Biomedical subjects
Publications and source records attributed to J Simpson.
Chronic lymphocytic leukemia (CLL) is incurable with conventional therapy. Recent data report favorable results with allogeneic transplant. We report a patient with CLL with persistent leukemia post-transplant who obtained remission after discontinuing immune suppression.
OBJECTIVES: (1) To investigate patients' experience of changes in their blood pressure (BP) in an every day setting and the accuracy of patients' predictions; and (2) to examine what influences patients' belief that they can tell when their BP is up. SUBJECTS: A total of 102 hypertensive patients were recruited sequentially as they presented for routine BP checks. The setting was an inner city general practice. DESIGN: Patients attended for BP checks on a weekly basis. Before each check they were asked whether they thought their BP was higher, lower or the same as usual. Subjects were classified as predictors if they thought they could tell when their BP was up. On completing their series of BP checks each subject completed symptom and Hospital Anxiety and Depression questionnaires. MAIN OUTCOME MEASURES: Accuracy of BP predictions, BP levels and variability, number of symptoms reported and anxiety level. RESULTS: One hundred and two hypertensive patients entered the study of whom 51 patients were predictors. The majority (86%) of predictors could not accurately predict their BP. There were no significant differences in either BP or variability between predictors and non-predictors. Predictors were significantly more anxious and reported more symptoms than non-predictors. CONCLUSIONS: For the majority of predictors there is no significant relationship between predictions of BP and clinical measurements. Predictor status is associated with the reporting of more symptoms and higher levels of anxiety. Doctors should counsel patients against using subjective BP assessments to guide their use of antihypertensive medication.
One hundred seventy-three patients with the diagnosis of non-small cell lung cancer (NSCLC) were treated with surgery and postoperative radiation therapy (RT) at the Radiation Oncology Center, Washington University, St. Louis. All patients had been retrospectively reviewed and restaged according to the new American Joint Committee (AJC) staging classification. Seventeen patients were stage I, 69 were stage II, 74 were stage IIIA, and 2 patients were stage IIIB. In 11 patients, accurate staging could not be determined. Indications for postoperative RT were positive surgical margins (32 patients), metastatic hilar nodes (78 patients), and metastatic mediastinal nodes (62 patients). Locoregional control for stages I, II, and IIIA was 85, 75, and 85%, respectively. Five-year actuarial survival was 35% for stage I and 20% for stages II and IIIA. Patients with N0 disease (positive margins) had 5-year survival of 25%, whereas patients with N1 and N2 disease had a 5-year survival of 20%.
Tacrolimus (FK 506) measurement by immunoassays in clinical samples of organ transplant patients often lacks a specific reference method. A method combining liquid chromatography (LC) with tandem mass spectrometry (MS/MS) was developed to quantify tacrolimus in whole blood. Liquid-liquid extraction was performed on 1 ml of sample before narrow-bore LC/MS/MS analysis. Ascomycin was used as an internal standard. The standard curve was composed of seven points ranging from 1 to 50 micrograms/l (average r2 = 0.9999). Limits of detection and quantitation were 0.25 and 0.75 microgram/l, respectively. Imprecision was < 5% across the therapeutic range. Tacrolimus recovery averaged 62%. The most abundant metabolites detected in clinical samples were 13-O- and 15-O-demethyl tacrolimus. This method was used in a comparison study with a microparticle enzyme immunoassay (MEIA): MEIA = 1.03 LC/MS/MS -0.084 (microgram/l), (Sy/x = 1.43), r2 = 0.933. With its high sensitivity and specificity, this LC/MS/MS method presents a good reference method for immunoassay evaluation as well as a valuable tool for metabolism studies.
BACKGROUND: Optic neuropathy is a rare manifestation of systemic lupus erythematosus (SLE). In a previous series most patients with optic neuropathy in association with SLE had a final visual acuity of 20/200 or less despite corticosteroid therapy. METHODS: Three patients (five affected eyes) with severe retrobulbar optic neuropathy in association with SLE were treated promptly with intravenous cyclophosphamide and corticosteroids. RESULTS: All patients recovered excellent visual acuity. CONCLUSION: Although optic neuropathy in association with SLE might have several different aetiologies, intravenous cyclophosphamide should be strongly considered as a therapeutic alternative.
