclear cells, compared with the rapid rejection of implants of human adult kidney tissue. Variable amounts of human mononuclear infiltrates were seen in the transplanted fetal kidney, however, prolonged survival of the fetal tissue (maintenance of graft architecture and significant growth) was independent of the cellular infiltrate. METHODS: We have used this experimental model to sequentially analyze transcript levels of interferon-gamma and interleukin (IL)-2 (T helper 1 cytokines), IL-4 and IL-10 (T helper 2 cytokines), RANTES, MIP1beta (beta chemokines) and their receptor CCR5, and Fas ligand (cytolytic effector molecule). Analysis was performed by reverse transcriptase-polymerase chain reaction, in both fetal and adult kidney grafts, after infusion of allogeneic human peripheral blood mononuclear cells. RESULTS: Transcript levels of interferon-gamma and IL-2 in the fetal grafts were markedly reduced throughout follow-up, compared with those observed in the adult implants. Peak levels of these cytokines appeared late in the rejection process. Concomitant with these findings, IL-4 mRNA was up-regulated during the early phase, whereas IL-10 mRNA persisted throughout the rejection process, indicating that a T helper 2 bias occurred in the fetal grafts. In addition, RANTES (after an early peak), MIP1beta, CCR5, and Fas ligand mRNA levels were suppressed in the fetal grafts compared with those in the adult grafts. CONCLUSIONS: These findings indicate that the immune response of kidney rejection is dependent on whether the target organ is of fetal or adult origin, and suggest that an allogeneic immune system mounts a T helper 2-biased response when the target organ is of fetal origin.

Adult↗
PubMed2000

Cellular localization of complement C3 and C4 transcripts in intestinal specimens from patients with Crohn's disease.

It has been suggested that the increase in C3 and C4 levels in jejunal perfusates of patients with Crohn's disease (CD) results from local intestinal synthesis of complement. The present study evaluated the expression of these complement genes in inflamed tissues from patients with CD. Surgically resected specimens from patients with CD and control tissue obtained from subjects with adenocarcinoma of the colon were evaluated for C3 and C4 gene expression by the use of 35S-labelled anti-sense RNA probes. All tissue samples, diseased and normal tissue, expressed C4 mRNA throughout in the intestinal epithelium. C3 mRNA was not detected in epithelial cells in histologically normal tissue, but in diseased specimens there was a focal distribution of C3 mRNA in epithelial cells of the crypts, but not in villous epithelium. Focal C3 gene expression correlated with crypt abscess formation and the presence of polymorphonuclear leucocytes in the lumen of the crypts. In addition, C3 mRNA was also found in macrophages of the submucosa. These macrophages were CD68+, fusiform with faint cytoplasm and morphologically different from the large rounded lamina propria macrophages, which do not express C3 mRNA. Multinucleated giant cells did not express either C3 or C4 genes. In addition to its presence in intestinal epithelium, C4 mRNA was also expressed in mast cells, which however did not express C3 mRNA. These observations identify cells in the intestinal wall expressing complement genes and support the hypothesis that there is local regulated production of complement in the intestine of patients with CD, and subsequent complement activation may contribute to the inflammatory process.

Adrenal Cortex Hormones↗
PubMed2000

Pseudomonas aeruginosa bacteremia in children: analysis of trends in prevalence, antibiotic resistance and prognostic factors.

