Showing papers by "St Thomas' Hospital published in 1992"

Co-transfer of vancomycin and other resistance genes from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus

Abstract: Conjugative transfer, in the apparent absence of plasmid DNA, of high-level vancomycin resistance from Enterococcus faecalis NCTC 12201 to Staphylococcus aureus B111 has been demonstrated in vivo and in vitro. Selection of transconjugants on media containing erythromycin or chloramphenicol may result in the transfer of resistance to erythromycin, chloramphenicol, gentamicin, streptomycin and vancomycin though these are capable of separate transfer. Vancomycin resistance has not been transmitted from staphylococcus to staphylococcus though transfer of erythromycin and of chloramphenicol resistance has been achieved.

The growth hormone deficiency syndrome in adults

Abstract: The effects of growth hormone (GH) deficiency in childhood are well recognized. These include shortness of stature with normal proportions, slow linear growth rate, delayed bone age with reduced bone density, excess adiposity with a predominantly truncal distribution, reduced lean tissue mass, and fasting hypoglycaemia (Collip et al., 1973; Hopwood et al., 1975; Tanner et al., 1977; Milner et al., 1979; Parra et al., 1979, Shore et al., 1980). These effects reflect the known metabolic actions of GH (Davidson, 1987; Press, 1988); GH promotes anabolism and lipolysis, and has complex actions on carbohydrate metabolism which can be summarized as insulinotrophic and insulin antagonistic. The effects of GH deficiency in adults have been appreciated only recently. There may be several reasons for this. Firstly, adults who developed panhypopituitarism from mass effects of a pituitary tumour or the treatment of the tumour survived, often returning to reasonably functional lives with conventional pituitary hormone replacement therapy. Secondly, GH treatment of such patients was not possible due to limited supplies of human pituitary-derived GH. The introduction of recombinant DNA technology has resulted in the production of authentic sequence human GH (rhGH) in potentially unlimited supplies, allowing treatment of conditions other than short stature. The aims of this review are to summarize the recent studies of GH treatment in adults with GH deficiency, thereby defining the syndrome of GH deficiency in adults, and to highlight areas for future investigation.

Intestinal permeability: functional assessment and significance.

Abstract: The intestinal epithelium demonstrates differential properties, providing both barrier and transport functions with respect to luminal molecules. Intestinal permeability relates to barrier function and, although it is the ‘permeation’ of molecular markers that is used to measure ‘permeability’, the terms are often confused. Permeability is that property of the intestinal epithelium or of a membrane which refers to the facility with which it allows molecules to pass through by non-mediated diffusion [ 11, whereas the term permeation describes the act of nonmediated diffusion itself. Non-mediated diffusion means the passage of molecules down a concentration (or pressure) gradient without the assistance of a passive or active biochemical carrier system. Intestinal permeability in a clinical context mainly concerns the permeation of molecules with a molecular mass > 150 Da, rather than ions such as sodium or chloride, to which the term membrane permeability is usually applied. In some respects the barrier function shows dynamic properties [2], as shown by the observation that altered permeability induced by hyperosmotic stress is reversible within a few hours [3]. Intestinal barrier function is also affected by disease, drugs, diet, cytokines, hormones or the environment, but does not appear to be much influenced by age, race or hereditary factors. The consequences of impaired barrier function for antigen access [4], which could initiate or perpetuate inflammation, and the potential for non-invasive assessment of disease or therapeutic manipulation, are reasons for the current interest in intestinal permeability. This review is divided into two parts. The first part outlines the nature of the intestinal epithelial barrier and our still incomplete understanding of the pathways of permeation, as well as mechanisms by which permeability can be altered. The second part discusses methods available for measuring intestinal permeability in vivo, the clinical circumstances in which it is altered, and the relevance of clinical tests of permeability. First, a brief history of intestinal permeability is appropriate.

Is the prevalence of atopic dermatitis increasing

Abstract: Several studies have suggested that the prevalence of atopic dermatitis has increased over the last three decades, and similar trends have been reported with asthma and hay fever. However, in common with other 'allergic' disease, the definition and measurement of atopic dermatitis in populations has been fraught with problems and has led to difficulties in separating any real changes in disease prevalence from secular changes in diagnosis. In this article, the evidence surrounding the claims of an increased prevalence of atopic dermatitis is examined, and possible reasons for such a change are suggested.

The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy. A prospective, randomized, double-blind trial.

