Biomedical subjects
Publications and source records attributed to R S Janssen.
This case-control study of 39 homosexual or bisexual men who were human immunodeficiency virus (HIV)-seropositive and had lymphadenopathy syndrome and 38 HIV-seronegative homosexual or bisexual men indicates an association between neurological and neuropsychological abnormalities and HIV infection in patients with lymphadenopathy syndrome.
PURPOSE: Human adult T-cell leukemia-lymphoma is a malignant, proliferative disease of CD4+ lymphocytes associated with infection with human T-cell lymphotropic virus type I (HTLV-I). Following the presentation of a patient who was infected with the virus, we undertook a study of his family members and sexual contacts to see if a cluster of infected persons could be identified. CASE REPORT: A black heterosexual North Carolina native with a history of drug abuse presented with jaundice, and pancytopenia subsequently developed. He then became hypercalcemic and leukemic, with high numbers of circulating, morphologically abnormal CD4+ lymphocytes. RESULTS: As determined by radioimmunoassay and immunoblot analyses, the serum of the index case contained antibodies against core proteins (p19 and p24) of HTLV-I. When cultured in vitro with interleukin-2, the lymphocytes expressed HTLV-I specific core proteins. The virus recovered from these T cells was transmitted to cord blood T cells, which became immortalized for continuous growth in vitro, expressed HTLV-I p19 protein, and displayed characteristic C-type particles by electron microscopy. Studies of family members and sexual contacts, all of whom were black, heterosexual central North Carolina natives, revealed five of 28 whose serum had anti-HTLV-I antibodies as determined by radioimmunoassay and immunoblot. Neither the patient nor the seropositive family/contacts had antibodies against human immunodeficiency virus proteins. Four of the six people with HTLV-I infection had no history of intravenous drug abuse. Three of the five seropositive family/contacts had circulating, morphologically abnormal lymphocytes suggestive of "preleukemic" or "smoldering" human adult T-cell leukemia-lymphoma.
Data from the Centers for Disease Control (CDC) and from the hospitals affiliated with the University of California, San Francisco show a significant incidence of neurological complications in AIDS patients and suggest that patients from different risk groups and geographic regions are at different relative risk for specific neurological complications. CDC national surveillance data show that Haitian-born AIDS patients are 3.7 times more likely to have neurological complications than are patients in other risk groups; neurological illness is also reported more often in intravenous drug abusers and black AIDS patients. Cryptococcal meningitis is most prevalent among intravenous drug abusers, Haitians, and blacks, and is most commonly reported in New Jersey, a state with a large proportion of AIDS patients in these three groups. Cerebral toxoplasmosis is reported much more often in Haitians than in other risk groups and is most prevalent in Florida among both Haitians and non-Haitians, probably because of greater exposure to Toxoplasma gondii organisms in the semitropical climate of Florida. The prevalence rates for progressive multifocal leukoencephalopathy (PML) and primary central nervous system lymphoma are similar throughout various risk groups and regions of the United States.
We report an outbreak of thyrotoxicosis without true hyperthyroidism that occurred between April 1984 and August 1985 among residents of southwestern Minnesota and adjacent areas of South Dakota and Iowa. One hundred twenty-one cases were identified through surveillance of medical clinics, laboratories, hospitals, and physicians' offices. Investigation of the outbreak demonstrated an association between the occurrence of thyrotoxicosis and the consumption of ground beef prepared from neck trimmings processed by a single slaughtering plant (odds ratio, 19.0; P = 0.0001). The cause was confirmed by the findings of bovine thyroid tissue in samples of these trimmings and high concentrations of thyroid hormone in implicated samples of ground beef and the demonstration of prompt increases in serum thyroid hormone concentrations in volunteers who ate the implicated ground beef. Bovine thyroid tissue had been introduced into the neck trimmings inadvertently during the process of "gullet trimming," a procedure that harvests muscles from the bovine larynx. The outbreak resolved after this procedure was discontinued at the plant. The clinical features of the illness suggested the diagnosis of silent thyroiditis, and it is possible that sporadic cases--or even outbreaks--of thyrotoxicosis factitia caused by this mechanism may have occurred in the past but were not recognized.
