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Biomedical subjects

S George

Publications and source records attributed to S George.

At least 109 records · Page 6Linked to original sources
PubMed1999

Erythrokeratoderma en cocardes.

The erythrokeratodermas are a distinct but clinically variable group of rare geno-dermatoses, characterized by circumscribed erythematous and hyperkeratotic lesions. All attempts to establish a valid classification have been based on purely clinical and morphologic criteria. Erythrokeratoderma en cocardes, also known as genodermatose en cocardes or Degos' syndrome, was first described by Degos in 1947. The condition is characterized by large round plaques with concentric erythema and scaling having a target configuration, which remit and recur, in addition to scaly plaques as seen in erythrokeratoderma variabilis. A case of this rare genodermatosis is described.

Adult↗
PubMed1999

Etomidate dose-response on somatosensory and transcranial magnetic induced spinal motor evoked potentials in primates.

There is growing interest and need to monitor reliably both motor (MEP) and somatosensory (SEP) evoked potentials under anesthesia. On a pre-established primate model, the present study examined the effect of incremental etomidate (ET) dosages on spinal neural MEPs to transcranial magnetic stimulation (TMS) and posterior tibial rate (PTN) SEPs. Through a small thoracic T11-T12 laminotomy, an insulated double bipolar electrode was inserted epidurally in seven cynomolgus monkeys. Spinal TMS-MEPs, PTN-SEPs, and frontal EEG were tested against graded increase of ET doses. Etomidate 0.5 mg kg-1 i.v. was initially given and followed by 30 min continuous infusion of 0.01 mg kg-1 min-1, 0.018, 0.032, 0.056, 0.1, and 0.18 mg kg-1 min-1 in that order. Measurable spinal MEPs and SEPs were recorded under deep ET anesthesia (total 12.38 mg kg-1 cumulative dose over 180 min). The EEG showed marked slow wave and graded burst suppression at cumulative dose of > or = 3.14 mg kg-1. The direct (D) and subsequent initial indirect (I) waves (I1, I2, I3) were reproducible at doses < 0.18 mg kg-1 min-1 infusion. The latter I-waves (I4 and I5) showed graded loss at infusion dosage 0.056 mg kg-1 min-1. Etomidate remains an anesthetic of attractive features in neuroanesthesia. In the primate model, neural MEPs-SEPs were reproducible despite the exceedingly high dose of ET and markedly depressed EEG. Moreover, MEP-SEP can be monitored during ET burst-suppressive neuroprotective state. The study may set a model in humans for intra-operative multi-modality neurophysiologic recording under ET-based anesthesia.

Animals↗
PubMed1999

Clinical and pathologic predictors of survival in patients with thymoma.

OBJECTIVE: To evaluate the Johns Hopkins Hospital experience with 136 thymomas over the past 40 years. This number of patients allowed quantitative estimation of the independent influence of common clinicopathologic risk factors using multivariate analysis. SUMMARY BACKGROUND DATA: Thymomas vary widely in terms of recurrence and influence on overall survival. Several series have indicated the importance of initial tumor invasion, as well as the extent of surgical resection, as predictors of recurrence and survival after thymoma resection. However, findings have been equivocal when other predictors of prognosis were examined. METHODS: The authors evaluated 136 patients seen at the Johns Hopkins Hospital between 1957 and 1997 with a pathologic diagnosis of thymoma. Demographic information, clinical staging data, surgical and adjuvant treatment details, and patient follow-up data were obtained from the patient record and from detailed patient or family interviews. Microscopic sections of all 136 patients were reviewed by two pathologists blinded to the clinical data. All data were analyzed by multivariate Cox regression analysis, which allowed the quantification of the independent predictive value of 12 putative clinicopathologic prognostic indicators. RESULTS: Completeness of follow-up was 99%, 99%, and 98% of eligible patients at 5, 10, and 15 years, respectively. Forty percent of the patients had associated myasthenia gravis and 27% had a secondary primary malignancy. Overall patient survival rates were 71%, 56%, 44%, 38%, and 33% at 5, 10, 15, 20, and 25 years, respectively. Overall, the thymoma-related mortality rate was 14%; the nonthymoma-related mortality rate was 26%. Incomplete resection, preoperative absence of myasthenia gravis, and advanced Lattes/Bernatz pathologic class were found to be independent predictors of poorer overall survival. CONCLUSIONS: These findings support a policy of aggressive, complete surgical resection of all thymomas when feasible. Thymoma behaves as a rather indolent tumor, with most deaths from causes unrelated to thymoma or its direct treatment. Clinicians should have an increased awareness of the possibility of second primary malignancies in patients with thymoma.

