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Biomedical subjects

L D George

Publications and source records attributed to L D George.

10 recordsLinked to original sources

Recovery of growth hormone secretion following cabergoline treatment of macroprolactinomas.

OBJECTIVE: Cabergoline therapy normalizes prolactin levels and reduces the size of macroprolactinomas. However there are no data indicating whether cabergoline can normalize growth hormone secretion in patients who were growth hormone deficient at the time of diagnosis of a macroprolactinoma. SUBJECTS AND METHODS: We studied nine patients with biochemical and radiological evidence of a macroprolactinoma who were also growth hormone deficient (peak growth hormone response to insulin-induced hypoglycaemia < 10 mU/l). Patients were assessed before and after cabergoline therapy to assess their growth hormone secretory status, IGF-I levels, cortisol response and change in tumour size. RESULTS: Treatment with cabergoline was associated with a significant reduction in prolactin concentration (74341 +/- 31939 mU/l vs. 265.9 +/- 86.3, P = 0.009). The mean change in peak growth hormone response to insulin-induced hypoglycaemia was significantly greater following cabergoline therapy compared with pretreatment levels (33.5 +/- 11.8 mU/l vs. 4. 34 +/- 1.21 mU/l, P = 0.022). However IGF-I levels were not different after treatment when compared with baseline although a nonsignificant trend towards improvement was noted (24.2 +/- 3.97 nmol/l vs. 18.4 +/- 4.94 nmol/l, P = 0.058). The mean peak cortisol concentration was 407.7 +/- 64.1 nmol/l before treatment with a nonsignificant rise to 477.4 +/- 84.8 nmol/l, P = 0.813 after treatment. These changes were associated with a significant reduction in mean maximal tumour diameter (21.2 +/- 2.9 mm vs. 29.1 +/- 2.8 mm, P = 0.009). There was no significant difference in either prolactin concentration or tumour size pre- or post-treatment between those who recovered growth hormone secretion and those that did not. Six of the nine (67%) patients recovered a normal growth hormone response (> 10 mU/l) after cabergoline therapy. Those that remained growth hormone deficient after treatment were all panhypopituitary at baseline while those that recovered showed only partial anterior hypopituitarism. CONCLUSION: These data indicate that growth hormone secretion may recover following successful reduction of prolactin levels after cabergoline therapy for a mean of 22 months (range 6-28 months) in most but not all subjects with a macroprolactinoma. It is therefore advisable that individuals with a macroprolactinoma in whom growth hormone replacement therapy is being considered undergo repeat assessment of growth hormone secretion following medical treatment.

Adolescent↗

Effect of software manipulation (Photoshop) of digitised retinal images on the grading of diabetic retinopathy.

AIMS: To determine whether software processing of digitised retinal images using a "sharpen" filter improves the ability to grade diabetic retinopathy. METHODS: 150 macula centred retinal images were taken as 35 mm colour transparencies representing a spectrum of diabetic retinopathy, digitised, and graded in random order before and after the application of a sharpen filter (Adobe Photoshop). Digital enhancement of contrast and brightness was performed and a X2 digital zoom was utilised. The grades from the unenhanced and enhanced digitised images were compared with the same retinal fields viewed as slides. RESULTS: Overall agreement in retinopathy grade from the digitised images improved from 83.3% (125/150) to 94.0% (141/150) with sight threatening diabetic retinopathy (STDR) correctly identified in 95.5% (84/88) and 98.9% (87/88) of cases when using unenhanced and enhanced images respectively. In total, five images were overgraded and four undergraded from the enhanced images compared with 17 and eight images respectively when using unenhanced images. CONCLUSION: This study demonstrates that the already good agreement in grading performance can be further improved by software manipulation or processing of digitised retinal images.

Diabetic Retinopathy↗

A comparison of digital retinal images and 35 mm colour transparencies in detecting and grading diabetic retinopathy.