Abstract: In this study, we report the results of a prospective, double-blind trial to determine whether high-dose topical corticosteroids have an effect on refractive outcome or anterior stromal haze after photorefractive keratectomy. A total of 113 patients were allocated randomly to either placebo- or steroid-treated groups (0.1% dexamethasone metasulphobenzoate for 3 months) and underwent either -3.00-diopter (D) or -6.00-D procedures. At 6 weeks, the mean change in refraction was significantly greater in the steroid-treated group than in the placebo-treated group (-3.00-D group, P = .0015; -6.00-D group, P = .0011). However, when corticosteroids were discontinued at 3 months, this difference became statistically insignificant. There was no statistically significant effect on anterior stromal haze at any stage. Since long-term use of corticosteroids to maintain the initial beneficial effect on refraction would be unacceptable, we conclude that these agents should not be used after photorefractive keratectomy.

Regions of human papillomavirus type 16 E7 oncoprotein required for immortalization of human keratinocytes

Abstract: Binding of the retinoblastoma gene product (pRB) by viral oncoproteins, including the E7 of human papillomavirus type 16 (HPV 16), is thought to be important in transformation of cells One of the steps in transformation is the immortalization process Here we show that mutations in E7 within the full-length genome which inhibit binding of pRB do not abrogate the ability of the HPV 16 DNA to immortalize primary human epithelial (keratinocyte) cells A mutation in one of the cysteines of a Cys-X-X-Cys motif which is contained in the carboxy half of the E7 and is part of a zinc finger arrangement completely eliminates the ability of HPV 16 DNA to immortalize cells The results indicate the importance of E7 in the immortalization of primary keratinocytes but suggest that the binding of pRB is not essential

Cytokines in human intraocular inflammation.

Abstract: The presence of interleukin 6 (IL-6), interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor (TNF) was investigated in vitreous and aqueous aspirates from eyes undergoing vitrectomy for the treatment of different inflammatory conditions. Cadaveric vitreous from 10 normal subjects were used as controls. IL-6 was observed in 5 specimens from eyes with idiopathic uveitis (range = 26–264 pg/ml), in 2 specimens from eyes with uveitis complicated with retinal detachment (28 and 279 pg/ml, respectively), in 6 samples from eyes with diabetic retinopathy (range = 5–480 pg/ml), in one sample from an eye with phacolytic glaucoma (1190 pg/ml) and in one specimen from an eye with Behcet's disease (366 pg/ml). Although IL-1 was detected in 80% of all the samples investigated, concentrations of this cytokine >3 pg/ml were only observed in 2 specimens from eyes with uveitis (5 and 20 pg/ml, respectively) and 2 samples from eyes with diabetic retinopathy (3 and 31 pg/ml, respectively). TNF was present in 3 ...

Fetal risks in herpes gestationis

Abstract: Background: The potential risks to the fetus in herpes gestationis have long been a controversial subject, but because of the rarity of the disease, have only occasionally been studied. Objective: The purpose of this study was to determine the incidence of fetal complications in herpes gestationis. Methods: We collected and analyzed the obstetric histories of 74 patients and compared their involved pregnancies with their uninvolved pregnancies. Results: There was an obvious tendency for premature delivery associated with herpes gestationis. A slight tendency toward small-for-gestational-age n ewborns associated with herpes gestationis was confirmed, but, perhaps surprisingly, no increase in spontaneous abortions or stillbirths was noted. The use of systemic steroids did not appear to influence risk. Conclusion: Herpes gestationis is associated with an increase in prematurity and small-forgestational-age infants.

Regurgitation and oesophageal rupture with cricoid pressure: a cadaver study.

Abstract: The efficacy of cricoid pressure was studied in 10 adult cadavers. The oesophageal pressure that would result in regurgitation during measured values of cricoid pressure was determined. Oesophageal pressure, recorded by a 2 mm diameter oesophageal tube, was increased by oesophageal distension with saline, and incremental levels of cricoid force, 20, 30 and 40 Newtons, were applied with a cricoid yoke. With each 10 Newton increment of cricoid force there was a significant rise in the oesophageal pressure required to provoke regurgitation (p < 0.01). Thirty Newtons of cricoid force prevented regurgitation of saline in all cadavers with oesophageal pressures of up to 40 mmHg. Rupture of the oesophagus occurred in three cadavers: one at 30 and two at 40 Newtons of cricoid force, but there was no rupture at 20 Newtons of cricoid force. In the other seven cadavers oesophageal pressures were also studied with a 4.6 mm diameter (14 FG) oesophageal tube, which did not reduce the efficacy of cricoid pressure in preventing regurgitation.

Peripheral nerve injury caused by injection needles used in regional anaesthesia: influence of bevel configuration, studied in a rat model

Abstract: We have studied the immediate and long term (up to 28 days) effects of short and long bevelled needle impalement of the rat sciatic nerve. Three techniques were used to assess neural trauma and its consequences: stained longitudinal nerve sections were assessed by light microscopy and scored for injury; the extravasation of Evan's Blue dye, after antidromic electrical nerve stimulation, was used as a test of unmye/inated fibre function; the flexion withdrawal times from a noxious stimulus were measured. The results of all three experiments suggested that, should a nerve fascicle become accidentally impaled during regional anaesthesia, the lesions induced by short bevelled needles are more severe, more frequent and take longer to repair than those induced by long bevelled needles. Nerve injury induced by short bevelled needles was associated with persisting signs of injury 28 days after the injury. These results suggest that the current practice of using short bevelled needles to prevent nerve injury complicating regional anaesthesia be reassessed. (Br. J. Anaesth. 1992; 69: 433–438).

