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Biomedical subjects

T L Jackson

Publications and source records attributed to T L Jackson.

At least 19 recordsLinked to original sources
PubMed2005

The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: first results of the endometrial sub-protocol following 2 years of treatment.

BACKGROUND: Tamoxifen treatment results in a doubling of the risk of endometrial cancer after 1-2 years of treatment and a quadrupling after 5 years. Anastrozole, a third-generation aromatase inhibitor, with superior efficacy to tamoxifen, may also offer tolerability benefits in terms of effects on the endometrium. METHODS AND RESULTS: A sub-protocol of the ATAC trial compared the incidence/type of intrauterine changes following treatment with these agents in a subgroup of patients (n = 285) from the main trial. After 2 years anastrozole treatment, endometrial thickness remained </= 5 mm (baseline: 3.0 mm); in patients receiving tamoxifen, endometrial thickness increased by 3.2 mm to 7.0 mm, with a similar trend in the combination group. At baseline, 26/285 patients (9.1%) had endometrial abnormalities, most commonly polyps. After 2 years the number of endometrial abnormalities appeared lower with anastrozole treatment compared with tamoxifen although these differences were not statistically significant (odds ratio: 0.44; 95% confidence interval 0.146, 1.314; P = 0.14). Most abnormalities occurred within the first year of treatment (anastrozole: 4/6; tamoxifen: 7/10; combination: 10/16; total: 21/32). Fewer patients in the anastrozole group (1.4%) required medical intervention (tamoxifen 12.5%; combination 13.6%). CONCLUSIONS: Fewer endometrial abnormalities occurred during 2 years treatment with anastrozole compared with tamoxifen although statistical significance was not reached in this sub-protocol analysis.

Anastrozole↗
PubMed2004

The ATAC ('Arimidex', Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: baseline endometrial sub-protocol data on the effectiveness of transvaginal ultrasonography and diagnostic hysteroscopy.

BACKGROUND: The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial is a randomized, double-blind trial comparing anastrozole ('Arimidex'), alone or in combination with tamoxifen, relative to tamoxifen alone as 5 year adjuvant treatment for post-menopausal women with early breast cancer. Since tamoxifen is associated with endometrial pathology, the ATAC endometrial sub-protocol was initiated to establish the background prevalence of intrauterine pathology, and to assess prospectively the incidence and nature of intrauterine changes following endocrine therapy. Another aim was to provide data from which advice could be generated on the best endometrium screening method for patients receiving tamoxifen. METHODS: Patients underwent endometrial assessments at entry to the sub-protocol. The baseline investigations comprised transvaginal ultrasound scanning (TVUS), a hysteroscopy and an endometrial biopsy. RESULTS: A total of 285 gynaecologically asymptomatic women from 31 centres in 10 countries entered the endometrial sub-protocol. The mean uterine volume was 47.7 cm3. The median endometrial thickness overall was 3 mm. Twenty-four histologically confirmed, pathological changes were observed. Twenty-three pathologies were confirmed by TVUS, and 21 were identified by hysteroscopy and confirmed by histopathology. Women with or without intrauterine pathology had median endometrial thickness of 5 and 3 mm respectively. CONCLUSIONS: The presence of pathology was associated with increased endometrial thickness. The relative sensitivity and specificity of hysteroscopy and endometrial thickness for the diagnosis of endometrial pathology was comparable to other studies. If screening of the endometrium prior to treatment is appropriate, this study supports the use of an endometrial thickness of 3 mm, as assessed by TVUS, as a threshold for needing further investigation. This study demonstrates that if the endometrial thickness is >3 mm, hysteroscopy and biopsy is the optimal method of detecting intrauterine pathology in women with breast cancer who are about to commence endocrine treatment.

Anastrozole↗
PubMed2003

The ATAC adjuvant breast cancer trial in postmenopausal women: baseline endometrial subprotocol data.

