The prognostic significance of progesterone receptor level in endometrial cancer

Previous studies of cholera transmission have been conducted in the middle or at the end of an epidemic. Since modes of transmission could be different in different phases of an epidemic, we initiated a case-referent study immediately after the first cases had been hospitalized in a recent cholera epidemic in Guinea-Bissau in West Africa in October 1994. The cases investigated were consecutive adult patients resident in the capital of Bissau who were admitted the the National Hospital during the first two weeks of the epidemic. Referents were matched for district, gender, and age. The study showed a protective effect of using limes in the main meal (odds ratio [OR] = 0.2, 95% confidence interval [CI] = 0.1-0.3) and having soap in the house (OR = 0.3, 95% CI = 0.1-0.8). Not eating with the fingers and using water from a public standpipe were also protective. No specific source or mode of transmission was identified. Thus, cholera control programs in Africa may have to emphasize general hygienic conditions and the use of acidifiers in food preparation.     

Monitoring of a whooping cough epidemic 1994/95 in Switzerland using the sentinel notification system. Sentinella Registry

Since June 1991 pertussis cases have been reported in the Swiss Sentinel Network (Sentinella). A total of 150-200 general practitioners, physicians specialized in internal medicine, and pediatricians participate in this system on a voluntary basis. Of the three specialties involved, this non-randomized sample represents 3.0%-3.5% of all physicians registered in Switzerland. The objective of this surveillance system is to monitor clinical pertussis over time. The case definition included all patients with a cough illness lasting at least 14 days with one of the following: paroxysms of cough, inspiratory "whoop", post-tussive vomiting (sporadic cases), or an epidemiological link to a pertussis case (epidemic cases). A laboratory diagnosis based on the polymerase chain reaction technique (PCR) was available for 82.7% of cases reported in 1994 and 1995. Of these, 27.7% had a positive PCR result. Reports of epidemic pertussis tested for Bordetella pertussis by PCR were confirmed by the laboratory in 46.5% of cases. The laboratory confirmation rate was more than twice as high among epidemic cases than among sporadic cases (20.7%). The crude incidence rate of whooping cough was 70 cases per 100,000 population per year in 1992 and 1993. Compared to previous years, pertussis incidence was significantly higher in 1994 and 1995 (370 cases per 100,000 population and 280 cases per 100,000 population respectively). The increase in reports was especially marked between July and October 1994 and whooping cough became epidemic in the third trimester of 1994 and at the beginning of 1995. In these 2 years, Switzerland experienced an estimated 40,000 clinical pertussis cases. Based on the proportion of PCR-positive pertussis cases in the sentinel sample, 12,500 of these would have been laboratory-confirmed. Most cases were observed in infants and in children up to 6 years of age. Assuming a vaccination coverage of 90%, the global efficacy of vaccination (3 or more doses versus less than 3) for 1994 and 1995 among children aged 12 to 47 months and not born before 1991 was 0.74 (0.59 and 0.88 for a vaccination coverage of 85% and 95% respectively). Vaccine efficacy was higher in PCR-positive cases (0.87; 0.79; 0.94) than in PCR-negative cases (0.54; 0.27; 0.78). Vaccination efficacy estimates on the basis of surveillance data are certainly less precise than those inferred from clinical trials. However, our results indicate that the efficacy of vaccination in children significantly declined with increasing age. Whooping cough still has the potential to cause epidemics in Switzerland in spite of a high vaccination coverage. With the introduction of acellular pertussis vaccines and new vaccination schemes in Switzerland, the Swiss Sentinel Network fulfills an important task as a monitoring system and contributes to the evaluation of new vaccination strategies.     