Adolescent↗
PubMed1999

Regulation of gelatinases in human airway smooth muscle cells: mechanism of progelatinase A activation.

Matrix metalloproteinases (MMPs) play an important role in tumor metastasis and invasion, inflammatory tissue destruction and remodeling, wound healing, and angiogenesis. The 72-kDa gelatinase A is the most widely distributed of all the MMPs, and along with the 92-kDa gelatinase B, both play an important role in the turnover of basement membrane. The role of MMPs in chronic airway inflammation and remodeling has received scant attention. In this study, we sought to examine the release and activation of gelatinases from human airway smooth muscle (ASM) cells and the effect of tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate (PMA) on this release and activation. The role of membrane type 1 MMP (MT1-MMP) and tissue inhibitor of MMP (TIMP)-2 in activating progelatinase A has been explored. We have demonstrated, using human airway smooth muscle cells in culture, that 1) ASM releases gelatinase A constitutively and when stimulated with PMA and tumor necrosis factor-alpha releases gelatinase B, and the release of gelatinase B is protein kinase C dependent because it is blocked by H-7 and staurosporin; 2) treatment of ASM cells with PMA or concanavalin A failed to activate progelatinase A despite these agents increasing cell expression of MT1-MMP; and 3) the inability of ASM cell membranes to activate progelatinase A is most likely secondary to the high levels of TIMP-2 on the cell membrane. In conclusion, our results demonstrate that human ASM cells constitutively secrete progelatinase A and when stimulated with proinflammatory mediators secrete gelatinase B. The released gelatinases A and B may be important factors in the airway remodeling that occurs in asthma.

Cell Membrane↗
PubMed1999

Generic health status measures are unsuitable for measuring health status in severely disabled people.

OBJECTIVES: To assess the perceived health status of disabled people. DESIGN: Perceived health status was evaluated with the Short Form 36 Health Survey (SF-36) and the Nottingham Health Profile as part of a needs assessment project exploring systematic differences in unmet needs for rehabilitation as perceived by disabled people, carers and professional staff. Disabled participants completed these health status questionnaires, as part of a face-to-face interview in participants' own homes. SUBJECTS: Ninety-two disabled people aged 16-65, recruited into the study from two disability registers. OUTCOME MEASURES: The Office of Population Censuses and Surveys (OPCS) Disability Severity Scale, Nottingham Health Profile, SF-36. RESULTS: Ninety-six disabled people took part in this study. Four were later excluded because of overwhelming communication difficulties. Median OPCS category was 8 (interquartile range 6-9.75). The pain and physical mobility domains of the Nottingham Health Profile were not completed by 46/92 participants (50%) because many questions referred to activities that these people could not perform, particularly walking. The physical functioning domain of the SF-36 showed severe floor effects. It was not therefore possible to use these measures to test the effectiveness of services provided to disabled people, particularly in the areas of physical functioning and pain. CONCLUSIONS: There is a continued need to develop and test instruments that can measure the outcomes of rehabilitation in severely disabled populations.

Adolescent↗
PubMed1999

Role of S-100 staining in differentiating leprosy from other granulomatous diseases of the skin.

