Dynamics of the HIV epidemic in southern China: sexual and drug-using behaviours among female sex workers and male clients in Yunnan.

To examine the HIV/sexually transmitted infection (STI)-related risk behaviours among community-based female sex workers (FSWs) and their clients in Yunnan Province, China, we performed a cross-sectional study of 705 FSWs and 100 male clients. We found that HIV seroprevalence among FSWs was 13.0% and the most prevalent STI was herpes simplex virus type 2 (HSV-2) (71.1%), followed by Chlamydia trachomatis (18.1%) and syphilis (8.8%). The 20% of FSWs who reported injection drug use also reported needle-sharing behaviours in the last three months. Drug-using FSWs had substantially higher HIV and HSV-2 prevalence, serviced more clients and had a longer history of sex work than non-using FSWs. In total, 57.0% of male clients did not consistently use condoms with FSWs, 2.0% reported illicit drug use and 17.0% had STI symptoms in the last year. The dual risk behaviours of drug-using FSWs and clients place them at greater risk of HIV infection. Intervention programmes must adopt comprehensive methods.

High frequency of low-level microsatellite instability in early colorectal cancer.

Molecular events in early colorectal cancers (CRCs) have not been well elucidated because of the low incidence of early CRCs in clinical practice. Therefore, we studied 104 sporadic early CRCs with invasion limited to submucosa compared with 116 advanced CRCs. Loss of heterozygosity as well as microsatellite instability (MSI) status was examined. A significantly high frequency of low-level MSI (MSI-L) phenotype was detected in early CRCs (51.0%) compared with advanced CRCs (25.9%; P = 0.0001). In early and advanced CRCs, samples with MSI-L phenotype differed from microsatellite stable (MSS) phenotype with respect to loss of heterozygosity at 1p32 and 8p12-22. MSI-L is a frequent genetic event in early CRCs and may be a novel pathway in colorectal carcinogenesis distinct from both MSI-H and MSS.

Liver cancer in atomic-bomb survivors: histological characteristics and relationships to radiation and hepatitis B and C viruses.

Histological features of primary liver cancer among atomic-bomb survivors and their relationship to hepatitis B (HBV) and C viral (HCV) infections are of special interest because of the increased risk of liver cancer in persons exposed to ionizing radiation and the high and increasing liver cancer rates in Japan and elsewhere. We conducted a pathology review of liver cancers occurring from 1958 to 1987 among subjects in the 120,321 member cohort of 1945 Hiroshima and Nagasaki residents. A panel of pathologists classified tumor histological types and defined accompanying cirrhotic changes of the liver. Archival tissue samples were assessed for HBV using pathology stains and PCR. Reverse transcriptase (RT) PCR was used to determine HCV status. We used unconditional logistic regression to compare 302 hepatocellular carcinoma (HCC) cases to 53 cholangiocarcinoma (CC) cases, adjusting for age, year of diagnosis, sex and viral status. Cirrhotic changes occurred significantly more often among HCC than CC cases (76% in HCC and 6% in CC). Compared to CC cases, HCC cases were 10.9 times more likely to be HBV-positive (95% confidence interval: 2.1-83.2) and 4.3 times more likely to be HCV-positive (95% confidence interval: 1.1-20.5). No significant differences were found between HCC and CC cases in radiation exposures. The predominance of HCC in the atomic-bomb survivors follows the background liver cancer pattern in Japan. Our findings suggest that HBV and HCV are involved in the pathogenesis of HCC with or without cirrhosis and are significantly less important in that of CC.

Temporal changes in liver cancer incidence rates in Japan: accounting for death certificate inaccuracies and improving diagnostic techniques.

