Injectional anthrax - new presentation of an old disease.

Bacillus anthracis infection (anthrax) has three distinct clinical presentations depending on the route of exposure: cutaneous, gastrointestinal and inhalational anthrax. Each of these can lead to secondary bacteraemia and anthrax meningitis. Since 2009,anthrax has emerged among heroin users in Europe,presenting a novel clinical manifestation, 'injectional anthrax', which has been attributed to contaminated heroin distributed throughout Europe; before 2009 only one case was reported. During 2012 and 2013,new cases of injectional anthrax were diagnosed in Denmark, France, Germany, and the United Kingdom.Here we present a comprehensive review of the literature and information derived from different reporting systems until 31 December 2013. Overall 70 confirmed cases were reported, with 26 fatalities (37% case fatality rate).The latest two confirmed cases occurred in March 2013. Thirteen case reports have been published,describing 18 confirmed cases. Sixteen of these presented as a severe soft tissue infection that differed clinically from cutaneous anthrax, lacked the characteristic epidemiological history of animal contact and ten cases required complimentary surgical debridement. These unfamiliar characteristics have led to delays of three to 12 days in diagnosis, inadequate treatment and a high fatality rate. Clinicians' awareness of this recently described clinical entity is key for early 'and successful management of patients.

Capillary and venous leukocyte adhesiveness/aggregation to differentiate between viral and bacterial infection.

BACKGROUND: A simple capillary leukocyte adhesiveness/aggregation test (CAPLAAT) might be helpful in determining the intensity of inflammation in acute viral and bacterial infections. PATIENTS AND METHODS: We included 30 patients with acute bacterial infections, 14 with viral infections as well as 48 healthy controls. The leukocyte adhesiveness/aggregation test (LAAT) test was performed using a simple slide test and image analysis. RESULTS: The CAPLAAT had a similar discrimination power between bacterial and viral infections as both the white blood cell count (WBC) and the erythrocyte sedimentation rate (ESR). It was more sensitive than the WBC and the ESR (77%, 68% and 66%, respectively) for the detection of bacterial infections and had a comparable negative predictive value. By analyzing the size distribution of the aggregated leukocytes, we found that a venous leukocyte adhesiveness/aggregation test (VLAAT) of four cells and more had the best positive predictive value (94%) and specificity (95%) for diagnosis of an acute bacterial infection (from all the acute phase response variables examined). CONCLUSION: The CAPLAAT might be attractive for the detection of inflammation and for the assessment of its severity at points of care where the services of a clinical laboratory are not available around the clock.

Reduced leukocyte adhesiveness in response to viral versus nonviral infection/inflammation.

BACKGROUND: Viral infection differs from nonviral infection/inflammation by not producing a significant acute phase response. Since inflammation can cause increased adhesiveness of peripheral white blood cells (WBC), we compared these adhesive properties in individuals with viral infection to those with nonviral infection/inflammation. PATIENTS AND METHODS: The state of leukocyte adhesiveness/aggregation in the peripheral blood of patients with viral versus nonviral infection/inflammation was examined in 101 consecutive patients with acute febrile disease. RESULTS: A significant difference was found between the two groups; 13.6 +/- 7% for viral infection versus 22.8 +/- 8.5% for nonviral infection/inflammation (p < 0.0001). There was also a significant difference in the concentration of fibrinogen (361 +/- 109 mg/dl vs 554 +/- 172 mg/dl, p < 0.0001), and in the CD11b/CD18 cell surface expression (175 +/- 66 vs 210 +/- 100 in peripheral blood polymorphonuclear leukocytes). CONCLUSION: The results of this study could explain, at least in part, the differential adhesive behavior of the WBC in the peripheral blood in the two populations.

The inflammation meter: novel technology to detect the presence of infection/inflammation in patients without leukocytosis but with increased leukocyte adhesiveness/aggregation.

