Activation of the androgen receptor alters the intracellular calcium response to glutamate in primary hippocampal neurons and modulates sarco/endoplasmic reticulum calcium ATPase 2 transcription.

Androgens have been shown to have a number of effects on hippocampal function. Although androgen receptors (AR) are found at high levels in hippocampal neurons, the intracellular mechanisms responsible for androgen's actions are unknown. If androgens were capable of altering internal calcium concentration ([Ca(2+)](i)), they could influence a variety of intracellular signaling pathways, maintain neuronal homeostasis and Ca(2+) induced excitotoxicity. In the present study, calcium imaging was used to measure the [Ca(2+)](i) in rat primary hippocampal neurons treated with either the AR agonist dihydrotestosterone (DHT), DHT+flutamide (AR antagonist), flutamide alone, or vehicle for 24 h and subsequently presented with an excitatory glutamate stimulus. In the absence of glutamate stimulation, DHT treatment caused a significant upward shift in baseline [Ca(2+)](i) when compared with neurons from all other groups. Glutamate had a greater effect on [Ca(2+)](i) in DHT-treated neurons and DHT-treated neurons returned to baseline levels significantly faster than all other groups. Cyclopiazonic acid, an inhibitor of sarco/endoplasmic reticulum calcium ATPase (SERCA) had a larger response in DHT-treated neurons compared with controls, suggesting increased Ca(2+) stores in DHT-treated neurons. In all cases the effects of DHT were blocked by treatment with flutamide indicating an AR-mediated mechanism. To determine a possible mechanism by which AR activation could be influencing [Ca(2+)](i), SERCA2 mRNA levels were measured in primary hippocampal neurons. SERCA2 is inserted into the endoplasmic reticulum (ER) membrane and functions to rapidly pump [Ca(2+)](i) into the ER. Following treatment of primary hippocampal neurons with DHT, SERCA2 mRNA was increased, an effect that was blocked in the presence of flutamide. Taken together these results indicate that DHT, working through AR, causes an up-regulation of SERCA2, which increases the sequestering of [Ca(2+)](i) in the endoplasmic reticulum of hippocampal neurons. Such changes may allow the neurons to respond more robustly to a stimulus and recover more quickly following a highly stimulatory challenge.

Outbreak of Serratia marcescens infections following injection of betamethasone compounded at a community pharmacy.

BACKGROUND: In June 2001, following the report of 4 patients with Serratia marcescens meningitis who received epidural injections of betamethasone compounded at a community pharmacy, we initiated an outbreak investigation. METHODS: All patients who received injections of betamethasone from the production lot common to the 4 patients were evaluated. A case patient was defined as a patient who received compounded betamethasone and had S. marcescens isolated from a sterile site or clinical and laboratory evidence of infection. We cultured all recovered betamethasone, environmental specimens from the pharmacy, and medications recovered from an ambulatory surgery center. The California Board of Pharmacy reviewed the procedures used to prepare the betamethasone. RESULTS: We identified 11 patients with culture-confirmed S. marcescens (8 patients) or clinical infection (3 patients) following injection of compounded betamethasone from 25 May through 31 May 2001. Case patients had meningitis (5 patients, with 3 deaths), epidural abscesses (5 patients), or an infected hip (1 patient). S. marcescens was isolated from 35 (69%) of 51 betamethasone vials recovered, from pharmacy specimens of 1% carboxymethylcellulose stock solution, from pharmacy surfaces, and from multiple parenteral materials used at the ambulatory surgery center. Pulsed-field gel electrophoresis patterns of S. marcescens isolates of representative specimens from patients, the betamethasone, the pharmacy, and the ambulatory surgery center were identical. Deficient practices in compounding of betamethasone included inadequate autoclaving temperatures and failure to perform terminal sterilization. CONCLUSIONS: This outbreak of serious S. marcescens infection followed improper compounding of betamethasone in a community pharmacy. Enforceable national standards for pharmaceutical compounding are needed to reduce the risk of such outbreaks.

Risk factors associated with a school-related outbreak of serogroup C meningococcal disease.

