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Biomedical subjects

Mark Levine

Publications and source records attributed to Mark Levine.

At least 37 records · Page 2Linked to original sources
PubMed2005

Enoxaparin in the treatment of deep vein thrombosis with or without pulmonary embolism: an individual patient data meta-analysis.

STUDY OBJECTIVES: Low-molecular-weight heparins have been compared with unfractionated heparin (UFH) for treatment of deep vein thrombosis (DVT). However, a comparison of their efficacy in the presence or absence of pulmonary embolism (PE) has not been studied. We estimated the efficacy and safety of enoxaparin vs UFH in patients with proximal DVT with/without symptomatic PE using a meta-analysis of individual data from randomized controlled trials. DESIGN AND SETTING: Randomized controlled trials were identified from MEDLINE, EMBASE, abstracts from international meetings on venous thromboembolism (VTE), previous meta-analyses, and trial data provided by the sponsor. PARTICIPANTS: For inclusion, randomized controlled trials had to be properly randomized; include patients with objectively diagnosed DVT; compare enoxaparin twice daily with UFH; use objective methods to assess recurrent symptomatic VTE, major bleeding, and death at 3 months; and include blind evaluation of clinical events. MEASUREMENTS: A meta-analysis was performed using the logarithm of the relative risk (RR) method. Enoxaparin in DVT treatment with/without symptomatic PE was considered noninferior to UFH for preventing VTE at 3 months if the upper limit of the 95% confidence interval (CI) of the RR (enoxaparin/UFH) was lower than a prespecified noninferiority margin (1.61). No increase in major bleeding or mortality should be observed. RESULTS: The meta-analysis included individual data from three randomized controlled trials (749 patients and 754 patients in the enoxaparin and UFH groups, respectively). The observed RR (enoxaparin/UFH) of VTE was 0.81 (95% CI, 0.52 to 1.26) for the intention-to-treat population (RR, 0.70; 95% CI, 0.43 to 1.13; for per-protocol analysis). Results did not differ for patients with clinical PE (235 patients; RR, 0.84) and without clinical PE (1,268 patients; RR, 0.71), with a nonsignificant heterogeneity test between groups (p = 0.76). A trend in favor of enoxaparin was observed for reduced mortality and major bleeding. CONCLUSIONS: The efficacy and safety of enoxaparin vs UFH for DVT treatment is not modified by the presence of symptomatic PE.

Anticoagulants↗
PubMed2005

Using administrative databases to measure waiting times for patients undergoing major cancer surgery in Ontario, 1993-2000.

PURPOSE: To determine how long patients in Ontario waited for major breast, colorectal, lung or prostate cancer surgery in the years 1993-2000. METHODS: "Surgical waiting time" was defined as the interval from date of preoperative surgeon consult to date of hospital admission for surgery. We created patient cohorts by linking appropriate diagnosis and procedure codes from Canadian Institutes of Health Information data. Scrambled unique surgeon identifiers were obtained from Ontario Health Insurance Plan data. Changes in median surgical waiting times were assessed with univariate time-trend analyses and multilevel models. Models were controlled for year of surgery and other patient (age, gender, comorbid conditions, income level, area of residence) and hospital level characteristics (teaching status, procedure volume status). RESULTS: Compared with 1993, median surgical waiting times in the year 2000 increased 36% for patients with breast cancer (to 19 d), 46% with colorectal (to 19 d), 36% with lung (to 34 d) and 4% with prostate cancer (to 83 d). Multilevel models confirmed significant increases in waiting times for all procedures. There were no concerning or consistent differences in waiting times among the categories of hospitals and patients examined. DISCUSSION: There were significant increases in surgical waiting times among patients undergoing breast, colorectal, lung or prostate cancer surgery in Ontario over years 1993-2000. Administrative databases can be used to efficiently measure such waits.

Breast Neoplasms↗
PubMed2004

6-Bromo-6-deoxy-L-ascorbic acid: an ascorbate analog specific for Na+-dependent vitamin C transporter but not glucose transporter pathways.

