Ergot and non-ergot dopamine agonists and heart failure in patients with Parkinson's disease.

PURPOSE: Some studies have suggested a potential risk of heart failure in patients with Parkinson's disease receiving dopamine (DA) agonists. However, the results are conflicting. We used VigiBase®, the World Health Organization (WHO) Global Individual Case Safety Reports (ICSRs) database, to investigate a potential signal strengthening of heart failure with DA agonists in Parkinsonian patients older than 45 years. METHODS: A case/non-case (disproportionality) analysis was performed in Vigibase® using ICSRs registered between 1978 and May 2016. The signal of disproportionality was calculated using reporting odds ratios (ROR). In our study, 154 ICSRs of heart failure occurring in 154 Parkinsonian patients (mean age 69.6 years, 51 % women) treated with DA agonists were included. RESULTS AND CONCLUSION: There was a significant signal between occurrence of heart failure and exposure to pergolide or cabergoline in particular and ergot derivatives in general. In contrast, none signal was found for rotigotine, pramipexole, apomorphine, or ropinirole in particular and non-ergot derivatives in general. The present study underlines the importance to prescribe as DA agonists in Parkinsonian patients only non-ergot derivatives, excluding ergot drugs.

[Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy]. / Ergotismo por uso simultáneo de ergotamínico y terapia antirretroviral: Report of one case.

High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results.

[Severe or life-threatening interactions between antiretrovirals and non-HIV drugs]. / Interacciones graves o potencialmente letales entre antirretrovirales y otros medicamentos.

Highly active antiretroviral therapy has helped to improved control of the HIV infection, and has led to a progressively older population with the infection having a life expectancy quite similar to that of the general population. On the other hand, it is also known that HIV infection, even in patients with undetectable viral loads and good immunity, carries an increased cardiovascular risk, as well as an increased incidence of certain cancers. Therefore, the majority of HIV-infected patients receive several drugs (either prescribed by the physician or self-administered) combined with antiretrovirals. This article reviews the interactions between antiretrovirals and other drugs that can cause significant damage to patients, or even be life-threatening and of whom clinicians, especially those not directly treating HIV-infected patients, should be aware. A review is also presented on the implications of interactions between antiretrovirals and other drugs in special situations, such as the co-administration with cytostatics, immunesuppressants used in solid organ transplantation, or patients receiving new treatments for hepatitisC. Generally, combinations with two nucleos(t)ide reverse transcriptase inhibitors and raltegravir (or in the near future, dolutegravir) are those with less potential for clinically significant interactions.

[Current pharmacotherapy in migraine]. / A migrén korszeru farmakoterápiája.

The exact pathomechanism of migraine is still unknown, currently there are no biomarkers for migraine diagnosis, and current animal models reflect only one aspect of migraine, therefore future migraine studies are necessary. The current treatment of migraine (both acute and preventive) is suboptimal. There are no specific preventive drugs for migraine, and current preventatives may become inefficient during long-term use. Triptans are useful abortive drugs, but not effective in some of the patients; severe cardio-or cerebrovascular side effects may occur. Triptans and ergot alkaloids (and also non-specific abortive agents) can cause medication overuse headache. A number of newly synthesized experimental drugs seem to be effective and promising for migraine therapy, but at present our experience with these is limited, therefore further studies are essential.

Drug-induced retroperitoneal fibrosis: short aetiopathogenetic note, from the past times of ergot-derivatives large use to currently applied bio-pharmacology.

Among the secondary forms of retroperitoneal fibrosis (RPF), that drug-induced shows very intriguing aspects given both the broad range of involved pharmaceuticals and the considerable interest arisen from the related pathogenetic mechanisms. The particular incidence, in the last four decades past century, of the RPF due to long-term use of ergot alkaloid derivatives (ergotamine, methysergide, pergolide, bromocriptine, cabergoline) and specific L-dopa derived agents, such as methyldopa, as well as to different analgesics, came progressively down given that their long-term use for either the prevention of migraine attacks or the therapy of chronic pathologies (Parkinson's disease, prolactinoma, pain management, etc) has been, year after year, supplanted or even made unavailable in many countries. More recently, instead, the occurrence of the RPF has been sometimes identified with the use of antitumoral chemotherapeutics, such as carboplatin and methotrexate, and, just lately, as an unusual side-effect of certain biological agents, about which it is timely to go into specific pathogenetic problems in more depth.

