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J M Connors

Publications and source records attributed to J M Connors.

At least 109 records · Page 6Linked to original sources
PubMed1988

Vasoactive intestinal peptide treatment that increases thyroid blood flow fails to alter plasma T3 or T4 levels in the rat.

Vasoactive-intestinal-peptide (VIP)-containing nerve fibers impinge upon both follicle cells and blood vessels in the thyroid gland. We have previously shown that VIP induces a specific, dose-related increase in thyroid blood flow in the rat. However, our VIP treatments had no effect on circulating thyroid hormone levels. Since a number of reports have indicated that VIP can enhance thyroid hormone secretion, we have expanded our studies to characterize more completely the conditions under which VIP might stimulate thyroid hormone secretion in the rat. In unanesthetized, unstressed rats with chronic catheters, 33 micrograms VIP/100 g body weight failed to alter triiodothyronine (T3) or thyroxine (T4) levels and did not affect the thyroid secretory response to a submaximal dose of bovine TSH. In euthyroid and hyperthyroid rats, the release of 125I was increased after exogenous TSH, but was not altered by VIP. The only condition in which we observed a rise in circulating T3 levels in response to VIP was during a continuous 2 h infusion of a high dose (0.25 microgram/min, i.v.) of this peptide. However, plasma TSH levels tended to be elevated in these rats, suggesting an indirect effect via TSH. This suggestion is strengthened by our observation that VIP failed to alter T3 or T4 release after topical application (0.1 microgram/microliter for 3 h) in vivo or after in vitro treatment (10(-6) M for 4 h), even though these preparations were fully responsive to bovine TSH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Testicular lymphoma: improved outcome with early brief chemotherapy.

We investigated the impact of early brief chemotherapy on the natural history of primary testicular lymphoma. We compared the outcome for patients seen before 1980--a group primarily managed with orchiectomy and regional radiation--with those seen from 1980 to 1986--a prospectively and consecutively gathered group who were offered brief chemotherapy in addition to standard orchiectomy and irradiation. The historical and study groups were similar in clinical characteristics. However, the chemotherapy group had a better relapse-free survival, 93% v 50% (P less than .02), and overall survival, 93% v 50% (P less than .02). With a median follow-up of 44 months in the chemotherapy group, it is clear that the use of early, brief chemotherapy strongly alters the natural history of testicular lymphoma by preventing relapses, the large majority of which occur early after regional therapy. We conclude that a program incorporating orchiectomy, early brief chemotherapy, and involved-field radiation therapy confers the following benefits on patients with primary testicular lymphoma: (1) laparotomy is not needed for staging; (2) relapses, including those in the opposite testicle and CNS, are largely prevented; and (3) toxicity can be kept to a modest level acceptable in elderly patients.

Aged↗
PubMed1988

Effects of thyrotropin on the vascular conductance of the thyroid gland.

It is well established that TSH from the anterior pituitary is the principal stimulatory agent in the physiological regulation of the thyroid gland. Chronic elevations of plasma TSH induce hyperplasia and hypertrophy of thyroid follicular cells and enlargement of blood capillaries. At low plasma TSH levels the thyroid gland atrophies. We have examined the vascular conductance (C = blood flow/mean arterial pressure) of the thyroid gland and several other tissues over a wide range of endogenous plasma TSH concentrations and after treatment with bovine TSH (bTSH) in rats. Tissue blood flows were determined using 15 +/- 5-microns diameter 141Ce-labeled microspheres in a modification of the reference sample microsphere technique. The microspheres were injected directly into the left cardiac ventricle via a 23-gauge needle passed through the chest wall, while the reference blood sample was collected and systemic arterial blood pressure was monitored through femoral arterial catheters. After the animals were killed, tissues were cleaned and weighed, and the tissue radioactivity was determined. Blood samples for determination of plasma hormone levels were obtained from the jugular vein before the injection of microspheres. In the first series of experiments, the vascular C per mass of thyroid gland was significantly decreased 4 and 8 days after hypophysectomy. Treatment of hypophysectomized rats with bTSH (185 mU/100 g.day as a continuous iv infusion for 2 or 6 days) restored thyroid vascular C per mass of tissue to control levels. In the second series of experiments, we manipulated circulating plasma TSH levels in intact rats by 6 days of treatment with propylthiouracil (2.0 mg/day, ip), thyroid hormones (1.5 micrograms T4, 0.4 micrograms T3 or 3.0 micrograms T4, plus 0.8 micrograms T3/100 g.day, sc by continuous infusion), TRH (240 micrograms/day, iv, by continuous infusion), bTSH (800 mU/day, iv, by continuous infusion), or combinations of these treatments. The vascular C per mass of thyroid gland was significantly decreased at very low chronic plasma TSH levels and increased at very high chronic plasma TSH levels. Thyroid vascular C per mass was unchanged, however, over a broad intermediate range of plasma TSH concentrations encompassing normal values, despite alterations in the size and function of the thyroid gland. At these intermediate levels of TSH stimulation, the thyroid gland may respond by adding or subtracting functional units without changing the blood flow per unit. The amount of blood flow per functional unit may be altered only at very high or very low levels of TSH stimulation.