OBJECTIVE: To determine the factors predisposing to Pseudomonas aeruginosa bacteremia as well as the prevalence, source of infection, outcome and prognostic factors in pediatric patients. METHODS: Retrospective review of pediatric patients with P. aeruginosa bacteremia, at a large tertiary care hospital during a 6.5-year period. RESULTS: Seventy patients with P. aeruginosa bacteremia were identified. The annual rate of P. aeruginosa bacteremia remained unchanged during the study period. Antibiotic susceptibility remained unchanged except for two patients with extensive burns who developed resistant strains. Underlying diseases were malignancy (50%), prematurity (6%), burns (7%) and others (37%). The overall mortality associated with P. aeruginosa bacteremia was 20%. The fatality rate was higher among the young infants (compared with older children) and those who received previous antibiotic therapy (P = 0.02). Mortality rate was higher in nosocomial than in community-acquired infections (25% compared with 11.5%). The mortality rate of low birth weight and burns patients was significantly higher when compared with oncology patients or other patients, 75 and 40% compared with 11 and 19%, P = 0.01. Multiple regression analysis revealed a correlation only between the underlying disease and mortality (P = 0.02). In the oncology patients the only significant risk factor for mortality was absolute neutrophil count < or =0.1 x 10(9)/l (P = 0.06). CONCLUSION: P. aeruginosa bacteremia, although apparently not increasing in incidence and antibiotic resistance, is still a common serious complication in immunocompromised children with a high mortality rate. We conclude that the underlying disease is the main determinant of the clinical outcome.

Anti-Bacterial Agents↗
PubMed1999

Modulation of the immune response by fetal kidney allografts.

Fetal kidneys modulate the allogeneic immune response by a synergistic effect: first, fetal kidney tissue tropism is abrogated by the initial relative lack of adhesion molecules. Second, the reduced expression of major histocompatibility complex (MHC) determinants is less effective in inducing the alloantigen-primed T cell response, which in turn induces the downregulation of Th1 cytokines, beta chemokines, and Fas ligand, but spares protective Th2 cytokines, and leads to minimal induction of MHC and adhesion molecules on immature renal parenchymal elements. Thus, at the onset and during this altered rejection process, cellular recruitment to the fetal renal site is less prominent than to the adult renal tissue, and effector cells in the fetal graft are less activated.

Adult↗
PubMed1999

Periodic fever, aphthous stomatitis, pharyngitis, and adenopathy syndrome: clinical characteristics and outcome.

We report 28 patients (20 male) with a syndrome characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis, and cervical adenopathy (PFAPA syndrome). Episodes of fever occurred at intervals of 5.1 +/- 1.3 weeks beginning at the age of 4.2 +/- 2.7 years. Fever, malaise, tonsillitis with negative throat cultures, and cervical adenopathy were reported in all 28 patients, aphthae in 19, headache in 5, abdominal pain in 5, and arthralgia in 3. Mild hepatosplenomegaly was observed in 6 patients. Mild leukocytosis, elevation of the erythrocyte sedimentation rate, and fibrinogen were found during attacks. These episodes of illness resolved spontaneously in 4.3 +/- 1.7 days. Serum IgD was found elevated (>100 U/mL) in 12 of the 18 patients tested (140.2 +/- 62.4 U/mL). Affected children grow normally, have no associated diseases, and have no long-term sequelae. Attacks were aborted by a single dose of oral prednisone (2 mg/kg) at the beginning of the attack in all 15 patients in whom this medication was prescribed. In 9 patients the syndrome has completely resolved (beginning at the age of 2.9 +/- 1.3 and lasting 8 +/- 2.5 years). In 3 other patients complete resolution of the attacks occurred after tonsillectomy was performed. PFAPA is sporadic, and no ethnic predilection was found. Increased awareness of the clinical syndrome has resulted in more frequent diagnosis and adequate treatment.

Age of Onset↗
PubMed1999

Safety and immunogenicity of Shigella sonnei and Shigella flexneri 2a O-specific polysaccharide conjugates in children.

O-specific polysaccharide conjugates of shigellae were safe and immunogenic in young adults, and a Shigella sonnei conjugate conferred protection [1-3]. Shigellosis is primarily a disease of children; therefore, the safety and immunogenicity of S. sonnei and Shigella flexneri 2a conjugates were studied in 4- to 7-year-old children. Local and systemic reactions were minimal. The first injection of both conjugates elicited significant rises in geometric mean levels of serum IgG only to the homologous lipopolysaccharide (LPS) (S. sonnei, 0.32-8.25 ELISA units [EU]; S. flexneri 2a, 1.15-20.5 EU; P<.0001). Revaccination at 6 weeks induced a booster response to S. flexneri 2a LPS (20.5-30.5 EU, P=.003). Six months later, the geometric mean levels of IgG anti-LPS for both groups were higher than the prevaccination levels (P<.0001). Similar, but lesser, rises were observed for IgM and IgA anti-LPS. The investigational Shigella conjugates were safe and immunogenic in children and merit evaluation of their efficacy.

