Dental Caries Severity and Nutritional Status of Nigerian Preschool Children.

INTRODUCTION: Malnutrition in children is one of the most prevalent global health challenges, and malnourished children have a higher risk of death from childhood diseases. Early childhood caries (ECC) is the most common chronic disease of childhood. Complications from ECC such as pain, loss of tooth/teeth, and infection can undermine a child's nutrition and growth. AIM: This study aims to evaluate the severity of decay, missing, and filled tooth (dmft) by nutritional status using the z scores of the anthropometric measurements: height for age (HFA), weight for age (WFA), weight for height (WFH), and body mass index for age (BMIA) among children with ECC in Nigeria. STUDY DESIGN: This is a cross-sectional study conducted in 5 local government areas (LGAs) in Lagos State, Nigeria. A multistage sampling technique was used. RESULTS: A total of 273 cases of ECC were included in the analyses (mean age 4.19 ± 0.96 y). Overall, the mean dmft was 3.04 ± 2.28, and most (96%) were accounted for by untreated decay. The distribution of dmft within the different z score categories of BMIA (<-3 = severely wasted, -2 to -3 = wasted, -2 to +2 = normal, +2 to +3 = overweight and >+3 = obese) showed the highest dmft scores among the combined severely wasted and wasted groups, lowest among children with normal z scores, and intermediate in the overweight and obese groups. There was a significant negative correlation between BMIA z score, WFH z score, and dmft (r = -0.181, P < 0.05 and r = -0.143, P < 0.05, respectively). However, the correlations between HFA z score, WFA z score, and dmft were positive but not significant (r = 0.048, P = 0.44 and r = 0.022, P = 0.77, respectively). CONCLUSION: Our study showed an increased severity of dental caries among severely wasted or wasted children with ECC compared to those of normal or overweight. KNOWLEDGE TRANSFER STATEMENT: The results from this study will raise awareness among clinicians and policy makers on the need for a primary prevention program for early childhood caries in countries with high burden of malnutrition and limited resources. Also, it will help draw the attention of clinicians to the caries status of malnourished children that can be managed to improve the nutritional outcomes.

Genome-wide Gene-by-Sex Interaction Studies Identify Novel Nonsyndromic Orofacial Clefts Risk Locus.

Risk loci identified through genome-wide association studies have explained about 25% of the phenotypic variations in nonsyndromic orofacial clefts (nsOFCs) on the liability scale. Despite the notable sex differences in the incidences of the different cleft types, investigation of loci for sex-specific effects has been understudied. To explore the sex-specific effects in genetic etiology of nsOFCs, we conducted a genome-wide gene × sex (GxSex) interaction study in a sub-Saharan African orofacial cleft cohort. The sample included 1,019 nonsyndromic orofacial cleft cases (814 cleft lip with or without cleft palate and 205 cleft palate only) and 2,159 controls recruited from 3 sites (Ethiopia, Ghana, and Nigeria). An additive logistic model was used to examine the joint effects of the genotype and GxSex interaction. Furthermore, we examined loci with suggestive significance (P < 1E-5) in the additive model for the effect of the GxSex interaction only. We identified a novel risk locus on chromosome 8p22 with genome-wide significant joint and GxSex interaction effects (rs2720555, p2df = 1.16E-08, pGxSex = 1.49E-09, odds ratio [OR] = 0.44, 95% CI = 0.34 to 0.57). For males, the risk of cleft lip with or without cleft palate at this locus decreases with additional copies of the minor allele (p < 0.0001, OR = 0.60, 95% CI = 0.48 to 0.74), but the effect is reversed for females (p = 0.0004, OR = 1.36, 95% CI = 1.15 to 1.60). We replicated the female-specific effect of this locus in an independent cohort (p = 0.037, OR = 1.30, 95% CI = 1.02 to 1.65), but no significant effect was found for the males (p = 0.29, OR = 0.86, 95% CI = 0.65 to 1.14). This locus is in topologically associating domain with craniofacially expressed and enriched genes during embryonic development. Rare coding mutations of some of these genes were identified in nsOFC cohorts through whole exome sequencing analysis. Our study is additional proof that genome-wide GxSex interaction analysis provides an opportunity for novel findings of loci and genes that contribute to the risk of nsOFCs.