Vitamin C intracellular accumulation is mediated by Na(+)-dependent vitamin C transporters SVCT1 and -2 and dehydroascorbic acid transporters GLUT1 and -3. It is unclear which pathways dominate in vivo. As a new step to resolve this issue, we identified and tested 6-bromo-6-deoxy-L-ascorbic acid as a specific candidate for SVCTs. In high performance liquid chromatography and electron paramagnetic resonance analyses, the reduced compounds ascorbic acid and 6-bromo-6-deoxy-L-ascorbic acid were similar. The oxidized products 6-bromo-6-deoxy dehydroascorbic acid (BrDHA) and dehydroascorbic acid (DHA) had comparable stabilities, based on reduction recoveries. Upon expression of GLUT1 or GLUT3 in Xenopus oocytes, BrDHA was neither transported nor bound, in contrast to robust transport of DHA. The findings were not explained by differences in the oocyte reduction of DHA and BrDHA because lysed oocytes reduced both compounds equally. Further, there was no transport of the reduced compound, 6-bromo-6-deoxy-L-ascorbic acid, by GLUT1 or GLUT3. As a prerequisite for investigating 6-bromo-6-deoxy-L-ascorbic acid transported by SVCTs, SVCT2 transport activity in oocytes was enhanced 14-fold by construction and use of a vector that added a fixed poly(A) tail to the 3' end of cRNA. For SVCT1 and SVCT2 expressed in oocytes, similar K(m) and V(max) values were observed for ascorbic acid and 6-bromo-6-deoxy-L-ascorbic acid. In human fibroblasts, predicted to have SVCT-mediated ascorbate accumulation, K(m) and V(max) values were again comparable for ascorbic acid and 6-bromo-6-deoxy-L-ascorbic acid. Using activated human neutrophils, predicted to have ascorbate accumulation mediated predominantly by DHA and GLUT transporters, 6-bromo-6-deoxy-L-ascorbic acid accumulation was <1% of accumulation when compared with ascorbic acid. We conclude that 6-bromo-6-deoxy-L-ascorbic acid is the first transport substrate identified as completely specific for SVCTs, but not GLUTs, and provide a new strategy to determine the contribution of each pathway to ascorbate accumulation.

Animals↗
PubMed2004

Effect of a decision aid on knowledge and treatment decision making for breast cancer surgery: a randomized trial.

CONTEXT: The long-term results of randomized trials have demonstrated equivalent survival rates for mastectomy and breast-conserving therapy for the treatment of early stage breast cancer. Consequently, the choice of treatment should be based on a patient's preferences. OBJECTIVE: To evaluate the impact of a decision aid regarding the different surgical treatment options on patient decision making. DESIGN AND SETTING: A cluster randomized trial for which general surgeons in the communities of central-west, and eastern Ontario, Canada, were randomly assigned to use the decision aid or not in the surgical consultation. Patients received the decision aid or not based on the surgeon seen. PARTICIPANTS: Twenty surgeons participated in the study. Of the 208 eligible women with newly diagnosed clinical stage I or II breast cancer seen by study surgeons, 201 agreed to be evaluated: 94 were assigned to the decision board and 107 to usual practice. Patients were recruited from November 1999 to April 2002. INTERVENTION: The decision board is a decision aid designed to help physicians inform their patients about different treatment options and to enable patients to express a preference for treatment. MAIN OUTCOME MEASURES: Patient knowledge about the surgical treatment of breast cancer; decisional conflict; satisfaction with decision making; and the treatment decision following the consultation. RESULTS: Patients in the decision board group had higher knowledge scores about their treatment options (66.9 vs 58.7; P<.001), had less decisional conflict (1.40 vs 1.62, P =.02), and were more satisfied with decision making (4.50 vs 4.32, P =.05) following the consultation. Patients who used the decision board were more likely to choose BCT (94% vs 76%, P =.03). CONCLUSIONS: The decision board was helpful in improving communication and enabling women to make a choice regarding treatment. Such instruments should be considered by surgeons when communicating the different surgical options to women with breast cancer.

Breast Neoplasms↗
PubMed2004

Clinical practice guidelines for the care and treatment of breast cancer: 16. Locoregional post-mastectomy radiotherapy.

