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Showing papers by "St Thomas' Hospital published in 1991"


Journal ArticleDOI
TL;DR: Comparisons between children with Williams syndrome and control group children matched for age, sex, social class, and verbal intelligence provide support for a cognitive and behavioural phenotype in Williams syndrome.
Abstract: Comparisons between children with Williams syndrome and control group children matched for age, sex, social class, and verbal intelligence provide support for a cognitive and behavioural phenotype in Williams syndrome. Children with the syndrome showed higher rates of behavioural and emotional difficulties when compared with the control group children, particularly in terms of concentration difficulties, excessive anxiety, and poor relationships with peers; and they also had significantly poorer visuo-spatial and motor skills. However, the Williams syndrome children were not uniformly poor in all areas of nonverbal abilities. Their visual recall skills were as good as those of the control group children, and their performance was superior to that of the control group children on a task of face recognition and on tasks requiring recall of verbal material.

328 citations


Journal ArticleDOI
TL;DR: In these biopsies, the inflammation induced in response to PPD differed from UV-B-induced inflammation in showing prolonged expression of endothelial ELAM-1, induction of VCam-1 on endothelium and other cells, and induction of keratinocyte ICAM- 1.

231 citations


Journal ArticleDOI
TL;DR: To date PRK appears to be a safe procedure that holds considerable promise for refractive surgery in the future, and considerable individual variation in response to this surgery, which is more marked in high myopia.
Abstract: The results of excimer laser photorefractive keratectomy (PRK) in 16 blind and 120 sighted eyes (136 patients) are presented. Follow up for the blind eyes was 22 months and for the sighted eyes 8 to 18 months (mean, 1 year). A Summit Technology UV200 excimer laser with fluence fixed at 180 mJ/cm2, beam diameter 4 mm, a frequency of 10 Hz, and ablation rate of 0.22 mu per pulse was used. The range of preoperative myopia was - 1.50 diopters to - 17.50 D (spherical equivalent). Ninety percent of patients undergoing a -2.00 D correction and 75% of patients undergoing a -3.00-diopter correction were within +/- 1.00 D of intended refraction at 6 months. This figure fell to 40% and 20% for the groups undergoing -6.00 D and -7.00 D corrections, respectively. While the trend is toward undercorrection, around 70% of patients in all groups have benefited from a reduction of their myopia by at least half that intended. A variable degree of anterior stromal "haze" was detected in 110 patients (92%) despite a rigid high dose topical corticosteroid regime over 3 months. Best spectacle corrected visual acuity, however, was greater than or equal to preoperative levels in 111 patients (93%). Six patients experienced a reduction of one line of Snellen acuity at 6 months and three of the high myopes lost two lines. No patients lost more than two lines of Snellen acuity. Ninety-four patients (78%) noticed a "halo" around lights at night, more marked in the early postoperative period, which we attribute to the 4-millimeter diameter ablation zone. With a large pupil, both central and paracentral cornea can contribute simultaneously to the retinal image. We have demonstrated considerable individual variation in response to this surgery, which is more marked in high myopia. Although follow up at the present time is limited, to date PRK appears to be a safe procedure that holds considerable promise for refractive surgery in the future.

229 citations


Journal ArticleDOI
TL;DR: Twenty-four girls who survived the sinking of the 'Jupiter' in October 1988 were screened 10 days after the accident on the Impact of Events Scale, the Birleson Depression Scale and the Revised Children's Manifest Anxiety Scale, and survivors were clearly differentiated from controls on all three measures.
Abstract: Twenty-four girls who survived the sinking of the 'Jupiter' in October 1988 were screened 10 days after the accident on the Impact of Events Scale, the Birleson Depression Scale and the Revised Children's Manifest Anxiety Scale. Scores at 10 days were associated strongly with help seeking over the following few months and were highly predictive of scores five months after the accident. Survivors were clearly differentiated from controls on all three measures. The battery seems useful in screening post-traumatic stress disorders in teenage children. Language: en