OBJECTIVE: The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial is a randomised, double-blind trial comparing 'Arimidex' (anastrozole), alone or in combination with tamoxifen, relative to tamoxifen alone as a five year adjuvant treatment for postmenopausal women with early breast cancer. Because tamoxifen is associated with endometrial pathology, the ATAC endometrial subprotocol was initiated to establish the background prevalence of pathology, and to assess prospectively the incidence and nature of intrauterine changes before and following endocrine therapy. SETTING: International. POPULATION AND STUDY DESIGN: Two hundred and eighty-five women entered the subprotocol: the mean age was 60 years (range 44-80 years); 113 women (40%) had taken hormone replacement therapy prior to randomisation, and 238 women were parous (84%). The age at onset of the menopause was 32-58 years, with the majority becoming menopausal between 46 and 55 years of age. Two hundred and seventy-two women had a hysteroscopy before they commenced trial medication. Hysteroscopy was performed successfully in 265 women. In six women, failure of hysteroscopy at baseline led to withdrawal from the study. Three of the women who withdrew had a pipelle biopsy taken. Therefore, the total number of endometrial biopsies at baseline was 268. MAIN OUTCOME MEASURES: To assess the demographic characteristics of women entering the endometrial subprotocol and their hysteroscopic and histological findings before commencing trial medication. RESULTS: At hysteroscopy, there was a diagnosis of endometrial polyps in 34 women (13%), fibroids in 16 women (6%) and one case of suspicious endometrium, which was confirmed as a polyp on histology. Only 21 of the 34 polyps seen hysteroscopically were proven histologically (62% accuracy of hysteroscopy). Final histology found the prevalence of endometrial diagnostic categories as follows: 123 inactive endometrium (46%), 20 benign polyps (7%), 17 secretory endometrium (6%), 7 proliferative endometrium (3%), 3 atypical hyperplasia (2 in a polyp), 1 simple hyperplasia (in a polyp) and 1 fibroid. The remaining women had pipelle samples with insufficient tissue obtained, indicating a normal endometrial cavity. CONCLUSION: This is the first study of such size in gynaecologically asymptomatic breast cancer patients. This paper describes the findings in individual patients before any trial treatment was given. In this baseline group, 82% (219/268) of women had a normal endometrial cavity; 18% (49/268) had endometrial activity (proliferative or secretory endometrium in 9%) or an intracavity abnormality (hyperplasia, polyps and a fibroid in 9%). In total, 36% of biopsies had insufficient tissue for diagnosis, which in combination with a normal hysteroscopy was classed as normal. The appearance of a polyp hysteroscopically in this group was not proven histologically in approximately 40% of cases. The development of uterine pathology over time in the ATAC study will subsequently be assessed against the findings of this baseline paper.

Adult↗
PubMed2002

Transurethral prostatic tissue ablation via a single needle delivery system: initial experience with radio-frequency energy and ethanol.

We report an initial clinical experience to evaluate the safety and efficacy of outpatient prostatic ablation for the treatment of symptomatic benign prostatic hyperplasia (BPH) using local anesthesia (OPAL) with radio-frequency energy and intraprostatic absolute ethanol injection (EI). Twenty-three patients were treated with OPAL and five patients were treated with EI. Pre-operative data for all patients included international prostate symptom score (IPSS), quality of life score (QL), maximum flow rate (Q(max)), and post void residual determination. Prostate specific antigen (PSA) and transrectal ultrasound prostate volume determination were also done for EI patients. Needle deployment into the prostate was carried out at the 2, 4, 8 and 10 o'clock positions for lateral lobe hyperplasia and the 6 o'clock position for middle lobe hyperplasia. IPSS, QL, Q(max) and post void residual data were collected at 1, 3, 6 and 12 months post procedure. Both procedures resulted in statistically significant reductions of IPSS and QL. Trends towards improvement were seen both for Q(max) and post void residual, with Q(max) significantly improved after OPAL. Among EI patients, the prostate volume was reduced at 6 months post treatment to 37.2+/-17.9 g from 53.0+/-19.0 g (P=0.03) preoperatively. OPAL was safe but suffered from a high re-treatment rate. EI demonstrated encouraging results with regards to safety, symptom improvement and prostate volume reduction.

Aged↗
PubMed2001

Protein release profiles and morphology of biodegradable microcapsules containing an oily core.

The protein release profiles and the morphology of poly(D,L-lactide-co-glycolide) (PLG) and poly(epsilon-caprolactone) (PCL) microcapsules were investigated. The microcapsules were prepared by the (oil(1)-in-oil2)-in-water emulsion solvent evaporation method using bovine serum albumin (BSA) as a model protein. The internal and external morphologies of the microcapsules were examined using a light microscope, scanning electron microscope and a laser scanning confocal microscope. A Coulter counter was used to determine particle size and particle size distribution. Protein quantitation and molecular integrity were performed by the bicinchoninic acid protein assay micro-method and SDS-PAGE, respectively. Microcapsules with a polymeric wall surrounding an oily core containing the protein were formed. The encapsulation efficiency (39-96%) for PLG and (13-90%) for PCL increased with polymer molecular weight and particle volume mean diameter (Vmd). Vmd ranged from 87-128 to 42-157 microm for PLG and PCL, respectively. The protein release profile for PLG microcapsules was either continuous or irregularly pulsatile depending on particle morphology and was completed after cavity breakdown. However, that of PCL microcapsules was essentially irregularly pulsatile and was completed after a longer period of time without cavity breakdown but with significant swelling. There was no detectable cleavage of the protein during 6 months storage of PLG and PCL microcapsules at 4 degrees C. Furthermore, insignificant degradation of protein occurred during in vitro release from PCL microcapsules. In contrast, significant degradation occurred in PLG microcapsules. This approach to microencapsulation of a protein may be promising for the controlled delivery of protein vaccines, and the oil core may enhance the immunogenicity of some weak subunit vaccine candidates.

