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Biomedical subjects

M S Gordon

Publications and source records attributed to M S Gordon.

At least 55 records · Page 3Linked to original sources
PubMed1995

Approaches for improving the stability of ketorolac in powder blends.

Methods for improving the stability of ketorolac powder blends under elevated humidity and temperature conditions were investigated. The approaches that were examined for potentially increasing the stability of ketorolac were varying the ketorolac salt form, altering the excipient ratios, and adding antioxidants or pH modifiers to the formulation. The ketorolac powder blends were stored for 3 months at 75% relative humidity (RH) and 40, 50, and 60 degrees C. The results showed that the salt form of ketorolac had a large impact on stability after 3 months of storage at 50 degrees C/75% RH. The calcium salt powder blend and the free acid powder blend exhibited only 0.2% and 0.5% drug loss, respectively, whereas the tromethamine salt powder blend showed a 10.2% drug loss. Varying the ratios of lactose, microcrystalline cellulose, and croscarmellose sodium in the powder blends of ketorolac tromethamine showed that croscarmellose sodium and microcrystalline cellulose destabilized ketorolac. Addition of propyl gallate (1% w:w) to ketorolac tromethamine powder blends increased the stability of the ketorolac significantly. Addition of pH modifiers caused a modest improvement in the stability of ketorolac.

Analgesics, Non-Narcotic↗
PubMed1995

In vivo effects of recombinant human stem cell factor treatment. A morphologic and immunohistochemical study of bone marrow biopsies.

Bone marrow (BM) aspirate and biopsy specimens from seven female patients with advanced or metastatic breast cancer and preserved marrow function treated on a phase I trial of recombinant methionyl human stem cell factor (r-metHuSCF; SCF) were evaluated by immunohistochemical staining before and after treatment with SCF. Doses of SCF included 10 g/kg/day in 2 patients, 25 micrograms/kg/day in 2 patients, and 50 micrograms/kg/day in 3 patients administered as subcutaneous bolus injections for 14 days. Following treatment, bone marrow cellularity increased up to 1.6-fold (P = NS), with an increased frequency of promyelocytes (P < .002), but an unchanged relative frequency of other marrow hematopoietic cells. The mean relative frequency of BM CD34+ progenitor cells increased from 0.9% to 1.8% (P < .001). The mean proportion of BM cells stained by Ki-67/MIB 1 and PCNA/PC10, monoclonal antibodies (MoAb) recognizing proliferation-associated nuclear proteins, increased from 18.6% to 35.4% (P < .003) and from 32.4% to 49.4% (P < .01), respectively. Most of the Ki-67 and PCNA positive cells were represented by promyelocytes, proerythroblasts, and myeloblasts. SCF therapy was not associated with marrow fibrosis or increases in the number of macrophages. Peripheral white blood cell counts increased 1.3- to 3.6-fold following SCF. The mean absolute neutrophil counts increased from 3.9 x 10(9)/L (range 2.6-5.3) to 7.2 x 10(9)/L (range 4.7-12.3), and reticulocyte counts increased by a mean of 1.5 fold (range 1.2-fold to 2.0-fold). No consistent difference in platelet counts was seen. These results suggest that SCF given in vivo is effective in increasing the frequency of CD34+ BM progenitor cells, and has the capacity to increase the proliferation and differentiation rate of hematopoietic precursor cells. These effects indicate that SCF may represent a cytokine capable of affecting multiple hematopoietic lineages.

Adult↗
PubMed1995

A phase II trial of subcutaneously administered recombinant human interleukin-2 in patients with relapsed/refractory thymoma.

The thymus is the site of T-cell maturation and contains T-cell precursors that differentiate into cytolytic T lymphocytes (CTLs) in vitro in the presence of interleukin-2 (IL-2). Malignant thymoma is often associated with a lymphocytic infiltration of these precursors. The antitumor effects of IL-2 are mediated in part by activated CTLs. Based on these considerations and anecdotal reports of its anti-tumor activity in thymoma, we conducted a Phase II trial of IL-2 in 14 patients with thymoma. IL-2 was administered s.c. at a dose of 12 x 10(6) IU/m2/day for 5 days for 4 weeks followed by a 2-week rest period. Patients were evaluated for response after each 6-week cycle, and those tolerating therapy with no disease progression were eligible for a maximum of 4 cycles. All patients had failed prior standard chemotherapy and 12 had received prior radiotherapy. All 14 patients were evaluable for toxicity and response. The median number of cycles received was two. One patient was removed from study during cycle 1 because of severe bronchospasm. Five patients required dose reductions for grade 3 toxicity (anorexia, nausea, hyperbilirubinemia, elevated SGPT, and skin desquamation, one patient each). Two patients developed new symptoms of myasthenia gravis while in the study and were removed (one for progressive disease, one for steroid requirement). There were no objective responses. The one patient who required steroids for newly diagnosed myasthenia gravis had a minor response. We conclude that subcutaneously administered IL-2, although it has acceptable toxicity, has no significant clinical activity in previously treated patients with advanced thymoma.

