Increase enalapril dose according to tolerance and administer intravenous turosemide.

A 73-year-old woman is admitted with progressive dyspnea until she becomes at rest, orthopnea and weight gain of 4 kg. Physical examination showed blood pressure of 150/84 mm Hg, heart rate 100 beats/minute, increased jugular venous pressure, crepitant in both bases and malleolar edema. Usual treatment: enalapril 5 mg every 12 hours, furosemide 80 mg per day. What is the most appropriate treatment at this time?

Increase enalapril dose according to tolerance and administer intravenous furosemide.

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as bolus in refractory congestive heart failure: long-term effects.

Diuretics have been accepted as first-line treatment in refractory congestive heart failure (CHF), but a lack of response to them is a frequent event. A randomized, single-blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory New York Heart Association (NYHA) class IV CHF and a normosodic diet during follow-up. Materials and Methods One hundred seven patients (39 women and 68 men, age range 65-90 years) with refractory CHF (NYHA class IV) of different etiologies, who were unresponsive to high oral doses of furosemide, angiotensin-converting enzyme inhibitors, digitalis, and nitrates, were enrolled. Inclusion criteria included an ejection fraction (EF) <35%, serum creatinine level <2 mg/dL, blood urea nitrogen level < or =60 mg/dL, reduced urinary volume, and low natriuresis. The patients were randomized in 2 groups (single-blind). Patients in group 1 (20 women and 33 men) received an intravenous (IV) infusion of furosemide (500-1000 mg) plus HSS (150 mL of 1.4%-4.6% NACl) twice a day in 30 minutes. Patients in group 2 (19 women and 35 men) received an IV bolus of furosemide (500-1000 mg) twice a day, without HSS, during a period lasting 6 to 12 days. Both groups received IV KCl (20-40 mEq) to prevent hypokalemia. At study entry, all patients underwent a physical examination and measurement of body weight (BW), blood pressure (BP), and heart rate (HR), an evaluation of signs of CHF, and measurement of control levels of serum Na, K, Cl, bicarbonate, albumin, uric acid, creatinine, urea, and glycemia daily during hospitalization, and measurements of the daily output of urine for Na, K, and Cl. A chest radiograph, electrocardiogram, and echocardiogram were obtained at study entry, during hospitalization, and at the time of discharge from the hospital. During the treatment and after discharge, the daily dietary Na intake was 120 mmol in group 1 versus 80 mmol in group 2, with a fluid intake of 1000 mL daily in both groups. An assessment of BW and 24-hour urinary volume, serum, and urinary laboratory parameters were performed daily until patients reached a compensated state, when IV furosemide was replaced with oral administration (250-500 mg/d). After discharge from the hospital, patients were observed as outpatients weekly for the first 3 months and, subsequently, once a month. The groups were similar in age, sex, EF, risk factors, treatment, and etiology of CHF. All patients showed a clinical improvement. Ten patients in both groups had hyponatremia at entry. A significant increase in daily diuresis and natriuresis was observed in both groups, but it was more significant in the group receiving HSS (P <.05). The serum Na level increased in group 1 and decreased in group 2 (P <.05). The serum K level was decreased in both groups (P <.05). BW was reduced in both groups (P <.05). Group 2 had an increase in serum creatinine level. Serum uric acid levels increased in both groups. BP values decreased and HR was corrected to normal values in both groups. In the follow-up period (31 +/- 14 months), 25 patients from group 1 were readmitted to the hospital for heart failure. In group 2, 43 patients were readmitted to the hospital at a higher class than at discharge. Twenty-four patients in group 1 died during follow-up, versus 47 patients in group 2 (P <.001). This treatment is effective and well tolerated, improves the quality of life through the relief of signs and symptoms of congestion, and may delay more aggressive treatments. The effects were also beneficial in a long period for mortality reduction (55% vs 13% survival rate) and for clinical improvement.

Loop diuretic

Pulmonary edema - Slow intravenous bolus dose of 40 to 80 mg furosemide at 4 mg per minute is indicated for patients with fluid overload and pulmonary odema. Such dose can be repeated after 20 minutes. After the bolus, a continuous intravenous infusion can be given at 5 to 10 mg per hour. For those with underlying renal impairment or severe heart failure, up to 160 to 200 mg bolus dose can be given.