Capsules↗
PubMed2001

Pupil block glaucoma in phakic and pseudophakic patients after vitrectomy with silicone oil injection.

PURPOSE: To describe pupil block glaucoma in phakic and pseudophakic patients after vitrectomy with silicone oil injection. DESIGN: Interventional case series. METHODS: Cases were collected from January 1997 to July 2000 from three tertiary referral centers. RESULTS: Seven phakic patients (seven eyes) and one pseudophakic patient (one eye) presented 1 to 90 days after vitrectomy and silicone oil injection with intraocular pressures of 36 to 70 mm Hg. Five patients had an observed or potential weakness of the iris-lens diaphragm. Treatment with Nd:YAG-laser peripheral iridotomy or inferior iridectomy provided a temporary reduction in intraocular pressure for some patients, but all eventually required removal of silicone oil. CONCLUSION: Pupil block glaucoma after silicone oil injection is well recognized in aphakic patients, but ophthalmologists should be aware that it can occur in phakic and pseudophakic patients, particularly in complicated cases and patients with a weakness of the iris-lens diaphragm.

Adult↗
PubMed2001

Optical coherence tomography of the vitreoretinal interface in macular hole formation.

AIMS: To image the vitreoretinal interface and provide further information on the pathogenesis of idiopathic macular hole formation. METHODS: Prospective recruitment of 80 eyes of 41 consecutive patients referred with a diagnosis of idiopathic full thickness macular hole (FTMH) to a teaching hospital retinal clinic. Both eyes of each patient underwent optical coherence tomography (OCT) imaging with vertical and horizontal scans centred on the fovea. RESULTS: A total of 30 eyes had stage 2 or 3 FTMHs and, of these, 21 had persistent vitreofoveal attachment and associated prefoveal opacities. 18 prefoveal opacities were identified by Goldmann contact lens examination and confirmed on OCT examination. Three prefoveal opacities were identified only on OCT examination. 10 eyes had stage 4 FTMHs and four cases were identified in whom the OCT appearance was consistent with impending, aborted, or lamellar macular holes. CONCLUSIONS: The wide range in OCT appearance of macular holes and associated prefoveal opacities suggests that, in at least some cases, a significant amount of retinal tissue is torn from the foveal area during macular hole formation. OCT imaging provides additional information on macular hole pathogenesis and is valuable in the planning of surgical intervention.

Aged↗
PubMed2000

Evidence of atmospheric sulphur in the martian regolith from sulphur isotopes in meteorites.

Sulphur is abundant at the martian surface, yet its origin and evolution over time remain poorly constrained. This sulphur is likely to have originated in atmospheric chemical reactions, and so should provide records of the evolution of the martian atmosphere, the cycling of sulphur between the atmosphere and crust, and the mobility of sulphur in the martian regolith. Moreover, the atmospheric deposition of oxidized sulphur species could establish chemical potential gradients in the martian near-surface environment, and so provide a potential energy source for chemolithoautotrophic organisms. Here we present measurements of sulphur isotopes in oxidized and reduced phases from the SNC meteorites--the group of related achondrite meteorites believed to have originated on Mars--together with the results of laboratory photolysis studies of two important martian atmospheric sulphur species (SO2 and H2S). The photolysis experiments can account for the observed sulphur-isotope compositions in the SNC meteorites, and so identify a mechanism for producing large abiogenic 34S fractionations in the surface sulphur reservoirs. We conclude that the sulphur data from the SNC meteorites reflects deposition of oxidized sulphur species produced by atmospheric chemical reactions, followed by incorporation, reaction and mobilization of the sulphur within the regolith.

Atmosphere↗
PubMed2000

A mathematical model to study the effects of drug resistance and vasculature on the response of solid tumors to chemotherapy.