5-aminolevulinic acid photodynamic therapy for the treatment of high-grade gliomas.

INTRODUCTION: Photodynamic therapy (PDT) is a two-step treatment involving the administration of a photosensitive agent followed by its activation at a specific light wavelength for targeting of tumor cells. MATERIALS/METHODS: A comprehensive review of the literature was performed to analyze the indications for PDT, mechanisms of action, use of different photosensitizers, the immunomodulatory effects of PDT, and both preclinical and clinical studies for use in high-grade gliomas (HGGs). RESULTS: PDT has been approved by the United States Food and Drug Administration (FDA) for the treatment of premalignant and malignant diseases, such as actinic keratoses, Barrett's esophagus, esophageal cancers, and endobronchial non-small cell lung cancers, as well as for the treatment of choroidal neovascularization. In neuro-oncology, clinical trials are currently underway to demonstrate PDT efficacy against a number of malignancies that include HGGs and other brain tumors. Both photosensitizers and photosensitizing precursors have been used for PDT. 5-aminolevulinic acid (5-ALA), an intermediate in the heme synthesis pathway, is a photosensitizing precursor with FDA approval for PDT of actinic keratosis and as an intraoperative imaging agent for fluorescence-guided visualization of malignant tissue during glioma surgery. New trials are underway to utilize 5-ALA as a therapeutic agent for PDT of the intraoperative resection cavity and interstitial PDT for inoperable HGGs. CONCLUSION: PDT remains a promising therapeutic approach that requires further study in HGGs. Use of 5-ALA PDT permits selective tumor targeting due to the intracellular metabolism of 5-ALA. The immunomodulatory effects of PDT further strengthen its use for treatment of HGGs and requires a better understanding. The combination of PDT with adjuvant therapies for HGGs will need to be studied in randomized, controlled studies.

Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate.

In contrast to the progress that has been made toward understanding the genetic etiology of cleft lip with or without cleft palate, relatively little is known about the genetic etiology for cleft palate only (CPO). A common coding variant of grainyhead like transcription factor 3 ( GRHL3) was recently shown to be associated with risk for CPO in Europeans. Mutations in this gene were also reported in families with Van der Woude syndrome. To identify rare mutations in GRHL3 that might explain the missing heritability for CPO, we sequenced GRHL3 in cases of CPO from Africa. We recruited participants from Ghana, Ethiopia, and Nigeria. This cohort included case-parent trios, cases and other family members, as well as controls. We sequenced exons of this gene in DNA from a total of 134 nonsyndromic cases. When possible, we sequenced them in parents to identify de novo mutations. Five novel mutations were identified: 2 missense (c.497C>A; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470delC; p.Gly158Alafster55), and 1 nonsense (c.1677C>A; p.Tyr559Ter). These mutations were absent from 270 sequenced controls and from all public exome and whole genome databases, including the 1000 Genomes database (which includes data from Africa). However, 4 of the 5 mutations were present in unaffected mothers, indicating that their penetrance is incomplete. Interestingly, 1 mutation damaged a predicted sumoylation site, and another disrupted a predicted CK1 phosphorylation site. Overexpression assays in zebrafish and reporter assays in vitro indicated that 4 variants were functionally null or hypomorphic, while 1 was dominant negative. This study provides evidence that, as in Caucasian populations, mutations in GRHL3 contribute to the risk of nonsyndromic CPO in the African population.

Association Studies and Direct DNA Sequencing Implicate Genetic Susceptibility Loci in the Etiology of Nonsyndromic Orofacial Clefts in Sub-Saharan African Populations.

