bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Utility of Peri-Operative C-Reactive Protein Testing in General Surgery
Authors: Cole Duncan S , Watts Andrew , Scott-Coombes David , Avades Tony
Published: May 2008

INTRODUCTION

C-reactive protein (CRP) is an acute-phase protein used clinically to diagnose infectious and inflammatory disease and monitor response to treatment. CRP measurement in the peri-operative period was audited and patterns of change analysed for elective general surgical patients.

PATIENTS AND METHODS

General surgical patients (201) admitted for elective general surgery over a 3-month period were considered for the study. CRP results pre- and postoperatively were recorded, and data on co-morbid conditions and surgical procedure were noted.

RESULTS

CRP was requested pre-operatively on 84% of patients. A high CRP was more likely to be found in patients with co-morbidity. Postoperatively, CRP was requested during the first 3 days on 69% of patients. CRP peaked at postoperative days two or three, and then fell. In patients who had a high pre-operative CRP, the peak CRP was higher and occurred later, than those who had a normal pre-operative CRP.

CONCLUSIONS

CRP requesting pre-operatively is common, but is not recommended in NICE guidelines. Postoperatively, CRP levels rise; as a result, its use as a tool to screen for infection is limited. CRP has a role in diagnosis of infection after the first three postoperative days and in monitoring response to treatment. Therefore, routine use of CRP measurements pre-operatively and in the first 2 or 3 days post-operatively is not recommended. A peri-operative CRP should only be requested if there is a clear clinical indication.
Primary Anastomosis Without Colonic Lavage for the Obstructed Left Colon
Authors: Cross KLR , Rees JR , Soulsby RHR , Dixon AR
Published: May 2008

INTRODUCTION

Resection, on-table lavage (OTL) and primary anastomosis is the treatment of choice for the obstructed left colon. OTL is time-consuming, requires considerable mobilisation/bowel handling, an enterotomy and potentially exposes the patient to mesenteric vascular injury, faecal contamination and a prolonged ileus. We have assessed outcome following primary resection and anastomosis without prior lavage.

PATIENTS AND METHODS

Twenty-four consecutive, obstructed patients underwent splenic flexure mobilisation and high anterior resection (concomitant small bowel resection in 2) with primary side-to-side colorectal anastomosis without either prior lavage or covering stoma. Outcome was audited.

RESULTS

Twenty-four patients, 17 female aged 48–92 years (median. 76 years) presented with left-sided obstruction due to carcinoma (Dukes' B [3], C [6], D [1]) or chronic diverticulitis (14). Median operative time was 85 min (range, 40–105 min). Colonic ileus resolved on day 2 (29%) and day 3 (58%). Median hospital stay was 7 days (range, 6–72 days); 92% discharged by day 10. There were no deaths or re-admissions. A return to theatre followed a reactionary haemorrhage in one. This latter patient's anastomosis leaked on day 4 (no faecal contamination) and was converted to an end stoma. Urinary and wound infections were seen in two. Late complications comprised two anastomotic strictures; both responded to balloon dilatation at 5 months.

CONCLUSIONS

Resection and primary anastomosis without on-table lavage is an easy, practical, predictable and safe treatment option for left-sided colonic obstruction with minimal complications.
Should Oesophagectomies be Performed by Trainees? – The Experience from a Single Teaching Centre Under the Supervision of One Surgeon
Authors: Baron Ryan , Sujendran Vijay , Maynard Nicholas
Published: May 2008

INTRODUCTION

Surgical training is threatened by anxieties about trainees performing major procedures. We have analysed the outcome of oesophagectomies performed by a consultant surgeon and compared these to the performance of trainees (years 4–6) operating under direct supervision.

PATIENTS AND METHODS

Data were collected retrospectively in a computerised database on all patients who underwent oesophagectomy at a teaching tertiary centre between December 1997 and April 2004 with a minimum 15 months' follow-up. Analysis of outcome was according to measures of technical adequacy, postoperative course, histological analysis, recurrence and survival.

RESULTS

During the study period, 241 oesophagectomies were carried out; 157 (65.1%) of these procedures were performed by the consultant and 84 (34.9%) were performed by surgeons-in-training under direct consultant supervision. Pre-operative, technical adequacy, postoperative course, histological analysis, recurrence and survival were comparable in both groups.

CONCLUSIONS

These data demonstrate comparable patient outcome when suitably experienced trainees are supervised in performing oesophagectomies and support its continued use in operative training.
The Long-Term Results of Percutaneous Drainage of Diverticular Abscess
Authors: Singh B , May K , Coltart I , Moore NR , Cunningham C
Published: May 2008

INTRODUCTION

Diverticulitis is a common condition occasionally complicated by abscess formation. Small abscesses may be managed by antibiotic therapy alone but larger collections require drainage, ideally by the percutaneous route. This minimally invasive approach is appealing but there is little information regarding the long-term follow-up of patients managed in this way. To address this question, we looked at a consecutive series of patients who underwent percutaneous drainage in our institution.

PATIENTS AND METHODS

A retrospective study was performed of patients undergoing percutaneous drainage of a diverticular abscess from 1999–2007.

