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Biomedical subjects

E A Davis

Publications and source records attributed to E A Davis.

At least 37 records · Page 2Linked to original sources
PubMed1998

Modulation of AT1 receptor-mediated contraction of rat uterine artery by AT2 receptors.

The aim of this study was to characterize the angiotensin II receptors in isolated uterine arteries from non pregnant and pregnant rats, since it has been reported from binding studies that ovine uterine arteries contain AT2 receptors. Uterine arterial segments were obtained from virgin, non-pregnant and late pregnant (18-21 days) Sprague-Dawley rats and mounted in small vessel myographs. Concentration-response curves were constructed to angiotensin II (1 nM-10 microM) in the absence and presence of various angiotensin II receptor subtype selective compounds. These included losartan (AT1 antagonist; 1, 10 and 100 nM), PD 123319 (AT2 antagonist; 1 microM) and CGP 42112 (AT2 agonist; 1 microM). Responses to angiotensin II were measured as increases in force (mN) and expressed as a per cent of the response to a K+ depolarizing solution. Losartan (1, 10 and 100 nM) caused significant concentration-dependent rightward shifts of the angiotensin II concentration-response curve in uterine arteries from non-pregnant and pregnant rats. The pA2 values calculated from these data were 9.8 and 9.2, respectively, although the slope of the Schild plot in the non-pregnant group was less than unity. PD 123319 (1 microM) caused significant 6- and 3 fold leftward shifts of the angiotensin II concentration-response curve in uterine arteries from non-pregnant and pregnant rats, respectively. In vessels from pregnant rats, PD 123319 also significantly increased the maximum response to angiotensin II. CGP 42112 (1 microM) attenuated the response to angiotensin II of uterine arteries from non-pregnant rats. This was reflected by a 14 fold rightward shift of the angiotensin II concentration-response curve and a decrease in the maximum response. In uterine arteries from pregnant rats, CGP 42112 (1 microM) caused a 3 fold rightward shift of the angiotensin II concentration-response curve, but had no effect on the maximum response. PD 123319 (1 microM) and CGP 42112 (1 microM) had no effect on the concentration-response curves to phenylephrine (PE) of uterine arteries from non-pregnant or pregnant rats. In addition, CGP 42112 (1 nM-1 mM) had no vasodilator effect on tissues precontracted with phenylephrine. These results suggest that the contractile responses of the rat uterine artery are mediated by the AT1 receptor. Furthermore, in this vascular preparation, the AT2 receptor appears to inhibit the response mediated by the AT1 receptor, although, this is not uniform between the non-pregnant and pregnant states.

Angiotensin II↗
PubMed1998

Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus.

Increased emphasis on strict glycaemic control of insulin dependent diabetes mellitus (IDDM) in young patients may be expected to cause increases in rates of significant hypoglycaemia. To evaluate whether this is the case for a large population based sample of IDDM children and adolescents rates of severe (coma, convulsion) and moderate (requiring assistance for treatment) hypoglycaemia were studied prospectively over a four year period. A total of 709 patients were studied yielding 2027 patient years of data (mean (SD) age: 12.3 (4.4); range 0-18 years, duration IDDM: 4.9 (3.8) years). Details of hypoglycaemia were recorded at clinic visits every three months when glycated haemoglobin (HbA1c) was also measured. Overall the incidence of severe hypoglycaemia was 7.8 and moderate was 15.4 episodes/100 patient years. Over the four years mean (SD) clinic HbA1c steadily fell from 10.2 (1.6)% in 1992 to 8.8 (1.5)% in 1995. In parallel with this there was a dramatic increase in the rate of hypoglycaemia, especially in the fourth year of the study, when severe hypoglycaemia increased from 4.8 to 15.6 episodes/100 patient years. This increase was particularly marked in younger children (< 6 years) in whom severe hypoglycaemia increased from 14.9 to 42.1 episodes/100 patient years in 1995. It is concluded that attempts to achieve improved metabolic control must be accompanied by efforts to minimise the effects of significant hypoglycaemia, particularly in the younger age group.

Adolescent↗
PubMed1998

Hypoglycemia in children with diabetes: incidence, counterregulation and cognitive dysfunction.

