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Biomedical subjects

A Price

Publications and source records attributed to A Price.

At least 127 records · Page 7Linked to original sources
PubMed1993

Survival, patterns of spread and prognostic factors in uterine sarcoma: a study of 76 patients.

We have analysed the medical records and diagnostic imaging of 76 patients presenting to this hospital for treatment of uterine sarcoma between 1970 and 1990. Patients were divided into those presenting before 1980 (n = 22) and after 1980 (n = 54), when sectional imaging (ultrasound, CT scanning) and more modern radiotherapy and chemotherapy were introduced. No survival difference was observed between these two groups. In those patients presenting after 1980, the median age was 54 years (range 18-80), and median survival 22 months from initial diagnosis. Factors associated with a significantly improved survival included low grade (although not histological type) of initial tumour (p = 0.001) and Stage I disease at presentation (p = 0.006). In 17 patients receiving pelvic radiotherapy following initial surgery, both the time to relapse (p = 0.005) and overall survival (p = 0.045) were increased. Adjuvant chemotherapy in 19 patients did not improve outcome. Most diagnoses of relapse were established clinically; they occurred most frequently in the pelvis, followed by lung and abdomen. Pulmonary relapse was accompanied by spontaneous pneumothorax in two cases. Bone and brain metastases were uncommon (< 10%). Following diagnosis of relapse, the median survival was 9 months, with the outcome significantly worse if multiple metastatic sites were involved (p < 0.001). No survival benefit was demonstrated from either local radiotherapy or combination chemotherapy once relapse had occurred. Prognostic factors and current policies for the diagnosis and management of uterine sarcomas are discussed.

Adolescent↗
PubMed1993

Interleukin-1 stimulates the release of interleukin-6 from cultured human pituitary adenoma cells.

Interleukin-6 (IL-6) was secreted by cultured cells of 7 out of 11 human pituitary adenomas that were examined. Interleukin-1 (IL-1) stimulated IL-6 release after a 24-h incubation period in five of the seven IL-6-secreting adenoma cultures and in all seven after 72 h. Tumour necrosis factor, interferon-gamma and epidermal growth factor did not significantly affect IL-6 secretion. Interleukin-1 failed to induce measurable IL-6 in the cultures that did not secrete IL-6 under basal conditions. Prostaglandin E2 did not influence basal IL-6 secretion and indomethacin did not inhibit IL-1-stimulated IL-6 release. In addition, pertussis toxin had no effect on IL-1-stimulated IL-6 release. The growth hormone (GH) secretory response to IL-1 varied, with stimulation in one GH-secreting adenoma culture, no significant effect in a second and inhibition in a third. Interleukin-1 did not significantly affect the release of prolactin, thyrotrophin, luteinizing hormone or follicle-stimulating hormone in any of the adenoma cultures. This study provides evidence that IL-1 is a stimulator of IL-6 release from cultured human pituitary adenoma cells that secrete IL-6. Stimulation of IL-6 release by IL-1 in these tumour cells is probably not mediated by prostaglandins or by a pertussis toxin-sensitive mechanism.

Adenoma↗
PubMed1993

Osteopathic medicine: a call for reform.

During the past 40 years, the osteopathic medical profession has undergone a transformation from "osteopathy" to "osteopathic medicine." The former was characterized by manipulative treatment; the latter, by full-service healthcare. During this transformation, the profession has won acceptance from the government, the military, and MDs. These changes in status have resulted in new problems for the profession because DO graduates are increasingly turning toward allopathic programs for residency training. Thus, osteopathic medicine's primary care orientation is being replaced by an emphasis on specialty training. The authors propose that osteopathic medicine return to its original mission of primary care, abandon or restrict specialty training to those who have completed primary care residencies, and rethink its separate-but-equal posture. They also propose that osteopathic medicine establish lines of communication with allopathic medicine, the American Medical Association, and the government to facilitate the development of a rational national policy for primary care that considers the potential osteopathic medicine has to offer in meeting the nation's primary care needs.

Education, Medical, Graduate↗
PubMed1993

The repair of ionising radiation-induced damage to DNA.

Exposure of DNA to ionising radiation produces a variety of lesions. Double-strand breaks are repaired by recombinational pathways including a rapid single-strand annealing process which results in deletion of DNA sequences, and a double-strand break repair pathway which conserves genetic information. Single-strand breaks are repaired by the sequential action of a 3'-phosphodiesterase, DNA polymerase beta and a DNA ligase. Damaged bases are excised by DNA glycosylases, and a single-base gap introduced, either by the action of an AP endonuclease activity and a DNA deoxyribophosphodiesterase, or by the AP lyase activity of the glycosylase and an AP endonuclease. Repair is completed by DNA polymerase beta and a DNA ligase.

