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Biomedical subjects

D L Madden

Publications and source records attributed to D L Madden.

At least 19 recordsLinked to original sources

Perinatal 'TORCH' infections identified by serology: correlation with abnormalities in the children through 7 years of age.

A matched case-control methodology was used to assess the risk for a wide range of abnormalities in children associated with serological evidence for 'TORCH' infections in the mothers. Specimens were selected from the large bank of sera from the approximately 54,000 pregnant women who participated in the Collaborative Perinatal Project. There was no clear association between any of the antigens studied and any specific damage to the child. These 'negative' findings are consistent with the absence of frequent significant effects due to these agents in the second and third trimesters of pregnancy.

Case-Control Studies

Increased peripheral lymphocytes, lymphoid hepatitis and anaemia in African vervet monkeys seropositive to retroviruses.

Wild-caught African Vervet monkeys are commonly infected by Simian T-lymphotropic virus I (STLV1) and Simian immunodeficiency virus (SIV), yet the natural histories of these infections are largely unknown. Seropositivity was associated with increased total, T and atypical lymphocytes. In seropositive females there was mild, normocytic, normochromic anaemia. Lymphoid hepatitis was present in seven seropositive cases. African Vervets used in biomedical research, vaccine production and organ transplantation research are often infected by exogenous retroviruses which can be oncogenic and immunosuppressive in captive monkeys. Elimination of these infections may be possible by breeding Vervets in captivity.

Anemia

Serological survey for viral diseases in the Cayo Santiago rhesus macaque population.

The free-ranging population of rhesus monkeys (Macaca mulatta) on Cayo Santiago was sero-surveyed for human measles, simian virus 40, B virus (Herpes simiae), rhesus cytomegalovirus, human and simian retroviruses and encephalomyocarditis virus to determine the prevalence of these viruses in the colony. The results of this study indicate that the colony is free of SV40, HTLVIII (HIV-1), STLVIII (SIV) and SRV1; has a low prevalence of measles and EMCV; and high prevalence rates for B virus, CMV and HTLVI.

Academies and Institutes

Antibody to human and simian retrovirus, HTLV-I, HTLV-II, HIV, STLV-III, and SRV-I not increased in patients with multiple sclerosis.

We have tested sera from patients with multiple sclerosis, matched controls, and those with other neurological diseases, as well as sera from patients with the acquired immunodeficiency syndrome and controls and patients with tropical spastic paraparesis (TSP) and controls for antibody to human T-lymphotropic virus type I (HTLV-I), HTLV-II, human immunodeficiency virus (HIV), simian T-lymphotropic virus type III, or simian retrovirus type I by immunofluorescent activity test, and for HTLV-I and HIV by the ELISA method. Sera from patients with multiple sclerosis and matched controls, and from patients with optic neuritis and Parkinson's or other neuromuscular diseases did not have antibody to any of the retroviruses tested. Specimens from TSP patients and some controls contained HTLV-I antibody. We conclude from our study that only TSP patients had serological evidence of infection with one of the retroviruses studied.

Acquired Immunodeficiency Syndrome

Multiple sclerosis in the Faroe Islands. IV. The lack of a relationship between canine distemper and the epidemics of MS.

Clinical onset of multiple sclerosis (MS) occurred in 32 native resident Faroese between 1943 and 1973, comprising 3 consecutive epidemics of decreasing frequency. Relationship of MS with the appearance of canine distemper (CD) was explored by serologic studies, questionnaires, and veterinarian reports. Tested were sera from 12 MS patients and 112 controls among the 22 patients and 192 controls with questionnaires in 1978-1979. The daily treatment ledgers of the Veterinarian of the Faroes 1940-1961 were also reviewed and additional Faroese interviewed 1987-1988 as to CD. History of CD was determined for residence of all 32 MS. There was no evidence of elevated CD antibody titers in MS vs controls for neutralizing titers or ELISA values, nor to ELISA for measles. In the questionnaires only one patient and 2 of his sibs reported owning (the same) dog(s) with CD during the war. One other patient reported a possibly sick dog but not CD. CD occurred in one southern village 1941-1942, was present on Vágar from 1941-1950, and was epidemic on Streymoy 1944-1945 with scattered cases there and elsewhere through 1950. There was no significant correlation between villages with CD and MS residents. We conclude that the occurrence of multiple sclerosis was not related to the presence of canine distemper or sick dogs in the Faroe Islands.

Animals

Serologic studies of MS patients, controls, and patients with other neurologic diseases: antibodies to HTLV-I, II, III.

We have studied the frequency of human retrovirus antibody (HTLV-I, II, III) in the serum and CSF of patients with MS, matched controls, and patients with optic neuritis, idiopathic and postencephalitic Parkinson's disease, neuropathies, polymyositis, ALS, and postpoliomyelitis. Except for the postpoliomyelitis samples, all samples were collected prior to 1980. Contrary to a previous published report, no significant levels of antibody to HTLV-I, II, or III were found in the MS patients or controls. No retrovirus antibody was detected in patients with the other neurologic diseases.