To identify which RNA segments of the California serogroup bunyaviruses determine virulence, we prepared reassortant viruses by coinfecting BHK-21 cells with two wild-type parents, La Crosse/original and Tahyna/181-57 viruses, which differed about 30,000-fold in virulence. The progeny clones were screened by polyacrylamide gel electrophoresis to ascertain the phenotype of the M and S RNA segments, and RNA-RNA hybridization was used to determine the genotype of selected clones. Two or three clones of each of the six possible reassortant genotypes were characterized quantitatively for neuroinvasiveness by determining the PFU/50% lethal dose (LD50) ratio after subcutaneous injection into suckling mice. The reassortants fell into two groups. (i) Six of seven reassortants with a La Crosse M RNA segment were as virulent as the parent La Crosse virus (about 1 PFU/LD50); the one exception was strikingly different (about 1,000 PFU/LD50) and probably represents a spontaneous mutant. (ii) The seven reassortants with a Tahyna M RNA segment were about 10-fold more virulent than the parent Tahyna virus (median 1,600 PFU/LD50 for reassortants and 16,000 PFU/LD50 for Tahyna virus). A comparative pathogenesis study in suckling mice of one reassortant virus and the parent Tahyna virus confirmed the greater neuroinvasiveness of the reassortant virus. From these data it was concluded that the M RNA segment was the major determinant of virulence, but that the other two gene segments could modulate the virulence of a nonneuroinvasive California serogroup virus.
La Crosse virus, a member of the California serogroup of the family Bunyaviridae, causes encephalitis in humans and laboratory rodents. A variant virus (V22) selected with a monoclonal antibody against the large (G1) glycoprotein showed diminished neuroinvasiveness after peripheral inoculation. This variant has an alteration in its fusion function, requiring a lower pH for the activation of fusion and demonstrating reduced efficiency of cell-to-cell fusion of BHK-21 cultures. V22 was studied in detail following the infection by intraperitoneal or intracerebral routes in suckling, weanling, or adult CD-1 mice. It exhibited a marked reduction in its ability to replicate in striated muscle and to produce viremia; however, after intracerebral injection V22 virus replicated almost as rapidly in brain as its parent, La Crosse virus. V22 virus thus represents an example of reduced neuroinvasiveness associated with an alteration at a specific epitope of the G1 glycoprotein. This same epitope also influences the fusion activity of the glycoprotein.
Central nervous system involvement in melioidosis is unusual. We describe a 34-year-old man who developed a Pseudomonas pseudomallei meningitis, manifested as bilateral third-nerve palsies, 13 years after having been in southeast Asia. Diagnosis was established by a fourfold rise in the serum antibody titer for the bacterium. Recovery occurred after treatment with rifampin, isoniazid hydrochloride, ethambutol, and trimethoprim-sulfamethoxazole. Since a long latent period from exposure to overt infection is possible, additional cases of melioidosis in the United States can still be expected in veterans of the Vietnam War.
We reviewed the records of 36 patients with myasthenia gravis who had CT of the anterior mediastinum before thymectomy in an effort to improve preoperative detection of thymoma. At surgery, 10 patients had thymomas, 21 had germinal center follicular hyperplasia, and 5 had histologically normal glands. CT performed on an EMI 5005 was abnormal in 23 of 36 patients; 10 had thymoma, 11 had hyperplasia, 1 had a normal gland, and 1 had a cyst. Tumors were detected by routine chest x-ray in 5 of 10 patients and by linear tomography in 7 of 8. All four patients with calcified masses on CT had thymomas (including the patient with normal linear tomograms). CT alone is too sensitive a screening test; 12 of 25 patients with hyperplasia or normal glands had abnormal scans. However, in combination with chest x-ray and linear tomography, we detected 10 of 10 patients with thymoma with reasonable certainty.
The Centers for Disease Control and Prevention has developed guidelines for determining HIV seroprevalence among patients seeking medical care at acute-care hospitals. The guidelines enable hospital staff members to perform a simple, rapid, and inexpensive survey to determine seroprevalence among the patient population, protecting the anonymity of those who are tested. The guidelines are based on national experience with large-scale anonymous, unlinked HIV serosurveys. The data from a rapid assessment survey are particularly useful for evaluating the need to provide routine, voluntary HIV counseling and testing and treatment for HIV infection. Beyond that, such data can be used in targeting education efforts, in reinforcing the use of appropriate universal precautions, in resource allocation, and in determining the need for further studies of HIV infection among the population in the hospital catchment area.