Drug-related cardiac valve disease.

Cardiac valve disease can involve one or more of the four heart valves. Chronic valve damage may remain asymptomatic for long periods but ultimately leads to haemodynamic overload of the heart. The most common causes of valve disease are rheumatic diseases, infections, chronic renal failure, malformations, and genetic diseases. Valve disease is often attributed to degeneration with no known cause.The frequency of drug-related valve disease has long been underestimated. Most implicated drugs have serotonergic properties, such as fenfluramine-derived amphetamines, including benfluorex. Rye ergot derivatives can also be implicated: these include dopamine agonists (bromocriptine, lisuride, pergolide and cabergoline), migraine treatments (methysergide, ergotamine and dihydroergotamine), and drugs used for cognitive and neurosensory deficits (nicergoline, dihydroergocryptine, etc.). "Ecstasy", an amphetamine, is sometimes also involved. The risk increases after a few months of exposure. Drug withdrawal is sometimes followed by an improvement. Patients exposed to a drug known to cause valve damage should be informed of the risk and receive long-term monitoring to detect these lesions before they become irreversible. The possible role of a drug should always be considered when cardiac valve disease is diagnosed, in order to facilitate active research and to avoid exposing other patients to this risk.

[Migraine - diagnostic features, acute therapy and prophylactics]. / Migräne - Klinik, Diagnostik, Therapie und Prophylaxe.

Migraine is a chronic. disabling, biologically determined, inherited brain disorder rendering life much less tolerable. The International Headache Society (IHS) offers guidelines for the classification and diagnosis of migraine headaches, in a document called 'The International Classification of Headache Disorders, 2nd edition' (ICHD-2). Migraine affects 10-16% of the population world-wide. For the 20-30% of migraine sufferers who experience migraine with aura, this aura comprises focal neurological phenomena that precede or accompany the attack. There are three main aspects of treatment: trigger avoidance, acute symptomatic control, and pharmacological prevention. Acute medications are more effective if used earlier in an attack. The goals of preventive therapy are to reduce the frequency, painfulness, and/or duration of migraines, and to increase quality of life.

Feeding yearling Angus bulls low-level ergot daily for 9 weeks decreased serum prolactin concentrations and had subtle effects on sperm end points.

Our objective was to determine whether feeding yearling bulls with the higher recommended Canadian limit of ergot alkaloids (∼3 mg/kg dry matter intake, DMI) would affect sperm characteristics and plasma prolactin concentrations. Aberdeen Angus bulls (12-13 mo old, n = 7/group) allocated by blocking for sperm concentration and body weight, were fed placebo or ergot alkaloids in gelatin capsules (60 µg/kg body weight daily, 3.4 mg/kg of DMI) for 9 wk. Semen samples were collected weekly by electroejaculation and examined with a computer assisted semen analyzer (CASA) and flow cytometry, for the intervals 5 wk before (Pre-exposure period), 9 wk during (Exposure period) and 9 wk after (Post-exposure period) treatment. Weekly plasma samples were analyzed for prolactin by radioimmunoassay. Plasma prolactin concentrations decreased markedly (mean ± SEM, 16.74 ± 3.70 in Exposure and 33.42 ± 3.08 ng/mL in Post-Exposure periods; P < 0.01) compared to Control (67.54 ± 21.47 and 42.59 ± 15.06 ng/mL). Treatment did not affect (P ≥ 0.17) body weight gain, sperm concentration, sperm count/ejaculate, motility or percent live sperm. Averaged over the exposure and post-exposure durations, the scrotal circumference was smaller (P = 0.02) by 2.7% in the Ergot group. Progressive motility remained unchanged from 59.92 ± 2.31% in Exposure to 59.61 ± 2.59% in Post-Exposure periods, compared to marked increase in Control (61.42 ± 1.60% to 67.52 ± 1.47%; P = 0.02). Straight-line sperm velocity decreased (-3.15 ± 1.53 µm/s) from exposure to post-exposure periods in Ergot group (P = 0.04) versus an increase (2.96 ± 2.17 µm/s) in Control. Midpiece defects decreased from Exposure to Post-exposure periods in Control group but remained unchanged in Ergot group (trt∗age, P < 0.01). Ergot feeding resulted in a smaller proportion of sperm with medium mitochondrial potential (Ergot: 22.65 ± 0.98%, Control: 24.35 ± 1.05%, P = 0.04). In conclusion, feeding ergot at Canadian permissible limit for 9-wk resulted in a 4-fold decrease in plasma prolactin concentrations. Semen end points were not significantly affected, although there were subtle effects on progressive motility, midpiece defects and mitochondrial membrane potential. Clinical relevance of observed changes requires further evaluation. Results supported our hypothesis that prolonged low-level ergot will adversely affect plasma prolactin. However, semen parameters were partially affected, supporting similar work on fescue toxicosis.