Treatment of severe hypertension with atenolol and betaxolol with once-daily regimens. Hemodynamic aspects.

The effectiveness and safety of once-daily administration of drugs in the treatment of moderate to severe hypertension was studied. Forty men taking diuretics were randomized to atenolol (A, n = 18), 50 mg/day, or betaxolol (B, n = 22), a new B1-blocker, 20 mg/day, if their SDAP was 105 to 125 mm Hg at baseline (weeks 2 to 4). At week 6, if SDAP was greater than 95 mm Hg, minoxidil (M), 5.5 mg/day, was added. The patients were seen every two weeks to week 16 (end of drug titration) and then every four weeks to week 32. The dosages were increased to 200 mg/day for A, 80 mg/day for B, and 20 mg/day for M as needed. Physical examinations, chest x-ray films, ECGs, echocardiograms, spirometric studies, 24-h ambulatory arterial pressures (AAP), and blood chemistry analyses were done at baseline and during treatment. A and B combined with a diuretic (furosemide, F) and M decreased the arterial pressures and heart rates equally well by both clinical and AAP measurements (p less than .001). The IVS was decreased (p less than .05), whereas LVIDd, RVIDd, and cardiothoracic ratios were increased by both A and B (p less than .05, p less than .01). No changes were noted in LVPW, LVM, EF, FS, spirometric values, or blood chemistry analyses. Common side effects were weight gain, edema, and hypertrichosis. Once-daily administration of A or B in combination with F and M were effective in the treatment of moderate to severe hypertension. Although effective, prolonged use of M may lead to volume overload and cardiomegaly. The significance of these latter findings is not yet known.

Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema.

Nitrates and furosemide, commonly administered in the treatment of pulmonary oedema, have not been compared in a prospective clinical trial. We compared the efficacy and safety of these drugs in a randomised trial of patients with severe pulmonary oedema and oxygen saturation below 90%. Patients presenting to mobile emergency units with signs of congestive heart failure were treated with oxygen 10 L/min, intravenous furosemide 40 mg, and morphine 3 mg bolus. 110 patients were randomly assigned either to group A, who received isosorbide dinitrate (3 mg bolus administered intravenously every 5 min; n=56) or to group B, who received furosemide (80 mg bolus administered intravenously every 15 min, as well as isosorbide dinitrate 1 mg/h, increased every 10 min by 1 mg/h; n=54). Six patients were withdrawn on the basis of chest radiography results. Treatment was continued until oxygen saturation was above 96% or mean arterial blood pressure had decreased by 30% or to below 90 mm Hg. The main endpoints were death, need for mechanical ventilation, and myocardial infarction. The analyses were by intention to treat. Mechanical ventilation was required in seven (13%) of 52 group-A patients and 21 (40%) of 52 group-B patients (p=0.0041). Myocardial infarction occurred in nine (17%) and 19 (37%) patients, respectively (p=0.047). One patient in group A and three in group B died (p=0.61). One or more of these endpoints occurred in 13 (25%) and 24 (46%) patients, respectively (p=0.041). High-dose isosorbide dinitrate, given as repeated intravenous boluses after low-dose intravenous furosemide, is safe and effective in controlling severe pulmonary oedema. This treatment regimen is more effective than high-dose furosemide with low-dose isosorbide nitrate in terms of need for mechanical ventilation and frequency of myocardial infarction.

Dose-ranging study of isosorbide-5-mononitrate in chronic congestive heart failure treated with diuretics and angiotensin-converting enzyme inhibitor.

