New Strategies for the Transition-Metal Catalyzed Synthesis of Aliphatic Amines.

Transition-metal catalyzed reactions that are able to construct complex aliphatic amines from simple, readily available feedstocks have become a cornerstone of modern synthetic organic chemistry. In light of the ever-increasing importance of aliphatic amines across the range of chemical sciences, this review aims to provide a concise overview of modern transition-metal catalyzed approaches to alkylamine synthesis and their functionalization. Selected examples of amine bond forming reactions include: (a) hydroamination and hydroaminoalkylation, (b) transition-metal catalyzed C(sp3)-H functionalization, and (c) transition-metal catalyzed visible-light-mediated light photoredox catalysis.

Streamlined Synthesis of C(sp3)-Rich N-Heterospirocycles Enabled by Visible-Light-Mediated Photocatalysis.

We report a general visible-light-mediated strategy that enables the construction of complex C(sp3)-rich N-heterospirocycles from feedstock aliphatic ketones and aldehydes with a broad selection of alkene-containing secondary amines. Key to the success of this approach was the utilization of a highly reducing Ir-photocatalyst and orchestration of the intrinsic reactivities of 1,4-cyclohexadiene and Hantzsch ester. This methodology provides streamlined access to complex C(sp3)-rich N-heterospirocycles displaying structural and functional features relevant to fragment-based lead identification programs.

Evaluation of suture reinforcement for stapled intestinal anastomoses: 77 dogs (2008-2018).

OBJECTIVE: To determine the influence of oversewing a transverse staple line in functional end-to-end stapled intestinal anastomoses (FEESA) in dogs. STUDY DESIGN: Retrospective observational study. SAMPLE POPULATION: Seventy-seven client-owned dogs that underwent 78 FEESA reinforced (n = 30) or not reinforced (n = 48) with suture at the transverse staple line. METHODS: The medical records database was searched and reviewed for dogs that had undergone a FEESA between January 2008 and September 2018. Data were collected regarding signalment, body weight, clinical presentation, indication for surgery, serum albumin, presence of septic peritonitis, previous surgeries, surgical techniques (ie, oversew, crotch suture, omental wrap, omental patch, serosal patch), histopathology results, and postoperative outcome. RESULTS: The only differences identified between groups consisted of higher preoperative albumin (2.89 ± 0.56 vs 2.34 ± 0.62 g/dL; P = .006) and lower postoperative dehiscence rate (0/30 vs 7/48; P = .028) in dogs with an oversewn FEESA. Oversewing the FEESA was identified as the significant factor in a model with oversewing and preoperative albumin fit to the outcome of dehiscence (oversew P = .010, albumin P = .761). The location of the dehiscence was specified in four of seven dogs, all along the transverse staple line. Patterns used for oversew were unspecified (n = 11), simple continuous (8), Cushing (4), simple interrupted (2), cruciate (1), interrupted horizontal mattress (1), and Lembert (1). CONCLUSION: Oversewing the transverse staple line in FEESA was associated with a reduced occurrence of postoperative dehiscence. CLINICAL SIGNIFICANCE: Our results provide evidence to support additional investigation of suture reinforcement (oversewing) at the transverse staple line of FEESA to reduce postoperative dehiscence.

Os clitoris in dogs: 17 cases (2009-2017).

Medical records of 17 client-owned dogs diagnosed with os clitoris on physical examination or diagnostic imaging were reviewed to describe the clinical signs and surgical management of this condition. All dogs were phenotypically female. The most common presenting complaints included an enlarged clitoris (n = 10), urinary tract infection (n = 5), and licking of the vulva (n = 3). Other frequently reported clinical signs included vaginal discharge and/or lower urinary tract signs such as pollakiuria. Ten dogs were surgically managed with os clitorectomy. Concurrent related procedures included gonadohysterectomy (n = 7), and episioplasty (n = 3). Clitorectomy in the surgically managed dogs created a more normal female anatomy and resolved clinical signs associated with the exposed clitoris.