Revisiting the role of ergots in the treatment of migraine and headache.

The harmful side effects of the ergots described by early civilizations have been overcome with efficacious treatment for headaches including migraine, cluster, and chronic daily headache. Use of ergots contributed to initial theories of migraine pathogenesis and provided the substrate for development of the triptans. Triptans are very efficacious for many migraineurs, and since their widespread use, use of ergots has significantly declined. Unfortunately, there remain many migraineurs who benefit little from triptans, yet respond very well to ergots. Discoveries in migraine pathophysiology have given us better understanding of the complex processes involved, although there remain many unknown factors in migraine treatment. Additional, unrecognized therapeutic targets may exist throughout the neuronal connections of the brainstem, cortex, and cerebral vasculature. Ergots interact with a broader spectrum of receptors than triptans. This lack of receptor specificity explains potential ergot side effects, but may also account for efficacy. The role of ergots in headache should be revisited, especially in view of newer ergot formulations with improved tolerability and side effect profiles, such as orally inhaled dihydroergotamine. Redefining where in the headache treatment spectrum ergots belong and deciding when they may be the optimal choice of treatment is necessary.

Postpartum hemorrhage: evidence-based medical interventions for prevention and treatment.

Postpartum hemorrhage (PPH) remains a significant contributor to maternal morbidity and mortality throughout the world. The majority of research on this topic has focused on efforts to prevent PPH. Sound data exist that active management of the third stage of labor can reduce the occurrence of PPH. Although there remains debate regarding the optimal protocol for active management, it appears at this time that oxytocin is the preferable uterotonic to use. Misoprostol may be a reasonable option where parenteral administration of an uterotonic is not feasible. There is little evidence to guide treatment decisions should PPH occur.

Drug-induced retroperitoneal fibrosis: a case/non-case study in the French PharmacoVigilance Database.

OBJECTIVES: The potential role of drugs in the onset of retroperitoneal fibrosis (RPF) is poorly understood. The aim of this study was to identify drugs that may cause RPF. METHODS: The authors used case/non-case method in the French PharmacoVigilance Database (FPVD). RESULTS: Among the 722992 reports recorded, 73 cases of RPF were identified. 67% were men and the median age was 60 years (range 26-87). In these 73 cases, 176 drugs were 'suspect.' Derivatives of ergot alkaloids (DEA) presented the most significant association with RPF. To a lesser extent, significant associations were found with many drugs used in cardiology, e.g. beta-blockers, platelet antiaggregant, statins, and antihypertensive drugs, drugs used in neuropsychiatry, e.g. hypnotics, antiepileptic drugs, anxiolytics, antipsychotics, and antidepressants, and with other pharmacological classes, e.g. TNF-alpha antagonists. CONCLUSION: This study confirmed an association between RPF and derivatives of ergot alkaloids. These data represent a pharmacovigilance signal despite the limits of non/non-case method (underreporting, confounding factors, etc.). Indeed, a significant signal was found with drugs less known (TNF-α antagonists) or not known (some hypnotics, antiepileptic drugs, antipsychotics, anxiolytics, and antidepressants) to induce such an adverse drug reaction (ADR). Finally, these data could contribute to realize prospective studies to confirm these signals.

Heart abnormalities in Parkinson patients after discontinuation or continuation of ergot-derived dopamine agonists: a treatment-blinded echocardiographic study.