An outbreak of Neisseria meningitidis sero-group C disease occurred in four eighth grade students and in a younger sibling of another eighth grade student attending an intermediate school (seventh and eighth grades) in Santa Clara County, CA. Four cases had onset within 3 days in January, 1989, with the fifth case occurring approximately 10 days later. A case-control study was performed to determine risk factors associated with serogroup C meningococcal infection (disease or carriage) in this eighth grade class. Students were more likely to be infected if they had had a preceding viral-like respiratory illness characterized by fever (odds ratio (OR) 5.3, P = 0.03) or cough (OR 5.1, P = 0.048). A ski trip (OR 6.3, P = 0.01) and a poster-making session for a school dance (OR 3.7, P = 0.08) were identified as possible settings for a common exposure. Spending time with two specific students during lunchtime or outside of school was associated with an increased risk of infection (OR 7.0, P = 0.054; OR 5.8, P = 0.04).

Invasive group A streptococcal infections in children with varicella in Southern California.

OBJECTIVE: To describe demographic and clinical features of invasive group A streptococcal (GAS) infections in children with varicella in Southern California in early 1994. METHODS: From hospitals of Los Angeles and Orange Counties, children with invasive GAS infections after varicella between January 1 and April 8, 1994, were identified by hospital infection control nurses. Medical records of patients were reviewed, and any available GAS isolate was further tested. RESULTS: Twenty-four cases were identified; 54% were male, 50% were Hispanic and the median age was 3 years (range, 0.5 to 8). Four cases died before hospitalization. The other 20 were hospitalized for a median of 10 days (range, 4 to 50): 14 presented with cellulitis (1 with concomitant epiglottitis), 2 with myositis/necrotizing fasciitis, 2 with pneumonia and 2 with bacteremia without apparent source. Five had evidence of multiorgan involvement including two patients fulfilling criteria of streptococcal toxic shock-like syndrome. Of 19 patients with blood cultures, 10 (53%) had GAS bacteremia. Onset of GAS infection was suggested, as a median, on Day 4 of varicella, with fever, vomiting and localized swelling being commonly reported. The mean maximum temperature on the day of admission was 39.4 degrees C (102.9 degrees F). Four GAS isolates were M1T1 and one was M3T3. Five isolates produced streptococcal pyrogenic exotoxins A and B. CONCLUSIONS: Invasive GAS disease, including streptococcal toxic shock-like syndrome, is a serious complication of varicella. Physicians should be alert for the complication of GAS when fever and localized swelling or signs of cellulitis develop 3 days or more after the onset of varicella. Widespread use of varicella vaccine may decrease invasive GAS infections in this setting.

Trichinosis acquired at sea--report of an outbreak.

In 1974, at least 13 persons acquired trichinosis aboard a luxury liner en route to Alaska. Epidemiologic investigation implicated ground beef served on the ship as the vehicle of transmission. The beef is thought to have been contaminated by pork which had previously been frozen, though presumably not under trichinacidal conditions. To our knowledge, this is the first report of trichinosis acquired at sea.

Epidemic and sporadic cases of nontuberculous mycobacterial keratitis associated with laser in situ keratomileusis.

PURPOSE: To report national case-finding results for nontuberculous mycobacterial keratitis and describe its association with laser in situ keratomileusis (LASIK). DESIGN: Enhanced passive disease reporting. METHODS: In April 2001, we investigated a California cluster of Mycobacterium chelonae keratitis associated with hyperopic LASIK using a contact lens mask. To identify other possibly related cases, the American Academy of Ophthalmology e-mailed its members asking them to report recent cases of nontuberculous mycobacterial keratitis to the Centers for Disease Control and Prevention. RESULTS: Forty-three additional cases of keratitis were reported (onsets between August 2000 and June 2001). Of these, 31 occurred as part of two unrelated LASIK-associated outbreaks. The 12 other reported cases occurred in sporadic fashion. Of the latter cases, 4 were associated with LASIK surgery. None of the reported cases were related to the M. chelonae cluster in California. CONCLUSIONS: Laser in situ keratomileusis-associated keratitis with nontuberculous mycobacteria may be more common than previously known.

An outbreak of Bacillus cereus food poisoning--are caterers supervised sufficiently.

