PubMed HealthSearch

Biomedical subjects

R Reid

Publications and source records attributed to R Reid.

At least 19 recordsLinked to original sources

Encephalitis and chorioretinitis associated with neurotropic African horsesickness virus infection in laboratory workers. Part II. Ophthalmological findings.

Four laboratory workers developed uveitis-chorioretinitis, associated with encephalitis in 3 cases. The retinitis was characterised by haemorrhages and areas of retinal oedema, most marked over the posterior polar regions, and was associated with exudative retinal detachments. The lesions progressed over weeks and showed a severe retinal arterial vasculopathy with arteriolar narrowing, ghost vessel formation and the development of optic atrophy. The picture in 2 of the patients resembled that of the acute retinal necrosis syndrome (ARN). Antibodies to African horsesickness (AHS) virus were detected. The serology for AHS virus was positive in all 4 patients as well as in 5 of 15 laboratory workers from the same facility who were clinically and ophthalmologically normal. This is to our knowledge the first description of subclinical and probable clinical neurotropic AHS virus infection in man. AHS is a hitherto-unrecognised possible cause of viral retinitis and the ARN syndrome.

Adolescent

Encephalitis and chorioretinitis associated with neurotropic African horsesickness virus infection in laboratory workers. Part IV. Experimental infection of the vervet monkey (Cercopithecus pygerythrus).

Neurotropic vaccine strains of African horsesickness (AHS) virus types 1 and 6 were implicated as the possible aetiological agents in 4 cases of encephalitis and uveochorioretinitis in laboratory workers accidentally exposed to the freeze-dried vaccine preparations of the virus. To date, AHS virus has not been known to infect man. To ascertain whether or not primates were susceptible to infection with AHS virus, vervet monkeys (Cercopithecus pygerythrus) were inoculated, either transnasally or intraconjunctivally, with vaccine strains of AHS virus types 1 and 6. The course of infection was monitored using parameters such as behavioural changes, febrile reaction, cerebrospinal fluid pleocytosis, serology, magnetic resonance imaging and autopsy. Encephalitis, manifested by varying degrees of fever, behavioural changes and pleocytosis, but no chorioretinitis was detected in all 6 transnasally infected monkeys. This was confirmed by autopsy, where a meningo-encephalitis affecting the medial temporal lobe but no lesions in the eyes was demonstrated. Neither virus appeared to infect the animals after intraconjunctival inoculation. These findings support the theory that the patients were infected by the inhalation of freeze-dried vaccine preparations. The pathogenesis of the eye lesions, however, remains uncertain.

African Horse Sickness

Superficial laser vulvectomy. V. Surgical debulking is enhanced by adjuvant systemic interferon.

Skillful laser ablation can remove any volume of human papillomavirus-associated vulvar disease but cannot prevent reactivation of the surrounding latent viral reservoir during postoperative healing. Conversely, interferon and 5-fluorouracil are relatively ineffective as primary therapies in clearing bulky lesions. In this study of 71 assessable patients, topical 5-fluorouracil and systemic interferon injections were used postoperatively. Success rates within the adjuvant 5-fluorouracil and laser alone arms were essentially the same (9 of 18 vs 8 of 20). In contrast, outcome in the interferon group was significantly better than that for the other two arms combined (27 of 33 [82%] vs 17 of 38 [45%]; chi 2 10.31; p less than 0.002). Moreover, 18 of 21 failures (86%) in the first two arms and 3 of 6 failures (50%) in the interferon arm were "rescued" from the need for a second laser surgical procedure by crossover to either the 1 or 3 MIU interferon regimen. Results from this open-label, randomized clinical trial suggest that even a relatively low dose of recombinant interferon, used in combination with effective surgical debulking, can markedly reduce the risk of postoperative recurrence.

Administration, Topical

A comparison study of human papillomavirus prevalence by the polymerase chain reaction in low risk women and in a gynaecology referral group at elevated risk for cervical cancer.

