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.

Maternal methadone use in pregnancy: factors associated with the development of neonatal abstinence syndrome and implications for healthcare resources.

OBJECTIVES: The objectives of this study were to investigate factors associated with the development of neonatal abstinence syndrome (NAS) and to assess the implications for healthcare resources of infants born to drug-misusing women. DESIGN: Retrospective cohort study from 1 January 2004 to 31 December 2006. SETTING: Inner-city maternity hospital providing dedicated multidisciplinary care to drug-misusing women. POPULATION: Four hundred and fifty singleton pregnancies of drug-misusing women prescribed substitute methadone in pregnancy. METHODS: Case note review. MAIN OUTCOME MEASURES: Development of NAS and duration of infant hospital stay. RESULTS: 45.5% of infants developed NAS requiring pharmacological treatment. The odds ratio of the infant developing NAS was independently related to prescribed maternal methadone dose rather than associated polydrug misuse. Breastfeeding was associated with reduced odds of requiring treatment for NAS (OR 0.55, 95% CI 0.34-0.88). Preterm birth did not influence the odds of the infant receiving treatment for NAS. 48.4% infants were admitted to the neonatal unit (NNU) 40% of these primarily for treatment of NAS. The median total hospital stay for all infants was 10 days (interquartile range 7-17 days). Infants born to methadone-prescribed drug-misusing mothers represented 2.9% of hospital births, but used 18.2% of NNU cot days. CONCLUSIONS: Higher maternal methadone dose is associated with a higher incidence of NAS. Pregnant drug-misusing women should be encouraged and supported to breastfeed. Their infants are extremely vulnerable and draw heavily on healthcare resources.

Functional disturbance of marrow stromal microenvironment in the myelodysplastic syndromes.

The potential contribution of abnormal marrow stromal function to ineffective haemopoiesis in the myelodysplastic syndromes is unclear. We have compared the ability of stromal layers from normal (n = 7) and myelodysplastic (n = 9) marrow to alter proliferation and survival of the granulocyte-macrophage colony-stimulating factor/interleukin-3-dependent cell line F-36P. Co-cultures for 72 h in the absence of exogenous cytokines were either in direct contact with stroma or separated by transwell inserts. On normal stromal layers, the ratio of adherent F-36P cells relative to stromal cells increased from a mean of 0.2 +/- 0.01 (s.d.) at 4 h of co-culture to 0.34 +/- 0.08 after 72 h (n = 7). Corresponding values on myelodysplastic stroma (0.2 +/- 0.02 at 4 h and 0.35 +/- 0.05 at 72 h; n = 9) indicated that the ability of myelodysplastic stromal layers to regulate short-term proliferation of F-36P cells may be similar to normal. Apoptosis of F-36P cells was quantified after co-culture with normal or myelodysplastic stroma: results from myelodysplastic co-cultures were standardized as a fraction of values from co-cultures with paired normal stroma (apoptotic ratio). Augmented apoptosis of F-36P cells was detected in 8/9 co-cultures with myelodysplastic stroma (mean = 15.7 +/- 9.7%, n = 9), compared with corresponding normal stroma (mean = 12.4 +/- 4.6%, n = 7, P < 0.05) with a mean apoptotic ratio of 1.4 +/- 0.5 (P < 0.05). There was no correlation between stroma-related apoptosis and FAB type, tumour necrosis factor-alpha concentrations in the culture supernatant or numbers of stromal macrophages, and no evidence of involvement of the Fas pathway. Increased apoptosis was detected in cells grown in transwell inserts over stroma (23.8 +/- 3%, n = 5) compared to adherent cells in cultures with normal stromal layers, but this survival difference was not observed in co-cultures with myelodysplastic stroma. These results suggest that abnormal stromal function in patients with myelodysplastic syndromes may contribute to increased apoptosis of haemopoietic cells within the marrow microenvironment. The effect appears to be dependent on close cellular contact, rather than the release of soluble factors, but the exact mechanism remains unclear.

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.

