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Biomedical subjects

J E Allen

Publications and source records attributed to J E Allen.

At least 55 records · Page 3Linked to original sources
PubMed1997

The prevention of experimentally induced postoperative adhesions.

For many years, various substances have been used to prevent postoperative adhesions, with suboptimal effectiveness. Saline has been postulated to have a positive effect, but it is reabsorbed from the abdominal cavity within 24 hours. To determine whether a longer-lasting intraperitoneal solution would be effective in preventing postoperative adhesions, 36 rats were divided into three groups: in 15 rats, a 2.5 per cent hyperosmolar solution of peritoneal dialysis fluid was injected intraperitoneally immediately following exploratory laparotomy, which included traumatization of the intestinal serosa at two sites; in 12 rats, normal saline was injected by the same procedure; and in 9 rats, no fluid was injected after the same operation. After 3 weeks, the group receiving the hyperosmolar peritoneal dialysis solution achieved the best results in both sites, the group that received normal saline showed marginal improvement, and the control group fared the worst.

Animals↗
PubMed1996

Insurance-related differences in the presentation of pediatric appendicitis.

In the pediatric population, there is strong evidence to suggest that a delay in treatment results in an increased risk of appendiceal perforation. However, it is not clear whether this delay arises from the parent seeking medical advice, the referring physician seeking surgical consultation, or the surgeon deciding to operate. To resolve this issue, the authors performed a retrospective chart review of all cases of confirmed acute appendicitis that presented to the pediatric surgical service of the Children's Hospital of Buffalo during a 4-year period (January 1990 through December 1993). All children (< or = 16 years of age) were categorized with respect to type of insurance coverage:Medicaid (or uninsured), health maintenance organization (HMO), or private fee-for-service. Their time until emergency room (ER) presentation, operating room (OR) presentation, and hospital discharge were recorded and compared. Their complications and perforation rates also were noted. Two hundred eighty-eight cases were reviewed. The rate of appendiceal perforation was significantly higher among the Medicaid patients (Medicaid, 44%; HMO, 27%; private, 23%; P < .05); their duration of symptoms before presentation was significantly longer (Medicaid, 47.3 +/- 4.1 hours; HMO, 29.3 +/- 1.9 hours; private, 23.1 +/- 2.5 hours; P < .01), and their hospital stay was longer (Medicaid, 7.9 +/- 0.9 days; HMO, 4.8 +/- 0.27 days; private, 4.6 +/- 0.44 days; P < .01). However, there were no significant differences in the time from presentation to the ER until definitive surgery in the OR. Children covered by Medicaid (or uninsured) presented later, had a higher risk of appendiceal perforation, and required a longer hospital stay. The parents of these children either failed to recognize the significance of their children's symptoms, or delayed seeking medical advice because of financial or logistical reasons. The gatekeeper consultation, required by the health maintenance organizations (HMO) did not result in a delay in presentation or have a negative impact on morbidity. Providing easier access to a primary care physician and improving parental health education/awareness may shorten the time until presentation for the uninsured/Medicaid patient.

Acute Disease↗
PubMed1996

APC from mice harbouring the filarial nematode, Brugia malayi, prevent cellular proliferation but not cytokine production.

Specific T cell hyporesponsiveness and depressed antibody production is a key feature of human infection with the filarial nematodes, Brugia malayi and Wuchereria bancrofti. Despite this immune suppression, responses indicative of Th2 subset activation are present, including unusually high levels of specific IgG4. We tested the possibility that infection with filarial nematodes causes a reduction in the co-stimulatory or antigen-presenting capacity of macrophages resulting in a failure to activate specific T cells. Adherent peritoneal exudate cells (PEC) from mice implanted with adult B. Malayi were used to present antigen to the conalbumin-specific T cell clone, D10.G4. Proliferation of the D10 cells at even background levels was completely blocked by the presence of implant-derived adherent PEC. However, cytokine production by these cells in response to antigen was intact, and thus PEC from implanted mice are capable of functionally processing and presenting antigen. The elicitation of a suppressive cell population was specific for live adults as cells from mice implanted with dead adult parasites effectively stimulated D10 proliferation. The block in cellular proliferation is not due to the production of factors typically associated with macrophage suppression such as nitric oxide, prostaglandins or catalase. These observations are consistent with the T cell hyporesponsiveness seen in human cases of patent Brugia infection and may provide a murine model for the immune suppression seen in lymphatic filariasis.