Os clitoridien chez les chiennes : 17 cas (2009­2017). Les dossiers médicaux de 17 chiennes appartenant à des clients qui avaient été diagnostiquées avec l'os clitoridien lors de l'examen physique ont été étudiés afin de décrire les signes cliniques et la gestion chirurgicale de cette affection. Tous les chiens étaient phénotypiquement femelles. Les plaintes les plus communes à la présentation incluaient un clitoris élargi (n = 10), une infection des voies urinaires (n = 5) et le léchage de la vulve (n = 3). Les autres signes cliniques fréquemment signalés incluaient l'écoulement vaginal et/ou des symptômes des voies urinaires inférieures comme la pollakiurie. Dix chiennes ont été gérées chirurgicalement par une clitoridectomie. Les interventions concomitantes incluent la gonado-hystérectomie (n = 7) et l'épisioplastie (n = 3). La clitoridectomie chez les chiennes gérées par chirurgie a créé une anatomie femelle plus normale et a donné lieu à une résolution des signes cliniques associés au clitoris exposé.(Traduit par Isabelle Vallières).

Catalytic sp3 -sp3 Functionalisation of Sulfonamides: Late-Stage Modification of Drug-Like Molecules.

A new application of Pd-catalysed allylation is reported that enables the synthesis of a range of branched sp3 -functionalised sulfonamides, a compound class for which few reported methods exist. By reacting benzyl sulfonamides with allylic acetates in the presence of Pd0 catalysts and base at room temperature, direct allylation was efficiently performed, yielding products that are analogues of structural motifs seen in biologically active small molecules. The reaction was performed under mild conditions and could be applied to nanomolar sigma-receptor binders, thus enabling a late-stage functionalisation and efficient expansion of drug-like chemical space.

Platelet lysate obtained via plateletpheresis performed in standing and awake equine donors.

BACKGROUND: Platelet preparations containing growth factors, attachment factors, and enzymes are appealing to enhance healing of injured tissues and as an alternative to xenogenic serum in cell culture media. Plateletpheresis is commonly used to collect platelets in human medicine but has not been validated in horses. STUDY DESIGN AND METHODS: Plateletpheresis to collect platelet concentrate was performed on six female, mixed breed, chemically restrained horses using commercially available apheresis equipment. Before and immediately after plateletpheresis, we performed physical examinations and collected blood for chemistry and coagulation panels and then again at 8, 16, 24, and 48 hours after the procedure. To produce platelet lysate, the platelet concentrate underwent two freeze-thaw cycles followed by centrifugation and filtration processing. The platelet lysate was then analyzed for cellular debris, fibrinogen, and growth factors. RESULTS: The collected platelet concentration contained a mean platelet yield of 390 × 103 /µL. Donor platelet count decreased from a mean of 193 × 103 /µL to 138 × 103 /µL after plateletpheresis, but no individual was at risk for hemorrhage. Pooled platelet lysate had minimal cellular residue and contained growth factor concentrations at 6.1 ng/mL for transforming growth factor-ß1, at 3.5 ng/mL for platelet-derived growth factor-BB, and at 13.8 ng/mL for vascular endothelial growth factor-A. CONCLUSION: Plateletpheresis using commercially available apheresis equipment is a feasible option for collecting platelet concentrate from equine donors. The lysate generated from the apheresis product contains growth factors and has potential to be used as a fetal bovine serum substitute for cell culture.

Blood use in neurosurgical cases at the university hospital of the west indies.

