Maternal and neonatal outcome of women before vs. after bariatric surgery: A single tertiary center experience.

BACKGROUND: Obesity is associated with short term perinatal risks, causing increased risks in pre- and post-term birth, small and large for gestational (SGA/LGA), congenital anomalies, and perinatal mortality. OBJECTIVE: This study evaluate maternal and neonatal outcomes of women with morbid obesity who delivered before BS as compared to their counterparts who delivered after BS. DESIGN: A retrospective analysis in a single institute. SETTINGS: We use the data according to the ICD-9 code and were extracted from hospital archive. PATIENTS: Patients were divided int0 two groups consisted of those of who conceived after BS and those who conceived before BS. INTERVENTIONS: All women who underwent any BS and retrieved their obstetric files before or after the surgery. MAIN OUTCOMES MEASURES: The pregnancy, delivery data and obstetric factors were collected, clinical variables, background data and surgical bariatric procedures, operating time, length of hospital stay. RESULTS: 149 morbidly obese women, of which 45 delivered after BS (group I) and 104 delivered prior to BS (group II). The most frequent comorbidity was diabetes mellitus, found in 67% of the women who delivered before BS. Time to delivery was longer in the women before BS, (P = 0.015) for the after BS group. Women who delivered before BS compared to women who delivered after BS had higher rates of anemia (p = 0.038), gestational diabetes (p = 0.064), and preeclampsia (p = 0.043). Women with deliveries before BS were characterized by higher birth weight in the neonates, (p < 0.001), more cases of premature membrane rupture, (14%, p < 0.018) and relatively high number of SGAs. A multivariate analysis of the data imply correlation to age and not causation. LIMITATIONS: This study was a small retrospective study and selection bias can occur which may reduce the accuracy of the results. CONCLUSIONS: There are clear health benefits of weight loss for morbidly obese women of reproductive age, and BS has an important role to play in this population.

eTEP inferior access with tailored retromuscular dissection for small to mid-sized umbilical hernia repair with or without inguinal hernia: early experience.

INTRODUCTION: The minimally invasive surgical repair of combined inguinal and ventral hernias often requires shifting from one approach or plane to another. The traditional enhanced-view totally extraperitoneal Rives-Stoppa repair consists of a large retro muscular dissection that is unjustified for small ventral hernias. Here we describe a modification to the minimally invasive Rives-Stoppa repair using a limited retro muscular dissection based on the ventral defect size for small/medium-sized hernias, with or without combined inguinal hernias. METHODS: From a single surgical team, a retrospective study was performed over a 1-year period. Demographics, hernia characteristics, surgical techniques, intraoperative/postoperative complications, and outcomes were all analyzed and reported. We also included detailed surgical steps, landmarks, pitfalls, and personal tips for this technique. RESULTS: Twenty-four patients underwent a laparoscopic limited retromuscular dissection ventral hernia repair utilizing the eTEP access technique. Eighteen were primary umbilical hernias and six postoperative incisional hernias, and nine were combined ventral and inguinal hernia repairs. Eight of the primary umbilical hernias were EHS classified as medium size, 11 small, and for the incisional hernias, three were classified as M3W1 and two as M3W2. One procedure was converted to TAPP. There were no intraoperative complications. The mean length of stay was 1.25 days (range 1-3). There was one postoperative retromuscular hematoma and no recurrence during the follow-up period. CONCLUSION: eTEP with limited dissection offers a good and safe solution for small to medium size hernias; it provides an efficient solution when an inguinal hernia is to be addressed as well.

How-we-do-it: the repair of postoperative ventral hernias after a Mercedes abdominal incision.