Adult↗
PubMed1996

Immunology of human helminth infection.

Parasitic helminths cause enormous morbidity among humans especially in developing countries. These large extracellular organisms have complex life cycles frequently involving an arthropod vector. Helminth parasites can be tissue dwelling or intestinal but all induce a dramatic expansion of the Th2 lymphocyte subset. It remains unclear whether these Th2-derived responses, including IgE, eosinophilia and mastocytosis are important in the protective immune response to the parasite, or are responsible for immune-mediated pathology, or both. Interestingly, despite high levels of IgE and other features of Th2 cell activation, allergic responses are rarely observed in infected individuals. Helminths can survive for years in the infected host, and have evolved elaborate immune evasion strategies to establish these long-lived infections including the induction of tolerance to parasite antigens. This review discusses the dynamics of infection with helminth parasites with specific emphasis on Th2 subset activation. The current knowledge of immune effector mechanisms, immunopathology and hopes for vaccine development are also discussed.

Allergens↗
PubMed1996

Choledochal cysts: a ten year experience.

Choledochal cyst (CC) is a rare disorder that usually presents in childhood. Prognosis depends on early diagnosis, complete excision of the cyst, and reconstruction by hepaticojejunostomy. This report details our 10-year experience and emphasizes innovations in our management. Sixteen patients presented with CC at a mean age of 3 years. (Range, newborn to 21 years, with a M:F ratio 1:4). Two groups could be identified on the basis of age at presentation. Group I (N = 7), presented in the neonatal period, three with obstructive jaundice and four without symptoms. In Group II (N = 9), all patients presented with ascending cholangitis at a mean age of 6 years. Thirteen patients had a type 1 CC, one patient had a type 3 CC, and two had type 4 CC. The patients with type 1 and type 4 CC underwent primary cyst excision with Roux-en-Y hepaticojejunostomy, whereas the patient with type 3 CC underwent cyst excision with sphincteroplasty of the ampulla. There was only one complication of postop cholangitis that cleared with antibiotic therapy. All patients have remained free from symptoms in the follow-up period (6 months-10 years). Our four most recent cases were diagnosed in utero by prenatal ultrasonography. This led to appropriate antenatal counseling and prospectively planned neonatal surgery. These infants were asymptomatic, with no clinical signs at birth, and antenatal ultrasonography prevented diagnostic delay. Excision of the choledochal cyst and primary hepatico-enteric anastomosis is confirmed as the therapy of choice. Antenatal sonography is a sensitive method in the diagnosis of CC and offers the opportunity for early diagnosis and planned surgery before the onset of complications.

Adolescent↗
PubMed1995

Infection of IL-4-deficient mice with the parasitic nematode Brugia malayi demonstrates that host resistance is not dependent on a T helper 2-dominated immune response.

Resistance of intact mice to infection with the filarial nematode, Brugia malayi is dependent on the presence of T cells. To investigate the role of Th2 cells in this protection, mice with a targeted disruption of the IL-4 gene were infected with different developmental stages of B. malayi. We examined the phenotypic changes in the immune response and the survival of each stage in these mice. In wild-type mice, adult female worms induce Th2 responses, characterized by antigen-specific IgG1 production, elevated IgE, and marked IL-4 secretion by splenocytes stimulated in vitro with Brugia extract. However, first stage larvae (microfilariae), induce Th1 responses with the appearance of antigen-specific IgG2a, IgG2b, and IgG3 and IFN-gamma secretion by splenocytes. Infection of IL-4-deficient mice revealed a dramatic change in the response to adult worms, with a severe reduction in IgG1 production and a corresponding increase in the production of IgG2a, IgG2b, IgG3, and IFN-gamma release. The switch to Th1-type responses was particularly marked in IL-4-deficient recipients of female worms, which continually release live microfilariae. In the absence of IL-4, down-regulation of the microfilarial-induced Th1 response does not occur. Despite these profound alterations to the immune response in IL-4-deficient mice, survival of infective larvae, adult worms, or microfilariae in the peritoneal cavity was unaffected. In mice, therefore, the prominent Th2-type response elicited by filarial parasites may not be an essential component of the host protective immune response.

Animals↗
PubMed1995

Spontaneous pneumothorax: a single-institution, 12-year experience in patients under 16 years of age.