Adult↗
PubMed1994

Nonmodulating trait may precede the development of hypertension.

The nonmodulating trait thought to explain development of hypertension in 25 to 35% of patients, is characterized by abnormal angiotensin II (AII)-mediated control of aldosterone release and renal blood flow (RBF). Some data support the possibility that nonmodulation is an inherited trait, but others argue that it is an acquired epiphenomenon of the hypertensive state. We report the first case of a normotensive patient with nonmodulation who subsequently developed frank hypertension. Patient RR was studied on six occasions over a 5-year period, two while normotensive, four while hypertensive. This patient consistently demonstrated an abnormally low plasma aldosterone response to AII (3 ng/kg/min) on a low salt (10 mEq sodium) diet while both normotensive and hypertensive. A consistently abnormally depressed RBF response to AII on a high salt (150 to 200 mEq sodium) diet as well as a depressed RBF increment when the diet was changed from low salt to high salt were also noted. Thus, RR demonstrated nonmodulation by multiple criteria while both normotensive and hypertensive. We conclude that the nonmodulating trait may be a heritable defect that leads to the development of hypertension and is not an epiphenomenon.

Aldosterone↗
PubMed1993

In vivo administration of recombinant methionyl human stem cell factor expands the number of human marrow hematopoietic stem cells.

A growing number of in vitro studies suggest that recombinant human stem cell factor (SCF) is capable of augmenting the proliferative capacity of human hematopoietic progenitor cells (HPC) and stem cells (HSC). We further evaluated this biologic effect by analyzing the response of bone marrow (BM) HPCs and HSCs to the administration of SCF in eight patients with locally advanced or metastatic breast cancer who were enrolled in an ongoing phase I study. SCF was administered for 14 days by daily subcutaneous injection at dosages of 10, 25, or 50 micrograms/kg/d. BM CD34+ HLA-DR+ and CD34+ HLA-DR- CD15- cells, previously shown by our laboratory to be enriched for various classes of differentiated and primitive HPCs, respectively, were quantitated in BM samples on day 0 (pretreatment) and day 15 (posttreatment). These CD34+ HLA-DR+ and CD34+ HLA-DR- CD15- cells were then isolated by cell-sorting and assayed for several classes of HPCs, including the high--proliferative potential colony-forming cell (HPP-CFC), the burst-forming unit--megakaryocyte (BFU-MK), and the long-term BM culture--initiating cell (LTBMC-IC). SCF administration resulted in a 3.3-fold (range, 1.4- to 18.8-fold; P = .018) increase in the absolute numbers of CD34+ cells, a 3.7-fold (range, 1.2- to 8.2-fold; P = .028) increase in the absolute numbers of CD34+ HLA-DR+ cells, and a 2.4-fold (range, 1.1- to 29.3-fold; P = .010) increase in the absolute numbers of CD34+ HLA-DR- CD15- cells. Following the infusion of SCF, a statistically significant increase in the absolute numbers of HPP-CFC (P = .018), BFU-MK (P = .046), CFU-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM: P = .043), BFU-erythrocyte (BFU-E; P = .043), CFU-granulocyte, macrophage (CFU-GM; P = .045), and CFU-megakaryocyte (CFU-MK; P = .028) per milliliter of marrow was observed. Stromal cell-free LTBMCs supplemented with SCF and interleukin-3 (IL-3), initiated with CD34+ HLA-DR- CD15- cells obtained on day 0, produced viable cells for 9.6 weeks, compared with 11.5 weeks for LTBMCs initiated with CD34+ HLA-DR- CD15- cells obtained on day 15. Cumulative cellular production by LTBMCs initiated with day 15 CD34+ HLA-DR- CD15- cells was statistically greater than that by day 0 LTBMCs (P = .031). These same cultures produced CFU-GM for 6.3 weeks (day 0) versus 9 weeks (day 15).(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗
PubMed1993

Effect of the mode of super disintegrant incorporation on dissolution in wet granulated tablets.