Adrenal Glands↗
PubMed1988

An update on the Vancouver experience in the management of advanced Hodgkin's disease treated with the MOPP/ABV Hybrid program.

Between February 1980 and July 1984, 79 patients with newly diagnosed advanced Hodgkin's disease were treated with a new seven-drug regimen, the mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine) MOPP/ABV) Hybrid. The treatment plan allowed for a course of involved-field radiotherapy (RT) (3,500 cGy in 20 fractions) to a single area of residual lymph-node-related abnormalities if still present after six cycles of chemotherapy. Of 76 evaluable patients, 74 (97.5%) achieved complete remission (CR), ten (13%) with assistance of involved-field RT. Only two patients (2.5%) were primary treatment failures. Seven patients (9.5%) relapsed; all relapses occurred in the first 24 months of follow-up. The majority of relapses were males with large mediastinal masses and B symptoms. The actuarial overall survival of all 79 patients with the maximum and median follow-up times of 80 and 53 months, respectively, is 93.5%. The actuarial relapse-free survival for the 74 CRs with the maximum and median follow-up times of 71 and 46 months, respectively, is 90.5%. The treatment tolerance was acceptable; only one patient died from causes directly related to the treatment, and less than 10% of patients required hospitalization for suspected or proven systemic infection. The treatment delivery was excellent, as greater than 75% of the treated patients took greater than 90% of the prescribed treatment; greater than 90% of patients received at least 75% of the calculated doses of drugs. This long-term follow-up report supports our initial impression that the MOPP/ABV Hybrid chemotherapy is an effective and well-tolerated program for patients with advanced Hodgkin's disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

MACOP-B chemotherapy for malignant lymphomas and related conditions: 1987 update and additional observations.

Between 1981 and 1986, we treated 179 newly diagnosed patients with advanced-stage malignant lymphoma or related conditions with methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin (MACOP-B). Experience with 12 different histologic subtypes indicates that MACOP-B is acceptably tolerated and effective for diffuse large cleaved cell, diffuse large noncleaved cell, diffuse mixed large and small cleaved cell, immunoblastic, and discordant lymphomas but not for angioimmunoblastic lymphadenopathy or for diffuse small cleaved cell, follicular large cell, follicular mixed large and small cleaved cell, acquired immune deficiency syndrome (AIDS)-related, unclassifiable, or small noncleaved cell lymphomas. Pooled long-term results for the 126 patients with variants of diffuse large cell lymphoma (cleaved, noncleaved, immunoblastic, and mixed) show an actuarial relapse-free survival of 67% for the 86% of patients who had a complete response and an overall survival for all patients of 65% at 78 months of follow-up. Analysis of toxicity reveals a substantially higher risk of lethal toxicity in patients over 59 years of age. MACOP-B should only be used for patients with one of the diagnoses for which it is effective; meticulous care should be taken to prevent severe toxicity in older patients.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Ketoconazole versus nystatin as prophylaxis against fungal infection for lymphoma patients receiving chemotherapy.

We evaluated the efficacy and toxicity of ketoconazole versus nystatin antimycotic prophylaxis in a prospective randomized study of 32 patients receiving intensive weekly outpatient combination chemotherapy for non-Hodgkin's lymphoma with crossover to the other drug if failure occurred. Thirteen patients were assigned to nystatin and 19 to ketoconazole. Fungal infections occurred in three patients receiving nystatin (16%) and one patient receiving ketoconazole (8%); one patient refused his assigned drug due to taste intolerance. Including the crossover courses of drug, the failure rate associated with ketoconazole was 6% while that for nystatin was 20% (p = 0.23). We favor ketoconazole as antifungal prophylaxis during antilymphoma chemotherapy because of at least equivalent and possibly superior efficacy, better acceptance by patients, easier administration, and systemic absorption.

Aged↗
PubMed1987

Immunoreactive prolactin in the rat hypothalamus: in vitro release and subcellular localization.