RESULTS

A total of 26 abscesses were identified in 16 patients. In 69% of cases, the abscess was located in the pelvis. The mean size of the abscesses was 8.5 ± 0.9 cm. Drainage was performed under CT (83%) or ultrasound guidance. The mean duration of drainage was 8 days. Fistula formation following drainage occurred in 38% of cases. Eight patients (mean age, 71 years) underwent subsequent surgical resection 9 days to 22 months (mean, 7 months) following initial presentation. Eight patients with significant co-morbid conditions were managed by percutaneous drainage only. The 1-year mortality was 20% and resulted from unrelated causes. The long-term stoma rate was 13%.

CONCLUSIONS

Percutaneous drainage can safely be performed in patients with a diverticular abscess. It can be used as a bridge before definitive surgery but also as a treatment option in its own right in high-risk surgical patients. We believe percutaneous drainage reduces the need for major surgery and reduces the risk of a permanent stoma.
Gastric Protection and Gastrointestinal Bleeding with Aspirin Thromboprophylaxis in Hip and Knee Joint Replacements
Authors: Madhusudhan TR , Rangan A , Gregg PJ
Published: May 2008

INTRODUCTION

Upper gastrointestinal (GI) bleeding in patients who undergo hip and knee arthroplasty tends to be associated with non-steroidal anti-inflammatory drug use, steroid intake, pre-existing peptic ulcers and smoking. The use of aspirin for thromboprophylaxis is an added risk for the occurrence of GI bleed. The aim of this study was to determine the incidence of upper GI bleeding and whether the use of peri-operative oral ranitidine reduces the incidence of upper GI bleeding when aspirin thromboprophylaxis is used for hip and knee arthroplasty.

PATIENTS AND METHODS

Data from 1491 and 886 patients who underwent hip and knee replacements at the James Cook University Hospital (group 1) and at Friarage Hospital, Northallerton (group 2), respectively, were analysed in retrospect. All patients received 150 mg of aspirin per day for a period of 6 weeks from the day of surgery. Additionally, patients operated at the Friarage Hospital received 300 mg of oral ranitidine per day, for three postoperative days.

RESULTS

We observed that patients in group 1 had a higher incidence of overt upper GI haemorrhage, which was statistically significant (P <0.014) compared to patients in group 2.

CONCLUSIONS

Based on this experience, we recommend the use of peri-operative gastric protection with ranitidine when aspirin is used for thromboprophylaxis in hip and knee arthroplasty.
The Use of a Patient-Based Questionnaire (The Oxford Shoulder Score) to Assess Outcome After Rotator Cuff Repair
Authors: Olley LM , Carr AJ
Published: May 2008

INTRODUCTION

It is increasingly important for surgeons to monitor the outcome of their practice for the purpose of audit. The main difficulty has been the lack of appropriate methods of assessing outcome. Outcome has traditionally been assessed by clinical means which can be inaccurate, irreproducible and subject to surgeon bias. In addition, the perspective of the patient and surgeon may differ with respect to outcome and interest has grown in patient-based scoring systems. The Oxford Shoulder Score (OSS) is one such patient-based scoring system. The main aim of this study was to assess whether a patient-based questionnaire, in this case the OSS, could be effectively used to audit outcome from shoulder surgery. A secondary aim was to assess the value of gathering outcome information by post.

PATIENTS AND METHODS

A total of 24 patients (14 male; median age 59 years; age range, 43–73 years) who had completed a pre-operative OSS questionnaire and had undergone rotator cuff repair were included in the study. Participants were assessed postoperatively at regular intervals using the OSS at hospital visits and by postal questionnaire.

RESULTS

The completion level for the OSS was 97% and the response rate to the postal questionnaire was 96%. At 3 months' post-surgery, 21 of 24 patients had improved; at final review (16–37 months), 23 patients had improved following surgery. The OSS was observed to be a robust tool for the quantitative assessment and tracking of patient outcomes after surgery.

CONCLUSIONS

This study shows the value of using a postal questionnaire to follow-up patients after surgery and demonstrates the successful use of a patient-based questionnaire to audit the outcome from shoulder surgery.
Acute Appendicitis – A Benign Disease?
Authors: Simpson J , Samaraweera APR , Sara RK , Lobo DN
Published: May 2008

INTRODUCTION

Appendicitis is the most common cause of the acute abdomen and can affect all age groups. Most patients recover quickly but a minority can suffer postoperative complications. This case-note review was undertaken to assess the frequency of these complications.

PATIENTS AND METHODS

Adult patients (> 16 years) undergoing an emergency appendicectomy at a University teaching hospital between February 2004 and January 2005 were identified from pathology records. Details of operative procedure, histology and postoperative complications were noted from the hospital case notes

RESULTS

A total of 199 patients with a median age of 31 years (range, 16–89 years) were identified. Of these, 58 (29%) patients experienced a postoperative complication. Eight (4%) patients were admitted to the surgical high dependency unit or intensive care unit postoperatively and there was one death (0.5%). Re-operation for a postoperative complication was required in 9 (4.5%) patients and there was a 13% re-admission rate (26 patients). Comparison between patients with histologically proven appendicitis (164 patients; 82%) and those patients having a negative appendicectomy (35 patients; 18%) showed no significant difference in the rate of complications as defined (43 of 164, 26% versus 15 of 35, 43%; P = 0.08). However, patients with positive histology were more likely to experience a septic complication (29 of 164, 18% versus 1 of 35, 3%; P = 0.028) and all re-operations came from this group. Despite this, patients with a negative appendicectomy were more likely to be re-admitted (12 of 35, 34% versus 14 of 164, 8.5%; P = 0.0002), predominantly with persistent abdominal pain.

