Comparison of total antibody and interferon-γ T-cell responses in patients following infection with brucellosis in Georgia.

Brucellosis is an ancient disease that still remains a significant threat to humans and is typically linked to exposure to infected animals and/or consumption of unpasteurized animal products. Despite this history, we have a relatively limited understanding of the host characteristics of this disease; consequently, further research is necessary. In this study, we examined the humoral immune response in 43 Georgian individuals that had been diagnosed with brucellosis 3-12 months before enrollment in the study, many of whom still had symptoms after the completion of antibiotic therapy. In total, 35 of 43 (83%) of the patients had antibodies that bound to Brucella lipopolysaccharide (LPS) by COMPELISA, and 34 of 38 (89%) patients had demonstrable specific antibodies to Brucellergene™ antigens; the results from the two ELISAs were highly correlated (p=0.031, r=0.851). We also studied the cellular immune responses in 15 patients. All of the patients generated interferon (IFN)-γ in response to ex vivo stimulation with Brucella protein antigens, and the majority of the patients maintained measurable humoral responses to both LPS and protein antigens. From this initial study, we conclude that measurement of antibody and of cellular (IFN-γ) responses to brucellergene OCB protein epitopes may be worthy of further investigation as an alternative or adjunct to current diagnostics.

Water-borne outbreak of oropharyngeal and glandular tularemia in Georgia: investigation and follow-up.

BACKGROUND: In November 2006, an outbreak of waterborne tularemia occurred in an eastern region in the Republic of Georgia. Outbreak investigation revealed 26 cases: 21 oropharyngeal and 5 glandular tularemia cases. METHODS: The presentation of the index case triggered an outbreak investigation involving the collection of clinical/ epidemiological data, application of tularine skin test, and laboratory confirmation of the possible cases using the tube agglutination test and polymerase chain reaction (PCR) testing. Serology results were verified by enzyme-linked immunosorbent assay (ELISA) and Western blot. A case- control study along with follow-up was conducted 4 months after the index case presentation. RESULTS: Exudative pharyngitis, predominantly laterocervical adenitis, fever, and headache were the most prevalent clinical signs/symptoms observed. Depressed mood, concentration difficulties, and sleep disturbance were also detected. Bubo aspirates tested by PCR were positive in 4/4 cases and pharyngeal swabs also tested by PCR were positive in 2/3 cases. Francisella tularensis was isolated from the water samples. Comparison of the cases and controls did not reveal any statistically significant risk factors. A follow-up investigation revealed cases with protracted symptoms of fatigue, headache, and sleep disturbance. Additionally, 8/26 cases still had cervical adenopathy of prominent size. A delay in diagnosis was associated with persistent lymphadenopathy on follow-up examination (p = 0.05). CONCLUSION: We observed unique features of persistent neuropsychiatric symptoms and lymphadenopathy 5 months after tularemia infection which were associated with delayed diagnosis and the lack of prompt response to therapy. This outbreak of oropharyngeal tularemia emphasizes the importance of a rapid diagnostic and investigative response to tularemia. This type of response can prevent ongoing exposure, as well as provide expeditious treatment to mitigate persistent symptoms.

Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine.

A retrospective review was conducted of yellow fever vaccination among laboratory workers receiving annual serologic assessment to determine the initial and long-term response after boosting. Patients were divided into three groups based on pre-vaccination serology: Group 1, 1:10; Group 2, 1:20-1:40 and Group 3, >1:40. The percent with > or = four-fold increase in titers after booster vaccination were: 78% (646/829, Group 1), 65% (79/121, Group 2) and 10% (8/79, Group 3) (p<0.0001). The median times to titer failure (<1:40) were 798 days (Group 1), 3340 days (Group 2) and 7709 days (Group 3) (p<0.0001). Pre-vaccination serology influenced the initial and long-term response to yellow fever booster vaccination.

Candida krusei renal cyst infection and measurement of amphotericin B levels in cystic fluid in a patient receiving AmBisome.

