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Biomedical subjects

A J Gray

Publications and source records attributed to A J Gray.

At least 37 records · Page 2Linked to original sources

Towards automatic cell identification in DIC microscopy.

A general method is proposed for constructing templates of cells in differential interference contrast (DIC) microscopy. This takes account of the optics which generate DIC images, and is applicable to both transparent and semi-transparent cells of simple and complex shapes. Then, a template matching methodology is presented, which uses fast Fourier transforms to fit templates of a range of sizes and orientations to images. For illustration, this is used to automatically identify and measure individual Candida yeast cells in clusters.

Automation↗

Out of hospital cardiac arrest and associated injury.

Three patients are described who sustained injuries around the time of a collapse that led to out of hospital cardiac arrest. In this group of patients the importance of taking a complete medical history and recording the circumstances of the syncopal episode cannot be overemphasised. If cardiac output is successfully restored the possibility of occult traumatic injury must be considered in high risk patients.

Aftercare↗

Radiation therapy for retinoblastoma: a retrospective review of 120 patients.

PURPOSE: To characterize the patient population and treatment outcomes in patients with Retinoblastoma (RB) referred for External Beam Orbital Radiotherapy (EBORT) to King Faisal Specialist Hospital & Research Centre (KFSH&RC), Riyadh, Saudi Arabia from 1976 to 1993. METHODS AND MATERIALS: A retrospective study of 120 patients with RB affecting a total of 192 eyes. Patients were divided into three groups. Group A are 60 patients (64 eyes) treated with EBORT to the intact eye to preserve vision. Reese-Ellsworth (RE) Staging was: 1: 12%; 2: 10%; 3: 12%; 4: 23%; and 5: 43%. Twenty-eight patients (47%) also received Vincristine, Adriamycin, and Cyclophosphamide chemotherapy (C/T). Mean follow-up, per patient, was 48.5 months. Standard treatment until 1992 was 45 Gy in 12 fractions of 3.75 Gy, three times weekly over 18 days. Assuming the alpha/beta ratio for early effects and tumor control at 10, Tk = 21 days, Tpot = 5 days, then the Biological Equivalent Dose (BED) was 62 Gy10 for early effects, and 101 Gy3 for late effects. Group B are 28 patients (28 eyes) treated for curative intent with EBORT to the orbit for locally advanced disease, usually after enucleation (24 eyes). Nineteen patients (83%) also had C/T. Mean follow-up was 22.6 months. Group C are 37 patients with advanced disease treated with radiotherapy for palliation. Seventeen (46%) also received C/T. Mean follow-up was 11.7 months. RESULTS: Group A-following EBORT useful vision was retained in RE Stage 1 to 5: 7 of 7, 6 of 6, 4 of 8, 10 of 15, and 7 of 28 eyes, respectively. There was no significant difference between patients who received adjuvant chemotherapy and those who did not. Complications included cataract (27%), retinopathy (25%), vitreous hemorrhage (19%), and orbital deformities (11%). In Group B the local control rate was 71%. In Group C, 10 (27%) of the 37 patients were alive at last contact, and 27 (73%) were either terminal or dead of disease. None of Group A or B patients had positive CSF cytology, bone scan, or bone marrow examination. In Group C 19% had positive CSF cytology, and bone marrow, and 14% had a positive bone scan. CONCLUSIONS: 1) EBORT preserved useful vision in a significant proportion of patients even in eyes with advanced RE Stage RB, but longer follow-up is likely to reveal an even higher complication rate with this regime. 2) High dose per fraction probably contributed to the increased complications. 3) Chemotherapy did not demonstrate any effect on retaining vision in this study. 4) For disease that is confined to within the eye clinically and radiologically, invasive procedures for CSF cytology, bone marrow examination, and bone scan do not seem warranted. 5) The optimum technique, fractionation, and dosage for RB is still not well defined.

Child↗

The ligamentum teres of the hip: an arthroscopic classification of its pathology.

Pathology of the ligamentum teres is rarely diagnosed. We describe the classification of the lesions seen at hip arthroscopy based on a group of 20 patients. Three groups are noted: complete rupture, partial rupture, and the degenerate ligamentum. The complete ligamentum teres rupture group had a history of either major trauma or surgery and had a high incidence of other hip pathology such as labral tears and articular damage. The partial ligamentum rupture group presented with a long history of ill-defined hip pain. Minor associated hip abnormalities were seen at arthroscopy. Degenerate ligamentum teres rupture presented with symptoms of the underlying osteoarthritis. Debridement or washout was performed but, at 2 years, patients had severe persistent symptoms or had had a joint replacement.