BACKGROUND AND AIM OF THE STUDY: Ergot-derived dopamine agonists (DAs) are used in the treatment of Parkinson's disease, but may be associated with valvular heart disease and pulmonary hypertension. The study aim was to examine changes in cardiovascular abnormalities after the discontinuation or continuation of anti-parkinson treatment. METHODS: Parkinson patients treated with either ergot-derived (n = 32) or non-ergot-derived (n = 8) DAs who had been diagnosed with valvular abnormalities or pulmonary hypertension, were included in this one-year follow up study. After an initial echocardiography, five patients continued ergot-derived DA treatment, while the remaining 35 either changed (n = 27) or continued (n = 8) non-ergot-derived DA treatment. The patients were followed up after a mean of 14 months (range: 12-18 months). Changes in the severity of valve disease and pulmonary hypertension were evaluated by an analysis of digitally stored echocardiograms. The recordings were performed blinded to medical treatment, while the analyses were blinded to both the medical treatment and the timing of image acquisition. RESULTS: Follow up revealed the risk of worsening cardiovascular abnormalities to be 60% in patients who continued ergot-derived DA treatment, compared to 14% in those who changed to, or continued with, non-ergot-derived DA medication (p < 0.05). Overall, patients who changed from ergot-derived to non-ergot-derived DAs did not exhibit any significant worsening or improvement of their valve abnormality, although the pulmonary artery pressure (PAP) fell from 26 +/- 12 mmHg to 22 +/- 8 mmHg at follow up (p < 0.005). CONCLUSION: At one year after discontinuation of ergot-derived DAs, a mild but statistically significant reduction in PAP was detected. Overall, valvular regurgitation remained without definite worsening or improvement in these patients. Among patients who continued ergot-derived DAs despite a cardiovascular abnormality, the follow-up indicated an increased risk of worsening.

Impact of slick hair trait on physiological and reproductive performance in beef heifers consuming ergot alkaloids from endophyte-infected tall fescue1.

Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue. The objective of this study was to evaluate the impact of the slick hair trait on physiological and reproductive parameters in heifers experiencing fescue toxicosis. Angus × Senepol heifers (n = 31) were blocked by weight (393.5 ± 17.3 kg) and phenotype relative to hair coat at birth, and randomly fed novel endophyte fescue (EN) or endophyte-infected fescue (EI) haylage in a total mixed ration for 91 d. Weekly measurements were collected to monitor heifer growth and response during ergot alkaloids exposure. Following 28 d of treatment, estrus was synchronized and heifers were inseminated. Ovary mapping and AI pregnancy rate were examined via transrectal ultrasonography. Blood samples were taken for genotyping: slick (S) or wildtype (W). Data were analyzed using repeated measures in PROC MIXED of SAS including fescue treatment (EN vs. EI), genotype (S vs. W), and sample collection time as main effects. Body condition scores were decreased for W heifers compared with S heifers (5.48 vs. 5.66, respectively; P < 0.0001). Surface temperature was greater for EI-W heifers (37.2 °C) compared with other groups (36.4, 36.6, 36.7 °C for EN-S, EN-W, EI-S, respectively; P < 0.05). Serum PRL concentrations were reduced for EI heifers compared with EN heifers (133.5 vs. 163.1 ng/mL, respectively; P < 0.05). The average number of 2 to 4 mm follicles were greater in EI-W heifers (13.8 follicles) compared with other groups (12.2, 10.6, and 11.1 for EN-S, EN-W, and EI-S, respectively; P < 0.0001). However, the average number of preovulatory follicles (≥9 mm) were reduced in EI-W heifers (0.52 follicles) compared with other heifer groups (0.94, 0.88, and 0.85 ± 0.04 for EN-S, EN-W, and EI-S, respectively; P < 0.05). Ovulatory follicle size was smaller in EI-W heifers compared with EN-W heifers (9.14 vs. 11.57 mm, respectively; P = 0.05). Corpus luteum area was reduced in EI-W heifers (235.1 mm2) compared with other heifer groups (297.2, 272.7, and 276.8 mm2 for EN-S, EN-W, and EI-S, respectively; P < 0.05). Concentrations of P4 were greater for EN heifers compared with EI heifers (2.7 vs. 1.8 ng/mL, respectively; P < 0.05). Pregnancy was not established in EI-W heifers (0%) compared with other heifer groups (37.5%, 57.1%, and 62.5% for EN-S, EN-W, and EI-S, respectively; P < 0.05). Overall, the slick hair mutation appears to aid in offsetting the physiological symptoms associated with fescue toxicosis and helps to improve reproductive performance.