Since Mycobacterium leprae are rarely demonstrable in the tuberculoid spectrum of leprosy, a confirmatory diagnosis of leprosy can be made on the basis of finding active destruction of cutaneous nerves by granulomatous inflammation in a skin biopsy. Immunoperoxidase staining for S-100 protein, which is a marker for Schwann cells, was used to delineate nerves in lesional skin biopsies of 25 patients with tuberculoid and borderline tuberculoid leprosy as well as 15 controls with nonleprous granulomatous inflammation. Four different patterns of nerve damage were observed: infiltrated, fragmented, absent, and intact. All of the nonleprous granulomatous dermatoses showed only intact nerves, either inside or outside the granuloma, and so S-100 staining can be used to rule out leprosy.

Diagnosis, Differential↗
PubMed1999

Teledermatology--UK experience of setting up an integrated teledermatology service.

Telemedicine has traditionally been seen as an all or nothing solution to the problem of providing medical service to remote communities. In the UK, however, the majority of the population lives within easy travelling distance of medical service, and it is inappropriate to apply telemedicine for the same reasons and in the same way. We describe an alternative approach, where telemedicine is used to complement the existing clinical infrastructure of the outreach clinic and hospital visit, and the patient may opt to have any follow up appointments by video conference. We also describe the concept of the virtual consultation that we have developed to support our work.

Dermatology↗
PubMed1998

Safety and effectiveness of nurse telephone consultation in out of hours primary care: randomised controlled trial. The South Wiltshire Out of Hours Project (SWOOP) Group.

OBJECTIVE: To determine the safety and effectiveness of nurse telephone consultation in out of hours primary care by investigating adverse events and the management of calls. DESIGN: Block randomised controlled trial over a year of 156 matched pairs of days and weekends in 26 blocks. One of each matched pair was randomised to receive the intervention. SETTING: One 55 member general practice cooperative serving 97 000 registered patients in Wiltshire. SUBJECTS: All patients contacting the out of hours service or about whom contact was made during specified times over the trial year. INTERVENTION: A nurse telephone consultation service integrated within a general practice cooperative. The out of hours period was 615 pm to 1115 pm from Monday to Friday, 1100 am to 1115 pm on Saturday, and 800 am to 1115 pm on Sunday. Experienced and specially trained nurses received, assessed, and managed calls from patients or their carers. Management options included telephone advice; referral to the general practitioner on duty (for telephone advice, an appointment at a primary care centre, or a home visit); referral to the emergency service or advice to attend accident and emergency. Calls were managed with the help of decision support software. MAIN OUTCOME MEASURES: Deaths within seven days of a contact with the out of hours service; emergency hospital admissions within 24 hours and within three days of contact; attendance at accident and emergency within three days of a contact; number and management of calls in each arm of the trial. RESULTS: 14 492 calls were received during the specified times in the trial year (7308 in the control arm and 7184 in the intervention arm) concerning 10 134 patients (10.4% of the registered population). There were no substantial differences in the age and sex of patients in the intervention and control groups, though male patients were underrepresented overall. Reasons for calling the service were consistent with previous studies. Nurses managed 49.8% of calls during intervention periods without referral to a general practitioner. A 69% reduction in telephone advice from a general practitioner, together with a 38% reduction in patient attendance at primary care centres and a 23% reduction in home visits was observed during intervention periods. Statistical equivalence was observed in the number of deaths within seven days, in the number of emergency hospital admissions, and in the number of attendances at accident and emergency departments. Conclusions Nurse telephone consultation produced substantial changes in call management, reducing overall workload of general practitioners by 50% while allowing callers faster access to health information and advice. It was not associated with an increase in the number of adverse events. This model of out of hours primary care is safe and effective.

Adolescent↗
PubMed1998

Opiate concentrations following the ingestion of poppy seed products--evidence for 'the poppy seed defence'.

