Hyperkalemia Accompanies Hemorrhagic Shock and Correlates with Mortality

OBJECTIVE:

This study was designed to evaluate the effects of terlipressin versus fluid resuscitation with normal saline, hypertonic saline or hypertonic-hyperoncotic hydroxyethyl starch, on hemodynamics, metabolics, blood loss and short-term survival in hemorrhagic shock.

METHOD:

Twenty-nine pigs were subjected to severe liver injury and treated 30 min later with either: (1) 2 mg terlipressin in a bolus, (2) placebo-treated controls, (3) 4 mL/kg 7.5% hypertonic NaCl, (4) 4 mL/kg 7.2% hypertonic-hyperoncotic hydroxyethyl starch 200/0.5, or (5) normal saline at three times lost blood volume.

RESULTS:

The overall mortality rate was 69%. Blood loss was significantly higher in the hypertonic-hyperoncotic hydroxyethyl starch and normal saline groups than in the terlipressin, hypertonic NaCl and placebo-treated controls groups (p<0.005). Hyperkalemia (K>5 mmol/L) before any treatment occurred in 66% of the patients (80% among non-survivors vs. 22% among survivors, p=0.019). Post-resuscitation hyperkalemia occurred in 86.66% of non-survivors vs. 0% of survivors (p<0.001). Hyperkalemia was the first sign of an unsuccessful outcome for the usual resuscitative procedure and was not related to arterial acidemia. Successfully resuscitated animals showed a significant decrease in serum potassium levels relative to the baseline value.

CONCLUSION:

Hyperkalemia accompanies hemorrhagic shock and, in addition to providing an early sign of the acute ischemic insult severity, may be responsible for cardiac arrest related to hemorrhagic shock.     

Embolization of pseudoaneurysm of the internal maxillary artery after orthognathic surgery

In orthognathic surgery, Le Fort I osteotomy is one of the most often used methods for the correction of dental-facial deformities and is considered technically safe. However, this procedure may lead to diverse complications, including uncommon vascular complications. A clinical case is described of late development of pseudoaneurysm in one of the branches of the maxillary artery in a 20-year-old patient who had undergone Le Fort I osteotomy, bilateral sagittal osteotomy of mandibular branch, and mentoplasty and subsequently treated with embolization. The main forms of treating vascular injuries are reviewed, and embolization is demonstrated to be a technically safe procedure with few complications.     

A common polymorphism in the renin angiotensin system is associated with differential outcome of antihypertensive pharmacotherapy prescribed to Brazilian older women

BACKGROUND: Since variations on the renin angiotensin (RA) system tend to exert effects on blood pressure, we investigated the association of the common ACE and AT1R polymorphisms with response to a multivariate pharmacotherapy. METHODS: This prospective study involved 169 hypertensive, community-dwelling older women. Genotypes were obtained by length analysis or direct sequencing of PCR products. Blood pressure-lowering pharmacotherapy was conducted according to current Brazilian Guidelines on Hypertension. RESULTS: Genotype frequencies were in agreement to the Hardy-Weinberg equilibrium. Interventions were found to represent actual hypertension-management practices in Brazil, and accounted for a significant reduction in both systolic (P<0.001) and diastolic (P<0.001) blood pressure. Concerning the effect of polymorphisms, no influence of the ACE and AT1R genotypes were found on the magnitude of the treatment-induced blood pressure reduction (P>0.05). Nonetheless, the clinical result varied according to the ACE alleles since mean systolic pressure was roughly 10 mm Hg higher in insertion (I) homozygotes than in the deletion (D) counterparts either in baseline (P=0.001) and endpoint (P=0.010). CONCLUSION: The outcome of the antihypertensive pharmacotherapy advocated by national guidelines was significantly influenced by the ACE I/D polymorphism but not by the AT1R 1166 A/C polymorphism among postmenopausal women.     

E-cadherin abnormalities resulting from CPG methylation promoter in metastatic and nonmetastatic oral cancer

BACKGROUND: This study aims to compare the alterations in the methylation profiles of E-cadherin in oral cancer, especially in tumors with lowest metatastic potential. METHODS: Nine oral verrucous carcinomas (VCs), 20 oral well-differentiated squamous cell carcinomas without lymph node involvement (SCC-pN0), and 17 with lymph node involvement (SCC-pN+) were analyzed using methylation-specific polymerase chain reaction and immunohistochemical expression of E-cadherin gene. RESULTS: The immunohistochemical expression of E-cadherin in VC was significantly higher (p = .016) when compared with SCC-pN0 and SCC-pN+ groups. The E-cadherin gene methylation was not correlated with its abnormal immunohistochemical expression in VC and SCC-pN0. All tumors of the SCC-pN+ group with unmethylated E-cadherin gene showed significant loss of E-cadherin immunoexpression (p = .044). CONCLUSIONS: The E-cadherin gene methylation presence in tumors with lowest invasive and metastatic potential, such as VC, suggests the early involvement of this epigenetic event in the multistep progression of the oral carcinogenesis.     