Transplantation and morphological studies of primary and passaged murine radiation-induced myeloid leukaemias.

Myeloid leukaemia can be induced reproducibly in CBA/H male mice following X-irradiation. After serial passage of the leukaemic cells into syngeneic recipients, they grow faster and require fewer cells for a take. Transplantation of primary leukaemias requires high cell doses unlike passaged lines derived from them. Passaging at low cell doses retains their primary-like growth and morphological properties. It would seem that these low cell dose passages may be a more useful model which can be used for investigating the biology and therapeutic responses of myeloid leukaemia than routinely passaged cell lines.

Persistence of murine myeloid leukaemic cells in long-term bone marrow cultures.

Patterns of growth in long-term bone marrow culture were compared for a number of murine myeloid leukaemias. A leukaemic pattern of haematopoiesis was maintained in culture for a period of at least 15 weeks for one of the lines. However in the other five murine myeloid leukaemic lines studies, the leukaemic cells appeared not to survive in culture and normal haematopoiesis was established. Transplantation of cells from these established cultures at weeks 7 or 11 into syngeneic recipients revealed that leukaemic cells were present. Thus leukaemic cells seem to persist in long-term bone marrow cultures even in morphologically normal cultures.

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.

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.

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.

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.

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.

Visual evoked potentials in infants exposed to methadone in utero.

We investigated the effects of maternal drug misuse on neonatal visual evoked potentials (VEPs). Flash VEPs were recorded within 4 days of birth from 21 term infants of mothers misusing drugs and prescribed substitute methadone and 20 controls. Waveforms were classified as typical, atypical, immature or non-detectable, and amplitude and latencies were measured. VEPs from drug-exposed infants were less likely to be of typical waveform and more likely to be immature or non-detectable (p<0.01) than those of control infants. They were also smaller in amplitude (median 10.8 vs 24.4 microV, p<0.001). VEPs of drug-exposed infants had matured after 1 week but remained of lower amplitude than VEPs of newborn controls (p<0.01) and were non-detectable in 15%. Flash VEPs differ between maternal drug-exposed and non-drug-exposed newborns. Future research should address the specific effects of maternal methadone and/or other illicit drug misuse on infant VEPs, and associations between neonatal VEPs and subsequent visual development.

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.

Social problems.

It has long been established that social deprivation adversely affects health, including that of the pregnant woman and her baby; it is therefore justifiable to use medical resources in the treatment of social problems. Antenatal inpatient care was originally seen as potentially beneficial for women without major medical problems, but such a philosophy is not reflected in current practice. Current antenatal outpatient services do not address the needs of women with social problems who, viewing such services as hostile, may fail to attend. Special services such as help with drugs problems or HIV counselling or screening may be rejected from fear of prejudice and consequent repercussions. Such prejudice often arises because staff do not fully understand the issues involved. Antenatal care for women with social problems should consider women in the context of their families and social environment and should be provided by a small number of familiar staff forming part of an integrated multidisciplinary team in close and regular contact. Antenatal admission, if it is the woman's wish, should be viewed as justified in the management of social problems; conversely, women should not be pressurized into admission or made to feel guilty if unable to comply. Outpatient antenatal services should be conveniently sited in the community close to other relevant services and should be flexible, not only in terms of organization and format, but also in the roles of the participants. They should be comprehensive, but with special services in addition to, not instead of, routine care, and provided by a team of appropriately trained staff. In the provision of antenatal care for women with social needs, no single format will be universally applicable or desirable, and the precise design and content of the service should be variable according to local requirements and should take account of the women's wishes as well as their needs. Ultimately it will only be if the women perceive the service as being in their interests and as meeting their needs that they will use it; only if they choose to use it, will it have any chance of success.

Drug use in pregnancy.

Drug use is on the increase and it impinges on many areas of clinical practice, posing complex management problems. It often provokes strong reactions--and never more so than when it involves pregnant women, with consequent implications for fetal wellbeing. In this emotive area we must objectively identify the real problems and distinguish clearly between medicine and morality.