Assessment of the kinetics of Treponema pallidum dissemination into blood and tissues in experimental syphilis by real-time quantitative PCR

Little is known about the size and kinetics of treponemal burdens in blood and tissues during acquired or experimental syphilitic infection. We used real-time quantitative PCR to measure Treponema pallidum DNA levels in rabbits infected intratesticularly with the prototype Nichols strain. At the outset, we performed a series of in vitro blood spiking experiments to determine the effect of blood processing procedures on the distribution of treponemes in various blood components. T. pallidum DNA levels in plasma and whole blood were approximately 10-fold higher than those in serum and more than 200-fold greater than those in peripheral blood mononuclear cells (PBMCs). Ten rabbits were inoculated intratesticularly with doses of treponemes ranging from 4 x 10(7) to 2 x 10(8) organisms. In five rabbits, T. pallidum DNA levels were measured sequentially in serum, plasma, whole blood, and PBMCs until sacrifice at peak orchitis, at which time brain, kidney, liver, spleen, and testicles were harvested; blood and organs were also harvested at orchitis from the other five rabbits. T. pallidum DNA was detected in plasma within 24 h postinfection. Treponeme levels in whole blood and blood components increased significantly with the development of peak orchitis. Overall, levels in serum and PBMCs were lower than those in plasma and whole blood; this disparity was particularly marked at early time points. Significantly greater numbers of spirochetes were found in the spleen than in liver, kidney, or brain tissue at the time of sacrifice. Our findings highlight the remarkable capacity of T. pallidum to disseminate from the site of infection to blood and tissues, and they identify the spleen as a prime target for treponemal invasion.     

Transient bacteraemia: a possible cause of sudden life threatening events

The concept proposed is that transient bacteraemia occurring in otherwise healthy individuals can cause acute life threatening events due to bacterial toxaemia even though the bacteraemia is rapidly cleared (<20 min). This is most likely to occur in infancy at around two to three months of age when anti-toxin IgG reaches its nadir. Sudden unexpected death in infancy, acute life threatening events, haemorrhagic shock and encephalopathy, and the triad of retinal haemorrhage, encephalopathy and bilateral thin film subdural haematomata are conditions which could be caused by this mechanism. Investigations need to be directed to measuring bacterial toxins in blood, CSF and urine; anti-toxin IgG in blood; and bacterial specific nucleic acid sequences in blood, CSF and urine using polymerase chain reaction in order to confirm recent bacteraemia. Furthermore the upper respiratory tract bacterial flora should be mapped in cases and appropriately matched live healthy community controls. Sudden onset, profound life threatening physiological dysfunction occurring in later life could also be caused by a similar mechanism and should be investigated in a similar way; candidate conditions include epilepsy, migraine, stroke and cardiac arrhythmias.     

White matter grade and ventricular volume on brain MRI as markers of longevity in the cardiovascular health study

High white matter grade (WMG) on magnetic resonance imaging (MRI) is a risk factor for dementia, stroke and disability. Higher ventricular size is a marker of brain "atrophy." In the Cardiovascular Health Study (CHS) (n=3245) mean age 75 years, 50% black and 40% men, we evaluated WM and ventricular grade (VG), total, cardiovascular and noncardiovascular mortality and longevity before and after adjusting for numerous determinants of longevity over an approximate 10-12 years of follow-up. A low WMG and VG was a marker for low total, cardiovascular and noncardiovascular mortality and for increased longevity over 10+ years of follow-up. We estimated that a 75-year-old with WMG below median would have about a 5-6 years greater longevity and for VG about 3 years, than above the median even after adjustment for numerous risk factors. Low WMG and VG on MRI is a powerful determinant of long-term survival among older individuals.     

The diagnostic effectiveness of an initial transvaginal scan in detecting ectopic pregnancy

BACKGROUND: To determine the effectiveness of an initial transvaginal ultrasound scan (TVS) in the detection of ectopic pregnancy in consecutive women attending an early pregnancy unit (EPU). METHODS: This was a prospective observational study. Unselected women attending a dedicated EPU underwent a TVS. Women were classified as having an intrauterine pregnancy (IUP), ectopic pregnancy or pregnancy of unknown location (PUL). Women with a PUL were followed up until the final location of the pregnancy was determined. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) with 95% confidence intervals (CIs) for the initial TVS in the diagnosis of ectopic pregnancy were calculated. RESULTS: During a one-year study period, 5318 consecutive women attended the EPU. Outcome data were available for 5240 (98.5%) women. Of these, the initial TVS showed an IUP in 4693 (89.6%) cases and an ectopic pregnancy in 91 (1.7%) cases. The remaining 456 (8.7%) women were classified as PUL, and of these 31 (6.8%) were subsequently found to have ectopic pregnancies. The overall sensitivity of the initial TVS in the diagnosis of ectopic pregnancy was 73.9% (95% CI: 65.1-81.6) with a specificity of 99.9% (95% CI: 99.8-100), a PPV of 96.7% (95% CI: 90.7-99.3) and an NPV of 99.4% (95% CI: 99.2-99.6). CONCLUSIONS: In unselected women attending an EPU, pregnancy location can be diagnosed accurately in over 90% of all pregnancies and in 73.9% of ectopic pregnancies with a single TVS.     