Elevated serum level of thioredoxin in patients with hepatocellular carcinoma

BACKGROUND: Acute infant bronchiolitis is a frequent seasonal disease which peaks in December. It often requires hospital care in Paris and in its surroundings. The exceptional bronchiolitis epidemic of December 1991 brought about a temporary saturation of hospital bed space at the Assistance Publique-H?pitaux de Paris (AP-HP). Hereafter, in order to organize care more efficiently, an epidemiological observation network called ERBUS was set up. METHODS: Thanks to daily reports of emergency pediatric admissions through the Minitel network, it has been possible to get real time information on the course of the past five epidemics in each of the 11 AP-HP hospitals with pediatric emergency units. RESULTS: Globally the results point to a similar situation every year: approximately 60% boys, 35% babies under 6 months; the ratio of very young patients who are admitted to hospital is multiplied by 1.5 at the mid-point of and at the end of the epidemic compared with the beginning; 70% of the babies under 3 months are admitted to hospital. The ratio of patients who come and are admitted to hospital has been on the decrease every year since 1991: globally from 36.8% down to 28.6% in five years (from 75.1% down to 65.3% among babies under 3 months). The rhythm and intensity of the epidemic have risen sharply: in five years, the number of patients has increased by 119% and that of patients admitted to hospital by 69%, while the epidemic peaks are earlier and higher. CONCLUSION: These statistics have actually been used to allocate additional resources in AP-HP hospitals during the epidemics. To avoid the saturation of bed space in the future, ambulatory care of patients not admitted to hospital should be favored.     

Pathogenesis of nervous system lesions in epidemic parotitis in children

The authors studied antibodies to the nervous tissue in the blood (pair serum with an interval of 10 days) and in the CSF in 155 patients with epidemic parotitis and signs of neurotoxicosis, parotit meningitis and meningoencephalitis. Depending upon the intensivity of antibody elaboration 3 groups were distinguished. The first group (40 cases), with a high content of antibodies to the nervous tissue, was characterized by a prevalence of encephalitic forms (in 30 of the 40 cases). In the second group (32 cases) with a less antibody content there was a prevalence of meningitis, while meningoencephalitis was seen only in 3 cases. The third group (83 cases) with a low concentration or absence of antibodies was characterized by a mild course of the disease. This group included as well patients with neurotoxicosis. These data may indicate involvement of allergic mechanisms of a retarded type in the pathogenesis of remote lesions of the nervous system in epidemic parotitis.     

Glutathione peroxidase degrades intracellular hydrogen peroxide and thereby inhibits intracellular protein iodination in thyroid epithelium

Protein iodination in the thyroid is largely confined to the surface of the epithelium. Intracellular iodine binding is insignificant. We have tested our hypothesis that the key mechanism in the control of intracellular iodination is the control of the intracellular availability of H2O2. The sites of iodination were identified by locating bound radioiodine in electron microscopic autoradiographs, produced from porcine thyroid epithelium grown on filter in Transwell bicameral culture chambers. Autoradiographs obtained after standard incubations with 125I for 15 min to 3 h were all characterized by concentrations of autoradiographic grains along the external surface of the plasma membrane and very few grains over the cytoplasm. The presence of 10 microM H2O2 in the incubation medium resulted in a drastically changed labeling pattern now showing a dissemination of grains over the entire cytoplasm. Epithelia with elevated GSH peroxidase activity produced autoradiographs showing the same restriction of grains to the cell surface as controls; this pattern was the same in the absence and presence of H2O2 (up to 10 microM). Cultures with subnormal GSH peroxidase activity presented cytoplasmic labeling both in the absence and presence of H2O2. In conclusion, iodine binding in filter-cultured thyroid epithelium under normal conditions is an extracellular process located at the cell surface. When H2O2 is available intracellularly, iodination takes place in the cytoplasm, evidently catalyzed by intracellular thyroperoxidase. Normally, this iodination is prevented by cytosolic GSH peroxidase that effectively degrades H2O2 and thus controls intracellular iodination. The observations should be applicable to the thyroid in vivo.     

Changes in the polypeptide assembly of guinea pig thyroglobulin induced by thyrotropin-regulated thyroid activity