A great deal of the care of patients with asthma takes place in general practices. The aim of the present study was to describe the impact of asthma in the community and to identify current asthma self-management practices. A two-part questionnaire survey was conducted in a random sample (23%; n=24,398) of persons aged 16-50 yrs, registered with one of the 41 general practices in Greenwich, London, UK. The two parts were: a screening questionnaire identifying persons with current asthma (defined as waking with shortness of breath in the last 12 months, attack of asthma in the last 12 months, or currently taking treatment for asthma); and an asthma questionnaire (completed by those with asthma) assessing quality of life, frequency of asthma symptoms, possession and use of self-management tools, and action in the event of an exacerbation of asthma. The crude response rate was 51%, but this may be an underestimate due to errors in the sampling frame. The prevalences of wheeze and asthma in the past 12 months were 26% and 14%, respectively. Among asthma patients: 43% reported symptoms occurring three or more times per week, and 20% were woken by asthma symptoms on three or more nights per week; most had asthma with a mild impact on quality of life; 26% used inhaled steroids on most days in the preceding month; 16% had a peak flow meter at home; and 7% had oral steroids available. Of the 44% of subjects with asthma, who could identify an exacerbation of asthma in the preceding 6 months: 19% had used a peak flow meter during the episode; 19% had changed their treatment without first being told to do so by a doctor; and 50% had sought urgent medical help. Smokers used less appropriate asthma management and subjects whose asthma had a severe impact on quality of life used more treatment and peak flow monitoring. In conclusion, the prevalence of asthma among adults in Greenwich, UK, has increased since a similar survey in 1986. Many people have fairly mild asthma and a smaller number have severe disease. Much remains to be done to promote appropriate strategies for self-management of asthma exacerbations.
PURPOSE: To examine the predictive value of tumor- and treatment-specific prognostic indicators of relapse-free survival (RFS) and overall survival (OS) in patients with high-risk breast cancer (HRBC) treated with high-dose chemotherapy (HDCT) and stem-cell rescue. PATIENTS AND METHODS: Between June 1989 and September 1994, 114 patients with HRBC (stage II with > or = 10 axillary lymph nodes involved, stage IIIA, and stage IIIB inflammatory carcinoma) received adjuvant chemotherapy followed by HDCT with etoposide, cyclophosphamide, and either doxorubicin (CAVP) or cisplatin (CCVP). Variables analyzed included stage, tumor size, number of axillary nodes involved, grade and receptor status, and types of adjuvant chemotherapy and radiation therapy and HDCT. RESULTS: With a median follow-up time of 46 months (range, 23 to 93), Kaplan-Meier estimates of 3.5-year OS for stage II, IIIA, and IIIB HRBC are 82% (95% confidence interval [CI], 67% to 97%), 79% (95% CI, 67% to 91%), and 72% (95% CI, 53% to 91%); RFS estimates are 71% (95% CI, 56% to 85%), 57% (95% CI, 43% to 72%), and 50% (95% CI, 29% to 71%) irrespective of the HDCT regimen. In univariate analysis, the risk of relapse was lower for patients with progesterone receptor (PR)-positive tumors (risk ratio [RR], 0.43; 95% CI, 0.22 to 0.81; P = .01) and higher for patients with inflammatory carcinoma (RR, 2.20; 95% CI, 1.02 to 4.76; P = .05). OS was better for patients with PR (RR, 0.16; 95% CI, 0.05 to 0.55; P = .003) and estrogen receptor (ER)-positive tumors (RR, 0.42; 95% CI, 0.17 to 1.02; P = .05); OS was worse for patients with high-grade primary tumors (RR, 4.08; 95% CI, 1.21-13.7; P = .02). In multivariate analysis, PR positivity was associated with improved RFS (P = .01) and OS (P = .001). CONCLUSION: HDCT in selected patients with HRBC is safe and warrants further evaluation. Patients with receptor-negative, high-grade, or inflammatory tumors require improvement in their therapeutic options. Better assessment of the role of HDCT awaits completion of ongoing randomized trials.