Bacillus cereus is an uncommonly reported cause of foodborne illness in the United States. In May 1989, an outbreak of B. cereus gastroenteritis occurred among 140 guests who had attended a catered wedding reception in Napa, CA. Investigation established Cornish game hens served at the event as the vehicle for disease transmission (OR = 29, P = 0.0001). Although the spores of B. cereus are ubiquitous, large numbers of toxin-producing organisms (more than 10(5) per gram of food) are required for illness to occur. In the Napa outbreak, bacterial multiplication was facilitated at several points during the preparation and transportation of the food. While a licensed restaurant kitchen was used, the facilities were clearly inadequate for the event. At present, the California Health and Safety Code does not address the scope of catering operations. As caterers increase in number, there will be a growing need for governmental oversight to ensure that food production on a large scale is conducted safely.

Profile of raw milk consumers in California.

OBJECTIVES: The authors sought to determine the prevalence of raw milk consumption in California--the largest producer of certified raw milk in the United States--and to describe the demographic and behavioral characteristics of raw milk consumers in that state. METHODS: The authors analyzed responses to questions on the 1994 California Behavioral Risk Factor Surveillance System Survey that asked respondents about whether they drank raw milk, the amount consumed, the reason for drinking raw milk, and where raw milk was most often obtained. RESULTS: Among 3999 survey respondents, 3.2% reported drinking raw milk in the previous year. Raw milk drinkers were more likely than nondrinkers to be younger than age 40, male, and Hispanic and to have less than a high school education. CONCLUSIONS: Raw milk continues to be consumed by some residents of California despite the documented hazards associated with this dietary practice.

High incidence of extra-intestinal infections in a Salmonella Havana outbreak associated with alfalfa sprouts.

OBJECTIVE: To determine a vehicle and point source for an outbreak of Salmonella Havana. METHODS: The authors conducted a case-control study and traceback investigation of 14 residents of California and four from Arizona with onsets of illness from Apr 15, 1998, to June 15, 1998, and Salmonella Havana infections with identical PFGE patterns. RESULTS: Seventeen of 18 patients were women. Seventeen were adults 20-89 years of age. Nine (50%) had diarrheal illness, 6 (33%) had urinary tract infections, 2 (11%) had sepsis, and one had an infected surgical wound after appendectomy. Four patients were hospitalized, and one died. Eating alfalfa sprouts was associated with S. Havana infection (OR = 10.0; 95% confidence interval 1.2, 83.1; P = 0.01). CONCLUSIONS: This outbreak resulted in a high incidence of extra-intestinal infections, especially urinary tract infections, and high morbidity. Raw alfalfa sprouts, often considered a safe "heath food," can be a source of serious foodborne disease outbreaks.

Alfalfa sprouts and Salmonella Kottbus infection: a multistate outbreak following inadequate seed disinfection with heat and chlorine.

Raw sprouts have been implicated in a number of foodborne disease outbreaks. Because contaminated seeds are usually responsible, many sprout producers attempt to disinfect seeds before germination and detect sprout contamination during production. In March 2001, we detected an increased number of Salmonella serotype Kottbus isolates in California. Overall, we identified 31 cases from three western states. To identify the cause, we conducted a case-control study with the first 10 identified case-patients matched to 20 controls by age, sex, and residential area. Our case-control study found illness to be statistically associated with alfalfa sprout consumption. The traceback investigation implicated a single sprouter, where environmental studies yielded Salmonella Kottbus from ungerminated seeds and floor drains within the production facility. Pulsed-field gel electrophoresis patterns of all patient, seed, and floor drain Salmonella Kottbus isolates were indistinguishable. Most implicated sprouts were from seeds that underwent heat treatment and soaking with a 2,000-ppm sodium hypochlorite solution rather than the Food and Drug Administration (FDA)-recommended 20,000-ppm calcium hypochlorite soak. Other implicated seeds had been soaked in a calcium hypochlorite solution that, when tested, measured only 11,000 ppm. The outbreak might have been averted when screening tests of sprout irrigation water detected Salmonella in January; however, confirmatory testing of these samples was negative (but testing improperly utilized refrigerated irrigation water). Producers should use the enrichment broth of positive screening samples, not refrigerated irrigation water, for confirmatory testing. Until other effective disinfection technologies are developed, producers should adhere to FDA recommendations for sprout seed disinfection.

