Synthesis and antiarrhythmic properties of novel 3-selena-7-azabicyclo[3.3.1]nonanes and derivatives. Single-crystal X-ray diffraction analysis of 7-benzyl-3-selena-7-azabicyclo[3.3.1]nonan-9-one and 7-benzyl-3-selena-7-azabicyclo[3.3.1]nonane hydroperchlorate.

Several members of the heterocyclic family 3-selena-7-azabicyclo[3.3.1]nonane have been synthesized and characterized via IR, 1H, 13C, 15N, and 77Se NMR spectroscopy and, in some cases, by X-ray diffraction analysis. Select members, namely the hydroperchlorates of the amines, were examined for antiarrhythmic properties in anesthetized dogs in which myocardial infarctions were induced by techniques previously described. In the predrug, or control state, sustained ventricular tachycardia were induced by ventricular paced beats at rates above 300/min. When 7-benzyl-3-selena-7-azabicyclo[3.3.1]nonane hydroperchlorate was administered at 3 and 6 mg/kg, the sustained ventricular tachycardia could no longer be induced. Similar doses of lidocaine, a commonly used antiarrhythmic, caused slowing of the sustained ventricular tachycardia below 300/min but did not abolish their inducibility. In addition, select members of the hydroperchlorates caused a moderate 10-20% increase in mean blood pressure whereas lidocaine caused either no change in or slightly reduced mean blood pressure. Some general conclusions are delineated concerning the structural requirements that appear to be necessary for activity in this family of heterocycles and that have not been reported previously.

Synthesis and characterization of selected heteroarotinoids. Pharmacological activity as assessed in vitamin A deficient hamster tracheal organ cultures. Single-crystal X-ray diffraction analysis of 4,4-dimethylthiochroman-6-yl methyl ketone 1,1-dioxide and ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate.

There is reported the first four members of heteroarotinoids, the names of which are ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b), ethyl (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoate (1c), ethyl (E)-p-[2-(4,4-dimethyl-1-oxothiochroman-6-yl)propenyl]benzoate (1d), and (E)-p-[2-(4,4-dimethylchroman-6-yl)propenyl]benzoic acid (1e). IR, 1H NMR and 13C NMR data have been recorded for each compound and support the structural assignments. To provide a firm basis for comparison purposes of future analogues, an X-ray analysis was performed on a single crystal of ethyl (E)-p-[2-(4,4-dimethylthiochroman-6-yl)propenyl]benzoate (1b) and a precursor 4,4-dimethylthiochroman-6-yl methyl ketone 1,1-dioxide (18). These data for the heteroarotinoid 1b revealed that the two aryl ring systems were nearly perpendicular in each of the two molecules present in the unit cell (86.37 degrees and 84.17 degrees, respectively). The space group for both molecules was P1 in triclinic systems. Unit cell dimensions (at 15 degrees C) are as follows: for 1b, a = 20.568 (6) A, b = 14.760 (3) A, c = 7.679 (2) A, alpha = 113.33 (2) degrees, beta = 79.45 (2) degrees, gamma = 79.98 (2) degrees, Z = 4; for 18, a = 9.292 (5) A, b = 9.291 (5) A, c = 7.951 (3) A, alpha = 102.16 (3) degrees, beta = 77.49 (3) degrees, gamma = 79.60 (4) degrees, Z = 2. The sulfur-containing ring is in a distorted half-chair in 1b and the methyl carbon C(12) is shown to be trans to H(13) at the C(11)-C(13) bond. The biological activity of these arotinoids was determined in the tracheal organ culture assay and compared with trans-retinoic acid for ability to reverse keratinization in vitamin A deficient hamsters. The ester 1b displayed activity about one-half log unit less than that of the reference while 1c and 1e had activity nearly one log until less than trans-retinoic acid. The sulfoxide was the least active of the heteroretinoids.

Synthesis, conformational analysis, and antiarrhythmic properties of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one, 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate, and 7-benzyl-9-phenyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ol hydroperchlorate and derivatives: single-crystal X-ray diffraction analysis and evidence for chair-chair and chair-boat conformers in the solid state.