We have previously reported that the relative proportion of three polypeptide chains in guinea pig thyroglobulin is closely related to the iodine content of the protein. The present work demonstrates that it is not the iodine content per se but, rather, TSH-regulated thyroid activity which modulates the substructure of thyroglobulin. In a first set of experiments, the impact of TSH stimulation on sodium dodecyl sulfate (SDS)-induced dissociation of 19S thyroglobulin into 12S subunits was compared to that of iodination. While in control animals the ratio of 12S to 19S thyroglobulin was 48:52, it changed to 35:65 in glands strongly stimulated with TSH and blocked with MMI. This rise in the relative proportion of 19S thyroglobulin occurred despite a simultaneous drop of iodine content from 0.6% to 0.24%. It was only after TSH suppression that the well known inverse correlation between the level of iodination and dissociability reappeared. In a second set of experiments, SDS-treated thyroglobulin was fully reduced by splitting disulfide bonds with mercaptoethanol. In addition to the previously described three polypeptide chains, A, B, and C, a hitherto neglected nonreducible fraction comigrated with 19S thyroglobulin on polyacrylamide gels. Native thyroglobulin with widely varying iodine contents was obtained from unstimulated glands and from glands strongly stimulated with TSH. Drastic changes in the polypeptide chain assembly, depending on the degree of TSH stimulation but entirely independent of iodination, were observed. There was a strong negative correlation between the nonreducible 19S thyroglobulin fraction and both the B and C polypeptide chains with all experimental manipulations. We conclude that thyroglobulin substructure is highly dependent on the degree of TSH stimulation of the thyroid. TSH, through stimulation of unknown metabolic pathways, is a more important determinant of thyroglobulin substructure than the degree of iodination of the protein.     

Epidemiological determinants of the pattern and magnitude of the vCJD epidemic in Great Britain

Understanding the epidemiology and aetiology of new-variant Creutzfeldt-Jakob (vCJD) disease in humans has become increasingly important given the scientific evidence linking it to bovine spongiform encephalopathy (BSE) in cattle and hence the wide exposure of the population of Great Britain (GB) to potentially infectious tissue. The recent analysis undertaken to determine the risk to the population from dorsal route ganglia illustrated the danger in presenting point estimates rather than ranges of scenarios in the face of uncertainty. We present a mathematical template that relates the past pattern of the BSE epidemic in cattle to the future course of any vCJD epidemic in humans, and use extensive scenario analysis to explore the wide range of possible outcomes given the uncertainty in epidemiological determinants. We demonstrate that the average number of humans infected by one infectious bovine and the incubation period distribution are the two epidemiological factors that have the greatest impact on epidemic size and duration. Using the time-series of the BSE epidemic and the cases seen to date, we show that the minimum length of the incubation period is approximately nine years, and that at least 20% of the cases diagnosed to date were exposed prior to 1986. We also demonstrate that the current age distribution of vCJD cases can only arise if younger people were either exposed to a greater extent, more susceptible to infection, or have shorter incubation periods. Extensive scenario analyses show that given the information currently available, the very high degree of uncertainty in the future size of the epidemic will remain for the next 3-5 years. Furthermore, we demonstrate that this uncertainty is unlikely to be reduced by mass screening for late-stage infection.     

Epidemiologic observations of influenza B virus infections in Houston, Texas, 1976-1977

Influenza B virus infections were documented in Houston, Texas, in 726 patients with febrile respiratory illnesses who presented to representative primary care facilities during the 1976-1977 respiratory disease season. This epidemic followed a "herald wave" of illness associated with influenza B during the preceding spring. Over one-half the virus isolates were from children aged 5-19 years, and school absenteeism rates indicated that about 40 per cent of the students in the Houston area were ill enough to miss school during the epidemic. The rapid rise in the number of cases among students after the school holiday recess demonstrated the importance of school attendance for the rapid dissemination of influenza viruses. During the later phase of the epidemic, most of the cases were preschool children and adults. In addition to disease of the respiratory tract, the epidemic was accompanied by cases of Reye's syndrome at a rate expected for an urban area.     

Detection of Salmonella cells within 24 to 26 hours in poultry samples with the polymerase chain reaction BAX system

The parents of 470 students randomly selected from 1321 students attending a state high school were surveyed during the 1993-94 measles epidemic, by means of a take-home questionnaire. The response rate was 87%. Thirty stated that their child had measles during this epidemic; nine of these 30 gave a history of previous vaccination. Overall, 312 of the 470 (76%) stated that their child had been vaccinated, but only 34% indicated that they had vaccination records. There were no measles cases during this epidemic in the group with records. Those not vaccinated were at 10 times increased risk of contracting measles compared to those who had been vaccinated with or without records. Vaccine efficacy estimated in general a decade after vaccination based on parental recall of vaccination status regardless of whether they had vaccination records or not was 91% (95% CI 80%-96%). This calculation excluded 123 who claimed to have had measles prior to 1993 and 30 uncertain of their vaccination status.     

