Boerhaave's syndrome: a pain in the neck.

Boerhaave's syndrome, or post-emetic rupture of the oesophagus, classically presents with vomiting, chest pain and subcutaneous emphysema. Mortality in this condition is very high and increases dramatically with delayed diagnosis and intervention. The vast majority of patients have a tear in the left posterior-lateral wall of the lower third of the oesophagus and require urgent surgical intervention. Spontaneous rupture of the cervical oesophagus is very rare and may present differently to oesophageal perforations elsewhere. A case is presented following vomiting in a 70-year-old woman, which was diagnosed by computed tomography scan and treated conservatively. The attending physician must be alert to the diagnosis of post-emetic cervical oesophageal perforation as prompt diagnosis and treatment is essential to reduce morbidity and mortality.

Participation of renal and circulating endothelin in salt-sensitive essential hypertension.

Salt sensitivity of blood pressure is a cardiovascular risk factor, independent of and in addition to hypertension. In essential hypertension, a conglomerate of clinical and biochemical characteristics defines a salt-sensitive phenotype. Despite extensive research on multiple natriuretic and antinatriuretic systems, there is no definitive answer yet about the major causes of salt-sensitivity, probably reflecting the complexity of salt-balance regulation. The endothelins, ubiquitous peptides first described as potent vasoconstrictors, also have vasodilator, natriuretic and antinatriuretic actions, depending on their site of generation and binding to different receptors. We review the available data on endothelin in salt-sensitive essential hypertension and conclude that abnormalities of renal endothelin may play a primary role. More importantly, the salt-sensitive patient may have blood pressure-dependency on endothelin in all states of salt balance, thus predicting that endothelin receptor blockers will have a major therapeutic role in salt-sensitive essential hypertension.

Regulation of plasma endothelin by salt in salt-sensitive hypertension.

BACKGROUND: Salt dependency of blood pressure (BP) characterizes most models of experimental hypertension in which endothelins play a significant vasoconstrictor role. Despite this, there are no data on the regulation of plasma endothelin by salt balance in human hypertension. METHODS AND RESULTS: Plasma endothelin was measured in 47 patients with essential hypertension. Endothelin, catecholamine, and plasma renin activity (PRA) responses to 24-hour sodium deprivation (decreasing Na) were assessed in 29 of these patients. Endothelin was higher in hypertensive patients (4.6+/-0.2 fmol/mL) than in 20 control subjects (3.3+/-0.3 fmol/mL, P:<0.002), was correlated with BP, and was negatively associated with PRA (P:<0.04). Salt-sensitive, salt-resistant, and indeterminate groups were defined by the tertiles of the t statistic for the difference in BP before and after decreasing Na. Systolic BP falls were -15+/-1, -2+/-2, and -9+/-1 mm Hg, respectively. PRA, its response to decreasing Na, and its level after decreasing Na were lowest (albeit nonsignificant) in salt-sensitive patients. Baseline catecholamine and endothelin levels did not differ among the groups. In response to decreasing Na, catecholamines increased more significantly in salt-sensitive patients (+2.4+/-0.9 nmol/L) than in the other groups (0.4+/-0.2 and 0.7+/-0.2 nmol/L for indeterminate and salt-resistant groups, respectively; P:<0.03), whereas endothelin increased in the salt-sensitive group (0.8+/-0.3 fmol/mL), decreased in the salt-resistant group (-0.4+/-0.3 fmol/mL), and sustained minimal change in the indeterminate group (0.2+/-0.3 fmol/mL) (P:<0.04). Thus, endothelin levels in the salt-depleted state were highest in salt-sensitive patients (5.2+/-0.4 fmol/mL) versus the other groups (3.4+/-0.4 and 4.4+/-0.4 fmol/mL for salt-resistant and indeterminate groups, respectively) (P:<0.02). Changes in endothelin during decreasing Na and levels after decreasing Na were correlated with changes in catecholamines (P:<0.02). CONCLUSIONS: -Our data suggest that salt-depleted salt-sensitive hypertensives with blunted renin responses exhibit enhanced catecholamine-stimulated endothelin levels and may therefore respond better than unselected patients with essential hypertension to endothelin receptor blockers.

