PubMed Health⌕ Search

Biomedical subjects

M C Jacobs

Publications and source records attributed to M C Jacobs.

33 records · Page 2Linked to original sources
PubMed1995

Regional release and removal of catecholamines and extraneuronal metabolism to metanephrines.

Norepinephrine (NE) and epinephrine (E) are metabolized extraneuronally by catechol-O-methyl-transferase to the metanephrines (MNs), normetanephrine (NMN) and metanephrine (MN). Subjects in this study received infusions of tritium-labeled NE and E. Concentrations of MNs and catecholamines were measured in plasma flowing into and out of the heart, forearm, lungs, kidneys, mesenteric organs (gastrointestinal tract, spleen, and pancreas), liver, and adrenals to examine the regional production of MNs from circulating and locally released catecholamines. NE spillover from mesenteric organs and kidneys accounted for 64% of the spillover from all tissues. There was detectable spillover of E from most extraadrenal tissues, but 91% was from the adrenals. The production of MNs from locally released and circulating catecholamines varied widely among tissues. The liver made the largest contribution to removal of circulating NE (57%) and E (32%) and the largest contribution to the production of NMN (54%) and MN (37%) from metabolism of circulating catecholamines. In all other tissues more NMN was produced from locally released than from circulating NE. Thus, the metabolism of circulating NE was responsible for only 19% of the total production of NMN. An even smaller portion (6%) of plasma MN was derived from metabolism of circulating E. Most plasma MN (91%) was produced within the adrenals, which also provided the largest single source (23%) of NMN. The regional variation in extraneuronal production of MNs indicates considerable heterogeneity in how circulating and locally released catecholamines are handled by different tissues. The substantial contribution of the adrenals to the production of MNs explains the extraordinary sensitivity of these metabolites for the diagnosis of pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1995

Highly sensitive and specific HPLC with fluorometric detection for determination of plasma epinephrine and norepinephrine applied to kinetic studies in humans.

An HPLC separation method combined with fluorometric detection was extended to enable simultaneous assessment of plasma 3H-labeled and endogenous epinephrine (E) and norepinephrine (NE). Forearm fractional extraction (FFE) of 3H-labeled E and NE and of endogenous E was measured in 40 healthy volunteers who were receiving a continuous infusion of 3H-labeled E and NE. Concentrations of arterial and venous E were 26.8 +/- 1.95 (mean +/- SE) and 6.8 +/- 0.75 ng/L, respectively. Arterial and venous NE and dopamine (DA) were also measured, with respective values of 140.7 +/- 8.5 and 192.1 +/- 15.1 for NE, and 13.1 +/- 0.78 and 11.3 +/- 0.70 ng/L for DA. The FFE of 3H-labeled E was slightly but significantly higher (0.790 +/- 0.016) than the that of either 3H-labeled NE or endogenous E (0.748 +/- 0.0146 and 0.745 +/- 0.0185, respectively; P < 0.001), the correlations being highly significant (r = 0.80, P < 0.001) in both cases. The small difference between the FFE of E and of 3H-labeled E allows the calculation of the apparent spillover of E. However, this spillover was negligible compared with forearm NE spillover (0.0112 +/- 0.0031 vs 1.369 +/- 0.128 ng/L per minute. The high sensitivity of this measurement of venous E widens the possibilities for studying E kinetics under physiological conditions.

Adult↗
PubMed1995

Chronic alpha-1-adrenergic blockade increases sympathoneural but not adrenomedullary activity in patients with essential hypertension.

OBJECTIVE: Doxazosin, a selective alpha1-adrenoceptor antagonist, lowers blood pressure by reducing peripheral vascular resistance without causing reflex tachycardia. To discover whether antihypertensive treatment with an alpha1-adrenoceptor blocker is accompanied by an increase in sympathoadrenomedullary activity, we studied plasma catecholamine kinetics before and during treatment with doxazosin. PATIENTS AND METHODS: Eleven patients with essential hypertension were studied before and after 3 months' treatment with doxazosin (4-8 mg a day). 3H-noradrenaline and 3H-adrenaline were infused simultaneously and blood samples were collected to calculate plasma catecholamine kinetics before and during sympatho-adrenomedullary stimulation (lower-body negative pressure). RESULTS: Doxazosin decreased systolic and diastolic blood pressure and forearm vascular resistance, whereas the heart rate did not change significantly. During doxazosin, baseline arterial plasma noradrenaline increased from 0.97 +/- 0.07 to 1.21 +/- 0.07 nmol/l, and this appeared to be due to an increase in total body noradrenaline spillover from 1.54 +/- 0.15 to 1.84 +/- 0.16 nmol/min; noradrenaline clearance did not change significantly. Forearm noradrenaline spillover also increased, from 0.89 +/- 0.18 to 1.48 +/- 0.23 pmol/100 ml per min. In contrast, arterial plasma adrenaline, total body adrenaline spillover and adrenaline clearance were not significantly affected by doxazosin treatment. The response of plasma noradrenaline and total body and forearm spillover of noradrenaline to lower-body negative pressure (-40 mmHg) was significantly increased during doxazosin administration, whereas the response of the adrenaline kinetic parameters were not altered. CONCLUSIONS: The blood pressure reduction induced by a chronic administration of the alpha1-adrenoceptor blocker doxazosin elicits a baroreceptor-mediated reflexive increase in sympathoneural but not in adrenomedullary activity. The latter finding might partly explain why the heart rate is not increased during chronic treatment with this alpha1-adrenoceptor blocking drug.