OBJECTIVES: To reveal the presence of infection/inflammation in patients with relatively normal white blood cell count (WBCC) by using the leukocyte adhesiveness/aggregation test (LAAT). METHODS: The LAAT was performed by using a simple slide test and image analysis (Inflamet), the WBCC, by an electronic cell analyzer, C-reactive protein, by Laser nephelometry and CD11b/CD18 by whole blood flow cytometry. RESULTS: Forty out of a cohort of 121 patients with nonviral acute febrile illness had a WBCC within normal limits. The intensity of the inflammatory response in these individuals as judged by either C-reactive protein, or fibrinogen concentrations, erythrocyte sedimentation or polymorphonuclear leukocyte CD11b/CD18 expression was similar to that observed in patients with a leukocytic response. Our present finding that 63% out of the group with documented infection/inflammation and no leukocytosis had a significantly increased LAAT suggest that the lack of leukocytosis is in part a pseudoleukopenia, or is associated with some degree of uncompensated tissue leukostasis. CONCLUSIONS: The lack of a leukocytic response in a patient with nonviral infection/inflammation is by no means a sign of a less inflammatory response. The increased state of leukocyte adhesiveness/aggregation might help to disclose the presence of inflammation in these individuals.

The appearance of L-selectin(low) polymorphonuclear leukocytes in the circulating pool of peripheral blood during myocardial infarction correlates with neutrophilia and with the size of the infarct.

BACKGROUND: It is assumed that not only leukocytosis, but also the activation of white blood cells (WBC) may play a role in the pathogenesis and prognosis of patients with myocardial infarction (MI). Activation of WBC includes upregulation of CD11b/CD18 and downregulation of CD62L (L-selectin) antigens. HYPOTHESIS: The activation of WBC is associated with the appearance of a larger MI. METHODS: CD11b/CD18 and CD62L were measured on the surface of WBC on Day 1 and Day 3 from the onset of MI. The size of the infarct with estimated by calculating the area under the curve of the creatine kinase enzyme, which was measured every 6 h. RESULTS: A negative correlation was noted between the absolute polymorphonuclear count and the availability of the CD62L on these cells during Day 1 (r = -0.46, p = 0.003) and Day 3 (r = -0.35, p = 0.05). There was a positive correlation between the size of MI and the WBC count (r = 0.46, p = 0.004) and a negative correlation with CD62L on polymorphonuclears (r = -0.35, p = 0.03). During Day 3, the CD11b/CD18 on the polymorphonuclears increased despite a decrement in the absolute number of these cells. CONCLUSION: The neutrophilia during the early phases of acute MI correspond to the appearance of the L-selectin(low) population of polymorphonuclear leukocytes. There is a correlation between the appearance of this population and the size of the infarct.

Increased expression of the CD11b/CD18 antigen on the surface of peripheral white blood cells in patients with ischemic heart disease: further evidence for smoldering inflammation in patients with atherosclerosis.

BACKGROUND: This study examined the availability of the CD11b/CD18 and CD62L antigens on the surface of peripheral blood leukocytes in patients with ischemic heart disease. METHODS AND RESULTS: The study population included 45 patients with angiographically documented ischemic heart disease admitted to our department of internal medicine and the cardiology department during 1 month (December 1997). Sixty-six healthy members of the hospital medical staff served as control subjects. Another 39 post-trauma patients who were admitted to the emergency room were also evaluated. Patients with ischemic heart disease had significantly (P <.002) higher concentrations of CD11b/CD18 antigen on the surface of their polymorphonuclear leukocytes and monocytes (mean fluorescence intensity of 203 +/- 81 and 261 +/- 75, respectively) compared with the control group (mean fluorescence intensity 158 +/- 68 and 211 +/- 74, respectively) and to the group of patients with acute stress (mean fluorescence intensity of 146 +/- 70 and 200 +/- 22, respectively). CONCLUSIONS: The presence of increased concentration of CD11b/CD18 suggests that circulating leukocytes are activated in patients with ischemic heart disease. This activation probably reflects the presence of an inflammatory response involving the atherosclerotic lesion and is not merely a result of acute stress.