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit a multifactorial pattern of inheritance, with genetic and environmental factors both playing crucial roles. Many loci have been implicated in the etiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries, through genome-wide association studies and candidate gene studies. However, few populations of African descent have been studied to date. Here, the authors show evidence of an association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia, and Nigeria). The authors genotyped 48 single-nucleotide polymorphisms that were selected from previous genome-wide association studies and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1,070 unaffected relatives, and 1,078 unrelated controls. The authors also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the subpopulations, with West African subpopulations (Ghana and Nigeria) showing a similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, P = 5.10 × 10(-3)), 8q24 (rs987525, P = 1.22 × 10(-3)), and VAX1 (rs7078160, P = 0.04) were nominally associated with NSCL/P, and MSX1 (rs115200552, P = 0.01), TULP4 (rs651333, P = 0.04), CRISPLD2 (rs4783099, P = 0.02), and NOG1 (rs17760296, P = 0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold overtransmission in NSOFC cases through the transmission disequilibrium test and through analyses of the family-based association for disease traits. Through DNA sequencing, the authors also identified 2 novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29 In conclusion, the authors have shown evidence for the association of many loci with NSCL/P and NSCPO. To the best of this knowledge, this study is the first to demonstrate any of these association signals in any African population.

Complement activation contributes to ventilator-induced lung injury in rats.

The complement system contributes to ventilator induced lung injury (VILI). We hypothesized that pretreatment with the C1 esterase inhibitor (C1INH) Berinert® constrains complement activation consecutively inducing improvements in arterial oxygenation and histological pulmonary damage. At baseline, male Sprague-Dawley rats underwent mechanical ventilation in a conventional mode (PIP 13 cm H2O, PEEP 3 cm H2O). In the Control group, the ventilator setting was maintained (Control, n = 15). The other animals randomly received intravenous pretreatment with either 100 units/kg of the C1-INH Berinert® (VILI-C1INH group, n = 15) or 1 ml saline solution (VILI-C group, n = 15). VILI was induced by invasive ventilation (PIP 35 cm H2O, PEEP 0 cm H2O). After two hours of mechanical ventilation, the complement component C3a remained low in the Control group (258 ± 82 ng/ml) but increased in both VILI groups (VILI-C: 1017 ± 283 ng/ml; VILIC1INH: 817 ± 293 ng/ml; P < 0.05 for both VILI groups versus Control). VILI caused a profound deterioration of arterial oxygen tension (VILI-C: 193 ± 167 mmHg; VILI/C1-INH: 154 ± 115 mmHg), whereas arterial oxygen tension remained unaltered in the Control group (569 ± 26 mmHg; P < 0.05 versus both VILI groups). Histological investigation revealed prominent overdistension and interstitial edema in both VILI groups compared to the Control group. C3a plasma level in the VILI group were inversely correlated with arterial oxygen tension (R = -0.734; P < 0.001). We conclude that in our animal model of VILI the complement system was activated in parallel with the impairment in arterial oxygenation and that pretreatment with 100 units/kg Berinert® did neither prevent systemic complement activation nor lung injury.

[Telephone enquiries on the topic of malignant hyperthermia: Evaluation of the content and subsequent diagnostic results at the MH Center Leipzig]. / Telefonische Anfragen zum Thema maligne Hyperthermie: Auswertung der Inhalte und der resultierenden Diagnostikergebnisse am MH-Zentrum Leipzig.