Hypoglycemia remains a critical problem in the treatment of IDDM and often limits our ability to consistently achieve excellent glycemic control. Ongoing studies will be important to increase our understanding of the factors responsible for its occurrence and the impact that hypoglycemia may have, particularly for the brain. Significant differences have been documented between adults and children in the incidence of this complication of insulin therapy as well as in the counterregulatory hormone responses to hypoglycemia and its effects on the CNS. While children with diabetes still need insulin treatment, the prevention of hypoglycemia will be a central aim of management. This will depend on effective and expert diabetes education and support for the patient and his or her family along with better efforts to achieve more physiological insulin replacement.

Adolescent↗
PubMed1998

Prolonged discordant xenograft survival by inhibition of the intrinsic coagulation pathway in complement C6-deficient recipients.

BACKGROUND: Xenotransplantation of vascularized organs between unmodified discordant species results in hyperacute graft rejection within minutes to hours after graft reperfusion. This process is due to the presence of natural xenoreactive antibodies and complement activation, which lead to vessel injury, thrombosis, and hemorrhage. Because multiple components of the coagulation and complement cascades interact with each other, we have investigated the effects of inhibiting these systems together. The recombinant Kunitz type serine protease inhibitor (KPI-BG022) tested in these experiments inhibits factor XIIa, kallikrein, and plasmin. METHODS: Cardiac xenografts from male Hartley guinea pigs were heterotopically grafted into male PVG rats that were either sufficient (C6[+]) or deficient (C6[-]) for the complement component C6 and thus formation of the membrane attack complex. Experimental animals received KPI 5 mg/kg intravenously before reperfusion, and control animals received saline placebo. RESULTS: C6(+) recipients rejected their grafts hyperacutely, without a significant difference between KPI-treated (0.12+/-0.05 hours) and placebo-treated (0.13+/-0.06 hours) recipients (n = 10). As expected, C6(-) recipients showed prolonged graft survival (17.65+/-3.45 hours, n = 5). However, a single intravenous bolus of KPI before releasing the clamps further delayed graft rejection in C6(-) recipients (46.2+/-3.3 hours; n = 5). Histologic examination at 2, 6, and 12 hours after transplantation showed platelet aggregation and inflammatory infiltrates were significantly decreased in KPI-treated (C6[-]) recipients. However, intragraft hemorrhage was apparent at 6 and 12 hours. CONCLUSIONS: We conclude that in vivo inhibition of the intrinsic clotting cascade by functional inactivation of factor XIIa has a synergistic effect with inhibition of membrane attack complex formation in preventing hyperacute discordant xenograft rejection.

Animals↗
PubMed1998

A comparison of the development of renal hypertension in male and female rats.

1. The objective of this study was to determine the influence of gender on the development of renal hypertension in Sprague-Dawley rats using the Goldblatt two-kidney, one-clip (2K1C) model. In addition, this study examined the effect of ovariectomy upon the development of hypertension in female rats.2. At 10 weeks of age, male, intact female and ovariectomized female rats underwent clipping of the right renal artery or sham operation. Tail-cuff plethysmography was used to monitor the systolic blood pressure of all animals for 7 weeks post-clipping or sham operation. Rats were sub-grouped according to whether or not they developed hypertension (systolic blood pressure >=150 mmHg).3. Within 2 to 3 weeks of clipping, hypertension was induced in only 53% (n=120) of the intact female 2K1C rats, but in 83% (n=18) of the male and 78% (n=18) of the ovariectomized female rats.4. Seven weeks after right renal artery clipping, plasma renin activity was determined in a subset of each group and was found to be 5-6 fold higher in male (17.29+/-4.04 ng angiotensin I.h-1.ml-1) and ovariectomized female (9.71+/-1.25 ng angiotensin I.h-1.ml-1) hypertensive rats compared with their respective normotensive or sham-operated counterparts (3.39+/-0.58 ng angiotensin I.h-1.ml-1 and 1.60+/-0.41 ng angiotensin I.h-1.ml-1 respectively) (P<0.05, analysis of variance). In contrast, the plasma renin activity measured in intact female hypertensive rats was not significantly different from that measured in the corresponding 2K1C normotensive or sham-operated groups.5. These results indicate that the success rate of inducing renal hypertension in Sprague-Dawley rats is higher in males than in intact females. Furthermore, these results suggest that the induction of 2K1C hypertension may be influenced by ovarian hormones.

