Dengue in north-east Africa.
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Biomedical subjects
Publications and source records attributed to R M Scott.
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An outbreak of measles presented an opportunity to examine the immune response of children initially immunized with measles vaccine before 1 year of age to reimmunization at 15 months of age with measles, mumps, and rubella vaccine. Eighteen previously immunized children had higher acute and convalescent hemagglutination inhibition titers than 13 control children. None of the previously immunized children had measles-specific IgM appear in convalescent serum samples. These results indicate a brisk secondary immune response to measles reimmunization in children immunized before 1 year of age. They support the recommendation of the American Academy of Pediatrics of reimmunization at 15 months of age for those children whose initial measles immunization was before 1 year of age.
The charts of 111 children with meningomyelocele were reviewed. Ninety-eight had shunted hydrocephalus. Twenty-five of 111 children (24 of 98 children with shunts) had seizures. Age at onset and type of seizure varied. Brain malformation (other than Arnold-Chiari), shunt infection, and perhaps number of shunt revisions were important risk factors in seizure development. The children with seizures were more likely to be developmentally delayed.
The optional 1143 bp intron in the yeast mitochondrial 21S rRNA gene (omega +) is nearly quantitatively inserted in genetic crosses into 21S rRNA alleles that lack it (omega -). The intron contains an open reading frame that can encode a protein of 235 amino acids, but no function has been ascribed to this sequence. We previously found an in vivo double-strand break in omega - DNA at or close to the intron insertion site only in zygotes of omega + X omega - crosses that appears with the same kinetics as intron insertion. We now show that mutations in the intron open reading frame that would alter the translation product simultaneously inhibit nonreciprocal omega recombination and the in vivo double-strand break in omega - DNA. These results provide evidence that the open reading frame encodes a protein required for intron transposition and support the role of the double-strand break in the process.
Serum concentrations of pregnancy associated alpha 2-glycoprotein (alpha 2-PAG) were measured serially by an enzyme linked immunosorbent assay during 24 pregnancies in 18 patients with Graves' disease and four with Hashimoto's thyroiditis. During each trimester, alpha 2-PAG levels were significantly higher than in normal pregnant controls, matched for week of gestation. Patients showing remission of disease activity had progressively higher alpha 2-PAG levels throughout pregnancy than those with active disease. The data support the idea that alpha 2-PAG may play an important role in inducing and maintaining the clinical remissions observed in some women with autoimmune thyroid disease during pregnancy.
Very late recurrent invasive squamous cell carcinoma of the cervix (over 10 years) after successful initial radiation treatment is a very rare occurrence (approximately 0.5%). Even though the treatment of choice has been radical surgery, there are a number of patients in whom surgery was regarded as undesirable. Ten such patients were reirradiated for these late recurrences after the full course of irradiation some 10 or more years ago. Six patients (six of ten) survived disease-free several years, while the remainder experienced relief of their symptoms. Factors determining success and failure are: (1) the extent of the recurrence (clinical stage); (2) the degree of tumor necrosis; (3) status of normal surrounding tissues; and (4) radiation treatment and doses, integration and individualization of the external beam and brachytherapy. Criteria for patient selection and treatment technique are discussed.
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In patients undergoing carotid endarterectomy, the role of preoperative computerized tomographic head scanning in predicting the risk of postoperative neurologic deficit was determined by a retrospective evaluation of a select group of 107 consecutive patients with preoperative scans. Patients with infarction determined preoperatively by computerized tomography were found to be at a significantly higher risk for postoperative neurologic deficit than patients with a normal preoperative computerized tomographic scan. History and physical examination alone detected only 66 percent of the infarctions found with preoperative computerized tomographic scanning in these patients. Because the incidence of infarction revealed computerized tomography in patients with symptoms of a reversible ischemic neurologic deficit was 22 percent, we have proposed a new definition of reversible ischemic neurologic deficit to include the necessary finding of a normal computerized tomographic scan. Patients who presented with transient ischemic attack and the unexpected finding of a subclinical infarction on the preoperative scan were at the same significantly higher risk for postoperative stroke and a permanent neurologic deficit. Computerized tomographic scanning of potential carotid endarterectomy patients is of benefit not only to rule out other sources of neurologic symptoms, but also to predict more accurately the risk of postoperative neurologic deficit.