BACKGROUND: Malignant hyperthermia (MH) is an autosomal dominant metabolic myopathy. The in vitro contracture test (IVCT) is still considered to be the gold standard for diagnosing a disposition for MH. However, advances in genetic testing for MH disposition have supplemented or even replaced the invasive procedure of the IVCT. Information about MH can be obtained by either contacting the hotline for MH as a nationwide 24 h/7 days a week service or one of the regional MH centers. METHODS: The protocols of telephone conversations concerning MH at the MH Center University Leipzig were retrospectively analyzed. Data were collected from January 2011 to March 2015. Additionally, the results of the IVCT and genetic testing evolving from the counseling interviews were examined. RESULTS: A total of 205 telephone calls were documented during the period in question and an IVCT was performed as a consequence of 112 of the telephone calls. The IVCT resulted in 27 individuals being identified as MH susceptible which was subsequently diagnosed in 15 individuals with known familial MH disposition and 12 individuals were identified as new index patients. In 24 individuals a total of 13 different mutations were detected and of these 4 mutations were causative concerning MH. Of the 205 telephone calls 131 were private and 74 of medical professional origin. Among the private enquiries MH disposition within the family was a frequent reason for contacting the MH Center (61.8%). Conversations relating to MH-like symptoms during general anesthesia were carried out with 35.1% of medical doctors and with 22.9% of private callers. Advice about neuromuscular symptoms of unknown genesis was given to 15.3% of private individuals and to 24.3% of medical doctors. Overall MH topics were discussed with 23% (N = 17) of the medical profession and approximately half of these were anesthesiologists (N = 8). Not a single call was documented for the treatment of a suspected MH crisis. CONCLUSION: Private individuals and families affected by a MH disposition often showed good compliance with respect to counseling and diagnostics for MH and contacted the MH center more often than medical doctors. A more comprehensive cooperation with the medical profession is preferable and necessary to obtain a systematic and broad synopsis of characteristic and uncharacteristic signs and symptoms of MH. The telephone conversations analyzed as well as the diagnostic results (IVCT and genetic testing) underline that MH disposition is still a current and relevant topic.

Colonization of liver transplant recipients with KPC-producing Klebsiella pneumoniae is associated with high infection rates and excess mortality: a case-control analysis.

PURPOSE: From mid-2010 to early 2013 there was a large single-center (Leipzig University Hospital, Germany) outbreak of Klebsiella pneumoniae carbapenemase (KPC) type 2 producing K. pneumoniae (KPC-2-KP) involving a total of 103 patients. The aim of this study was to compare KPC-positive liver transplant recipients (LTR) and KPC-negative controls to determine both the relative risk of infection following colonization with KPC-2-KP and the case fatality rate associated with KPC-2-KP. METHODS: The study cohort of this retrospective observational study comprised nine patients who had undergone orthotopic liver transplantation (LTx) (median age of 52 years, range 28-73 years) with confirmed evidence of colonization with KPC-2-KP. The data from these nine LTR were matched to 18 LTR (1:2) in whom carbapenem-resistant pathogens were not present and compared for clinical outcomes. RESULTS: Of these nine cases, eight (89 %) progressed to infection due to KPC-2-KP, and five (56 %) were confirmed to have bloodstream infection with KPC-2-KP. Matched-pair analysis of KPC-positive LTR and KPC-negative controls revealed a substantially increased relative risk of 7.0 (95 % confidence interval 1.8-27.1) for fatal infection with KPC-2-producing K. pneumoniae after transplantation with a mortality rate of 78 % (vs. 11 %, p = 0.001). CONCLUSIONS: Colonization with KPC-2-KP in LTR leads to high infection rates and excess mortality. Therefore, frequent screening for carbapenem-resistant bacteria in patients on LTx waiting lists appears to be mandatory in an outbreak setting. Patients with evidence of persistent colonization with KPC-producing pathogens should be evaluated with extreme caution for LTx.

Genetic and environmental factors associated with dental caries in children: the Iowa Fluoride Study.