Adult↗

Treatment results for 149 medulloblastoma patients from one institution.

PURPOSE: Retrospective analysis of patients with medulloblastoma to determine the effectiveness of previous treatments for medulloblastoma and plan for future management strategies. METHODS AND MATERIALS: During the period March 1976 to December 1991, 172 patients with cerebellar medulloblastoma were referred to King Faisal Specialist Hospital and Research Center. One hundred and forty-nine patients were treated with curative intent. There were six postoperative deaths, and 10 patients planned for radiotherapy treatment failed to complete the prescribed course. One hundred and thirty-three patients completed a course of radiotherapy after surgery. Adjuvant chemotherapy was not used routinely (six patients only). Tumors were staged retrospectively according to the Chang staging system. There were no T1 patients, 32 patients had T2 tumors, 76 had T3 tumors, and 29 had T4 tumors. The T stage could not be allocated in 12 patients. Ninety-nine patients required a shunting procedure either pre- or postoperatively. Forty-six patients had complete resection of tumor, 91 had incomplete resection, and 6 patients had biopsy only. The extent of resection could not he determined in six patients. The median radiation dose for the whole brain was 34 Gy, spine 32.5 Gy, and posterior fossa 52.8 Gy. Fraction sizes ranged from 1.7-1.8 Gy for craniospinal fields and 2 Gy for the posterior fossa boost. Seventy percent completed the prescribed course within 7 weeks. RESULTS: Actuarial survival for the whole group of 149 patients was 53% at 5 years and 38% at 10 years. On univariate analysis, patients with T2 tumors did significantly better as compared to patients with T3 and T4 tumors. Survival of patients who had clinical and radiological complete resection of tumor at surgery was significantly better than patients with incomplete tumor removal. The presence of a ventriculoperitoneal (VP) shunt had a significant negative impact on survival. Treatment failure by site was analyzed with respect to the radiation dose. Doses greater than 50 Gy for the posterior fossa, and greater than 30 Gy for craniospinal axis, resulted in significantly better survival. On multivariate analysis, the only significant prognostic factor was the presence of a VP shunt in patients with T2 tumors. CONCLUSION: T stage, VP shunt, radiation doses and extent of surgery were important prognostic factors. In this study, radiation doses of more than 50 Gy to the posterior fossa and 30 Gy to the craniospinal axis resulted in improved survival.

Adolescent↗

Pericardial metastasis in carcinoma of the uterine cervix.

Cardiac metastasis from gynecological malignancies is rare. Only six cases of carcinoma of the uterine cervix have been reported where the diagnosis of malignant pericardial effusion was made antemortem. The treatment of neoplastic pericardial effusion is controversial; both surgical and nonsurgical treatments are advocated. We present a patient with pericardial effusion secondary to carcinoma of the cervix and recommend subxiphoid pericardial fenestration for reliable long-term control of malignant effusion.

Female↗

Role of the plain radiograph and urinalysis in acute ureteric colic.

OBJECTIVE: (1) To determine the accuracy of accident and emergency (A&E) doctors' diagnosis of radio-opaque ureteric calculi on plain abdominal radiographs; (2) to study the predictive value of haematuria with a history suggestive of ureteric colic. DESIGN: A prospective study of all patients seen in a three month period with a provisional diagnosis of ureteric colic. Intravenous urography (IVU) was used as the gold standard for diagnosis of ureteric calculi. SETTING: The accident and emergency department and medical unit of a large teaching hospital. SUBJECTS: 60 patients who were admitted with an initial diagnosis of ureteric colic, 51 subsequently undergoing intravenous urography. RESULTS: A&E doctors achieved a calculated sensitivity of 29% (95% confidence intervals 13% to 49%) and a specificity of 73% (52% to 90%) for identification of renal calculi on plain abdominal radiograph, compared with figures of 68% (48% to 84%) and 96% (78% to 100%) respectively for consultant radiologists. The difference between these results was highly significant (P = 0.0011). No patient with a definitive diagnosis of ureteric colic had a negative result for haematuria on urinary dipstick analysis. CONCLUSIONS: A&E doctors are poor at identifying radio-opaque ureteric calculi on plain abdominal radiographs. If haematuria is absent on urinalysis then ureteric colic is an unlikely diagnosis.