Antibodies, Bacterial↗
PubMed1999

Local complement genes expression in the mammary gland: effect of gestation and inflammation.

Complement components in breast milk may enhance the local immune response in the gut of infants. In this study, we investigated the expression of complement genes in the mammary gland and attempted to determine possible regulatory mechanisms. We have studied the expression of C3, C4, factor B, and HLA-DRalpha mRNA by in situ hybridization in gestational mammary gland specimens and compared these findings to those in breast tissue affected with an inflammatory process, lactating adenoma or idiopathic gynecomastia. In normal resting breast, only C4 mRNA was noted in some ductal epithelium. In gestational mammary gland, there was a diffuse expression of C4, C3, and factor B mRNA in the epithelial cells of the acini. A similar pattern of complement gene expression was found in localized areas of an infectious inflammatory process. In addition, in the inflammatory specimens, there was also expression of C3 mRNA in infiltrating macrophages (CD 68 positive cells). In gynecomastia, C4 mRNA was noted in ductal epithelium, and there was a marked increased expression of C3 mRNA in the proliferating epithelium of the lactating adenoma. HLA-DRalpha was observed only in macrophages involved in the inflammatory response. Our findings, which reflect the hormonal and inflammatory events in vivo, provide new insights as to in situ complement gene expression.

Adenoma↗
PubMed1998

Intraarticular corticosteroid injection in the management of children with chronic arthritis.

OBJECTIVE: Intraarticular (IA) corticosteroid injection is a common therapeutic approach in the management of adult rheumatoid arthritis. This study examined the safety and efficacy of IA corticosteroid injection in 71 patients with juvenile arthritis who were being seen at the Sheba Medical Center during the years 1991-1996. METHODS: Sixty-one patients fulfilled the American College of Rheumatology revised criteria for the diagnosis of juvenile rheumatoid arthritis (JRA), 6 patients had reactive arthritis, and 4 patients had various other arthritic conditions. The mean +/- SD age was 9.4 +/- 5.6 years (range 0.5-18 years); 47 were female (mean age 8.1 +/- 5.5 years) and 24 were male (mean age 10.8 +/- 5.4 years). A total of 300 joints were injected with triamcinolone hexacetonide. The most common sites of injection were the knees (124 injections), ankles (71 injections), wrists (46 injections), shoulders (10 injections), and elbows (7 injections). Children under the age of 6 (n = 17), or older children who received more than 4 joint injections at one time (n = 10) were sedated with either ketamine HCI or propofol. All other children received their joint injections under local anesthesia. RESULTS: Full remission of the joint inflammation lasting >6 months following injection was achieved in 246 of the 300 injections (82.0%). In 54 (18.0%) of the injected joints, the inflammation recurred within 6 months of injection. In patients with pauciarticular arthritis, 115 of 141 injections (81.6%) resulted in full remission. Discontinuation of all oral medications was accomplished in 43 patients (60.6%) of the total group of 71 patients and in 32 of the 43 patients with pauciarticular disease (74.4%). Correction of joint contraction was achieved in 42 children (55 joints). In all 11 patients with Baker's cyst and in 12 patients with tenosynovitis, complete remission was achieved following injection. No infection or other serious complications occurred in any of the patients following the procedure. CONCLUSION: IA corticosteroid joint injection in children with juvenile arthritis is a safe and effective mode of therapy. It may be the only therapy needed in patients with pauciarticular JRA, obviating the need for prolonged oral medications, and is effective in correcting joint contractions and deformities.