A mathematical model is developed that describes the reduction in volume of a vascular tumor in response to specific chemotherapeutic administration strategies. The model consists of a system of partial differential equations governing intratumoral drug concentration and cancer cell density. In the model the tumor is treated as a continuum of two types of cells which differ in their proliferation rates and their responses to the chemotherapeutic agent. The balance between cell proliferation and death within the tumor generates a velocity field which drives expansion or regression of the spheroid. Insight into the tumor's response to therapy is gained by applying a combination of analytical and numerical techniques to the model equations.

Animals↗
PubMed2000

A prospective study of cost, patient satisfaction, and outcome of treatment of chalazion by medical and nursing staff.

AIM: To study prospectively the outcome of conservative and surgical treatment of chalazia provided by medical and nursing staff. METHODS: During a 5 month recruitment period all patients attending a district general eye hospital for treatment of chalazion were included in the study. 129 patients (217 visits) with chalazia were seen by either a senior nurse or a trainee ophthalmologist (senior house officer, SHO) or both. Patients received either conservative treatment or eversion of the eyelid with incision and curettage. Patients were mailed a questionnaire asking them if their cyst had resolved and how they rated their treatment. Marginal cost analysis was used to determine the cost of treatment. RESULTS: The outcome of treatment could be determined in 170 of the 217 visits. Conservative treatment was successful for 29% of cysts while surgical treatment was successful for 72%. There was no significant difference in treatment outcome between nurse and SHO groups. Patients found nurse treatment acceptable with a high level of patient satisfaction. The marginal cost of treatment by a nurse was 9.91 pounds sterling per cyst compared with 12.10 pounds sterling for SHOs. There were no surgical complications and no evidence of malignancy in six biopsies. CONCLUSIONS: Surgical treatment of chalazion is safe and effective and successfully treats approximately three quarters of selected cysts. With conservative treatment approximately one third of selected chalazia will resolve within 3 months. Nurse treatment of chalazion is safe, effective, and acceptable to patients.

Adolescent↗
PubMed2000

Screening for CMV retinitis using chromatic discrimination thresholds and achromatic contrast sensitivity.

BACKGROUND: Many patients with cytomegalovirus retinitis (CMVR) are unaware of visual disturbance so screening is advocated for patients with HIV and low CD4 counts. Many tests of retinal function have been recommended but few are effective at detecting CMVR. We assess the potential of chromatic discrimination thresholds and achromatic contrast sensitivity as screening tests for patients with CMVR. METHOD: 11 HIV+ patients with CMVR, 16 age matched HIV+ patients, and 29 age matched controls were recruited. Visual acuity, chromatic discrimination thresholds, and achromatic contrast sensitivity were measured. Fundal examination was performed by slit lamp biomicroscopy for HIV+ patients. Those with CMVR were photographed and the CMVR graded from the photographs. RESULTS: Loss of chromatic discrimination was found in patients with CMVR (tritan p<0.0005, red/green p<0.05). The same group had deterioration in achromatic contrast sensitivity at 2.2, 3.4, and 10 cpd (p<0.05). There was correlation between the zone of CMVR with chromatic gratings (tritan r=0.83, p<0.005). No statistically significant difference was found between the HIV+ patients and the controls for all tests (p>0.1). CONCLUSIONS: HIV+ patients with CMVR have a loss of chromatic discrimination and achromatic contrast sensitivity and this may be used to screen HIV+ patients for CMVR.

AIDS-Related Opportunistic Infections↗
PubMed1999

Stealth monensin liposomes as a potentiator of adriamycin in cancer treatment.

Small unilamellar stealth monensin liposomes (SMLs) were prepared from multilamellar liposomes (MLVs). The MLVs were prepared by using dipalmitoyl phosphatidylcholine (DPPC), cholesterol, distearoyl glycerophosphoethanolamine coupled to poly(ethylene glycol) (DSPE-PEG) and stearylamine in the molar ratio of 10:5:1.4:1.4 (32.8 mM total lipid). The encapsulation efficiencies of monensin in MLVs and small unilamellar vesicles (SUVs) was 6x10++(-6) and 10(-7) M, respectively. The stability of SMLs was studied at 4 degrees C. The amount of leakage of monensin from SMLs was less than 20% after four weeks of storage. The in vitro release of monensin from SMLs in human serum was determined, and t1/2 was found to be 10 h. Pharmacokinetic studies on SMLs were carried out in BALB/c mice. More than 20% of SMLs remained in blood circulation after 24 h. SMLs increased the uptake of adriamycin (AM) in HL-60-resistant cells by more than two fold, compared to monensin in solution. SMLs potentiated the effect of AM against both sensitive and resistant HL-60 cells (six- and tenfold potentiation, respectively) and human LOVO tumor cells (four- and 200-fold potentiation, respectively). However, the highest potentiation was observed against resistant human breast tumor MCF7 cells, and was found to be 2400 times in comparison to AM alone. Transmission electron microscopic (TEM) studies carried out with HL-60-resistant tumor cells incubated with SMLs showed that SMLs caused dilation of the golgi of tumor cells within 10 min. The dilation of golgi was reversible after reincubation of the cells in fresh medium. SMLs showed considerable potential as a potentiator in combination with AM in overcoming drug resistance.

