Does the use of a flap during abdominoperineal resection decrease pelvic wound morbidity?

We hypothesized that the use of muscle flaps, known as tissue transfer (TT), at the time of abdominoperineal resection (APR) reduces perineal wound complications. A restrospective review of patients undergoing an APR at the University of Washington (1984-2003) was conducted. Perineal wound complications and eventual wound healing were compared in patients with and without TT. Ninety-two patients (mean age, 56.6 years) underwent APR; 23.9 per cent (n = 22) had concurrent TT. Patients undergoing TT were more likely to have cancer (91% vs. 77%, P = 0.05) and radiation therapy (86% vs. 52%, P < 0.01). Operative times were nearly 2 hours longer in patients having TT (7.4 hours +/- 2.5 hours vs. 5.6 hours +/- 1.8 hours, P = 0.03), but lengths of stay were similar (13 +/- 5.9 days vs. 12 +/- 7.6 days, P = 0.5). Patients undergoing TT had a higher rate of all wound-healing complications (59% vs. 40%, P = 0.1) and major wound-healing complications (32% vs. 26%, P = 0.6). However, these differences were not statistically significant. No differences in major complications were identified in patients with and without preoperative radiation therapy (26% vs. 28%, P = 0.8). Fifteen per cent (n = 14) of all patients failed to heal wounds at 6 months, but only 9 per cent (n = 2) of patients undergoing TT failed to heal their wounds at 6 months compared with 17 per cent (n = 12) in the non-TT group (P = 0.3). After controlling for important covariates, patients undergoing TT during an APR did not have a significantly lower rate of wound complications. The impact of TT on wound healing in patients with recurrent cancer and preoperative radiation therapy is suggestive of a benefit but requires prospective investigation.     

Secondary abdominal compartment syndrome: risk factors and outcomes

Secondary abdominal compartment syndrome (ACS), defined as intra-abdominal hypertension with associated pulmonary, renal, or hemodynamic compromise in the absence of preceding abdominal operation or injury, can markedly increase surgical morbidity and mortality. We performed a retrospective chart review of the physiologic parameters and outcomes of 10 patients with secondary ACS. Ten patients developed secondary ACS after aggressive resuscitation, at an average of 20.2 hours. Four of the patients sustained burns greater than 40 per cent, three of the patients had penetrating extremity trauma, one patient had blunt abdominal trauma, one patient was struck by lightning, and one patient developed a retroperitoneal bleed while on heparin. The average bladder pressure was 40.6. The average volume given in the first 24 hours was 33,001 cc (range, 12,400 to 69,000). The average base deficit at admission was -12 (range, +1 to -25). Seven of the 10 patients had decreased urine output. Nine of the 10 patients had decreased tidal volumes on pressure control ventilation. All 10 patients were hypotensive, with 7 of the 10 requiring vasopressors. Overall mortality was 60 per cent, with 43 per cent mortality for those decompressed. Prompt recognition and treatment are mandatory for survival of ACS. We recommend routine bladder pressure monitoring for patients with ongoing resuscitation greater than 500 cc/hr.     

Preliminary evidence for ethnic differences in primary hyperoxaluria type 1 genotype

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is caused by a deficiency of peroxisomal alanine:glyoxylate aminotransferase (AGT). In about one third of patients, enzymatically active AGT is synthesized but is mistargeted to mitochondria. There are more than 50 mutations identified in the gene for AGT. Four mutations, G170R, 33_34insC, F152I and I244T account for more than 50% of PH1 alleles. The question arose whether there are ethnic differences in PH1 genotype. METHODS: The published data on mutations in the AGT gene were examined with respect to recurrences and geographic or ethnic association. The mutations that have been found in at least 2 unrelated individuals were considered. RESULTS: Two common mutations, G170R and 33_34insC showed no obvious ethnic associations and have been found in a variety of populations. A third common PH1 mutation, I244T, has a strong association with people from a Spanish or North African background. A particularly high frequency among Canary Islands PH1 patients suggests a probable founder effect. Between these two extremes are a number of mutations that recur at low frequency within certain ethnic groups. CONCLUSIONS: Ethnic associations of PH1 genotypes span a spectrum ranging from limited recurrences confined to a population group, to a probable founder effect.     