Effects of endophyte-infected tall fescue seed and protein supplementation on stocker steers: I. Growth performance and hemodynamic responses.

Fescue toxicosis is a multifaceted syndrome common in cattle grazing endophyte-infected tall fescue and is detrimental to growth and performance. Recent research has shown that supplementing protein has the potential to enhance growth performance in weaned steers. Therefore, the objective of this study was to evaluate the effect of supplemental CP on physiological parameters in stocker steers experiencing fescue toxicosis. Thirty-six weaned Angus steers (6 mo of age) stratified by weight (196.1 ± 3.6 kg) were assigned to a 2 × 2 factorial arrangement for 56 d: endophyte-free (EF) seed and 14% CP (EF-14; n = 9), EF seed and 18% CP (EF-18; n = 9), endophyte-infected (EI) seed and 14% CP (EI-14; n = 9), and EI seed and 18% CP (EI-18; n = 9). Steer growth and hemodynamic responses were collected weekly during ergot alkaloid exposure. On day 14 of the trial, iButton temperature data loggers were subcutaneously inserted in the lateral neck region to record hourly body temperature for 42 d. Data were analyzed using PROC MIXED of SAS with repeated measures. No differences were observed in DMI, BW, ADG, F:G, or BCS during the treatment period (P > 0.05). Hair shedding scores, rectal temperatures, surface temperatures, and respiration rates were greater in EI steers compared to EF steers regardless of supplemental CP (P < 0.05). However, subcutaneous body temperature was greater in EI-14 steers (37.94 °C) compared to other steer groups (37.60, 37.68, 37.72 ± 0.04 °C for EF-14, EF-18, and EI-18, respectively; P < 0.05). Prolactin concentrations tended to be greater in EF steers when compared to EI steers (P = 0.07). Heart rate and hematocrit were reduced for EI-18 steers compared to other steer groups (P < 0.05). Caudal artery diameter was reduced in EI-18 steers compared to EI-14 steers (2.60 vs. 2.75 ± 0.05 mm, respectively; P < 0.05) and caudal vein diameter was reduced in EI-18 steers (3.20 mm) compared to all other steer groups (3.36, 3.39, 3.50 mm for EF-14, EF-18, and EI-14, respectively; P < 0.05). However, there was no difference observed in systolic or diastolic blood pressure during the treatment period (P > 0.05). Based on the data, exposure to low to moderate levels of ergot alkaloids during the stocker phase had a negative impact on hemodynamic responses and supplemental CP had minimal impact to alleviate symptoms. Therefore, feeding additional protein above established requirements is not expected to help alleviate fescue toxicosis.

Heart valve disease associated with treatment with ergot-derived dopamine agonists: a clinical and echocardiographic study of patients with Parkinson's disease.

OBJECTIVE: To elucidate the association between treatment with ergot-derived dopamine agonists (EDDA) and valvular abnormalities amongst patients with idiopathic Parkinson's disease (IPD) and secondly, to analyse the yield of clinical screening for valvular heart disease. DESIGN: A cross-sectional controlled study. SETTING: The cohort of IPD patients treated in the outpatient clinic, Department of Neurology, Aarhus University Hospital, Denmark. SUBJECTS: A total of 138 IPD patients [median age 64 (39-87) years, 62% men] treated with either EDDA (n = 85) or non-EDDA (n = 53) for at least 6 months. Interventions. Patients were screened for valvular heart disease by clinical means and by examiner-blinded echocardiography. Main outcome measure was valvular regurgitation revealed by echocardiography. RESULTS: Severe aortic regurgitation (n = 4) or moderate aortic (n = 12), mitral (n = 3) or tricuspidal valve regurgitation (n = 5) was found in 22 EDDA patients (25.9%). Two patients had coexistent moderate mitral and tricuspid valvular regurgitation. Two non-EDDA patients had moderate valve insufficiency (3.8%, P < 0.05). The adjusted relative risk for at least moderate valve insufficiency in the EDDA patients was 7.2% (P < 0.05). The sensitivity of detecting at least moderate valvular disease by cardiac murmur, dyspnoea, or the heart failure marker NT-proBNP (natriuretic peptide) was 62% for the neurologists and 93% for the cardiologist but with equally low specificity (30-35%). CONCLUSION: EDDA was associated with a clinically important and statistically significant risk of at least moderate valve regurgitation. Clinical screening for valve disease was inadequate and it seems advisable to offer EDDA patients control with echocardiography.