Three Angiotensin paradigms in one patient : etiology of hypertension, glomerular hemodynamics, and long-term glomerular protection.

This chapter on new methods of molecular biology applied to the investigation of the renin-angiotensin system (RAS) contains a description of a clinical case in its first section. There are two reasons for this. First, the case will illustrate the importance of increased understanding of the RAS, because of research by basic scientists, for clinical scientists, clinicians, and human health. Second, and more importantly, describing the applicability of scientific advances in the understanding of RAS to a particular patient is a fitting tribute to two remarkable clinician scientists, Irvin Page and Eduardo Braun Menendez, the co-discoverers of angiotensin II (Ang II) in the United States and Argentina, respectively (1,3). Their insurmountable curiosity was driven by a desire to help patients, at a time at which human hypertension was an untreatable and devastating problem.

Evidence for linkage between essential hypertension and a putative locus on human chromosome 17.

Several clinical and animal studies indicate that essential hypertension is inherited as a multifactorial trait with a significant genetic and environmental component. In the stroke-prone spontaneously hypertensive rat model, investigators have found evidence for linkage to blood pressure regulatory genes (quantitative trait loci) on rat chromosomes 2, 10, and X. In 1 human study of French and UK sib pairs, evidence for linkage has been reported to human chromosome 17q, the syntenic region of the rat chromosome 10 quantitative trait loci (QTL). Our study confirms this linkage (P=0.0005) and refines the location of the blood pressure QTL.

The effects of atenolol and zofenopril on plasma atrial natriuretic peptide are due to their interactions with target organ damage of essential hypertensive patients.

The effects of 10 weeks of treatment with atenolol (n = 9) or the converting enzyme inhibitor zofenopril (n = 25) on plasma atrial natriuretic peptide (ANP) were studied in 34 essential hypertensive patients. After 4 weeks on placebo, pretreatment ANP, 56 +/- 7 pg/ml, was slightly but not significantly higher than that of 29 controls (41 +/- 4) and correlated with age (r = 0.44), ECG score for left ventricular hypertrophy (LVH) (r = 0.51) and serum creatinine (r = 0.67), and negatively with creatinine clearance (r = -0.39). Atenolol reduced blood pressure (BP) by 0 +/- 6/8 +/- 2 mm Hg (ns/P < 0.01), and zofenopril by 14 +/- 4/6 +/- 2 (P < 0.01/P < 0.01), not significantly different between the two agents. Heart rate was decreased by atenolol (-16 +/- 4 bpm, P < 0.01) but not by zofenopril (+1 +/- 2 bpm, ns). Atenolol increased ANP in all patients but one (delta = +42 +/- 9 pg/ml, P < 0.01), while zofenopril did not change it significantly (-6 +/- 6 pg/ml), due to 15 patients exhibiting decreases and 10 increases in plasma ANP. The effect of atenolol on ANP positively correlated with duration of hypertension (r = 0.74), ECG score for LVH (r = 0.73) and serum creatinine (r = 0.68). Individual changes in ANP by zofenopril negatively correlated with pretreatment ANP (r = -0.69), ECG score for LVH (r = -0.44) and serum creatinine (r = -0.41). No correlations were found between BP, heart rate or their changes by treatment and the effect of either agent on plasma ANP. Multiple linear regression showed that the change in ANP was explained by the therapeutic agent used, the pretreatment plasma level of ANP, and the ECG score for LVH (F = 12.5, P < 0.001, r2 = 0.56). We conclude that the effect of antihypertensives on plasma ANP is independent of their action on BP, but dependent on an interaction between the type of drug employed and those clinical characteristics of the patient that reflect pre-existing hypertensive target organ damage.

Regulation of growth of the adrenal gland in DOC-salt hypertension. Role of angiotensin II receptor subtypes.