A sham vaccine, prepared with the C6/36 cell line derived from larval Aedes albopictus mosquitoes, was skin tested on 12 volunteers. Although no reactions were observed after prick tests, three immediate reactions did occur after intradermal tests. Subcutaneous administration of the C6/36 sham vaccine was initially performed on the nine subjects who did not demonstrate immediate reactions. Five of these subjects developed delayed reactions at the site of the intradermal test within 12 hr after inoculation. A Prausnitz-Küstner test was performed on the back of one unsensitized subject by use of both unheated and heated sera from three subjects who had immediate skin reactions, three who demonstrated a delayed reaction, and one who had a negative skin response. In the Prausnitz-Küstner test, immediate skin reactions were observed with all seven unheated sera but with none of the heated serum aliquots. The determination that skin reactivity was associated with a heat-labile serum factor suggested the mechanism was IgE-mediated. Under close surveillance, the C6/36 sham vaccine was administered subcutaneously to one volunteer who had previously demonstrated an immediate response. This subject developed an anaphylactic reaction characterized by hives at the site and more distantly from the site of the subcutaneous inoculation. Hypersensitivity to A. albopictus larval antigens is common and precludes the use of C6/36 cell culture as a substrate for viral vaccines.
Eighty patients with nasopharyngeal carcinoma were treated with radiotherapy in the Radiation Center at the University of Louisville from January 1955 to December 1980. Among the patients were 70 whites, nine blacks and one Chinese; their ages ranged from eight to 82 years. There was a 40% recurrence rate within the nasopharynx, and a 29% recurrence rate within neck nodes. The five year survival and relapse-free survival rates of the entire group were 36 and 33%, respectively. Forty-nine patients died of cancer, four patients died of intercurrent disease and eight patients were lost to follow-up. Nineteen patients are alive and free of disease. Factors considered in this study included tumor and nodal status, the presence of cranial neuropathy, the size and area irradiated, and dose delivered. Primary site relapse was not demonstrated to be dependent on T group or nodal status, but was likely to be related to inadequacy of original treatment volume and dose. A higher survival was noted with our lymphoepithelioma category (p = .056).
A live dengue virus type 2 (dengue-2) vaccine (PR-159/S-1) was tested for reactogenicity and immunogenicity in a placebo-controlled, double-blind clinical trial involving 98 soldiers. Seroconversion rates based on the development of neutralizing antibody to dengue-2 were 90% in 70 recipients with immunity to yellow fever and 61% in 28 vaccinees without such immunity (P less than .01). Peak titers of neutralizing antibody were three times higher in recipients with antibody to yellow fever virus and persisted in most for at least 18 months. Individuals seroconverting to the vaccine virus more frequently experienced systemic symptoms than those who received placebo (P less than .02). Future users of this dengue-2 vaccine may wish to employ immunization schedules that include preliminary immunization against yellow fever and must be prepared to accept mild vaccine-related symptoms in some recipients.
Two different radioimmunoassays were used to detect virus-specific antibodies in sera from human volunteers inoculated with an attenuated dengue type 2 (DEN-2) vaccine (PR-159/S-1). An indirect radioimmunoassay required purified DEN-2 virions for optimal reactivity but was 10 to 500 times more sensitive than neutralization or hemagglutination inhibition tests. An antibody capture radioimmunoassay was able to utilize crude antigens from either DEN-infected mouse brains or Aedes albopictus cell culture supernatants. When the two radioimmunoassay techniques were compared, the indirect method appeared to be the best assay for immunoglobulin G (IgG), whereas the antibody capture method was more sensitive for IgM detection. Selected human sera were examined for IgG, IgM, and IgA responses by using both techniques at various intervals after immunization. Although there were differences in magnitude, yellow fever immune as well as flavivirus nonimmune volunteers responded to DEN-2 vaccination by demonstrating IgG, IgM, and IgA antibody responses. In the nonimmune group, the most prevalent immunoglobulin detected was IgM, whereas in the yellow fever immune group, the predominant post-DEN-2 vaccine immunoglobulin was IgG. The preponderance of DEN-2-specific neutralizing antibodies were associated with either IgM or IgG according to the immune status of the volunteer. All classes of immunoglobulins attained maximum levels between 21 and 60 days postvaccination. In the majority of volunteers, IgM responses were relatively transient and could not be detected 6 months after immunization, whereas IgG and IgA antibodies were still detectable after this period.
Five patients who experienced temporary neurological deterioration after extracranial to intracranial bypass procedures are reported in detail. These patients suffered transient ischemic attacks or more prolonged deficits usually of a different nature than the preoperative symptoms. All patients had a good outcome and the spells ceased; the neurological deficits improved within a maximum of 2 weeks. Obvious causes of deterioration such as intra- or extracerebral hematomas, occlusion of a previously stenotic vessel, or graft occlusion were ruled out by computed tomography and angiography in each case. Intraoperative causes of neurological deterioration such as anesthetic effect, hypotension, and temporary occlusion of the cortical vessel or sacrifice of its small branches were not likely to be the cause of the deficits because in each case, the patient awoke satisfactorily and deterioration occurred hours to days later. In each case, postoperative angiography showed good perfusion of at least one major division of the middle cerebral territory. Anticoagulation with heparin in three patients did not change the clinical course. In one patient who was not anticoagulated, embolism could have been responsible for a single prolonged ischemic event, but in the other patients thromboembolism does not seem likely to have been responsible for the deficits. The cause of the deterioration in these patients remains unexplained. We speculate that hyperperfusion of chronically ischemic brain tissue and shifts in the watershed region resulting from the new flow pattern after bypass grafting are two mechanisms that may have been of importance in the etiology of these deficits.