Primary liver cancer (PLC) rates have risen dramatically during the past few decades in some regions, particularly in Japan, where PLC is now the third major cause of cancer death. PLC is one of the most difficult tumors to diagnose correctly, because (i) the liver is a frequent site of cancer metastasis and (ii) death from PLC is often attributed to cirrhosis or chronic hepatitis. Also, because the disease is often rapidly fatal, a large proportion of liver cancer cases are identified based on death certificates alone without confirmation by clinical records. Thus, worldwide differences in published incidence rates for this disease reflect regional or national differences in both the accuracy of death certificates and the sensitivity of diagnostic methods. By comparing death certificate causes of death with those based on pathology review, we were able to adjust 1958--1994 incidence rates for a large Japanese cohort for these errors. Although the death certificate false-positive error rate declined, the false-negative error rate remained high throughout the study. The introduction of improved liver cancer diagnostic methods in Japan in the early 1980s was associated with a sharp increase in PLC incidence. We conclude that errors in death certificate causes of death and changes in liver cancer diagnostic techniques have had an important impact on the reported incidence of this disease. Taking these factors into account, rates of hepatocellular carcinoma rose between 2.4- and 4.3-fold in our Japanese cohort from 1960 to 1985, peaked about 1993 and declined thereafter. Incidence rates of cholangiocarcinoma remained stable through 1987.

Patterns of memory performance in children with controlled epilepsy on the CVLT-C.

Decreased memory skills have been reported in children with epilepsy. However, standardized instruments to evaluate learning and memory in children have been unavailable until recently. The present study was designed to assess memory patterns in children with epilepsy based on the California Verbal Learning Test-Children's Version (CVLT-C). The test was administered to 44 children with complex partial seizures and 21 children with generalized seizures between 8 and 13 years of age. Children in the study had been treated for epilepsy for at least 6 months, had well-controlled seizures on monotherapy, and had no evidence of anticonvulsant toxicity. Children with head injuries, learning disabilities, or hyperactivity were excluded. Test results did not reflect differences in memory performance based on seizure type. Scores for the entire sample indicated intact new learning, decreased intrusions and perseverative responses, and better short-term than long-term delayed recall. Recognition skills were stronger than long-term delayed recall skills and suggested that memory performance may be improved for these children when a multiple-choice format is available in academic settings.

Bladder-cancer incidence in relation to vegetable and fruit consumption: a prospective study of atomic-bomb survivors.

We examined the relation between consumption of 22 dietary items and subsequent bladder-cancer incidence in a cohort of atomic-bomb survivors in Japan. Subjects were 38,540 people (14,873 men and 23,667 women) who responded to a mail survey carried out between 1979 and 1981 and who had no known cancer diagnosed before the start of follow-up (1 January 1980 for men, 1 February 1981 for women). Consumption frequencies for 22 dietary items were ascertained with pre-coded answers. As of the end of 1993, there were 114 (83 men and 31 women) incident cases of bladder cancer among 450,326 person-years at risk. Statistical analysis was done using Poisson regression for grouped survival data Consumption of green-yellow vegetables and fruit were protectively associated with risk. Adjusted for gender, age, radiation exposure, smoking status, educational level, body-mass index and calendar time, the relative risk (RR) for those consuming green-yellow vegetables 2-4 times per week and almost everyday was 0.62 [95% confidence interval (CI) 0.39-0.98] and 0.54 (95% CI 0.30-0.94) respectively, as compared with those consuming once per week or less. The corresponding RR for fruit consumption was 0.50 (0.30-0.81) and 0.62 (0.39-0.99) respectively. Chicken consumption was unexpectedly associated with decreased risk, but additional adjustment for consumption did not change the relation of green-yellow vegetables or of fruit to risk. The consumption of the other dietary items, including meat and green tea, was not related to risk. The findings add to evidence that high consumption of vegetables and fruit are protective against bladder cancer.

Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan.

The association between soya foods and breast cancer risk was investigated in a prospective study of 34759 women in Hiroshima and Nagasaki, Japan. Women completed dietary questionnaires in 1969-1970 and/or in 1979-1981 and were followed for incident breast cancer until 1993. The analysis involved 427 cases of primary breast cancer in 488989 person-years of observation. The risk for breast cancer was not significantly associated with consumption of soya foods: for tofu, relative risks adjusted for attained age, calendar period, city, age at time of bombings and radiation dose to the breast were 0.99 (95% CI 0.80-1.24) for consumption two to four times per week and 1.07 (0.78-1.47) for consumption five or more times per week, relative to consumption once a week or less; for miso soup, relative risks were 1.03 (0.81-1.31) for consumption two to four times per week and 0.87 (0.68-1.12) for consumption five or more times per week, relative to consumption once a week or less. These results were not materially altered by further adjustments for reproductive variables and were similar in women diagnosed before age 50 and at ages 50 and above. Among 17 other foods and drinks examined only dried fish (decrease in relative risk with increasing consumption) and pickled vegetables (higher relative risk with higher consumption) were significantly related to breast cancer risk; these associations were not prior hypotheses and, because of the large number of comparisons made, they may be due to chance.