PURPOSE: To describe the abdominal wall reconstruction technique with an Ultrapro mesh and outcome for the repair of postoperative ventral hernias after the use of a Mercedes incision during the initial abdominal operation. METHOD: A retrospective review of all the patients undergoing elective postoperative ventral hernia repair between 2013 and 2019. The cohort of these patients that had an initial Mercedes incision was used for this study. RESULTS: Fourteen patients met the criteria for this study. Thirteen of the patients were transplant patients (10 liver transplant and 3 combined pancreas and kidney transplant), and one patient was after a hepatectomy. Fifty-seven percent of these hernias were multiple defects. All the patients underwent the same repair of a modified Rives-Stoppa, transversus abdominis release, and a bilateral transverse plication. A partially absorbable Ultrapro mesh was used for all the patients, with two of the patients needing an additional Symbotex mesh in order to bridge a portion of the posterior fascia. There were 6 minor early postoperative complications (hematoma, superficial wound infection, and seroma) that did not require reoperation. Two patients were readmitted for observation of a wound hematoma, and two patients (14.2%) had recurrence during the follow-up period. The average length of hospitalization was 5.6 days. CONCLUSION: This technique, with the use of an Ultrapro mesh, was found to be safe and effective for the repair of a postoperative ventral hernia due to an initial Mercedes incision.

Successful management of the open abdomen with hydrocolloid dressing in a resource-constrained setting.

PURPOSE: To evaluate and detail the management of a difficult, long-term, open abdomen in a resource constraint setting with the use of Hydrocolloid dressing. METHOD: An observational retrospective study was conducted at a single level-1 trauma center. Over a 5-year period, all the open abdomen patients were evaluated and the cohorts who were treated with Hydrocolloid dressings were described in detail from their admission to their discharge. RESULTS: During this period, there were 147 open abdomens. 7.5% (11) patients required long-term open abdomen management, in which Hydrocolloid dressing was utilized. Of this group, there were no entero/colonic-atmospheric fistulas, and there was either de-novo complete skin coverage, successful skin graft placement, or definitive abdominal wall repair in all the patients. De-novo complete skin coverage took an average of 7.4 months. All the patients were discharged home after an average of 107 days hospitalized. CONCLUSION: Despite not being an optimal management of an open abdomen, there are always a small group of these patients who lose abdominal domain, are critically ill or injured, and have prolonged hospitalization with an open abdomen. In this cohort, and especially in resource constraint settings, Hydrocolloid dressing is a cost-efficient, simple, and effective method to treat the 'long-term' open abdomens.

ACTUALITIES IN ENDOCRINOLOGY- PARATHYROID IMAGING.

Parathyroid imaging modalities have been used to guide clinicians and surgeons in finding the source of hyperparathyroidism for over 40 years. Primary hyperparathyroidism (PHPT) is generally caused by a parathyroid gland(s) autonomous production of parathyroid hormone (PTH), associated by enlargement of one or more glands. Noninvasive imaging procedures that are used in the management of hyperparathyroidism are anatomical (ultrasound, computer tomography, magnetic resonance imaging) and/or functional (nuclear medicine techniques: planar scintigraphy, single photon emission tomography, positron emission imaging) and/or hybrid imaging.

Cryptogenic stroke in hanging. A case report.

This paper reports the unique neuroimaging findings of a 37-year-old woman who attempted suicide by hanging. To our knowledge, this is the first reported case describing neuroimaging findings of unilateral lesions instead of the well-documented bilateral lesions after a hanging event. Computed tomography demonstrated a low density area in the right thalamus and no hemorrhage. 3.0 T Magnetic resonance revealed a hyperintense area on both T2-weighted and FLAIR images on the right thalamus. Diffusion weighted images demonstrated no area of diffusivity restriction. Another smaller lesion with the same signal characteristics was found in the left cerebellum. A second relevant point of this report is the observation that the most probable cause of the documented unilateral lesions was an ischemic-arterial event.

Thymosin beta4 promotes angiogenesis, wound healing, and hair follicle development.

New blood vessel formation is important in many physiological process, including development, wound repair, and tumor growth. In aged animals, angiogenesis is reduced resulting in poor wound healing. We have identified a novel small molecule, thymosin beta(4), that promotes angiogenesis and wound repair in both normal and aged rodents. It also promotes hair growth in normal and aged rodents. It acts by increasing angiogenesis and cell migration and is currently in clinical trials for wound repair.

Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR.

Candida albicans and Cryptococcus neoformans cause both superficial and disseminated infections in humans. Current antifungal therapies for deep-seated infections are limited to amphotericin B, flucytosine, and azoles. A limitation is that commonly used azoles are fungistatic in vitro and in vivo. Our studies address the mechanisms of antifungal activity of the immunosuppressive drug rapamycin (sirolimus) and its analogs with decreased immunosuppressive activity. C. albicans rbp1/rbp1 mutant strains lacking a homolog of the FK506-rapamycin target protein FKBP12 were found to be viable and resistant to rapamycin and its analogs. Rapamycin and analogs promoted FKBP12 binding to the wild-type Tor1 kinase but not to a rapamycin-resistant Tor1 mutant kinase (S1972R). FKBP12 and TOR mutations conferred resistance to rapamycin and its analogs in C. albicans, C. neoformans, and Saccharomyces cerevisiae. Our findings demonstrate the antifungal activity of rapamycin and rapamycin analogs is mediated via conserved complexes with FKBP12 and Tor kinase homologs in divergent yeasts. Taken together with our observations that rapamycin and its analogs are fungicidal and that spontaneous drug resistance occurs at a low rate, these mechanistic findings support continued investigation of rapamycin analogs as novel antifungal agents.

Development of Saccharomyces cerevisiae as a model pathogen. A system for the genetic identification of gene products required for survival in the mammalian host environment.

Saccharomyces cerevisiae, a close relative of the pathogenic Candida species, is an emerging opportunistic pathogen. An isogenic series of S. cerevisiae strains, derived from a human clinical isolate, were used to examine the role of evolutionarily conserved pathways in fungal survival in a mouse host. As is the case for the corresponding Candida albicans and Cryptococcus neoformans mutants, S. cerevisiae purine and pyrimidine auxotrophs were severely deficient in survival, consistent with there being evolutionary conservation of survival traits. Resistance to the antifungal drug 5-fluorocytosine was not deleterious and appeared to be slightly advantageous in vivo. Of mutants in three amino acid biosynthetic pathways, only leu2 mutants were severely deficient in vivo. Unlike the glyoxylate cycle, respiration was very important for survival; however, the mitochondrial genome made a respiration-independent contribution to survival. Mutants deficient in pseudohyphal formation were tested in vivo; flo11Delta mutants were phenotypically neutral while flo8Delta, tec1Delta, and flo8Delta tec1Delta mutants were slightly deficient. Because of its ease of genetic manipulation and the immense S. cerevisiae database, which includes the best annotated eukaryotic genome sequence, S. cerevisiae is a superb model system for the identification of gene products important for fungal survival in the mammalian host environment.

Effect of peptide-carrier coupling on peptide-specific immune responses.

Synthetic peptides are covalently linked to immunogenic carrier proteins to enhance the anti-peptide immune response. To investigate whether the method of conjugation influences the immune response, we evaluated two distinctly different choices of linker for a peptide-carrier construct. HPG-30, a synthetic peptide derived from the p17 gag protein of human immunodeficiency virus 1, was covalently linked to keyhole limpet hemocyanin by either glutaraldehyde or a maleimide ester. Glutaraldehyde linkage enhanced the anti-peptide antibody and native protein response compared to maleimide. The maleimide-linked conjugate was more effective at inducing a peptide-specific cellular response. Thus, manipulation of the conjugation method can modify the magnitude and character of the immune response to a synthetic peptide vaccine.

Thymosinalpha1 is chemopreventive for lung adenoma formation in A/J mice.