Induction of mucosal and systemic immunity to a recombinant simian immunodeficiency viral protein.

Abstract: Heterosexual transmission through the cervico-vaginal mucosa is the principal route of human immunodeficiency virus (HIV) infection in Africa and is increasing in the United States and Europe. Vaginal immunization with simian immunodeficiency virus (SIV) had not yet been studied in nonhuman primates. Immune responses in macaques were investigated by stimulation of the genital and gut-associated lymphoid tissue with a recombinant, particulate SIV antigen. Vaginal, followed by oral, administration of the vaccine elicited three types of immunity: (i) gag protein p27-specific, secretory immunoglobulin A (IgA) and immunoglobulin G (IgG) in the vaginal fluid, (ii) specific CD4+ T cell proliferation and helper function in B cell p27-specific IgA synthesis in the genital lymph nodes, and (iii) specific serum IgA and IgG, with CD4+ T cell proliferative and helper functions in the circulating blood.

Quantifying proliferation of cultured human and rabbit airway smooth muscle cells in response to serum and platelet-derived growth factor.

Abstract: Development of suitable methods for the quantification of the proliferative response of airway smooth muscle (ASM) cells in culture will assist the investigation of the cellular mechanisms underlying the hyperplasia and hypertrophy of ASM as seen in asthmatic airways. In this study, two rapid and simple colorimetric assays have been modified to enable the growth of human bronchial and rabbit tracheal smooth muscle in culture to be assessed. One method depends upon the reduction by living cells of the tetrazolium salt MTT to form a blue formazan product, whereas the other relies on rapid binding of the dye Coomassie brilliant blue to protein at acidic pH. Experiments demonstrated the validity of both assays in quantifying the proliferative response of cultured human and rabbit ASM cells. The increase in optical density observed for each assay correlated directly, throughout the duration of culture, with the increase in cell number determined by hemocytometry in human and rabbit ASM cells proliferating in response to fetal calf serum (1.25 to 10%). This relationship held also for rabbit tracheal ASM cells proliferating in response to the heterodimer of platelet-derived growth factor (1 to 50 ng/ml). Application of these methods to adherent proliferating cultures of human and rabbit ASM cells demonstrated their adaptability to the generation of growth curves in response to serum and to a defined growth factor. These methods allow both total cellular protein and proliferation to be estimated in human and rabbit ASM cells in culture, using assays that are rapid, reproducible, inexpensive, and easy to perform while negating the use of radioisotopes. It is intended that these additional methods should be useful in delineating some of the mechanisms that might contribute to the proliferative response of these cells--particularly since there has been a resurgence in interest in culturing smooth muscle cells derived from the airways.

A quantitative histological study of the vascularity of the rotator cuff tendon

Abstract: Previous perfusion studies of the rotator cuff have demonstrated an area of hypovascularity in the distal part of the supraspinatus tendon. This has been implicated in the pathogenesis of its rupture. We performed a quantitative histological analysis of the vascularity of the tendons of supraspinatus and infraspinatus. Vessel number, size and the percentage of the tendon occupied by vessels were measured at 5 mm intervals from the humeral insertions to the muscle bellies. Both tendons were hypovascular in their distal 15 mm. No significant difference was demonstrated between the vascularity of supraspinatus and infraspinatus. We conclude that factors other than vascularity are important in the pathogenesis of supraspinatus rupture.

Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases.

Abstract: Epidermolysis bullosa (EB) refers to a group of hereditary mechano-bullous conditions, many of which are associated with chronic scarring. Several forms of the disease have been reported in association with cutaneous malignancy. We present a series of 10 EB patients (eight generalised recessive dystrophic EB, one dominant dystrophic EB, one non-lethal junctional EB) aged 24-55 years with a total of 29 squamous cell carcinomas (SCC). Three patients died from metastatic disease associated with invasive, poorly differentiated SCC. Six cases had multiple primary SCC, including three patients with simultaneous multifocal disease. Twenty-eight of the 29 SCC arose on the limbs. Histology revealed that most of the SCC were well or moderately differentiated (22/29). Unusual histological findings included two verrucous SCC, as well as a spindle cell (angiosarcoma-like) SCC. Most of the SCC developed in areas of chronic non-healing ulceration (10/29) or longstanding hyperkeratotic crusting (14/29). The dermis around or beneath the carcinomas was densely scarred, more so than in non-malignant areas. In some cases it was difficult to distinguish the clinical appearances of certain areas of chronic ulceration, scarring, and crusting typical of dystrophic EB from many of the SCC. This study underlines the need for constant vigilance for the development of carcinomas in this group of patients, the occasional diagnostic difficulty, and the potential for metastasis.