Animals↗
PubMed1992

Action of Escherichia coli and human 5'----3' exonuclease functions at incised apurinic/apyrimidinic sites in DNA.

The 5'----3' exonuclease activity of E. coli DNA polymerase I and a related enzyme activity in mammalian cell nuclei, DNase IV, are unable to catalyse the excision of free deoxyribose-phosphate from apurinic/apyrimidinic (AP) sites incised by an AP endonuclease. Instead, the sugar phosphate residue is slowly released as part of a short oligonucleotide. These products have been characterised as dimers and trimers by comparison of their retention time on reverse-phase HPLC with reference compounds prepared by acid depurination of a dinucleotide, trinucleotide and tetranucleotide containing a 5'-terminal dAMP residue. The similar mode of action of these enzymes at 5'-incised AP sites provides an explanation for the minority of repair patches larger than one nucleotide observed when AP sites are repaired by E. coli and mammalian cell extracts in vitro and strengthens the functional analogy between the two activities.

Apurinic Acid↗
PubMed1992

Primary radiotherapy for T4 breast cancer.

In Edinburgh in 1982, radiotherapy for patients with T4 breast cancer was modified by an increase in tumour absorbed dose from 42.5-45.0 Gy to 60-75 Gy by using tumour boosts and changing from alternate day to daily fractions. To assess whether this improved local control or survival, the records of all females with T4-N0-3M0 breast cancer referred between January 1978 and December 1985, who received radiotherapy without initial mastectomy or adjuvant chemotherapy, were reviewed. There were 193 patients in the study. Minimum follow-up was 36 months. Actuarial survival at 5 years was 27.1% and median survival 29 months. Local control was achieved by 25.9%. On multivariate analysis, the probability of survival fell with increasing tumour size, advanced clinical node status and the presence of inflammatory change. Radiotherapy technique also affected prognosis. Four-field techniques were associated with a better chance of survival than the breast and axillary jig or other treatment methods. The probability of local control increased with reduced tumour size and showed the same relationship to radiotherapy technique as did survival. Dose was not a significant variable for either survival or local control. No improvement in survival or local control was apparent in comparison with a previous study. It is concluded that radiotherapy alone at a dose of 60 Gy is insufficient to produce durable local control for the majority of women with T4 breast cancer.

Aged↗
PubMed1992

The crisis in osteopathic medicine.

During the last 30 years the osteopathic profession has undergone a remarkable transformation from osteopathy, characterized by manipulative therapy, to osteopathic medicine, characterized by full-service health care, and in the process it has won acceptance from the government, the military, and physicians. These changes in status have resulted in new problems for the profession, because D.O. graduates are turning increasingly toward M.D. programs for residency training, and osteopathic medicine's primary care orientation is being replaced by an emphasis on specialty training. The authors advocate that osteopathic medicine return to its original mission of primary care, abandon specialty training or restrict it to those who have completed primary care residencies, abolish its separate-but-equal posture, and establish lines of communication with allopathic medicine and the American Medical Association to facilitate the development of a rational national policy for primary care that considers the potential osteopathy has to offer in meeting the nation's primary care needs.

Education, Medical, Graduate↗
PubMed1992

Comparison of methods for the determination of unbound triiodothyronine in pregnancy.

OBJECTIVE: To study the changes in unbound T3 concentration in the first trimester of pregnancy. DESIGN: We measured serum unbound T3 concentration before and after termination of pregnancy. PATIENTS: Twenty-six clinically euthyroid women. MEASUREMENTS: We used one non-analogue assay (Sclavo) and three analogue assays (Amersham, Becton Dickinson and Diagnostic Products Corporation). RESULTS: Regression analysis did not show any significant agreement between the analogue and non-analogue assays. After termination of pregnancy, unbound T3 concentration as measured by Sclavo and Amersham assays did not change whereas unbound T3 concentration increased and decreased as measured by Becton Dickinson and Diagnostic Products assays respectively. Changes were not directly related to albumin or thyroid binding globulin. CONCLUSION: We believe unbound T3 concentrations as measured by the analogue assays used in this study are due to a balance of errors and cannot be used to determine true physiological changes in pregnancy.

Abortion, Induced↗
PubMed1992

Thyrotoxicosis and hyperemesis gravidarum associated with a serum activity which stimulates human thyroid cells in vitro.