The universally accepted 300 ng/ml cut-off limit for opiate assays stated to be mandatory for all drug screening laboratories by the Substance Abuse and Mental Health Services Administration, has been questioned recently due to positive results being obtained following the ingestion of poppy seed containing food products. To establish the plausibility of the 'the poppy seed defence' the concentrations of codeine, norcodeine, morphine, normorphine and thebaine (a potential marker for seed ingestion) in several varieties of poppy seeds from different countries were quantified by GC-MS. The country of origin of the seed specimen analysed and the preparation of the seeds prior to their culinary use was found to influence the alkaloid concentration determined. The maximum morphine and codeine concentrations determined in the seeds were found to be 33.2 and 13.7 micrograms/g seed respectively. In addition, thebaine concentrations were found to vary with each seed sample analysed. Following the consumption of bread rolls (mean 0.76 g seed covering per roll) by four subjects, all urine specimens analysed produced negative results (using the Dade Bebring EMIT II opiate screening assay) with the exception of one subject (body weight 63.0 kg) who consumed two poppy seed rolls. In this subject opiate positive screening results were obtained for up to 6 h post ingestion with maximum urinary morphine and codeine concentrations of 832.0 ng/ml (@ 2-4 h post ingestion) and 47.9 ng/ml (@ 0-2 h post ingestion) respectively being achieved. Following the ingestion of poppy seed cake containing an average of 4.69 g of seed per slice by four individuals, opiate positive screening results were obtained for up to 24 h. In one subject (dose equivalent to 0.07 g poppy seed/kg body weight) maximum urinary morphine and codeine concentrations of 302.1 ng/ml (@ 0-2 h) and 83.8 ng/ml (@ 2-4 h) respectively were recorded. The elimination of thebaine was found to vary widely between individuals, therefore suggesting that its absence from a specimen is not necessarily indicative of opiate abuse. These findings demonstrate that the poppy seed defence could be used as an argument in medico-legal and employment medical cases. Great care should therefore be taken when interpreting the data produced when screening for opiates.

Administration, Oral↗
PubMed1998

An epidemiological needs assessment of carotid endarterectomy in an English health region. Is the need being met?

OBJECTIVE: To compare the level of provision of carotid endarterectomy (an intervention of proved efficacy for prevention of stroke in patients with symptomatic high grade carotid artery stenosis) with estimates of need. DESIGN: Comparison of regional, district, and age-sex specific operation rates derived from hospital episode statistics with estimates of need based on demographic and epidemiological data; interviews with regional vascular surgeons and a joint provider-purchaser workshop to discuss implications. SETTING: Former Wessex Regional Health Authority, 1991-2 to 1995-6. SUBJECTS: All residents covered by Wessex region treated for carotid artery reconstruction. MAIN OUTCOME MEASURES: Regional, district, and age-sex operation rates as three year average 1993-6 (use) compared with respective estimates of need for carotid endarterectomy among those who presented with symptomatic carotid disease-transient ischaemic attack or minor stroke. RESULTS: The operation rate more than doubled between 1991-2 and 1995-6, from 35 to 89 per million population, compared with an estimated level of need in the region's general population of 153 per million population (transient ischaemic attack 77, minor stroke 76). The ratio of use to need was 0.47 (95% confidence interval 0.4 to 0.54); district ratios were 0.28 (0.19-0.38) to 0.81 (0.62 to 1.06). The annual use:need ratio rose over the three years 1993-6 from 0.38 to 0.59. Use:need ratios were lower in elderly and female patients. Providers were keen to develop guidelines for referral and to increase access to diagnostic facilities; purchasers were more reluctant, given the limited impact of this intervention on the incidence of stroke and the relatively high cost of the operation. CONCLUSION: Although treatment rates increased in Wessex there is still unmet need. Further research is needed to determine the referral pathways of patients with symptomatic carotid disease for diagnosis and operation and to evaluate strategies to improve access to diagnostic facilities.

Adolescent↗
PubMed1998

Granulocyte colony-stimulating factor administration to HIV-infected subjects augments reduced leukotriene synthesis and anticryptococcal activity in neutrophils.