Animals↗
PubMed1997

Law enforcement agencies and out-of-hospital emergency care.

STUDY OBJECTIVE: We sought to assess the involvement of law enforcement agencies in out-of-hospital emergency medical care and their attitudes toward expanded roles in emergency medical services (EMS) systems. METHODS: We mailed a 20-question survey to 800 police chiefs and sheriffs randomly selected from a list of all law enforcement agencies in the United States. The questions focused on the characteristics of each law enforcement agency, its current level of involvement in providing out-of-hospital emergency medical care, and the characteristics of its associated community and local EMS system. The survey concluded with four statements to assess officer attitudes toward an expanded role in EMS-related activities. We used the chi 2 or Fisher exact test to analyze differences in proportions. The alpha-error rate was set at .05. RESULTS: Seventeen surveys were returned as undeliverable. Of the remaining 783 surveys, we received 602 responses (77%). Five hundred forty-nine (70.1%) of the respondents were the primary law enforcement agencies in their communities; they make up the final sample. The median number of officers per agency was 12 (range, 1 to 2,623), and the median population served was 6,936 (range, 150 to 1,500,000). Responses indicated that 442 (80.7%) agencies responded to one or more specific types of medical emergencies and 263 (50.3%) provided some level of patient care. Law enforcement officers frequently arrived at the scene of medical emergencies before EMS personnel (81.5%), with a roll-time interval of less than 8 minutes (87.2%). Only 14 agencies (2.6%) used automatic external defibrillators. Fifty-three percent agreed with the statement that EMS-related activities would interfere with their law enforcement duties. However, more than 60% of respondents agreed that law enforcement agencies should be involved in providing emergency medical services for life-threatening emergencies, that their officers would be willing to undertake extra medical training and that EMS-related activities would improve their public images. CONCLUSION: Many law enforcement agencies are involved to some extent in providing out-of-hospital emergency medical care, and most of the agencies we surveyed would support additional medical training and new or expanded roles for themselves in EMS systems.

Attitude↗
PubMed1997

Coactivators and TAFs of transcription activation in wheat.

Transcription regulation often activates quiescent genes in a tissue-specific or developmental manner. Activator proteins bind to a DNA sequence upstream of the promoter, interact with the general transcription proteins via bridging proteins, and elevate transcription levels. One group of bridging proteins, the coactivators, have been characterized in animals as polypeptides tightly associated with the general transcription factor TATA-binding protein (TBP). They are referred to as TAFs (TBP-associated factors), and together with TBP comprise general transcription factor IID. We provide biochemical evidence that wheat IID contains coactivators. An activator protein with an acidic activation domain facilitates the binding of IID to the template, and potentiates activated in vitro transcription with wheat IID, but not with wheat TBP. Using antibodies to wheat TBP, we demonstrate that wheat IID also contains TAFs. This is the first demonstration that a plant contains coactivators and TAFs.

Animals↗
PubMed1997

Hypoglycemia: incidence and clinical predictors in a large population-based sample of children and adolescents with IDDM.

OBJECTIVE: To determine the frequency of moderate and severe hypoglycemia and to identify clinical predictors associated with its occurrence in a large population-based sample of children and adolescents with IDDM. RESEARCH DESIGN AND METHODS: A total of 657 patients (age: 12.1 +/- 4.4 years, mean +/- SD) were included in the study, yielding 1,449 patient-years of data. A prospective assessment of severe hypoglycemia (an event resulting in a seizure or coma) and moderate hypoglycemia (an event requiring assistance of another, excluding severe episodes) was made over a 3-year period. Patients and caregivers detailed episodes of significant hypoglycemia (moderate and severe events) and these were recorded at each 3-month clinic visit along with HbA1c. Data were analyzed using generalized estimating equation models fitted with the exchange correlation structure. RESULTS: The overall incidence of severe events was 4.8/100 patient-years and of moderate events was 13.1/100 patient-years. Over 3 years, severe events occurred in 8.5% of children and moderate events occurred in 26.9%. Significant hypoglycemia was rare in the first 12 months after diagnosis. Rates of hypoglycemia were increased in children < 6 years of age versus > 6 years of age (40.9 vs. 16.6/100 patient-years, age < or = 6 years vs. age > 6 years, P < 0.001). Rates of hypoglycemia doubled when HbA1c fell below 8%, and children with HbA1c < 7% had a threefold increase in both moderate and severe hypoglycemia (e.g., severe episodes 14.9 vs. 4.1/100 patient-years, HbA1c < or = 7% vs. HbA1c > 7%, P < 0.001). Most severe events were seizures, and 75% of them occurred at night. The majority of events were related to missed meals or increased activity. However, in 38% no predisposing factor was evident. CONCLUSIONS: Newly diagnosed children appear to be protected from severe hypoglycemia. Rates increase with lower glycated hemoglobin, especially when mean HbA1c is < 8.0%. Younger children, who may be more susceptible to the adverse effects of neuroglycopenia, are at a particular risk of significant hypoglycemia.