The synthesis of the title ketone has been completed via a type of Mannich reaction starting from 4- thianone . An X-ray diffraction analysis has revealed that the solid system is a chair-boat conformer with the sulfur atom in the boat portion of the bicyclic ring compound. Wolff- Kishner reduction of the ketone group gave 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane, which was isolated as the hydroperchlorate . However, X-ray diffraction analysis of the salt showed this solid to be a chair-chair conformer. Addition of phenylmagnesium bromide to the ketone gave a tertiary alcohol with the C-C6H5 bond being equatorial with respect to the thiane ring and axial with respect to the piperidine ring. The reaction of the Grignard reagent with the ketone to give this alcohol seems to be very stereospecific. An X-ray analysis of the hydroperchlorate of the alcohol confirmed the system to be a chair-chair form in the solid. The title compounds were screened for antiarrhythmic activity in anesthetized mongrel dogs in which myocardial infarctions had been created when the left anterior descending coronary artery was ligated. Vagal-induced slowing of the sinus mode firing rate was used to determine the underlying ventricular automaticity in the dogs, which averaged 164 +/- 27 beats/min. Ventricular pacing was initiated to rates between 240 and 390/min. This technique resulted in the induction of rapid and sustained ventricular tachycardia. At doses of 3 and 6 mg/kg of body weight, 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane hydroperchlorate in alcohol (the solution was administered intravenously) was able to suppress markedly the induced ventricular tachycardia in five of six dogs. The compound also caused a 10-15% increase in blood pressure within a few minutes. The antiarrhythmic properties of this compound and others of related structure are discussed, and some comparison is made with the action of lidocaine in similar dog preparations.

The kinematics and kinetics of slipknots for arthroscopic Bankart repair.

An apparatus has been developed to enable the in vitro measurement of the kinematics and kinetics of a slipknot, both while the knot is being tightened and with the knot in place and the tension removed. During tightening, the apparatus provides a linearly increasing resistance, which may be considered analogous to the resistance experienced when the labrum is drawn toward and apposed to the edge of the glenoid cavity during a Bankart repair. The tension to close the knot is measured with a tensiometer, in tandem with the closure of the capsule model onto the bone anchor, which is measured with a datalogger. The tightening tension was limited to 25 N and intraoperator and interoperator comparisons were made for four knots tied by six participants. Failure of a knot was taken to be reverse slippage of 2 mm. A second criterion of ease of slide was used to assess each knot. We found wide interoperator variability with regard to slipknot tying. A methodology for quality control of slipknot tying is presented.

Community obstetric care in West Berkshire.

OBJECTIVE: To assess the effects of a revised obstetric booking policy whereby all low risk pregnant women received their antenatal care entirely in the community. DESIGN: Comparison of the distribution of antenatal clinic attendances, transfers, and perinatal mortality rates for 1987 and 1989, before and after introduction of the revised policy. SETTING: West Berkshire Health District. SUBJECTS: All women who delivered with a registrable birth in the district in 1987 (5817 women) and 1989 (5372). MAIN OUTCOME MEASURES: Attendances at community and consultant antenatal clinics; bookings transferred from community care to consultant care; perinatal mortality rates. RESULTS: Of 5372 women delivering in West Berkshire in 1989, 3185 (58.3%) were originally booked for general practitioner-midwife care, of whom 1567 (49.2% of general practitioner-midwife bookings) were transferred to consultant care. 1618 women (30.1% of all women delivered) received their entire obstetric care from general practitioners and midwives. Attendance at hospital antenatal clinics was reduced by 16%. In 1989 the perinatal mortality rates (1987 values) for the district were 6.3 (7.6) per 1000 births overall; 8.2 (8.3) per 1000 consultant bookings; 5.0 (4.7) per 1000 for community bookings; and 10.2 (14.4) per 1000 for women transferred to consultant care. CONCLUSION: Antenatal care of low risk pregnant women may safely be provided by their general practitioner and midwife.

A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia.