Circadian rhythm of acute pulmonary edema.

We found that the onset of acute pulmonary edema demonstrates circadian periodicity. Most episodes occur in the morning or at night. Pulmonary edema occurs more frequently during the colder months.

Neutrophilia of infection/inflammation: are we really dealing with "inflamed" leukocytes?

We adopted whole blood flow cytometry and direct labeling of the CD11b/CD18 and CD62L antigens to study the relationship between their expression and leukocytosis in patients with infection/inflammation, acute stress and healthy volunteers. Mean +/- S.D. channel fluorescence intensity of CD11b/CD18 antigen on peripheral blood polymorphonuclears did not differ between patients with infection/ inflammation (173+/-78) and controls (167+/-72), but was significantly (p = 0.04) reduced in stress (135+/-60). No correlation was found between CD11b/CD18 antigen level and either polymorphonuclears absolute number or serum C-reactive protein. A significant negative correlation was noted between CD62L antigen expression on polymorphonuclears and their absolute number. We assume that cells with increased CD11b/CD18 surface concentrations are retained in the capillaries and that part of the leukocytes in the peripheral blood are stressed leukocytes with reduced CD11b/CD18. Thus, leukocytes detected in peripheral blood are not necessarily the most "inflamed" ones.

Down-regulation of the CD62L antigen as a possible mechanism for neutrophilia during inflammation.

The expressions of both the CD11b/CD18 and CD62L (L-selectin) antigens as well as the absolute number of white blood cells in the peripheral circulating pool of blood in 116 patients with various inflammatory conditions were determined. A highly significant (P<0.0001) negative correlation (r = -0.57) was noted between the absolute number of peripheral blood polymorphonuclear leucocytes and the expression of the CD62L antigen on their surface. In view of the role of CD62L antigen in the rolling of leucocytes along endothelial cells in the microvasculature, its down-regulation might explain, at least in part, the demargination and appearance of neutrophilia during inflammation.

The leukocyte adhesiveness/aggregation test as an inflammation-related, plasma-dependent agglutination phenomenon.

The leukocyte adhesiveness/aggregation test (LAAT) is a non-specific marker of inflammation. In the present study, we examined the expression of the CD11b/CD18 as well as the CD62L antigens on the surface of peripheral blood leukocytes in 84 patients with various inflammatory conditions and 60 controls by using whole blood flow cytometry. We also conducted several in vitro experiments in order to explain the mechanism of the leukocyte adhesiveness/aggregation. A significant (r= -0.36, p<0.001) negative correlation was found between the expression of CD62L on the surface of peripheral blood polymorphonuclears and the state of LAA. There was no correlation between the availability of the CD11b/CD18 antigen and the adhesive state of these cells. In a series of in vitro experiments, we could show that it is possible to significantly reduce the number of aggregated leukocytes in the peripheral blood by using dilutions with buffer but not with plasma. There is no change in the degree of aggregation following incubation at low temperature in the presence of an aerobic metabolism blocker or following incubation with a divalent ion chelator. Additionally, white blood cells could be seen to adhere to protein-rich areas in the peripheral slides. We assume that the state of LAA in the peripheral blood as revealed by the LAA test is more a plasma factor-dependent agglutination than a firm aggregation phenomenon. Factors other than the leukocyte integrins or selectins should be sought as being responsible for this LAA phenomenon.

Dissociation between the state of leukocyte adhesiveness/aggregation in the peripheral blood and the availability of the CD11B/CD18 and CD62L antigens on the surface of the cells in patients with stress.