180 citations


Journal ArticleDOI
01 Jan 1991-Eye
TL;DR: Observations provide further evidence that cytokine-mediated pathways of inflammation are involved in the pathogenesis of PVR and point to the possible involvement of IL-1, IL-6 and IFNγ in cellular interactions leading to chronicity.
Abstract: This study determined the presence of interleukin 1 (IL-1), interleukin 6 (IL-6), tumour necrosis factor alpha (TNF alpha), tumour necrosis factor beta (TNF beta), interferon gamma (IFN gamma), transforming growth factor beta 2 (TGF beta 2) and fibroblast proliferation activity (FPA) in vitreous aspirates from eyes undergoing vitrectomy for the treatment of retinal detachment complicated by proliferative vitreoretinopathy (PVR) or uncomplicated retinal detachment (RD). Cadaveric vitreous from normal subjects were used as controls. The results showed that IL-1 and IL-6 predominated in vitreous from eyes with PVR or RD, and that concentrations of IL-6 greater than 20 pg/ml were more frequently found in PVR than in RD (p = 0.031) or control specimens (p = 0.006). Low levels of TNF alpha were observed in 4/18 eyes with PVR, 1/15 eyes with RD and 1/15 control vitreous, and small concentrations of TNF alpha were seen in 3/18 eyes with PVR, 1/15 eyes with RD and 2/15 control vitreous. IFN gamma was detected in 12/18 eyes with PVR, but only in 5/15 eyes with RD (p = 0.048) and 6/15 control specimens. TGF beta 2 was present in all vitreous samples at concentrations ranging from 100 to 4,500 pg/ml with no significant differences among the three groups. Control vitreous possessed the greatest FPA when compared with vitreous from eyes with PVR (p = 0.031) or RD (p = 0.048). These observations provide further evidence that cytokine-mediated pathways of inflammation are involved in the pathogenesis of PVR and point to the possible involvement of IL-1, IL-6 and IFN gamma in cellular interactions leading to chronicity.

179 citations


Journal ArticleDOI
TL;DR: Four sequelae of reperfusion that might be designated as "reperfusion injury" are defined, possible underlying mechanisms are identified, and whether any of these forms of reperFusion injury are of clinical relevance are considered.

178 citations


Journal ArticleDOI
TL;DR: The combined psychological/physiotherapy treatment conditions improved significantly more than the physiotherapy-only conditions from pre to posttreatment on measures of pain intensity, self-rated functional impairment and pain-related dysfunctional cognitions.

167 citations


Journal ArticleDOI
TL;DR: Treatment with recombinant human growth hormone in adults with growth hormone deficiency resulted in small increases in left ventricular pre-load, due to the sodium-retaining action of growth hormone, and activation of the renin-aldosterone system was involved in such changes.
Abstract: 1. In adult humans with growth hormone deficiency, treatment with growth hormone has recently been shown to have major anabolic effects and to improve exercise performance. The cardiovascular effects of growth hormone in adults with growth hormone deficiency were examined in 24 patients treated with recombinant human growth hormone (0.07 units/kg at night) in a double-blind, placebo-controlled trial lasting 6 months. 2. Compared with placebo, resting M-mode echocardiography showed increases in left ventricular end-diastolic dimension and stroke volume in the group treated with recombinant human growth hormone. No differences were noted between the groups with respect to left ventricular end-systolic dimension, fractional shortening, wall thicknesses or mean arterial blood pressure. Left ventricular myocardial mass increased in the group given recombinant human growth hormone. 3. The supine plasma renin activity was increased and remained elevated over the 6 months, whereas the plasma aldosterone concentration was unchanged, after treatment with recombinant human growth hormone. Clinical signs of sodium retention were evident during the first 3 months of treatment with recombinant human growth hormone. 4. We conclude that treatment with recombinant human growth hormone in adults with growth hormone deficiency resulted in small increases in left ventricular pre-load, due to the sodium-retaining action of growth hormone. Activation of the renin-aldosterone system was involved in such changes. Myocardial hypertrophy was observed without changes in mean arterial pressure, reflecting the anabolic action of growth hormone.