The effect of the mode of super disintegrant incorporation in wet granulated tablets was investigated with three super disintegrants: sodium starch glycolate, crospovidone, and croscarmellose sodium. The disintegrants were incorporated extragranularly or intragranularly or distributed equally between the two phases. Lactose, naproxen, or dibasic calcium phosphate was used as the principal tablet component to provide various degrees of solubility to the formulations. The formulations were dried to three different levels of moisture content. The results indicated that, for the formulations studied, extragranular incorporation resulted in faster dissolution than did equal distribution intragranularly and extragranularly, which in turn was superior to intragranular incorporation. Granulation moisture content was found to have a formulation-specific impact on tablet dissolution, with each main tablet component behaving in a different fashion. When all other factors were kept constant, there was a tendency for croscarmellose sodium to produce faster tablet dissolution than sodium starch glycolate or crospovidone. The super disintegrants tended to promote faster dissolution in a neutral pH medium than in an acidic medium.

Biological Availability↗
PubMed1993

The in vitro and in vivo effects of stem cell factor on human hematopoiesis.

The c-kit ligand or stem cell factor (SCF) and the c-kit ligand receptor (KR) are thought to play pivotal roles in the regulation of human hematopoiesis. When added to interleukin 3 (IL-3) and/or granulocyte-macrophage colony stimulating factor (GM-CSF), SCF has an especially profound effect on the in vitro proliferation of several classes of primitive hematopoietic progenitor cells including the burst forming unit megakaryocyte (BFU-MK), the high proliferative potential colony forming cell (HPP-CFC) and the long-term bone marrow culture-initiating cell (LTBMC-IC). These primitive hematopoietic progenitor cells are present in a CD34+HLA-DR- fraction of marrow which has in vivo marrow populating ability and thereby resembles the pluripotent hematopoietic stem cell. Furthermore, the CD34+HLA-DR- marrow subpopulation which expresses KR contains virtually all of the marrow BFU-MK, HPP-CFC and LTBMC-IC, indicating that the human stem cell is KR positive. The addition of SCF, IL-3 and GM-CSF to suspension cultures initiated with CD34+HLA-DR- cells results in an exponential expansion of the numbers of hematopoietic progenitor cells. Large numbers of such progenitor cells generated ex vivo may be useful as transfusion products for the treatment of chemotherapy induced cytopenias. The therapeutic potential of the in vivo administration of SCF has also been evaluated in a phase I trial of recombinant methionyl SCF. SCF administration led to an increase in both differentiated and primitive hematopoietic progenitor cells within the marrow. Such studies suggest that in vivo SCF administration may be useful for improving the quality of bone marrow grafts to be used either for autologous or allogeneic bone marrow transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1992

Renal and adrenal responsiveness to angiotensin II: influence of beta adrenergic blockade.

The increase in aldosterone secretion that occurs in response to Angiotensin II (AII) is enhanced when normal humans are in external balance on a low salt diet. The responsible mechanism has not been identified. Angiotensin converting enzyme inhibition reduces blood levels of AII and aldosterone, but does not decrease PRA or AI and does not modify adrenal responsiveness to AII in the sodium-depleted state. This study was designed to assess the possibility that the enhanced adrenal response reflects plasma renin activity (PRA), plasma AI concentration, or catecholamines acting via a beta adrenergic receptor. Nine healthy males were studied when in balance on a high sodium intake (200 mmol Na/day), a low sodium diet (10 mmol Na) and after 4 days of beta adrenergic blockade with either nadolol or propranolol. The adequacy of beta adrenergic blockade was assessed with a postural stimulus and significant blockade was achieved, somewhat more with nadolol (40 mg/day) than with propranolol (Inderal LA, 80 mg every 12 hrs). Beta blockade enhanced the renal vascular and pressor response to AII but did not modify the adrenal response to posture or to AII. This study confirms the role for AII levels in the modulation of renal vascular and pressor responses to AII and rules out a role for PRA, AI, or catecholamines acting via a beta adrenergic receptor in the modulation of adrenal responsiveness to AII.

Adrenal Glands↗
PubMed1992

Regulation of angiotensinogen gene expression by estrogen.