Adolescent↗
PubMed1997

The use of biothesiometry to detect neuropathy in children and adolescents with IDDM.

OBJECTIVE: To develop clinically useful reference ranges for vibration perception thresholds (VPTs), using biothesiometry in children and adolescents and to assess the reliability of the technique to identify subclinical neuropathy in subjects with IDDM at this age and to examine a large population-based sample of pediatric patients. RESEARCH DESIGN AND METHODS: VPTs were measured using a handheld biothesiometer at the medial malleolus and hallux in 232 nondiabetic children and adolescents aged 7-18 years (12.9 +/- 4.2 years) and a population-based sample of 307 young IDDM patients (13.3 +/- 4.6 years of age). The mean of three readings at each site was correlated with height, pubertal status, and age for all subjects and, in addition for the IDDM sample, with the duration of IDDM, ambient blood glucose, and mean HbA1c from diagnosis. Those IDDM subjects found to have elevated VPTs (> 97th percentile), and a control group of patients with IDDM underwent nerve conduction studies to determine the sensitivity and specificity of biothesiometry to detect abnormal neural function in children. Interoperator reliability was assessed in a separate trial in which two operators measured VPTs independently in the same 11 children. RESULTS: In the nondiabetic control subjects, height demonstrated the best correlation with VPT measures, and a reference range was thus established with percentile charts, using mean VPT and height. VPTs were higher in the diabetic sample, compared with the nondiabetic sample (P < 0.05). Of the children, 28 (9.1%) had VPT values > 97th percentile developed from studies of the nondiabetic subjects; of these, 11 were younger than 11 years and 8 were prepubertal. Nerve conduction studies confirmed reduced conduction velocity and prolonged distal latencies in those with abnormal VPTs, compared with normal control subjects and IDDM patients with normal VPTs. Sensitivity of biothesiometry to reflect abnormal nerve function was estimated as 82% and specificity as 75% at this age. Interoperator variation was small (7.25% of total variance). CONCLUSIONS: Biothesiometry is a useful noninvasive tool for the detection of subclinical neuropathy in children and adolescents. The use of height-related reference ranges may make screening for neuropathy more feasible in younger patients and allow large-scale longitudiral analysis of its development.

Adolescent↗
PubMed1997

The role of CD11b/CD18 mediated neutrophil adhesion in complement deficient xenograft recipients.

Hyperacute rejection (HAR) of discordant xenografts is dependent on local complement activation. The formation of a functional complex of the complement components C5b-9 (membrane attack complex, MAC) causes endothelial injury and activation leading to coagulation and inflammation. In PVG rats which selectively lack the C6 component of complement, the MAC complex is not formed, whereas early split products of the complement cascade are produced normally. We reported previously that HAR is averted in C6 deficient xenograft recipients, and that subsequent accelerated acute rejection (AAR) can be delayed by inhibition of CD11b/CD18 (Mac-1) dependent neutrophil adhesion using leumedin, a member of a novel class of anti-inflammatory agents. Here we report the in vivo effects of a dose-response study using 2 new members of another class of Mac-1 directed agents designated nactins. Discordant cardiac xenografts from Hartley guinea pigs were heterotopically grafted into PVG(C6-) and PVG(C6+) rats. Experimental animals were divided into 3 groups receiving leumedin (group 1) or nactin (groups 2 and 3). Control animals received intravenous saline solution only. All C6(+) rats rejected their grafts hyperacutely within 10 to 15 min, irrespective of mode or dosage of treatment. C6 deficient controls rejected grafts within 17.7 +/- 3.5 h (n = 10). Treatment with leumedin/nactin prolonged graft survival up to 61.0 +/- 4.7 h (n = 4-6), with dose dependent differences in effectiveness among the 3 compounds tested. Histology showed that treatment was associated with less edema, hemorrhage, and neutrophil infiltrate at 2, 6, and 12 h. The marked decrease in hemorrhage seen in nactin-treated animals may reflect an interaction of Mac-1 with blood coagulation factors. Our data confirm that the neutrophil adhesion pathway is involved in AAR, especially when complement mediated injury due to MAC is restricted.