151 citations


Journal ArticleDOI
TL;DR: Staining with PC10 may be of particular value in the identification of patients at greatest risk of rapid tumour metastasis and early death in cases of haemangiopericytoma.
Abstract: Forty-two cases of haemangiopericytoma were studied retrospectively using immunohistochemical staining with PC10, a monoclonal antibody to PCNA The percentage of tumour cells with positive staining for PCNA was found to correlate well with histological grading Clinical follow-up data were available in 25 adults and showed no known deaths in 11 cases with a low proportion (< 14%) of positive cells Out of 14 cases with a high number (greater-than-or-equal-to 14%) of positive cells, seven patients are known to have died, two had metastases, and in a further two there have been multiple recurrences of tumour DNA flow cytometry was performed on 26 cases but this showed no correlation with PC10 staining or clinical outcome Staining with PC10 may be of particular value in the identification of patients at greatest risk of rapid tumour metastasis and early death

148 citations


Journal Article
TL;DR: Clinical evidence of prosthetic valve infection was found in 79% of MVR and 67% of AVR and a heavily calcified aortic annulus, found in 47% of patients, may also have contributed to PPL after AVR.
Abstract: Paraprosthetic leak (PPL) is a rare but potentially serious complication of cardiac valve replacement. Between 1974 and 1988, 1175 prosthetic valves were implanted in 1026 patients by one cardiac surgeon at St. Thomas' Hospital, London. Of these 539 (52.5%) were aortic (AVR), 334 (32.6%) mitral (MVR), 7 (0.7%) tricuspid, and 144 (14%) AV and MV double valve replacements (DVR). There were only 2 triple valve replacements. The prosthetic valves implanted were the Starr-Edwards (7%), Bjork Shiley (11.8%), Lillehei-Kaster (23%), Carpentier-Edwards bioprosthesis (35.2%), Duromedics bileaflet (16.4%) and a variety of other mechanical and bioprosthetic valves (6.6%). Over the 15 year period there were a total of 82 (7%) valve failures of which PPL was diagnosed in 29 (2.5%) valves in 24 patients. Presenting features included cardiac decompensation in 72%, bacterial endocarditis in 12% and haemolytic anaemia in 12%. One patient (4%) had no symptoms. Nineteen patients underwent re-operation. Median time to re-operation was 15 months (range 1-65 months) with a re-operative mortality of 22%. Clinical evidence of prosthetic valve infection was found in 79% of MVR and 67% of AVR. A heavily calcified aortic annulus, found in 47% of patients, may also have contributed to PPL after AVR.

143 citations


Journal ArticleDOI
TL;DR: The identity of LAD and CBDC antigens are confirmed to be the same and to differ from previously described basement membrane proteins.
Abstract: Disease-associated autoantibodies to basement membrane proteins have been used to characterize structural components of the epidermal basement membrane such as bullous pemphigoid (BP) antigen and epidermolysis bullosa acquisita (EBA) antigen (type VII collagen). The autoimmune bullous diseases characterized by IgA autoantibodies to the basement membrane zone (BMZ), i.e. linear IgA disease of adults (LAD) and chronic bullous disease of childhood (CBDC) may have circulating antibodies. Previous studies of tissue distribution and ultrastructural binding have suggested that the LAD and CBDC antigens are similar, if not identical, and differ from the target antigens of the other bullous diseases. We present the molecular characterization of the LAD/CBDC antigens by Western blotting of a large series of antisera. Seven of 33 sera (21%) were positive on immunoblotting and bound to the same antigen which has a molecular weight (MW) of 285 kDa. Using both defined polyclonal antisera to BP and LH 7.2 monoclonal antibody to type VII collagen (carboxy terminal) we have shown that the LAD and CBDC antisera both bind to an identical molecular weight protein which clearly differs from both the BP and EBA (type VII collagen) antigens. Although detectable in dermal tissue extracts like EBA, the MW of 285 kDa is heavier than type VII collagen (250 kDa, in our system, using non-collagenous standards). This study confirms the identity of LAD and CBDC antigens to be the same and to differ from previously described basement membrane proteins.

Journal ArticleDOI
TL;DR: Thoracoscopic debridement and irrigation used routinely as a first-line measure in empyema thoracis is a safe and relatively atraumatic procedure, does not exclude the use of any subsequent surgical measure, and provides valuable time to improve the condition of debilitated patients so that they may tolerate more aggressive surgical procedures.