Candida krusei is an opportunistic pathogen commonly implicated in urinary tract infections in immunocompromised patients. We present the first case of C. krusei renal cyst infection, occurring in a post-liver and kidney transplant patient with autosomal dominant polycystic kidney disease. Her persistent candiduria and fevers were refractory to prolonged therapy with AmBisome (Fujisawa Pharmaceuticals Co. Ltd., Osaka, Japan). She eventually required bilateral nephrectomies of her native kidneys. Cystic fluid was aspirated from six hemorrhagic and six nonhemorrhagic cysts. Cystic fluid cultures yielded C. krusei. Fluid from the nonhemorrhagic cysts was also analyzed for amphotericin B levels, measured using a bioassay. Free amphotericin B levels in the cysts were lower than the minimal inhibitory concentration for amphotericin B for this organism. We provide the first description of amphotericin B levels in cystic fluid obtained during bilateral nephrectomies.

The effects of estrogen replacement therapy on airway function in postmenopausal, asthmatic women.

BACKGROUND: Data from multiple clinical, epidemiologic, and in vitro studies are conflicting regarding the effect of estrogen replacement therapy (ERT) on airway function in postmenopausal women with asthma. OBJECTIVE: To determine the impact of withdrawal of estrogen administration in postmenopausal, asthmatic women. METHODS: Twenty asthmatic women who were postmenopausal for at least 2 years and undergoing ERT were recruited for this prospective crossover study. Subjects continued taking baseline estrogen for 28 days, stopped taking estrogen for 28 days, and then resumed taking the medication for 14 days. Objective measurements were obtained by recording daily peak flows in the morning and evening and formal spirometry at days 14, 28, 42, 56, and 70. Compliance was measured by evaluating serum estradiol levels at days 28 and 56. Daily use of short-acting beta-agonist bronchodilators was also recorded. RESULTS: Differences in estradiol levels indicated compliance with the medication regimen. The combined day 14 and 28 (taking estrogen) mean percent predicted forced expiratory volume in 1 second (FEV(1)) was 77% compared with the combined day 42 and 56 (not taking estrogen) mean FEV(1) of 78% and the day 70 (taking estrogen again) FEV(1) of 76% (P>.05). Average peak flow measurements were 295.5 L/min for the duration of ERT, 293.9 L/min while not undergoing ERT, and 291.8 L/min when ERT was restarted for the final 2 weeks of the study (P>.05). Use of short-acting beta-agonist bronchodilators did not differ between study periods. CONCLUSION: These data indicate that neither the discontinuation nor reinitiation of ERT in postmenopausal, asthmatic women has any effect on objective measures of airway obstruction.

Availability of smoking cessation resources for U.S. Army general medical officers.

Adequate resources are a necessity in providing effective smoking cessation interventions to active duty soldiers. The availability of smoking cessation resources was measured by a survey of Army general medical officers (GMOs). Questionnaires were successfully mailed to 232 Army GMOs, which was the entire population of this group in 1997. One hundred fifty GMOs (65%) returned the questionnaire voluntarily and anonymously. Fifty-three percent of GMOs identified the nicotine patch as a formulary item. All responders indicated that some form of nicotine replacement was available on formulary or for purchase in the area. Eighty-two percent of GMOs reported that group smoking cessation programs were available. The widespread availability of group smoking cessation programs may reflect an emphasis on this strategy by the Army's health promotion program. Additional attention needs to address the availability of nicotine replacement items and other adjunctive medications without cost to the beneficiary at military installations.

Subacute thyroiditis manifesting as fever of unknown origin.

Subacute thyroiditis (SAT) usually occurs in women in middle age with a viral prodrome, thyroid or neck tenderness, classic symptoms of thyrotoxicosis, and elevated erythrocyte sedimentation rate (ESR). We report a case in an 81-year-old man who initially had 2 days of fever to 101.2 degrees F, confusion, and bilateral lower extremity weakness. Extensive evaluation was remarkable only for the following laboratory values: thyrotropin (TSH) 0.02 microIU/mL, free thyroxine (FT4) 3.1 ng/dL, free triiodothyronine (FT3) 6.0 pg/mL, and ESR 98 mm/hr. One week later, the patient had persistent fevers to 102 degrees F; no source was found. The fever resolved, and 3 months later the patient had profound hypothyroidism (TSH >44.0 microIU/mL, FT4 0.4 ng/dL, ESR 13 mm/hr). A painless thyroid gland and atypical manifestations of hyperthyroidism are unusual in SAT. When fever is of unknown origin, SAT should be considered even if classic features are absent.

