Anatomy of medial plantar superficial branch artery perforators: Facilitation of medial plantar superficial branch artery perforator (MPAP) flap harvesting and design for finger pulp reconstruction.

BACKGROUND: Medial plantar artery perforator (MPAP) flap was proposed as proper option for finger pulp reconstruction. To provide the previously unavailable vessel information required for this small flap design, this study aimed to gather all necessary anatomy of MPA, MPAP, and their territories of blood supply to apply in clinical MPAP flap reconstruction minimizing perforator injury. METHODS: Dissection of 30 Thai cadaveric feet for visualizing superficial branch of MPA and its perforators (MPAP) using acrylic dye cannulation were performed. Diameter, length, number of branches, course, distributing areas of these vessels, and also their areas of blood supply were recorded in relation to specified landmarks, eg, C-MTH line; medial calcaneal tuberosity to plantar side of the first metatarsal head and S point; emerging point of superficial branch of MPA from deep fasciae into subcutaneous layer. RESULTS: Average diameter of MPA at its origin and total length are 1.63 ± 0.3 and 52.8 ± 16.1 mm, respectively. It provides 1-3 perforators, with an average size and length of 0.36 ± 0.11 and 23.2 ± 5.47 mm, respectively. Its distribution is mostly in the posteromedial quadrant within 50 and 30 mm from the midpoint of C-MTH line and the S point, respectively. The estimated perforator flap area is 2.5 cm × 1.5 cm and 4.5 cm × 2.5 cm for single and double perforators, respectively. CONCLUSIONS: MPAP flap was proved as another ideal option for finger pulp reconstruction. Its limitation is small size of perforators but this can be overcome by using MPA for microsurgical anastomosis instead.

Vascular Nature and Existence of Anastomoses of Extrinsic Postauricular Fascia: Application for Staged Auricular Reconstruction.

A staged auricular reconstruction in microtia patients was developed by using superficial mastoid fascia (as part of extrinsic postauricular fascia) to cover the cartilagenous framework due to its highly vascularized nature. Three branches of external carotid artery (superficial temporal artery, posterior auricular artery and occipital artery) were found to supply this fascia, this study was therefore aimed to investigate the dimension of blood supply from each vessel and also to demonstrate the existence of anastomoses among these arteries. Thirty-eight pinnas and postauricular fascias from Thai fresh adult cadavers were included to document the anastomoses by showing both perfused dye connection (10 dissections) and visible anastomotic branches (8 dissections) among them. Distribution of each vessel trunk and its branches were demonstrated using superimposed illustration in the other 20 dissections with dye injection into each artery to designate 3 zones of anastomotic area between each arterial pair. Maximal size of viable postauricular fascial flap for staged reconstruction according to this vascular study was thus estimated to be at least 5 cm above and 3 cm below the Frankfurt horizontal plane and about 6 cm posterior to external acoustic meatus owing to the course of posterior auricular artery and its anastomoses. In addition, greater size of flap with dual blood supply from both superficial temporal and posterior auricular arteries can be raised by harvesting beyond 5 cm above external acoustic meatus.

A variant in the CD209 promoter is associated with severity of dengue disease.

Dengue fever and dengue hemorrhagic fever are mosquito-borne viral diseases. Dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN1, encoded by CD209), an attachment receptor of dengue virus, is essential for productive infection of dendritic cells. Here, we report strong association between a promoter variant of CD209, DCSIGN1-336, and risk of dengue fever compared with dengue hemorrhagic fever or population controls. The G allele of the variant DCSIGN1-336 was associated with strong protection against dengue fever in three independent cohorts from Thailand, with a carrier frequency of 4.7% in individuals with dengue fever compared with 22.4% in individuals with dengue hemorrhagic fever (odds ratio for risk of dengue hemorrhagic fever versus dengue fever: 5.84, P = 1.4 x 10(-7)) and 19.5% in controls (odds ratio for protection: 4.90, P = 2 x 10(-6)). This variant affects an Sp1-like binding site and transcriptional activity in vitro. These results indicate that CD209 has a crucial role in dengue pathogenesis, which discriminates between severe dengue fever and dengue hemorrhagic fever. This may have consequences for therapeutic and preventive strategies.

Characteristics of lower airway parameters in an adult Asian population related to endotracheal tube design: a cadaveric study.