Outbreak of epidemic typhus associated with trench fever in Burundi

BACKGROUND: After a 12-year absence, epidemic typhus has re-emerged among the displaced population of Burundi. Following the outbreak of civil war in 1993, over 760000 people now inhabit refugee camps, under appalling conditions. A typhus outbreak occurred among prisoners in a jail in N'Gozi in 1995. At the time, the disease was not recognised, and was referred to as sutama. Reports of sutama among the civilian population date back to late 1995 and, in association with body-louse infestation, the disease has subsequently swept across the higher and colder regions of the country. METHODS: During a field study in February, 1997, 102 refugees with sutama underwent clinical examination and interview. Serum samples were collected and infesting body lice removed. Microbiological analysis included antibody estimations and specific PCRs aimed at diagnosis of Rickettsia prowezekii, Bartonella quintana, and Borrelia recurrentis. Between January and September, 1997, nationwide epidemiological data on the prevalence and distribution of sutama was obtained through liaison with local health services. A second field study in March, 1997, entailed the collection of further serum samples from suspected cases of sutama in different regions of Burundi. FINDINGS: Most of the 102 patients with sutama during initial assessment presented with manifestations similar to those previously described for typhus in Africa, though skin eruptions occurred in only 25 (25%) cases. Microbiological testing revealed evidence of R prowazeki infection in 76 (75%) patients, confirming that most cases of clinically-diagnosed sutama were epidemic typhus, and supporting the reliability of clinical diagnosis as a basis for the nationwide surveillance of the disease. Up to September, 1997, 45558 typhus cases were clinically diagnosed, most of which occurred in regions at an altitude of over 1500 m. Serological testing of 232 individuals from different regions of Burundi provided microbiological evidence to support clinical diagnoses in seven provinces, confirming the widespread nature of the outbreak. Serum from 13 of the original 102 patients and 19 (8%) of the 232 suspected cases had raised antibody titres against B quintana. A fatality rate of 15% among jail inmates fell to 0.5% after administration of a single dose of 200 mg doxycycline to suspected cases. INTERPRETATION: A gigantic outbreak of R prowazekii-induced typhus and B quintana-induced trench fever is continuing in Burundi. Transmission of both diseases to such a large number of people has followed a widespread epidemic of body-louse infestation. Diagnosis of typhus could be reliably made by means of clinical criteria, and the disease could be efficiently and easily treated by antibiotics. This epidemic highlights the appalling conditions in central-African refugee camps and the failure of public-health programmes to serve their inhabitants. Louse-associated disease remains a major health threat in this and other war-torn regions of the world.     

Rhodococcus equi pneumonia in patients infected with the human immunodeficiency virus. Report of 2 cases and review of the literature

Rhodococcus equi is a cause of lung infection in immunosuppressed hosts. Since the start of the HIV epidemic, 76 cases of R. equi lung infection (MEDLINE 1985-96) affecting this population have been described. We report 2 additional cases and review the clinical data, radiological findings, treatment and outcome of these 78 patients. The mean age of these patients was 33 y; 69 were male. 71 met the criteria for AIDS (CDC 1993). Fever and cough were the presenting complaints in the majority of patients (84.3%). A single cavitary lung lesion in the upper lobes was the most common radiological finding (57.7%), although multiple cavitations, alveolar infiltrates and pleural effusion were also found. Treatment usually was based on synergistic antibiotic combinations for a long period of time determined on an individual basis. Surgery was performed only in 11 patients. Death attributable directly to R. equi infection is low (15.4%), however only half of the patients (53.8%) were completely cured. We conclude that R. equi infection should be strongly considered in any HIV patient who presents with cavitary lesions in the lung, especially if mycobacteria are not identified. Treatment must be based on synergistic antibiotic combinations, and surgery relegated to cases of chronic single cavitary lesions not responding to antibiotics.     