Journal ArticleDOI
01 Nov 1991-Lupus
TL;DR: Valvular heart disease, particularly affecting the mitral and aortic valves, is common in patients with the 'primary' antiphospholipid syndrome, especially in those over 40 years old.
Abstract: A prospective echocardiographic study was carried out on 55 patients with the recently described 'primary' antiphospholipid syndrome derived from three university medical centres. The prevalence of valvular lesions in patients with this syndrome was 38% compared with 4% in a control group of 55 healthy volunteers (P < 0.001). Mean age of patients with valve was 42 ± 12 years and of those without, 30 ± 10 years (P < 0.05). One patient had a morphologic echocardiographic pattern suggestive of non-infective verrucous mitral endocarditis. Twenty patients had a two-dimensional or Doppler echocardiographic pattern of significant valvular dysfunction —either regurgitation or stenosis—without evidence of vegetations. Mitral and aortic regurgitation were the most common lesions in these patients. During follow-up of patients with valvular disease, haemodynamically significant clinical valve disease developed in four and surgery was required in one. Eleven patients had cerebrovascular occlusions. Thus, valvular hea...

Journal ArticleDOI
TL;DR: Individual cases were associated with congenital lymphoedema, Klippel‐Trenaunay syndrome and early‐onset varicose veins, and showed a predilection for the extremities.
Abstract: Spindle cell haemangioendothelioma is an uncommon vascular lesion, of which 35 cases have been previously reported. A further 20 cases are reported herein. These lesions affected a wide age range in both sexes, and showed a predilection for the extremities. Twelve patients had multiple lesions and, in these cases, local progression over many years but no true recurrence was typical. None of the 20 patients developed metastases, but one later developed an angiosarcoma. Individual cases were associated with congenital lymphoedema. Klippel-Trenaunay syndrome and early-onset varicose veins. Histologically, in addition to the admixture of cavernous spaces and solid spindle cell/epithelioid cell areas, the presence both of irregularly distributed and perivascular smooth muscle cells and of malformed variably-sized vessels at the periphery of almost every lesion was noted in each case. Reticulin staining, immunohistochemistry and electronmicroscopy revealed the presence of primitive vessel formation and partial endothelial differentiation in the solid spindle cell areas. Combining these data with those from previously published series, it is suggested that spindle cell haemangioendothelioma is a non-neoplastic lesion (rather than a borderline malignancy as it is currently regarded) and that its development correlates with histological and/or clinical evidence of a malformed vasculature at the affected site.

Journal ArticleDOI
TL;DR: In physiological Ca2+, using K+-filled pipettes, NP was found to induce spontaneous bursts of outward currents, which are probably activated by the release of Ca2+ from Ca2-overloaded stores.
Abstract: Using the patch-clamp technique, we have characterised the inward current from enzymatically dispersed rabbit pulmonary arterial cells, and investigated the effects of the vasodilator, nitroprusside (NP), on these and other membrane currents. With Cs+-filled pipettes, inward currents were recorded during brief depolarizing voltage steps in both physiological Ca2+ and 10 mM Ba2+. The threshold for current activation was positive to -40 mV and the current peaked at 0 mV for Ca2+ and +10mV for Ba2+. During the first few minutes of recording, inward currents increased or “ran-up”. This could not be attributed to blockade of outward current or the inclusion of adenosine triphosphate (ATP) in the patch pipette. Experiments revealed that all the inward current was carried through a single type of voltage-activated Ca2+ channel, namely the high-threshold, dihydropyridine-sensitive channel. It was unaffected by tetrodotoxin but was abolished at all potentials by low concentrations of Cd2+ (100 μM) or nifedipine (1–2μM). NP (1 μM) suppressed peak inward Ba2+ current at +10 mV by approximately 45%. Higher concentrations (50 μM) did not produce further blockade of the current. This decrease was associated with increased inactivation of the current, and both effects required the presence of ATP in the patch pipette. In physiological Ca2+, using K+-filled pipettes, NP was found to induce spontaneous bursts of outward currents, which are probably activated by the release of Ca2+ from Ca2+-overloaded stores. These results are consistent with NP lowering cytosolic Ca2+, and hence causing vasodilation, by inhibiting Ca2+ influx through voltage-gated Ca2+ channels and by promoting Ca2+ uptake into the sarcoplasmic reticulum.

Journal ArticleDOI
TL;DR: The spectrum of CNS manifestations present in systemic lupus erythematosus, their diagnosis and pathogenesis, as well as an approach to their treatment and prognostic implications are reviewed.
Abstract: Management of central nervous system (CNS) involvement is one of the most challenging problems in systemic lupus erythematosus. This article reviews the spectrum of CNS manifestations present in this disease, their diagnosis and pathogenesis, as well as an approach to their treatment and prognostic implications.