OBJECTIVE: To investigate in-vitro thyroid stimulatory activity in the serum of patients with hyperemesis gravidarum and thyrotoxicosis. DESIGN: Serum from hyperthyroid patients was incubated with cultures of human thyroid cells. Attempts were made to neutralize stimulatory activity with antisera to hCG. PATIENTS: Five patients presenting in early pregnancy with hyperemesis and thyrotoxicosis. MEASUREMENTS: Serum concentrations of thyroid hormones (total and free), TSH and hCG. Accumulation of extracellular cAMP in response to serum. RESULTS: All five patients had biochemical hyperthyroidism with no evidence of an underlying autoimmune disease. The mean cAMP accumulation over 4 hours with sera from 12 non-pregnant controls was 130.6 (121.8-142.8), from 12 pregnant controls 132.4 (118.1-143.8), compared with values of 144.7, 159.1, 166.2, 178.9 and 320.5 for the thyrotoxic patients. The stimulatory activity could not be neutralized by addition of anti-hCG or by depleting the sera of hCG. CONCLUSIONS: Thyrotoxicosis may present with hyperemesis in early pregnancy. Clinical and biochemical features may be masked by the pregnancy or by the intercurrent illness. The hypothesis that hCG is a thyroid stimulator in patients with hyperemesis gravidarum is not supported by the immuno-neutralization data in this study.

Cells, Cultured↗
PubMed1992

Generation of single-nucleotide repair patches following excision of uracil residues from DNA.

The extent and location of DNA repair synthesis in a double-stranded oligonucleotide containing a single dUMP residue have been determined. Gently prepared Escherichia coli and mammalian cell extracts were employed for excision repair in vitro. The size of the resynthesized patch was estimated by restriction enzyme analysis of the repaired oligonucleotide. Following enzymatic digestion and denaturing gel electrophoresis, the extent of incorporation of radioactively labeled nucleotides in the vicinity of the lesion was determined by autoradiography. Cell extracts of E. coli and of human cell lines were shown to carry out repair mainly by replacing a single nucleotide. No significant repair replication on the 5' side of the lesion was observed. The data indicate that, after cleavage of the dUMP residue by uracil-DNA glycosylase and incision of the resultant apurinic-apyrimidinic site by an apurinic-apyrimidinic endonuclease activity, the excision step is catalyzed usually by a DNA deoxyribophosphodiesterase rather than by an exonuclease. Gap-filling and ligation complete the repair reaction. Experiments with enzyme inhibitors in mammalian cell extracts suggest that the repair replication step is catalyzed by DNA polymerase beta.

Apurinic Acid↗
PubMed1992

Metronidazole reduces intestinal inflammation and blood loss in non-steroidal anti-inflammatory drug induced enteropathy.

This study assessed the effect of metronidazole on the gastroduodenal mucosa, intestinal permeability, blood loss, and inflammation in patients on non-steroidal anti-inflammatory drugs (NSAIDs). Thirteen patients were studied before and after 2-12 weeks' treatment with metronidazole 800 mg/day, while maintaining an unchanged NSAID intake. Intestinal inflammation, as assessed by the faecal excretion of indium-111 labelled neutrophils, and blood loss, assessed with chromium-51 labelled red cells, were significantly reduced after treatment (mean (SD) 111In excretion 4.7 (4.7)% v 1.5 (1.3)% (N < 1.0%), p < 0.001, 51Cr red cells loss 2.6 (1.6) ml/day v 0.9 (0.5) ml/day (N < 1.0 ml/day), p < 0.01). Intestinal permeability assessed as the 5 hour urinary excretion ratio of 51CrEDTA/L-rhamnose did not change significantly (0.133 (0.046) v 0.154 (0.064), p > 0.1) and there were no significant changes in the endoscopic or microscopic appearances of the gastroduodenal mucosa. These results suggest that the neutrophil is the main damaging effector cell in NSAID induced enteropathy. The main neutrophil chemo-attractant in this enteropathy may be a metronidazole sensitive microbe.

Aged↗
PubMed1992

Human chorionic gonadotropin may not be responsible for thyroid-stimulating activity in normal pregnancy serum.