Acute Disease↗
PubMed1996

Bioprosthetic versus mechanical prostheses for aortic valve replacement in the elderly.

BACKGROUND: Many centers advocate bioprosthetic valves in the elderly to avoid anticoagulation, in particular when patient survival is less than the expected valve durability. Because expected survival in the elderly is increasing and age-specific risk of anticoagulation in the elderly is not known, we examined valve- and anticoagulation-related morbidity in elderly patients after aortic valve replacement (AVR) with bioprostheses or mechanical prostheses. METHODS AND RESULTS: Between January 1980 and June 1994, 211 patients age > or = 70 years underwent isolated AVR; there were 109 men (52%) and 102 women (48%). Mean age was 75.9 +/- 4.8 years. Aortic stenosis was present in 194 (92%) patients. Bioprostheses were used in 145 (69%) and mechanical prostheses were used in 66 (31%). Chronic anticoagulation was maintained in all patients with a mechanical valve and in 18 patients (12%) with a bioprosthetic valve. Follow-up data were obtained for 98% (194 of 197) of hospital survivors at a mean follow-up of 3.8 years. Operative mortality was 6.6%; survival at 3 and 5 years was 75.3 +/- 3% and 64.6 +/- 4%, respectively. There was no significant difference in operative or late mortality between patient groups. Rates of freedom from thromboembolic events, endocarditis and anticoagulant-related hemorrhage for bioprosthetic and mechanical valve patients were similar. Prosthetic failure was identified in three bioprosthetic valves (2%); furthermore, the 4 patients in the series who required reoperation had received bioprostheses at the first operation. CONCLUSIONS: In conclusion, (1) elderly patients undergoing isolated AVR can be managed with either mechanical or bioprosthetic valves with similar early and late risk, as long as there are no specific contraindications to anticoagulation; (2) anticoagulation-related risk of hemorrhage is low in this group of elderly patients; and (3) the low but significant risk of reoperation following the use of bioprostheses suggests that mechanical valves may be underused in the elderly.

Aged↗
PubMed1996

Inhibition of complement, evoked antibody, and cellular response prevents rejection of pig-to-primate cardiac xenografts.

Complement (C) inhibition alone using a recombinant soluble form of complement receptor type 1 (sCR1) prevents hyperacute rejection but not subsequent irreversible accelerated acute rejection of discordant pig-to-cynomolgus monkey cardiac xenografts, which occurs within 1 week. To inhibit accelerated acute rejection, which is associated with a rise in serum xenoreactive antibody (Ab) and a cellular infiltrate, triple therapy with standard immunosuppressive agents (cyclosporine, cyclophosphamide, and steroids [CCS]) was combined with continuous C inhibition using sCR1. Each of two monkeys that received sCR1 + CCS showed minimal evidence of rejection when killed on days 21 and 32 in comparison to a monkey that received sCR1 + subtherapeutic CCS (rejected at 11 days) and a control that received CCS alone (rejected at 38 min). Prolonged xenograft survival was associated with low Ab levels and a minimal cellular infiltrate, suggesting that combined inhibition of C, xenoreactive Ab responses, and cellular immunity may be a useful approach in overcoming the immune barriers to discordant xenotransplantation.

Animals↗
PubMed1996

Induction of heat shock protein in cardiac allograft rejection--a cyclosporine-suppressible response.

