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Biomedical subjects

D Cooper

Publications and source records attributed to D Cooper.

At least 73 records · Page 4Linked to original sources

Sustained cellular immune responses to Borrelia burgdorferi: lack of correlation with clinical presentation and serology.

Fifty-one patients with erythema migrans were followed up prospectively with serial clinical evaluations, serologic determinations for antiborrelial antibodies, and lymphocyte stimulation responses to Borrelia burgdorferi antigens to determine (i) the factors associated with sustained cellular immune responses and (ii) whether lymphocyte stimulation is a good indicator of prior exposure to B. burgdorferi in patients treated early after erythema migrans. Positive lymphocyte stimulation responses ( > 2 standard deviations above normal control values) were found in 15 (29%) of 51 patients 3 months after treatment for erythema migrans and in 8 (18%) of 44 patients 1 year posttreatment. Heightened lymphocyte responses were not associated with the number or duration of erythema migrans lesions prior to treatment, the mean size of the largest erythema migrans lesion, or the number of symptoms at the time of presentation. The development of Jarisch-Herxheimer reaction, choice of antibiotic, and clinical outcome also were not associated with a positive lymphoproliferation assay result. Changes in the lymphocyte stimulation indices between the two time points assessed (3 months and 1 year posttreatment) also did not correlate with the above variables. When serologic results and lymphoproliferative responses were evaluated as categorical or continuous variables, there were no correlations between values. One year after treatment for early Lyme disease, lymphocyte reactivity is not a good indicator of prior infection with B. burgdorferi.

Adult

Ductus arteriosus smooth muscle cell migration on collagen: dependence on laminin and its receptors.

During permanent closure of the ductus arteriosus, smooth muscle cells migrate through the extracellular matrix (ECM) to form intimal mounds that occlude the vessel's lumen. Smooth muscle cells (SMC) migrate over surfaces coated with collagen in vitro. During the migration SMC also synthesize fibronectin (FN) and laminin (LN). Antibodies against FN and LN inhibit migration on collagen by 30% and 67%, respectively. Because of the apparent importance of LN in migration, we examined how SMC interact with LN and LN fragments (P1, E8, P1', E1', E3, E4, and G). Ductus SMC adhere to high concentrations of LN and two fragments of the molecule: P1 and E8. They use a unique set of integrin receptors to bind to LN (alpha 1 beta 1, alpha 6 beta 1 and alpha v beta 3), to P1 (alpha 1 beta 1, alpha v beta 3), and to E8 (alpha 6 beta 1, alpha v beta 3). The alpha v beta 3 integrin binds to the P1 fragment of LN in an RGD peptide-dependent manner, and to the E8 fragment in an RGD-independent manner; the RGD site on the P1 fragment probably is not available to the cell in intact LN. Antibodies against beta 1 integrins completely inhibit SMC adhesion to LN; antibodies against the alpha v beta 3 integrin do not block SMC adhesion to LN, but do prevent cell spreading. LN is also capable of interfering with SMC adhesion to other ECM components. The antiadhesive effect of LN is located in the E1' domain. Both exogenous and endogenous LN increase SMC motility on collagen I. The locomotion-promoting activity of LN resides in the E1' antiadhesive domain, and not in its adhesive (P1, E8) domains. LN causes a decrease in the number of focal contacts on collagen I. This might enable SMC to alter their mobility as they move through the extracellular matrix to occlude the ductus arteriosus lumen.

Amino Acid Sequence

Polymerase chain reaction amplification of culture supernatants for rapid detection of Borrelia burgdorferi.

A combination of culture and polymerase chain reaction (PCR) amplification was employed to detect Borrelia burgdorferi in in vitro cultures of skin biopsy specimens. Spirochetes were observed by microscopic examination in 56% (20/36) of the cultures from patients with erythema migrans who had not received prior antibiotic treatment. No growth of Borrelia burgdorferi was detected in control cultures or those from patients who had received antibiotics. PCR analysis of culture supernatants agreed with microscopic evaluation in 50/51 evaluable cultures tested (both positive and negative). At two weeks of incubation Borrelia burgdorferi could be detected by PCR in 19/20 cultures (95%) compared to 14/20 (70%) by visual inspection. This study indicates that a combined culture-PCR test for detection of Borrelia burgdorferi is more rapid and specific than culture alone.