The effects of thymosin (THN) alpha1 were investigated using the urethane injection carcinogenesis A/J mouse model. Lung adenomas were observed 2.5, 3, and 4 months after urethane injection (400 mg/kg i.p.) into female A/J mice. Daily administration of THNalpha1 (0.4 mg/kg, s.c.) reduced lung adenoma multiplicity significantly, by approximately 45, 40, and 17%, respectively, 2.5, 3, and 4 months after urethane injection. Animals treated with THNalpha1 had a significantly greater white cell density than control A/J mice. Endogenous THNalpha1-like peptides were detected in the mouse lung. By radioimmunoassay and by Western blot, prothymosin alpha was detected in the mouse lung. By immunocytochemistry, THNalpha1-like peptides were detected in all lung compartments including the bronchus, adenoma, bronchioles, and alveoli. These results indicate that exogenous THNalpha1 prevents lung carcinogenesis in A/J mice.

Thymosin alpha1 is a time and dose-dependent antagonist of dexamethasone-induced apoptosis of murine thymocytes in vitro.

It is well established that glucocorticoid hormones induce apoptosis in immature developing thymocytes. Thymocyte apoptosis can be modulated by growth factors, anti-oxidants and adhesion receptors. We have previously demonstrated that thymosin alpha1 (Talpha1) antagonizes dexamethasone-induced apoptosis of CD4+CD8+ thymocytes. In the present study, we further characterize the dose and time dependence of Talpha1's antagonism of dexamethasone-induced thymocyte apoptosis. Talpha1 is effective at concentrations ranging from 2 to 100 microg/10(6) thymocytes. Talpha1 pre-treatment is necessary to achieve its anti-apoptotic activity. Talpha1 provides temporary protection to thymocytes by slowing dexamethasone's apoptotic activity up to 12 h post dexamethasone treatment. Additionally, Talpha1's activity is not sensitive to cycloheximide treatment, suggesting Talpha1's activity is independent of protein synthesis. Finally, Talpha1 is unable to antagonize apoptosis induced by the reactive oxygen species, H2O2, suggesting Talpha1's antagonism of dexamethasone occurs at the early stages of dexamethasone-induced apoptosis, prior to the production of reactive oxygen species. This evidence suggests that Talpha1 may provide a mechanism to transiently extend the life of a thymocyte during thymic selection.

Three new dominant drug resistance cassettes for gene disruption in Saccharomyces cerevisiae.

Disruption-deletion cassettes are powerful tools used to study gene function in many organisms, including Saccharomyces cerevisiae. Perhaps the most widely useful of these are the heterologous dominant drug resistance cassettes, which use antibiotic resistance genes from bacteria and fungi as selectable markers. We have created three new dominant drug resistance cassettes by replacing the kanamycin resistance (kan(r)) open reading frame from the kanMX3 and kanMX4 disruption-deletion cassettes (Wach et al., 1994) with open reading frames conferring resistance to the antibiotics hygromycin B (hph), nourseothricin (nat) and bialaphos (pat). The new cassettes, pAG25 (natMX4), pAG29 (patMX4), pAG31 (patMX3), pAG32 (hphMX4), pAG34 (hphMX3) and pAG35 (natMX3), are cloned into pFA6, and so are in all other respects identical to pFA6-kanMX3 and pFA6-kanMX4. Most tools and techniques used with the kanMX plasmids can also be used with the hph, nat and patMX containing plasmids. These new heterologous dominant drug resistance cassettes have unique antibiotic resistance phenotypes and do not affect growth when inserted into the ho locus. These attributes make the cassettes ideally suited for creating S. cerevisiae strains with multiple mutations within a single strain.

Thymosin beta4 accelerates wound healing.

Angiogenesis is an essential step in the repair process that occurs after injury. In this study, we investigated whether the angiogenic thymic peptide thymosin beta4 (Tbeta4) enhanced wound healing in a rat full thickness wound model. Addition of Tbeta4 topically or intraperitoneally increased reepithelialization by 42% over saline controls at 4 d and by as much as 61% at 7 d post-wounding. Treated wounds also contracted at least 11% more than controls by day 7. Increased collagen deposition and angiogenesis were observed in the treated wounds. We also found that Tbeta4 stimulated keratinocyte migration in the Boyden chamber assay. After 4-5 h, migration was stimulated 2-3-fold over migration with medium alone when as little as 10 pg of Tbeta4 was added to the assay. These results suggest that Tbeta4 is a potent wound healing factor with multiple activities that may be useful in the clinic.