Journal ArticleDOI
01 Mar 1991

Journal ArticleDOI
TL;DR: It is considered that PRK is an effective form of refractive surgery and the marginal loss of corneal transparency should only be a problem during the first three or four months postoperatively.
Abstract: Postoperative changes in corneal transparency is a major concern after PRK. Data were obtained from 69 human eyes treated with excimer laser photorefractive keratectomy in order to evaluate a relationship between objective measurements of corneal transparency and visual performance. A CCD-camera device was employed and by using polarizing filters the system could discriminate between reflected and scattered light. We observed two groups of postoperative behaviour in corneal transparency. Each group showed an increase in both scattered and reflected light signals with a maximum at around two months postoperatively. In the majority group (70%) this was followed by a subsequent decline of the scattered light signal, whereas the combined signal generated by reflected and scattered light showed a biphasic curve with a second peak at around 4 to 5 months postoperatively. In the minority patient group (30%) the timebase variations in pattern of both signals were indistinguishable throughout the period of observation. In all patients we observed a good correlation between the signal generated by scattered light alone and the reduction in the 5% contrast visual acuity performance, whereas correlation was poor when the combined signal of reflected and scattered light was considered. These disturbances in low contrast visual performance were only significant during the first three to four months postoperatively and thereafter most patients returned to their preoperative value. Eighteen percent of our patients discontinued topical steroids postoperatively. No differences in either corneal transparency or final refraction was observed. We consider that PRK is an effective form of refractive surgery and the marginal loss of corneal transparency should only be a problem during the first three or four months postoperatively.

Journal ArticleDOI
TL;DR: Nineteen patients out of 250 subjects with antiphospholipid antibodies, who had initially presented to the lupus clinic at St Thomas's Hospital, London five or more years ago with a history of venous/arterial occlusions, were entered into the study.
Abstract: Nineteen patients out of 250 subjects with antiphospholipid antibodies, who had initially presented to the lupus clinic at St Thomas's Hospital, London five or more years ago with a history of venous/arterial occlusions, were entered into the study. The patients were divided into two main groups: I those who remained well without any further thromboembolic complications (n = 10); II those who developed recurrent thrombotic events in the five year period (n = 9). The patients were followed up to determine the relation between the level or the isotype of the anticardiolipin antibodies, or both, to the recurrent thromboembolic events, and the effect of a variety of treatments (corticosteroids, immunosuppression, anticoagulation) in the prevention of further vascular occlusions. Lupus activity over the five year period varied considerably between the two groups--those in group I tending to be relatively inactive compared with those in group II. For some patients in group II thromboembolic events seemed to occur at the time of lupus activity. Antiphospholipid antibodies remained positive in all patients, the levels remaining fairly constant. Levels fell in only one patient in group I and in two in group II. Patients in group II had more systemic lupus erythematosus related disease than those in group I; most were receiving concomitant steroid and immunosuppressive therapy, but this did not seem to protect against the development of further occlusions. All patients were given anticoagulation treatment (warfarin/heparin) or salicylates (low dose aspirin 75 mg daily), or both. Patients with deep vein thromboses developed more complications during anticoagulation therapy than those with cerebrovascular symptoms. Problems in anticoagulation control and recurrent thromboses consequent on warfarin withdrawal despite the administration of subcutaneous heparin were responsible for complications in most patients in group II.

Book ChapterDOI
01 Jan 1991
TL;DR: A differential equation model of carbohydrate metabolism was implemented in the form of a causal probabilistic network that permitted explicit represen-tations of the uncertainties associated with model based predictions of 24-hour blood glucose profiles.
Abstract: A differential equation model of carbohydrate metabolism was implemented in the form of a causal probabilistic network. This permitted explicit represen-tations of the uncertainties associated with model based predictions of 24-hour blood glucose profiles. In addition, the implementation gave automatic learning and adjustment of model parameters based on measured blood glucose profiles. Insulin therapy was adjusted using a decision theoretical approach. Losses were assigned to blood glucose values that deviated from normal, and the insulin therapy was adjusted to minimize the expected total loss. The system was tested retrospectively on cases from 12 insulin dependent patients and seemed to compare favourably with clinical practice.