Antibodies, Viral

Toxoplasmosis: maternal and pediatric findings in 23,000 pregnancies.

An analysis of the antibody titers to toxoplasmosis for 22,845 pregnant women in the Collaborative Perinatal Project was conducted in relation to clinical and laboratory findings in the mothers and children through 7 years of age. More than 900 observations were considered for each mother and child. The major findings were in the children and included a predicted doubling in the frequency of deafness among children born to women with antibody to toxoplasmosis, a predicted 60% increase in microcephaly, and a 30% increase in low IQ (less than 70) in association with the presence of high maternal antibody titer (256 to 512) to toxoplasma. A serologically defined high-risk group of mothers was identified on the basis of high indirect hemagglutination antibody levels or seroconversions and increased IgM toxoplasma antibody levels (indirect fluorescent antibody greater than or equal to 32, enzyme-linked immunosorbent assay greater than or equal to 0.7). Of the 15 pregnancies in this group, two children had congenital toxoplasmosis and three were stillborn.

Antibodies

Human T-lymphotropic virus type I antibodies in the serum of patients with tropical spastic paraparesis in the Seychelles.

Tropical spastic paraparesis (TSP), a chronic myelopathy of unknown etiology, was studied in the Seychelles. Human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus antibodies were determined using an enzyme-linked immunosorbent assay and confirmed with an indirect fluorescent antibody test in serum samples of 20 patients with TSP and 16 controls. Test results indicated that 17 patients (85%) and two controls (transverse myelopathy and clinically probable multiple sclerosis) were positive for HTLV-I. Serum samples of nine healthy controls and five with other neurologic diseases were negative for HTLV-I. No serum samples were positive for human immunodeficiency virus. Estimated relative risk for TSP in those subjects whose serum is positive for HTLV-I antibodies is 40. This result is highly statistically significant. Although primarily associated with adult T-cell leukemia and non-Hodgkin's lymphoma, HTLV-I could also be an etiologic agent of TSP.

Adult

Predictors of clinical AIDS in young homosexual men in a high-risk area.

One hundred and sixty-seven homosexual men in Los Angeles characterized by HIV antibody, T-cell numbers, titres to cytomegalovirus (CMV), and specific sexual practices were followed for two years for immune changes and for more than three years for development of clinical AIDS. Thirty-five per cent had antibody to HIV at baseline. The mean level of T-helper (Th) cells was significantly lower and of T-suppressor (Ts) cells significantly higher in HIV seropositives than in seronegatives. The annualized incidence of HIV seroconversion was 7%. Eight men developed AIDS, an attack rate of 14% in those with HIV antibody at baseline. A number of observations were made: T-cell alterations, except a transient elevation in Ts cells, were unusual in the absence of HIV antibody; a seropositive man with a T-cell alteration was significantly less likely to revert to 'within normal limits' than was a seronegative man; a steady decline in the number of Th cells preceded onset of clinical AIDS; the number of Ts cells remained higher in men subsequently developing AIDS than in other seropositive men; clinical AIDS occurred only in men with HIV antibody whose CMV antibody levels were above the median for the group (1:1600); and the attack rate for clinical AIDS was 50% in men with HIV antibody and elevated CMV who at baseline had either: fewer than 325 Th cells/cc, or whose Th/Ts ratio was below 0.8 (but whose levels of Th and Ts cells were within normal limits).(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome

Difficulties associated with serological diagnosis of Toxoplasma gondii infections.

Physicians often rely on serology to help determine whether a patient has had a recent infection with Toxoplasma gondii and as an aid in estimating the possible teratogenic effect on the fetus. For this reason the diagnostic laboratory should take every precaution to avoid misleading results. The best serological analysis is based on a rise in IgG titer with two appropriately spaced serum samples. Also, the presence of a high IgM titer in one serum sample is generally considered to be good evidence that infection has occurred recently. The indirect fluorescent antibody (IFA) test has been the most widely used test for detection of IgG or IgM. Recently enzyme-linked immunosorbent assays (ELISA) have also been developed for this purpose. In this study we reaffirm that false IgM positive results can occur with these tests because of the presence of rheumatoid factor in serum, and false negative results can also occur because of competitive inhibition by specific IgG. We show that a preabsorption of serum with a Staphylococcus/Streptococcus preparation (Staffinoc, MA Bioproducts, Walkersville, MD) removes IgG and IgA and eliminates many of the false reactions. We have also found that elevated levels of specific IgM can persist for at least several years in some women. This suggests that the presence of IgM alone is not always an indication of recent infection.

Enzyme-Linked Immunosorbent Assay

Administration of recombinant human leukocyte alpha 2-interferon in patients with amyotrophic lateral sclerosis.

Recombinant leukocyte alpha 2-interferon (with greater than 98% purity) was evaluated in a pilot treatment in six patients with amyotrophic lateral sclerosis and one patient with slowly progressive postpoliomyelitis motor neuron disease. Interferon, administered subcutaneously in doses of 2 million units three times per week for four months, was ineffective in improving, arresting, or slowing the pace of progression in all the patients who were followed up for ten to 14 months after the end of therapy.