Adrenergic alpha-Antagonists↗
PubMed1994

Atrial natriuretic factor potentiates the human forearm vasoconstrictor response to sympathetic stimulation.

1. Atrial natriuretic factor has been suggested to affect human sympathetic nervous system activity. The interaction between atrial natriuretic factor and the sympathetic nervous system has not been fully elucidated yet, but may occur at different sites. We studied this modulator effect at the level of the forearm vascular bed: the forearm vasoconstrictor response was examined after alpha-adrenergic sympathetic stimulation in healthy subjects during the locoregional administration of atrial natriuretic factor, sodium nitroprusside and placebo. As a sympathetic stimulation test, the technique of the lower body negative pressure (-20 mmHg) was used. 2. Lower body negative pressure increased the forearm vascular resistance by +37 +/- 8% during concomitant intra-arterial infusion of placebo (n = 10). During a predilator state achieved by infusion of atrial natriuretic factor (10 ng min-1 100 ml-1 forearm volume) into the brachial artery, lower body negative pressure subsequently induced a forearm vasoconstrictor response of +153 +/- 22% (P < 0.05 versus placebo), whereas this was +64 +/- 14% when predilatation was achieved by infusion of an equipotent vasodilator dose of sodium nitroprusside (P > 0.1 versus placebo; P < 0.05 versus atrial natriuretic factor). The potentiation of the forearm vasoconstrictor response to lower body negative pressure by atrial natriuretic factor only occurred in the experimental and not in the contralateral arm. According to calculations on simultaneously sampled arterial and venous plasma catecholamine concentrations, the augmented forearm vasoconstrictor response seemed not to be caused by an increased release of noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

24-hour ambulatory blood pressure monitoring and spirapril in mild to severe essential hypertension: a randomized dose comparison.

This was a multicentre randomized, double-blind, parallel-group study to compare the antihypertensive efficacy of spirapril at 3 mg with 12 mg once daily, as determined by 24-hour ambulatory blood pressure monitoring (ABPM), in patients with mild to severe essential hypertension. Following a 4-week placebo run-in phase, 52 male and female outpatients, aged 23-67 years with mild to severe essential hypertension [diastolic blood pressure (DBP) > or = 100 mmHg and < 120 mmHg] were randomized to receive spirapril at either 3 mg or 12 mg once daily for 8 weeks. At the end of active treatment and using the standard mercury sphygmomanometer, the number of responders (sitting DBP < 90 mmHg, but decrease > or = 10 mmHg) was the same in both groups (32% and 37%). There were mean decrease in both systolic blood pressure (SBP) and DBP at trough with both 3 mg and 12 mg doses: -9/-7 mmHg and -12/-7 mmHg, respectively. The rate of normalization (trough DBP < or = 90 mmHg) was 12% and 30% with the 3 mg and 12 mg doses, respectively. Of the 44 patients whose daytime ABPM could be compared, one of 20 patients taking 3 mg of spirapril, and 9 of 24 taking 12 mg of spirapril achieved a DBP < or = 90 mmHg for all time intervals while awake. The differences in blood pressure-lowering were significant with both SBP and DBP during the day and at the end of the dosing interval (p < 0.001 and p < 0.01, respectively). The changes from baseline at 24 hours postdose for SBP/DBP were -3/-6 mmHg with 3 mg and -14/-12 mmHg with 12 mg of spirapril.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Effect of chronic smoking on endothelium-dependent vascular relaxation in humans.

1. Cigarette smoking is one of the major risk factors for the development of atherosclerosis. It is not clear, however, whether chronic cigarette smoking impairs the normal physiological function of the endothelium before the development of morphological vascular lesions. To test this, we investigated endothelium-dependent vascular relaxation in young habitual smoking subjects. 2. In 11 non-smokers and 10 habitual smokers we measured the changes in bilateral forearm blood flow, arterial blood pressure and forearm vascular resistance (ratio between mean arterial blood pressure and forearm blood flow) during three interventions: post-occlusive forearm hyperaemia, intrabrachial infusion of methacholine which causes vasodilatation by stimulating the release of endothelium-dependent relaxing factor, and intrabrachial infusion of sodium nitroprusside which causes vasodilatation independently from the endothelium by a direct effect on the vascular smooth muscle wall. 3. During infusion of the highest dose of methacholine, forearm vascular resistance decreased by 91.7 +/- 1.4% in the smokers and by 89.9 +/- 1.8% in the non-smokers. During infusion of sodium nitroprusside, forearm vascular resistance decreased by 80.0 +/- 3.8% in the smokers as compared with 80.7 +/- 6.1% in the non-smokers. There was no difference in basal forearm vascular resistance or in post-ischaemic reactive hyperaemia between smokers and non-smokers. Thus, vasodilatation induced by both methacholine and sodium nitroprusside was not significantly different between smokers and non-smokers. 4. We conclude that in young habitual cigarette smokers the endothelium-dependent vasodilation in the forearm seems to be preserved, suggesting that habitual smoking does not result in permanent endothelial dysfunction in the human forearm.