Heterologous URA3MX cassettes for gene replacement in Saccharomyces cerevisiae.

Heterologous gene replacement cassettes are powerful tools for dissecting gene function in Saccharomyces cerevisiae. Their primary advantages over homologous gene replacement cassettes include reduced gene conversion (leading to efficient site-specific integration of the cassette) and greater independence of strain background. Perhaps the most widely used cassettes are the MX cassettes containing the dominant selectable kanamycin resistance gene (kanr), which confers resistance to G418 (Wach et al., 1994). One limitation of the kanMX cassettes is that they are not counterselectable and therefore not readily recyclable, which is important when constructing strains with more than one gene deletion. To address this limitation, and to expand the choices of heterologous markers, we have created two new MX cassettes by replacing the kanr ORF from plasmids pFA6-kanMX3 and pFA6-kanMX4 with the Candida albicans URA3 ORF. These plasmids, pAG60 (CaURA3MX4) and pAG61 (CaURA3MX3) are identical to the kanMX cassettes in all other respects but have the added advantage of being counterselectable and therefore readily recyclable in S. cerevisiae.

Direct allelic variation scanning of the yeast genome.

As more genomes are sequenced, the identification and characterization of the causes of heritable variation within a species will be increasingly important. It is demonstrated that allelic variation in any two isolates of a species can be scanned, mapped, and scored directly and efficiently without allele-specific polymerase chain reaction, without creating new strains or constructs, and without knowing the specific nature of the variation. A total of 3714 biallelic markers, spaced about every 3.5 kilobases, were identified by analyzing the patterns obtained when total genomic DNA from two different strains of yeast was hybridized to high-density oligonucleotide arrays. The markers were then used to simultaneously map a multidrug-resistance locus and four other loci with high resolution (11 to 64 kilobases).

Dbp5p/Rat8p is a yeast nuclear pore-associated DEAD-box protein essential for RNA export.

To identify Saccharomyces cerevisiae genes important for nucleocytoplasmic export of messenger RNA, we screened mutant strains to identify those in which poly(A)+ RNA accumulated in nuclei under nonpermissive conditions. We describe the identification of DBP5 as the gene defective in the strain carrying the rat8-1 allele (RAT = ribonucleic acid trafficking). Dbp5p/Rat8p, a previously uncharacterized member of the DEAD-box family of proteins, is closely related to eukaryotic initiation factor 4A(eIF4A) an RNA helicase essential for protein synthesis initiation. Analysis of protein databases suggests most eukaryotic genomes encode a DEAD-box protein that is probably a homolog of yeast Dbp5p/Rat8p. Temperature-sensitive alleles of DBP5/RAT8 were prepared. In rat8 mutant strains, cells displayed rapid, synchronous accumulation of poly(A)+ RNA in nuclei when shifted to the non-permissive temperature. Dbp5p/Rat8p is located within the cytoplasm and concentrated in the perinuclear region. Analysis of the distribution of Dbp5p/Rat8p in yeast strains where nuclear pore complexes are tightly clustered indicated that a fraction of this protein associates with nuclear pore complexes (NPCs). The strong mutant phenotype, association of the protein with NPCs and genetic interaction with factors involved in RNA export provide strong evidence that Dbp5p/Rat8p plays a direct role in RNA export.

Thymosin alpha 1 stimulates endothelial cell migration, angiogenesis, and wound healing.