Effect of dexamethasone on osseointegration: a preliminary experimental study.

The peri-implant reparative process is one of the factors involved in osseointegration. Local and systemic factors may contribute to the peri-implant micro-environment. The aim of this study was to assess the effect of dexamethasone (DXM) on the first stages of the post-implantation reparative process using a quantitative osseointegration experimental model previously developed at our laboratory. A titanium laminar implant was inserted into the right tibiae of nine male Wistar rats under ether anesthesia, following a technique we previously described. Six rats received 120 micrograms/kg/day i.p. doses of DXM (Decadron Sidus, Argentina) for 14 days pre-implantation and 14 days post-implantation. The remaining three (controls) were injected with an equivalent volume of saline. On day 14 post-implantation, all animals were killed, and their tibiae were resected, radiographed, and processed before being embedded in methylmethacrylate. Microscopic observation and histomorphometric studies were performed. Results show that, in this experimental model, the extension of osteogenic peri-implant response was greater in DXM-treated animals than in controls. Thus, our laminar implant test may prove useful to study the effects of corticosteroids on the osseointegration process.

Salmonella infections associated with mung bean sprouts: epidemiological and environmental investigations.

We investigated an outbreak of Salmonella Enteritidis (SE) infections linked to raw mung bean sprouts in 2000 with two case-control studies and reviewed six similar outbreaks that occurred in 2000-2002. All outbreaks were due to unusual phage types (PT) of SE and occurred in the United States (PT 33, 1, and 913), Canada (PT 11b and 913), and The Netherlands (PT 4b). PT 33 was in the spent irrigation water and a drain from one sprout grower. None of the growers disinfected seeds at recommended concentrations. Only two growers tested spent irrigation water; neither discarded the implicated seed lots after receiving a report of Salmonella contamination. We found no difference in the growth of SE and Salmonella Newport on mung beans. Mung bean sprout growers should disinfect seeds, test spent irrigation water, and discontinue the use of implicated seed lots when pathogens are found. Laboratories should report confirmed positive Salmonella results from sprout growers to public health authorities.

Outbreak of cryptosporidiosis at a California waterpark: employee and patron roles and the long road towards prevention.

In August-September 2004, a cryptosporidiosis outbreak affected >250 persons who visited a California waterpark. Employees and patrons of the waterpark were affected, and three employees and 16 patrons admitted to going into recreational water while ill with diarrhoea. The median illness onset date for waterpark employees was 8 days earlier than that for patrons. A case-control study determined that getting water in one's mouth on the waterpark's waterslides was associated with illness (adjusted odds ratio 7.4, 95% confidence interval 1.7-32.2). Laboratory studies identified Cryptosporidium oocysts in sand and backwash from the waterslides' filter, and environmental investigations uncovered inadequate water-quality record keeping and a design flaw in one of the filtration systems. Occurring more than a decade after the first reported outbreaks of cryptosporidiosis in swimming pools, this outbreak demonstrates that messages about healthy swimming practices have not been adopted by pool operators and the public.

A multi-state outbreak of Salmonella serotype Thompson infection from commercially distributed bread contaminated by an ill food handler.

Foodborne transmission is estimated to account for 95% of non-typhoidal Salmonella infections reported in the United States; however, outbreaks of salmonellosis are rarely traced to food handlers. In August 2000, an increase in Salmonella serotype Thompson infection was noted in Southern California; most of the cases reported eating at a restaurant chain (Chain A) before illness onset. A case-control study implicated the consumption of burgers at Chain A restaurants. The earliest onset of illness was in a burger bun packer at Bakery B who had not eaten at Chain A but had worked while ill. Bakery B supplied burger buns to some Chain A restaurants in Southern California and Arizona. This outbreak is notable for implicating a food handler as the source of food contamination and for involving bread, a very unusual outbreak vehicle for Salmonella . Inadequate food-handler training as well as delayed reporting to the health department contributed to this outbreak.

A large outbreak of scombroid fish poisoning associated with eating escolar fish (Lepidocybium flavobrunneum).