The reported prevalence of human papillomavirus (HPV) type 16 in the genital tracts of women with various gynaecological conditions is highly variable. In particular, some results with the polymerase chain reaction (PCR) technique have suggested that HPV-16 is a ubiquitous or very common virus. We undertook this study to help clarify the current confusion. PCR with HPV consensus L1 primers and specific E6 primers was used to study 89 women attending two gynaecology referral clinics, as well as 99 women attending a health maintenance organization (HMO) clinic; 70 of these latter women had no current or prior history of genital HPV disease. HPV-16 was detected in less than 5% of cytologically normal women from either group and in 17% (6/36) and 31% (9/29) of women with cervical intraepithelial neoplasia (CIN) from the referral clinic and the HMO, respectively. The other high-risk or intermediate-risk HPVs (types 18, 31, 33 or 35) were less prevalent than HPV 16 in all groups of women. A majority of the HPV types detected by the L1 primers in normal women were uncharacterized HPVs. Overall these uncharacterized HPVs were detected in 37% (46/123) of the normal women and in 48% (31/65) of the women with CIN. Using the most sensitive PCR product detection method employed in the study, HPV DNA was detected in 36% (4/11) of swab specimens obtained from the external abdomen.

Base Sequence

Prevention of Haemophilus influenzae type b infections in Apache and Navajo children.

Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos. The attack rate in children less than 5 years of age is 5-10 times higher than in the general US population. Three vaccines were evaluated. Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants. HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses. The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels. PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose. This vaccine was greater than 90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age. Even a single dose achieved a high protective efficacy.

Antibodies, Bacterial

Human papillomavirus infection of the cervix: relative risk associations of 15 common anogenital types.

During the years 1982-1989, 2627 women were recruited into eight studies analyzing the relationship between human papillomavirus (HPV) infection and cervical neoplasia. Subsequently, each individual was assigned as either a case or control, and each cervical sample was rescreened for HPV DNA by low-stringency Southern blot hybridization. Positive samples were retested at high stringency with specific probes for HPVs 6/11, 16, 18, 31, 33, 35, 42, 43, 44, 45, 51, 52, 56, and (in most instances) 58. Most cases (153 cancers, 261 high-grade and 377 low-grade squamous intraepithelial lesions) had target or cone biopsies; all 270 borderline atypia subjects and more than 85% of the 1566 normal controls had cytology plus colposcopy/cytology. Scientists performing HPV testing were masked to the clinical diagnoses. Human papillomavirus DNA was detected in 79.3% of specimens from women with definite cervical disease (627 of 791), in 23.7% of borderline atypia subjects (64 of 270), and in 6.4% of normal subjects (101 of 1566). Graphic analysis of odds ratios at each point in the diagnostic spectrum defined four categories: 1) "low risk" (HPVs 6/11, 42, 43, and 44), present in 20.2% (76 of 377) of low-grade lesions but absent in all 153 cancers; 2) "intermediate risk" (HPVs 31, 33, 35, 51, 52, and 58), detected in 23.8% (62 of 261) of high-grade squamous intraepithelial lesions but only 10.5% (16 of 153) of cancers; 3) "high risk/HPV 16," associated with 47.1% of both high-grade intraepithelial lesions (123 of 261) and cancers (72 of 153); and 4) "high risk/HPV 18" (HPVs 18, 45, and 56), found in 26.8% (41 of 153) of invasive carcinomas but only 6.5% (17 of 261) of high-grade intraepithelial lesions. The presence of an oncogenic HPV type conferred relative risks ranging at 65.1-235.7 for the occurrence of a high-grade lesion and 31.1-296.1 for an invasive cancer.

Blotting, Southern

Children with Haemophilus influenzae bacteremia initially treated as outpatients: outcome in 85 American Indian children.

Eighty-five American Indian children less than 16 years of age with Haemophilus influenzae bacteremia were retrospectively determined to have been treated as outpatients after their initial evaluation. We hoped to determine the proportion that developed new foci, the time interval to this development and whether age or temperature at presentation predicted outcome. Fifty-one (60%) presented with nonfocal findings. Seventy-two (85%) were treated with antibiotics at the initial visit. Although 49 (58%) of the patients were never hospitalized, a new focus was identified in 25 (29%), including 13 (15%) with a final diagnosis of meningitis. The new foci were identified within 6 days of presentation (median, 2 days). An additional 15 (18%) patients had no new focus but were febrile and/or ill at follow-up. All patients with meningitis or a second positive culture were hospitalized at the first follow-up visit. Age and temperature at presentation did not help predict outcome. All patients with H. influenzae bacteremia require prompt reevaluation and close follow-up by an experienced physician.

Ambulatory Care

A significant proportion of patients with osteosarcoma may belong to Li-Fraumeni cancer families.