The impact of chronic urticaria (CU) on the quality of life is undocumented. We assessed quality of life in patients with CU, including patients with associated delayed pressure urticaria (DPU). One hundred and forty-two out-patients completed self-administered questionnaires: a disease-specific, purpose designed questionnaire, and the Nottingham health profile (NHP). Many patients reported problems attributable to their skin condition in facets of everyday life including home management, personal care, recreation and social interaction, mobility, emotional factors, sleep, rest and work. The NHP part I scores showed restriction in the areas of mobility, sleep, energy, and demonstrated pain, social isolation and altered emotional reactions. Part II of the NHP showed that patients experienced difficulties in relation to work, looking after the home, social life, home relationships, sex life, hobbies and holidays. The patients with DPU had significantly more problems with mobility, gardening and choice of clothing than the uncomplicated CU patients. They also suffered more pain, had more problems with work and were more restricted in their hobbies.
Patient-generated dermatology quality of life scales (DQOLS) were developed to assess the impact of skin conditions on patients' psychosocial state and everyday activities. The items were derived from the self-reported impacts of their skin condition by 50 dermatology out-patients. The resulting 17 psychosocial items and 12 activities items were assigned five-point scales and self-completed by 118 out-patients. Factor analyses grouped the items into four psychosocial subscales (embarrassment, despair, irritableness, distress) and four activities subscales (everyday, summer, social, sexual). Tests of the psychometric properties indicated that the internal consistency of responses was high, with Cronbach's alpha coefficients of 0.92 for the 17 psychosocial items and 0.83 for the 12 activity items. Assessment of reliability based on 41 psoriasis patients attending phototherapy treatment identified good short-term test-retest reliability, with intraclass correlation coefficients of 0.84 for both the psychosocial and activities scales. Construct validity was confirmed by the ability of the scales to identify clinically expected differences and their greater sensitivity to the impacts of skin problems compared with a widely used generic health status measure. The DQOLS thus form a robust measure of patient-perceived impacts. They were quickly self-completed and provide information that complements traditional clinical indicators. These scales should assist in informing treatment decisions by identifying impacts of different skin conditions and variations in responses among social and cultural groups, as well as guiding priorities for services within the specialty.
The effect of incubating alpha T3-1 cells with phorbol 12,13-dibutyrate (PDBu) on the protein kinase C (PKC) isoform content (predominantly alpha, epsilon and zeta isoforms) was assessed by immunoblotting, enzyme activity assay and [3H]PDBu binding. After exposure to PDBu for 17 h the immunoreactivity detected for both PKC alpha and PKC epsilon had disappeared from cytosol and had increased slightly in membranes. Immunoreactivity for PKC zeta was present as two bands in cytosol; after PDBu treatment both bands decreased in intensity, the higher molecular weight band more than the lower. The lower molecular weight band corresponded with a component of constitutive PKC activity eluting from DEAE cellulose that was defined by inhibition of basal activity with GF 109203X or H7. Investigation of very short treatment times with PDBu using binding, immunoblot and activity measurements (in the presence/absence of Ca2+) indicated that translocation of PKC alpha and epsilon was very rapid-detectable by 10 sec, maximal within minutes. Reduction of these isoforms in membranes took much longer, and was not apparent up to 150 min. The immunoblot data for PKC zeta in cytosol showed no detectable effect of PDBu treatment on the low molecular weight band up to 150 min although it was reduced at 17 h. Translocation of the upper band was detectable at 10 sec but this band may have resulted from cross-reaction with other PKC isoforms. The constitutive activity and low molecular weight ("authentic') PKC zeta immunoreactivity were partially affected after long exposure only, suggesting an action of PDBu on PKC zeta secondary to activation of the other PKC isoforms. An endogenous receptor agonist, luteinising hormone-releasing hormone (LHRH), was also used to assess by immunoblotting, translocation of the PKC isoforms. Although all the isoforms did translocate from cytosol to membrane fractions, they did so with distinctly different time courses: PKC epsilon moved more rapidly than PKC zeta which appeared to translocate more quickly than PKC alpha. After downregulation of the responsive PKC isoforms with PDBu, the remaining PKC zeta was not translocated by LHRH.
