Outbreak of Mycobacterium Abscessus Infection After Soft Tissue Augmentation

BACKGROUND: Illicit soft-tissue augmentation performed in New York City resulted in an outbreak of Mycobacterium abscessus infection in 2002. OBJECTIVE: To report two cases of women who developed tender, subcutaneous nodules of the face and buttocks after illicit soft-tissue augmentation with a hyaluronic acid derivative. METHODS: Two case reports are presented, and the literature is reviewed. RESULTS: Empiric treatment with clarithromycin (for M. abscessus infection) and prednisone (for foreign body reaction) resulted in clearance of lesions. CONCLUSION: Contaminated or impure material used for soft-tissue augmentation can result in a clustered outbreak of infection or foreign body reaction.     

Oxygen Reverses Deficits of Cognitive Function and Memory and Increased Heart Rate Induced by Acute Severe Isovolemic Anemia

Background: Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia.

Methods: Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test.

Results: Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia.     

IFN-alpha enhances CD40 ligand-mediated activation of immature monocyte-derived dendritic cells

Type I IFN are immune modulatory cytokines that are secreted during early stages of infection. Type I IFN bridge the innate and the adaptive immune system in humans and mice. We compared the capacity of type I and II IFN to induce the functional maturation of monocyte-derived dendritic cells (MoDC). Extending our earlier observation that type I IFN promote DC maturation, we report that these cytokines also enhance DC differentiation by augmenting CD40 ligand (CD40L)-induced cytokine secretion by MoDC. Type I IFN alone were poor inducers of MoDC maturation as compared with other stimuli. They up-regulated the expression of HLA-DR, CD80, CD86, partially CCR7 but not CD83, partially reduced antigen-uptake function, increased the levels of IL-12p35 mRNA, and prolonged surface expression of peptide-MHC class I complexes for presentation to cytotoxic T lymphocytes, but did not induce migration towards CCL21 chemokine. However, type I IFN were potent co-factors for CD40L-mediated function. Here, they enhanced CD40L-mediated IL-6, IL-10 and IL-12p70 secretion. Furthermore, when combined with IL-1beta and/or IL-4, IFN-alpha2a type I IFN increased CD40L-mediated IL-12p70 production by 2- to 3-fold, and biased the IL-12 p40/p70 ratio towards the IFN-gamma inducing p70 heterodimer, this correlating with higher levels of IFN-gamma secretion by allogeneic T cell subsets and NK cells. Our results suggest that the rapid expression of CD40L, IFN and IL-1beta at sites of infection and inflammation can act in concert on immature DC, thereby linking innate and adaptive immune responses. In this way, type I IFN play a dual role as DC maturation factors and enhancers of CD40L-mediated DC activation.     

Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.      

The action of metabolic inhibitors on microgametogenesis in Plasmodium yoelii nigeriensis

Summary Mature gametocytes of Plasmodium yoelii nigeriensis were incubated in vitro with a variety of antibiotics whose activities were directed against DNA, RNA, protein and microtubule assembly. Following incubation for periods between 5 and 90 min, exflagellation was induced and the degree of inhibition produced by each drug was assayed microscopically.The results obtained show that de novo synthesis of axonemes and proteins is essential to the events of microgametogenesis. The inhibitory effect of actinomycin-D suggests that de novo RNA synthesis is also required. However, the inactivity of 8-azaguanine, a drug also effective against m-RNA metabolism, casts some doubt on the requirement for m-RNA synthesis.DNA synthesis is not required during the three successive mitotic divisions of the parasite genome during microgametogenesis. The mature microgametocyte therefore contains the 8c DNA required for microgamete production.     

Subcutaneous perfusion and oxygen during acute severe isovolemic hemodilution in healthy volunteers

HYPOTHESIS: Acute severe isovolemic anemia (to a hemoglobin [Hb] concentration of 50 g/L) does not decrease subcutaneous wound tissue oxygen tension (PsqO(2)). SETTING: University hospital operating room and inpatient general clinical research center ward. SUBJECTS: Twenty-five healthy, paid volunteers. METHODS: Subcutaneous oxygen tension and subcutaneous temperature (Tsq) were measured continuously during isovolemic hemodilution to an Hb level of 50 g/L. In 14 volunteers (initially well-perfused), "normal" perfusion (Tsq >34.4 degrees C) was achieved by hydration and systemic warming prior to starting isovolemic hemodilution, while in 11 volunteers (perfusion not controlled [PNC]), no attempt was made to control perfusion prior to hemodilution. MAIN OUTCOME MEASURES: Measurements of PsqO(2), Tsq, and relative subcutaneous blood flow (flow index). RESULTS: While PsqO(2), Tsq, and flow index were significantly lower in PNC vs well-perfused subjects at baseline, there was no significant difference between them at the Hb of 50 g/L (nadir). Subcutaneous PO(2) did not decrease significantly in either group. Arterial PO(2) was not different between the groups, and did not change significantly over time; Tsq and flow index increased significantly from baseline to nadir Hb in both groups. CONCLUSIONS: The level of PsqO(2) was maintained at baseline levels during hemodilution to Hb 50 g/L in healthy volunteers, whether they were initially well-perfused or mildly underperfused peripherally. Given the significant increase in Tsq and flow index, this resulted from a compensatory increase in subcutaneous blood flow sufficient to maintain oxygen delivery. Wound healing depends to a large extent on tissue oxygen delivery, and these data suggest that even severe anemia by itself would not be sufficient to impair wound healing. Thus, transfusion of autologous packed red blood cells solely to improve healing in surgical patients with no other indication for transfusion is not supported by these results.     

Electrocardiographic ST-segment changes during acute, severe isovolemic hemodilution in humans

BACKGROUND: Controversy exists regarding the lowest blood hemoglobin concentration that can be safely tolerated. The authors studied healthy resting humans to test the hypothesis that acute isovolemic reduction of blood hemoglobin concentration to 5 g/dl would produce an imbalance in myocardial oxygen supply and demand, resulting in myocardial ischemia. METHODS: Fifty-five conscious healthy human volunteers were studied. Isovolemic removal of aliquots of blood reduced blood hemoglobin concentration from 12.8 +/- 1.2 to 5.2 +/- 0.5 g/dl (mean +/- SD). Removed blood was replaced simultaneously with intravenous fluids to maintain constant isovolemia. Hemodynamics and arterial oxygen content (Cao2) were measured before and after removal of each aliquot of blood. Electrocardiographic (ECG) changes were monitored continuously using a Holter ECG recorder for detection of myocardial ischemia. RESULTS: During hemodilution, transient, reversible ST-segment depression developed in three subjects as seen on the electrocardiogram during hemodilution. These changes occurred at hemoglobin concentrations of 5-7 g/dl while the subjects were asymptomatic. Two of three subjects with ECG changes had significantly higher heart rates than those without ECG changes at the same hemoglobin concentrations. When evaluating the entire study period, the subjects who had ECG ST-segment changes had significantly higher maximum heart rates than those without ECG changes, despite having similar baseline values. CONCLUSION: With acute reduction of hemoglobin concentration to 5 g/dl, ECG ST-segment changes developed in 3 of 55 healthy conscious adults and were suggestive of, but not conclusive for, myocardial ischemia. The higher heart rates that developed during hemodilution may have contributed to the development of an imbalance between myocardial supply and demand resulting in ECG evidence of myocardial ischemia. However, these ECG changes appear to be benign because they were reversible and not accompanied by symptoms.