Biomedical subjects
Publications and source records attributed to E M Holt.
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.
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 The results of treatment are discussed with reference to the published literature and two additional large unpublished series; one of 500 resections carried out in Oxford by 19 surgeons, of widely differing experience, with a follow-up period from 1 to 5 years; the other a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.
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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.
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.
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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.
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.
The molecular and crystal structures of the C alpha,alpha-dialkylated alpha-amino acid residue 1-aminocyclopropane-1-carboxylic acid hemihydrate (H2+-Ac3c-O-.1/2 H2O) and nine derivatives and dipeptides have been determined by X-ray diffraction. The derivatives are pBrBz-Ac3c-OH, Piv-Ac3c-OH, Z-Ac3c-OH, the alpha-and beta-forms of t-Boc-Ac3c-OH, Z-Ac3c-OMe, and the 5(4H)-oxazolone from pBrBz-Ac3c-OH; the dipeptides are H-(Ac3c)-OMe and c(Ac3c)2. The values determined for the torsion angles about the N-C alpha (phi) and C alpha-C' (psi) bonds for the single Ac3c residue of Piv-Ac3c-OH, the alpha- and beta-forms of t-Boc-Ac3-OH and Z-Ac3c-OMe, and the C-terminal Ac3c residue of H-(Ac3c)2-OMe correspond to folded conformations in the "bridge" region of the Ramachandran map. The structures of pBrBz-Ac3c-OH and Z-Ac3c-OH, however, are unusual in having a semi-extended conformation for the phi, psi angles. The N-terminal Ac3c residue of H-(Ac3c)2-OMe adopts a novel type of C5 conformation, characterized inter alia by an (amino) N. . .H-N (peptide) intramolecular hydrogen bond. While the acyl N alpha-blocking groups form trans amides (pBrBz-Ac3c-OH and Piv-Ac3c-OH), the urethane groups may adopt either the trans [Z-Ac3c-OH and t-Boc-Ac3c-OH (alpha-form)] or the cis amide conformations [t-Boc-Ac3c-OH(beta-form) and Z-Ac3c-OMe]. The five- and six-membered rings of the 5(4H)-oxazolone and the 2,5-dioxopiperazine, respectively, are planar. The four independent molecules in the asymmetric unit of the free alpha-amino acid are zwitterionic.
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.
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.
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.
Maternal serum alpha-fetoprotein (AFP) estimation as a routine screening test for neural tube defect (NTD) was introduced into the West Berkshire Health District, where 17 per cent of all deliveries and most of the antenatal care is undertaken by the general practitioners. In the first year, 4458 patients were screened and 43 of those (0.96 per cent) had raised serum AFP levels. Amniocentesis was performed on 31 patients (0.69 per cent). Ten fetuses with severe NTDs and one with exomphalos were detected and the pregnancies terminated. In six patients, raised serum AFP levels were due to fetal death. No normal pregnancy was terminated. Acceptability by patients was high. Provided that a good diagnostic ultrasound facility is available locally, maternal serum AFP estimation seemed to be a valuable screening test.
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Intrauterine transfusion was performed or attempted in 101 cases during a period of four and a half years. After exclusion of six cases, for reasons detailed in the text, 95 cases are considered in detail. Intrauterine transfusion was successfully performed in 93 of these, with a mean of 2.8 transfusions each. Forty-four babies (46.3%) survived and all but one are so far developing normally.
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