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Biomedical subjects

S Tucker

Publications and source records attributed to S Tucker.

At least 55 records · Page 3Linked to original sources

The clonogenic growth of advanced breast tumour lesions adds no value to that of established clinical prognosticators for survival.

We measured the clonogenic growth of 110 breast cancer samples obtained from 107 patients with advanced disease. We determined clonogenicity under conventional conditions and under conditions supplemented with growth factors and hormones that target breast tissue. After a median follow-up period of 6 years we analyzed our data to determine if and to what degree clonogenic growth of metastatic breast tumours was related to the survival of patients. We found that tumour clonogenicity and patient survival correlated weakly, particularly if compared to the strong correlations of patient survival with either performance status or tumour bulk. Furthermore, an association between tumour clonogenicity and patient survival was visible only for clonogenicity that was determined under hormone-supplemented conditions, and only for tumour lesions that formed 50 or more colonies per 500,000 cells cultured. Thus, we conclude that clonogenic growth of breast tumour samples incompletely reflects the tumour features that determine the course of advanced disease.

Breast Neoplasms↗

Understanding women's responses to treatment for cervical intra-epithelial neoplasia.

Laser treatment is held to prevent the development of cervical intra-epithelial neoplasia, or CIN, into invasive carcinoma of the cervix. Recent work has found that such treatment represents a considerable emotional upset in the lives of many women. In this study, the impact of treatment was further investigated, using a control group to separate the effects of diagnosis from those of treatment. The main findings showed that the diagnosis of CIN is traumatic. Women experience high levels of intrusive thoughts and avoidance, and in response to perceived threats to their health, and existing beliefs about themselves, they also experience high levels of anger. An impact of treatment over and above that of diagnosis was not found. From the interview data, diagnosis has its traumatic impact through women's understanding of CIN's association with cervical cancer, a potentially life-threatening disease. Interview data also suggest that body image and sexual relationships suffer following diagnosis because of CIN's postulated causal relationship to the sexually transmitted wart virus. Fear of the progression of CIN to cervical cancer is consistent with the medical model which provides the rationale for preventative laser treatment. It is speculated that once women are diagnosed as having CIN, the spectre of cancer is raised and their anxiety may be such that being monitored and not immediately treated may cause them great distress.

Adult↗

Radial keratotomy in the soldier-aviator.

Radial keratotomy (RK) is an ophthalmological procedure that alters the shape of the cornea, making it "flatter," causing the desired shift to farsightedness. Complications can be minor and "normal" in the immediate post-operative period, or can include problems that occur in many eyes, that persist but do not decrease best corrected visual acuity, or may include events that potentially or actually threaten vision and may produce blindness. At best, only 50% of patients can expect to have 20/20 uncorrected vision 2-3 years after surgery. Diurnal fluctuations in vision (two-five Snellen lines) can persist years after RK. Perhaps 1% of patients may have a two-three Snellen line loss of best corrected vision or ghost images that interfere with clear vision. Disabling glare can disrupt daily activities. Eyes that have undergone RK are at increased risk of corneal rupture after blunt eye trauma. The visual demands of the active duty military, and more dramatically the military aviator, are incompatible with RK. Therefore, RK should not be performed on active duty soldiers, nor should enlistees be accepted if they have undergone the procedure.

Aerospace Medicine↗

The hydrophobic membrane-spanning sequences of the gp52 glycoprotein are required for the pathogenicity of Friend spleen focus-forming virus.

Friend spleen focus-forming virus (SFFV) codes for a transport-defective envelope glycoprotein designated gp52, which is responsible for the leukemogenic properties of the virus. gp52 is a monotopic integral membrane protein anchored in the membrane by a stretch of hydrophobic amino acid residues located near the carboxy terminus of the molecule. We have constructed a mutant SFFV envelope gene in which the sequences that code for the hydrophobic membrane-spanning domain have been deleted, and we expressed this gene by using recombinant vaccinia virus vectors or retroviral vectors. The mutant SFFV envelope gene was found to encode a truncated glycoprotein (gp52t) which was also transport defective; a majority of gp52t remained cell associated, while a small proportion of the molecules underwent oligosaccharide processing. The processed form of gp52t was secreted from the cells. Retroviral vectors carrying the mutant SFFV envelope gene were found to be nonpathogenic in adult mice. These results indicate that the hydrophobic membrane-spanning region of gp52 is required for pathogenicity of SFFV and suggest that these sequences may play a role in signal transduction. The results also indicate that the transport defect of SFFV gp52 is due to structural features of the ectodomain of the molecule.

Amino Acid Sequence↗

VAD-based regimens as primary treatment for multiple myeloma.

An alternating VCAD-VAD regimen, combining vincristine-doxorubicin by continuous infusion with cyclophosphamide and pulse dexamethasone, or VAD alone, was given to 175 previously untreated patients with multiple myeloma. The response rate with primary VAD-based regimens of 55% was virtually identical to the 54% in comparable patients treated previously with similar programs by using bolus vincristine-doxorubicin. Despite responses to VAD that were more rapid in onset than any previous treatment, remission and survival times were similar. This may be due to major differences in drug sensitivity between progenitor and differentiated plasma cells. A VAD-based regimen seems better for newly diagnosed patients when rapid control of multiple myeloma is necessary.