The hemodynamic response of isosorbide-5-mononitrate (IS-5-MN) to the addition of the widely used therapy of diuretic drugs and the maximally tolerated dose of enalapril for heart failure was assessed in 8 patients with congestive heart failure (CHF) (New York Heart Association class II and III). The diuretic therapy was furosemide, 40 to 80 mg/day, with or without amiloride, 5 to 10 mg/day. The dose of enalapril was 5 to 20 mg/day. Four hours after the administration of the morning dose of enalapril, a Swan-Ganz catheter was positioned in the pulmonary artery. Patients received increasing doses of IS-5-MN to produce a satisfactory decrease in pulmonary capillary wedge pressure. Two of the first 3 patients studied had a large reduction in blood pressure when given 10 mg of IS-5-MN. Subsequent patients were therefore given an initial dose of 5 mg, the total dose being 5 to 20 mg over 2 hours. Results at baseline and 1 hour after the final dose of IS-5-MN are expressed as mean +/- standard deviation. Both pulmonary artery systolic and diastolic pressures decreased significantly (p less than 0.05) by 12.2 +/- 8.9/4.2 +/- 5.2 mm Hg, from 47.2 +/- 16.0/21.6 +/- 6.0 mm Hg to 35.0 +/- 15.2/17.4 +/- 9.3 mm Hg. Pulmonary capillary wedge pressure decreased by 8.6 +/- 4.4 mm Hg, from 22.1 +/- 5.4 to 13.6 +/- 7.5 mm Hg (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term efficacy, tolerability, and safety of the combination of enalapril and felodipine ER in the treatment of hypertension. Enalapril-Felodipine ER Factorial Study Group.

A recent 8-week, double-masked, placebo-controlled, 3 x 4 factorial-design study demonstrated that enalapril-felodipine extended-release (ER) combinations had statistically significant additive effects for reducing both sitting systolic blood pressure (SiSBP) and sitting diastolic blood pressure (SiDBP) and were generally well tolerated in hypertensive patients with SiDBPs ranging from 95 to 115 mm Hg. The present open-label study was undertaken to assess the long-term efficacy, tolerability, and safety of such combinations. Patients from the factorial study were eligible for the 1-year, open-label extension. Initially, all patients received enalapril 5 mg-felodipine ER 2.5 mg once daily; if SiDBP was not controlled (< 90 mm Hg) after 4 weeks of treatment, the dose was titrated upward at 2- to 4-week intervals to a maximum of enalapril 10 mg-felodipine ER 10 mg. Hydrochlorothiazide (HCTZ) 12.5 mg was added to the regimen of patients whose hypertension was not controlled at the highest enalapril-felodipine ER dose. A total of 507 patients were enrolled, of whom 502 were assessable. At their last study visit, 391 (78%) of the assessable patients were receiving only an enalapril-felodipine ER combination. The enalapril-felodipine ER combinations resulted in mean trough SiDBPs of 85 to 89 mm Hg (decreases of 13 to 16 mm Hg from baseline) and SiSBPs of 137 to 140 mm Hg (decreases of 13 to 21 mm Hg). Overall, 407 (81%) of the 502 assessable patients achieved an SiDBP < 90 mm Hg or a reduction from baseline > or = 10 mm Hg (responders); such a response was recorded in 331 patients (66%) taking a combination of enalapril-felodipine ER alone and 76 patients (15%) taking the combination with the addition of HCTZ 12.5 mg. Blood pressure reductions were maintained throughout the treatment period. Drug-related adverse events were relatively infrequent, often transient, usually mild, and apparently not dose related. The most frequently reported drug-related adverse events were edema/swelling, asthenia/fatigue, dizziness, cough, and headache. These results suggest that combination therapy with enalapril-felodipine ER is effective for long-term blood pressure reduction, has an excellent safety profile, and is generally well tolerated. Addition of low-dose HCTZ to the enalapril-felodipine ER combination appears to provide further blood pressure control without increasing drug-related adverse events.

Ascites

Monitoring diuresis: Diuresis can be monitored by weighing the person daily. The goal is weight loss of no more than 1.0 kg/day for people with both ascites and peripheral edema and no more than 0.5 kg/day for people with ascites alone. If daily weights cannot be obtained, diuretics can also be guided by the urinary sodium concentration. Dosage is increased until a negative sodium balance occurs. A random urine sodium-to-potassium ratio of > 1 is 90% sensitivity in predicting negative balance (> 78-mmol/day sodium excretion). Diuretic resistance: Diuretic resistance can be predicted by giving 80 mg intravenous furosemide after 3 days without diuretics and on an 80 mEq sodium/day diet. The urinary sodium excretion over 8 hours < 50 mEq/8 hours predicts resistance.