OBJECTIVE: Many neurosurgical cases are done without the need for blood transfusion, yet blood is unnecessarily cross-matched, resulting in wasted resources. This study was undertaken to document and compare the number of units of blood components requested, cross-matched and transfused in neurosurgical cases at the University Hospital of the West Indies (UHWI). METHODS: A prospective, observational study was undertaken over one year. Data collected for each patient included demographic information, relevant perioperative data, and blood banking data including blood components requested, cross-matched and transfused. Data were analysed using SPSS version 16. RESULTS: Data were analysed on 152 patients, 71 females (46.7%) and 81 males (53.3%). The mean age was 48.7 ± 19.6 years and 100 of the procedures were done electively (65.8%). Blood components were ordered in 114 (75%) cases, red cells more commonly in 113 (74.3%) patients, and plasma in 19 (12.5%) patients. Overall, 20 patients (13.2%) were transfused. Most patients (90.9%) needed one to two units of blood. Of the 236 units of blood components that were cross-matched or prepared, only 62 were transfused. The cross-match/preparation to transfusion ratio (CTR/PTR) was 6.00 for red cells and 1.31 for plasma. Preoperative haemoglobin ≤ 10.0 g/dL (p = 0.001), estimated blood loss of ≥ 1 litre (p < 0.001), higher American Society of Anesthesiologists (ASA) physical status score (p < 0.03) and a resident as lead surgeon (p < 0.05), were significant predictors of blood transfusion. CONCLUSION: The transfusion rate was low with a high cross-match to transfusion ratio, suggesting that less cross-matching is needed. A new approach to blood ordering for neurosurgical cases is recommended.

Growth factor and cytokine characterization of canine platelet lysate with variable leukocyte concentration, plasma content, and heat-sensitive proteins.

Background: Platelet lysate is an acellular platelet product containing factors released from secretory granules, including cytokines and growth factors. This study aimed to evaluate different centrifugation methods used to prepare canine platelet lysate with variable content of leukocytes, plasma, and heat-sensitive proteins. Methods: Whole blood was collected from six dogs and two double-spin preparation methods were used to generate the platelet-rich plasma with reduced (PRP) and high (L-PRP) concentration of leukocytes. A portion of both methods underwent plasma depletion via centrifugation and platelet lysate was generated via freeze-thaw cycles. A portion of the generated platelet lysate underwent complement inactivation via heat treatment. Growth factors (TGF-ß1, VEGF, TNF-α, PDGF-BB, HGF) were quantified in all different platelet lysate preparations using ELISAs. Results: Both platelet-rich plasma preparations had a 6.7-fold increase in platelet concentration. White blood cell (WBC) concentration compared to whole blood increased 1.2-fold times in PRP and 1.9-fold times in L-PRP. Negligible concentrations of platelets, WBC, and hematocrit were identified in all lysate groups. Statistically significant differences were identified for PDGF, VEGF, and TNF-α, and not for TGF-ß or HGF. No growth factor differences were noted between centrifugation methods. PDGF was significantly higher in platelet lysate that was plasma depleted. VEGF was significantly higher in heat-treated lysate groups. TNF-α concentrations were overall very low, though were noted to significantly increase following plasma depletion. Conclusion: These results support that growth factors and cytokine release can be affected by the platelet lysate preparation and processing.

The provision of surgical care for children with cardiac disease: the Jamaican experience--an 18-year review.

The aim of this article is to review the local experience over the last 18 years (1994-2011) in providing surgical intervention for children with heart conditions in Jamaica. Eight hundred and sixty-three children received cardiac surgery during this period, 441 were done with the assistance of visiting overseas teams and 422 by the local surgical teams. The majority of cases receiving cardiac surgery were for congenital heart defects; however 3% of cases were for rheumatic heart disease. The overall survival rate was 94% for the period 1994 to 2008.

The development of anaesthetic services in Jamaica.

The development of anaesthetic services in Jamaica arose out of the recognition that dedicated physicians offered a better morbidity/mortality profile to patients. From untrained personnel offering anaesthesia at the turn of the 20th century, much progress has been made, such that specialized anaesthetists have been trained for the various surgical subspecialties.

The development of postgraduate anaesthesia and intensive care training at the University of the West Indies.

The one-year Diploma in Anaesthetics (DA) was the first postgraduate programme offered by the then Faculty of Medicine of The University of the West Indies (UWI). It was instituted in 1966, when the need for trained physician anaesthetists became paramount. Over 200 physicians have been awarded the DA which was discontinued in 1994. The four-year Doctor of Medicine in Anaesthetics [DM (Anaesthetics)] was commenced in 1974 and continues to train most of the region's physician anaesthetists. The majority of the 119 graduates (as of December 2011) are providing invaluable services to the people of the Caribbean. The time has come for the establishment of a regional certifying body, the Caribbean College of Anaesthetists. This college would determine the standards for the training and clinical practice of anaesthetists as perioperative physicians including: the conduct of anaesthesia, critical care, acute and chronic pain management. It would also facilitate continuing medical education and recertification of all practising anaesthetists within the region.