The risk of endotracheal tube (ETT) placement includes endobronchial intubation and subglottic injury. This study aimed to describe the lengths of lower airway parameters related to cuff location and vocal cord markings in different adult-sized ETTs. Eighty cadavers were examined for the lengths of the lower airway, including their correlations and linear regressions with height. Thirty adult-sized ETTs from seven different brands were examined for Mark-Cuff and Mark-Tip distances. The depth of ETT placement was simulated for each brand using vocal cord marking. The mean (standard deviation) lengths from the subglottis, trachea, vocal cord to mid- trachea, and vocal cord to carina were 24.2 (3.5), 97.9 (8.6), 73.2 (5.3), and 122.1 (9.0) mm, respectively. Airway lengths were estimated as: (1) subglottis (mm) = 0.173 * (height in cm) - 3.547; (2) vocal cord to mid-trachea (mm) = 0.28 * (height in cm) + 28.391. There were variations in the Mark-Cuff and Mark-Tip distances among different ETTs. In the simulation, endobronchial intubation ranged between 2.5 and 5% and the cuff in the subglottis ranged between 2.5 and 97.5%. In summary, the lower airway parameters were height-related. ETT placement using vocal cord marking puts the patient at a high risk of cuff placement in the subglottis.

Germinated brown rice protects against glutamate toxicity in HT22 hippocampal neurons through the jnk-mediated apoptotic pathway via the GABAA receptor.

The anti-apoptosis effect of germinated brown rice (GBR) focusing on differentiated HT22 cells results in improved nutritional values after the germination process of GBR which contains total phenolic compounds and γ-aminobutyric acid (GABA). Cell death induced by 5 mM glutamate was investigated for 24 h to determine whether GBR mediates cell death through GABA receptors by using antagonists. The results showed that GBR (100 µg/ml) suppressed glutamate-induced cytotoxicity and caused arrest at the G1/S phase of the cell cycle in differentiated HT22 cells. Furthermore, GBR significantly decreased the expression level of c-Jun, while its active form, p-c-Jun, is the downstream product of the JNK-mediated apoptotic pathway and causes subsequent cell death. In addition, bicuculline (12.5 nM), a GABAA antagonist, could eliminate GBR effects, but phaclofen (1 mM), a GABAB antagonist, could not. Surprisingly, GBR exhibited a better neuroprotective effect than a pure commercial GABA compound (0.115 µM). These results indicated that GBR possessed high anti-apoptotic activity and inhibited cell death in differentiated HT22 cells by perturbing re-entry of the cell cycle and apoptosis via the GABAA receptor. Hence, GBR could be further used as a valuable nutritional compound to prevent apoptosis-induced neurodegenerative diseases.

Germinated Brown Rice Attenuates Cell Death in Vascular Cognitive Impaired Mice and Glutamate-Induced Toxicity In HT22 Cells.

Germinated brown rice (GBR) with unpolishing, soaking, and germinating processes can improve the texture, flavor, and nutritional value, including GABA and phenolic contents. The effect of GBR was first investigated in vascular cognitive impaired mice and glutamate-induced toxicity in HT22 cells with respect to standard pure GABA. Feeding mice with GBR for 5 weeks showed neuroprotection. In this study, the modified bilateral common carotid artery occlusion mice model was mild but a significant difference in cognitive impairment was still shown. Like pure GABA, GBR decreased cognitive deficits in memory behavioral tests and significantly attenuated hippocampal neuronal cell death at P < 0.001. Similarly to 0.125 µM of GABA, 100 µg/mL of GBR increased HT22 cell viability after glutamate toxicity. GBR affected less apoptotic cell death and less blocking by the GABAA antangonist bicuculline in comparison to GABA. When the results are taken together, the underlying mechanism of GBR protection may mediate though the GABAA receptor and its phenolic contents.

Inferior External Pudendal Artery Anastomosis: Additional Approach to Prevent Skin Necrosis in Replanted Penis.

BACKGROUND: Microsurgical anastomosis of the dorsal artery of the penis either with or without anastomosis of the cavernosal artery is the preferred technique for penile replantation. However, postoperative penile skin necrosis is commonly reported with this technique. This study aimed to characterize the anatomy of the vascular supply of the penis pertinent to penile replantation surgery and to report a successful case of penile replantation without postoperative necrosis using anastomosis of the inferior external pudendal artery. METHODS: The authors dissected 15 penises of fresh cadavers under acrylic dye injection by means of the inferior external pudendal and dorsal arteries of the penis to identify vascular anastomoses between arteries supplying the penis and to measure other parameters of the arteries. RESULTS: Mean diameters at the base of the penis of the inferior external pudendal, dorsal, and cavernosal arteries were 0.94, 1.43, and 0.80 mm, respectively. Penile skin is mainly supplied by the inferior external pudendal artery under three patterns with anastomoses across the midline. Preputial skin receives additional blood supply from perforators of the dorsal artery without visible anastomosis between the perforators and the inferior external pudendal artery. Deep structures receive blood supply from the dorsal, cavernosal, and urethral arteries, with visible anastomoses between the arteries. In a patient with amputated penis, the inferior external pudendal artery diameter was 0.7 mm, which was sufficient for microsurgical anastomosis. No postoperative necrosis developed, and patency of the inferior external pudendal artery was confirmed with duplex ultrasound. CONCLUSION: The diameter of the inferior external pudendal artery at the base and midshaft of the penis is sufficiently large for microsurgical anastomosis, and additional vascular anastomosis of at least one inferior external pudendal artery may help to prevent postoperative penile skin necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Hemoglobin Pakse: presence on red blood cell membrane and detection by polymerase chain reaction-single-strand conformational polymorphism.