OBJECTIVE: Clarification of the role of estrogen in the regulation of angiotensinogen gene expression in multiple tissues. DESIGN: The effect of 17 beta-estradiol (E2; 10 micrograms/100 mg body weight) administration in ovariectomized (OVX) rats upon angiotensinogen messenger RNA (mRNA) levels in multiple tissues was assessed. Confounding ovarian factors were thus removed by studying the animals in the castrate state. Controls consisted of OVX and intact female rats. METHODS: Adult female Sprague-Dawley rats were ovariectomized and experiments begun 21 days postsurgery. Animals were injected with E2 and studied after 0, 1, 4, and 24 h of treatment. Levels of angiotensinogen mRNA were determined by Northern blot analysis using beta-actin mRNA as an internal standard. RESULTS: A single angiotensinogen mRNA species with molecular size of approximately 1800 bp was observed in rat liver, aorta, kidney, cardiac atria, hypothalamus and whole brain. Little or no angiotensinogen mRNA was identified in the pituitary gland. Angiotensinogen mRNA was most abundant in rat liver, hypothalamus, aorta and progressively less abundant in whole brain, cardiac atria and kidney. A twofold induction of hepatic angiotensinogen mRNA levels in E2-OVX rats was observed by 4h. The angiotensinogen mRNA levels in kidney were threefold higher by 4 h compared with OVX control animals. In aorta, the angiotensinogen mRNA level was also threefold higher by 1 h after E2 treatment. No significant effect of estradiol treatment was observed in cardiac atria although the level of angiotensinogen mRNA was higher in intact female rats compared with OVX controls. CONCLUSION: These results suggest that estrogen modulates angiotensinogen gene expression in a tissue-specific manner.

Angiotensinogen↗
PubMed1992

Desmoid tumors of the chest wall. A locally recurrent problem.

Desmoid tumors, in general, are known for their propensity to recur. To evaluate treatment and results, we reviewed the records of 32 patients admitted to our institution with a chest wall desmoid tumor from 1948 to 1988. There were 13 men and 19 women whose ages ranged from 12 to 67 years (median 36 years). Four patients had Gardner's syndrome. Treatment was wide resection. Median follow-up was 110 months. The overall 5-year survival was 93%; 5-year disease-free survival was 71%. The 5-year local recurrence rate was 29%. Since death from disease is uncommon after resection, but local recurrence is common, we recommend aggressive wide resection in patients who have desmoid tumors of the chest wall when seen initially.

Adolescent↗
PubMed1991

Effect of formulation solubility and hygroscopicity on disintegrant efficiency in tablets prepared by wet granulation, in terms of dissolution.

The effect of tablet formulation solubility and hygroscopicity on the dissolution efficiency of three "super disintegrants" (sodium starch glycolate, crospovidone, and croscarmellose sodium) in tablets prepared by wet granulation was investigated. Lactose, calcium phosphate dibasic, sorbitol, and naproxen sodium, alone or in combination, provided varying degrees of solubility and hygroscopicity in the formulations. To monitor in vitro dissolution, 1% p-aminobenzoic acid was added to the formulation as a tracer. The results indicate that highly soluble and/or hygroscopic ingredients decrease the effectiveness of super disintegrants in promoting in vitro dissolution. The greater the overall hygroscopicity and solubility of the tablet formulation, the larger the decrease in the efficiency of the super disintegrant.

Calcium Phosphates↗
PubMed1991

Soft tissue sarcomas of the chest wall. Results of surgical resection.