Dental caries remains the most common chronic childhood disease. Despite strong evidence of genetic components, there have been few studies of candidate genes and caries. In this analysis we tried to assess genetic and environmental factors contributing to childhood caries in the Iowa Fluoride Study. Environmental factors (age, sex, race, tooth-brushing frequencies and water fluoride level) and three dental caries scores (d(2)fs-total, d(2)fs-pit/fissure, and d(2)fs-smooth surface) were assessed in 575 unrelated children (mean age 5.2 years). Regression analyses were applied to assess environmental correlates. The Family-Based Association Test was used to test genetic associations for 23 single nucleotide polymorphism (SNP) markers in 7 caries candidate genes on 333 Caucasian parent-child trios. We evaluated the associations between caries status and the level of both single and multiple SNPs (haplotype) respectively. Permutation procedure was performed for correction of inflated type I errors due to multiple testing. Age, tooth-brushing frequency and water fluoride level were significantly correlated to at least one carious score. Caries on pit and fissure surfaces was substantially higher than on smooth surfaces (61 vs. 39%). SNPs in three genes (DSPP, KLK4 and AQP5) showed consistent associations with protection against caries. Of note, KLK4 and AQP5 were also highlighted by subsequent haplotype analysis. Our results support the concept that genes can modify the susceptibility of caries in children. Replication analysis in independent cohorts is highly needed in order to verify the validity of our findings.

Stability of Cholesterol, 7-Ketocholesterol and ß-Sitosterol during Saponification: Ramifications for Artifact Monitoring of Sterol Oxide Products.

Cholesterol has been used to monitor artifact generation. Stability differences among cholesterol oxide products (COPs) and cholesterol in thermal and alkaline conditions are theorized. Thus, use of cholesterol may be unsuitable for detection of artifacts generated from COPs. Stability of cholesterol was compared to that of 7-ketocholesterol (7-keto) and ß-sitosterol (ßS) under various thermal and alkaline saponification conditions: 1 M methanolic KOH for 18 h at 24 °C (1 M18hr24°C, Control), 18 h at 37 °C (1M18hr37°C), 3 h at 45 °C (1M3hr45°C), and 3.6 M methanolic KOH for 3 h at 24 °C (3.6M3hr24°C). Trends indicated that cholesterol in solution was more stable than 7-keto under all conditions. Compared to ßS, cholesterol was more stable under all conditions except for 1M18hr37°C for which stabilities were similar. Compounds were more labile in heat than alkalinity. Poor recoveries of 7-keto during cold saponification with high alkalinity were attributed to alkaline instability. 7-Keto, less stable than cholesterol, should be used to monitor artifact generation during screening of various methods that include thermal and alkaline conditions. In a preliminary analysis of turkey meat, more 3,5-7-one was generated from spiking with cholesterol than with 7-keto.

[Mechanical ventilation and fluid management in acute lung injury. Effects on gas exchange and hemodynamics]. / Beatmung und Volumentherapie beim akuten Lungenversagen. Auswirkung auf Gasaustausch und Hämodynamik.

Basic therapy of acute lung injury (ALI) covers a pressure-limited lung protective mechanical ventilation with low tidal volumes (6-8 ml/kg ideal body weight), adequate positive end-expiratory pressure (PEEP) combined with early recruitment maneuvers and a restrictive fluid management (in hypoproteinemic patients preferably with albumin and diuretics). These measures aim at providing sufficient oxygenation while simultaneously minimizing airway pressure, atelectasis and edema formation. The main hemodynamic effects are a decrease in cardiac output and in systemic arterial pressure potentially reducing organ perfusion. However, successful therapy reduces hypoxic pulmonary vasoconstriction and hypercapnia, thus lowering pulmonary artery pressure, unloading the right ventricle, and stabilising hemodynamics.

[Infrarenal abdominal aortic aneurysm: endovascular repair with stent grafts]. / Infrarenales Bauchaortenaneurysma: Endovaskuläre Stent-Graft-Therapie.

As an alternative to surgery, endovascular therapy with stent grafts has become the second main treatment option for infrarenal abdominal aortic aneurysms. Unlike surgery, endovascular treatment with stent grafts is also applicable in patients unfit for open repair. Despite current improvements in endovascular repair devices, significant anatomic barriers still exclude this technique for a large number of patients. Computed tomography, magnetic resonance imaging, and ultrasound are essential for diagnostics, preintervention planning, and postintervention follow-up of abdominal aneurysms treated with stent grafts. This review covers etiology, pathology, and diagnostic aspects. Materials and methods for endovascular treatment of abdominal aortic aneurysms are presented in detail, and clinical results and complications are discussed.