We adopted whole blood flow cytometry and direct labeling of the CD11b/CD18 and the CD62L antigens to study the relationship between their expression on the surface of peripheral leukocytes and the state of leukocyte adhesiveness/aggregation (LAA) as revealed by the leukergy test. We examined patients with infection/inflammation, acute stress and controls. The mean +/- S.D. channel fluorescence intensity of CD11b/CD18 antigen did not differ between patients with infection/inflammation (173 +/- 78) and controls (167 +/- 72). However, a significant (p < 0.0001) difference between these groups was noted regarding LAA state. There was a significant (p = 0.04) reduction in CD11b/CD18 in stress (135 +/- 60) and a significant (p < 0.001) increment in LAA. In both study groups, there was a significant reduction in CD62L. Patients were divided into those with CD11b/CD18 above and below the control's average. No correlation was found between the antigens and LAA. We assume that LAA in patients with stress state is CD11b/CD18 and CD62L independent.

Head banger's whiplash.

OBJECTIVE: The current trend in dancing includes "head banging" with extreme flexion, extension, and rotation of the head and cervical spine. We suggest that dance-related severe pain in the cervical area may result from head banging. DESIGN: A cohort of 37 eighth graders ages 13 or 14 participated in a dance marathon for charity lasting 7 h. There were 26 girls and 11 boys. SETTING: During the dance marathon, three "heavy metal" songs were played during which head banging could be done. PATIENTS: The painful syndromes that relate to head banging were evaluated by a convenience sample of the 37 marathon dancers in the eighth grade. INTERVENTIONS: None. MAIN OUTCOME MEASURES: A self-selected age-matched control group is included since 17 adolescents participated in head banging and 20 did not. RESULTS: Of the head bangers, 81.82% of the girls and 16.6% of the boys had resultant cervical spine pain that lasted 1-3 days. Only 26.2% of non-head-banging girls and 0% of non-head-banging boys had cervical spine pain lasting 1-3 days. Of all the 8th-grade participants, 62.16% had pain somewhere. Other types of pain included leg pain, back pain, and headache. Only three adolescents took any medication for their pain. CONCLUSIONS: The head-banger's whiplash is a self-limiting painful disorder. The easy resolution of the pain problem in adolescents is a tribute to the resilience of youth.

Persistent high-altitude headache and aguesia without anosmia.

High-altitude headache and taste dysfunction are usually cured within a few months by descent to sea level. We studied a patient who had persistent bitemporal throbbing headache with the associated findings of high-altitude headache syndrome 15 years after a compression chamber accident. He also had loss of taste without loss of smell since the incident.

Benign encephalopathy of pregnancy. Preliminary clinical observations.

A survey of 67 pregnancies in 51 professional women (physicians, psychologists, nurses, administrators, etc.) revealed the occurrence of symptoms of cognitive dysfunction such as forgetfulness, disorientation, confusion and reading difficulties in 28 pregnancies occurring in 21 women. These were unrelated to such factors as age of delivery, percentage weight gain, the baby's sex or birth weight, alcohol consumption, smoking, a history of migraine or allergy or other symptoms occurring during pregnancy such as sleepiness and lack of concentration, irritability, loss of interest in job or nightmares. Nor was there any correlation with hypertension, proteinuria, glycosuria, ketonuria, anemia, or morning sickness. Furthermore, these cognitive disturbances were not related to depression or sleep deprivation. Despite these symptoms, none of the women suffering from them were forced to interrupt their professional activities during pregnancy. The syndrome of benign encephalopathy of pregnancy should be recognized so that simple precautions can be taken to prevent any interference with professional or other activities. The etiology of the syndrome is unknown.

Hypothalamic hypothyroidism causing spastic paraplegia: recovery following thyroid medication.

A 63-year-old woman with longstanding spastic paraplegia and neurological evidence of long tract disturbance was found to have hypothyroidism, partial diabetes insipidus, hyperprolactinemia, and gonadotropin deficiency of hypothalamic origin. Replacement therapy with thyroxine and prednisone induced complete remission of the neurological abnormalities. The association of spastic paraplegia with hypothalamic insufficiency has not been reported previously. The possibility of hypothalamic disease should be considered in cases of spastic paraplegia of unknown cause.