Family history of cancer in children and young adults with colorectal cancer.

BACKGROUND: Family history of colorectal cancer among adult patients has been reported in the literature. Although extremely rare in children, colorectal cancer in this population may represent a unique group in whom genetic factors play a significant etiologic role. The aim of the present study was to assess genetic contribution, as measured by family history, to the development of colorectal cancer in probands under 21 years of age at diagnosis. PROCEDURE: Detailed family histories were obtained from surviving patients or their parents. The risk [standardized incidence ratio (SIR)] of cancer in the relatives was calculated by comparing the observed and the expected incidence based on rates in the general population and person-years at risk. RESULTS: Twenty-five patients (median age at diagnosis 15 years) diagnosed with colorectal cancer at St. Jude Children's Research Center since 1964 or their surviving next of kin were available for interview. The 461 relatives contributed 18,908 person-years of follow-up. Statistically significant increased risk of colorectal cancer was present among all relatives (SIR = 6.0, 95% CI, 2.7-10.6), and the increased risk of colorectal cancer was confined to relatives of probands who were under 15 years of age at diagnosis (SIR = 10.0, 95% CI, 4.5-17.6). In addition, there was an excess of uterine/cervical cancer among all female relatives (SIR = 6.5, 95% CI, 3.2-10.9). CONCLUSIONS: The observed excess of colorectal cancer, in relatives of younger probands, suggests the need to examine these kindreds for genetic instability resulting from defects in mismatch repair genes to characterize further the patterns of risk observed.

Cognition and behavior after temporal lobectomy in pediatric patients with intractable epilepsy.

The increased use of surgical intervention for intractable epilepsy during childhood has resulted in a critical need for information concerning possible cognitive and behavioral changes in pediatric patients after surgery. In this pilot study, comprehensive neuropsychologic evaluations were completed on nine children who had a temporal lobectomy for intractable epilepsy before 16 years of age. Performances before and after surgery were compared using cognitive and behavioral measures. Repeated measures analysis of variance did not indicate differences in performance on the basis of laterality of surgery, although the number of left (n = 5) vs right (n = 4) temporal resections was small. Paired comparison t tests, which included all patients, did not suggest marked changes in cognitive functioning after surgery, although decreases in delayed verbal memory were evident. Positive effects on quality of life during the first year after surgical intervention were suggested by reduced internalizing symptoms and increased social interaction. Replication of this study is recommended with a larger number of patients and multicenter collaboration.

A comparison of rectal diazepam gel and placebo for acute repetitive seizures.

BACKGROUND: Acute repetitive seizures are readily recognizable episodes involving increased seizure frequency. Urgent treatment is often required. Rectal diazepam gel is a promising therapy. METHODS: We conducted a randomized, double-blind, parallel-group, placebo-controlled study of home-based treatment for acute repetitive seizures. Patients were randomly assigned to receive either rectal diazepam gel, at a dosage varying from 0.2 to 0.5 mg per kilogram of body weight on the basis of age, or placebo. Children received one dose at the onset of acute repetitive seizures and a second dose four hours later. Adults received three doses -- one dose at onset, and two more doses 4 and 12 hours after onset. Treatment was administered by a care giver, such as a parent, who had received special training. The number of seizures after the first dose was counted for 12 hours in children and for 24 hours in adults. RESULTS: Of 125 study patients (64 assigned to diazepam and 61 to placebo) with a history of acute repetitive seizures, 91 (47 children and 44 adults) were treated for an exacerbation of seizures during the study period. Diazepam treatment was superior to placebo with regard to the outcome variables related to efficacy: reduced seizure frequency (P<0.001) and improved global assessment of treatment outcome by the care giver (frequency and severity of seizures and drug toxicity) (P<0.001). Post hoc analysis showed diazepam to be superior to placebo in reducing seizure frequency in both children (P<0.001) and adults (P=0.02), but only in children was it superior with regard to improvement in global outcome (P<0.001). The time to the first recurrence of seizures after initial treatment was longer for the patients receiving diazepam (P<0.001). Thirty-five patients reported at least one adverse effect of treatment; somnolence was the most frequent. Respiratory depression was not reported. CONCLUSIONS: Rectal diazepam gel, administered at home by trained care givers, is an effective and well-tolerated treatment for acute repetitive seizures.