Loop diuretic

Clinical use Loop diuretics are principally used in the following indications: Heart failure - Giving 2.5 times of previous oral dose twice daily for those with acute decompensated heart failure is a reasonable strategy. However, daily assessment of clinical response is needed to adjust the subsequent doses. Edema associated with liver cirrhosis, and nephrotic syndrome Cerebral edema - intravenous furosemide can be combined with mannitol to initiate rapid diuresis. However, the optimum duration of such treatment remains unknown. Frequent fluid status monitoring is required to prevent intravascular volume depletion which leads to reduced cerebral perfusion. A bolus intravenous dose of 10 or 20 mg of furosemide can be administered and then followed by intravenous bolus of 2 or 3% hypertonic saline to increase the serum sodium level.

Effect of felodipine in refractory hypertension.

Felodipine (Plendil), a new drug, has been used in the treatment of five patients with refractory essential hypertension (WHO II-III). Their mean blood pressure at the last outpatient visit before the study was opened was 195 +/- 25/129 +/- 21 mmHg (mean +/- s.d.) (range 175-235/110-165 mmHg), despite treatment with combinations of diuretics, beta-blockers and vasodilators, including minoxidil and captopril. Felodipin is a dihydropyridine derivative, a calcium antagonist that exerts a relaxant effect on resistance vessels. The first period of the study consisted of a 5-day stay in hospital followed by 3 months during which observations were carried out at the Outpatients' Department. After the first days in hospital felodipine therapy was introduced at a dose of 25 mg three times daily, given together with diuretics, beta-blockers and, in one case, captopril. At 8.00 immediately before the first dose was given, the blood pressure was 178 +/- 19/118 +/- 19 mmHg (mean +/- s.d.); 2 h later it was 144 +/- 18/85 +/- 4 mmHg, at which level it remained throughout the rest of the study. At the 3-month follow-up the mean pressure (recorded at the Outpatients' Department) was 138 +/- 20/89 +/- 14 mmHg. Side-effects included headache, flushing, palpitations and ankle oedema (in two patients during the second part of the study); they were of a mild to moderate degree and did not interfere with the treatment. There was no evidence of general fluid retention, and the body weight remained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of amlodipine and enalapril on renal function in adults with hypertension and nondiabetic nephropathies: a 3-year, randomized, multicenter, double-blind, placebo-controlled study.

Placebo-controlled trials have found that angiotensin-converting enzyme inhibitors (ACEIs) decrease proteinuria and slow the progression of nondiabetic nephropathies. However, head-to-head comparisons of ACEIs and calcium channel blockers (CCBs) have shown conflicting results. Indeed, a recent metaanalysis concluded that there is still uncertainty about the greater renoprotection seen with ACEIs or angiotensin II receptor blockers in nondiabetic patients with renal disease, particularly when using true glomerular filtration rate (GFR) as the primary outcome. The objective of this 3-year, randomized, multicenter, double-blind, placebo-controlled study was to compare true GFR decline (measured by yearly 51Cr-EDTA blood clearance) in nondiabetic, nonnephrotic adult hypertensive patients with estimated creatinine clearance of 20 to 60 mL/min.1.73 m(2), when randomized to a CCB (amlodipine, 5-10 mg/d) or an ACEI (enalapril, 5-20 mg/d). Patients (aged 18-80 years) entered a 4-week placebo run-in washout period and previous antihypertensive drugs were tapered off over 2 weeks. Add-on treatments were atenolol (50-100 mg/d), loop diuretics (furosemide, 20-500 mg/d or torsemide, 5-200 mg/d), alpha-blockers (prazosin, 2.5-5 mg/d or doxazosin, 1-16 mg/d), and centrally acting drugs (rilmenidine, 1-2 mg/d or methyldopa, 250-500 mg/d). The primary end point was true GFR measured by yearly (51)Cr-EDTA blood clearance. Secondary end points included a clinical composite of renal events and tolerability collected by a full clinical and laboratory evaluation at each study visit. Post hoc analyses for the change in GFR, proteinuria, and time to clinical events were also planned on baseline proteinuria subgroups (<1 and >or=1 g/d) before unblinding the database. Three hundred eighteen patients entered the run-in period and 263 patients (156 men/107 women; mean age, 58 years) were randomized to receive either amlodipine (5 mg/d, n=132) or enalapril (5 mg/d, n=131). Blood pressure declined from 165/102 mm Hg to 138/84 mm Hg and 138/85 mm Hg with amlodipine and enalapril, respectively (no between-group significance). Only 20.8% of the patients randomized to ACEI treatment received diuretics at the last observation. No statistically significant difference was found between amlodipine and enalapril in GFR decline (-4.92 and -3.98 mL/min.1.73 m(2), respectively, at last observation) and composite secondary end point after a median follow-up of 2.9 years, including in the subgroup of patients with proteinuria >1 g/d at baseline. Protein excretion rate decreased significantly from baseline in patients taking enalapril plus diuretics (median -270 mg/d; P<0.001) but not in patients taking amlodipine plus diuretics (-25 mg/d at last observation). In this cohort of nondiabetic, nonnephrotic hypertensive patients, no statistically significant difference in true GFR decline was found over 3 years between amlodipine-treated patients and enalapril-treated patients with main add-on treatment with ss-blockers, including in the subgroup of patients with proteinuria >1 g/d.