CONCLUSIONS

Appendicectomy is associated with a significant morbidity. Patients with an inflamed appendix were more likely to experience a septic complication but re-admission was more common in patients with a histologically normal appendix because of unresolved abdominal pain.
Assessment of Surgical Skills of Trainees in the UK
Authors: Beard Jonathan D
Published: May 2008

Surgical training and assessment in the UK has been criticised in the past for lacking transparency, reliability and validity. The new Intercollegiate Surgical Curriculum Programme (ISCP) has a well-defined, competence-based syllabus and a system of workplace-based assessments and examinations that map to the syllabus. The main aims of workplace-based assessment are to aid learning through objective feedback and to provide evidence that the competencies required to progress to the next level of training have been achieved. Reduction in surgical experience means that more training will need to be undertaken on simulations, although experience and assessment in the operating room must remains the ‘gold-standard’. Simulation training will require the provision of properly resourced surgical skills facilities in every hospital. The key to reliable assessment and constructive feedback is well-trained trainers. Training is a skill that must be learned, and assessment and feedback techniques form part of this. In surgery, it has been assumed that all consultants are trainers but this is clearly not the case. Surgeons will need to follow the example of primary care, where trainers are selected from experienced general practitioners who demonstrate enthusiasm and ability. The reward for the trainer should be protected time for training. The reward for the National Health Service will be better trained surgeons.
The Calcium Sensing Receptor: From Understanding Parathyroid Calcium Homeostasis to Bone Metastases
Authors: Mihai Radu
Published: May 2008

The cloning of the calcium sensing receptor (CaR) confirmed that parathyroid cells monitor extracellular calcium concentration ([Ca2+]ext) via a receptor-type mechanism. This lead to the hypothesis that abnormalities in the expression and/or function of the CaR could explain the biochemical abnormalities in primary hyperparathyroidism (PHPT).

Cultured cells from parathyroid adenomas of patients operated for PHPT were used to monitor real-time changes in intracellular calcium concentration ([Ca2+]i) as measured by fluorescent microscopy using the Fura-2/AM dye. We found that CaR agonists trigger release of intracellular calcium pools and such responses are amplified by increasing the affinity of IP3 receptors. Using confocal microscopy to monitor membrane trafficking in living parathyroid cells labelled with the fluorescent dye FM1-43, we found that a decrease in [Ca2+]i rather than an absolute change in [Ca2+]ext is the main stimulus for exocytosis from human parathyroid cells. These data suggest that, in PHPT, a defective signalling mechanism from the CaR allows cells from parathyroid adenomas to maintain low [Ca2+]i with uninhibited PTH secretion in the face of hypercalcaemia.

Over longer periods of time, CaR controls parathyroid proliferation via changes in tyrosine phosphorylation. We found that multiple proteins of molecular weight 20–65 kDa are phosphorylated within 10–60 min in response to CaR agonists.

Further work demonstrated that high [Ca2+]i stimulates the expression of bcl-2 oncoprotein in cultured human parathyroid cells and that, in parathyroid adenomas, predominant expression of bcl-2 rather than bax oncoprotein might prevent apoptosis and explain the slow growth rate of these tumours.

More recently, it became apparent that CaR stimulates cell proliferation in several cell types not involved in calcium homeostasis. Using archived histological material from 65 patients who died with metastatic breast cancer, we identified CaR expression predominantly in tumours from patients who developed bone rather than visceral metastases (35 of 49 versus 7 of 16; P < 0.01, chi-squared test).

These data suggest that CaR expression has the potential to become a new biological marker predicting the risk of bone metastases in patients with breast cancer. A prospective study should investigate if patients with CaR-positive tumours are more likely to develop bone metastases and whether they could benefit more from prophylactic treatment with bisphosphonates or the newly developed CaR antagonists.
Primary dental care in the NHS 1948–2008
Authors: Eaton Ken
Published: May 2008

As in other areas of health care the NHS has shaped many of the changes that have occurred in dentistry during the last 60 years. Many of the advances in technology and treatment would have occurred whether there was an NHS or not as they have been heavily influenced by global advances. However, judging by countries of similar wealth but with little publicly funded dentistry the improvement in oral health since 1948 would probably not have been as significant without the NHS and many of the developments in dental education and the increasing emphasis on team dentistry may not have evolved.
Croeso i Gymru – Welcome to Wales
Authors: Hill Mike
Published: May 2008

Mike Hill has represented Wales on the Faculty of Dental Surgery (FDS) Board for the last five years. He is also chair of the Academy of Medical Royal Colleges in Wales. Here, he writes about some of his experiences in moving to a foreign land…
NHS at 60: advances in surgery
Authors: Worrall Matthew
Published: May 2008

With most surgeons practising in the UK today having known nothing other than the National Health Service, it seems difficult to imagine a time when it wasn't around. A time when everyone in society made private arrangements for their health care, no matter how basic or ad hoc, is only now starting to fall out of common memory. However, 60 years isn't such a great length of time, which emphasises the pace of change in health care over that period – not just in terms of technical achievements, but also in how our society understands health care.
Supporting surgeons in the workplace
Authors: Hermans Louisa
Published: May 2008

The College is embarking on an exciting new venture to pilot a local structure to support surgeons in the workplace. Its aim is to provide a unified voice for surgery in relation to service delivery and professional standards, and to support individual surgeons through the revalidation process and with their continuing professional development (CPD). It is currently being piloted within the West Midlands and South West Strategic Health Authority (SHA) boundaries for one year. During this time it will be rigorously evaluated to determine its suitability and whether or not it will be implemented across England, Wales and Northern Ireland in the long term.
Music in theatre benefits patients and surgeons
Authors: King Mary
Published: May 2008