OBJECTIVE: To provide information and recommendations to assist women with breast cancer and their physicians in making decisions regarding the use of locoregional post-mastectomy radiotherapy (PMRT). OUTCOMES: Locoregional control, disease-free survival, overall survival and treatment-related toxicities. EVIDENCE: This guideline is based on a review of all meta-analyses, consensus statements and other guidelines published between 1966 and November 2002. Searches of MEDLINE and CANCERLIT for English-language randomized controlled trials published between 1995 and November 2002 were also conducted to supplement the literature previously reviewed by the American Society of Clinical Oncology (ASCO) Health Services Research Committee panel in its published guideline. A nonsystematic review of the literature was continued through June 2003. RECOMMENDATIONS: Locoregional PMRT is recommended for women with an advanced primary tumour (tumour size 5 cm or greater, or tumour invasion of the skin, pectoral muscle or chest wall). Locoregional PMRT is recommended for women with 4 or more positive axillary lymph nodes. The role of PMRT in women with 1 to 3 positive axillary lymph nodes is unclear. These women should be offered the opportunity to participate in clinical trials of PMRT. Locoregional PMRT is generally not recommended for women who have tumours that are less than 5 cm in diameter and who have negative axillary nodes. Other patient, tumour and treatment characteristics, including age, histologic grade, lymphovascular invasion, hormone receptor status, number of axillary nodes removed, axillary extracapsular extension and surgical margin status, may affect locoregional control, but their use in specifying additional indications for PMRT is currently unclear. PMRT should encompass the chest wall and the supraclavicular, infraclavicular and axillary apical lymph node areas. To reduce the risk of lymphedema, radiation of the entire axilla should not be used routinely after complete axillary dissection of level I and II lymph nodes. A definite recommendation regarding the inclusion of the internal mammary lymph nodes in PMRT cannot be made because of limited and inconsistent data. The use of modern techniques in radiotherapy planning is recommended to minimize excessive normal tissue exposure, particularly to the cardiac and pulmonary structures. Common short-term side effects of PMRT, including fatigue and skin erythema, are generally tolerable and not dose-limiting. Severe long-term side effects, including lymphedema, cardiac and pulmonary toxicities, brachial plexopathy, rib fractures and secondary neoplasms, are relatively rare. The optimal sequencing of PMRT and systemic therapy is currently unclear. Regimens containing anthracyclines or taxanes should not be administered concurrently with radiotherapy because of the potential for increased toxicity. VALIDATION: The authors' original text was submitted for review, revision and approval by the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Subsequently, feedback was provided by 11 oncologists from across Canada. The final document was approved by the steering committee. SPONSOR: The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada. COMPLETION DATE: November 2003.

Breast Neoplasms↗
PubMed2004

Vitamin C pharmacokinetics: implications for oral and intravenous use.

BACKGROUND: Vitamin C at high concentrations is toxic to cancer cells in vitro. Early clinical studies of vitamin C in patients with terminal cancer suggested clinical benefit, but 2 double-blind, placebo-controlled trials showed none. However, these studies used different routes of administration. OBJECTIVE: To determine whether plasma vitamin C concentrations vary substantially with the route of administration. DESIGN: Dose concentration studies and pharmacokinetic modeling. SETTING: Academic medical center. PARTICIPANTS: 17 healthy hospitalized volunteers. MEASUREMENTS: Vitamin C plasma and urine concentrations were measured after administration of oral and intravenous doses at a dose range of 0.015 to 1.25 g, and plasma concentrations were calculated for a dose range of 1 to 100 g. RESULTS: Peak plasma vitamin C concentrations were higher after administration of intravenous doses than after administration of oral doses (P < 0.001), and the difference increased according to dose. Vitamin C at a dose of 1.25 g administered orally produced mean (+/-sd) peak plasma concentrations of 134.8 +/- 20.6 micromol/L compared with 885 +/- 201.2 micromol/L for intravenous administration. For the maximum tolerated oral dose of 3 g every 4 hours, pharmacokinetic modeling predicted peak plasma vitamin C concentrations of 220 micromol/L and 13 400 micromol/L for a 50-g intravenous dose. Peak predicted urine concentrations of vitamin C from intravenous administration were 140-fold higher than those from maximum oral doses. LIMITATIONS: Patient data are not available to confirm pharmacokinetic modeling at high doses and in patients with cancer. CONCLUSIONS: Oral vitamin C produces plasma concentrations that are tightly controlled. Only intravenous administration of vitamin C produces high plasma and urine concentrations that might have antitumor activity. Because efficacy of vitamin C treatment cannot be judged from clinical trials that use only oral dosing, the role of vitamin C in cancer treatment should be reevaluated.

