Synergistic interactions between two skeletal mutations in mice: individual and combined effects of the semidominants cleidocranial dysplasia (Ccd) and short digits (Dsh).

Heterozygotes for cleidocranial dysplasia (Ccd) and short digits (Dsh) were crossed to test whether synergistic interactions occur between different dominant mutations whose individual pleiotropic phenotypic effects exhibit a common feature. These unlinked mutations are homozygous lethal, and they are congenic on the C57BL/10 background. Each mutation caused more than 10 different anomalies and showed variable expressivity. Each mutation produced several malformations that were present in every heterozygote. Seven different synergistic interactions were found, including one that yielded an entirely new abnormality not predicted from any abnormalities found in either of the single heterozygotes. Although synergistic interactions between dominant mutations have not, to our knowledge, been described in humans, these findings in mice increase the probability that they occur in humans. Under certain circumstances in human populations, the segregation of mutations causing synergistic interactions of the type demonstrated might be confused with recessive inheritance. It will be important to learn whether synergistic interactions can occur between other mutations. If they can, it will probably become important to take synergistic interactions into account when estimating the genetic hazards to humans from mutagens. Three antagonistic interactions were also found.

Connective tissue disease in southeast Georgia. A community based study of immunogenetic markers and autoantibodies.

HLA antigens, C4 allotypes and T cell antigen receptor (TcR)beta DNA polymorphisms were determined in a community based study of connective tissue diseases (CTD). HLA-B8, DR3 and C4A null phenotypes occurred frequently in Caucasian patients with CTD, especially those with systemic lupus erythematosus (SLE), but were also more commonly found among healthy white controls of this southeast Georgia community. TcR beta gene polymorphisms also showed differential segregation patterns between patients with SLE and scleroderma. High frequencies of ANA and anti-ssDNA antibodies occurred among apparently healthy family members and local controls. Genetic factors predisposing to CTD in a community setting appear to be similar to those reported from referral centers.

Recovery of hepatitis A virus from a water supply responsible for a common source outbreak of hepatitis A.

An outbreak of hepatitis A occurred in a north Georgia trailer park served by a private well. Of 18 residents who were serosusceptible to hepatitis A virus (HAV), 16 (89%) developed hepatitis A. Well water samples were collected 3 months after illness onset in the index case and 28 days after illness onset in the last trailer park resident. Hepatitis A virus antigen (HAVAg) was detected in the samples by enzyme immunoassay from three of the five cell lines following two 30-day passages and from a fourth cell line following a third passage of 21 days.

Epidemiologic evidence that prior antimicrobial exposure decreases resistance to infection by antimicrobial-sensitive Salmonella.

Exposure to antimicrobials is known to increase the risk of infection with antimicrobial-resistant strains of Salmonella, but this effect has not been previously demonstrated with antimicrobial-sensitive strains. The effect of prior antimicrobial exposure was studied during a multistate outbreak of salmonellosis caused by an antimicrobial-sensitive strain of Salmonella havana: 19 (26%) of 72 persons infected had taken an antimicrobial within 30 days before onset of symptoms. Antimicrobial therapy was begun a mean of 15.9 days before and stopped a mean of 7.9 days before onset. In a case-control study, 11 (31%) of 35 case-patients had taken antimicrobials within 30 days of onset compared with 9 (13%) of 70 age- and neighborhood-matched controls (matched odds ratio, 4.3; 95% confidence interval, 1.3, 13.5). The association remained when controlled for the presence of underlying illness or immunosuppression. Prior antimicrobial exposure appears to increase the risk of infection with antimicrobial-sensitive and resistant strains of Salmonella. The delay between antimicrobial use and onset of symptoms suggests that the effect may be due to prolonged alteration of the colonic bacterial flora, resulting in decreased resistance to colonization.

Mass sociogenic illness by proxy: parentally reported epidemic in an elementary school.

In a cluster of illness reported among students at an elementary school parents mentioned many signs and symptoms including headache, pallor, dark circles under the eyes, nausea, and vomiting--which they attributed to exposure to recurrent leaks of natural gas at the school. It is likely that the parents spread among themselves the notion of toxic exposure at the school. A questionnaire revealed no spatial clustering, but increased reports of symptoms were related to intense media coverage. A thorough environmental and epidemiological investigation was negative, there being no evidence of a continuing gas leak or other potential causes. At a strictly biological level, the complaints in this reported "cluster" apparently represented the sporadic occurrence of common childhood illnesses. The possibility of an epidemic from toxic exposure at the school caused intense parental concern and led to a major public health problem. The established term "mass sociogenic illness" seems inapplicable here because complaints did not come principally from the students and the apparent epidemic illness was not transmitted among them. The term "mass sociogenic illness by proxy" is proposed to describe this incident, in which transmission in one group (the parents) resulted in reports of an epidemic in another group (students).

The health and economic burden of cigarette smoking in Georgia in 1985.

Using the estimated prevalence of current and former cigarette smoking among Georgians, death certificate data in 1985, and the available literature on smoking-related health risks, we estimated the health and economic impact of cigarette smoking in Georgia in a single year. We estimated, using relatively conservative assumptions, the mortality and years of life lost prematurely, as well as the costs of medical care for ill individuals, lost wages due to death, and lost wages due to illness attributable to smoking. In 1985, past or present smoking was the cause of death for more than 7,700 Georgians, accounting for over 120,000 years of expected life lost prematurely, and with an overall societal cost exceeding $1.5 billion dollars. Cardiovascular diseases were the major cause of all estimated deaths associated with smoking. The prevalence of current smokers is higher in Georgians than the national average; this approach to examining the risks may be useful in lowering that prevalence by influencing patient education in Georgia.