Borrelia burgdorferi Group

Failure to isolate Borrelia burgdorferi after antimicrobial therapy in culture-documented Lyme borreliosis associated with erythema migrans: report of a prospective study.

BACKGROUND: Borrelia burgdorferi, the etiologic agent of Lyme borreliosis, has occasionally been isolated from tissues or body fluids of patients after antimicrobial treatment. A prospective study of patients with Lyme borreliosis associated with erythema migrans (EM) was initiated in Westchester County, New York, to determine: (1) the clinical and laboratory parameters associated with culture positivity, and (2) the microbiologic response to treatment. METHODS: Skin biopsies were performed in patients with EM and cultured for B. burgdorferi in modified Barbour-Stoenner-Kelly medium at 33 degrees C. Subsequent biopsies for culture were performed adjacent to the original biopsy site for culture-positive patients after the completion of antimicrobial therapy. RESULTS: Initial biopsy cultures were performed for 44 patients; 6 were unevaluable due to culture contamination with other bacteria. Cultures were positive in 21 of 29 patients prior to treatment (72%), but in none of 9 patients during treatment (p < 0.001). The only other identified factor associated with successful recovery of B. burgdorferi was shorter duration of EM. When patients who had received prior antimicrobial therapy were excluded, the mean duration of the EM lesion for those with positive cultures was 5.0 +/- 5.2 days compared with 14.6 +/- 9.9 days for those with negative cultures (p < 0.01). B. burgdorferi could not be reisolated from any of 18 evaluable subsequent biopsies of skin from 13 culture-positive patients 4 to 209 days after completion of a course of antimicrobial therapy. Five patients had negative subsequent biopsy cultures on two separate occasions 3 to 5 months apart. CONCLUSIONS: After brief courses of antibiotics, B. burgdorferi appears to be rapidly eliminated from the skin at EM sites. The ability to recover B. burgdorferi from skin biopsy cultures of untreated patients with EM lesions wanes with increasing duration of EM, suggesting that this organism may also be spontaneously cleared from skin over time.

Adult

AIDS-associated Kaposi's sarcoma in Romanian children.

BACKGROUND: Kaposi's sarcoma (KS) is commonly associated with the acquired immunodeficiency syndrome (AIDS) in adults. Little is known regarding its occurrence in children. OBJECTIVE: Our purpose was to report the clinical and epidemiologic characteristics of KS in three Romanian children with AIDS and to compare them with previously reported AIDS-associated KS in children. METHODS: This was a clinicopathologic study and computer-based literature review. RESULTS: All three Romanian children had skin involvement; two had involvement of lymph nodes and internal organs. All had acquired human immunodeficiency virus (HIV) infection postnatally. Including these children, 33 cases of AIDS-associated KS in children have been reported. Thirteen of 30 evaluable patients had acquired HIV infection postnatally; nine of these children (69%) had cutaneous involvement by KS. A perinatal route of transmission was present in the remaining 17 cases; only two of these children (12%) with KS had cutaneous involvement. No case was noted in which intravenous drug use was the sole parental HIV risk factor. CONCLUSION: The data support the contention that KS is caused by a second infectious agent prevalent only in certain HIV-infected populations. Children of parents in high-risk groups for KS and children who acquire HIV via contaminated blood or blood products are at highest risk for KS. The route of acquisition of HIV infection may also be associated with different clinical manifestations of KS in children.

Acquired Immunodeficiency Syndrome

NMR studies of diffusional water permeability of red blood cells from macropodid marsupials (kangaroos and wallabies).