OBJECTIVE: To characterize the natural history and outcome of spontaneous pneumothorax in patients under age 16 years. DESIGN: This is a retrospective review in which all patients admitted to the authors' institution (between December 1980 and July 1993) with a diagnosis of spontaneous pneumothorax were included. Information was obtained from the hospital records. SETTING: This study was performed in a university childrens' hospital. PATIENTS: All patients under 16 years with a diagnosis of spontaneous pneumothorax were included. RESULTS: Seventeen patients were admitted and analyzed. Only three admissions were for recurrence. The main symptoms included chest pain (100%), shortness of breath (41%), and cough (6%). Chest tube drainage was successful in 65% of the cases; the median time was 4 days. Two patients had a persistent air leak. An underlying cause was recognized in 42% of cases. Seven operations were necessary, and the mean follow-up periods is 31 months, with no recurrence reported to date. CONCLUSION: Spontaneous pneumothorax occurs in the pediatric population, although it is less common in adults. An underlying pathology is more frequently observed in pediatric patients, but recurrence is less common. Chest tube drainage alone is sufficient treatment for the majority of patients; however, a significant number require some form of surgical intervention.

Adolescent↗
PubMed1995

Duplication of the cervical esophagus in children.

True duplication of the cervical esophagus is rare. An 18-month-old girl presented with a large asymptomatic neck mass, which was found to be an intramural duplication of the esophagus. The evaluation and treatment of this patient is presented as well as a review of the six previously reported cases.

Esophagus↗
PubMed1995

The gp15/400 polyprotein antigen of Brugia malayi binds fatty acids and retinoids.

Gp15/400 is a surface-proximal antigen of the filarial nematode Brugia malayi, produced as a large polyprotein precursor comprising an array of polypeptide units of approx. 14.5 kDa. Here we describe a biochemical function for gp15/400. A single 14.5-kDa unit of gp15/400 has been expressed in Escherichia coli, and found to dimerise spontaneously. This protein (designated P-RUNG) has high-affinity fatty acid and retinoid binding activity, suggesting that the parent polypeptide itself has these properties. Fluorescent fatty acid probes show significant enhancement of fluorescence intensity and shifts in emission wavelength in the presence of P-RUNG, which can be reversed by competing non-fluorescent fatty acids (oleic, palmitic, steric, arachidonic), retinoids (retinol and retinoic acid) and oleoyl Coenzyme A, but not by tryptophan, cholesterol, caproic acid, squalene, tocopherol, tocopherol acetate, succinyl CoA, 2-methylbutyric acid and 2-methylvaleric acid. Changes in intrinsic fluorescence of retinol or retinoic acid confirmed the retinoid binding function. The results of fluorescence titration experiments are consistent with stoichiometric binding to a single protein site per monomer unit with affinities (Kd) in the range 2 x 10(-6) M (for the fluorescent probe 11-((5-dansyl)amino)undecanoic acid) and 2 x 10(-7) M (for oleic acid). The extreme blue shift of the fluorescent fatty acid-protein complex suggests an unusually low polarity for the protein binding site. The intrinsic fluorescence of the single tryptophan residue of P-RUNG indicates that it also is deeply buried in a non-polar environment, but is probably not involved in ligand binding. Gp15/400, therefore, represents a new class of lipid binding protein which is possibly restricted to nematodes.

Animals↗
PubMed1995

Fat cells in red bone marrow of human rib: their size and spatial distribution with respect to the radon-derived dose to the haemopoietic tissue.

Samples of human rib were collected at autopsy and 20 were selected for marrow fat cell measurement, representing an age range of 16-96 years. The mean diameter of fat cells in red bone marrow of human rib was found to increase from around 48 microns at ages 16-29 years to around 65 microns at ages 82-96 years. There was a greater number of fat cells of smaller size range in younger ages compared with that in older ones. The maximum size of fat cells was found to be 102 microns. Calculated radon-derived doses to haemopoietic tissue ranged from 60 to 162 microSv y-1 at average UK exposures of 20 Bq m-3. It was concluded that the bone marrow fat fraction is the important parameter as far as alpha-radiation dose from radon in fat is concerned. This updates the theoretical estimates of dose carried out by Richardson et al. (1991).

Adipocytes↗
PubMed1995

Fine specificity of the genetically controlled immune response to native and recombinant gp15/400 (polyprotein allergen) of Brugia malayi.