Music and healing have had an association for thousands of years: in ancient Greece, Apollo was the god of both music and medicine. Nowadays many surgeons use background music to relieve stress both for themselves and their patients during long, repetitive operations. David Pothier, an SpR in otolaryngology at Royal United Hospital in Bath, says music in theatre can be controversial: 'You either love it or you hate it. I enjoy it, but some surgeons find it irritating and would never allow it because they find it affects concentration. Obviously, procedures that rely on sensitive audio equipment also make it impossible to have background music.'
Experimental duo incorporate surgery into music
Authors: Hackett Jon
Published: May 2008

Though many surgeons listen to music in theatre, there can be few musicians who have repaid the compliment by incorporating elements of surgery directly into their music. Electronica duo Matmos (based in Baltimore, Maryland and perhaps best known for their work on a couple of Bjork's albums) are an exception: the instrumental credits on A Chance to Cut is a Chance to Cure (Matador, 2001) include surgery samples, lasers, straw and water (to supplement the liposuction sounds, naturally), a human skull and a goat spine. Apart from the record's conceptual wit and experimental brio, A Chance to Cut is informed by the fact that both members of Matmos, Drew Daniel and Martin Schmidt, have parents who are surgeons. I spoke to Drew about the record.
Post-CCT fellowships
Authors: Ribeiro Bernard
Published: May 2008

A proposal to promote excellence in surgical practice has, rather surprisingly, been met with mixed feelings from trainees and trainers alike. Many excellent surgical departments in the UK provide clinical fellowships to support surgeons wishing to enhance their experience in specific subspecialties. It is common practice for trainees approaching the award of the Certificate of Completion of Training (CCT) to seek fellowship posts overseas to improve their knowledge and skills in order to make them more competitive for the consultant posts of their choice. I have often quoted the experience gained by many of my ex-registrars who have undertaken fellowships in Australia, Canada and America and who confirm the added benefits gained when embarking on consultant practice. So the concept of fellowships is not new.
Role of CYP3A5 in Abnormal Clearance of Methadone
Authors: Fazio Salvatore De , Gallelli Luca , Siena Antonella De , Sarro Giovambattista De , Scordo Maria Gabriella
Published: May 2008

Objective:

To report a case of unusually low concentrations of methadone in a polydrug abuser during maintenance treatment with methadone.

Case Summary:

A 25-year-old man (weight 55 kg, height 165 cm) with a 12-year history of polydrug abuse was admitted to an opiates withdrawal methadone program. At the time of our observation, he was using both cannabinoids and heroin; no other medical conditions were discovered. Within the opiates withdrawal methadone program, under medical supervision, the patient started methadone therapy (20 mg/day). Two weeks later, an Abuscreen assay for methadone screening in the urine was negative and, to prevent the development of withdrawal symptoms, the dose of methadone was increased to 60 mg/day. One day later, the patient was asked to collect another urine sample in the presence of a nurse. The Abuscreen for methadone in urine remained negative. Evaluation of urinary samples collected over 24 hours documented low concentrations of methadone and high levels of 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (the primary metabolite of methadone). Evaluation for the presence of the most common polymorphisms in the cytochrome P450 and P-glycoprotein genes showed that the patient was heterozygous for the CYP3A531 allele and for 2 single nucleotide polymorphisms in the P-glycoprotein gene (1236C/T and 3435C/T).

Discussion:

In this patient, poor methadone adherence was ruled out because of the presence of physicians and nurses during both methadone maintenance treatment and Abuscreen screening. Moreover, because the patient reported only heroin and cannabis at the time of evaluation, drug interactions were ruled out as possible causes for the rapid clearance of methadone.

Conclusions:

In this case, CYP3A5 polymorphism may have played a role in the rapid methadone metabolism.
Möbius Syndrome in a Neonate After Mifepristone and Misoprostol Elective Abortion Failure
Authors: Bos-Thompson Marie-Andrée , Hillaire-Buys Dominique , Roux Clarisse , Faillie Jean-Luc , Amram Daniel
Published: May 2008

Objective:

To report a case of a child born with Möbius syndrome following exposure in utero to mifepristone and misoprostol for elective abortion.

Case Summary:

In the seventh week of pregnancy, a woman was administered mifepristone 600 mg and, 2 days later, misoprostol 400 μg for abortion. One month later, despite significant metrorrhagia, an ultrasound examination showed ongoing gestation. At 33 weeks and 3 days of gestation, the woman gave birth to a male with left facial palsy, microretrognathia, and axial hypotonia related to Möbius syndrome.

Discussion:

Möbius syndrome is characterized by unilateral or bilateral palsy of the abducens (VI) and facial (VII) cranial nerves. Other cranial nerves (eg, the hypoglossal [XII]), craniofacial or orofacial anomalies, and limb malformations are often associated. The etiology of the Möbius syndrome remains largely unknown and probably involves multiple factors. The most likely etiological hypothesis is disruption of the developing vascular system, with transient ischemia (particularly in the vertebral arteries) and fetal hypoxia. A teratogenic cause of Möbius syndrome has been suggested. The critical period for the development of Möbius syndrome following teratogen exposure appears to be 5–8 weeks of gestation. To date, mifepristone alone does not appear to have induced Möbius syndrome. In contrast, oral or vaginal misoprostol administration can lead to a significant increase in Doppler-measured uterine artery resistance and may induce uterine contractions. If these occur during the critical embryonic period, they may cause flexion in the areas of the sixth and seventh cranial nerves and decreased blood flow.