[The Hypertension Optimal Treatment Study: efficacy and tolerability on the 36th month].

The international, prospective, randomized HOT study was aimed at determining the influence of a targeted BP reduction on cardiovascular morbidity and mortality. Patients were randomly allocated to 3 DBP targets (< 80, < 85, < 90 mmHg). In addition, the impact of a coprescription of aspirin was studied. The BP target had to be reached within 3 months, according to a well-defined strategy : felodipine 5 mg o.d. as a 1st intention drug, 1, 2 or 3 additional drugs, if necessary, on the following steps. BP measurements were made, using an oscillometric automatic device (Hestia). From April 1992 to October 1994, 18,790 patients with an age range 50-80 years, coming from 26 countries, entered the study. The data collected on the 36th month were in agreement with those obtained on the 12th and the 24th months. Baseline DBP was reduced by 21, 23 and 25 mmHg in the 90, 85 and 80 mmHg target groups, respectively. The rate of patients whose DBP reached the target, obviously increased from the 3rd to the 12th month: from 43 to 56%, 60 to 70%, 74 to 83% in the 90, 85 and 80 mmHg, target groups, respectively. From the 2nd to the 3rd year, BP control was further improved, with a slightly higher rate of controlled patients in the elderly (age > 60 y), especially in the 80 mmHg target group. From inclusion to the 3rd month, one-drug treated patients decreased, whereas 2- or 3-drug treated patients increased. Felodipine-treated patients decreased on the 36th month, but remained over 80%. From the 6th to the 36th month, additional prescription of a betablocker or an ACE-inhibitor increased from 36 to 39%, and from 23 to 28%, respectively; moreover, the side-effects rate decreased from 10.5 to 3.6%, with a special decline in ankle edema from 4 to 1%. In conclusion, the BP reduction observed on the 36th month was of the same extent as that observed in the first months. It seems obviously possible to reach a targeted DBP and to maintain it over time, along with a good acceptability of the treatment. Targeted DBP could be more easily achieved in elderly patients, possibly due to a better drug compliance.

Hypersensitivity myocarditis associated with ephedra use.