Immunocytochemical studies have identified immunoreactive prolactin (IR-PRL) in the hypothalamus and other areas of the rat brain. However, neither the release of IR-PRL from the hypothalamus nor its subcellular localization have been demonstrated. In this study, the release of IR-PRL from hypothalami obtained from female rats was examined using hypothalamic units incubated in vitro in Krebs-Ringer bicarbonate-glucose buffer. Hypothalamic tissue spontaneously released IR-PRL, and this release was increased by depolarizing concentrations of potassium by a calcium-dependent mechanism. Hypothalamic IR-PRL was also released from hypothalamic tissue obtained from hypophysectomized rats (14 days). The subcellular localization of IR-PRL was investigated using equilibrium-density centrifugation. Tissue homogenates from intact or hypophysectomized rats were centrifuged at 150 g at 4 degrees C for 10 min, and the supernatants were layered onto continuous sucrose gradients (1.00-1.27 g/ml) and centrifuged at 100,000 g (max.) for 16 h. IR-PRL in pituitary supernatants showed a high equilibrium-density peak with a modal density of 1.23 g/ml. Fractionation of the supernatant from ventral or dorsal hypothalamic tissue resulted in two high-equilibrium density peaks, a primary peak with a modal density of 1.23 g/ml and a smaller peak with a modal density of 1.10 g/ml. Both high-density peaks were maintained in tissue obtained from hypophysectomized rats and were disrupted by homogenization in hypo-osmotic medium. Together, these data suggest that hypothalamic IR-PRL is stored in membrane-bound particles which have densities similar to those of secretory granules and is released by a calcium-dependent mechanism when the tissue is depolarized.

Animals↗
PubMed1987

The pituitary TSH response to TRH is inversely related to the plasma TSH concentration and directly related to the pituitary TSH content during hypothyroidism in the rat.

We studied the effects of degree and duration of hypothyroidism on the pituitary TSH concentration and the pituitary TSH secretory response to TRH. Varying degrees of hypothyroidism were achieved in thyroparathyroidectomized rats (THYREX) by continuous sc infusion of T3 (0.2, 0.3, 0.4, or 0.5 microgram/100 g X day) or T4 (0.6, 1.2, or 1.8 microgram/100 g X day). While T3 was more potent than T4, both resulted in a dose-dependent suppression of the post-thyroidectomy rise in TSH. After 7 or 14 days of severe hypothyroidism (nonreplaced THYREX rats) the pituitary TSH secretory response to TRH (250 ng/100 g body weight, iv) was found to be decreased when compared to that of euthyroid rats. Decreasing the degree of hypothyroidism increased the pituitary secretory response to TRH and the pituitary TSH content. The results indicate that in the hypothyroid rat: severe hypothyroidism results in a blunted pituitary TSH response to TRH through 14 days after thyroidectomy, at 7 and 14 days after thyroidectomy the pituitary TSH response to exogenous TRH is inversely related to the basal plasma TSH concentration, the pituitary TSH concentration increases with the duration of hypothyroidism, the pituitary TSH content is increased by low rates of thyroid hormone replacement, and the pituitary TSH response to exogenous TRH is directly related to the pituitary TSH content.

Animals↗
PubMed1987

Brief chemotherapy and involved field radiation therapy for limited-stage, histologically aggressive lymphoma.

STUDY OBJECTIVE: To determine the efficacy and toxicity of brief chemotherapy and involved field radiation therapy for treatment of limited-stage, histologically aggressive malignant lymphoma. DESIGN: Single-arm prospective trial. SETTING: Comprehensive cancer treatment center serving the entire population of British Columbia. PATIENTS: Consecutive enrollment of 78 patients ranging in age from 21 to 82 years (median, 64) with limited-stage (no B symptoms, Ann Arbor stage I or II, tumors less than 10 cm in diameter), diffuse large cell, mixed or immunoblastic histologic characteristics of malignant lymphoma seen at our institution between May 1980 and December 1984. All eligible patients were evaluated for response and relapse-free and overall survival. INTERVENTIONS: Chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) for three cycles followed by involved field radiation therapy to the original site of disease in a dose equivalent to 3000 cGy in ten fractions. MAIN RESULTS: The complete response rate was 99% (77 of 78 patients). With a median follow-up off treatment of 30 months the actuarial relapse-free survival is 84% and the overall survival is 85%. No deaths due to toxicity occurred. CONCLUSIONS: Brief chemotherapy and involved field radiation therapy is highly successful treatment for patients with limited-stage, histologically aggressive malignant lymphoma. Toxicity of this approach is acceptable, even in the elderly. Staging laparotomy is not needed to select these patients. Future trials should incorporate more effective chemotherapy programs.