The cellular response to a wide variety of stresses results in the synthesis of a family of proteins termed heat shock proteins (HSPs). To determine if acute allograft rejection could induce these proteins in a transplanted graft, we examined the HSP response to acute cardiac allograft rejection and analyzed the effect of immunosuppression upon this response. Donor hearts obtained from either Lewis (LEW) or ACI rats were heterotopically transplanted in recipient LEW rats. There were 4 experimental groups: untreated isografted (LEW to LEW) animals (n = 14), untreated allografted (ACI to LEW) animals (n = 14), cyclosporine-treated (10 mg/kg SQ/day) isografted animals (n = 12), and cyclosporine-treated allografted animals (n = 12). Animals were sacrificed on posttransplantation day 2, 4, or 6 (time of rejection for untreated allografts); n = 4-5 for each time point per group. At these times tissue obtained from the transplanted heart was examined histologically and analyzed for HSP72 by quantitative Northern and Western blots. The level of HSP72 in the untreated allografts progressively increased between 2, 4, and 6 days posttransplantation and was significantly greater than that of the untreated isografts at all time points. The HSP72 response in cyclosporine-treated allografts was significantly reduced at 4 and 6 days posttransplantation compared with the untreated allografts. In contrast, there was no difference in the HSP response in treated versus untreated isografts. Additionally, there was no difference in HSP levels in cyclosporine-treated isografts and allografts. These findings demonstrate that HSP expression in the transplanted heart correlates directly with the evolution of acute allograft rejection, and that immunosuppressive therapy inhibits the HSP response. These studies also raise the possibility of a functional role for HSPs in the allogeneic immune response.

Animals↗
PubMed1996

Aortic aneurysm complicating bacterial endocarditis in childhood.

Bacterial endocarditis is an uncommon diagnosis in childhood with significant morbidity and mortality. Aortic aneurysm as a complication is well described in adults but there are few reports in the paediatric literature. Two children with bacterial endocarditis are described, whose illnesses were complicated by aortic aneurysm formation requiring surgical intervention.

Adolescent↗
PubMed1996

Esophagectomy for benign disease: trends in surgical results and management.

BACKGROUND: Esophagectomy for benign disease is uncommon. METHODS: From July 1987 to April 1995, 45 consecutive patients (30 men, 15 women; mean age, 50 years) were evaluated in whom the senior author (R.F.H.) performed an esophagectomy, esophageal reconstruction, or both. The study period was divided into two time intervals, July 1987 to January 1992 (time 1) and February 1992 to April 1995 (time 2). RESULTS: Indications for operation included obstruction (23 patients, 51%), benign neoplasia (17.38%), and perforation (5 patients, 11%). A nonthoracotomy approach was used in 19 (42%) patients: 15 transhiatal and 4 substernal. Thoracotomies were performed in 26 (58%) patients through a left thoracoabdominal or multiincisional techniques. Morbidity occurred in 15 (33%) patients, and there was one operative death (2%). CONCLUSIONS: Despite an operative morbidity of 33%, esophagectomy for benign disease may be performed with acceptably low mortality. We observed the following trends: (1) an increase in patients with benign neoplasia and a decline in patients with obstruction, (2) an increased use of transhiatal esophagectomy, (3) a decreased use of colon, an increased use of stomach for esophageal replacement; and (4) a decreased length of hospital stay.

Adolescent↗
PubMed1995

Functionality of sugars: physicochemical interactions in foods.

Basic and selected functional properties of simple sugars, sugar alcohols, corn and maple syrups, honey, and high-fructose corn syrups are discussed. Properties that relate to sweetness and properties that play roles in component interaction as a basis for product formulation are described. The implications of such functionality are illustrated for the development of low-energy foods and for the microwave heating of foods. Among the properties discussed are solubility, hygroscopicity, crystallinity, and viscosity. Interrelations among water mobility, water activity, and hydration of proteins, lipids, and carbohydrates are described in the context of food formulation. Application of polymer chemistry principles to explain functional properties of amorphous molecules is reviewed.

Carbohydrates↗
PubMed1994

Factors influencing the implementation of the CNS role in a private practice.

Factors to be considered by the CNS before implementing the role in private practice with a physician are discussed. Four CNSs were interviewed regarding their experiences in such a practice. The CNS subroles of expert practitioner, educator, consultant, and researcher are described as they apply in private practice with a physician. A four-step process is proposed to guide the CNS considering entry into private practice. The steps discussed are: self-assessment, evaluation of the legal and financial aspects, development of marketing and cost-justification strategies, and negotiating for a position. A method for cost justification is proposed, and some elements of marketing and negotiating are reviewed.

Financial Management↗