Conclusions:

Ineffective use of mifepristone and misoprostol in the first trimester of pregnancy may be associated with a risk of Möbius syndrome, primarily due to misoprostol activity. Women with ongoing pregnancy after failed abortion with misoprostol administration should be informed of this risk.
Acarbose for Polycystic Ovary Syndrome
Authors: Kircher Christine , Smith Katherine P
Published: May 2008

Objective:

To review the evidence for use of acarbose in the management of polycystic ovary syndrome (PCOS).

Data Sources:

Relevant publications were identified through a systematic search of PubMed English-language literature (1950–February 2008) using the MeSH terms and key words acarbose and polycystic ovary syndrome.

Study Selection and Data Extraction:

The literature search retrieved 6 primary literature citations. Three randomized controlled clinical trials and one open-label study were evaluated. The other 2 citations were not evaluated due to only a peripheral mention of PCOS in relation to diabetes.

Data Synthesis:

PCOS is a complex disorder presenting most commonly with oligomenorrhea or amenorrhea, infertility, hirsutism, acne, and obesity. Acarbose is a promising therapy for PCOS because of its effects on postprandial insulin levels. In multiple clinical studies, acarbose improved hirsutism, acne, and menstrual irregularities through reduction in androgen concentrations and through increased androgen binding. When compared with metformin in women with PCOS and clomiphene-resistant infertility, acarbose induced greater weight loss and improved menstrual regularity and signs of fertility to a similar degree. Markers of cardiovascular risk were also significantly improved following 6 months of acarbose therapy in obese women with PCOS. Adverse effects, specifically gastrointestinal, were documented. Despite promising results, the studies were limited by small sample sizes and, in some cases, methods that were not clearly defined.

Conclusions:

Several trials have evaluated the use of acarbose in the management of PCOS with positive clinical evidence, but the results of these trials have not been corroborated by more rigorous studies.
High-Dose Carisoprodol During Pregnancy and Lactation
Authors: Briggs Gerald G , Ambrose Peter J , Nageotte Michael P , Padilla Guadalupe
Published: May 2008

Objective:

To report a case of use of high-dose carisoprodol during pregnancy and breast-feeding.

Case Summary:

A 28-year-old woman with severe back muscle spasm took carisoprodol 2800 mg/day before and throughout an uncomplicated pregnancy and while exclusively breast-feeding her infant during the first month after birth. Serum drug concentrations of carisoprodol and the active metabolite meprobamate were measured in the mother and infant. Concentrations of these agents also were measured in breast milk. Developmental toxicity was not observed in the near-term infant, whose birth weight was at the 10th percentile for gestational age. Only slight sedation was noted in the infant during breast-feeding, and no signs or symptoms of withdrawal were noted when nursing was stopped.

Discussion:

Carisoprodol and meprobamate are excreted into breast milk. Although the published human pregnancy data are limited to 15 cases, carisoprodol does not appear to cause developmental toxicity (growth restriction, structural anomalies, functional/neurobehavioral deficits, or death), even when the mother is taking high doses. No signs or symptoms of withdrawal were noted in our infant or in a previously published case when breast-feeding was stopped. Long-term follow-up has not been conducted in exposed infants, and the possibility of functional/neurobehavioral I deficits appearing later in life cannot be excluded.

Conclusions:

Except for mild sedation, no other toxicity was observed in a near-term infant exposed to carisoprodol throughout gestation and during breast-feeding in the first month after birth.
Catalysts through self-assembly for combinatorial homogeneous catalysis
Authors: Breit Bernhard
Published: May 2008

Inspired by the principle of DNA base-pairing, a new concept for the self-assembly of molecular catalysts is described herein. Thus, employing A-T analogous complementary hydrogen-bonding templates, self-assembly of monodentate to bidentate ligands in the coordination sphere of a transition-metal salt occurs to give defined self-assembly catalysts. This approach is intrinsically combinatorial and allows the facile generation of defined catalyst libraries through simple component mixing. From the study of these ligand libraries, excellent catalysts for linear-selective hydroformylation, asymmetric hydrogenation, and anti-Markovnikov hydration of terminal alkynes have emerged.
Ruthenium catalysts for selective nucleophilic allylic substitution
Authors: Bruneau Christian , Renaud Jean-Luc , Demerseman Bernard
Published: May 2008

Recent developments in the chemistry of η3-allylruthenium(IV) complexes are due to their straightforward synthesis resulting from oxidative addition of allylic substrates to a ruthenium(II) center. Subsequent reaction with a nucleophile is the basis of their involvement in the catalytic allylic substitution reaction. We focus here on ruthenium-catalyzed substitution of allylic substrates by C-, N-, and O-nucleophiles and show that selected ligands make regio- and enantioselective reactions possible.
New methods in asymmetric catalysis based on new hemi-labile bidentate ligands
Authors: Charette André B. , Côté Alexandre , Desrosiers Jean-Nicolas , Bonnaventure Isabelle , Lindsay Vincent N. G. , Lauzon Caroline , Tannous Jad , Boezio Alessandro A.
Published: May 2008