OBJECTIVE: To determine the advantages and disadvantages of endometrial resection and abdominal hysterectomy for the surgical treatment of women with menorrhagia. DESIGN: Randomised study of two treatment groups with a minimum follow up of nine months. SETTING: Royal Berkshire Hospital, Reading. SUBJECTS: 51 of 78 menorrhagic women without pelvic pathology who were on the waiting list for abdominal hysterectomy. TREATMENT: Endometrial resection or abdominal hysterectomy (according to randomisation). Endometrial resections were performed by an experienced hysteroscopic surgeon; hysterectomies were performed by two other gynaecological surgeons. MAIN OUTCOME MEASURES: Length of operating time, hospitalisation, recovery; cost of surgery; short term results of endometrial resection. RESULTS: Operating time was shorter for endometrial resection (median 30 (range 20-47) minutes) than for hysterectomy (50 (39-74) minutes). The hospital stay for endometrial resection (median 1 (range 1-3) days) was less than for hysterectomy (7 (5-12) days). Recovery after endometrial resection (median 16 (range 5-62) days) was shorter than after hysterectomy (58 (11-125) days). The cost was 407 pounds for endometrial resection and 1270 pounds for abdominal hysterectomy. Four women (16%) who did not have an acceptable improvement in symptoms after endometrial resection had repeat resections. No woman has required hysterectomy during a mean follow up of one year. CONCLUSION: For women with menorrhagia who have no pelvic pathology endometrial resection is a useful alternative to abdominal hysterectomy, with many short term benefits. Larger numbers and a longer follow up are needed to estimate the incidence of complications and the long term efficacy of endometrial resection.

Litigation relating to conditions affecting the shoulder and elbow: an analysis of claims against the National Health Service.

We present a review of claims made to the NHS Litigation Authority (NHSLA) by patients with conditions affecting the shoulder and elbow, and identify areas of dissatisfaction and potential improvement. Between 1995 and 2012, the NHSLA recorded 811 claims related to the shoulder and elbow, 581 of which were settled. This comprised 364 shoulder (64%), and 217 elbow (36%) claims. A total of £18.2 million was paid out in settled claims. Overall diagnosis, mismanagement and intra-operative nerve injury were the most common reasons for litigation. The highest cost paid out resulted from claims dealing with incorrect, missed or delayed diagnosis, with just under £6 million paid out overall. Fractures and dislocations around the shoulder and elbow were common injuries in this category. All 11 claims following wrong-site surgery that were settled led to successful payouts. This study highlights the diagnoses and procedures that need to be treated with particular vigilance. Having an awareness of the areas that lead to litigation in shoulder and elbow surgery will help to reduce inadvertent risks to patients and prevent dissatisfaction and possible litigation.

Chromium, cobalt and titanium metallosis involving a Nottingham shoulder replacement.

Metallosis after shoulder replacement has not previously been described in the literature. We report a patient who developed extensive metallosis after implantation of an uncemented Nottingham shoulder replacement. He underwent a revision procedure. Examination of the retrieved prosthesis showed that the titanium porous coating was separating from the humeral stem and becoming embedded in the ultra-high-molecular-weight polyethylene glenoid component, resulting in abrasive wear of the humeral component. There was metallosis despite exchange of the modular humeral head. Both components had to be exchanged to resolve the problem.

Endometrial resection.

The development of hysteroscopy and endometrial resection is reviewed and instrumentation is described. Suitable fluids for uterine distension and methods of delivery are discussed and safe limits to fluid absorption suggested. Selection of patients, preoperative investigation and preparation are described. Anaesthesia and operative technique are discussed with particular reference to the methods used by the authors and some common operative problems and their solutions are described. The results of treatment are discussed with reference to the published literature and two additional large unpublished series; one of 500 resections carried out in Oxford by 19 surgeons, of widely differing experience, with a follow-up period from 1 to 5 years; the other a personal series of 585 cases done by one of the authors (E.M.H.) with a follow-up period of 1 to 4 years. Factors affecting the likely success of the procedure, operative and post-operative complications, the difficulty and results of repeated resections and the indications for subsequent hysterectomy are discussed. Finally, the economic aspects of the technique and the author's conclusions as to the place of endometrial resection in the treatment of menorrhagia are given.

Three methoxy-substituted diethyl 4-phenyl-2,6-dimethyl-1, 4-dihydropyridine-3,5-dicarboxylate compounds.

Diethyl 4-(2,5-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3, 5-dicarboxylate, C(21)H(27)NO(6), (I), diethyl 4-(3, 4-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3, 5-dicarboxylate, C(21)H(27)NO(6), (II), and diethyl 2, 6-dimethyl-4-(3,4,5-trimethoxyphenyl)-1,4-dihydropyridine-3, 5-dicarboxylate, C(22)H(29)NO(7), (III), crystallize with hydrogen-bonding networks involving the H atom bonded to the N atom of the 1,4-dihydropyridine ring and carbonyl O atoms in (I) and (II). Unusually, (III) shows O atoms of methoxy groups serving as hydrogen-bond acceptors.