Coinfection of wild ducks by influenza A viruses: distribution patterns and biological significance.

Coinfection of wild birds by influenza A viruses is thought to be an important mechanism for the diversification of viral phenotypes by generation of reassortants. However, it is not known whether coinfection is a random event or follows discernible patterns with biological significance. In the present study, conducted with viruses collected throughout 15 years from a wild-duck population in Alberta, Canada, we identified three discrete distributions of coinfections. In about one-third of the events, which involved subtypes of viruses that appear to be maintained in this duck reservoir, coinfection occurred at rates either close to or significantly lower than one would predict from rates of single-virus infection. Apparently, the better adapted an influenza A virus is to an avian population, the greater is its ability to prevent coinfections. Conversely, poorly adapted, nonmaintained viruses were significantly overrepresented as coinfectants. Rarely encountered subtypes appear to represent viruses whose chances of successfully infiltrating avian reservoirs are increased by coinfection. Mallards (Anas platyrhynchos) and pintails (A. acuta) were significantly more likely to be infected by a single influenza A virus than were the other species sampled, but no species was significantly more likely to be coinfected. These observations provide the first evidence of nonrandom coinfection of wild birds by influenza A viruses, suggesting that reassortment of these viruses in a natural population does not occur randomly. These results suggest that even though infections may occur in a species, all subtypes are not maintained by all avian species. They also suggest that specific influenza A virus subtypes are differentially adapted to different avian hosts and that the fact that a particular subtype is isolated from a particular avian species does not mean that the virus is maintained by that species.

Late mortality of long-term survivors of childhood cancer.

PURPOSE: To determine the frequency and patterns of late mortality among long-term survivors of childhood cancer. MATERIALS AND METHODS: Medical records of patients who survived at least 5 years after the diagnosis of childhood cancer were reviewed to determine the causes of subsequent deaths. Estimated 15-year survival and standardized mortality ratios for deaths from nonneoplastic treatment complications were compared with adjusted United States population estimates. The study included 2,053 patients who had survived > or = 5 years, grouped by treatment eras that reflected increased intensity of therapy and significantly improved survival (early era, 1962 to 1970; recent era, 1971 to 1983). RESULTS: There have been 258 subsequent deaths in the 2,053 childhood cancer survivors; 169 occurred 5 to 10 years postdiagnosis and 89 > or = 10 years post diagnosis. For the study period as a whole, deaths were attributed to recurrent primary malignancy in 61% of cases, second malignancy in 20%, nonneoplastic treatment complication in 10%, and unintentional injury/suicide in 8%. Late death from recurrent disease decreased significantly for survivors treated in the recent era (P < .0001), while the risk of death from second malignancies increased, although not statistically significantly (P = .10). Projected 15-year survival estimates for all > or = 5-year survivors in both treatment eras was greater than 90%, but differed from expected rates. CONCLUSION: Late mortality from recurrence after treatment for childhood cancer decreases with more effective initial therapy. Prolonged disease-free status is associated with an expected survival that approaches that of the general population for patients treated from 1971 through 1983. The impact of more recent intensified and novel therapies for high-risk patients remains to be determined.

Ultrasonography for thyroid screening after head and neck irradiation in childhood cancer survivors.