Journal ArticleDOI
TL;DR: The peripheral branches of primary afferents have the capacity to regenerate successfully over long distances, and the possibility that when they do so, the neurones' status changes to facilitate greatly the sprouting of afferent fibres within the dorsal horn is examined.
Abstract: We have studied the ability of primary afferent neurones to proliferate within the grey matter of the dorsal horn following the degeneration of other, nearby, afferent fibres. The peripheral branches of primary afferents have the capacity to regenerate successfully over long distances, and we have examined the possibility that when they are so doing, the neurones' status changes to facilitate greatly the sprouting of afferent fibres within the dorsal horn. “Spared root” preparations (rhizotomies of L3, L4, L6, S1, and the caudal half of L5, sparing the rostral half of the L5 dorsal root) were made in adult rats. In some animals (acute preparations) the distribution of the central terminals of the spared root was assessed by labelling the sciatic nerve with WGA-HRP at the time of the rhizotomies. In other animals (chronic preparations, symmetrical bilateral spared roots were made and the sciatic nerve on one side was concomitantly crushed to trigger regrowth of the peripheral branches of these axons. Eight to 10 weeks later the sciatic nerves on both sides were labelled with HRP-WGA. In the acute preparations the reaction product was found in a limited rostrocaudal and mediolateral region of the dorsal horn. In lamina II (the lamina of densest labelling the labelled terminals occupied an average of 1.17 ± 0.21 mm2. In chronic preparations, the area of labelled terminals on the side of the uncrushed sciatic nerve was 1.34 ± 0.28 mm2 (not significantly different from acute animals). However, the labelled area on the side of the crushed sciatic nerve was significantly greater, averaging 2.17 ± 0.14 mm2. Hence, primary afferent nerve fibres show greatly enhanced sprouting within the grey matter of the dorsal horn of the spinal cord when two conditions are fulfilled; 1) vacant synaptic sites are created by the degeneration of other primary afferent fibres; and 2) the peripheral branches of the axons are actively regenerating.

Journal Article
TL;DR: Larger studies are now needed to confirm a role for selective zinc supplementation in at-risk pregnancies, and most measured indices of labour and fetal health were better in the supplemented group.
Abstract: A double-blind randomised trial of oral zinc supplementation was carried out during the last two trimesters of pregnancy. Fifty-six women at risk of delivering a small-for-gestational-age baby received either zinc supplement (22.5 mg daily) or placebo. Twenty-nine of the women were compliant. Zinc significantly reduced the incidence of intrauterine growth retardation, and most measured indices of labour and fetal health were better in the supplemented group. Larger studies are now needed to confirm a role for selective zinc supplementation in at-risk pregnancies.

Journal ArticleDOI
TL;DR: It is concluded that orf and milkers' nodule infection have distinctive histopathologic features, and, in contrast to some previous reports, viral changes may frequently be found.
Abstract: We report the clinical and histopathologic features of 17 patients with orf or milkers' nodule infection. The majority were male, 12 to 65 years of age, and gave a history of contact with farm animals. Most lesions affected the hands or arms, ranged in size from 1 to 3 cm, and occurred on average 3 weeks after presumed exposure. On low-power examination the epidermis showed endophytic strandlike proliferations and the dermal papillae were distended by intense edema. There was massive capillary proliferation and dilation and a dense inflammatory infiltrate. High-power examination revealed epidermal viral cytopathic changes with inclusion bodies, clumping of keratohyalin, and cytoplasmic vacuolation that had a distinctive "spongiform" appearance within follicular structures. We conclude that orf and milkers' nodule infection have distinctive histopathologic features, and, in contrast to some previous reports, viral changes may frequently be found.