Adult↗
PubMed1987

Updated clinical experience with MACOP-B.

This paper summarizes our experience with MACOP-B chemotherapy (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) in 125 patients with advanced stage, diffuse, large cell non-Hodgkin's lymphoma referred to the Cancer Control Agency of British Columbia between April 1981 and June 1986. Complete response (CR) was achieved in 105 patients (84%), partial response (PR) in 18 patients (14.4%) and primary treatment failure occurred in two patients (1.6%). Fifteen of the PRs and both nonresponders succumbed to their disease. Of the 105 CRs, 23 patients (21%) suffered a relapse; 14 of the relapsers eventually died from their lymphoma, five are in second CR, three are receiving further therapy, and one has histologic evidence of asymptomatic, low-grade lymphoma. Three deaths were unrelated to lymphoma. Overall toxicity was acceptable, with only six treatment-related deaths (4.8%). The incidence of nonfatal systemic proven or suspected infections was 10%. Mucocutaneous side effects remain the most frequent toxicity of the MACOP-B protocol. More than half of the 125 patients received at least a portion of MACOP-B from community oncologists. The results of treatment with MACOP-B remain at least comparable to the best reported in the literature, yet they have been achieved with less toxicity, over shorter periods of time, and with diminished socioeconomic impact on patients. However, improvement on these results is necessary both in terms of efficacy and toxicity. A new variant of MACOP-B is now being tested and our preliminary experience has been encouraging.

Adult↗
PubMed1987

MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease.

Seventy-six patients with previously untreated advanced Hodgkin's disease have been treated with the MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomycin, vincristine) hybrid program. Ten patients also received involved field radiation to the mediastinum for residual nodal disease after six cycles of chemotherapy. Of the 74 evaluable patients, 71 (96%) had a complete response. The actuarial relapse-free survival for the complete responders after 62 months off treatment is 90% (median follow-up from treatment completion was 35 months; range, 4 to 62 months). Actuarial overall survival for all 76 patients including all causes of death is 95% (median follow-up time from diagnosis was 43 months; range, 4 to 70 months). Toxicity was modest. Only one death occurred during treatment, and toxicity-related hospitalization was necessary for only 8% of patients. Failure analysis indicates that a disproportionate number of treatment failures occurred in the sub-group with B symptoms and a mediastinal mass ratio greater than one third the transthoracic diameter. This updated report confirms the efficacy and safety of the MOPP/ABV hybrid program for advanced Hodgkin's disease, which is now being tested in a prospective, randomized, multicenter trial.

Adolescent↗
PubMed1986

Subcellular localization of immunoreactive thyroid-stimulating hormone in the rat hypothalamus.

Hypothalamic tissue contains TSH-like material which is biologically, immunologically, and physicochemically similar to pituitary TSH. Immunoreactive thyroid-stimulating hormone (IR-TSH) is released from hypothalamic tissue in vitro by depolarizing concentrations of potassium or veratridine by a calcium-dependent mechanism. In the present study, we investigated the subcellular localization of IR-TSH using equilibrium density centrifugation. Tissue homogenates from intact, hypophysectomized or thyroidectomized rats were centrifuged at 150 g at 4 degrees C for 10 min and the supernatants were layered onto continuous sucrose gradients (1.00-1.27 g/ml) and centrifuged at 100,000 g (max) for 16 h. IR-TSH in pituitary supernatants from intact and thyroidectomized rats showed high equilibrium density peaks with a modal density around 1.2 g/ml. Fractionation of the supernatant from ventral or dorsal hypothalamic homogenates resulted in a bimodal distribution of IR-TSH. In supernatants from both tissues, IR-TSH containing particles were found at the top of the gradient in a low equilibrium density peak between 1.0 and 1.08 g/ml. In addition, IR-TSH containing particles were found in ventral and dorsal hypothalamic supernatants with modal densities at 1.16 and 1.25, respectively. These high density IR-TSH particles were present in tissue taken from hypophysectomized rats, and were not appreciably affected by thyroidectomy. Homogenization of the tissue in a hypo-osmotic medium disrupted the high density IR-TSH particles resulting in a single low density peak at the top of the gradient. These data suggest that hypothalamic IR-TSH is stored in membrane bound particles which have densities similar to that of secretory granules.

Animals↗
PubMed1985

A phase II study of spirogermanium as second line therapy in patients with poor prognosis lymphoma. An NCI Canada Clinical Trials Group Study.