1. The water permeabilities of the red blood cell (RBC) membranes of five species of macropodid marsupials were monitored by using a Mn(2+)-doping 1H nuclear magnetic resonance (NMR) technique. 2. Since this appears to be the first time that this type of measurement at 400 MHz for 1H has been reported, an analysis of instrumental parameters influencing the estimated value of the water exchange time (Te), and of the diffusional water permeability (Pd), was performed on samples of human RBC. 3. It was found that a short interpulse delay in the Carr-Purcell-Meiboom-Gill pulse sequence had to be used (around 100 microseconds) to avoid an underestimation of the relaxation times, that occurred as the result of molecular diffusion through non-uniform local magnetic fields in and around the cells. 4. There were no significant differences, in the water permeabilities of the RBC membranes, between the five species (Macropus rufogriseus, M. parma, M. eugenii, M. parryi and Wallabia bicolor). 5. There were also no significant differences between various colonies of M. eugenii living in different habitats. 6. The average values of Pd were 9.1 x 10(-3) cm/sec at 24.6 degrees C, 10.4 x 10(-3) cm/sec at 30 degrees C, 12.6 x 10(-3) cm/sec at 37 degrees C, and 14.7 x 10(-3) cm/sec at 42.1 degrees C; these were more than twice as high as those for human RBC. 7. In agreement with the high water permeability the RBC of macropodids displayed a relatively low activation energy of water diffusion across their membranes, approximately 21 kJ/mol, compared with 25 kJ/mol for human RBC.

Animals

The management of acute bronchiolitis. Thoracic Society of Australia and New Zealand.

The management of acute bronchiolitis is mainly supportive, but infants require minimal handling. Of those who are hospitalized, less than 3% require intensive care and ventilation but in these children the condition is life threatening. Oxygen, fluid replacement and careful observation remain the cornerstones of management. Bronchodilators should be avoided in young infants and antiviral therapy should only be considered in critically ill infants who have an underlying cardiopulmonary condition.

Acute Disease

Randomized trial of umbilical arterial catheter position: clinical outcome.

In order to determine if umbilical arterial catheter position affects the incidence of necrotizing enterocolitis, clinical outcome was analysed in 308 infants whose umbilical arterial catheter had been randomly allocated to a high (n = 162) or a low (n = 146) position. Necrotizing enterocolitis was classified as suspected or confirmed; all renal, lower limb and local catheter complications were also recorded. High umbilical arterial catheters were in place for longer than low catheters, provided more samples and were removed as an emergency less often. Lower limb blanching and cyanosis were more common with low catheters. Eleven cases of confirmed necrotizing enterocolitis occurred in the "high" group and nine in the "low" group. One case of fatal aortic thrombosis was encountered in the high group. Positioning umbilical arterial catheters in a high position allowed longer functional use and did not increase the incidence of necrotizing enterocolitis.

Catheterization

Early detection of de novo hepatitis C infection in patients after liver transplantation by reverse transcriptase polymerase chain reaction.

BACKGROUND: Reverse transcriptase polymerase chain reaction (RT-PCR) can detect the viral genome and show hepatitis C recurrence in patients who undergo transplantation for chronic hepatitis C viral (HCV) infection. We investigated the utility of an RT-PCR-based HCV assay for early detection of viral RNA in de novo HCV infection after liver transplantation. METHODS: Pretransplantation antibodies and explanation HCV viral RNA status were obtained from 117 patients. Follow-up liver biopsy specimens were examined for evidence of hepatitis activity. Plasma samples during the period of time of the biopsy were assayed for HCV antibody and viral RNA. RNA was extracted from samples and reverse transcribed to cDNA. cDNA was amplified by PCR, and products were detected by liquid hybridization. RESULTS: Clinical hepatitis developed in seventeen of 117 patients who, before transplantation, were HCV antibody negative and explant viral RNA negative. Ten patients were plasma PCR negative and had known non-hepatitis C causes for the biopsy findings. Of the remaining seven patients, five (70%) were plasma RT-PCR positive before seroconversion in matched plasma samples. CONCLUSIONS: In liver transplant patients, the incidence of de novo clinical hepatitis is low, and HCV viral RNA in de novo clinical hepatitis C infection can be detected in the absence of HCV antibodies.

Base Sequence

Varicella-zoster virus infection in Romanian children infected with the human immunodeficiency virus.