Anatomic variants of the coracoacromial ligament.

Cadaveric anatomic dissections of 50 shoulders have been done with measurement and histologic analysis of the coracoacromial ligament. In subjects older than 50 years of age the coracoacromial ligament does not have a constant form. Three main types were identified: quadrangular, Y-shaped, and a broad band. A previously unreported type of coracoacromial ligament the multiple banded ligament, was found. It had the largest coracoid attachment. This ligament was similar to the Y form but with an additional band extending inferiorly and medially toward the base of the coracoid. Histologic analysis indicates the multiple banded type could be more common than this study suggests.

Diethyl 4-(2,5-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, conformational change with solvent of crystallization.

The title compound, C(21)H(27)NO(6), has been crystallized from ethanol containing nitrobenzene and shows the phenyl ring, B, in an ap conformation. This structure may be compared with that of the molecule crystallized from ethanol alone, in which the B ring is seen in an sp conformation. The isolation of this rotamer has implications for the understanding of the docking of calcium beta-blocking dihydropyridine molecules with their receptor site.

Tension free vaginal tape: is the intra-operative cough test necessary?

The tension-free vaginal tape (TVT) procedure is recognised as an effective treatment for genuine stress incontinence. It was first described using local anaesthesia, with an intra-operative cough test helping to correctly position the tape. Many patients prefer general anaesthesia and often, patients with genuine stress incontinence do not leak when supine. This aim of this study was to compare the outcome in TVTs performed under general anaesthesia with those performed under spinal anaesthesia. Retrospective analysis of 105 patients, all of whom had urodynamically proven genuine stress incontinence and underwent TVT procedure, was performed: 52 under spinal anaesthesia and 53 under general anaesthesia. The primary and secondary outcome measures were the success or failure of the procedure and the complication rate, respectively. There was no significant difference in outcome or complication rate between the two groups. The type of anaesthetic used does not influence the outcome and we question the necessity of an intra-operative cough test.

Chondroblastoma of the acromion.

We describe a rare case of chondroblastoma of the acromion in a 29-year-old man. In addition to the radiological progression and confirmatory histological evidence of the lesion, the relevant and more unusual aspects of this tumour are discussed.

Bismuth(V) iron(III) tris(phosphate) oxide.

Bi(V)(0.4)Fe(3)(III)O(PO(4))(3) crystallizes with two Fe atoms (one on an inversion centre and one on a mirror plane) displaying octahedral geometry and a third Fe atom (on a mirror plane) with trigonal bipyramidal coordination. Fe atoms are seen in oxygen-bridged chains. Bi(V) atoms are found in the interstitial sites between these chains. Bi shows sevenfold coordination, with Bi-O distances between 2.357 (7) and 2.529 (6) A.

Conformational properties of 2,3-methanopyroglutamic acid in peptides: NMR and x-ray diffraction studies.

The effects of replacing L-pyroglutamic acid with the cyclopropane analogue 2,3-methanopyroglutamic acid (2,3-MeGlp) on conformation and enzymatic stability have been investigated in 2,3-MeGlp-NHMe and the novel thyrotropin releasing hormone (TRH) analogue [2,3-MeGlp1]-TRH by x-ray diffraction and nmr. While 2,3-MeGlp-NHMe adopts a folded conformation (small psi angle) in the solid state, several conformations are available to the molecule in solution. 1H-nmr of the diastereomeric mixture [(+/- )-2,3-MeGlp1]-TRH indicates a close orientation of the pyrrolidone and imidazole rings. The 2,3-MeGlp-His amide bond is considerably more stable to pyroglutamate aminopeptidase than the Glp-His bond in TRH.

Locked intramedullary nailing for recent lower limb fractures.

This paper reports the results in a prospective series of recent fractures of both the femur and tibia treated by the Grosse and Kempf locking system of intramedullary nailing. Although the technique requires some attention to detail, it has been possible to treat a wide range of relatively severe injuries with a short hospital stay and rapid rehabilitation, with benefit to both the patient and hospital services.