In August 2003, an outbreak of scombroid fish poisoning occurred at a retreat centre in California, USA. In a retrospective cohort study, 42 (75%) of the 56 dinner attendees who ate escolar fish (Lepidocybium flavobrunneum) met the case definition. Individuals who ate at least 2 oz of fish were 1.5 times more likely to develop symptoms than those who ate less (relative risk 1.5, 95% confidence interval 0.9-2.6), and to develop more symptoms (median 7 vs. 3 symptoms, P = 0.03). Patients who took medicine had a longer duration of symptoms than those who did not (median 4 vs. 1.5 h, P = 0.05), and experienced a greater number of symptoms (median 8 vs. 3 symptoms, P = 0.0002). Samples of fish contained markedly elevated histamine levels (from 2000 to 3800 ppm). This is one of the largest reported outbreaks of scombroid fish poisoning in the United States and was associated with a rare vehicle for scombroid fish poisoning, escolar.

Coccidioidomycosis in Northern California. An outbreak among archeology students near Red Bluff.

An outbreak of coccidioidomycosis occurred among 39 archeology students in the summer of 1972. The students excavated Indian ruins near Red Bluff in Tehama County, California, 20 miles north of the previously recognized northernmost limit of endemicity. At least 17 persons contracted an illness clinically compatible with a diagnosis of coccidioidomycosis. Coccidioidomycosis was documented by skin test conversion as well as by specific serologic reactions. Coccidioides immitis was also isolated from two soil samples taken at the excavation site. In light of its ecological requirements, it is doubtful that C. immitis will be recovered much farther north than Red Bluff. The occupational hazard of coccidioidomycosis to archeologists and others employed in known endemic areas remains a substantial threat to health.

Botulism--diagnosis, management and public health considerations.

Botulism is an uncommon but often fatal disease associated with ingestion of a potent neurotoxin present in improperly preserved foods. Exposures to commercially preserved foods with an odd or peculiar taste almost never represent exposure to botulism toxin. Improperly prepared home-canned products which are tasted or consumed without heating are more likely to be associated with botulism. The management of suspect and confirmed cases of botulism is presented by medical epidemiologists in the State Department of Public Health, Bureau of Communicable Disease Control, to provide physicians in California with a practical approach to this problem.

Epidemiology of Aeromonas infections in California.

In May 1988, California became the first state to make aeromonas infection a reportable condition, thereby permitting the first population-based study of the epidemiology of infection caused by Aeromonas organisms. Case investigations were carried out on 219 of the 280 patients whose infections were reported during the first year of notification. The overall incidence rate for Aeromonas isolation was 10.6 cases per 1 million population. The gastrointestinal tract was the most commonly reported site from which Aeromonas was isolated (81%), with wounds being the next most common source (9%). Five (2%) of the 219 patients died; all five had serious underlying medical conditions apart from aeromonas infection. No common-source enteric outbreaks were reported. The high rate of gastrointestinal symptoms and isolation of organisms from medically vulnerable patients and the fact that other bacterial enteric pathogens were rarely isolated from symptomatic patients support evidence from previous studies that Aeromonas is an enteric pathogen. The evidence from these case reports in California suggests that aeromonas infections are not an important public health problem and are largely nonpreventable. Thus, public health surveillance is not necessary and mandatory reporting has been discontinued.

Association between raw milk and human Salmonella dublin infection.

Between 1971 and 1975 the mean annual incidence of human Salmonella dublin infection in California increased more than five-fold. Investigation of the increase showed an association with exposure to raw milk in 44 out of 113 cases. Of these 44 patients, 35 had used certified raw milk from a single dairy. Faecal swabs confirmed S dublin infection in the dairy herd and the milk, and so a pasteurisation order was issued. S dublin appears to be an unusually invasive and life-threatening salmonella serotype: 65% of isolations were obtained from non-faecal specimens (mainly blood cultures), 89 patients (80%) were admitted to hospital and 22 patients died. Almost three-quarters of the patients were aged 20 or over, and half had serious underlying diseases, particularly leukaemias and lymphomas. Five patients presented with infected vascular lesions that included aneurysms with abscesses and infections of previous arterial graft sites. The public's increasing desire for a "health food" such as raw milk should be tempered with an appreciation of its attendant risk to health.