Adult

Cross-sectional seroepidemiologic study of the prevalence of cytomegalovirus and herpes simplex virus infection in a Canadian Inuit (Eskimo) community.

The prevalence of antibody to cytomegalovirus (CMV) and herpes simplex virus (HSV) was determined, using enzyme-linked immunosorbent assay techniques, in a cross-sectional serologic survey of an isolated northern Canadian Inuit (Eskimo) community. The population studied included 155 Inuit and 11 Caucasian residents. By 6 years of age, 80% of the Inuit population were seropositive for CMV and 100% for herpes simplex virus. While only 7/63 Inuit greater than 20 years were seronegative for CMV, 5/11 Caucasian residents were seronegative (p = 0.01). For the Inuit population, no association between seropositivity for CMV and seropositivity for hepatitis A or hepatitis B was observed. This prevalence survey shows a serologic profile for infection with CMV and HSV in this northern Inuit community with an early age of acquisition and high prevalence of infection characteristic of socioeconomically deprived populations throughout the world, and is distinct from that observed in many other North American populations.

Adolescent

Immune defects in simian acquired immunodeficiency syndrome.

We recently reported a Simian Acquired Immunodeficiency Syndrome (SAIDS) in rhesus macaques at the California Primate Research Center. Here, we studied in vitro lymphocyte response to the mitogens Concanavalin A (Con A), phytohemagglutinin (PHA) and pokeweed mitogen (PWM) with and without interleukin 2 (IL-2). Immunoglobulin (IgG and IgM) and complement (C3 and C4) concentrations were determined by radial immunodiffusion. T helper and T suppressor lymphocytes were identified with the monoclonal antibodies OKT4 and OKT8. Concentrations of IgG and IgM were significantly (p less than .05) decreased. Complement component C3 did not change but C4 was increased. The absolute lymphocyte count decreased but the OKT4:OKT8 ratio was unchanged from controls. A decreased lymphocyte response to all mitogens occurred early and became more severely depressed near death. IL-2 caused a complete or partial restoration of the response to the mitogens CON A and PHA. Both the humoral and cell mediated immune responses are affected in SAIDS. The role of IL-2 in this immune defect must be studied further.

Acquired Immunodeficiency Syndrome

Immunologic alterations in monkeys with simian acquired immunodeficiency syndrome (SAIDS).

Levels of lymphocyte responsiveness to T- and B-cell-specific mitogens and expressions of Ia, T4, T8, and T11 surface markers were monitored during the course of Simian acquired immunodeficiency syndrome (SAIDS) in four Rhesus macaques that either died or became ill and survived. The monkey that died showed progressively suppressed responses to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM), and Staphylococcus aureus Cowan I strain (SAC) through the time of death (5 1/2 weeks). For the three animals that survived, the responses of peripheral blood mononuclear cell (PBMC) to the same mitogens were decreased significantly during the period 4-6 weeks after inoculation. Levels of Ia-bearing cells in the PBMC population were markedly reduced in the moribund monkey but were not significantly decreased in the three survivors. There was no significant change in the percentage of T11-bearing cells in any of the study animals. The ratio of T4- and T8-positive cells did not vary significantly during the 18 weeks of observation in any of the animals. The infected animals showed other evidence of immunosuppression including neutropenia, lymphopenia, and depletion of lymphocytes in lymph nodes. The animal that had progressive disease and death also had Kaposi-like lesions and staphylococcal septicemia. These results indicated that in vitro evidence of immunosuppression due to SAIDS appears within a few weeks after infection and this may progress in animals that die.

Acquired Immunodeficiency Syndrome

Improved separation of rhesus monkey lymphocytes with Percoll.

The total yield and the proportions of Rhesus monkey peripheral blood mononuclear cells (PBMC) with detectable T4, T8, T11 and Ia markers that were purified by density gradient centrifugation through solutions of polyvinyl pyrrolidone (Percoll) were significantly greater than those found in PBMC suspensions obtained by using Ficoll-Hypaque. The percentages of recovery of PBMC and of cells expressing the above markers were lowest among PBMC isolated with a Ficoll-Hypaque mixture of density 1.077 and highest among PBMC obtained by using a solution of Percoll of density 1.077. Percoll of density 1.077 was also better than Ficoll-Hypaque in that it yielded PBMC with the lowest levels of erythrocyte (less than 1%) and granulocyte (less than 1%) contamination. The reduced levels of PBMC with detectable markers appeared to result from an effect of either Ficoll or Hypaque on the lymphocytes rather than from loss of lymphocyte subpopulations since higher proportions of cells bearing T4, T8, T11 and Ia were found when PBMC were isolated with a solution of Percoll which yielded a percentage of PBMC as low as that recovered with Ficoll-Hypaque. Altered marker expression by cells obtained with Ficoll-Hypaque was not seen with similarly prepared human PBMC.

Animals