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Biomedical subjects

J L Sever

Publications and source records attributed to J L Sever.

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

Detection of human immunodeficiency virus type 1 infection in young pediatric patients by using polymerase chain reaction and biotinylated probes.

Polymerase chain reaction (PCR) testing using up to four primer pairs and biotinylated probes was 97.9% sensitive (188 of 192 specimens positive) and 100% specific (267 of 267 specimens negative) for detecting the presence or absence of human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells from pediatric patients whose HIV status has been confirmed. SK38/39 and SK145/150 were the most sensitive primer pairs, respectively detecting HIV DNA in 95.6 and 95.9% of peripheral blood mononuclear cell specimens from HIV-infected children and collectively detecting all adequately tested PCR-positive specimens. Primer pairs SK29/30 and SK68/69 respectively detected HIV DNA in only 76.4 and 76.6% of HIV-positive specimens. Among infants born to HIV-seropositive mothers, 30 who subsequently were confirmed to be infected were sampled when they were less than or equal to 6 months of age; in all but one infant, HIV DNA was found in the first specimen collected. Among the nine youngest infected infants tested, all were PCR positive by 38 days of age. PCR methods thus have reliably detected vertically transmitted HIV infection early in life.

Acquired Immunodeficiency Syndrome

Toxoplasmosis.

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Adult

Limitations in the laboratory diagnosis of vertically acquired HIV infection.

At present, the only well-standardized and widely available diagnostic techniques for HIV infection are detection of IgG HIV antibodies and HIV antigen. The antibody detection is sensitive, but is useful only in infants and children older than 15 months because of the presence of maternal antibodies. The utility of HIV antigen testing in neonates and young infants has not been established. A number of sensitive techniques, such as PCR, ELISPOT, and detection of HIV-specific IgM and IgA antibodies, are under development and promise to be very useful in the early diagnosis of vertical HIV infection. However, we will be able to accurately establish the sensitivity or specificity of the individual tests only when we have results of large prospective studies. These studies should compare different diagnostic methods and correlate the results of tests performed sequentially in neonates and young infants with the natural history of their disease process and eventual clinical outcome.

AIDS Serodiagnosis

Perinatally acquired infections and screening.

For hepatitis B, universal screening of pregnant women for HBsAg along with the combined use of hepatitis B vaccine and HBIG in infants of infected mothers appears to be the best way to detect and prevent vertically transmitted infection. Cytomegalovirus is the most common congenital viral infection, but the lack of a good screening test precludes its accurate and rapid diagnosis. For HPV-B19, larger and more controlled studies are needed to confirm the safety and effectiveness of fetal blood transfusions in the management of hydrops fetalis caused by this infection. Finally, the fact that most mothers of HSV- and toxoplasma-infected neonates have no history of infection, and are asymptomatic at the time of delivery, underscores the need for a high index of clinical suspicion in sick neonates.

Cytomegalovirus Infections

HIV: biology and immunology.

The HIV virus grows in lymphocytes, monocyte-macrophages and possibly a few other cells of the human body. This is an RNA virus that attaches at the CD4 receptor, enters the cell, and makes DNA by using a reverse transcriptase enzyme. The virus is about 100 nm in diameter and expresses several surface and core antigens. Growth of the virus in the helper (T4) lymphocytes results in destruction of these cells. This, in turn, results in loss of cellular immune functions that causes susceptibility to infections and malignancies. Monocyte-macrophage cells are also infected but these cells are not lysed. Antigen to HIV appears in blood a few weeks after infection but disappears as antibody begins to be present. Antibody can be detected by a variety of tests but ELISA and Western blot assays are used most frequently. New latex and other methods are being licensed for use under certain circumstances.

Acquired Immunodeficiency Syndrome

AIDS and neurological disorders: an overview.

Neurological disease occurs frequently in patients infected with the human immunodeficiency virus. Disorders may affect either the central or peripheral nervous systems and may be the presenting manifestation of human immunodeficiency virus-related disease. Opportunistic infections and lymphomas are major causes of central nervous system disease. Increasingly, however, human immunodeficiency virus infection of the central nervous system is being recognized and is now associated with a syndrome of progressive dementia in adults, referred to as the acquired immunodeficiency syndrome dementia complex, and an encephalopathy in infants born to human immunodeficiency virus-infected mothers. Whether brain disease related to this virus will respond to antiretroviral drugs will be a major focus of future research. Although less frequent than central nervous system disease, disorders of the peripheral nervous system are increasingly being recognized, including cases that probably have an autoimmune basis.

Acquired Immunodeficiency Syndrome

Treatment of human immunodeficiency virus-related polyneuropathy with 3'-azido-2',3'-dideoxythymidine.

A 72-year-old woman with human immunodeficiency virus (HIV)-related axonal polyradiculoneuropathy of the lower extremities was treated with 3'-azido-2',3'-dideoxythymidine (AZT), 250 mg every 4 hours. Before therapy she had rapidly progressive weakness in both legs and when treatment began she could move only her toes. Six weeks after therapy, there was mild improvement in her strength, which peaked 2 months later. At her best, she was able to lift her leg 30 degrees off the bed and stand with assistance. Improvement, which was also demonstrated electrophysiologically, was short lived and partially declined when AZT was discontinued. This case demonstrates that some patients with HIV-related axonal neuropathies even in advanced stages can show objective signs of improvement when given AZT. A systematic trial with AZT in the treatment of patients with HIV-related polyneuropathies is therefore warranted.

Acquired Immunodeficiency Syndrome

Tropical spastic paraparesis: clinical, immunological, and virological studies in two patients from Martinique.

Two patients from Martinique with tropical spastic paraparesis had antibodies to human T-lymphotropic virus type I (HTLV-I) in serum and spinal fluid but no antibodies to other retroviruses tested. They presented with spastic weakness of both lower extremities, hyperreflexia with upgoing toes, sphincteric dysfunction, and normal sensation. By means of agarose isoelectric focusing and selective immunoblotting we demonstrated an increased intrathecal synthesis of IgG antibodies to HTLV-I in the spinal fluid. Unique oligoclonal bands of IgG antibodies to HTLV-I were present in the cerebrospinal fluid. Using a battery of monoclonal antibodies we also found in these patients an increased number of circulating T cells that expressed activation markers. We conclude that the HTLV-I retrovirus associated with tropical spastic paraparesis has both lymphocytotropic and neurotropic properties.

Adult

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

Risk of adverse outcomes of pregnancy after human parvovirus B19 infection.

Human parvovirus B19 (B19) infection during pregnancy has been associated with fetal deaths. We conducted several studies to develop data needed to make recommendations for preventing fetal death associated with infection. In the first study, after an outbreak of B19 infection, specimens of cord blood from 47 infants with congenital anomalies, 10 with suspected intrauterine infection, and gestational age-matched controls were tested for IgG and IgM antibodies to B19. None had evidence of recent infection. Next, 192 women with unknown exposure to B19 who had stillbirths or spontaneous abortions were studied. Two patients and two controls had evidence of recent B19 infection. In a second case-control study of women who had stillbirths after outbreaks of erythema infectiosum in area schools, none of the 20 patients or 26 controls were IgM positive at the time of delivery. The rate of infection, as demonstrated by IgM positivity, among 267 pregnant control subjects was approximately 1%. These studies suggest that among pregnant women unselected for exposure to B19, neither infection nor stillbirths are common.

Antibodies, Viral

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