Ephedrine has previously been described as a causative factor of vasculitis but myocarditis has not yet been associated with either ephedrine or its plant derivative ephedra. A 39-year-old African American male with hypertension presented to Rush Presbyterian St. Luke's Medical Center with a 1-month history of progressive dyspnea on exertion, orthopnea, and dependent edema. He was taking Ma Huang (Herbalife) 1-3 tablets twice daily for 3 months along with other vitamin supplements, pravastatin, and furosemide. Physical examination revealed a male in mild respiratory distress. The lung fields had rales at both bases without audible wheezes. Internal jugular venous pulsations were 5 cm above the sternal notch. Medical therapy with intravenous furosemide and oral enalapril was initiated upon admission. Cardiac catheterization with coronary angiography revealed normal coronary arteries, a dilated left ventricle, moderate pulmonary hypertension, and a pulmonary capillary wedge pressure of 34 mm Hg. The patient had right ventricular biopsy performed demonstrating mild myocyte hypertrophy and an infiltrate consisting predominantly of lymphocytes with eosinophils present in significantly increased numbers. Treatment for myocarditis was initiated with azothioprine 200 mg daily and prednisone 60 mg per day with a tapering course over 6 months. Anticoagulation with warfarin and diuretics was initiated and angiotensin-converting enzyme inhibition was continued. Hydralazine was added later. One month into therapy, an echocardiogram demonstrated improved left ventricular function with only mild global hypokinesis. A repeat right ventricular biopsy 2 months after the first admission showed no evidence of myocarditis. At 6 months, left ventricular ejection fraction was normal (EFN 50%) and the patient asymptomatic. Ephedra (Ma Huang) is the suspected cause of hypersensitivity myocarditis in this patient due to the temporal course of disease and its propensity to induce vasculitis.

Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist.

Sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5), is a well-tolerated and highly effective treatment for erectile dysfunction. The mechanism of action of sildenafil depends on activation of the nitric oxide (NO)-cGMP pathway during sexual stimulation, which results in corpus cavernosal smooth muscle relaxation and penile erection. Endogenously derived NO is also involved in blood pressure regulation through its effect on basal vascular tone, which is mediated by cGMP levels. Organic nitrates and NO donors exert their therapeutic effects on blood pressure and vascular smooth muscle by the same mechanism as endogenous NO. Since both sildenafil and organic nitrates exert their pharmacologic effects via increases in cGMP concentrations, a double-blind, placebo-controlled, crossover study was undertaken to investigate the effects of sildenafil coadministered with glyceryl trinitrate on blood pressure and heart rate in healthy male subjects. The hemodynamic effects of sildenafil were also evaluated in a second placebo-controlled crossover study in men with hypertension who were taking the calcium antagonist amlodipine, which has a mechanism of action that does not involve the cGMP pathway. In the first crossover study, subjects were treated with oral sildenafil (25 mg, 3 times a day for 4 days) or placebo and then challenged on day 4 with a 40-minute, stepwise, intravenous infusion of glyceryl trinitrate (0.5 mg/mL in 5% dextrose at an initial infusion rate of 2.5 microg/min and doubling every 5 minutes to a maximum rate of 40 microg/min) 1 hour after taking sildenafil or placebo. On day 5, subjects received a sublingual glyceryl trinitrate tablet (500 microg) 1 hour after taking 25 mg of sildenafil or placebo. During sildenafil treatment, the subjects were significantly less tolerant of intravenously administered glyceryl trinitrate than during placebo treatment, based on the occurrence of a >25 mm Hg decrease in blood pressure or the incidence of symptomatic hypotension (p <0.01). When a sublingual glyceryl trinitrate tablet was administered on day 5, a 4-fold greater decrease in systolic blood pressure was observed for the subjects during the sildenafil treatment period than during the placebo treatment period. The changes in heart rate were negligible during both glyceryl trinitrate challenges. In conclusion, sildenafil potentiated the hypotensive effects of glyceryl trinitrate, an organic nitrate. Thus, sildenafil administration to patients who are using organic nitrates, either regularly and/or intermittently, in any form is contraindicated. In the second crossover study, men with hypertension, who were taking 5 or 10 mg/day of amlodipine, received a single oral dose of 100 mg sildenafil or placebo. Coadministration of sildenafil did not significantly affect the pharmacokinetics of amlodipine. In the 4 hours after dosing, differences in the mean maximum change from baseline in supine systolic and diastolic blood pressures between the sildenafil plus amlodipine and the placebo plus amlodipine treatment periods were -8 mm Hg and -7 mm Hg, respectively (p < or =0.002). The mean maximum supine heart rate increased 2.1 beats/min during sildenafil plus amlodipine treatment and decreased 1.5 beats/min during placebo plus amlodipine treatment (p <0.02). The adverse events in this study were predominantly mild or moderate and did not cause discontinuation of treatment. Adverse events considered to be related to sildenafil treatment included headache, nausea, and dyspepsia. In patients with hypertension who were taking amlodipine therapy, sildenafil produced additive, but not synergistic, reductions in blood pressure. The difference in the mean maximum change from baseline in blood pressure between sildenafil plus amlodipine and placebo plus amlodipine was comparable to the decrease in blood pressure reported for healthy men taking sildenafil alone. (ABSTRACT TRUNCATED)

[Comparative study of 2 diuretic-containing combination preparations in patients with edematous heart failure].