Development and evaluation of a novel topically applied sildenafil citrate hydrogel and its influence on wound healing in dogs.

OBJECTIVE: To develop a topical sildenafil hydrogel and evaluate its effect on wound healing in dogs. ANIMALS: 6 purpose-bred, sexually intact, adult Beagles. PROCEDURES: Hydrogels containing sildenafil citrate, N-methyl-2-pyrrolidone, propylene glycol, and poloxamer 407 were developed. Four excision wounds were created along the dorsum of the dogs. Each wound was treated for 21 days with a nonadherent bandage (C) or with a hydrogel containing 0% (G), 5% (5S), or 10% (10S) sildenafil. Daily bandage changes with wound imaging were performed. Biopsy specimens were collected 5 times. RESULTS: Hydrogels were homogenous at room temperature and released > 90% of the sildenafil within 8 hours in vitro. Time to first granulation tissue was significantly shorter for the sildenafil groups (mean ± SD, 2.8 ± 0.8 days [5S and 10S]), compared with the control groups (5.2 ± 0.4 days [C] and 6.3 ± 1.4 days [G]). The G wounds had a 10% to 14% lower contraction rate, compared with the C, 5S, and 10S wounds. 5S wounds had a total wound area 0.7 ± 0.3 cm2 larger than 10S wounds. No significant differences were present when C wounds were compared with 5S and 10S wounds for total wound area, contraction, or epithelialization. Histologic acute inflammatory scores were higher for 5S and 10S wounds in the early and late stages of wound healing, with higher reparative scores on day 7. Neovascularization was higher for 10S wounds on day 7 and 14. CLINICAL RELEVANCE: The topical sildenafil hydrogel promoted early granulation tissue, which may be beneficial for secondary wound closure in clinical settings.

Laparoscopic gonadectomy in a dog with 78,XX/78,XY chimerism and underdeveloped reproductive organs.

CASE DESCRIPTION: A 1-year-old externally sexually intact female Great Dane was referred for further evaluation of abnormal and underdeveloped internal reproductive organs. CLINICAL FINDINGS: Physical examination findings included a cranioventrally displaced vulva and a grade 2/6 left apical systolic heart murmur. No uterus or ovaries were identified during abdominal ultrasonography. Computed tomography with retrograde vaginourethrography revealed an underdeveloped uterus and possible left intra-abdominal gonad. Karyotyping revealed mixed sex chromosomes (70% XY and 30% XX). Analysis of a serum sample yielded positive results for anti-Müllerian hormone; other findings included mid range estradiol concentration (48.2 pg/mL [within reference intervals for sexually intact and neutered males and females]), low progesterone concentration (< 0.2 ng/mL [within reference intervals for anestrous females]), and low testosterone concentration (< 20 ng/dL [similar to the expected concentration in neutered males]). Overall, the results of the sex hormone analyses were consistent with findings for either a sexually intact female or a neutered male dog. The dog's cardiac structure and function were echocardiographically normal. TREATMENT AND OUTCOME: The dog was anesthetized and underwent laparoscopic gonadectomy. The gonads, although abnormal and underdeveloped, were readily identified intraoperatively and successfully removed. On the basis of histologic findings, the removed gonads were confirmed to be rudimentary testicles. The dog recovered from anesthesia and surgery without complications. CLINICAL RELEVANCE: Laparoscopic surgery was effective for visualization of abnormal and hypoplastic reproductive organs when abdominal ultrasonography and CT were of limited diagnostic usefulness, and laparoscopic surgery allowed straightforward gonadectomy in a 78,XX/78,XY chimeric dog.

Pulmonary hypertension: a review of the aetiology, pathophysiology and management.