Neutrophil (PMN) dysfunction occurs in HIV infection. Leukotrienes (LT) are mediators derived from the 5-lipoxygenase (5-LO) pathway that play a role in host defense and are synthesized by PMN. We investigated the synthesis of LT by PMN from HIV-infected subjects. There was a reduction (4.0+/-1.3% of control) in LT synthesis in PMN from HIV-infected compared with normal subjects. This was associated with reduced expression of 5-LO-activating protein (31.2+/-9.6% of normal), but not of 5-LO itself. Since HIV does not directly infect PMN, we considered that these effects were due to reduced release of cytokines, such as granulocyte colony-stimulating factor (G-CSF). We examined the effect of G-CSF treatment (300 microgram daily for 5 d) on eight HIV-infected subjects. PMN were studied in vitro before therapy (day 1) and on days 4 and 7. LTB4 synthesis was increased on day 4 of G-CSF treatment, and returned toward day 1 levels on day 7. 5-LO and 5-LO-activating protein expression were increased in parallel. As a functional correlate to this increase in PMN LT synthesis by G-CSF, we examined the effects on killing of Cryptococcus neoformans. Anticryptococcal activity of PMN from HIV-infected subjects was less than that of PMN from normal subjects. G-CSF treatment improved fungistatic activity of PMN. This increase in antifungal activity was attenuated by in vitro treatment with the LT synthesis inhibitor, MK-886. In conclusion, PMN from HIV-infected subjects demonstrate reduced 5-LO metabolism and antifungal activity in vitro, which was reversed by in vivo G-CSF therapy.

5-Lipoxygenase-Activating Proteins↗
PubMed1998

Effects of Dispersant Treatment on the Acute Aquatic Toxicity of Petroleum Hydrocarbons

The acute effects of both untreated and dispersant-treated Prudhoe Bay crude oil on the early life-stages of three marine species were investigated. Identification of which water-accommodated fraction (undispersed or chemically dispersed) was considered "more toxic" was dependent on species, time, and endpoint (and by inference, test protocol). Generally, the data showed that at roughly equivalent hydrocarbon concentrations untreated oil solutions resulted in higher initial effects (< 1 h) in mysid and topsmelt tests, whereas dispersed oil solutions elicited higher levels of larval abnormality in abalone tests and higher levels of mortality in mysid tests. While differences in test protocols existed among the species tested, topsmelt were the most sensitive species to untreated oil solutions, with mysids being most sensitive to dispersed oil solutions.

Journal Article↗
PubMed1998

Iodine-123 salmon calcitonin, an imaging agent for calcitonin receptors: synthesis, biodistribution, metabolism and dosimetry in humans.

Calcitonin is used to reduce high serum calcium levels in patients with malignancy, and as therapy for osteoporosis and Paget's disease. Receptors for the peptide have been identified in some human cancer cells including those of lung, breast, bone, prostate, and medullary carcinoma of the thyroid, suggesting that an imaging agent for the receptors might be useful in nuclear oncology. A modified chloramine-T method was used to label a pharmaceutical form of salmon calcitonin (SCT) with iodine-123. Labelling can be performed within 5 min including purification, resulting in >95% radiochemical purity and 70% yield. Digestion analysis shows labelling with two iodine atoms on the tyrosine residue. A Chinese hamster ovary cell-based assay showed that the receptor binding and activation were not impaired by the labelling. Biodistribution in mice was similar to that of commercially available mono-iodinated 125I-labelled SCT, kidney being the principal target organ. Evaluation in three patients previously diagnosed as having Paget's disease (injected with 37 MBq [123I]diiodotyrosyl22-SCT, containing less than 4 IU hormone, imaged dynamically up to 0.5 h and at intervals up to 24 h) shows early uptake in liver, kidney and sites of known Paget's disease but not in normal bone, and later uptake in thyroid and stomach. Blood clearance was fitted to a biexponential with half-lives of 3.4-7.4 min and 3-34 h. Radiation dosimetry was estimated using MIRDOSE 3. The highest doses (mean mGy/MBq) were to thyroid (6.8x10(-1)) and kidney (6.0x10(-2)), with a whole-body dose 3.0x10(-2). High performance liquid chromatography analysis revealed that urinary radioactivity was mostly in the form of iodide and diiodotyrosine within minutes of injection, indicating rapid in vivo breakdown. In summary, [123I]diiodotyrosyl22-SCT binds to calcitonin receptors and can image sites of Paget's disease but its imaging potential is not optimal because of rapid breakdown and clearance from target tissues, and an alternative radiolabelling approach is required.