Journal ArticleDOI
01 Oct 1991-Cancer
TL;DR: Results indicate that in mycosis fungoides (MF) T‐cell clones can be detected in skin biopsy specimens from the majority of patients with early stage disease, γδ T-cell clones are only rarely found, and TCR gene analysis can detect T‐ cell clones in the peripheral blood with a greater degree of specificity than conventional light microscopic study.
Abstract: The authors have analyzed the configuration of immunoglobulin (Ig) and beta, gamma and delta T-cell receptor (TCR) genes in DNA extracted from skin, lymph nodes, and peripheral blood mononuclear cells obtained from 41 patients with mycosis fungoides (MF), 14 patients with Sezary syndrome, and 13 patients with benign inflammatory dermatoses. No discrete rearranged bands (DRB) were detected in patients with inflammatory dermatoses. In tissue DNA from 19 patients with MF DRB were detected with beta and gamma, but not delta TCR probes. Only one patient with MF had a rearrangement of gamma and delta with germ line beta TCR genes. In 13 patients multiple biopsies were analyzed and DRB, when present, were identical in different lesions from individual patients. In three patients analysis of DNA from dermatopathic lymph nodes did not reveal DRB. Analysis of peripheral blood DNA from 24 patients revealed a discrete rearrangement of the gamma TCR gene in four patients and both beta and gamma genes in four additional patients. In MF DRB were detected more frequently with advancing stage of disease in tissues (P less than 0.01) but not in peripheral blood (P equals 0.36). Of 14 patients with Sezary syndrome, eight had DRB in peripheral blood DNA with both beta and gamma probes and in three of these patients identical DRB were also detected in DNA from skin biopsy samples. In contrast, DRB were not detected in the peripheral blood of the other six patients. In both MF and Sezary syndrome there was no restricted usage of particular V gamma genes. These results indicate that in MF (1) T-cell clones can be detected in skin biopsy specimens from the majority of patients with early stage disease, (2) gamma delta T-cell clones are only rarely found, and (3) TCR gene analysis can detect T-cell clones in the peripheral blood with a greater degree of specificity than conventional light microscopic study. In Sezary syndrome these studies also suggest that a subset of patients have a polyclonal population of circulating atypical lymphoid cells. In addition these patients appear to have a better prognosis than those with monoclonal disease.

Journal ArticleDOI
TL;DR: In some chronic pain states, notably causalgia and reflex sympathetic dystrophy, activity in sympathetic efferent neurones can exacerbate the pain and sympathectomies relieve it, and several specific hypotheses have been advanced as to the primary pathophysiological cause of pain in these patients.
Abstract: In some chronic pain states, notably causalgia and reflex sympathetic dystrophy, activity in sympathetic efferent neurones can exacerbate the pain and sympathectomies relieve it. These patients are said to have sympathetically maintained pain (SMP). In normal tissue, activity in postganglionic sympathetic efferents does not produce pain, nor is it capable of activating nociceptive sensory neurones. It can, however, induce modest firing in some mechanoreceptors. SMP is often held to result from a vicious circle of events which include changes in peripheral and central somatosensory processes, and most importantly a positive feedback element in the form of sympathetic efferent neurones which, by activating sensory neurones in the periphery, completes the vicious circle. Several specific hypotheses have been advanced as to the primary pathophysiological cause of pain in these patients. Suggestions, largely deriving from observations on animal models, include: ephaptic transmission, adrenergic receptors on sensory neurones, indirect coupling of sympathetic and sensory neurones, sensitization of nociceptive afferents, and, in the central nervous system, sensitization of dorsal horn neurones. All these suggestions have some supporting evidence, but none are able to adequately explain all the disturbances seen in patients with SMP.

Journal ArticleDOI
TL;DR: In this paper, the authors developed a systematic study of the parthenogenetic activation and early development of human oocytes and found that fresh and aged oocytes can be activated using a calcium ionophore but at lower rates than seen for mouse oocytes.

Journal ArticleDOI
TL;DR: It will be seen that the development of a six fraction regime, given over a period of three weeks leads to comparable results to other reported series, whether assessed as a local response or by survival curves, and to the economical use of scarce resources.