The National Cancer Institute of Canada Clinical Trials Group conducted a phase II study of spirogermanium given daily for 5 days every 3 weeks to patients with poor prognosis non-Hodgkin's lymphomas. All patients had had a maximum of one prior treatment regimen. No responses were seen in 13 evaluable patients. Toxicity was primarily neurologic and mild or moderate in most patients. There is no evidence of activity of spirogermanium given in this schedule in this subset of lymphoma patients.

Aged↗
PubMed1985

Diffuse malignant lymphoma with cerebriform nuclei: A B-cell lymphoma studied with monoclonal antibodies.

A lymph node biopsy performed on a 55-year-old woman with asymptomatic generalized lymphadenopathy revealed a diffuse, malignant lymphoma composed of small to intermediate-sized lymphocytes with cerebriform-shaped nuclei; electron microscopy confirmed the nuclear complexity. The cerebriform nuclear configuration, coupled with an interfollicular pattern of nodal involvement with encroachment upon residual germinal centers, was presumptive of either mycosis fungoides or a peripheral T-cell lymphoma. Immunologic evaluation, however, indicated that the cerebriform lymphocytes represented a monoclonal B-cell population (IgM-IgD, lambda). Staining with monoclonal antibodies disclosed a phenotype of Ia+, B1+, BA-1+, BA-2+, Leu-1+; the neoplastic cells were unreactive with T-cell, lineage-specific antibodies (anti-Leu-2a, -3a, -4, -5) and with J5 (CALLA). In light of the immunophenotype and the distributional pattern, the cerebriform-shaped lymphocytes may represent an extreme morphologic variant of intermediate lymphocytic lymphoma.

Antibodies, Monoclonal↗
PubMed1985

Distribution and release of immunoreactive thyroid-stimulating hormone in the rat hypothalamus: effects of thyroidectomy, hypophysectomy and treatment with thyroid hormones.

Immunoreactive thyroid-stimulating hormone (IR-TSH) has been detected in the hypothalamus and is released in vitro by a calcium-dependent mechanism when the tissue is depolarized. Recently, immunocytochemical studies have revealed that IR-TSH is present in thyrotropes in the pars tuberalis. Therefore, because these thyrotropes are associated with the median eminence, the area with the highest concentration of IR-TSH, it is of interest to determine if 'hypothalamic' IR-TSH is from neural or pituitary cells. We addressed this issue by studying the effects of hypophysectomy, thyroidectomy, or chronic administration of triiodothyronine (T3) or thyroxine (T4) on the distribution and in vitro release of IR-TSH in the hypothalamus. We reasoned that, if hypothalamic IR-TSH is dependent on the thyrotropes of the pars tuberalis, then changes in hypothalamic IR-TSH concentration and release should be parallel to those measured in pituitary extracts. IR-TSH was measured in tissue extracted in ice-cold 2% NaCl, with a final pH of 4.5. For the in vitro studies, tissues were incubated for 20-min periods in Krebs-Ringer bicarbonate buffer at 37 degrees C. In untreated rats, the concentration of IR-TSH is greater in the ventral than the dorsal portion of the hypothalamus (39.3 +/- 8.2 vs. 4.0 +/- 1.5 ng/mg wet wt.). Upon finer dissection of the hypothalamus into median eminence and anterior, middle, and posterior portions of the remainder, IR-TSH was only detectable in the middle hypothalamus (5.3 +/- 1.5 ng/mg), and the median eminence (149 +/- 41 ng/mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Treatment of nasopharyngeal carcinoma with human leukocyte interferon.

Nasopharyngeal carcinoma (NPC) is a human neoplasm closely associated with Epstein-Barr virus (EBV). Human leukocyte interferon (IFN) has known antiviral and antineoplastic properties. After initial IFN treatment in one NPC patient demonstrated acceptably low toxicity, 12 additional patients were treated on a protocol with IFN, 10 X 10(6) units intramuscularly (IM) daily for 30 days. IFN did not affect serum anti-EBV antibody titers (IgA and IgG antiviral capsid and early antigens). Of six patients tested, none was found to excrete EBV in saliva before, during, or after IFN. Four patients had measurable tumor regression (two partial responses and two minor responses), three had stable disease, and five patients plus the initial preprotocol patient had progressive disease. Toxicity included fever, fatigue, and myalgias in all patients, thrombocytopenia in two patients, and neutropenia in three patients. Three patients were withdrawn from the study, one each for severe fatigue, neutropenia, and hypotension. This study demonstrates that IFN has sufficient activity in advanced NPC to justify further investigation.

Adult↗