Pulmonary hypertension (PH) is defined as a systolic pulmonary artery pressure (PAP) above 30 mmHg and a mean PAP above 25 mmHg. Pulmonary hypertensive diseases (PHDs) encompass a myriad of conditions that cause pulmonary hypertension (PH), hence the Evian Classification was developed for the categorization of the various causes. Pulmonary hypertensive diseases are complex conditions that are difficult to treat and in the case of primary pulmonary hypertension, there is no known cure. Dyspnoea on exertion is the main symptom. This usually worsens as the disease progresses and can lead to syncope as a result of right ventricular failure. Prostacyclin has been the mainstay of treatment for decades, but several new drugs and alternate methods of treatment are currently available.

Synthesis of a Protected keto-Lysidine Analogue via Improved Preparation of Arabino-isoCytosine Nucleosides.

Anhydrouridines react with aliphatic amines to give N-alkyl isocytosines, but reported procedures often demand very long reaction times and can be low yielding, with narrow scope. A modified procedure for such reactions has been developed, using microwave irradiation, significantly reducing reaction time and allowing facile access to a diverse range of novel nucleosides on the gram scale. The method has been used to prepare a precursor to a novel analogue of lysidine, a naturally occurring iminonucleoside found in tRNA.

Platelet lysate as a novel serum-free media supplement for the culture of equine bone marrow-derived mesenchymal stem cells.

BACKGROUND: Mesenchymal stem cells (MSCs) produced for clinical purposes rely on culture media containing fetal bovine serum (FBS) which is xenogeneic and has the potential to significantly alter the MSC phenotype, rendering these cells immunogenic. As a result of bovine-derived exogenous proteins expressed on the cell surface, MSCs may be recognized by the host immune system as non-self and be rejected. Platelet lysate (PL) may obviate some of these concerns and shows promising results in human medicine as a possible alternative to FBS. Our goal was to evaluate the use of equine platelet lysate (ePL) pooled from donor horses in place of FBS to culture equine MSCs. We hypothesized that ePL, produced following apheresis, will function as the sole media supplement to accelerate the expansion of equine bone marrow-derived MSCs without altering their phenotype and their immunomodulatory capacity. METHODS: Platelet concentrate was obtained via plateletpheresis and ePL were produced via freeze-thaw and centrifugation cycles. Population doublings (PD) and doubling time (DT) of bone marrow-derived MSCs (n = 3) cultured with FBS or ePL media were calculated. Cell viability, immunophenotypic analysis, and trilineage differentiation capacity of MSCs were assessed accordingly. To assess the ability of MSCs to modulate inflammatory responses, E. coli lipopolysaccharide (LPS)-stimulated monocytes were cocultured with MSCs cultured in the two different media formulations, and cell culture supernatants were assayed for the production of tumor necrosis factor (TNF)-α. RESULTS: Our results showed that MSCs cultured in ePL media exhibited similar proliferation rates (PD and DT) compared with those cultured in FBS at individual time points. MSCs cultured in ePL showed a statistically significant increased viability following a single washing step, expressed similar levels of MSC markers compared to FBS, and were able to differentiate towards the three lineages. Finally, MSCs cultured in ePL efficiently suppressed the release of TNF-α when exposed to LPS-stimulated monocytes similar to those cultured in FBS. CONCLUSION: ePL has the potential to be used for the expansion of MSCs before clinical application, avoiding the concerns associated with the use of FBS.

Paediatric day surgery: revisiting the University Hospital of the West Indies experience.

Day surgery is cheaper and allows for less time delay. In developing countries with limited health budgets, these factors lead to higher patient turnover and shortened waiting lists. The decreased psychological trauma for both parents and children is significant. Paediatric day surgery (PDS) has been done at the University Hospital of the West Indies (UHWI) for over 40 years. A total of 975 paediatric general surgical (PGS) procedures were performed on 963 patients at the UHWI during the four-year period, January 2001 to December 2004. Paediatric day surgery numbered 727 (74.6%). Males outnumbered females 2:1, the age range was 2 weeks to 15 years, with an average age of 4 years. Ninety-seven (13.3%) of these patients were less than six months old, including eight neonates. One hundred and forty-five (20%) had more than one surgical procedure. Most children, 314 (43.2%) had inguinal hernia repair. Umbilical/supra-umbilical/epigastric herniorrhaphy (20.1%) was the next most frequently performed procedure, followed by circumcision (13.3%) and orchidopexy (5.9%). Ninety per cent of these patients were discharged home within 2-4 hours after surgery. Unplanned admissions were 2.1% of the cases. These were due to age, unplanned extensive surgical procedure, drug reaction and fever There was no mortality in this study population. This review showed that the number of PDS has increased from 60% in 1984 to 75%. These procedures were performed safely with a low complication rate. Further expansion of the service is recommended.