Adolescent↗
PubMed1997

Severe malabsorption in autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome successfully treated with immunosuppression.

A 15 year old boy with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome suffered recurrent episodes of severe intractable diarrhoea, steatorrhoea, and hypocalcaemia. The only treatment modality, which controlled the malabsorption syndrome, was immunosuppression with intravenous high dose methylprednisolone and oral methotrexate maintenance therapy.

Adolescent↗
PubMed1997

Hodgkin's lymphoma in systemic onset juvenile rheumatoid arthritis after treatment with low dose methotrexate.

We describe the occurrence of malignant lymphoma as a possible complication of immunosuppression associated with low dose methotrexate (MTX) therapy for juvenile rheumatoid arthritis (JRA). A 6-year-old girl with systemic onset JRA who had received low dose MTX therapy for 16 months developed diffuse peripheral lymphadenopathy and enlargement of the lymph nodes in the mediastinum, hilum of the lungs, and liver. Lymph node histology disclosed mixed cellularity Hodgkin's lymphoma; the neoplastic cells were positive for CD30 and CD15, but negative for Epstein-Barr virus RNA or EBV latent membrane protein. After chemotherapy, the girl had complete remission of her disease lasting for 18 months; however, the disease relapsed and autologous peripheral stem cell transplantation was performed. Although the occurrence of lymphoma may be associated with autoimmune diseases, our observations suggest that in pediatric patients, the increasing use of low dose MTX therapy for JRA may be an additional factor for the development of lymphoproliferative disease.

Arthritis, Juvenile↗
PubMed1996

Systemic lupus erythematosus presenting as idiopathic intracranial hypertension.

We describe a 13-year-old girl who presented with an acute febrile disease accompanied by headache, dizziness, nausea, decreased visual acuity, and diplopia. Examination showed papilledema, enlarged blind spots, and visual field defects with an otherwise normal neurological examination. The diagnosis of idiopathic intracranial hypertension was confirmed by increased intracranial pressure (cerebrospinal pressure > 200 mm water) in the absence of any abnormal radiological findings of the brain. Initially, only positive serology tests showing elevated titers of anti-DNA antibodies and positive tests for anti-Sm and anti-RNP antibodies were found; however, 6 mo later clinical and laboratory findings were compatible with systemic lupus erythematosus (SLE). Our patient illustrates that the possibility of SLE needs to be considered in the differential diagnosis of idiopathic intracranial hypertension.

Adolescent↗
PubMed1995

Shigella lipopolysaccharide antibodies in pediatric populations.

Shigellosis is the most common cause of bacterial dysentery. To study the specific immunity to the two major groups causing shigellosis, we assayed antibodies to lipopolysaccharide (LPS) by enzyme-linked immunoadsorbent assay to both Shigella sonnei and Shigella flexneri 2a serotypes in the following populations: (1) women immediately after delivery and their infants to assess the transfer of passive immunity by placenta and the presence of secretory antibodies in breast milk; (2) children of different ages; and (3) the kinetics of antibody production in pediatric patients, who had culture-proved shigellosis. The sera of these women showed variable concentrations of antibodies of all three isotypes to LPS of S. sonnei and S. flexneri 2a. These serotype-specific antibodies were not cross-reactive. Transfer of IgG anti-LPS across the placenta was significantly correlated with concentration of the specific antibody in the mother (S. sonnei, r = 0.96; S. flexneri, r = 0.84). Varying concentrations of anti-LPS IgA were present in colostrum, which was correlated with serum anti-LPS IgA titers in the case of S. sonnei (r = 0.44; P < 0.05) but not S. flexneri (r = 0.17). Healthy children between the ages of 6 months and 4 years in our population had undetectable or relatively low titers of anti-S. sonnei IgG. More children had detectable antibody titers to S. flexneri 2a than to S. sonnei. The relatively high concentrations of these natural antibodies are particularly noteworthy because there is a far lower incidence (< 10% of patients) with S. flexneri than with S. sonnei disease in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