A dengue 4 (strain H241, PDK35-TD3 FRhL p3) vaccine attenuated by passage in primary dog kidney cells followed by passage and final vaccine preparation in DBS-FRhL-2 cells was tested in five yellow fever-immune volunteers. Only two volunteers seroconverted by producing hemagglutination-inhibiting and neutralizing antibodies. Mild illness, compatible with dengue infection was found only in the individuals who later developed antibodies. Both volunteers developed a rash by the 8th day following vaccination, coinciding with a slight elevation in temperature and leukopenia. Additionally, several serum enzymes were elevated during the observation period. Dengue 4 virus was isolated from the blood of the two infected volunteers starting as early as day 5 post vaccination. During the viremic period, which lasted 5 days, phenotypically-changed virus was recovered, indicating genetic instability of the vaccine virus. The clinical disease and immune response in the two infected individuals was probably related to replication of the variant virus. Further testing of this vaccine in its present form is not indicated.
The Immunization Practices Advisory Committee ( ACIP ) has devised noninvasive, historical criteria for determining individuals who are susceptible to measles. These criteria, which involve proof of vaccination, are incorporated into school entrance regulations and are used to indicate people who require vaccination during outbreaks. In a recent measles epidemic in El Paso , TX, 120,000 records were screened using these criteria, and as a result 13,000 students were vaccinated. During this outbreak, 91 adolescents, who were susceptible to measles by ACIP criteria, were serologically tested for measles antibody. Although none of these students had documentation of vaccination, only 11.0% of them lacked measles hemagglutination-inhibiting (HAI) antibody at a titer of 5. Assuming a minimum cost for vaccine of +2.60 per dose, a conservative estimate of the cost to the El Paso Health Department for 20,000 doses of measles vaccine would be +52,000. If these data can be extrapolated to the total student population, then upwards of 85% of vaccinated students were already immune. Thus, +44,200 was spent unnecessarily. In addition, as the ACIP criteria did not select for measles susceptibility, an estimated 12,000 students in El Paso were not protected against measles. Other methods to determine measles susceptibility should be developed for optimal control of future outbreaks.
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To assess the feasibility of jet injection for mass immunization against hepatitis B virus, inactivated, alum-adsorbed hepatitis B vaccine (Merck, Sharp, and Dohme Research Laboratories, West Point, PA) was administered subcutaneously by automatic jet injection to 19 volunteers lacking antibody to hepatitis B surface antigen (anti-HBs). Three 20-microgram doses were given at 0, 1, and 6 months. Of 19 volunteers, 5 (26%) developed anti-HBs by 1 month after the first injection, and 15 of 19 (79%) were anti-HBs-positive 6 to 8 weeks after the first booster administration. Following the second booster, 16 of 19 (84%) recipients had detectable anti-HBs. Possible systemic reactions were limited to low-grade fever (37.8 degrees C) in one volunteer following one injection, and mild lethargy in a second recipient. Local reactions to jet injection of vaccine occurred more frequently, with indurated, nodular lesions 3-10 mm in diameter developing at the site of 19 of 57 (33%) vaccine injections, compared with 2 of 57 (3%) saline placebo injections. Such nodules were generally painless. Sore arms were noted in 11 of 57 (19%) vaccine injections. With the exception of frequent but minor local reactions, subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection is safe, and results in vaccine immunogenicity approximating that associated with intramuscular needle injection.
Computed tomography (CT) has shown to be of great value in the treatment of cancer with radiation therapy. It is used more and more in the estimation of tumor volume and for treatment planning, with the aid of the computerized treatment unit. At the James Graham Brown Cancer Center, Department of Radiation Oncology, CT has been used routinely for the treatment planning. From October 1, 1981 to June 30, 1982, we performed 180 CT scans for the treatment planning, 380 simple dose calculations, 237 complex treatment plans, and 42 intracavitary dosimetry using the treatment planning unit. This is a review of our experience with some illustrations. Accurate tumor dose can be delivered with reducing the complications with the use of CT and the computerized treatment unit.