OBJECTIVE: Varicella-zoster virus (VZV) infections can cause severe disease in immunocompromised individuals. To evaluate the spectrum of VZV infections in human immunodeficiency virus (HIV)-infected children, we retrospectively analyzed all the cases of VZV infection in a cohort of children cared for at a hospital for infectious diseases in Bucharest, Romania. METHODS: The records of 391 HIV-infected children admitted to the acquired immunodeficiency syndrome pavilion of Colentina Hospital during the period January 1, 1991, through March 31, 1992, were reviewed for evidence of VZV infection. The diagnosis of varicella or zoster was made clinically and information was collected concerning course of the illness, number of skin lesions, and clinical evidence of complications. Lymphocyte subpopulation typing, as an estimate of immune function, was performed by either a standard fluorescent activated flow cytometric method or by immunofluorescent technique. RESULTS: Thirty-eight cases of varicella (9.7%) and seven cases of zoster (1.8%) were adequately documented among the 391 records reviewed. The duration of varicella was prolonged; in 57% of the children it was greater than 10 days. Forty percent of children with varicella developed a complication, including superinfection of the skin, pneumonia, or thrombocytopenia. None of the children developed clinical hepatitis or encephalitis. Two children (5%) died during varicella, both of respiratory failure. None of the 7 children with zoster had chronic, recurrent, or disseminated lesions. Lymphocyte subset analysis was available for 22 of 38 children with varicella and 3 of 7 children with zoster. Fifteen of the 22 children had normal, age-adjusted, absolute CD4 counts within 3 months of the diagnosis of varicella. All 3 children with zoster who had lymphocyte subset analysis had low CD4 counts and absolute numbers. None of the 45 children received antiretroviral therapy and only 1 child with varicella and 1 with zoster received acyclovir. CONCLUSIONS: The spectrum of VZV infection in this hospitalized group of HIV-infected children was broad. The majority (57%) experienced a prolonged course of disease and a higher rate of complications than normal children hospitalized with varicella.

CD4-Positive T-Lymphocytes

Use of a novel technique of cutaneous lavage for diagnosis of Lyme disease associated with erythema migrans.

OBJECTIVE: Determining the microbial cause of cellulitis is often difficult. In this study, a novel two-needle lavage technique was used to culture Borrelia burgdorferi from the skin of suspected erythema migrans lesions. DESIGN: The yield of lavage cultures for B burgdorferi was compared with that of a 2-mm skin biopsy sample. SETTING: A Lyme disease diagnostic center located in an area in which Lyme disease is epidemic. PATIENTS: Forty-five patients with suspected erythema migrans who had not been treated with antimicrobial agents. INTERVENTION: Cutaneous lavage of the advancing edge of a suspected primary erythema migrans lesion was done for all 45 participants, 33 of whom also had a skin biopsy of the same lesion at an identical (14) or an adjacent (19) site. MAIN OUTCOME MEASURES: Growth of B burgdorferi in in vitro culture. RESULTS: Lavage fluid cultures grew B burgdorferi in 13 (29%) of the 45 cases (95% confidence interval [CI], 16% to 44%). Among the 33 cases in which both lavage and skin biopsy cultures were done, the yield of lavage culture was less than that of biopsy culture (P less than .09, 12/33 vs 20/33). If contaminated cultures are excluded, this difference is significant (P less than .05, 12/30 vs 20/27). CONCLUSION: Cutaneous lavage is a new diagnostic technique for recovery of B burgdorferi from erythema migrans lesions that has potential applicability to other types of cutaneous infections.

Biopsy

Growth of the normal human lower urinary tract from 12 to 21 weeks gestation.

Normal development of the human lower urinary tract was studied between the 14th and 20th week of gestation using 3 modes of fixation. Fixation by direct distension provides a high degree of reproducibility of parameters used to study the growth of the fetal bladder. Using this method, fetuses ranging from 12 to 21 weeks gestation were studied. Results obtained demonstrate that the length of the bladder, the inter-ureteric distance, and the distance between the apex of the trigone and the distal tip of the urethra occur in a linear mode. Furthermore, the rate of growth of the male urethra was evidently higher when compared to that of the female from the 12th week of gestation. Data from this work can be used for a more accurate assessment of cases with abnormal lower urinary tract development.

Female

Photosensitivity, abnormal porphyrin profile, and sideroblastic anemia.

Cutaneous photosensitivity in a 43-year-old man with idiopathic sideroblastic anemia associated with an abnormal porphyrin profile is reported. This condition was associated with elevated free erythrocyte porphyrin, plasma protoporphyrin, urine porphyrins (predominantly coproporphyrin), stool porphyrins (predominantly protoporphyrin), decreased ferrochelatase activity, and deletion of portions of the long arms of chromosomes 18 and 20. Five other patients with sideroblastic anemia and abnormal porphyrin profiles have been described; all but one of these patients had photosensitivity. The porphyrin profile of this patient is similar to that of three other previously described patients.

Adult