Polyprotein allergens are a family of structurally homologous molecules from parasitic nematodes which induce specific immunoglobulin E in infected individuals. We show here that both H-2 and non-H-2 factors determine the ability of mice to generate T- and B-cell responses to the filarial polyprotein allergen (Brugia malayi gp15/400). Further, H-2 and non-H-2 genes can complement one another to overcome nonresponsiveness to this molecule. However, these genetic restrictions govern only responses to the native glycoprotein and all strains of mice respond equivalently when immunized with a recombinant polypeptide. Overlapping fragments of gp15/400 were constructed to compare the T-cell and antibody responses to native versus recombinant gp15/400 in responder (BALB/c H-2d) and nonresponder (B10.D2 H-2d, CBA H-2k, and BALB.K H-2k) strains. BALB/c mice generated T-cell responses to the same fragment (positions 89 to 133 and 1 to 21) whether immunized with native or recombinant material, although the antibody responses differed in fine specificity, H-2k mice, unresponsive to the native molecule, generated T cells responsive to the centrally located peptide (positions 57 to 100) only when immunized with the recombinant. Antibody responses in H-2k mice were directed at the peptide (positions 11 to 67) which is glycosylated in the native molecule. Our findings suggest that recognition of gp15/400 is affected by modifications that occur in the parasite but are absent when the molecule is produced in bacteria. This study provides a detailed evaluation of the immune response to an important nematode antigen as a start to the unraveling of the complex interaction of these multicellular parasites with mammalian hosts.

Animals↗
PubMed1994

Adult and microfilarial stages of the filarial parasite Brugia malayi stimulate contrasting cytokine and Ig isotype responses in BALB/c mice.

Natural infection with filarial nematode parasites shows many characteristics of a Th2 immune response. In these infections, long-lived adult worms inhabit the lymphatics, releasing laval microfilariae (Mf) into the blood stream. To compare the effect of these different developmental stages on the mammalian immune system, Mf and adult worms of either sex were implanted into BALB/c mice, in which they survive for at least 28 days. Serum Ab responses showed that whereas Mf stimulated specific Abs of all IgG subclasses, but little total IgE, adult worms stimulated only IgG1 and IgE responses. Splenocytes from implanted mice were stimulated in vitro with specific Ag or Con A and assayed for proliferation and profiles of cytokine secretion. Cells from Mf-infected mice secreted high levels of IFN-gamma (30 U/ml) throughout infection, but very little IL-4 at the early time points. By day 28 postinfection, however, splenocytes from Mf-infected mice showed some IL-4 secretion in response to specific Ag (40 U/ml). The IFN-gamma response to Mf was found to be independent of the inoculum dose in the range of 10(2) to 10(6) organisms. In contrast, splenocytes taken from adult worm-implanted mice on days 14, 21, and 28 postinfection produced high levels of IL-4 (up to 435 U/ml) and negligible amounts of IFN-gamma despite the production of large numbers of Mf by adult female worms. CD4+ cells were primarily responsible for this IL-4 production. These results demonstrate that adult filarial parasites, and females in particular, exert a rapid polarization of the immune response in a Th2-like direction, but that this effect may be modulated by the Mf stage.

Age Factors↗
PubMed1994

Spatial distribution of naturally occurring 210Po and 226Ra in children's teeth.

Deciduous and permanent teeth extracted from juveniles for orthodontic purposes have been analysed using alpha-sensitive plastic track detectors for the spatial distribution of total alpha-activity and naturally occurring 210Pb-supported 210Po and 226Ra. The distribution of these radionuclides is non-uniform, with 210Po being primarily associated with outer enamel and 226Ra with the pulp. The observations suggest that 210Pb/210Po concentrates at the interface of enamel with saliva or blood, by means of unidirectional ionic exchange with calcium. In contrast, 226Ra concentrates in the predentine band at the interface with pulp and with systemic blood circulation, where its uptake is permitted by the incomplete calcification in this band. Activity concentration was measured in 900 teeth. Total concentration on the outer enamel surface of deciduous teeth, permanent teeth from children < or = 10 years and permanent teeth from children > 10 years give respective mean values of 8.63 +/- 0.26, 5.76 +/- 0.48 and 7.00 +/- 0.15 Bq kg-1. 226Ra concentration on the corresponding longitudinal sections comprising pulp, dentine and annular enamel give respective mean values of 0.715 +/- 0.055, 0.418 +/- 0.083 and 0.514 +/- 0.029 Bq kg-1. Mean activity concentration in 32 foetal teeth was 2.05 +/- 0.31 Bq kg-1. The results form the basis of more detailed studies of (1) age-dependent uptake of alpha-radionuclides in teeth and their microdistribution, and (2) the geographical variation in activity concentration with respect to environmental factors such as domestic radon exposure.