The efficacy and tolerability of two combinations, namely 50 mg spironolactone + 20 mg furosemide (SF) or 50 mg spironolactone + 5 mg butizide (SB), were compared in a randomised intraindividual trial in 22 patients with congestive heart failure. The parameters used were: weight, ankle- and calf-circumference, blood pressure, resting pulse, resting ECG, spirometry and blood chemistry. The physicians' judgement of the success of treatment was also recorded. Clinical symptoms improved clearly in both groups and in most cases there was significant improvement of the various parameters. The trend towards improvement was more apparent with SF. The physicians considered SF to be more effective in 12 cases compared to one case with SB. In all other cases both treatments were considered equally effective. The blood chemistry data showed relevant differences: serum-potassium levels were less scattered with SF and showed a - desirable - shift into the upper normal range. The number of patients with elevated serum-creatinin-levels increased during SB-treatment whereas the opposite was noted with SF. This could be due to furosemide's positive effects on renal functions.

Paracetamol poisoning

Intravenous acetylcysteine is given as a continuous infusion over 20 hours for a total dose 300 mg/kg. Recommended administration involves infusion of a 150 mg/kg loading dose over 15 to 60 minutes, followed by a 50 mg/kg infusion over four hours; the last 100 mg/kg are infused over the remaining 16 hours of the protocol. Intravenous acetylcysteine has the advantage of shortening hospital stay, increasing both doctor and patient convenience, and allowing administration of activated charcoal to reduce absorption of both the paracetamol and any co-ingested drugs without concerns about interference with oral acetylcysteine. Intravenous dosing varies with weight, specifically in children. For patients less than 20 kg, the loading dose is 150 mg/kg in 3 mL/kg diluent, administered over 60 minutes; the second dose is 50 mg/kg in 7 mL/kg diluent over 4 hours; and the third and final dose is 100 mg/kg in 14 mL/kg diluent over 16 hours.

A long-term open study of a frusemide/amiloride combination ('Frumil') in elderly patients with congestive cardiac failure.

Twenty-seven patients (mean age 72 years) with symptoms of congestive cardiac failure who had been controlled by treatment with 1 to 2 tablets per day of a combination preparation of frusemide (40 mg) and amiloride (5 mg) for at least 12 weeks were studied. The study was designed to assess the efficacy and tolerability of continuing treatment with the combination for a further 9 months, i.e. a total period of 12 months. Assessments of disease status and laboratory data were made every 3 months. Reasonable control of symptoms was achieved over the 12-month period although the majority of patients did not show a clinically important change. Some overall trends towards increasing oedema, dyspnoea and orthopnoea were observed as the study progressed, but these changes were not regarded as unusual considering the patients' age group. Significant increases in pulse rate and decreases in blood pressure were demonstrated, suggesting that diuresis was maintained. The combination preparation was well tolerated without any reports of side-effects.

Severe hypertension and pulmonary edema associated with systemic absorption of topical phenylephrine in a child during retinal surgery.