UNLABELLED: Primary soft tissue sarcomas of the chest wall are uncommon, and data concerning treatment and results are sparse. Most studies have categorized these tumors as truncal sarcomas and inferred a poor prognosis. To assess the results of surgical treatment, we reviewed our 40-year experience. METHODS: Records of 189 patients admitted to our institution from 1948 to 1988 were reviewed. Pathologic material was available for review in the 149 cases (79%) that comprise this report. Survival was calculated by the Kaplan-Meier method, with comparisons by log-rank analysis and significance defined as p less than 0.05. RESULTS: Ages ranged from 3 weeks to 86 years (median, 38 years); the ratio of male to female patients was 2:1. The initial complaint was mass or pain in 97% of the cases. Ninety sarcomas (60%) were high grade and 59 (40%) were low grade. Histologic types were as follows: desmoid tumor (n = 32, 21%); liposarcoma (n = 23, 15%); rhabdomyosarcoma (n = 18, 12%); fibrosarcoma (n = 17, 11%); embryonal rhabdomyosarcoma (n = 14, 9%); malignant peripheral nerve tumor (n = 13, 9%); malignant fibrous histiocytoma (n = 11, 7%); spindle cell sarcoma (n = 4, 3%); tenosynovial sarcoma (n = 3, 3%); hemangiopericytoma (n = 3, 3%); alveolar soft part sarcoma (n = 3, 3%); and other types (n = 12, 9%). Resection was the primary treatment in 140 cases (94%). Local recurrence developed in 27%. Metastases occurred in 52 (35%) of the cases (metachronous in 42, synchronous in 10) and were more common in patients with high-grade disease (46/90, 51%) than in those with low-grade disease (6/59, 10%). Overall 5-year survival was 66%. Five-year survival rate for those with high-grade sarcomas (49%) was significantly lower than that for low-grade sarcomas (90%, p less than 0.0001). Tumor size and age of patient were not prognostic. CONCLUSIONS: Survival of patients with primary soft tissue sarcomas of the chest wall after resection is similar to that of patients with sarcomas of the extremities. Resection alone provides acceptable survival (90% at 5 years) for those with low-grade sarcomas, but adjuvant treatment should be considered for those with high-grade sarcomas.

Adolescent↗
PubMed1990

Effect of the mode of croscarmellose sodium incorporation on tablet dissolution and friability.

A computer-optimized experimental design was used to study the effect of incorporating a "super disintegrant", croscarmellose sodium, intragranularly, extragranularly, or distributed equally between the two phases of a tablet in which a poorly soluble drug constituted at least 92.5% of the formulation. The results were analyzed by means of a general quadratic response surface model and suggest that tablets with the same total concentration of super disintegrant dissolve at a faster rate when the super disintegrant is included intragranularly. Tablet friability was not affected by the method of super disintegrant incorporation.

Carboxymethylcellulose Sodium↗
PubMed1990

Dopamine and nonmodulating hypertension.

Sodium loading reduces aldosterone responses to angiotensin II (AII) when compared to the sodium restricted state. Recent investigations suggest that dopamine inhibits the aldosterone secretion and may contribute to the alteration in aldosterone response to AII with sodium intake, since administration of the dopamine antagonist, metoclopramide, enhances the aldosterone responses to AII on a high but not a low salt diet. Nonmodulating hypertension is characterized, in part, by a decreased aldosterone response to AII, raising the possibility that an increased dopaminergic inhibition of aldosterone secretion underlies the adrenal defect in nonmodulating hypertension. To assess this possibility, 69 patients with hypertension were characterized in relationship to their modulation status on a low sodium intake. Dopamine levels were significantly higher (P less than .05) in nonmodulators. To assess the physiologic relevance of these findings, the aldosterone response to AII infusion was assessed before and during administration of the dopamine antagonist, metoclopramide, in 13 patients. The adrenal response to AII did not change after metoclopramide in either hypertensive subgroup. Thus, it is unlikely that the adrenal defect is due to the increase in dopamine levels observed in nonmodulators. In the next study, the impact of dietary sodium intake on urinary dopamine levels was compared in normotensive and hypertensive subjects characterized as modulators and nonmodulators. Both modulators and normotensive subjects demonstrated an increase in urinary dopamine excretion in response to a high sodium intake--a feature that was not observed in the nonmodulators. Thus, the sodium retaining tendency of nonmodulators may reflect, at least in part, a reduction in intrarenal dopamine production in response to a sodium load.

Adrenal Glands↗
PubMed1990

Cardiology patient simulator and computer-assisted instruction technologies in bedside teaching.

The design and uses of an innovative technology-based approach which addresses critical problems with bedside teaching during ward rounds in the current health care situation are described. A cardiology patient simulator (HARVEY) and an accompanying computer-based interactive laserdisk system provide medical students, house officers and other health professionals with the opportunity to encounter a wide variety of clinical problems for learning and assessment. A group of cardiologists and medical educators from a consortium of US medical schools has guided the development and formal assessment of the entire system over the past 10 years. The system and simulator can be configured and programmed to provide appropriate heart sounds, laboratory data, and test results upon request; hands-on experience to practise examination skills is also available. The system, whole or in part, can be used in a variety of instructional modes from self-instruction to demonstration teaching, and from self-assessment to the final clinical examination. The system's effectiveness for teaching medical clerks is summarized, as is its use in providing continuing education for primary care doctors in rural practice.

Cardiology↗