Antineoplastic Combined Chemotherapy Protocols↗

The effect of concomitant disorders in childhood depression on predicting treatment response.

Children with pure depression or depression plus an anxiety-related disorder (n = 14) had a higher drug response rate (57%) and a lower placebo response rate (20%) when compared to children with depression plus a concomitant conduct or oppositional disorder (n = 17) (33% drug response rate and 67% placebo response rate). These findings could explain why studies of prepubertal-onset depression found no differences between drug and placebo treatment assuming that a large percentage of the studies' subjects had concomitant conduct or oppositional disorders. The children with pure depression or depression plus an anxiety-related disorder had different symptom clusters from those with depression plus a concomitant conduct or oppositional disorder. The former had more severe CDRS ratings on sleep, appetite disturbance, depressed feelings, and psychomotor retardation. In contrast, those with a concomitant conduct or oppositional disorder had shorter attention spans and were more likely to disturb other children (based on Conners scale scores).

Child↗

Followup of adolescents initially treated for prepubertal-onset major depressive disorder with imipramine.

This preliminary followup of adolescents (n = 16) with prepubertal-onset major depressive disorder (MDD) suggests that a significant number continue to be depressed or possibly depressed (62%) and have moderate to severe ongoing psychosocial adjustment problems. A concomitant diagnosis of conduct or oppositional disorder at index assessment was a risk factor for an increased incidence of interim depressive episodes and more severe psychosocial adjustment problems including alcohol and drug abuse.

Adolescent↗

Posterior horizontal and vertical tightening to treat combined punctal ectropion with medial canthal tendon laxity.

The classical operations to treat either medial canthal tendon laxity or punctal aversion occurring alone possess drawbacks if they are used to treat these conditions when they occur simultaneously. A simplified procedure is described whereby tissue is removed via a posterior eyelid approach so that the eyelid may be tightened both horizontally and vertically, thus inverting the punctum and fixating it in the lacrimal lake. This procedure is quite easy to perform and can be done under local anesthesia in the office.

Ectropion↗

Sexual assault evidence collection.

The evidentiary exam following sexual assault provides crucial evidence that can be used by the prosecuting attorney to obtain a conviction in sexual assault cases. Evidence is collected for three purposes: to corroborate the use of force; to corroborate that recent sexual contact occurred; and to identify the perpetrator. Relatively few assailants (4%) go to jail for rape. To a great extent this is because of a lack of corroborating evidence and misinterpretation of this lack of evidence by police, courts, and jurors. This paper presents the results of a study to determine the likelihood of obtaining corroborating evidence of recent coitus along with an explanation of what negative results mean. Based on the results, recommendations are presented for sexual assault evidence collection in emergency departments.

Acid Phosphatase↗

In vitro thermo-chemosensitivity screening of spontaneous human tumors: significant potentiation for cisplatin but not adriamycin.

The in vitro thermal enhancement of Adriamycin (ADR) and Cisplatin (CDDP) was investigated in 18 surgical biopsy specimens of human tumors cultured in the Adhesive Tumor Cell Culture System. Experimental conditions were adopted to simulate "therapeutic" trials: (a) temperature of 37.0 degrees C, 40.5 degrees C or 42.5 degrees C; (b) hyperthermic duration of 30, 60, or 120 min; and (c) 4-dose drug range normalized to human bone marrow toxicity. Drug concentrations that inhibited 90% of tumor growth (IC90) at 37.0 degrees C were compared to the IC90 at 40.5 degrees C and 42.5 degrees C, adjusted for the effect of heat alone. CDDP plus heat was a better combination than ADR plus heat, regardless of the temperature and the exposure duration: significant synergism (p less than 0.001) occurred in 37% of heat-CDDP combinations, as compared with 15% of heat-ADR combinations, and antagonism was significantly lower (p less than 0.001) for heat-CDDP than for heat-ADR (4.4% versus 21% of combinations, respectively). Within the CDDP group, higher temperature and longer heat exposure resulted in an increased incidence of chemosensitivity. No specific pattern of synergism was evident within the ADR group, but a trend toward a higher incidence of antagonistic effects with increasing hyperthermic duration was observed.

Cisplatin↗

A new serologic staging system for large-cell lymphomas based on initial beta 2-microglobulin and lactate dehydrogenase levels.

We report results of our investigation of prognostic factors for patients with large-cell lymphoma who were entered on the same treatment protocol and who had known pretreatment serum beta 2-microglobulin (beta 2M) and lactate dehydrogenase (LDH) levels. beta 2M and LDH levels were the most significant and independent variables for predicting time to treatment failure (TTF) and survival. The serum level of beta 2M correlated with tumor burden. These two serum markers defined three significantly different prognostic groups. All 27 patients in the low-risk group remain alive and in remission; in contrast, 22 of the 27 patients (81%) in the high-risk group have failed treatment, and only seven (26%) remain alive. In comparison with the Ann Arbor staging system, serum levels of beta 2M and LDH may provide a more precise system for defining risk groups and thereby allow a more rational approach to the development and analysis of treatment strategies.