Breathing pattern, CO2 elimination and the absence of exhaled NO in freely diving Weddell seals.

UNLABELLED: Weddell seals undergo lung collapse during dives below 50 m depth. In order to explore the physiological mechanisms contributing to restoring lung volume and gas exchange after surfacing, we studied ventilatory parameters in three Weddell seals between dives from an isolated ice hole on McMurdo Sound, Antarctica. METHODS: Lung volumes and CO(2) elimination were investigated using a pneumotachograph, infrared gas analysis, and nitrogen washout. Thoracic circumference was determined with a strain gauge. Exhaled nitric oxide was measured using chemiluminescence. RESULTS: Breathing of Weddell seals was characterized by an apneustic pattern with end-inspiratory pauses with functional residual capacity at the end of inspiration. Respiratory flow rate and tidal volume peaked within the first 3 min after surfacing. Lung volume reductions before and increases after diving were approximately 20% of the lung volume at rest. Thoracic circumference changed by less than 2% during diving. The excess CO(2) eliminated after dives correlated closely with the duration of the preceding dive. Nitric oxide was not present in the expired gas. CONCLUSION: Our data suggest that most of the changes in lung volume during diving result from compression and decompression of the gas remaining in the respiratory tract. Cranial shifts of the diaphragm and translocation of blood into the thorax rather than a reduction of thoracic circumference appear to compensate for lung collapse. The time to normalise gas exchange after surfacing was mainly determined by the accumulation of CO(2) during the dive. These findings underline the remarkable adaptations of the Weddell seal for restoring lung volume and gas exchange after diving.

Thirty-eight-negative kinase 1 (TNK1) facilitates TNFalpha-induced apoptosis by blocking NF-kappaB activation.

Thirty-eight-negative kinase 1 (TNK1) is a member of the ACK-family of nonreceptor tyrosine kinases and was originally cloned from CD34+/Lin-/CD38-hematopoietic stem/progenitor cells. The signaling pathways induced by TNK1 are largely unknown. Here, we report that expression and consequent activation of TNK1 enables tumor necrosis factor alpha (TNFalpha)-induced apoptosis by selectively inhibiting TNFalpha-induced activation of nuclear factor-kappaB (NF-kappaB). TNK1 has no effect on NF-kappaB DNA binding or the composition of the NF-kappaB complex; however, the kinase markedly prevents TNFalpha-induced NF-kappaB transactivation. TNK1 therefore acts as a novel molecular switch that can determine the properties of TNFalpha signaling and therefore cell death.

Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancer.

BACKGROUND AND OBJECTIVES: Interstitial photodynamic therapy (PDT) is an emerging modality for the treatment of solid organ disease. Our group at the University of Pennsylvania has performed extensive studies that demonstrate the feasibility of interstitial PDT for prostate cancer. Our preclinical and clinical experience is herein detailed. STUDY DESIGN/MATERIALS AND METHODS: We have treated 16 canines in preclinical studies, and 16 human subjects in a Phase I study, using motexafin lutetium-mediated PDT for recurrent prostate adenocarcinoma. Dosimetry of light fluence, drug level and oxygen distribution for these patients were performed. RESULTS: We demonstrate the safe and comprehensive treatment of the prostate using PDT. However, there is significant variability in the dose distribution and the subsequent tissue necrosis throughout the prostate. CONCLUSIONS: PDT is an attractive option for the treatment of prostate adenocarcinoma. However, the observed variation in PDT dose distribution translates into uncertain therapeutic reproducibility. Our future focus will be on the development of an integrated system that is able to both detect and compensate for dose variations in real-time, in order to deliver a consistent overall PDT dose distribution.

Photodynamic therapy with motexafin lutetium for rectal cancer: a preclinical model in the dog.