We studied the pedigrees of 17 index patients with osteosarcoma, recording malignant disease and cause of death for first- and second-degree relatives. There were seven cancers and five cancer deaths per 2151.5 person-years in first-degree relatives of osteosarcoma patients under the age of 50 years, a significantly greater incidence than in an age- and sex-matched population group (p < 0.001). This excess of malignancy was largely due to two families which fulfilled the criteria for the Li-Fraumeni cancer family syndrome. Both of these families were shown to have the genetic alterations in the p53 gene which have been implicated in this syndrome. Our study suggests that orthopaedic surgeons seeing new cases of osteosarcoma should arrange screening for familial malignancy.

Adolescent

High incidence rates of invasive pneumococcal disease in the White Mountain Apache population.

OBJECTIVE: In this article we determine the incidence and clinical spectrum of invasive pneumococcal disease in the White Mountain Apache population, a group known to have a high incidence of invasive disease due to Haemophilus influenzae type b. DESIGN: Patients from whom cultures of normally sterile body sites yielded Streptococcus pneumoniae were identified retrospectively through review of hospital laboratory records from a 6.8-year period. Clinical data were reviewed and incidence rates were computed. SETTING: The Whiteriver Indian Health Service Hospital is located on the 1.7-million-acre White Mountain Apache Reservation in eastern Arizona. PATIENTS: Approximately 10,000 members of the White Mountain Apache Tribe reside on or near the reservation and receive health care through the Whiteriver Indian Health Service Hospital. OUTCOME MEASURES: The average annual incidence rates of invasive pneumococcal disease were calculated and clinical characteristics were reviewed. RESULTS: One hundred thirty-eight cases of invasive pneumococcal disease were identified. The average annual incidence rate was 207 per 100,000 population, and 156 per 100,000 population when adjusted for age by direct standardization to the 1988 US population. The incidence rate was highest in children between 1 and 2 years--2396 per 100,000. The overall case-fatality rate was 5%. Pneumococcal pneumonia was the diagnosis in 79% of the patients 5 years of age or older. Alcohol abuse, identified in 66% of the cases in adults, was the most common underlying medical condition. CONCLUSION: The incidence rates in White Mountain Apaches are the highest reported for any population. A vaccine effective in children would greatly benefit this population.

Adolescent

Enterotoxigenic Bacteroides fragilis: epidemiologic studies of its role as a human diarrhoeal pathogen.

Strains of Bacteroides fragilis which produce enterotoxin(s) (ETBF) have been associated with diarrhoeal diseases in young domestic animals and have also been isolated from humans with diarrhoea. We have determined epidemiologically that ETBF are significantly associated with diarrhoea in humans. We studied Apaches, primarily children, with diarrhoea attending an outpatient facility in Whiteriver, Arizona, from July 1986 through July, 1988. Stool cultures for isolation of ETBF and other diarrhoeal pathogens were taken from these persons as well as from age and time-matched control persons who did not have diarrhoea. ETBF were isolated significantly more often from persons with diarrhoea (12%) than from controls (6%), p = 0.03. Isolation was highest (20-24% of stool cultures positive) during the second and third years of life. The diarrhoeal syndrome associated with ETBF was non-specific, and most characteristic of a secretory, rather than inflammatory, type of diarrhoea. ETBF are significantly associated with acute diarrhoea in Apache children, and may be an important newly described cause of diarrhoea in humans.

Acute Disease

The efficacy in Navajo infants of a conjugate vaccine consisting of Haemophilus influenzae type b polysaccharide and Neisseria meningitidis outer-membrane protein complex.

BACKGROUND AND METHODS: Several conjugate vaccines against Haemophilus influenzae type b have been developed in the search for one that induces protection even in young infants. We evaluated the safety and efficacy of a conjugate vaccine that links the H. influenzae type b capsular polysaccharide to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B. We conducted a double-blind, placebo, controlled trial in Navajo infants, who are at high risk for systemic infections caused by H. influenzae type b. The infants were randomly assigned to receive the first dose of vaccine or placebo at 42 to 90 days of age and the second at 70 to 146 days of age. RESULTS: Of the infants in the trial, 2588 were assigned to receive the vaccine and 2602 to receive placebo. The mean follow-up was 269 days in the vaccine group and 267 days in the placebo group. Before the age of 18 months, there was 1 systemic H. influenzae type b infection in the vaccine group, as compared with 22 in the placebo group (P less than 0.001; point estimate of efficacy, 95 percent; 95 percent confidence interval, 72 to 99 percent). Of the 22 H. influenzae type b infections in the placebo group, 13 were meningitis. Among the children who received both doses, there was 1 H. influenzae type b infection in the vaccine group (n = 2056) and 14 in the placebo group (n = 2105) (P less than 0.001; point estimate of efficacy, 93 percent; 95 percent confidence interval, 53 to 98 percent). The single infection in the vaccine group occurred at 15 1/2 months of age in an infant with osteomyelitis. Between the first and second doses there were no H. influenzae type b infections in the vaccine group and eight in the placebo group (P less than 0.005; point estimate of efficacy, 100 percent; 95 percent confidence interval, 41 to 100 percent). CONCLUSIONS: The H. influenzae type b OMPC vaccine, administered at 2 and 4 months of age, is safe and induces a high rate of protection against invasive disease caused by H. influenzae type b in infants under the age of 18 months. Protection begins after the first dose.