We prospectively used ultrasonography to detect thyroid abnormalities in 96 long-term survivors of childhood cancer, who received head and neck radiation therapy at a median age of 8.9 years. The median time interval since irradiation was 10.8 years (range 5.6-22.8 years). Most survivors of leukemia received 24 Gy cranial irradiation for central nervous system prophylaxis; patients with solid tumors received between 20 and 66 Gy (median 37.5 Gy). The total evaluation included clinical history, physical examination, thyroid function tests, and thyroid ultrasonography; radionuclide scans were performed in patients whose abnormalities persisted on subsequent ultrasound exams. Clinical history and physical examination revealed thyroid abnormalities in 14 patients (15%), but ultrasound detected abnormalities in 42 patients (44%). These findings included inhomogeneity (n = 29), cysts (n = 15), and nodules (n = 22) and occurred in nearly half of patients treated with 15 Gy or more directly to the thyroid gland. Radionuclide scans confirmed the presence of thyroid nodules in 13 of 15 patients with ultrasonographic evidence of nodules. Six patients had thyroid neoplasia, including one case of papillary carcinoma. All patients with neoplasia had nodules demonstrated on ultrasonography. Our experience suggests that in childhood cancer survivors, ultrasonography is a sensitive, affordable, and noninvasive means of detecting subtle parenchymal abnormalities. We recommend thyroid ultrasonography for childhood cancer survivors who received head and neck irradiation. A baseline study should be obtained within 1 year of completion of therapy. The frequency of subsequent examinations should be based on the radiation dose and the patient's age at the time of irradiation.

An epidemiological study of influenza viruses among Chinese farm families with household ducks and pigs.

To examine the possibility of interspecies transmission and genetic reassortment of influenza viruses on farms in Southern China, we surveyed 20 farm families living outside the city of Nanchang who raised pigs and ducks in their homes. Weekly interviews of family members and virus isolation studies of throat swabs and faecal samples, collected from September 1992 to September 1993, established the seasonal pattern of respiratory tract infections in these families and identified 11 influenza viruses (6 in humans and 5 in ducks). Most of the human isolates were type A of H3N2 subtype. Serologic studies of farm pigs indicated infection by the same human viruses circulating in family members, but there was no evidence that either swine or avian viruses had been transmitted to pigs. Eight of 156 human serum samples inhibited the neuraminidase activity of two of the duck isolates, raising the possibility of interspecies transmission of these avian viruses. Genotype analysis of duck and human isolates provided no evidence for reassortment. Our finding support the concept that intermingling of humans, pigs and ducks on Chinese farms is favourable to the generation of new, potentially hazardous strains of influenza virus.

Hereditary spastic paraplegia linked to chromosome 15q: Analysis of candidate genes.

We previously reported an extended kindred with autosomal dominant uncomplicated hereditary spastic paraplegia (HSP) and found close linkage between the disorder and microsatellite polymorphisms on chromosome 15q. Multipoint linkage analysis reached a maximum LOD score (10.16) between D15S128 and D15S156, a region that includes genes encoding alpha5 and beta3 subunits of GABAA receptor. Theoretically, abnormal GABA-mediated neurotransmission could produce spasticity and possibly other changes of HSP. We used genetic linkage analysis to evaluate these two HSP candidate genes and observed obligate recombinants for polymorphisms immediately adjacent to (or within untranslated regions of) genes encoding alpha5 and beta3 GABAA receptor subunits. Although these genes are linked tightly to the HSP locus, our findings conclusively exclude these genes from being responsible for HSP in this kindred.

Genetic reassortment in pandemic and interpandemic influenza viruses. A study of 122 viruses infecting humans.

The human influenza pandemics of 1957 and 1968 were caused by reassortant viruses that possessed internal gene segments from avian and human strains. Whether genetic reassortment of human and avian influenza viruses occurs during interpandemic periods and how often humans are infected with such reassortants is not known. To provide this information, we used dot-blot hybridization, partial nucleotide sequencing and subsequent phylogenetic analysis to examine the 6 internal genes of 122 viruses isolated in humans between 1933 and 1992 primarily from Asia, Europe, and the Americas. The internal genes of A/New Jersey/11/76 isolated from a human fatality at Fort Dix, New Jersey in 1976 were found to be of porcine origin. Although none of the geographically and temporally diverse collection of 122 viruses was an avian-human or other reassortant, cognizance was made of the fact that there were two isolates from children from amongst 546 influenza A isolates obtained from The Netherlands from 1989-1994 which were influenza A reassortants containing genes of avian origin, viruses which have infected European pigs since 1983-1985. Thus, genetic reassortment between avian and human influenza strains does occur in the emergence of pandemic and interpandemic influenza A viruses. However, in the interpandemic periods the reassortants have no survival advantage, and the circulating interpandemic influenza viruses in humans do not appear to accumulate avian influenza virus genes.