To investigate the role of the renin-angiotensin system in the regulation of adrenal growth in deoxycorticosterone (DOC)-salt hypertensive rats, and the adrenal gene expression of angiotensin AT1 and AT2 receptors, three groups of uninephrectomized rats + DOC pellet + 0.9% NaCl were given water (DOC), losartan (DOC-L), or ramipril (DOC-R) by gavage. Controls had sham surgery and water gavage. Tail-cuff systolic and mean intra-arterial blood pressures were significantly higher in the three DOC groups than in controls and not different among the groups. Adrenal weight of DOC was slightly but not significantly greater than that of controls, while those of DOC-L and DOC-R were greater than that of controls (P < .01). Northern blots showed that AT1 and AT2 gene expression was significantly reduced in DOC (by 33% and 60%), while that of AT1 (but not AT2) was significantly reduced further (versus control and DOC) in DOC-L and DOC-R. There were negative correlations between adrenal weight and AT1 (r = -.80, P < .0001) or AT2 (r = -.60, P < .005). We conclude that DOC-salt hypertension downregulates adrenal AT1 and AT2 gene expression by different mechanisms. Removal of the effects of angiotensin by losartan or ramipril downregulates AT1 further and promotes adrenal growth, indicating the presence of an AT1-mediated growth-inhibitory action of angiotensin II on the adrenal gland. These observations constitute an additional example of a growth-inhibitory role for the AT1 receptor, opposite to its more common growth-promoting actions in other organs and tissues.

Suboptimal outcome of management of metabolic cardiovascular risk factors in Hispanic patients with essential hypertension.

We studied outcome of management of metabolic cardiovascular risk factors in 155 randomly chosen Hispanic hypertensive patients (mean age, 63 +/- 1 years; 79% female) screened for dyslipidemia. Hypertriglyceridemia (n = 12) or high risk-adjusted low-density lipoprotein cholesterol (LDL-C) (n = 89) was found in 65%. Triglycerides did not change (6.16 +/- 0.58 to 7.44 +/- 2.34 mmol/L; P = NS) over 2.2 +/- 0.5 years. Only 58 patients with high LDL-C were treated, and 8 had no follow-up lipid tests. In the other 50, LDL-C decreased by 10 +/- 3% (P < .001) over 2.8 +/- 0.2 years but attained goal in only 12. In a subset of 24 patients with extended follow-up (3.8 +/- 0.2 years), there was an initial marked decline in LDL-C, followed by a rebound to baseline levels. In 29 of 54 patients with normal LDL-C, lipid testing was markedly overused compared with recommendations. Obesity (n = 94, 61%) did not improve in those with repeated data (+0.6 +/- 0.8 kg; P = NS; n = 40) over 2.7 +/- 0.3 years. Forty-four of 63 patients with type II diabetes had repeated measurement of glycosylated hemoglobin, with no change (10.5 +/- 0.5% to 11.2 +/- 0.5%; P = NS) over 2.2 +/- 0.3 years. Ten-year risk of coronary events (Framingham cohort parametric regression) calculated for 61 patients with known untreated blood pressures (169 +/- 3/98 +/- 1 mm Hg) was 21.0 +/- 1.7%, with a skewed distribution reaching high values (66%) and attributable in large part (72%) to modifiable risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Cough induced by angiotensin-converting-enzyme inhibitors: Airway responses to inhalation of methacholine in patients who have essential hypertension.

We investigated whether patients with cough due to angiotensin-converting-enzyme inhibitors have a common pattern of airway responses to methacholine inhalation. Studies assessing only presence or absence of hyperresponsiveness to this agent have produced conflicting results. Spirometric testing before and after methacholine was performed in 14 hypertensive patients at least two weeks after discontinuation of these inhibitors, when cough had abated or disappeared. Subjects were predominantly female (86%) nonsmokers (93%), with high prevalence of respiratory atopic illnesses (57%) probably due to ethnic background (72% Hispanic). Premethacholine spirometric values were normal. Postmethacholine bronchoconstriction of varying degrees was observed in seven patients, but reached the level of hyperresponsiveness in only one patient with asthma. The other seven subjects exhibited no bronchoconstriction. The two groups did not differ in age, concomitant illnesses (e.g., atopy) and medications, or blood pressure reduction. We conclude that airway responses to cholinergic stimulation do not exhibit a common pattern and are randomly distributed in hypertensive patients who develop cough induced by angiotensin-converting-enzyme inhibitors.

Predictors of the pressor response to the clinic visit in essential hypertensives with and without diabetes mellitus.