Acute renal failure post coronary artery bypass grafting at the University Hospital of the West Indies.

OBJECTIVES: The purpose of the study was to determine the period prevalence of acute renal failure (ARF) after coronary bypass surgery (CABG) at the University Hospital of the West Indies and to identify risk factors. METHOD: A retrospective analysis of patients who underwent CABG during the period 1994-2004 was done. Data collected included; age, gender, weight, the presence of hypertension (HTN), diabetes mellitus (DM), hypercholesterolaemia, previous myocardial infarction (MI), blood pressure on admission, urea and creatinine one year prior to surgery, on admission for surgery and post-surgery, duration of intra-operative hypotension, duration of cardiopulmonary bypass, perfusion pressure and the perioperative medications. RESULTS: The case notes of 62 patients (68.9%) were obtained for analysis. There were 47 (75.8%) males and 15 females (24.2%)--a 3:1 ratio. The prevalence of HTN and DM in the study sample was 78% and 72% respectively, hypercholesterolaemia was 31% and a previous MI was 29%. There were no differences based on gender. Post CABG complications were: persistent postoperative hypotension (6.8%), congestive cardiac failure (CCF) (6.8%), arrhythmia (6.8%), sepsis (6.8%), lower respiratory tract infection (LRTI) and pleural effusion (5.1%), heart block (3.4%), pulmonary embolism (1.7%), cellulitis and haematoma formation were 1.7%. Three patients had increases in postoperative creatinine values > 89 micromol/L over the postoperative value resulting in a prevalence of ARF of 5%. One of the three patients died and none received dialysis. There were no statistical difference in pre-operative clinical and biochemical characteristics based on the presence or absence of ARE. The presence of diabetes and increased length of stay were significant predictors of increasing postoperative creatinine values adjusting for pre-operative creatinine values. In addition, the presence of diabetes mellitus and male gender were significant predictors of increasing postoperative urea values. CONCLUSION: DM is a significant risk factor for the development of ARF post CABG.

Open splenectomy in Jamaican children with sickle cell disease.

A total of 110 patients with sickle cell disease who had open splenectomy at the University Hospital of the West Indies over a 10-year period are reviewed Patients with homozygous sickle cell disease numbered 94, S beta0 and S beta+ thalassaemias (11 and 4 respectively) and one patient with SC disease. Postoperative acute chest syndrome was the most common complication (9 of 110). There were no life threatening emergencies and no mortalities. Eleven patients received preoperative blood transfusion and operative times were short averaging 60 minutes among the 110 patients. Open splenectomy remains the gold standard for patients with sickle cell disease requiring splenectomy.

Vomiting post tonsillectomy at the University Hospital of the West Indies.

A three-year observational study of patients undergoing tonsillectomy at the University Hospital of the West Indies was conducted to determine the incidence of postoperative vomiting. Data were collected to assess possible risk factors for vomiting as well as possible alleviating agents. Two hundred and fifty-two patients were included in the study and a thirteen per cent incidence of postoperative vomiting was found. This is significantly less than that quoted in other studies (40-73%). Results also showed that steroids significantly reduced the incidence of postoperative vomiting in the study population. Muscle relaxants reversal agents and antibiotics particularly co-trimoxazole and ceftriaxone significantly increased its incidence. Usual antiemetic agents including dimenhydrinate (gravol) and promethazine (phenergan), as well as drugs known to possess antiemetic properties such as midazolam and propofol, lacked any significant protective effect against emesis. Opioid analgesia, inhalational induction and blood loss of greater than 10% of estimated blood volume appeared to increase emesis but failed to achieve statistical significance.