Administration, Oral↗
PubMed2004

Clinical practice guidelines for the care and treatment of breast cancer: 15. Treatment for women with stage III or locally advanced breast cancer.

OBJECTIVE: To define the optimal treatment for women with stage III or locally advanced breast cancer (LABC). EVIDENCE: Systematic review of English-language literature retrieved from MEDLINE (1984 to June 2002) and CANCERLIT (1983 to June 2002). A nonsystematic review of the literature was continued through December 2003. RECOMMENDATIONS: The management of LABC requires a combined modality treatment approach involving surgery, radiotherapy and systemic therapy. Systemic therapy: chemotherapy. Operable tumours. Patients with operable stage IIIA disease should be offered chemotherapy. They should receive adjuvant chemotherapy following surgery, or primary chemotherapy followed by locoregional management. Chemotherapy should contain an anthracycline. Acceptable regimens are 6 cycles of FAC, CAF, CEF or FEC. Taxanes are under intense investigation. Inoperable tumours. Patients with stage IIIB or IIIC disease, including those with inflammatory breast cancer and those with isolated ipsilateral internal mammary or supraclavicular lymph-node involvement, should be treated with primary anthracycline-based chemotherapy. Acceptable chemotherapy regimens are FAC, CAF, CEF or FEC. Taxanes are under intense investigation. Patients with stage IIIB or IIIC disease who respond to primary chemotherapy should be treated until the response plateaus or to a maximum of 6 cycles (minimum 4 cycles). Patients with stage IIIB disease should then undergo definitive surgery and irradiation. The locoregional management of patients with stage IIIC disease who respond to chemotherapy should be individualized. In patients with stage IIIB or IIIC disease who achieve maximum response with fewer than 6 cycles, further adjuvant chemotherapy can be given following surgery and irradiation. Patients whose tumours do not respond to primary chemotherapy can be treated with taxane chemotherapy or can proceed directly to irradiation followed by modified radical mastectomy, if feasible. Systemic therapy: hormonal therapy. Operable and inoperable tumours. Tamoxifen for 5 years should be recommended to pre- and postmenopausal women whose tumours are hormone responsive. Locoregional management. Operable tumours. Patients with stage IIIA disease should receive both modified radical mastectomy (MRM) and locoregional radiotherapy if feasible. They may be managed with MRM followed by chemotherapy and locoregional radiotherapy, or chemotherapy first followed by MRM and locoregional radiotherapy. Breast-conserving surgery is currently not a standard approach. Locoregional radiotherapy should be delivered to the chest wall and to the supraclavicular and axillary nodes. The role of internal mammary irradiation is unclear. Inoperable tumours. Patients with stage IIIB disease who respond to chemotherapy should receive surgery plus locoregional radiotherapy. The locoregional management of patients with stage IIIC disease who respond to chemotherapy is unclear and should be individualized. Patients whose disease remains inoperable following chemotherapy should receive locoregional radiotherapy with subsequent surgery, if feasible. VALIDATION: The authors' original text was revised by members of the Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer. Subsequently, feedback was provided by 9 oncologists from across Canada. The final document was approved by the steering committee. SPONSOR: The Steering Committee on Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was convened by Health Canada. Completion date: December 2003.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Short-term and long-term vitamin C supplementation in humans dose-dependently increases the resistance of plasma to ex vivo lipid peroxidation.

To assess the effects of short-term and long-term vitamin C supplementation in humans on plasma antioxidant status and resistance to oxidative stress, plasma was obtained from 20 individuals before and 2h after oral administration of 2g of vitamin C, or from eight subjects enrolled in a vitamin C depletion-repletion study using increasing daily doses of vitamin C from 30 to 2500 mg. Plasma concentrations of ascorbate, but not other physiological antioxidants, increased significantly after short-term supplementation, and increased progressively in the long-term study with increasing vitamin C doses of up to 1000 mg/day. Upon incubation of plasma with a free radical initiator, ascorbate concentrations were positively correlated with the lag phase preceding detectable lipid peroxidation. We conclude that vitamin C supplementation in humans dose-dependently increases plasma ascorbate concentrations and, thus, the resistance of plasma to lipid peroxidation ex vivo. Plasma and body saturation with vitamin C in humans appears desirable to maximize antioxidant protection and lower risk of oxidative damage.