A survey of smoking cessation knowledge, training, and practice among U.S. Army general medical officers.

BACKGROUND: Historically, cigarette-smoking rates have been higher among military personnel than among civilians, although recently these rates have decreased. METHODS: In March 1997, a questionnaire assessing (1) training received on smoking cessation, (2) objective knowledge of smoking-cessation techniques, (3) frequency of practice habits, and (4) personal tobacco use among physicians, was successfully mailed to 232 of the total population of 279 Army general medical officers (GMOs). RESULTS: One-hundred-fifty (65%) GMOs returned questionnaires. Of these, 3.3% reported personal cigarette smoking, and 7.3% regularly used smokeless tobacco. During internship, few (13%) GMOs received smoking-cessation training. Primary care programs provided training more frequently than did surgery internship programs. The mean score on the objective knowledge portion was 72%. GMOs had a variable practice pattern in their use of smoking-cessation techniques (percent answering "usually" or "always"): helping patients set quit dates (35%), offering to prescribe the nicotine patch (59%), referring patients to a behavior-modification program (86%). Physicians who received training during internship were significantly more likely (p < 0.01) to help their patients set a quit date. Training did not result in a statistically increased frequency of other practice habits. CONCLUSIONS: GMOs received minimal training on smoking cessation during internship. GMOs refer patients to smoking-cessation classes, reflecting the strategy of the Army Health Promotion program. Strategies to increase the frequency that GMOs prescribe nicotine replacement and assist patients in setting a quit date are needed. Military smoking-cessation efforts may provide valuable lessons for the civilian community.

Autoimmune idiopathic thrombocytopenic purpura with the subsequent occurrence of systemic lupus erythematosus.

Cutaneous manifestations of petechiae, purpura, and ecchymosis can lead the physician to discover an underlying platelet abnormality. Autoimmune idiopathic thrombocytopenic purpura (AITP) is a diagnosis of exclusion, mediated by a destructive IgG antibody response to the platelets' membrane components. In addition to showing evidence of cutaneous and mucosal bleeding (ie, epistaxis, hematuria), patients with AITP are at an increased risk for systemic lupus erythematosus (SLE). Therefore, it is suggested that patients with AITP be closely monitored for SLE.

Mees' lines in a patient with multiple parasitic infections.

Mees' lines, or transverse striate leukonychia, are classically associated with arsenic poisoning, but have been described in other cases of acute or chronic illness. Their pathogenesis is thought to be a disruption of nail plate keratinization secondary to systemic stress. Mees' lines are observed in a patient with helminthic and amebic infections and no history of arsenic exposure. This case demonstrates another clinical setting in which Mees' lines can appear, providing further evidence that Mees' lines may chronicle systemic disease.

Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats.

This study investigated the effect of delta opioid receptor blockade by naltrindole on the development of physical dependence and tolerance to the antinociceptive and respiratory depressive effects of morphine in rats. Chronic morphine was delivered either by s.c. injection of increasing amounts of morphine over 5 days or by s.c. implantation of morphine pellets. Animals were cotreated with saline or naltrindole. Antinociception and respiratory depression were assessed after administration of a challenge dose of morphine, and withdrawal signs were determined after naloxone challenge. Naltrindole significantly attenuated the development of antinociceptive tolerance after all three chronic treatment regimens. In addition, rats pretreated with naltrindole displayed significantly fewer withdrawal symptoms and less weight loss after a naloxone challenge. In contrast, naltrindole did not prevent the development of tolerance to morphine-induced respiratory depression. These results imply that tolerance to antinociception and physical dependence involves adaptations at interacting mu and delta receptor populations, whereas tolerance to respiratory depression reflects actions of independent mu and delta receptor populations. These findings suggest that delta antagonists may have potential clinical application for decreasing the rapid development of tolerance to opiate-induced analgesia, while allowing for the development of protective tolerance to respiratory depression.