PURPOSE: Local recurrence of rectal cancer remains a significant clinical problem despite multi-modality therapy. Photodynamic Therapy (PDT) is a cancer treatment which generates tumor kill through the production of singlet oxygen in cells containing a photosensitizing drug when exposed to laser light of a specific wavelength. PDT is a promising modality for prevention of local recurrence of rectal cancer for several reasons: tumor cells may selectively retain photosensitizer at higher levels than normal tissues, the pelvis after mesorectal excision is a fixed space amenable to intra-operative illumination, and PDT can generate toxicity in tissues up to 1 cm thick. This study evaluated the safety, tissue penetration of 730 nm light, normal tissue toxicity and surgical outcome in a dog model of rectal resection after motexafin lutetium-mediated photodynamic therapy. METHODS: Ten mixed breed dogs were used. Eight dogs underwent proctectomy and low rectal end to end stapled anastomosis. Six dogs received the photosensitizing agent motexafin lutetium (MLu, Pharmacyclics, Inc., Sunnyvale, CA) of 2 mg/kg preoperatively and underwent subsequent pelvic illumination of the transected distal rectum of 730 nm light with light doses ranging from 0.5 J/cm(2) to 10 J/cm(2) three hours after drug delivery. Two dogs received light, but no drug, and underwent proctectomy and low-rectal stapled anastomosis. Two dogs underwent midline laparotomy and pelvic illumination. Light penetration in tissues was determined for small bowel, rectum, pelvic sidewall, and skin. Clinical outcomes were recorded. Animals were sacrificed at 14 days and histological evaluation was performed. RESULTS: All dogs recovered uneventfully. No dog suffered an anastomotic leak. Severe tissue toxicity was not seen. Histological findings at necropsy revealed mild enteritis in all dogs. The excitation light penetration depths were 0.46 +/- 0.18, 0.46 +/- 0.15, and 0.69 +/- 0.39 cm, respectively, for rectum, small bowel, and peritoneum in dogs that had received MLu. For control dogs without photosensitizer MLu, the optical penetration depths were longer: 0.92 +/- 0.63, 0.67 +/- 0.10, and 1.1 +/- 0.80 cm for rectum, small bowel, and peritoneum, respectively. CONCLUSION: Low rectal stapled anastomosis is safe when performed with MLu-mediated pelvic PDT in a dog model. Significant tissue penetration of 730 nm light into the rectum and pelvic sidewall was revealed without generation of significant toxicity or histological sequelae. Penetration depths of 730 nm light in pelvic tissue suggest that microscopic residual disease of less than 5 mm are likely to be treated adequately with MLu-mediated PDT. This approach merits further investigation as an adjuvant to total mesorectal excision and chemoradiation for rectal cancer.

Intra- and extravascular volume status in patients undergoing mitral valve replacement: crystalloid vs. colloid priming of cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: Cardiopulmonary bypass is associated with changes of intra- and extravascular volume status often resulting in cardiopulmonary dysfunction. The purpose of this prospective double-blind study was to evaluate the influence of different priming solutions of the extracorporeal circuit on intra- and extravascular volume status and haemodynamics in patients undergoing elective mitral valve replacement. METHODS: Twenty-two patients with mitral valve insufficiency were randomly allocated into two equal groups. In Group 1 cardiopulmonary bypass was primed with a nearly isooncotic solution consisting of 4% albumin. The second group received a pure crystalloid priming solution. The thermo-dye indicator dilution technique was used for the assessment of cardiac output, central and pulmonary blood volume, right ventricular end-diastolic volume and total blood volume. RESULTS: Patients in the crystalloid group showed increased intraoperative fluid requirements. Significantly more fluid was accumulated in the extravascular space whereas total blood volume was decreased after surgery. Stroke volume index (SVI) was significantly decreased in the immediate postoperative period when compared to baseline. As indicated by the increase in extravascular fluid content after surgery, both colloid and crystalloid priming volumes were transferred to the extravascular space. CONCLUSION: The use of colloid priming solutions in patients with mitral valve insufficiency leads to less fluid requirements and significantly reduced fluid shift in the interstitium. However, these changes are not associated with changes in haemodynamic parameters or short term outcome.