Antibody Formation

Should cervical cytologic testing be augmented by cervicography or human papillomavirus deoxyribonucleic acid detection?

Criticism of the Papanicolaou smear in the lay press and recent federal legislation regulating cytology laboratories indicate a need to reappraise cervical cancer screening programs. This study directly compares three potential screening tests, used alone or in combination. A total of 1012 women aged 18 to 35 years were screened by cytologic testing, cervicography, and hybridization for human papillomavirus deoxyribonucleic acid, with discrepancies being referred by the last two authors. After findings from the entire lower genital tract were combined, 116 women (11.5%) showed definite clinical abnormalities (either exophytic vulvovaginal condylomas or cervical squamous intraepithelial lesions). Another 72 (7.2%) had positive Southern blot hybridizations without accompanying viral expression, yielding a cumulative frequency for established disease or latent infection of 18.6%. When associated vulvovaginal condylomas are disregarded, final groupings with regard to cervical pathologic classification were: 23 high-grade and 71 low-grade squamous intraepithelial lesions, 164 cases of equivocal atypia (34 of which had detectable human papillomavirus deoxyribonucleic acid), and 754 cases with negative results (38 of which had detectable human papillomavirus deoxyribonucleic acid). Cervical screening tests were compared principally by plotting increasingly liberal recall criteria onto receiver operating characteristic curves (i.e., graphs of true-positive results on the Y axis versus false-positive results on the X axis). Used individually, each screening test was valid, but none was substantially better than the others. No matter how liberal the recall criteria, no single test was able to detect all of the 23 definite precursors in this sample. Applying conventional recall criteria (i.e., high- or low-grade lesion suspected), cytologic testing alone detected 12 high-grade squamous intraepithelial lesions (52.2%), at a cost of having to perform colposcopy in 8.7% of the sample. Combining all three tests and setting the end point as just a high-positive result by at least one test, 19 high-grade squamous intraepithelial lesions (83%) were detected, with a recall of 7%. Optimal test performance (96% sensitivity, 4% recall) would have been attained by recalling all patients with high-grade cytologic results or positive cervicography results, plus any patients with low-grade morphologic atypia in which hybridization detected an oncogenic human papillomavirus type. Our conclusions are as follows: (1) Cytologic detection rates are markedly improved by a second or third test; (2) increased screening costs could be offset by not recalling patients with minor lesions with no apparent potential for progression.

Adolescent

Computed tomographic findings in two patients with vascular hamartomas.

The clinical, computed tomographic (CT) and histological findings of two patients with vascular hamartomas are presented. The appearances on CT of the two lesions were markedly different. Although both lesions were histopathologically benign, one showed a more disorganized architecture on histology and clinically behaved in a more aggressive manner. The CT findings in this case reflected the histological picture and could have been interpreted as a malignant process if viewed in isolation. Review of the literature and the cases presented suggest that the CT appearances of vascular hamartomas can be diverse, and to avoid a misdiagnosis the radiological features should be considered in conjunction with the clinical and histopathological findings.

Adolescent

The distribution of alternative agents for targeted radiotherapy within human neuroblastoma spheroids.

This study aims to select the radiopharmaceutical vehicle for targeted radiotherapy of neuroblastoma which is most likely to penetrate readily the centre of micrometastases in vivo. The human neuroblastoma cell line NB1-G, grown as multicellular spheroids, provided an in vitro model for micrometastases. The radiopharmaceuticals studied were the catecholamine analogue metaiodobenzyl guanidine (mIBG), a specific neuroectodermal monoclonal antibody (UJ13A) and beta nerve growth factor (beta NGF). Following incubation of each drug with neuroblastoma spheroids, autoradiographs of frozen sections were prepared to demonstrate their relative distributions. mIBG and beta NGF were found to penetrate the centre of spheroids readily although the concentration of mIBG greatly exceeded that of beta NGF. In contrast, UJ13A was only bound peripherally. We conclude that mIBG is the best available vehicle for targeted radiotherapy of neuroblastoma cells with active uptake mechanisms for catecholamines. It is suggested that radionuclides with a shorter range of emissions than 131I may be conjugated to benzyl guanidine to constitute more effective targeting agents with potentially less toxicity to adjacent normal tissues.