Demonstration of Epstein-Barr viral DNA in paraffin-embedded tissues of Burkitt's lymphoma from Argentina using the polymerase chain reaction and in situ hybridization

Burkitt's lymphoma (BL) is the most frequent non-Hodgkin's lymphoma in children in Argentina. Although epidemiologic studies have linked Epstein-Barr virus (EBV) to more than 90% of African BL cases but to only 10-20% of American and French cases, increased EBV-specific antibody titers were demonstrated in 73% of Argentinian patients with BL. To characterize the relationship between EBV and BL in Argentina, we analyzed paraffin-embedded tissues from 16 cases of BL for the presence of EBV DNA using the polymerase chain reaction (PCR) and in situ hybridization (ISH). PCR analysis showed that only 4 of 16 specimens contained the EBV BamW fragment, and these specimens were all from cases diagnosed in 1984. Results of ISH performed with a specific biotinylated DNA probe against the NotI/PstI fragment of EBV correlated with the PCR findings. EBV sequences were detected with ISH in 70-90% of the tumor cells from the 4 positive cases. These data may suggest an epidemic outbreak of EBV-related BL in 1984 superimposed on sporadic cases of BL, for which EBV may not have been an essential factor. This study also demonstrates the value of using molecular techniques on archival tissue to track epidemiologic trends.     

Primary cerebral lymphoma in Zimbabwe: a report of three patients

Primary central nervous system lymphoma (PCNSL) is steadily increasing. Immunosuppressed individuals are at particular risk. In AIDS patients a clinical diagnosis of PCNSL is made in 0.5 to 8.4%, and a post mortem diagnosis in up to 11% of cases. In spite of the extensive HIV epidemic in parts of Africa, a literature search revealed only one African report of this condition. The reasons for this apparent infrequency are not clear. Possibilities include under diagnosis or early demise of patients due to other AIDS related illnesses of earlier onset. Three patients with primary cerebral lymphoma from Zimbabwe are presented. All were young, with tumours of high grade showing typical features.     

An outbreak of Oropouche virus diease in the vicinity of santarem, para, barzil

An epidemic of human febrile illness caused by Oropouche virus was studied in the village of Mojui dos Campos, Pará State, in February 1975. The major clinical symptoms, fever, chills, headache, myalgia, arthralgia and dizziness persisted for 2 to 7 days. Leukopenia was commonly observed. Some patients were severely ill but no deaths were attributed to the disease. Recurrence of symptoms was reported in several people. 55 cases of recent infection were diagnosed in Mojuí dos Campos between February and April. In the same period 26 cases were recorded from the Palhal area, near to Mojuí. Two additional cases were observed, one in the small settlement of Terra Preta and the other in the town of Santarém, which are 12 and 20 km from Mojuí, respectively. Of the 83 infections, 65 were proven by virus isolation from the blood of patients and 18 by the demonstration of an increasing antibody level to the agent. Both sexes of the population were infected in equal proportions. Most patients were below 20 years of age. In the village of Mojuí dos Campos with a population of about 2,900, 45 (40,1%) out of 112 students aged 4 to 18, had HI antibodies to the virus when examined late in February. The epidemic, however, only declined after the middle of March. Two isolations of Oropouche virus were obtained from some 15,000 Culicoides inoculated into mice. About 4,000 Culicoides and all the 9,420 mosquitoes captured during the outbreak remain to be inoculated. Over 95% of the Culicoides were C. paraensis. Only 1 rodent of the genus Proechimys had HI antibodies to Oropouche virus out of the 602 wild and domestic mammals captured in the area. All 5 reptiles examined were negative. 34 (4.9%) out of the 681 wild birds and 12 (5.8%) out of the 206 domestic birds examined were positive for the presence of HI antibodies to the agent.     