Upper oesophageal sphincter pressure and the effect of cricoid pressure.

Abstract: Summary Upper oesophageal sphincter pressure has been measured in 24 patients with a sleeve device. The median sphincter pressure when awake was 38 mmHg. and when anaesthetised and paralysed was 6 mmHg. After tracheal intubation, cricoid pressure was applied at measured values between 5 and 50 N using a hand-held cricoid yoke while the sphincter pressure was recorded in two head and neck positions: with and without a standard intubating pillow with neck support. A cricoid force of 40 N increased sphincter pressure to above 38 mmHg in all the patients and the use of the pillow did not alter this effect. With the application of cricoid pressure, operating department assistants raised sphincter pressure to above 38 mmHg in only 50% of patients. Laryngoscopy made little difference to the effect of cricoid pressure except in one patient in whom it reduced the sphincter pressure by 27 mmHg.

Correlations between laser flare measurements and anterior chamber protein concentrations.

Abstract: The laser flare cell meter quantifies anterior chamber (AC) protein (flare) by measuring light scattering of a helium-neon laser beam in the AC. The relationship between photon count and protein concentration both in vitro and in vivo was assessed. The reproducibility of the in vitro photon count measurements was 7.3%. There was a significant linear relationship between photon count and the concentration of both albumin (r = 1.0, P = 0.0001) and immunoglobulin G (IgG, r = 0.99, P = 0.0001) in vitro, but the linear-regression formulas were different with greater light scattering by IgG than by albumin at the same concentration. Laser flare measurements were done on 22 patients (12 normal eyes, 5 eyes with Fuchs' heterochromic cyclitis, and 5 uveitic eyes) before cataract surgery. Aqueous humor obtained from these patients by paracentesis was analyzed for total protein, albumin, and IgG concentration. There was a significant linear relationship (r = 0.88, P = 0.0001) between the laser flare value (range, 5.8-107.8 photons/msec) and the total aqueous protein concentration (range, 14-388 mg/dl). Use of an in vitro albumin calibration curve to convert photon count into protein concentration was found to overestimate the actual protein concentration. This overestimation was slight in normal eyes and increased with increased blood-aqueous barrier breakdown. The use of such a calibration curve therefore is not appropriate in studies on diseased eyes. The authors recommended that laser flare results be expressed in either photons per milliseconds or converted into an equivalent protein concentration using a calibration curve based on actual AC protein measurements.

Clinical and mycological diagnostic aspects of onychomycoses and dermatomycoses.

Abstract: The most common fungal disease of man is tinea pedis, and it has been estimated that 10-15% of the adult population in developed countries are affected at any one time. This prevalence may be even higher among at-risk groups such as swimmers and coal miners. There is no published data on the extent of onychomycoses in the general population but, extrapolating from the above figures and assuming that one-third of subjects will have some form of nail involvement, Evans' postulated that about 5% of the general population could have fungal disease. In view of the dimensions of these clinical conditions and because of their relatively poor response to treatment, it is important to summarize the natural history and diagnosis of nail and foot infections.

A review of local radiotherapy in the treatment of bone metastases and cord compression.

Abstract: Local radiotherapy plays an important role in the management of bone metastases. Because it is given with palliative intent to patients with limited, if variable, life expectancy, radiotherapy schedules need to be identified which give maximum patient benefit (short and long term) with minimum associated morbidity and minimum disruption of the patients' remaining life. For localized bone pain, a single fraction of radiotherapy, repeated if necessary, appears to fulfill these criteria in patients with a short life expectancy. There are, however, unanswered questions regarding fraction size and the adequacy of one fraction for long-term control and for all pathological tumor types. Only randomized trials can answer these questions. Uncertainties also exist regarding the precise indications for radiotherapy to prevent and treat pathological fractures and the optimal dose schedule which will provide adequate local tumor control without inhibiting bone healing or interfering with bone integrity. Because of the many variables, guidelines on selection of cases of spinal cord compression for decompression by surgery or radiotherapy are likely to be of more value than randomized prospective studies in this condition. Experimental work and clinical experience to date suggest an advantage for a few large fractions of radiotherapy, at least initially, to achieve a rapid response, but this too needs confirmation. Treatment decisions based on past teaching and local custom rather than on valid clinical trial data have led to considerable differences in clinical practice among radiotherapists. Bone metastases are common and warrant a great deal more experimental and clinical study than they have received to date.