Aged↗
PubMed1998

Venous allografts prepared from stripped long saphenous vein. Is there a need for antibiotic sterilisation?

AIM: Can useful lengths of vein be retrieved from varicose vein stripping procedures; is it necessary to sterilise this tissue prior to use as vein allografts? METHOD: Stripped long saphenous vein was retrieved at operation. Vein samples were cultured using direct plate inoculation and enrichment culture. Further samples were immersed in two low concentration antibiotic solutions and recultured. Smooth muscle viability was assessed after antibiotic immersion and storage by cryopreservation. RESULTS: High quality vein could be retrieved by vein stripping. Vein segments grew skin commensals on enrichment culture despite negative cultures with standard media plate inoculation (Chi-squared = 53.34 1 d.f. p < 0.001). Low concentration antibiotic solutions sterilised processed vein. Smooth muscle cell viability was reduced by cryopreservation, Mann-Whitney p = 0.008 (control 98% S.E. 0.93 vs. cryopreserved 64% S.E. 6.58), but prior exposure to antibiotics did not compound this effect. CONCLUSION: Useful lengths of vein grafts can be retrieved from varicose vein stripping procedures. Venous segments are frequently contaminated by skin commensals. Enrichment culture is required to detect contamination. Low concentration antibiotics sterilise venous-tissue without affecting smooth muscle cell viability.

Anti-Bacterial Agents↗
PubMed1998

Comparison of multiple immunization schedules for Haemophilus influenzae type b-conjugate and tetanus toxoid vaccines following bone marrow transplantation.

Antibody concentrations to vaccine-preventable diseases decline following BMT and an optimal schedule for vaccination after transplant has not been established. We examined antibody responses to tetanus toxoid (TT) and Haemophilus influenzae type b-conjugate (HIB) vaccines of BMT patients immunized at 6, 12 and 24 months (6 month group, n = 21) and compared them to those previously reported for patients immunized at 3, 6, 12 and 24 months (3 month group, n = 74) or at 12 and 24 months (12 month group, n = 17) following transplantation. Geometric mean total anti-HIB and IgG anti-TT concentrations were significantly higher after the 12 month dose in the 3 and 6 month immunization groups compared to the group who received their first dose at 12 months. Although HIB antibody concentrations were higher in the 3 month and 6 month groups 12 to 24 months after BMT, the proportion of patients with protective levels was not significantly different from the proportion protected in the 12 month group. Following the 24 month immunizations, geometric mean antibody concentrations to HIB and TT were similar for all three immunization groups. The proportion of patients in each group with protective levels of HIB antibody after the 24 month dose was > or = 80%. A two dose schedule of HIB and TT vaccines at 12 and 24 months after BMT should afford protection.

Adolescent↗
PubMed1998

The association of HLA-DQ7 with bullous pemphigoid is restricted to men.

This study examines in detail the HLA associations of 74 patients (40 women and 34 men) with bullous pemphigoid (BP) and compares their immunogenetic profile with that of 604 unrelated control subjects (238 women and 366 men). Correlations were sought between HLA antigens and the various BP disease parameters investigated. The presence of milia was the only clinical or laboratory finding which was linked with a specific HLA antigen, HLA-DQ6, in both men and women with BP (P < 0.01). BP has previously been linked with the HLA-DQ7 antigen and this association was confirmed in 39 of our patients (14 women and 25 men). Twelve of these patients (four women and eight men) were homozygous for HLA-DQ7. The association of HLA-DQ7 with BP was gender-restricted and only significant for men (P < 0.01). No equivalent HLA disease susceptibility risk factor could be identified for our female BP patients. This difference in HLA association between men and women with BP has not been reported previously, and its significance for disease pathogenesis is not known. No specific link could be found between HLA-DQ7 and BP for any of the clinical, immunofluorescence, western blotting, treatment or prognostic disease factors studied.

Aged↗