Book ChapterDOI
TL;DR: It is still difficult to explain adequately the reduced inotropic state that characterizes stunning; however, it seems likely that the calicum overload is transient and that the stunned myocardium rapidly reestablishes normal levels of intracellular calcium.
Abstract: The recovery from trauma, whether ischemia or some other form of tissue injury, is never instantaneous; time is always required for repair and the return of normal metabolism and function. To what extent the delay in recovery of contractile activity (stunning) after a brief period of ischemia represents convalescence from ischemia-induced injury, as opposed to the expression of reperfusion-induced injury, is perhaps not as clear as the proponents of stunning would hope. Definitive evidence for a distinct reperfusion-induced pathology, which compromises the recovery of contractile function from the depressed state induced by ischemia, is elusive. If reperfusion-induced injury accounts for a significant proportion of stunning, then the molecular mechanisms responsible for initiating the event and those responsible for orchestrating the event at the level of the contractile protein are far from clear. Perturbations of calcium homeostasis are frequently cited as responsible for the depressed contractile state, however, some metabolic derangement must precede any pathologically induced ionic disturbance. In this connection, evidence indicates that free-radical-induced oxidant stress, during the early moments of reperfusion, may modify the activity of a number of thiol-regulated proteins that are directly, or indirectly, responsible for controlling the movement of calcium. Sarcolemmal sodium-calcium exchange and the calcium release channel of the sarcoplasmic reticulum may be activated, whereas the sarcolemmal calcium pump and sodium-potassium ATPase, together with the calcium pump of the sarcoplasmic reticulum, may be inhibited. Under the conditions prevailing during ischemia and reperfusion, this would be expected to promote an early intracellular calcium overload. It is difficult to reconcile such a change with the decreased inotropic state that characterizes stunning; however, it seems likely that the calicum overload is transient and that the stunned myocardium rapidly reestablishes normal levels of intracellular calcium. It is still difficult to explain adequately the reduced inotropic state; clearly, the mechanism of stunning is not quite as simple as its definition.

Journal ArticleDOI
TL;DR: Results suggest that chlorhexidine appears to be as effective as a hand-washing agent for MRSA isolates with or with out NAB plasmids as it is for MSSA isolate.
Abstract: Chlorhexidine (Hibiscrub; ICI) is generally accepted to be effective as an antiseptic hand wash for methicillin-susceptible Staphylococcus aureus (MSSA), but there is dispute whether the chlorhexidine MIC for methicillin-resistant S. aureus (MRSA) strains is higher than that for MSSA strains and, indeed, whether it is relevant. In addition, the link between resistance to chlorhexidine, gentamicin, and "nucleic acid-binding" compounds (NAB; which code, in particular, for propamidine isethionate and ethidium bromide) requires clarification. We performed chlorhexidine MIC and rate of kill tests on a number of MSSA and MRSA isolates. Two gentamicin-resistant MRSA isolates without NAB plasmids were more susceptible (0.25 and 0.5 microgram/ml) than four of eight MSSA that we tested (range, 0.25 to 2 microgram/ml). Chlorhexidine MICs were higher (4 to 8 micrograms/ml) for seven distinct MRSA isolates with plasmids conveying resistance to gentamicin and NAB (GNAB). Curing of the GNAB plasmid from MRSA strains resulted in a fall in the MIC (1 to 3.3 micrograms/ml), but no consistent fall in killing by chlorhexidine was observed. No effect on the chlorhexidine MIC or killing was observed when we cured strains of methicillin resistance. GNAB plasmid transfer resulted in a rise in the chlorhexidine MIC for the strains but not consistent fall in killing by chlorhexidine. Ethical approval was granted for 10 volunteers to each have a methicillin-susceptible, GNAB-resistant, derived transcipient and its GNAB-susceptible isogenic parent applied to separate sites in an in vivo skin test; no significant difference was seen in survival rates after the application of chlorhexidine. These results suggest that chlorhexidine appears to be as effective as a hand-washing agent for MRSA isolates with or with out NAB plasmids as it is for MSSA isolates.

Journal ArticleDOI
TL;DR: Using both spinal and extradural anaesthesia with a 26-gauge, long spinal needle through a 16- gauge Tuohy needle for elective Caesarean section is recommended because it allows rapid onset of anaesthesia and the advantages of an extradural catheter.
Abstract: We have used both spinal and extradural anaesthesia with a 26-gauge, long spinal needle through a 16-gauge Tuohy needle for elective Caesarean section. Four different subarachnoid solutions of bupivacaine were compared: 0.5% heavy bupivacaine alone, or with adrenaline, fentanyl or adrenaline and fentanyl. The incidence of complications and time of regression of the sensory block were analysed. The technique is recommended because it allows rapid onset of anaesthesia and the advantages of an extradural catheter. The subarachnoid solution of choice was 0.5% heavy bupivacaine 12.5 mg with fentanyl 10 μg