Follow-up in 103 patients with catecholamine-secreting tumours

BACKGROUND: It is necessary to have an easy and quickly test to distinguish "false positive" rubella IgM results and residual antibodies from the antibodies produced in the primary infection, in pregnant women. The avidity of IgG antibodies test seems to differentiate between primary rubella infection and past infections, reinfections or postvaccination, showing its utility in the diagnosis of primary infection in other infectious diseases. METHOD: For 30 months, 178 sera from 157 patients with clinical and/or epidemiological rubella suspicion or with a positive rubella IgM result as result of an accidental serological finding, were remitted to our laboratory for a serological follow up. We distinguished 3 patient groups: outbreak group, 112; pregnant women, 36, and newborn 11. Rubella IgM antibodies by indirect EIA previous the rheumatoid factor absorption; IgG antibodies of low avidity by indirect EIA previous treatment of serum with 6 M urea, were detected in the sera. It considered a positive result, a rubella avidity index (AI) < 50%. RESULTS: In the epidemic outbreak group, 90.2% of the patients were not vaccinated. 80% of cases occurred in young men between 14 an 20 years old. From 109 patients (97.3%) with rubella IgG antibodies, 92 (84.4%) showed AI-IgG lower than 50%. In this group, the mean rate of AI-IgG rubella was 29.0%. In the pregnant women group, except for two of them, rubella IgM antibodies were an accidental finding in a serological pregnancy screening. Thirty patients (83.8%) showed AI-IgG rubella > 50%. The two pregnant women who had evidence of clinical and epidemiological rubella showed AI-IgG rubella of 37.4% and 20.9%. Another four pregnant women showed AI-IgG rubella close to cut-off (44.7-49.0%). The mean AI-IgG rubella in this group was 71.8%. The mean AI-IgG Rubella between the epidemic outbreak group and the pregnant women group, 29.0 and 71.8% respectively, was statistical significance (p < 0.001). CONCLUSIONS: The avidity IgG test is simple and quickly, and it allow to exclude most of positive results because of residual IgM antibodies and false reactive.     

The short-term health outcome of out-patient rheumatology consultations in relation to rationing: a pilot study

Although Bombay (Mumbai) appears to be the main focus for acquired immunodeficiency syndrome (AIDS) in India, rapid spread has occurred through other major cities as well. The first AIDS patient in the northern state of Punjab was reported in May 1987. The present study, spanning a decade, shows that the incidence in high-risk groups increased from 3 per 1000 in 1987 to 59 per 1000 in 1997, 73% of the cases being in the third and fourth decades of life, i.e. the most productive years. The male to female ratio was 3.1:1, and 29% of the patients had the full-blown disease. A total of 80.5% acquired the infection heterosexually and only 2% of the patients were intravenous drug users. The percentage of patients acquiring infection through blood, blood products, and haemodialysis dropped from 20% in 1987 to 5% in 1997, but the cumulative figure was still 12%. The intervention programme launched by the National AIDS Control Organization (NACO) appears to have had little impact on the epidemic. There is an urgent need therefore for more interactive programmes that include education concerning the modes of spread, course, financial implications and fatal outcome of the disease, instead of passive dissemination of information by posters and the media.     

The scourge of HIV-related tuberculosis: a cohort study in a district general hospital in Malawi

Malawi is similar to a number of other African countries in having an escalating, HIV-related, tuberculosis (TB) epidemic. A prospective study was carried out to determine the pattern of disease and HIV serostatus in unselected, adult, TB patients consecutively admitted to a large, district general hospital in Zomba (in the Southern region of Malawi). Clinical details were obtained, from the district TB register, for the 714, adult TB patients, aged > or = 15 years, who were registered with the district TB officer between 1 July and 31 December in 1995. Patients were counselled, and offered HIV testing using an ELISA and particle agglutination test. Concordant HIV-test results were available for 686 (96%) of the subjects: 547 (80%) of these were HIV-seropositive and 139 seronegative. The HIV-positive patients were significantly younger than the HIV-negative patients and significantly more HIV-positive patients were males (P < 0.05 for each). The proportions of HIV-positive subjects who were new patients, had been previously treated for TB, had pulmonary TB (PTB), had smear-positive PTB or had different types of extrapulmonary TB were similar to those of the HIV-negative. A high percentage of an unselected cohort of adult TB patients admitted to a district, general hospital in Malawi, particularly of the younger age groups was therefore HIV-positive. The pattern of disease was uninfluenced by the HIV serostatus. The large number of cases registered emphasises the severity of the current epidemic of TB in Malawi and its impact upon young adults.