Healthcare seeking and treatment for menopausal symptoms in the United States

OBJECTIVES: A population-based study was used to describe healthcare seeking behavior for menopausal symptoms and treatment among women 40-65 years old in the United States. METHODS: Participants were recruited into the Menopause Epidemiology Study from the KnowledgePanel(SM), which is selected by random digit dialing and probability sampling from the US population. From this source, 6201 women 40-65 years old were contacted and 4402 women participated. From the 3135 peri- and postmenopausal women, detailed information was obtained on menopausal symptoms, healthcare seeking, medication usage, and symptom relief from the medication. RESULTS: Many women (60%) reported seeking health care for their menopausal symptoms. More than half of these women sought health care in the past 12 months. Vasomotor symptoms were the most frequently reported menopause symptoms across all races/ethnicities, and the most common symptoms discussed with a health care professional. One-third of the women (34%) used only hormone therapies, 12% used complementary and/or alternative medicines, and 16% used both for treatment of menopausal symptoms. CONCLUSIONS: This study has shown that a large number of women consult healthcare providers for menopausal symptoms, indicating these symptoms are bothersome. Yet, in the United States, there is considerable variation in the symptomatology, healthcare seeking, and use of therapies for menopausal symptoms across cultures. To alleviate these symptoms women have tried alternative treatments as well as hormone therapies, yet many women did not get complete relief of specific symptoms.     

Anti-IgE treatment of eosinophil-associated gastrointestinal disorders

BACKGROUND: Eosinophil-associated gastrointestinal disorders (EGIDs) are commonly associated with atopy and are being recognized with increasing frequency. Current therapy for EGIDs is inadequate. OBJECTIVE: We sought to determine the efficacy of anti-IgE therapy in EGIDs and investigate the role of IgE in disease pathogenesis. METHODS: Nine subjects with EGIDs received omalizumab every 2 weeks for 16 weeks while other therapy was held constant. Blood absolute eosinophil counts, tissue eosinophil counts, symptom scores, and free IgE levels were serially measured. Allergen skin testing and flow cytometry for basophil activation and FcepsilonRI were determined at baseline and at week 16. RESULTS: Omalizumab was associated with a decrease in absolute eosinophil count at both the week 16 (34%, P = .004) and combined weeks 12 to 16 (42%, P = .012) time points. Tissue eosinophils decreased in the duodenum (59%) and gastric antrum (69%) but did not reach statistical significance (P = .074 and .098, respectively). Esophageal eosinophil counts remained unchanged. Basophil and dendritic cell FcepsilonRI expression and free IgE levels were all significantly decreased (P < .005). Omalizumab increased the concentration of allergen required to trigger half-maximal basophil activation by 170-fold. Allergen skin test wheal and erythema responses decreased by 78% and 82%, respectively. Symptom scores were decreased at both the midstudy (63%) and end of study (70%) time points (P < .005 for both). CONCLUSION: These results demonstrate that IgE-mediated processes contribute to the generation of eosinophilic inflammation in EGIDs and suggest that anti-IgE therapy might be effective in these disorders. CLINICAL IMPLICATIONS: Anti-IgE might be a potential therapy for EGIDs.     

American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis

The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma and Immunology Executive Committees formed the Omalizumab Joint Task Force with the purpose of reviewing the Genentech Xolair (omalizumab) clinical trials and postmarketing surveillance data on anaphylaxis and anaphylactoid reactions. Using the definition of anaphylaxis proposed at a 2005 multidisciplinary symposia, the Omalizumab Joint Task Force concluded that 35 patients had 41 episodes of anaphylaxis associated with Xolair (omalizumab) administration between June 1, 2003, and December 31, 2005. With 39,510 patients receiving Xolair (omalizumab) during the same period of time, this would correspond to an anaphylaxis-reporting rate of 0.09% of patients. Of those 36 events for which the time of reaction was known, 22 (61%) reactions occurred in the first 2 hours after one of the first 3 doses. Five (14%) of the events after the fourth or later doses occurred within 30 minutes. Considering the timing of these 36 events, an observation period of 2 hours for the first 3 injections and 30 minutes for subsequent injections would have captured 75% of the anaphylactic reactions. The OJTF report provides recommendations for physicians who prescribe Xolair (omalizumab) on (1) the suggested wait periods after administration and (2) patient education regarding anaphylaxis.