Adult↗
PubMed2004

Comparison of the genomic structure and variation in the two human sodium-dependent vitamin C transporters, SLC23A1 and SLC23A2.

Vitamin C (L-ascorbic acid) is an essential co-factor for eight mammalian enzymes and quenches reactive oxygen species. Sodium-dependent vitamin C transport is mediated by two transporters, SVCT 1 and SVCT 2, encoded by SLC23A1 and SLC23A2. We characterized the genomic structures of SLC23A1 and SLC23A2, determined the extent of genetic variation and linkage disequilibrium across each gene, analyzed nucleotide diversity to estimate the effect of selective pressure, and compared sequence variation across species. In SLC23A1, the majority of single nucleotide polymorphisms (SNPs) are population-specific in either African Americans or Caucasians, including three of four non-synonymous SNPs. In contrast, most SNPs in SLC23A2 are shared between African Americans and Caucasians, and there are no non-synonymous SNPs in SLC23A2. Our analysis, combined with previous in vitro and in vivo studies, suggests that non-synonymous variation appears to be tolerated in SLC23A1 but not SLC23A2, and that this may be a consequence of different selective pressures following past gene duplication of the sodium-dependent vitamin C transporters. Genetic association studies of these two genes will need to account for the differences in haplotype structure and the population-specific variants. Our data represent a fundamental step toward the application of genetics to refining nutrient recommendations, specifically for vitamin C, and may serve as a paradigm for other vitamins.

Base Composition↗
PubMed2004

Identity, place, and bystander intervention: social categories and helping after natural disasters.

The authors developed a Self-Categorization Theory (SCT) approach to bystander behavior. Participants were 100 undergraduates at an English university. The authors made either a European or a British identity salient. Participants then rated their likelihood of offering both financial and political help after natural disasters in Europe and South America. When European (but not British) identity was salient, participants were less likely to offer help for disasters in South America than Europe. They were also more likely to offer financial help after disasters in Europe when European non-British identity was salient. There were no differences in levels of emotional response to disasters by identity salience. Results indicate that social category relations rather than geographical proximity or emotional reaction are most important in increasing helping behavior after natural disasters.

Adult↗
PubMed2003

Reduction of atherosclerotic plaques by lysosomal acid lipase supplementation.

OBJECTIVE: Proof of principle is presented for targeted enzyme supplementation by using lysosomal acid lipase to decrease aortic and coronary wall lipid accumulation in a mouse model of atherosclerosis. METHODS AND RESULTS: Mice with LDL receptor deficiency were placed on an atherogenic diet and developed predictable aortic and coronary atheroma. alpha-Mannosyl-terminated human lysosomal acid lipase (phLAL) was produced in Pichia pastoris, purified, and administered intravenously to such mice with either early or late lesions. phLAL injections reduced plasma, hepatic, and splenic cholesteryl esters and triglycerides in affected mice. phLAL was detected in hepatic Kupffer cells and in atheromatous foam cells. Repeated enzyme injections were well tolerated, with no obvious adverse effects. In addition, the coronary and aortic atheromatous lesions were (1) eliminated in their early stages and (2) quantitatively and qualitatively reduced in their advanced stages. CONCLUSIONS: These results support the potential utility of lysosomal acid lipase supplementation for the treatment of atherosclerosis, a leading cause of mortality and morbidity in Westernized nations.

Animals↗
PubMed2003

The Initial Health Assessment: an intervention to identify the supportive care needs of cancer patients.