Chiral bidentate hemi-labile bis(phosphine) monoxide ligands were shown to be quite effective in various copper-catalyzed transformations. Among them, the nucleophilic addition to imines, the conjugate addition to α,β-unsaturated nitro derivatives, and the conjugate reduction of α,β-unsaturated sulfones generally gave good to excellent yields and high enantiomeric excesses.
New preparative methods for allylic boronates and their application in stereoselective catalytic allylborations
Authors: Hall Dennis G.
Published: May 2008

Stereocontrolled additions of allylic metal reagents to carbonyl compounds constitute one of the most useful classes of transformations in organic synthesis. The recent development of Lewis and Brønsted acid-catalyzed manifolds for the allylboration of carbonyl compounds has opened doors toward an ideal carbonyl allylation methodology using stable and nontoxic allylic boronates as reagents. This paper describes the development of acid-catalyzed allylborations, mechanistic investigations of these new processes, and ongoing efforts toward general catalytic enantioselective allylboration methodologies. The preparation of optically enriched α-substituted allylic boronate reagents is discussed, as well as their applications in Lewis acid-catalyzed additions to afford skeletally diverse products like propionate units, polysubstituted furans, vinylcyclopropanes, and larger ring systems.
Asymmetric synthesis: From transition metals to organocatalysis
Authors: Kočovský Pavel , Malkov Andrei V.
Published: May 2008

Umpolung in the allylation reaction is discussed with examples drawn from transition-metal-catalyzed allylic substitution (with the allylic unit acting as an electrophile) and Lewis base-catalyzed allylation of aldehydes with allyltrichlorosilane (with the allyl acting as a nucleophile). Iridium-catalyzed electrophilic allylation ofO-nucleophiles has been employed in our new approach toC-nucleoside analogs, where the C-O bond (rather than C-C) was constructed stereospecifically. Variation of the absolute configuration in the starting segments allowed the synthesis of all four combinations of D/L-α/β-ribosides. In the nucleophilic allylation of aldehydes, chiral pyridine-typeN-oxide catalysts are presented, in particular QUINOX and METHOX, and the intriguing behavior of QUINOX is discussed. Here, the π-π interactions between the substrate aldehyde and the catalyst are suggested to rationalize the experimental observations. Good correlation between the calculated energies for the transition states and the experimentally observed enantioselectivities has been obtained.
Enantio- and regioselective CpRu-catalyzed Carroll rearrangement
Authors: Austeri Martina , Buron Frederic , Constant Samuel , Lacour Jerome , Linder David , Müller Jessica , Tortoioli Simone
Published: May 2008

The addition of unstabilized carbonyl nucleophiles to allyl-metal fragments still represents a challenge for generating stereoselectively tertiary (and quaternary) stereogenic centers. In this context, the decarboxylative Carroll rearrangement of secondary and tertiary allyl β-ketoesters is particularly interesting since chiral γ,δ-unsaturated ketones are obtained. Herein, we show that CpRu half-sandwich complexes can, in the presence of selected enantiopure diimine ligands, catalyze this transformation and afford complete conversions and decent level of enantiomeric excess. Zwitterionic adducts of a hexacoordinated phosphorus anion and CpRu moieties were also associated and shown to generate air-, moisture-, and microwave-stable catalysts that can be readily purified and recycled. Carroll rearrangements of allylic β-ketoesters performed with these zwitterionic species occur with better regio- and enantioselectivity.
Palladium-catalyzed selective activation of allyl alcohols as allyl cations, allyl anions, and zwitterionic trimethylenemethanes
Authors: Tamaru Yoshinao , Kimura Masanari
Published: May 2008

Pd-Et3B catalytic system promotes the generation of allyl cations, allyl anions, and zwitterionic trimethylenemethane species from the corresponding allylic alcohols. Allyl cations react with a wide variety of nucleophiles, e.g., amines, active methylene compounds, 1,3,5-trihydroxybenzene, indoles, aldehydes (at the α-position). The reaction is extended to dehydrative Grob fragmentation of 1,3-diols. Allyl anions react with aldimines to give homoallyl amines. Zwitterionic trimethylenemethane, generated from 2-methylene-1,3-propanediol, reacts with aldehydes and aldimines to provide 3-methylenecyclopentanols and 3-methylenepyrrolidines, respectively. Vinyl epoxide can be utilized as a synthetic equivalent of 3-butenyl 2-anion-1-cation.
Asymmetric Lewis acid-catalyzed 1,3-dipolar cycloadditions
Authors: Bădoiu Andrei , Brinkmann Yasmin , Viton Florian , Kündig E. Peter
Published: May 2008

Highly tuned, one-point binding chiral iron and ruthenium complexes selectively coordinate and activate α,β-unsaturated aldehydes and ketones toward asymmetric catalytic Diels-Alder cycloaddition reactions. Here we focus on the application of these transition-metal Lewis acids to asymmetric catalytic 1,3-dipolar cycloaddition reaction between enals and cyclic and acyclic nitrones as well as aryl nitrile oxides to give isoxazolidines and isoxazolines, respectively.
Copper-catalyzed asymmetric allylic substitution reactions with organozinc and Grignard reagents
Authors: Geurts Koen , Fletcher Stephen P. , van Zijl Anthoni W. , Minnaard Adriaan J. , Feringa Ben L.
Published: May 2008