Nondeletional gene mutations giving rise to alpha-thalassemia can be found at polymorphic frequency in Southeast Asia. Although the most common is hemoglobin Constant Spring (Hb CS), caused by a termination codon mutation (UAA --> CAA, Gln) in the alpha2-globin gene and resulting in reduced synthesis of the elongated alpha-globin variant, Hb Pakse (UAA --> UAU, Tyr) also has been observed at a significant prevalence. Western blot analysis of ghost membrane proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from an individual with alpha-thal 1/Hb Pakse revealed the existence of a higher molecular weight globin of 18 kd consistent with an alpha(Pakse)-globin chain. The presence of alpha(Pakse)-globin on membranes of Hb Pakse-containing red blood cells affords an explanation for the severity of anemia observed in such patients. However, because the 2 Hb variants cannot be distinguished by current biochemical techniques, we developed a convenient single-tube polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) protocol for the simultaneous diagnosis of Hb CS and Hb Pakse by amplifying a short fragment covering the termination codon of the alpha2-globin gene. This PCR-SSCP method required no internal control coamplification or use of restriction enzymes and has the potential of identifying all the other possible termination codon mutations in a single reaction with only 1 pair of primers.

Alpha-hemoglobin stabilizing protein: molecular function and clinical correlation.

The discovery of alpha-hemoglobin stabilizing protein (AHSP), a chaperone for free alpha-hemoglobin (alpha-Hb), has provided a satisfactory solution to the perplexing problem of balanced globin levels for Hb production in erythroid cells in the face of a two-fold excess of alpha-globin to beta-globin gene dosage. Unmatched alpha-Hb is unstable and precipitates onto membranes, where the released heme exerts oxidative damages resulting in ineffective erythropoiesis and hemolytic anemia, the underlying causes of pathology in the hereditary anemia of beta-thalassemia. The interaction of alpha-Hb with AHSP involves surfaces normally employed in binding to beta-Hb. However, a conformational change to the AHSP-bound alpha-Hb results in an oxidized heme, but in a pocket that is now less exposed to the outside environment, thereby protecting against both peroxide-induced heme loss and iron-induced redox reaction. Studies in both mice and humans indicate that reduction in AHSP can result in hematological pathology. Conversely, alpha-Hb variants that are compromised in their ability to bind with AHSP produce beta-thalassemia-like symptoms. Disease conditions like some forms of thalassemia that are directly associated with AHSP structural and/or functional defects can now be included within the category of chaperonopathies.

Heritability of P. falciparum and P. vivax malaria in a Karen population in Thailand.

The majority of studies concerning malaria host genetics have focused on individual genes that confer protection against rather than susceptibility to malaria. Establishing the relative impact of genetic versus non-genetic factors on malaria infection and disease is essential to focus effort on key determinant factors. This relative contribution has rarely been evaluated for Plasmodium falciparum and almost never for Plasmodium vivax. We conducted a longitudinal cohort study in a Karen population of 3,484 individuals in a region of mesoendemic malaria, Thailand from 1998 to 2005. The number of P. falciparum and P. vivax clinical cases and the parasite density per person were determined. Statistical analyses were performed to account for the influence of environmental factors and the genetic heritability of the phenotypes was calculated using the pedigree-based variance components model. The genetic contribution to the number of clinical episodes resulting from P. falciparum and P. vivax were 10% and 19% respectively. There was also moderate genetic contribution to the maximum and overall parasite trophozoite density phenotypes for both P. falciparum (16%&16%) and P. vivax (15%&13%). These values, for P. falciparum, were similar to those previously observed in a region of much higher transmission intensity in Senegal, West Africa. Although environmental factors play an important role in acquiring an infection, genetics plays a determinant role in the outcome of an infection with either malaria parasite species prior to the development of immunity.

Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal.

Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10(-4), Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved.

Impaired interaction of alpha-haemoglobin-stabilising protein with alpha-globin termination mutant in a yeast two-hybrid system.

Alpha-thalassaemia caused by alpha-globin gene termination codon mutations (alphaT-globin) has been explained by their inherent mRNA instability and by oxidative damage arising from the presence of membrane-bound alphaT-globin chains. To better understand the latter phenomenon, a yeast two-hybrid system was used to assay the interaction between alphaT-globin and its molecular chaperone, alpha-haemoglobin-stabilising protein (AHSP) and impaired binding of alphaT-globin with AHSP compared with alpha(wild-type)-globin was observed.