We compared digital retinal images and 35 mm colour transparencies taken with the Canon CR5 retinal camera for the detection and grading of diabetic retinopathy in a clinical setting, in a randomized, blinded study of diabetic patients with a spectrum of severity of diabetic retinopathy. Forty patients were photographed, giving a total of 75 eyes including non-diabetic eyes as controls. Images were graded according to the validated European guidelines. There was exact agreement between grades obtained from both the 2 field 45 degrees 35 mm colour transparencies and digital images in 93.3% (70/75) of eyes, with Cohen's Kappa statistic for the comparison being 0.92. Overall, when grading from the digital images 5.3% (4/75) eyes were undergraded with three cases of sight threatening diabetic retinopathy (STDR) graded as non-sight threatening (NSTDR) (3/48, 6.3%). One eye was overgraded (1/75, 1.3%). Two of the three cases of STDR undergraded as NSTDR had small numbers of intra-retinal microvascular abnormalities (IRMA) discernible on the colour transparencies but which were not visible from the digital image. The third had multiple small cotton wool spots graded as laser photocoagulation scars from the digital images. In conclusion there is good to excellent agreement between retinopathy grades using the Canon CR5 digital retinal imaging system compared to 35 mm colour transparencies.

Diabetic Retinopathy↗

Can digitised colour 35 mm transparencies be used to diagnose diabetic retinopathy?

Retinal photography is an adjunct to ophthalmoscopy in screening for diabetic retinopathy (DR). Digital retinal cameras allow a retinal image to be displayed immediately on a high resolution video display monitor. We conducted a pilot study to investigate the agreement in retinopathy grading from digitized images in comparison to original colour transparencies as 35 mm slides. One hundred and fifty macula-centred, 45 degree, non-stereoscopic retinal images were digitized onto CD ROM by Kodak at base resolution of 768 x 512 pixels. The anonymized images were displayed on a 17" monitor running Windows at 800 x 600 resolution in 64,000 colours (PC images) and graded in random order. Alternatively the transparencies were graded on a Slidex viewer. A quality control set were also graded with exact agreement in 93% of cases (91% (73/80) of PC images and 94% (75/80) of slide images). Compared to colour transparencies, 95% (84/88) of sight threatening diabetic retinopathy (STDR) and 100% (62/62) of non-STDR cases were diagnosed using the PC. One case of pre-proliferative DR and three cases of non-proliferative DR were graded as non-STDR from the PC. There was good agreement between PC displayed digitized retinal images and 35 mm colour transparencies.

Diabetic Retinopathy↗

Lipopolysaccharide induction of tissue factor expression in THP-1 monocytic cells. Protein-DNA interactions with the promoter.

Tissue factor, the cellular receptor for factor VII/VIIa, activates both the intrinsic and extrinsic pathways of blood coagulation. In this analysis we have used DNase I footprinting to map the sites of protein-DNA interaction along the promoter (-383 to +8) using nuclear extracts prepared from uninduced and lipopolysaccharide-induced THP-1 cells. We have identified six regions that interact with nuclear factors in both uninduced and induced extracts. Four footprints are contained within a region reported to confer base-line high level expression and lipopolysaccharide and serum induction. Two additional footprints map to a region reported to reduce basal transcription by 50%. The only qualitative change in the footprint pattern with uninduced and induced extracts is the appearance of two hypersensitive sites with uninduced extracts. In addition, changes in the level of protein- DNA binding are detected with only one probe by DNA mobility shift analysis. A combination of well characterized transcription factors (AP1), primarily lymphoid cell specific regulatory proteins (NF-kappa B- and/or Ets-1-related proteins), as well as additional, uncharacterized proteins appear to interact with these sequences. Our data suggest that post-translational modification of existing transcription factors, and not induction of new DNA-binding activity, mediates the lipopolysaccharide induction of tissue factor synthesis in THP-1 cells.

Base Sequence↗

Differential in vitro effects of chemotherapeutic agents on primary cultures of human ovarian carcinoma.

The treatment of ovarian cancer principally relies on the use of platinum and taxane chemotherapeutic agents. Short-term clinical results have been encouraging, but long-term responses remain limited. In this report, an in vitro assay system that utilizes cells grown from human tumor explants has been used to quantitatively evaluate responses to relevant concentrations of alternative chemotherapeutic agents. The results suggest that there are significant differences in the responses of explant-derived cultured cells to the different agents tested. In an evaluation of 276 primary ovarian cancer specimens, five nonstandard drugs were tested in 51 cases. Of these 51 cases, cyclophosphamide had the highest rate of response at 67%, followed by doxorubicin at 61%, gemcitabine at 49%, etoposide at 48%, and topotecan at 14%. Venn diagrams, representing the in vitro responses to the platins and taxanes, as well as the responses to the nonstandard drugs, illustrate that there clearly are distinct differences among patients in a given population. These data underscore the potential importance of evaluating each patient's response to a number of different drugs to optimize the therapeutic decision-making process.

Antineoplastic Agents↗