BACKGROUND: The first step in effective supportive care delivery is an assessment of patient needs. The Initial Health Assessment Form (IHA) was developed to aid clinicians in recognition and documentation of a patient's supportive care needs during their first visit to a comprehensive cancer centre. The purpose of this study was to determine the relative effectiveness of this instrument as compared to routine practice. METHODS: A before-after study was performed. Charts of consecutive patients with newly diagnosed cancer attending the Hamilton Regional Cancer Centre were selected randomly. Each chart was reviewed to determine the documentation at the initial patient assessment of 22 supportive care items under eight domains of need: physical, psychological, daily living, social, financial, informational, special needs and personal resources. The pre-intervention evaluation (T1) occurred over a 3-month period followed by the introduction of the IHA into clinical practice. Three months after its introduction, the post-intervention (T2) evaluation took place over the ensuing 3 months. RESULTS: A total of 306 charts were evaluated (153 each in T1 and T2). Patients from the two time periods were comparable with respect to background demographic variables. Introduction of the IHA increased the mean documentation of supportive care needs and resources from 26% in T1 to 49% in T2 ( p=0.001). Significant improvements were found in all domains of need. Despite improvements, documentation of assessment continued to remain low for daily living, social, financial, and informational needs. CONCLUSIONS: The IHA improved documentation of supportive care needs and resources. There is still room for improvement.

Adult↗
PubMed2003

Risk of acute leukemia following epirubicin-based adjuvant chemotherapy: a report from the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Cyclophosphamide, epirubicin, and fluorouracil (CEF), compared with classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy. has lead to an improvement in relapse-free and overall survival in premenopausal women with node-positive breast cancer. We undertook this analysis to more accurately define the estimate of risk of secondary acute leukemia (sAL) following epirubicin-containing chemotherapy regimens. PATIENTS AND METHODS: We assessed the conditional probability of sAL among 1,545 women who received adjuvant (n = 1,477) or neoadjuvant (n = 68) chemotherapy in four National Cancer Institute of Canada Clinical Trials Group trials from 1990 to 1999. The risks associated with epirubicin-containing regimens (CEF or epirubicin and cyclophosphamide [EC]) and other regimens (doxorubicin and cyclophosphamide [AC] or CMF) were determined. RESULTS: A total of 10 cases of sAL were observed (eight acute myelogeneous leukemia, two acute lymphoblastic leukemia): seven among women treated with CEF, two who had received AC, and one following CMF. Using competing risk statistics, the conditional probability of sAL was 1.7% (95% confidence interval [CI], 0.5 to 3.6) among 539 women treated with CEF chemotherapy at a follow-up of 8 years, 0.4% (95% CI, 0% to 1.3%) among the 678 who received CMF, and 1.3% (95% CI, 0% to 4.7%) among the 231 treated with AC. The conditional probability of death from breast cancer at 8 years for the entire group of women treated with epirubicin-containing regimens in all four trials was approximately 34.9%. CONCLUSION: CEF chemotherapy for breast cancer carries a small increased risk of sAL compared with CMF. These estimates of acute leukemia risk are important in discussing treatment with women, especially patients with a lower risk of death from breast cancer, such as those with node-negative breast cancer.

Acute Disease↗
PubMed2003

Impaired adrenal catecholamine system function in mice with deficiency of the ascorbic acid transporter (SVCT2).

Ascorbic acid (vitamin C) is a cofactor required in catecholamine synthesis for conversion of dopamine to norepinephrine by dopamine beta-hydroxylase. Mutant mice lacking the plasma membrane ascorbic acid transporter (SVCT2) have severely reduced tissue levels of ascorbic acid and die after birth. We therefore investigated whether these mice might have impaired synthesis of catecholamines. Levels of catecholamines in brain were unaffected by SVCT2 deficiency. In heart, the only evidence for impaired dopamine beta-hydroxylase activity was a twofold increase in tissue dopamine. An influence of the deficiency on tissue catecholamines was most prominent in the adrenals where norepinephrine was decreased by 50% and epinephrine, by 81%. On the ultrastructural level, adrenal chromaffin cells in SVCT2 null mice showed depletion of catecholamine storage vesicles, increased amounts of rough endoplasmic reticulum, signs of apoptosis, and increased glycogen storage. Decreased plasma levels of corticosterone indicated additional effects of the deficiency on adrenal cortical function. These data show that deranged catecholamine system function in SVCT2 null mice is largely restricted to the adrenal medulla and cannot account for the lethality in these animals. The data, however, establish a crucial role for ascorbic acid in adrenal chromaffin cell function.

Adrenal Glands↗