Child↗
PubMed1994

TASTRAK spectroscopy of polonium-210 alpha-particle activity at bone surfaces: evidence for a concentrated surface deposit less than 3 microns deep.

The technique of alpha-particle spectroscopy by CR-39 type TASTRAK plastic has been used to study the depth distribution of natural alpha-particle emitters at the surface of human bone. The predominant component of this alpha-particle activity was 210Po supported by 210Pb, although a smaller activity of 226Ra was also detected. Autopsy samples of human femur and cranium were obtained from subjects age 63 to 86. Both cortical and trabecular surfaces were analyzed. The results indicate that 210Pb-supported 210Po is concentrated at the surfaces of human bone from elderly subjects, in a narrow band 3 microns deep or less, by a factor of about four. As a result, the alpha-particle dose to the nuclei of cells lining bone surfaces is around 1.8 times greater than that calculated for a uniform volume distribution. Polonium-210 activity indicates the distribution of 210Pb, and of stable lead, received by continuous intake throughout life at a very low level. A persistent bone surface concentration of lead and other osteotropic metals may be associated with the hypermineralized layer about 1 micron thick which occurs at the surface of resting bone mineral.

Aged↗
PubMed1993

An intermolecular mechanism of T cell help for the production of antibodies to the bacterial pathogen, Chlamydia trachomatis.

Antibodies that neutralize infectivity are directed at the antigenically variant major outer membrane protein (MOMP) of Chlamydia trachomatis. A vaccine for chlamydia will need to include T cell determinants that elicit T helper (Th) cells which provide help to MOMP-specific B cells. A limited number of determinants on MOMP are able to elicit Th cells and sequence diversity in the MOMP molecule may alter T cell recognition of these determinants. We investigated whether two sequence invariant proteins of C. trachomatis that are both abundant and immunogenic could elicit T cell help for the production of antibody to MOMP. We found that outer membrane protein 2 (OMP2) but not outer membrane protein 3 (OMP3) was able to prime BALB/c mice for an anamnestic anti-MOMP response following boost with the intact organism. This demonstration of an intermolecular mechanism of T cell help in a bacterial system has important implications for the development of a chlamydial vaccine as well as the design of vaccines for other antigenically variant non-viral pathogens.

Animals↗
PubMed1993

Drug-induced photosensitivity.

Characteristics and diagnosis of photosensitivity are discussed, and drugs available in the United States that cause photosensitivity are identified. In phototoxic reactions, the drug absorbs energy from ultraviolet A (UVA) light and releases it into the skin, causing cellular damage. In photoallergic reactions, light may cause a structural change in a drug so that it acts as a hapten, possibly by binding to proteins in the skin. Once a hapten-protein complex is formed, Langerhans' cells residing in the epidermis can present the antigen to immunocompetent cells, causing hypersensitivity. Phototoxicity is much more common than photoallergy. Drugs that can cause phototoxic reactions include amiodarone, quinolones, and tetracyclines. Drugs that have been associated with photoallergic reactions include thiazides and benzocaine. Pharmacists should be aware of drugs that can cause photosensitivity and should counsel patients taking these drugs to avoid excessive exposure to sunlight.

Chronic Disease↗
PubMed1992

Comparative analysis of successful and unsuccessful candidates for the pediatric surgical matching program.

Only one third of the applicants for training in pediatric surgery obtain a position through the pediatric surgery matching program. In order to identify factors that contribute to a successful outcome, we conducted a retrospective survey of all participants in the matching process for positions during the years 1983 to 1991. This survey was designed to identify characteristics associated with success in the match through comparison of successful and unsuccessful applicants. Significant factors associated with a successful match included: a greater incidence of residency-supported research (P = .012) with a greater number of publications (P = .003) and national presentations (P = .014), specifically at the annual meetings of the American Pediatric Surgical Association (P = .05) and the American Academy of Pediatrics (P = .05). In addition, successful candidates had more contact with (P = .004) and letters of recommendation from (P = .015) well-known pediatric surgeons involved in the general surgical residency program. This information should be invaluable to those counseling medical students and residents interested in a career in pediatric surgery.

Adult↗