Colic↗

Excretion and metabolism of tipredane, a novel glucocorticoid, in the rat, mouse, monkey, and human.

The excretion and metabolism of [3H]tipredane, a novel glucocorticoid, has been studied in mice, rats, marmosets, rhesus and cynomolgus monkeys, and humans. After oral administration, [3H]tipredane was rapidly absorbed, metabolized, and excreted into urine and feces. In mice and male rats, radioactivity was excreted primarily into feces or bile, whereas in female rats, monkeys, and humans, excretion was mainly via the renal route. Some sex differences in the proportions excreted into urine and feces were noted in rodents, with females eliminating relatively more radioactivity in urine. Tipredane was shown to be extensively metabolized, but the routes were highly species-dependent and, in the rat, they were sex-dependent. Unchanged tipredane was not detected in any urine, bile, or blood extracts. Urinary and blood extract profiles indicated that there were between 10 and 30 metabolites in rats and mice, the majority of which constituted < 2% of the dose. In these species, the major pathways involved loss of the thioethyl moiety, S-oxidation of the thiomethyl group, and saturation of the adjacent saturated C16-17 bond. Hydroxylation of the steroid B-ring was seen in the 7 alpha-position in mice and female rats, and in the 6 beta-position in male rats. Metabolism of tipredane in rhesus and cynomolgus monkeys and humans was similar, but less extensive and different to that seen in rodents. The major products, the 6 beta-hydroxylated sulfoxide and sulfone metabolites of tipredane, accounted for 21-36% of the dose in human and monkey urine, and were also major components in blood. In contrast to mice and rats, S-oxidation and an unsaturated C16-17 bond were evident in primates. Metabolism of tipredane was rapid and complex, with significant species differences, although the disposition in rhesus and cynomolgus monkeys seemed to be similar to humans.

Administration, Topical↗

The mitogenic effects of the B beta chain of fibrinogen are mediated through cell surface calreticulin.

We have previously shown that soluble partially degraded fibrin(ogen) remains in solution after fibrin clot formation and is a potent fibroblast mitogen (Gray, A.J., Bishop, J.E., Reeves J.T., Mecham, R.P., and Laurent, G.J. (1995) Am. J. Cell Mol. Biol. 12, 684-690). Mitogenic sites within the fibrin(ogen) molecule are located on the A alpha and B beta chains of the protein (Gray, A.J., Bishop, J. E., Reeves, J.T., and Laurent, G.J. (1993) J. Cell Sci. 104, 409-413). However, receptor pathways through which mitogenic effects are mediated are unknown. The present study sought to determine the nature of fibrin(ogen) receptors expressed on human fibroblasts which interact with the fibrinogen B beta chain. Receptor complexes were isolated from 125I-surface-labeled fibroblasts and purified on a fibrinogen B beta chain affinity column. Subsequent high performance liquid chromatography and SDS-polyacrylamide gel electrophoresis analysis indicated fibrinogen B beta chain bound specifically to a 60-kDa surface protein. Sequence analysis of the amino terminus of this protein indicated 100% homology to human calreticulin. Immunoprecipitation experiments employing a polyclonal anti-calreticulin antibody provided further evidence that the 60-kDa protein isolated in this study was calreticulin. Further, polyclonal antibodies to human calreticulin significantly inhibited the mitogenic activity of fibrinogen B beta chain on human fibroblasts. The present study has shown that cell surface calreticulin binds to the B beta chain of fibrinogen mediating its mitogenic activity.

Amino Acid Sequence↗

Role of thrombin in pulmonary fibrosis.

Pulmonary fibrosis commonly develops in systemic sclerosis. We assessed the role of thrombin in promoting fibroblast proliferation in the lungs in this disorder. Bronchoalveolar lavage fluid (BALF) thrombin concentrations were higher in ten patients with systemic sclerosis than in 12 healthy controls (14.6 vs 3.6 nmol/L, p < 0.02), but values in patients with cryptogenic fibrosing alveolitis (n = 10) or sarcoidosis (n = 10) were not increased. BALF from all patients induced fibroblast proliferation. This proliferation was attenuated by thrombin inhibitors for BALF from systemic sclerosis patients only. We suggest thrombin contributes to lung fibroblast proliferation in this disorder.