A possible perianesthetic serotonin syndrome related to intrathecal fentanyl.

Serotonin syndrome occurs with selective serotonin reuptake inhibitors, opioids, and other serotonergic agents. We describe a possible serotonin syndrome related to intrathecal fentanyl in a patient taking multiple drugs and substances such as ergot alkaloids, marijuana, methylenedioxy-N-methylamphetamine, and ephedrine.

Assessment of semen quality and fertility in young growing beef bulls exposed to ergot alkaloids.

The objective of this study was to evaluate semen quality and fertility in beef bulls grazing the ergot alkaloid (EA) producing tall fescue cultivar, Kentucky 31 (KY31), compared to a novel endophyte (NE) cultivar lacking EA. Two studies were conducted over a 3-year period. In studies 1 (n = 10; ages ≥ 24 mo) and 2 (n = 53 over two years; ages 12-16 mo), Angus (AN) bulls were stratified by body weight (BW), body condition score (BCS), and scrotal circumference (SC), and then allotted to graze either KY31 or NE for 56 days. Semen samples were collected, and BW, BCS, and SC were evaluated at the start of treatment (TRT) on day (d) 0 and every 28 days to the end of each study. In addition, blood samples were collected on d 0 and every 28 days for assessment of circulating prolactin (PRL) levels in study 2. On d 56, for both studies, semen from bulls (n = 2 per treatment in study 1 and n = 4 per treatment in study 2) with similar and acceptable quality were extended, kept at 19° C, and used for timed artificial insemination (TAI) of primi- and multiparous AN and AN- crossbred females. Pregnancy was evaluated at 35 and 90 days post-TAI via transrectal ultrasonography to determine pregnancy rates. Serum PRL concentrations showed a TRT by d effect (P ≤ 0.05), with values for bulls grazing KY31 decreased on d 28 and d 56 of grazing compared to NE. In studies 1 and 2, bull BW and BCS were affected by d (P ≤ 0.05), but not by TRT. No TRT or TRT by d effect on semen quality was observed in either study; however, d impacted both velocity and concentration in study 2 (P ≤ 0.05). In study 1, TAI pregnancy rates at 35 days post-TAI were lower (P ≤ 0.05) in the group inseminated with semen from bulls grazing KY31; however, in study 2, pregnancy rates did not differ due to treatment 35 post-TAI (P > 0.05). Grazing KY31 negatively impacted serum PRL concentrations, supporting previous observations; however, consumption of KY31 had no effect on growth or semen quality of AN bulls ranging from 12 to ≥24 mo of age. Furthermore, fertility data is inconsistent between studies and requires further investigation.

High blood pressure. A side effect of drugs, poisons, and food.

Arterial hypertension, either transient or persistent, may be induced or aggravated by ingestion of various chemical agents, such as drugs, poisons, and food. Most of these agents either cause sodium retention and expand extracellular fluid volume or act as direct or indirect sympathomimetics. Others act directly on arteriolar smooth muscle. For a few agents, no precise mechanism has been ascertained. Hypertensive reactions may also occur as a result of drug interactions or food and drug interactions. In addition, paradoxical increases in pressure may be encountered during or after discontinuance of antihypertensive therapy. In general, these pressure increases are small and transient; however, a few have been associated with severe hypertension involving encephalopathy, strokes, and irreversible renal failure. Careful review of a patient's drug regimen, including over-the-counter preparations, may avoid chemically induced hypertension. Identification of any offending or incriminating agent will prevent the labeling of a chronic illness and obviate the need for lifelong antihypertensive therapy.