3-Iodobenzylguanidine

A field study of the safety and efficacy of two candidate rotavirus vaccines in a Native American population.

A double-blind, randomized, placebo-controlled trial was conducted to evaluate the safety and efficacy of a rhesus rotavirus vaccine and RIT 4237, a bovine rotavirus vaccine, in a Navajo population. Infants aged 2-5 months were randomized to receive one dose of either 10(4) pfu of the rhesus rotavirus vaccine or 10(8) pfu of the RIT 4237 vaccine or placebo. Eleven (10.2%) of 108 infants in the rhesus vaccine group, 11 (10.4%) of 106 in the RIT 4237 group, and 9 (8.4%) of 107 in the placebo group experienced rotavirus diarrhea during the follow-up period of 17 months. Thus, in this population, neither vaccine was efficacious in preventing rotavirus diarrhea.

Diarrhea, Infantile

Safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine in a high risk American Indian population.

The safety and immunogenicity of a Haemophilus influenzae type b polysaccharide conjugate vaccine linked to the outer membrane protein complex of Neisseria meningitidis (Hib-OMP) were evaluated among Apache and Navajo infants and children. One dose of the Hib-OMP was given to 42 children who were from 12 and 60 months of age. Ninety-two infants 6 to 8 weeks old were given one dose of Hib-OMP at the time of enrollment. A subsequent dose of the vaccine was given 2 months later and a third dose was offered between 12 and 15 months of age. All of the 12- to 60-month-old children achieved a protective antibody concentration (greater than 1 microgram/ml) 1 month postvaccination. Among the 6- to 8-week-old infants only 11% of the Apaches and 8% of Navajos had a protective anti-PRP antibody concentration prevaccination. One month post vaccination 68% of the Apaches and 69% of the Navajos had protective anti-PRP antibody concentrations. One month after the second immunization 67% of the Apaches and 75% of Navajos had protective anti-PRP concentrations. Among the infants that received the third (booster) immunization (N = 28) 74% had protective anti-PRP antibody titers just before the booster immunization. One month after the booster immunization all of the infants had protective concentrations of anti-PRP antibody. We conclude that the Hib-OMP is safe and highly immunogenic among Apache and Navajo infants and children.

Antibodies, Bacterial

Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and invasive cervical neoplasm.

The integration of human papillomavirus (HPV) DNA into the human genome has been generally accepted as a characteristic of malignant lesions. To gain a better understanding of this phenomenon, genomic DNA from 181 cervical biopsy specimens was isolated and analyzed for HPV type and physical state of the HPV genome. These specimens represented the full spectrum of cervical disease, from condyloma to invasive carcinoma. Discrimination between integrated and episomal HPV DNA was accomplished by the detection of HPV-human DNA junction fragments on Southern blots. In most cases in which ambiguous Southern blot results were obtained, the specimens were reanalyzed by two-dimensional gel electrophoresis. Of the 100 biopsy specimens of cervical intraepithelial neoplasia analyzed, only 3 showed integrated HPV DNA, in contrast to 56 (81%) of 69 cervical carcinomas (P less than 0.001) showing integrated HPV DNA. Of the 40 carcinomas containing HPV 16 DNA, 29 (72%) had integrated HPV DNA, of which 8 (20%) also had episomal HPV DNA. In 11 (27%) cancers, only episomal HPV 16 DNA was detected. All 23 HPV 18-containing carcinomas had integrated HPV DNA, and 1 also had episomal HPV 18 DNA. The difference between HPV types 16 and 18 with respect to frequency of integration was statistically significant (P less than 0.01). The results of this study indicate that detectable integration of HPV DNA, regardless of type, occurs infrequently in cervical intraepithelial neoplasia. The absence of HPV 16 DNA integration in some carcinomas implies that integration is not always required for malignant progression. In contrast, the consistent integration of HPV 18 DNA in all cervical cancers examined may be related to its greater transforming efficiency in vitro and its reported clinical association with more aggressive cervical cancers.

Blotting, Southern