Alveolitis, Extrinsic Allergic↗

Doctors' legal position in treating temporarily incompetent patients.

Doctors in accident and emergency departments are sometimes presented with patients with potentially life threatening conditions who refuse to consent to treatment. The doctors then face a dilemma: to withhold necessary treatment or to act against a patient's express wishes. Two such cases are presented, and we asked a lawyer, two medical ethicists, a psychiatrist, and an accident and emergency physician to comment on the implications.

Adult↗

Insulin-like growth factor I is a major fibroblast mitogen produced by primary cultures of human airway epithelial cells.

1. The ability of airway epithelial cells to produce insulin-like growth factor I may be important in the pathogenesis of subepithelial fibrosis observed in the airways of patients with asthma. We determined whether human airway epithelial cells are capable of producing polypeptide mediators that could induce fibroblast proliferative activity, in particular insulin-like growth factor I. 2. We examined 12 primary cultures of human airway epithelial cells grown to confluence on collagen gel-coated dishes. Using a colorimetric assay based on the uptake and subsequent release of Methylene Blue, increased proliferation of human fetal lung fibroblasts was detected in conditioned media from airway epithelial cells. The median stimulation of fibroblast proliferation was 49.9% (range 25.6-113.3%) above control values (observed at 1:2 dilution of media). 3. A neutralizing antiserum to insulin-like growth factor I partly inhibited fibroblast proliferation induced by epithelial cell conditioned media by 52.2% (49.9-109%; n = 5). 4. Radioimmunoassay for insulin-like growth factor I in conditioned media demonstrated a median concentration of 54.1 ng/ml (32.4-96.8 ng/ml). 5. Insulin-like growth factor I mRNA was detected in epithelial cell monolayers by Northern blot analysis using an insulin-like growth factor I cDNA probe. 6. The insulin-like growth factor I gene is expressed in cultured human airway epithelial cells, which also secrete insulin-like growth factor I protein. Insulin-like growth factor I also accounts for the major mitogenic activity for fibroblasts of cultured human epithelial cell conditioned media. Insulin-like growth factor I may function in a paracrine manner to modulate fibroblast behaviour and may be involved in airway processes, such as those occurring in asthma.

Bronchi↗

Management of retained ear-rings using an ear block.

A local anaesthetic block of branches of the greater auricular and auriculotemporal nerves was used to facilitate the extraction of retained butterfly backs and ear-ring studs. A total of 28 ear blocks were performed on 26 patients. Two patients required bilateral ear blocks, and 17 earlobes were infected. Complete analgesia was obtained in 25 cases, and two patients complained of tolerable discomfort during removal of the ear-ring. Assessment of analgesia was not possible in one 5-year-old child. We recommend this quick and simple technique for removal of retained ear-rings, particularly when there is associated soft tissue infection, in which case infiltration of local anaesthetic into the earlobe is contraindicated.

Adolescent↗

Partially degraded fibrin(ogen) stimulates fibroblast proliferation in vitro.

The conversion by thrombin of soluble plasma fibrinogen to an insoluble fibrin matrix is central to hemostasis and subsequent wound healing. Fibroblasts adhere to and rapidly grow into fibrin clots, resulting in collagen deposition and, ultimately, scar formation. Although a number of soluble mediators have been implicated in this process, a role for fibrin(ogen) itself has not been described. The present study further investigated the nature of mitogenic activity remaining in solution after in vitro fibrin clot formation. Liquid expressed from a fibrin clot (clot supernatant) elicited a mitogenic response of up to 83 +/- 4.7% above media control. Upon addition of a polyclonal fibrinogen antibody, this activity was reduced by 50%. The remaining activity was attributed to the presence of thrombin and was neutralized by the addition of a specific thrombin inhibitor. Fibrinogen cleavage products were separated by molecular sieve chromatography and the mitogenic potential of each fraction assessed. A peak of activity was observed in fractions containing proteins with apparent molecular weights of 200 to 300 kD. Enhanced chemiluminescence Western blotting of these fractions established the presence of several fibrin(ogen)-derived protein bands. It is therefore proposed that thrombin cleavage of fibrinogen, in addition to producing fibrin, generates high-molecular-weight soluble cleavage products that may play an important role during normal wound healing and in the pathogenesis of disease states associated with vascular leakage and fibrosis.

Cell Division↗