Influenza infection in humans and pigs in southeastern China.

The three last pandemic strains of influenza A virus-Asian/57, Hong Kong/68 and Russian/77-are believed to have originated in China. The strains responsible for the 1957 and 1968 human pandemics were reassortants incorporating both human and avian influenza viruses, which may have arisen in pigs. We therefore undertook a population-based study in the Nanchang region of Central China to establish the prevalence, types and seasonal pattern of human influenza infection and to screen serum samples from animals and humans for evidence of interspecies transmission of influenza viruses. Two definite influenza seasons were demonstrated, one extending from November to March and the other July to September. The profile of antibodies to commonly circulating human influenza viruses was no different in Nanchang and neighboring rural communities than in Memphis, Tennessee, USA. In particular, Chinese women who raised pigs in their homes were no more likely to have been exposed to influenza virus than were subjects who seldom or never had contact with pigs. However, we did obtain evidence using isolated H7 protein in an enzyme-linked immunoabsorbent assay for infection of pig farmers by an avian H7 influenza virus suggesting that influenza. A viruses may have been transmitted directly from ducks to humans. The results of the serological survey also indicated that pigs in or near Nanchang were infected by human H1N1 and H3N2 influenza viruses, but not with typical swine viruses. We found no serological evidence for H2 influenza viruses in humans after 1968.

Interspecies transmission of influenza viruses.

In this report we examine the hypothesis that aquatic birds are the primordial source of all influenza viruses in other species. Two partly overlapping reservoirs of influenza A viruses exist in migrating water-fowl and shorebirds throughout the world. These species harbor influenza viruses of all the known hemagglutinin and neuraminidase subtypes. In contrast to the rapid, progressive changes in both the nucleotide and amino acid sequences of mammalian virus gene lineages, avian virus genes show far less variation and, in most cases, appear to be in evolutionary stasis. There are periodic exchanges of influenza virus genes or whole viruses between species, giving rise to pandemics of disease in humans, lower animals, and birds. The periodic exchange of influenza viruses between species has been illustrated by the appearance of new pandemic influenza viruses in humans, including the Spanish influenza of 1918, the Asian influenza of 1957, and the Hong Kong influenza of 1968. Transmission of avian influenza viruses to swine in Europe in 1979 has resulted in the appearance of human-avian reassortant influenza viruses in pigs in Italy and in children in the Netherlands. These studies provide evidence supporting the possibility that pigs serve as a mixing vessel for reassortment between influenza viruses in mammalian and avian hosts and raise the question of whether the avian influenza viruses now circulating in European swine are the precursors of the next human pandemic virus.

Aspirin and reduced risk of esophageal carcinoma.

BACKGROUND: Aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) have been shown experimentally to inhibit chemically induced esophageal cancers. An epidemiologic study of more than 600,000 adults in the United States followed for 6 years found that aspirin use was associated with a reduced risk of death from esophageal cancer. METHODS: The relation of aspirin use and esophageal cancer was examined using data from the National Health and Nutrition Examination Survey (NHANES I) and the National Epidemiologic Follow-up Studies (NEFS). Of the 14,407 United States residents followed for 12-16 years, esophageal cancer developed in 15. Persons were classified as nonusers, occasional users, or regular users of aspirin based on their response to two questions at the baseline examination: whether they had taken aspirin in the past 30 days and whether they had used pain medications regularly during the prior 6 months. RESULTS: Occasional use was associated with a 90% decreased risk (95% confidence interval, 0.01-0.76) of developing esophageal cancer, and no person classified as a regular user developed the disease. Adjusting for cigarette smoking (ever vs. never) and alcohol intake (at least monthly vs. not) did not explain the finding. CONCLUSION: Aspirin use was associated with a 90% decreased risk of developing esophageal carcinoma. Further studies to determine whether aspirin is protective against both squamous cell esophageal carcinoma and adenocarcinoma of the esophagus are indicated.