Detection of Chlamydophila pneumoniae in the bone marrow of two patients with unexplained chronic anaemia

Anaemia of chronic disease (ACD) is a common finding involving iron deficiency and signs of inflammation. Here, we report on two patients with ACD where a persistent infection with Chlamydophila (Chlamydia) pneumoniae (CP) was detected in bone marrow (BM) biopsies. Infection was suspected by routine cytology and confirmed by immunofluorescence, electron microscopy, polymerase chain reaction (PCR) including different primer sets and laboratories and sequencing of the PCR product. This is a first report of chlamydial presence in the BM of anaemic patients. The cases are presented because persistent chlamydial infection may contribute more frequently to chronic refractory anaemia than previously suspected.     

Legionella pneumophila mediated activation of dendritic cells involves CD14 and TLR2

In this study, we analyzed the activation of bone-marrow derived dendritic cells (BMDCs) from mice lacking the cd14-gene with purified Legionella pneumophila lipopolysaccharide and with viable or formalin-killed L. pneumophila. We found that low concentrations of LPS and doses of L. pneumophila that are relevant to infection are dependent on CD14 to activate BMDCs. Higher concentrations of LPS are able to overcome the lack of CD14 indicating that other receptors areinvolved. We, therefore, included studies using BMDCs from mice lacking functional TLR2 and/or TLR4 molecules. We found that purified L. pneumophila LPS as well as L. pneumophila either viable or formalin-killed are able to activate BMDCs from TLR4-deficient C3H/HeJ mice but fail to activate BMDCs from TLR2-knockout mice. Our data show that not only purified LPS from L. pneumophila but also the microorganism itself stimulate BMDCs via TLR2 and that this stimulation is dependent on CD14 in this mouse model.     

Lysosomal enzymes in preeclamptic women in northern Nigeria

BACKGROUND: The incidence of preeclampsia is high in northern Nigeria, as it is in many other developing countries, and preeclampsia is associated with significant maternal and fetal morbidity and mortality. We inquired if proteinuria or hypertension alone could account for the altered concentrations of urinary lysosomal hydrolases that have been reported in preeclamptic women and pregnant women without preeclampsia. METHODS: The activities of urinary beta-hexosaminidase and beta-galactosidase were determined fluorometrically in pregnant women assigned to one of four groups: Group I: 41 preeclamptic women; Group II: 31 hypertensive aproteinuric women; Group III: 44 normotensive proteinuric women; and Group IV: 52 healthy pregnant women (controls). RESULTS: The urinary beta-hexosaminidase concentrations were decreased in the preeclamptic women (P<0.005) and proteinuric women (P<0.001) when compared to the healthy pregnant controls. There was no significant difference in beta-hexosaminidase concentrations between the hypertensive women and the healthy pregnant controls. The urinary beta-galactosidase concentrations for preeclamptic, hypertensive, and proteinuric women did not differ significantly versus healthy pregnant controls. CONCLUSIONS: The reduced urinary excretion of beta-hexosaminidase in preeclamptic women is associated with proteinuria, but not hypertension. Measuring urinary concentrations of lysosomal hydrolases alone or in conjunction with urinary protein concentrations is not likely to be useful in predicting or monitoring the clinical course of preeclampsia; however, it might prove important in gaining a more complete understanding of the pathogenesis of renal tubular epithelial cell injury and proteinuria that occurs in preeclampsia.     

Increased matrix metalloproteinase-13 production with aging by human articular chondrocytes in response to catabolic stimuli

Chondrocyte anabolic activity has been shown to decline with aging, but catabolic activity has received little attention. In this study, the effect of aging on the chondrocyte catabolic response was determined by stimulating isolated human chondrocytes with fibronectin fragments (FN-f) or interleukin-1beta and measuring matrix metalloproteinase-13 (MMP-13) production as a catabolic response. A significant age-related increase in chondrocyte MMP-13 production was noted. FN-f stimulation of MMP-13 expression was blocked using a nuclear factor kappa-B (NFkappaB) inhibitor suggesting a role for NFkappaB in this chondrocyte catabolic response. Chondrocyte production of the NFkappaB-regulated cytokine interleukin-1beta was also found to increase with donor age in unstimulated cells. These results demonstrate a significant age-related increase in chondrocyte catabolic responsiveness which could contribute to the development of osteoarthritis in older adults.