Connective tissue disease in southeastern Georgia: a case-control study of etiologic factors.

The authors conducted a population-based case-control study of connective tissue disease in a four-county area in southeastern Georgia. Interviews with 44 cases and 88 controls were conducted in September and October of 1986. The association with a family history of these disorders was reconfirmed, and a positive association with the use of hair dyes was found. A negative association was found with a family history of diabetes mellitus.

Large community outbreak of cryptosporidiosis due to contamination of a filtered public water supply.

Between January 12 and February 7, 1987, an outbreak of gastroenteritis affected an estimated 13,000 people in a county of 64,900 residents in western Georgia. Cryptosporidium oocysts were identified in the stools of 58 of 147 patients with gastroenteritis (39 percent) tested during the outbreak. Studies for bacterial, viral, and other parasitic pathogens failed to implicate any other agent. In a random telephone survey, 299 of 489 household members exposed to the public water supply (61 percent) reported gastrointestinal illness, as compared with 64 of 322 (20 percent) who were not exposed (relative risk, 3.1; 95 percent confidence interval, 2.4 to 3.9). The prevalence of IgG to cryptosporidium was significantly higher among exposed respondents to the survey who had become ill than among nonresident controls. Cryptosporidium oocysts were identified in samples of treated public water with use of a monoclonal-antibody test. Although the sand-filtered and chlorinated water system met all regulatory-agency quality standards, sub-optimal flocculation and filtration probably allowed the parasite to pass into the drinking-water supply. Low-level cryptosporidium infection in cattle in the watershed and a sewage overflow were considered as possible contributors to the contamination of the surface-water supply. We conclude that current standards for the treatment of public water supplies may not prevent the contamination of drinking water by cryptosporidium, with consequent outbreaks of cryptosporidiosis.

Life-style factors among patients with melanoma.

For the period 1975 to 1980, melanoma incidence in persons 10 through 49 years of age in a southwest Georgia town was significantly increased compared with US rates (expected = 9; observed = 41) and Atlanta rates (expected = 13; observed = 41). We surveyed 36 white patients with melanoma and 74 unaffected control subjects to identify risk factors possibly associated with melanoma in this population. When compared with the controls, the patients more often had a history of melanoma in family members [odds ratio (OR) = 8.00; 95% confidence limits (CL) = 0.89 to 71.6; P = .063]; skin sensitivity to sun exposure (OR = 1.63; CL = 1.04 to 2.56; P = 0.016); or preexisting pigmented nevi (OR = infinity; one-sided 95% lower limit = 1.94, P = .005). More male patients had melanomas on covered body sites, though 67% of melanomas in both sexes occurred on normally covered sites. Patients in our study also had been exposed more often than controls to sick animals in the year before onset (OR = 3.18; CL = 0.92 to 11.0; P = .055) and to pesticides in nonoccupational settings (OR = 3.56; CL = 0.87 to 14.5; P = .059).

Pseudomonas aeruginosa serotype 0:9. New cause of whirlpool-associated dermatitis.

In a five-day period, dermatitis developed in nearly one fourth of the guests staying at a large Georgia hotel. Dermatitis was associated with use of the hotel's whirlpool (p less than 0.001) and indoor swimming pool (p less than 0.001). Attack rates were highest among persons more frequently exposed to the whirlpool, in persons under 10 years of age, and during periods of heaviest bather load. Pseudomonas aeruginosa was isolated from skin lesions of 13 of 20 patients from whom culture specimens were taken. Ten isolates were serotype 0:9. The whirlpool's water grew P. aeruginosa serotype 0:9; however, the whirlpool's automatic chlorinator was functioning properly, the pH of the water was 7.2, and the free chlorine level was 0.6 mg/liter. This is the first report of a whirlpool-associated outbreak caused by P. aeruginosa serotype 0:9. Our findings suggest that this strain may not be readily sensitive to recommended chlorine concentrations.

Norwalk gastroenteritis associated with a water system in a rural Georgia community.

An outbreak of acute gastroenteritis occurred during January 4-9, 1982, in a rural community in north Georgia. A systematic telephone survey revealed that 63% of persons living in homes served by the community water system had symptoms of acute gastroenteritis in contrast to 9% of persons in homes served by private wells or other sources (P less than .001). A fourfold rise in antibody titer to the Norwalk virus occurred in 20 of 22 serum pairs obtained from ill persons. Fecal coliforms (greater than 16 MPN/100 ml) were detected in a spring which served as one water source for the community system. Surface runoff from a heavy rainfall, which preceded the outbreak, may have contaminated the system. Outbreaks of gastroenteritis should be promptly reported and investigated to facilitate corrective measures and to identify causative agents such as Norwalk virus.

Epidemiology of an outbreak of head lice in Georgia.

An outbreak of head lice infestation (pediculosis) occurred in elementary school children in Barrow County, Georgia, in January 1974. An investigation was initiated to define the magnitude of the outbreak, determine factors that contribute to transmission, and disseminate information on control. All elementary school children in the county were examined for head lice and answered a questionnaire. Fifty-three (3%) of 1,783 white pupils were infested, but none of the 500 black pupils was infested. Distribution of infestation in the white pupils was influenced by grade, bed-sharing, socioeconomic status, infestation of other family members, crowding in the home, and family size; distribution was not influenced by hair length or the sex of the pupil. Recommendations for control based on the results of the investigation included procedures for identifying and processing cases, distributing free pediculicides, continuing surveillance, educating school personnel and parents on how to control the parasite.