Although hCG can activate thyroid cells in culture there is considerable doubt as to whether it is responsible for the changes in thyroid function which occur during normal pregnancy. Thyroid-stimulating activity (TSA), measured using iodide uptake into FRTL-5 cells, was demonstrated in 32/51 (63%) first and 15/29 (52%) third trimester sera. Free T3 was increased (P less than 0.001) and TSH decreased (P less than 0.01) in first trimester. In the early pregnancy group there was a positive correlation between hCG and TSA (r = 0.594, P less than 0.001) and a negative correlation between hCG and TSH (r = -0.329, P less than 0.02). In third trimester hCG concentration was often below that required to produce TSA in vitro and TSA could not be neutralized by antibodies to hCG. There was no correlation between hCG and TSH or thyroid hormones in the third trimester. In 26 women TSA decreased in parallel with serum hCG concentration after termination of pregnancy (P less than 0.001). Free T3 also decreased (P less than 0.01) and TSH increased (P less than 0.05) after termination. TSA persisted in many patients even after hCG was either very low or undetectable. Purified hCG stimulated iodide uptake in a concentration-dependent manner. Stimulation of iodide uptake by TSH was inhibited by the simultaneous presence of low concentrations of hCG while activity was restored with high concentrations. hCG may contribute to the thyroid changes in early pregnancy. However the poor correlation between TSA and thyroid tests suggests that other factors may be involved. The partial agonist activity of hCG may account for some of the inconsistencies observed but TSA in serum from late pregnancy or after termination of pregnancy is almost certainly due to another hormone or growth factor.

Adult↗
PubMed1991

Enzymatic release of 5'-terminal deoxyribose phosphate residues from damaged DNA in human cells.

Activities that catalyze or promote the release of 5'-terminal deoxyribose phosphate residues from DNA abasic sites previously incised by an AP endonuclease have been identified in soluble extracts of several human cell lines and calf thymus. Such excision of base-free sugar phosphate residues from apurinic/apyrimidinic sites is expected to be obligatory prior to repair by gap filling and ligation. The most efficient excision function is due to a DNA deoxyribophosphodiesterase similar to the protein found in Escherichia coli. The human enzyme has been partially purified and freed from detectable exonuclease activity. This DNA deoxyribophosphodiesterase is a Mg(2+)-requiring hydrolytic enzyme with an apparent molecular mass of approximately 47 kDa and is located in the cell nucleus. By comparison, the major nuclear 5'----3' exonuclease, DNase IV, is unable to catalyze the release of 5'-terminal deoxyribose phosphate residues as free sugar phosphates but can liberate them at a slow rate as part of small oligonucleotides. Nonenzymatic removal of 5'-terminal deoxyribose phosphate from DNA by beta-elimination promoted by polyamines and basic proteins is a very slow mechanism of release compared to enzymatic hydrolysis. We conclude that a DNA deoxyribophosphodiesterase acts at an intermediate stage between an AP endonuclease and a DNA polymerase during DNA repair at apurinic/apyrimidinc sites in mammalian cells, but several alternative routes also exist for the excision of deoxyribose phosphate residues.

Animals↗
PubMed1991

Controlled intraoral delivery of hydrocortisone sodium succinate.

Controlled release of hydrocortisone sodium succinate from a device consisting of a drug containing a core of polymethyl methacrylate was achieved by the use of a design incorporating impermeable barriers to drug diffusion and the use of a semipermeable membrane. Initial in vivo study showed sustained intraoral delivery of hydrocortisone sodium succinate during a 6-day period.

Administration, Oral↗
PubMed1991

The N-terminal heptad repeat region of reovirus cell attachment protein sigma 1 is responsible for sigma 1 oligomer stability and possesses intrinsic oligomerization function.

The oligomerization domain of the reovirus cell attachment protein (sigma 1) was probed using the type 3 reovirus sigma 1 synthesized in vitro. Trypsin cleaved the sigma 1 protein (49K molecular weight) approximately in the middle and yielded a 26K N-terminal fragment and a 23K C-terminal fragment. Under conditions which allowed for the identification of intact sigma 1 in the oligomeric form (approximately 200K) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the N-terminal 26K fragment was found to exist as stable trimers (80K) and, to a less extent, as dimers (54K), whereas the C-terminal fragment remained in the monomeric form. A polypeptide (161 amino acids) containing the N-terminal heptad repeat region synthesized in vitro was capable of forming stable dimers and trimers. Using various criteria, we demonstrated that the stability of the intact sigma 1 oligomer is conferred mainly by the N-terminal heptad repeat region. Our results are summarized in a model in which individual heptad repeats are held together in a three-stranded alpha-helical coiled-coil structure via both hydrophobic and electrostatic interactions.

Amino Acid Sequence↗
PubMed1991

Nodal involvement in poorly differentiated breast cancer.

The degree of nodal involvement in a consecutive series of 400 patients with invasive ductal breast cancer is presented. A positive correlation was observed between the number of metastatic nodes identified and the number of axillary nodes examined for poorly but not moderately differentiated tumours. The relevance of this observation to breast cancer trials is discussed.

Adult↗