Asymmetric allylic alkylations (AAAs) are among the most powerful C-C bond-forming reactions. We present a brief overview of copper-catalyzed AAAs with organometallic reagents and discuss our own contributions to this field. Work with zinc reagents and phosphoramidite ligands provided a framework for later developments which employ Grignard reagents and ferrocenyl ligands. High yields and excellent regioselectivities and enantioselectivities are achieved. The AAAs may be more general than previously envisioned, in terms of using substrates functionalized with heteroatoms at various positions; heteroatom substituents at the γ-position provide densely functionalized building blocks. These h-AAA reactions rely on the design of appropriate substrates containing heteroatoms and have allowed us to demonstrate viable new approaches toward the synthesis of versatile organic building blocks. We illustrate that the chiral secondary allylic alcohols, primary homo-allylic alcohols and amines can readily be obtained in high enantiomeric purity in a catalytic asymmetric fashion by copper-catalyzed AAAs. Furthermore, we show that manipulation of the terminal olefin provides chiral building blocks where the ee of the starting materials is preserved.
Golden opportunities in catalysis
Authors: Krause Norbert , Belting Volker , Deutsch Carl , Erdsack Jörg , Fan Hong-Tao , Gockel Birgit , Hoffmann-Röder Anja , Morita Nobuyoshi , Volz Frank
Published: May 2008

The gold-catalyzed endo-cycloisomerization of allenes bearing nucleophilic substituents in the α- or β-position opens up a versatile access to various five- and six-membered heterocycles. Key features of these transformations are the high reactivity of the allene in the presence of Lewis-acidic, carbophilic gold(I) or gold(III) catalysts, and the chirality transfer from the allenic axis of chirality to the new stereogenic center in the cyclization product. Recent contributions of our group include the optimization of chirality transfer by using σ-donor ligands to gold, and applications in the total synthesis of natural products, e.g., of the β-carboline alkaloids (-)-isocyclocapitelline and (-)-isochrysotricine.
Rhodium-catalyzed CO gas-free carbonylative cyclization using aldehydes
Authors: Morimoto Tsumoru , Fujioka Masahiko , Fuji Koji , Tsutsumi Ken , Kakiuchi Kiyomi
Published: May 2008

A new protocol for CO gas-free carbonylation, in which aldehydes are used as a substitute for CO, is described. The protocol consists of two Rh-mediated processes; the Rh-mediated decarbonylation of aldehydes, which leads to the formation of Rh carbonyl, and subsequent Rh-catalyzed carbonylative cyclization utilizing the in situ formed Rh carbonyl species.
First palladium- and nickel-catalyzed oxidative diamination of alkenes: Cyclic urea, sulfamide, and guanidine building blocks
Authors: Muñiz Kilian , Hövelmann Claas H. , Streuff Jan , Campos-Gómez Esther
Published: May 2008

We recently reported the first catalytic diamination of alkenes. This protocol calls for the use of Pd(II) as catalyst in combination with PhI(OAc)2as terminal oxidant and furnishes the final diamines as cyclic ureas. It consists of an unprecedented two-step reaction of aminopalladation and Csp3-N-bond formation involving a Pd(IV) species. Introduction of Ni(II) catalysts for homogeneous oxidation allows for an efficient diamination with sulfamides, which lead to convenient liberation of the free diamines. In related protocols, the substrate scope of the diamination has been broadened to the formation of cyclic guanidines.
Asymmetric synthesis of planar-chiral ferrocenes by Mo- or Ru-catalyzed enantioselective metathesis
Authors: Ogasawara Masamichi , Watanabe Susumu , Nakajima Kiyohiko , Takahashi Tamotsu
Published: May 2008

Kinetic resolution of planar-chiral 1,1'-diallylferrocene derivatives was realized by Mo- or Ru-catalyzed asymmetric ring-closing metathesis (RCM). The Mo catalyst showed much better performance than the Ru catalyst in the present reactions, and nearly perfect resolution of the racemic ferrocenes was achieved. This is the first example of highly enantioselective metal-catalyzed methods of preparing optically active planar-chiral metallocenes.
Nickel-catalyzed [2+2+2] cycloaddition of two alkynes and an imine
Authors: Ogoshi Sensuke , Ikeda Haruo , Kurosawa Hideo
Published: May 2008

The reaction ofN-benzenesulfonylbenzaldimine with Ni(cod)2and PCy3gave the corresponding η2-iminenickel complex quantitatively. Diphenylacetylene reacted with the η2-iminenickel complex to generate five-membered aza-nickelacycle. Insertion of second alkynes into the five-membered aza-nickelacycle led to the formation of the corresponding seven-membered aza-nickelacycles. Heating the solution of the seven-membered aza-nickelacycles induced the reductive elimination to give 1,2-dihydropyridine. In the presence of 10 mol % of Ni(cod)2and PMetBu2at 100 °C, the intermolecular [2+2+2] cycloaddition ofN-benzenesulfonylbenzaldimine and 2-butyne occurred to give the expected 1,2-dihydropyridine in 87 % yield. In the presence of PCy3, the reaction also proceeded catalytically, however, PMetBu2gave better results. Less bulky or less basic phosphine, PnBu3or P(o-tol)3, was not efficient for the reaction. Although Ni(0)-NHC complex was a good catalyst for [2+2+2] cycloaddition of two alkynes and a ketone or an aldehyde, this reaction did not proceed in the presence of an NHC ligand, 1,3-bis-(2,4,6-trimethylphenyl)imidazol-2-ylidene.
Toward the total synthesis of ritterazine N
Authors: Taber Douglass F. , Joerger Jean-Michel , Taluskie Karen V.
Published: May 2008