Adult↗
PubMed1993

Endothelium-dependent vascular relaxation in patients with type I diabetes.

The endothelium plays an important role in the regulation of vascular tone. Although animal data show evidence for an impaired endothelium-dependent vasodilation in diabetes, human in vivo data are scarce. We investigated 11 type I diabetic patients and 11 matched healthy control subjects. The diabetic patients were selected on their relatively poor metabolic regulation (HbA1c > 8.5%), but none showed signs of microvascular complications. In all subjects, we recorded the forearm vasodilator responses to three different stimuli: 1) 5 min of forearm ischemia to obtain a maximal vasodilator response; 2) infusion of MCh into the brachial artery (dosages: 0.03-0.3-1.0 micrograms.min-1.100 ml-1 forearm volume) to evaluate endothelium-dependent vasodilation; and 3) intra-arterial infusion of SNP (dosages: 0.06-0.2-0.6 micrograms.min-1.100 ml-1) to evaluate endothelium-independent vasodilation. The diabetic patients had their usual subcutaneous insulin dose and breakfast 90 min before the start of the test. Baseline levels of BP and FBF were similar in both groups. The PORH response was similar in both groups, with a percentage fall in FVR of 92 +/- 1% in diabetic patients and 94 +/- 1% in control subjects. In the control subjects, MCh infusions exerted a dose-dependent vasodilator response with a maximal fall in the FVR of 90 +/- 2%. The highest dose of SNP induced a fall in FVR of 81 +/- 6% in this group. In diabetic patients, the percentage decrements in FVR during the several dosages of MCh and SNP were similar when compared with the control group. We conclude that chronic hyperglycemia, as occurred in our patients with uncomplicated diabetes mellitus, does not impair endothelium-dependent vasodilation in vivo.

Adult↗
PubMed1991

Collaborative feasibility study of a biphasic system (Roche Septi-Chek AFB) for rapid detection and isolation of mycobacteria.

A study to delineate the feasibility of a biphasic-culture approach for detection and isolation of mycobacteria from clinical specimens except blood was conducted in four medical centers. The biphasic system (Septi-Chek AFB, Roche Diagnostic Systems, Nutley, N.J.) was compared with conventional mycobacterial isolation media and the BACTEC system. Septi-Chek AFB showed the highest degree of mycobacterial recovery. In addition, Septi-Chek AFB consistently shortened the time required for recovery of mycobacteria from clinical specimens and supported the growth of small inoculum numbers of stock cultures of 14 mycobacterial species. The study indicates the feasibility and potential advantages of the biphasic approach for detection and isolation of mycobacteria.

Bacteriological Techniques↗
PubMed1989

Carboplatin (CBDCA) and radiotherapy for stage IV carcinoma of the head and neck: a phase I-II study.

The prognosis of patients with squamous cell carcinoma (SQC) of the head and neck (H&N) depends on the primary site and anatomical extent of the disease. Recurrence rates after conventional surgery (S) and/or radiotherapy (RT) remain low for localized tumors, whereas in advanced loco-regional disease they occur in over 60% of all cases. Several combinations of treatment modalities have been attempted in order to improve local control in Stages III and IV. Unfortunately, the recurrence rate remains high with added morbidity when conventional surgery is combined with pre or post-operative radiotherapy. Induction chemotherapy (CT) with Cisplatinum and Bleomycin has resulted in severe toxicities when combined with radiotherapy. To evaluate the toxicity of Carboplatin (CBDCA), a second generation platinum analog, when given simultaneously with conventional doses of radiotherapy, 26 patients with Stage IV SQC of the head and neck were treated at the University of Maryland Medical Systems. There were 23 males and 3 females; median age was 59 years and median Karnofski performance status was 60. Twenty patients had received no prior therapy; six had surgical exploration and excision with measurable residual disease. Anatomically, six patients had tumors of the oral cavity, twelve in the pharynx, one in the nasopharynx, four in the larynx, one in the hypopharynx, one in the maxillary antrum, and one was an unknown primary. These patients were treated as out-patients with weekly injections of Carboplatin. The dose was escalated: two patients received 60 mg/M2, seven received 75 mg/M2, thirteen were treated with 100 mg/M2, and four with 400 mg/M2. The radiotherapy was given daily with conventional fractions of 180 cGy and total tumor doses of 60-75 Gy. Toxicities were mainly hematological with median nadirs decreasing with increasing doses of Carboplatin. Mucositis was seen in over 80% of the patients, but interestingly enough, it has never been more severe than that observed with radiotherapy alone. So far, there has not been any kidney, ear, or neurotoxicities. Of 25 evaluable patients, 19 (76%) responded with 13 (52%) showing complete response. The overall median survival time is 266+ days (324+ for responders and 179+ for non-responders). The follow-up is still short, 10-14 months, but 9 of 13 patients with complete response have not yet progressed.

Antineoplastic Agents↗