Predictive models for the pressor response to the outpatient clinic visit (PRC) in essential hypertensives with and without diabetes are proposed. The hypotheses are derived from previous studies about the univariate correlates of this response. PRC was measured with ambulatory monitors. Twenty-four hour blood pressures and average PRCs were similar in the two groups. Diabetics had faster 24-h heart rates, decreased heart rate variability, a broader range of PRCs and more depressor responders. PRC of nondiabetics correlated with duration of hypertension and was dependent on race; the predictive model had R2 of 0.19. In contrast, PRC of diabetics exhibited correlations with age, weight, BP and blood glucose and the model had R2 of 0.71. The data suggest that: diabetics had autonomic dysfunction, that their PRC can be modelled with predictors that are accepted correlates of autonomic neuropathy, and that these predictors attenuated PRC or its buffering. If these results were confirmed by prospective application of the model to a larger group of patients, 'true' blood pressures could be estimated by subtraction of predicted PRC from office blood pressures in diabetic, but not in nondiabetic, hypertensive patients.

Bayesian analysis supports use of ambulatory blood pressure monitors for screening.

To assess whether there is a role for ambulatory blood pressure monitoring (ABPM) in screening for hypertension, we conducted Bayesian analysis of office blood pressure (OBP) as a diagnostic "test" in populations with different prior probabilities (PP) of hypertension. OBP was considered a positive test if systolic blood pressure was greater than 140 mm Hg or diastolic pressure was greater than 90 mm Hg. Chosen daytime ABPM cutoffs for a "gold standard" diagnosis of hypertension were systolic pressure of 139 and diastolic pressure of 88 mm Hg. Sensitivity and specificity of OBP were determined in 72 patients with established hypertension (PP = 1). After 3 weeks off therapy, OBP was 168 +/- 3/101 +/- 1 and ABPM was 151 +/- 2/94 +/- 1 mm Hg. Systolic ABPM was in the normotensive range in 17 patients and diastolic in 15 patients. OBP was falsely positive in 14 and 15 of these patients, respectively. Thus, sensitivity and specificity of OBP were 0.8909 and 0.1765 (systolic) and 0.9825 and 0 (diastolic). These data cannot be extrapolated to populations with lower PPs for use of Bayes' theorem. Hence, we calculated sensitivity and specificity for PP = 0 from published series of ABPM in normotensive subjects and used our measurements and these calculations in arithmetic interpolations for populations with PP 0.1-0.9. Sigmoid relations between PP and predictability of hypertension by a positive OBP were disclosed by use of Bayes' theorem. Their best-fit cubic polynomials predict that an elevated OBP will misdiagnose hypertension 46-50% of the time in a general population (PP = 0.2) but only 8-9% in a specialty practice (PP = 0.9).(ABSTRACT TRUNCATED AT 250 WORDS)

Magnitude, reproducibility, and components of the pressor response to the clinic.

We investigated the magnitude of the pressor response to the clinic with ambulatory monitors by comparing blood pressure readings related to the medical visit with all clinic-unrelated readings during the day. One hundred studies were conducted on 51 hypertensive patients who were placed either on placebo (67) or on monotherapy with hydrochlorothiazide, atenolol, or the converting enzyme inhibitors captopril or zofenopril. On placebo, clinic-related systolic (162 +/- 2), diastolic (101 +/- 1), and pulse (61 +/- 2) pressures (mm Hg) were significantly higher than the respective clinic-unrelated values (149 +/- 2, 93 +/- 1, and 56 +/- 1 mm Hg). Heart rates were not different. Despite significant reductions of blood pressure, the same pattern was found during treatment. After initiating the monitoring and while in transit to job or home (initial component of the clinic-related readings), systolic (166 +/- 2 mm Hg) and pulse (64 +/- 2 mm Hg) pressures were higher than those during return to the office the next day (final component, 158 +/- 3 and 58 +/- 2 mm Hg). Blood pressures of both components, however, were significantly higher than the clinic-unrelated ones. In 19 repeat studies carried out 2-24 months apart on placebo, the average pressor response did not change from the first (13 +/- 3/11 +/- 2) to the second (13 +/- 4/11 +/- 2 mm Hg) procedure. No correlation, however, was found between the first and second study responses of individual patients.(ABSTRACT TRUNCATED AT 250 WORDS)