In wound healing, lymphoid cells release soluble factors that attract fibroblasts and macrophages, initiating repair, endothelial cell migration, angiogenesis, and matrix production. We analyzed the effect of thymosin alpha1 (Talpha1) on endothelial cell migration, angiogenesis, and wound healing. Talpha1, a 28 amino acid peptide initially isolated from the thymus, enhanced the morphologic differentiation of endothelial cells and was a potent chemoattractant for endothelial cells and monocytes in vitro. In vivo, Talpha1 stimulated angiogenesis in a subcutaneous model. When given either topically or i.p., it accelerated wound healing in a punch model, demonstrating that Talpha1 promotes angiogenesis and wound healing.

Thymosin fraction 5 inhibits the proliferation of the rat neuroendocrine MMQ pituitary adenoma and C6 glioma cell lines in vitro.

Cytokines such as interleukin-1 (IL-1) and IL-6 stimulate the hypothalamic-pituitary-adrenal (HPA) axis. In addition, these proteins affect pituitary cell proliferation in vitro. Thymosin fraction 5 (TF5) is a partially purified preparation of the bovine thymus that enhances immune system functioning. Because TF5 similarly stimulates the HPA axis, we examined the effects of this preparation on neuroendocrine tumor cell proliferation. Cells of the PRL-secreting rat anterior pituitary adenoma, MMQ (5-50 x 10(3) cells/well), were exposed to vehicle (RPMI-1640 containing 2.5% FCS, 7.5% horse serum, and antibiotics) or TF5 (100-500 microg/ml) for up to 96 h and the proliferation of MMQ cells monitored using the MTT assay (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide). TF5-mediated inhibition of cell proliferation was dependent on both TF5 concentration and the initial MMQ cell number. Minimal reductions in optical densities resulted from exposure to 100 microg/ml TF5, whereas the highest concentration of this preparation (i.e. 500 microg/ml) completely blocked MMQ cell division. The concentration-dependent effects of TF5 were particularly striking at initial plating densities of 25 and 50 x 10(3) MMQ cells/well; in contrast, all concentrations of TF5 completely inhibited MMQ cell growth at 5 and 10 x 10(3) cells/well. The antiproliferative actions of TF5 on MMQ cells were demonstrable within 24 h and remained for up to 96 h as determined by the MTT assay and actual cell counts. Because the highest densities of MMQ cells were partially refractive to the antiproliferative effects of TF5, we examined the effects of PRL (1-1000 nM) and MMQ cell conditioned medium (50%) on TF5 inhibition of MMQ adenoma proliferation. The TF5 concentration-dependent inhibition of MMQ cell growth was largely reversed by the 50% conditioned medium, whereas PRL slightly potentiated the antiproliferative actions of TF5. The proliferation of the rat C6 glioma cell line (10-30 x 10(3) cells/well) demonstrated greater sensitivity to TF5: concentrations as low as 10 microg/ml TF5 inhibited C6 cell proliferation (P < 0.01), and near-maximal inhibition was noted at 200 microg/ml TF5. Significant reductions in MMQ and C6 cell viabilities accompanied decreases in cell number and morphological analysis indicated these cells were dying by apoptosis. The peptides thymosin alpha1 (T alpha1), thymosin beta4 (T beta4), MB35, and MB40 had no effect on either MMQ or C6 cell proliferation, indicating that these TF5 components are not the principle active peptides. Therefore, TF5 was further separated into 60 fractions by preparative reverse phase HPLC. HPLC fractions 17, 25, 26, and 27 significantly suppressed MMQ cell proliferation (P < 0.01) to the same extent as TF5; other HPLC fractions had no effect. These data demonstrate a new biological property of TF5: the inhibition of cell proliferation and the induction of apoptosis in neuroendocrine tumor cells. The proliferation effects were time and concentration dependent and could be partially reversed by an activity present in the MMQ cell conditioned medium. Thus, TF5 and cytokines have opposite effects on adenoma cells because IL-2 and IL-6 stimulate GH3 cell proliferation. We propose that circulating thymic peptides may act to prevent pituitary adenoma and glioma tumor formation, an action opposed by autocrine growth factors secreted by these tumors.