Zr-mediated equilibrating cyclocarbonylation of a designed triene led with high diastereocontrol to the ABC 6-6-5 tricyclic core of ritterazine N. The 5-5 EF spiroketal side chain of ritterazine N was prepared by equilibrating cyclization of an acyclic keto diol. The two components were coupled, and the D ring was assembled by intramolecular aldol condensation.
Rhenium-catalyzed synthesis of indene derivatives via C-H bond activation
Authors: Kuninobu Yoichiro , Nishina Yuta , Kawata Atsushi , Shouho Makoto , Takai Kazuhiko
Published: May 2008

Rhenium complex, [ReBr(CO)3(thf)]2-catalyzed reactions between aromatic imines and either acetylenes or α,β-unsaturated carbonyl compounds gave indene derivatives in good to excellent yields. These reactions proceed via C-H bond activation, insertion of acetylenes or α,β-unsaturated carbonyl compounds, intramolecular nucleophilic cyclization, and reductive elimination. Indene derivatives were also obtained from aromatic ketones and α,β-unsaturated carbonyl compounds in the presence of catalytic amounts of the rhenium complex and p-anisidine. Sequential ruthenium-catalyzed hydroamination of aromatic acetylenes with anilines, and rhenium-catalyzed reactions of the formed aromatic ketimines with α,β-unsaturated carbonyl compounds also provided indene derivatives.
New cyclizations via catalytic ruthenium vinylidenes
Authors: Varela Jesús A. , González-Rodríguez Carlos , Rubín Silvia G. , Castedo Luis , Saá Carlos
Published: May 2008

New carbocyclizations that proceed via catalytic metal-vinylidenes are presented. Metal-vinylidene catalytic species, which are easily accessible from terminal alkynes and catalytic amounts of transition-metal complexes, can be involved either in pericyclic reactions or in tandem processes triggered by nucleophilic attack at the electrophilic position of the vinylidene. In both cases, a wide variety of valuable cyclic compounds are easily accessible. Some recent carbocyclizations will be described.
Spatial Summation Can Explain the Attentional Modulation of Neuronal Responses to Multiple Stimuli in Area V4
Authors: Ghose Geoffrey M. , Maunsell John H. R.
Published: May 2008

Although many studies have shown that the activity of individual neurons in a variety of visual areas is modulated by attention, a fundamental question remains unresolved: can attention alter the visual representations of individual neurons? One set of studies, primarily relying on the attentional modulations observed when a single stimulus is presented within the receptive field of a neuron, suggests that neuronal selectivities, such as orientation or direction tuning, are not fundamentally altered by attention (Salinas and Abbott, 1997; McAdams and Maunsell, 1999; Treue and Martinez Trujillo, 1999). Another set of studies, relying on modulations observed when multiple stimuli are presented within a receptive field, suggests that attention can alter the weighting of sensory inputs (Moran and Desimone, 1985; Luck et al., 1997; Reynolds et al., 1999; Chelazzi et al., 2001). In these studies, when preferred and nonpreferred stimuli are simultaneously presented, responses are much stronger when attention is directed to the preferred stimulus than when it is directed to the nonpreferred stimulus. In this study, we recorded neuronal responses from individual neurons in visual cortical area V4 to both single and paired stimuli with a variety of attentional allocations and stimulus combinations. For each neuron studied, we constructed a quantitative model of input summation and then tested various models of attention. In many neurons, we are able to explain neuronal responses across the entire range of stimuli and attentional allocations tested. Specifically, we are able to reconcile seemingly inconsistent observations of single and paired stimuli attentional modulation with a new model in which attention can facilitate or suppress specific inputs to a neuron but does not fundamentally alter the integration of these inputs.
Interdomain Cytoplasmic Interactions Govern the Intracellular Trafficking, Gating, and Modulation of the Kv2.1 Channel
Authors: Mohapatra Durga P. , Siino Dominic F. , Trimmer James S.
Published: May 2008

Voltage-gated potassium (Kv) channels comprise four transmembrane α subunits, often associated with cytoplasmic β subunits that impact channel expression and function. Here, we show that cell surface expression, voltage-dependent activation gating, and phosphorylation-dependent modulation of Kv2.1 are regulated by cytoplasmic N/C interaction within the α subunit. Kv2.1 surface expression is greatly reduced by C-terminal truncation. Tailless Kv2.1 channels exhibit altered voltage-dependent gating properties and lack the bulk of the phosphorylation-dependent modulation of channel gating. Remarkably, the soluble C terminus of Kv2.1 associates with tailless channels and rescues their expression, function, and phosphorylation-dependent modulation. Soluble N and C termini of Kv2.1 can also interact directly. We also show that the N/C-terminal interaction in Kv2.1 is governed by a 34 aa motif in the juxtamembrane cytoplasmic C terminus, and a 17 aa motif located in the N terminus at a position equivalent to the β subunit binding site in other Kv channels. Deletion of either motif disrupts N/C-terminal interaction and surface expression, function, and phosphorylation-dependent modulation of Kv2.1 channels. These findings provide novel insights into intrinsic mechanisms for the regulation of Kv2.1 trafficking, gating, and phosphorylation-dependent modulation through cytoplasmic N/C-terminal interaction, which resembles α/β subunit interaction in other Kv channels.