Animals↗
PubMed1999

Theoretical analysis of conjugate localization in two-step cancer chemotherapy.

Considerable research has been aimed at improving the efficacy of chemotherapeutic agents for cancer therapy. A promising two-step approach that is designed to minimize systemic drug toxicity while maximizing activity in tumors employs monoclonal antibody-enzyme conjugates for the activation of anti-cancer prodrugs. A mathematical model based on the biology of human 3677 melanoma xenografts in nude mice is presented, analyzed, and numerically simulated to study the biodistribution, pharmacokinetics, and intratumoral localization properties of L49-beta-lactamase fusion proteins in solid tumor masses. The model predictions were compared with published experimental data and an excellent correlation was found to exist. Analytic expressions for the total concentration of conjugate in the tumor, the time at which the concentration is maximal, and the half life of conjugate in the tissue were derived. From these results, key parameters were isolated; and the effects of the tumor vasculature, binding kinetics, and administration schedule were investigated. The antibody-antigen dissociation ratio, the conjugate permeability, and the inter-capillary half distance within the tumor mass were found to strongly influence localization and retention in the tumor. The model was used to examine various dosing strategies in an attempt to determine which regimen would provide the best biodistribution results. The results of administering a uniform dose of conjugate via bolus injection, multiple injections, and continuous infusion were compared. The model predicts that when saturation of binding sites does not occur, dosing strategy has little effect on the amount of conjugate that localizes in the tumor.

Animals↗
PubMed1999

Hypotensive ischemic optic neuropathy and peritoneal dialysis.

PURPOSE: To report anterior ischemic optic neuropathy associated with systemic hypotension in a patient undergoing continuous ambulatory peritoneal dialysis. METHODS: Case report. A 58-year-old man undergoing continuous ambulatory peritoneal dialysis developed painless blurred vision in both eyes and bilateral optic disk swelling with an altitudinal field defect in the left eye. Twenty-four-hour ambulatory blood pressure monitoring was requested in addition to other routine investigations. RESULTS: Routine blood pressure measurement in the clinic was 130/86 mm Hg, but ambulatory blood pressure monitoring demonstrated pronounced early morning hypotension with individual readings as low as 91/41 mm Hg. CONCLUSIONS: Renal dialysis can render patients hypotensive, and this may be associated with anterior ischemic optic neuropathy. The overnight drop in blood pressure may not be appreciated with routine blood pressure measurement. Therefore, 24-hour ambulatory blood pressure monitoring should be considered when investigating patients with suspected anterior ischemic optic neuropathy who are undergoing renal replacement.

Blood Pressure↗
PubMed1999

Mathematical and experimental analysis of localization of anti-tumour antibody-enzyme conjugates.

Considerable research has been aimed at improving the efficacy of chemotherapeutic agents for cancer therapy. A promising two-step approach that is designed to minimize systemic drug toxicity while maximizing activity in tumours employs monoclonal antibody (mAb)-enzyme conjugates for the activation of anticancer prodrugs. We present, analyse and numerically simulate a mathematical model based on the biology of the system to study the biodistribution, pharmacokinetics and localization properties of mAb-enzyme conjugates in tumour tissue. The model predictions were compared with experimental observations and an excellent correlation was found to exist. In addition, the critical parameters affecting conjugate half-life were determined to be the inter-capillary half-distance and the antibody-antigen binding affinity. An approximation is presented relating the per cent injected dose per gram to inter-capillary half-distance and time. Finally, the model was used to examine various dosing strategies in an attempt to determine which regimen would provide the best biodistribution results. We compared the results of administering a uniform dose of fusion protein via bolus injection, multiple injections and continuous infusion. The model predicts that dosing strategy has little effect on the amount of conjugate that localizes in the tumour.

Animals↗