PURPOSE: In patients with T1,T2 oral tongue carcinoma treated with surgical resection, postoperative radiation therapy (RT) is required especially when surgical margins contain tumors. Irradiation techniques include external beam, interstitial implants, or a combination of the two modalities. We investigated whether positive surgical margin remains a poor prognostic factor after radiation therapy, and the contribution of interstitial implants to disease control. METHODS AND MATERIALS: Between 1972 and 1989, 55 patients were treated postoperatively at the Mallinckrodt Institute of Radiology for T1,T2 squamous cell carcinomas of the oral tongue. Surgeries included 26 wide excisions or excisional biopsies and 29 composite resections or hemiglossectomies. Thirty-nine patients received external radiation therapy alone and 16 patients had an interstitial implant (ISI) as part of the treatment. The minimum follow-up is 4 years. RESULTS: At 2 and 5 years, the overall survivals for all patients were 82 and 68%. The disease-free survivals (DFS) were 82 and 70%, respectively. There was no significant difference in the pattern of failure and DFS when stratified by the status of surgical margins and the type of the surgical procedure. Local control was achieved in 15 of 18 patients when surgical margins were involved by tumor and in 29 of 37 patients without tumor involving margins (p > 0.05). Ten of 18 (56%) patients with tumor involving resection margins were treated with ISI, whereas only 3 of 33 (9%) of those with negative margins received ISI. Local control was achieved in 32 of 39 patients treated with external beam RT alone, and 13 of 16 patients who received interstitial implant (p > 0.05). Four patients treated with ISI developed persistent soft tissue ulceration and mandibular bone exposures. CONCLUSIONS: Postoperative radiation therapy converted the ominous outcome of patients with tumor involving surgical margins. Patients with positive surgical margins were often selected to be treated with interstitial implants. We found that the local control was as good as in those with a more favorable pathology (negative margins) and treated with external RT alone. Further investigation is needed to optimize the implant treatment to minimize the complications.
A sensitive high-performance liquid chromatographic method with ultraviolet detection was developed to quantitate methotrexate in serum-based calibrators, controls and patient samples. Sample clean-up was achieved with C18 Sep-Pak Classic cartridges. The chromatographic separation was accomplished on a 5-microns Ultrasphere ODS Beckman column. 8-Chlorotheophylline was used as an internal standard. The method was validated by recovery, linearity, accuracy and precision studies. Two standard curves were constructed to cover the high and the low ends of the calibrator range (0.05-1.0 mumol/l). Response was found linear over the whole range of the calibrator set with a correlation coefficient of 0.999 and 1.00 for the low-level and the high-level curves, respectively. Accuracy varied from 12% at the lowest level to 1.2% at the highest level. The precision study showed a C.V. of 14.4% at the lowest level and 3.3% at the highest level.
The disaccharides methyl 2-O-(alpha-L-fucopyranosyl)-beta-D-galactopyranoside and methyl 2-O-(alpha-L-fucopyranosyl)-alpha-D-galactopyranoside have been synthesised using the assisted halide reaction of tri-O-benzyl-alpha-L-fucopyranosyl bromide with methyl 3,4,6-tri-O-benzyl-beta-D-galactopyranoside and methyl 3,4,6-tri-O-benzyl-alpha-D-galactopyranoside to construct the interresidue glycosidic linkages. A crystal structure of methyl 2-O-(alpha-L-fucopyranosyl)-beta-D-galactopyranoside was determined using Mo-K alpha X-ray data at 183 K. The space group is P1 (No. 1) with the unit cell containing two molecules of the disaccharide with unique conformations and a water molecule. The structure was refined to R = 0.0566 for 2969 reflections. The L-fucopyranosyl and D-galactopyranosyl residues have the nominal 1C4 and 4C1 conformations, respectively. The interresidue torsion angles are comparable with those generated in a recent molecular modelling study.
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Certain physiological events in anterior pituitary tissue are regulated by protein kinase C that is relatively resistant to the inhibitor, H7. In the present studies we have shown that two H7-resistant protein kinase C activities may be isolated from (pituitary) gonadotroph-derived alpha T3-1 cells using hydroxyapatite chromatography. These activities have the characteristics of PKC zeta and an apparently novel PKC isoform. The availability of clonal alpha T3-1 cells will facilitate investigations of the pituitary events.
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