Adult↗

Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep.

Leukotrienes have been suggested to play a role in the endotoxin-induced changes of the pulmonary hemodynamics and airway mechanics. Since Ca2+ is necessary for contraction of airway and vascular smooth muscle as well as for activation of phospholipase A2 and 5-lipoxygenase enzymes, we wondered whether the calcium antagonist verapamil would modify the endotoxin-mediated pulmonary effects as well as the generation of circulating eicosanoids. In twelve conscious sheep, measurements of pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), lung resistance (RL), arterial PO2 (PaO2), leukocyte (WBC) count, arterial thromboxane B2 (TxB2), prostaglandin (PG) F2 alpha, and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentrations were obtained before and at predetermined intervals after a 10-min infusion of Escherichia coli endotoxin (0.3 microgram/kg). On separate occasions, the sheep received a bolus injection of verapamil (150 micrograms/kg) before endotoxin, followed by a continuous infusion of verapamil [10 micrograms.kg-1.min-1 (n = 5) or 20 micrograms.kg-1.min-1 (n = 7)] for up to 4 h post-endotoxin. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 326 and 276% of base line during phase I (0-1 h) and lesser increases to 177 and 157% of base line during phase II (1.5-4 h), respectively (P less than 0.05). SVR also showed biphasic increases of 44 and 42% during phase I and II, respectively. Mean PaO2 decreased by 16 Torr and WBC count decreased from 6.4 +/- 1.5 to 3.3 +/- 1.1 thousand/mm3, associated with marked increases in plasma TxB2, PGF2 alpha, and 6-keto-PGF1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Evaluation of drugs for elimination of leukemic cells from the bone marrow of patients with acute leukemia.

Relatively nonmyelotoxic drugs and drug combinations were investigated for their ability to eliminate malignant cells from human bone marrow. In vitro 90% inhibitory concentration (IC90) doses were established on granulocyte macrophage colony-forming units (GM-CFU) in culture of bone marrow by using the GM-CFU assay for the following drugs: 4-hydroperoxycyclophosphamide (4-HC), Adriamycin, L-asparaginase, bleomycin, hydrocortisone, VP-16, spirogermanium, Taxol, and vincristine. The leukemic cell kill efficiency of these drugs at IC90 doses was compared with that of 4-HC on acute lymphoid leukemia (ALL) cell lines by using the limiting-dilution assay. Under these conditions, no single drug was superior to 4-HC. To increase the in vitro effect in leukemic cell kill, combinations of vincristine with hydrocortisone, Adriamycin, VP-16, and 4-HC were investigated. Vincristine at 1 to 5 micrograms/mL increased the marrow cytotoxicity of hydrocortisone, Adriamycin, and VP-16, but it was protective (subadditive) with 4-HC. Vincristine and 4-HC in combination was additive to supraadditive on ALL cell lines, increased the leukemic cell kill by one to two logs above 4-HC alone at IC90 doses (P less than .05), and was not affected by the addition of excess marrow cells. The recommended doses for chemopurging in clinical studies are vincristine, 1 to 5 micrograms/mL, plus 4-HC, 5 micrograms/mL.

Antineoplastic Agents↗

Prevention and reversal of endotoxin-induced pulmonary hypertension by a leukotriene antagonist.

We investigated the role of leukotrienes in endotoxin-induced changes in pulmonary circulation. In six conscious sheep, haemodynamic measurements were obtained for the calculation of pulmonary vascular resistance (PVR), along with measurements of arterial oxygen tension (PaO2), leucocyte count (WBC), thromboxane B2 (TxB2), 6-Keto-PgF1 alpha and PgF2 alpha, before and at predetermined intervals after a 10-min infusion of E. coli endotoxin (0.3 microgram/kg), with and without treatment with the leukotriene receptor antagonist, FPL-57231. Endotoxin caused a biphasic response (i.e., phase I = 0-1 h, phase II = 1.5-4 h), with a mean +/- SE increase in PVR to 415 +/- 112% of baseline during phase I and a lesser increase of 175% (range = 153-199%) of baseline during phase II. Mean +/- SE PaO2 decreased from 86 +/- 4 to 67 +/- 6 mmHg and WBC count decreased from 8.6 +/- 0.6 to 2.8 +/- 0.7 thousand/mm3 during phase I, whereas TxB2 increased from 145 +/- 28 to 3164 +/- 1082 pg/ml, 6-Keto-PgF1 alpha from 129 +/- 14 to 438 +/- 114 pg/ml and PgF2 alpha from 122 +/- 7 to 242 +/- 43 pg/ml. One hour infusion of FPL-57231 (1 mg/kg/min) administered prior to and throughout phase I attenuated the phase I increases in PVR without preventing the increases in TxB2; however, it partly attenuated 6-Keto-PgF1 alpha and enhanced generation of PgF2 alpha during phase I. Discontinuation of FPL-57231 was followed by an exaggerated response of PVR during phase II to an average of 209% of baseline (range = 186-235%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