Aberrant promoter methylation can be useful as a marker of recurrent disease in patients with cervical intraepithelial neoplasia grade III

INTRODUCTION: Although studies of risk factor profiles have been conducted to identify biological markers to predict the natural history of cervical intraepithelial neoplasia (CIN) grade III, there is not sufficient information to support the routine clinical use of any biomarker. OBJECTIVES: The purpose of this study was to examine aberrant promoter methylation, which is implicated in cancer development and progression, in CIN III lesions in order to identify markers associated with more aggressive biological behavior that could be used to recognize women who are at higher risk of recurrence. PATIENTS AND METHODS: We used methylation-specific polymerase chain reaction to analyze promoter hypermethylation of 8 genes (p16, RARbeta, GSTP1, MGMT, p14, TIMP3, E-cad and DAPk) in 33 uterine cervix cones with CIN III that were also submitted to human papillomavirus (HPV) genotyping. All 33 patients in this study had been clinically followed after conization with Papanicolaou smears, colposcopy, and biopsy when indicated, every 6 months during 5 years. RESULTS: Of the 33 patients, 12 (36%) underwent immediate hysterectomy after conization for having compromised cone margins, 14 (43%) have not relapsed, and 7 (21%) presented CIN relapse. The frequency of HPV infection in this group was 97% and no significant difference between the groups was observed. HPV of high oncogenic risk was present in 29 (87.9%) cases; HPV 16 was the most frequent (69.7%), while HPV 18 was found in 33.3%; however, it was associated with HPV 16 in 15.1%. Concomitant infection by HPV 6/11 was detected in 21.2% (15.1% with HPV 16 and 6.1 with HPV 18). 85.7% (6/7) of patients with recurrence had HPV 18 vs 0% (0/14) of patients without recurrence (P = 0.0001). At least 1 of the 8 genes was found hypermethylated in all samples. Concomitant hypermethylation of several genes was frequently found. However, CIN relapse was only seen in the cases with hypermethylation of 3 or more of the 8 genes studied (P = 0.0039). CONCLUSION: We suggest that aberrant promoter methylation may play a role and may serve as a useful biomarker in the recurrence of CIN.     

Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ).

BACKGROUND AND OBJECTIVE: Human Papillomavirus (HPV) persistence after high-grade cervical intra-epithelial neoplasia (CIN) removal may be associated with residual lesions or risk of disease recurrence. Knowledge regarding the factors associated with HPV persistence following CIN treatment is still limited. The main purpose of this longitudinal study was to assess the association between characteristics of the patients and their cervical lesions with high-risk HPV-type persistence, detected by commercially available Hybrid Capture II (HC II), after CIN 2 and 3 treatment with large loop excision of the transformation zone (LLETZ). STUDY DESIGN: For this cohort study, a total of 94 women submitted to LLETZ between March 2001 and September 2002 were included. Only women with at least one follow-up visit at 6 or 12 months and confirmed CIN 2 or 3 in the cone specimen were considered. In each visit women answered to a questionnaire and undertook Pap smear and HC II specimens collection. McNemar's, chi-square and Fisher tests were used for univariate analysis. Generalized Estimating Equations (GEE) were used for multivariate analysis. All calculations were performed within 95% confidence intervals (95% CI). RESULTS: Histological evaluation showed 12 (13%) women with CIN, 2 and 82 (87%) with CIN 3 and conization margins were compromised in 27 (29%) cases. Eighty-seven (92%) women showed positive HC II tests prior to LLETZ. Of women initially HPV negative, none had a positive HC II during follow-up. The proportion of positive HPV tests was reduced from 92% to 20%(P < 0.01) at the first visit and to 22% (P < 0.01) at the second visit after LLETZ. Multivariate analysis showed that smoking and age above 35 years (irrespective of margin status) were strongly associated with positive HPV during follow-up. CONCLUSION: HPV persistence following LLETZ was associated with smoking and with the interaction between age and conization margins.     

Relationship between sarcopenic obesity-related phenotypes and inflammatory markers in postmenopausal women

Ageing is associated with changes in body composition that may result in sarcopenic obesity (SO). Interleukin-6 (IL-6) and C-reactive protein (CRP) are important inflammatory markers related to ageing. SO has been examined as an important public health problem, but its association with inflammatory markers has yet to be investigated. The aim of this study was to investigate the association between SO-related phenotypes and inflammatory markers in postmenopausal women. A total of 130 women (66·7 ± 5·2 years) underwent body composition evaluation using dual-energy X-ray absorptiometry. Volunteers were classified according to a SO definition previously described in the literature. Waist circumference (WC) and handgrip strength (HG) were also measured. Blood samples were collected for CRP, tumour necrosis factor and IL-6 measurements. All the inflammatory markers were higher in SO individuals when compared to non-SO; however, only IL-6 reached statistical significance (median 3·34 versus 1·37 pg ml⁻¹; P<0·05). Also, CRP was significantly correlated (P<0·01) with body mass index (r_s = 0·34), fat mass (FM; r_s = 0·25) and WC (r_s = 0·33). Similarly, IL-6 levels were significantly correlated (P<0·05) to age (r_s = 0·19), FM (r_s = 0·19) and WC (r_s = 0·17). HG was found to be significantly reduced among subjects with higher IL-6 levels (P = 0·02). In summary, the combination of reduced muscle mass and excess body fat (i.e. SO) is associated with elevated inflammatory markers in postmenopausal women. Moreover, CRP and IL-6 are associated with SO-related phenotypes in this population.