Topical phenylephrine solutions are widely used in eye procedures to promote pupil dilation without cycloplegia. We report a case of intraoperative severe hypertension and acute pulmonary edema occurring in a child during retinal surgery after possible systemic absorption of topical phenylephrine eyedrops. Our objective is to discuss the proper treatment and preventive strategies for such a complication. A 4-year-old, male patient, 18.4 kg in weight, physical status ASA I was admitted for right retinal detachment surgery. Anesthesia was induced with sevoflurane in oxygen, followed by glycopyrrolate (5.0 μg/kg), propofol 25 mg, fentanyl 50 μg and cisatracurium 0.15 mg/kg given intravenously. Anesthesia was maintained with sevoflurane 2-2.5% in a mixture of nitrous oxide and oxygen (60%:40%). After incision, two drops of 10% aqueous phenylephrine were administered topically by the surgeon to the right eye for further pupil dilation. Few minutes later, the noninvasive blood pressure rose to 220/120 mmHg and the heart rate increased to 140 beats/min. Oxygen saturation (SpO(2)) dropped from 99% (with an inspired oxygen concentration (FiO(2)) of 0.4) to 82%. Auscultation revealed crepitations throughout the chest and a blood-stained frothy fluid was aspirated from the trachea with possible development of acute pulmonary edema. Hydralazine (5 mg) and furosemide (10 mg) were administered intravenously. Seven minutes later, the blood pressure returned to normal and the SpO(2) increased to 92% on FiO(2) of 1.0, with decreased intratracheal secretions. After approximately 20 minutes, the SpO(2) had improved to 99%, with a FiO(2) of 1.0 and the blood pressure was 109/63 mmHg and heart rate was 121 beats/min. The FiO(2) gradually reduced back to 0.4 over 30 min with no further desaturation. The patient was discharged from the post anesthesia care unit 5 h after surgery with adequate spontaneous breathing, SpO(2) 99% on room air, normal blood pressure and pulmonary auscultation. Anesthesiologists and ophthalmologists should be aware of the possible cardiovascular side-effects of topical phenylephrine, and it should be used cautiously with appropriate intraoperative monitoring of hemodynamic variables. Moreover, preventive strategies to minimize systemic absorption of the drug should be taken.

Treatment of heart failure with normal left ventricular ejection fraction.

Underlying causes and precipitating causes of heart failure (HF) should be treated when possible. Persons with HF and normal left ventricular ejection fraction (LVEF) should have maintenance of sinus rhythm, treatment of hypertension, myocardial ischemia, dyslipidemia, and anemia, slowing of the ventricular rate below 90 bpm, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers and angiotensin-converting enzyme (ACE) inhibitors. If persons are unable to tolerate ACE inhibitors because of cough, angioneurotic edema, rash, or altered taste sensation, angiotensin II type I receptor antagonists (ARBs) should be given. If HF persists despite diuretics, beta blockers, and ACE inhibitors or ARBs, isosorbide dinitrate plus hydralazine should be administered. Beta blockers, verapamil, diltiazem, and digoxin may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with HF in sinus rhythm with normal LVEF. Exercise training should be encouraged in persons with mild to moderate HF to improve functional status and to decrease symptoms.

Greater efficacy of aldosterone blockade and diuretic reinforcement vs. dual renin-angiotensin blockade for left ventricular mass regression in patients with resistant hypertension.

We report the results of an echocardiographic substudy carried out in a trial comparing the effects of two different treatment strategies - mineralocorticoid receptor blockade (MRB) and dual renin-angiotensin system blockade (RASB) - in patients with resistant hypertension. Both strategies reduce left ventricular mass index (LVMI), but they have not been compared in patients with resistant hypertension. After 4-week treatment with 300 mg irbesartan + 12.5 mg hydrochorothiazide + 5 mg amlodipine, 86 patients with resistant hypertension were randomized to the add-on 25 mg spironolactone (MRB group, n = 46) or 5 mg ramipril (RASB group, n = 40) groups for 12 weeks. Treatment intensity was increased at week 4, 8 or 10 if home blood pressure (BP) was equal to or above 135/85 mmHg, by sequentially adding 20-40 mg furosemide and 5 mg amiloride (MRB group), or 10 mg ramipril and 5-10 mg bisoprolol (RASB group). Transthoracic echography was performed at baseline and week 12. Daytime ambulatory BP decreased by 19 ± 12/11 ± 8 mmHg in the MRB group and by 8 ± 13/7 ± 7 mmHg in the RASB group (P = 0.0003/0.03). LVMI decreased by 8.2 ± 18.9 g/m in the MRB group, whereas it increased by 1.8 ± 19.1 g/m in the RASB group (P = 0.03). The decreases in posterior wall thickness, left ventricular (LV) end-systolic diameter, E/e' ratio and left atrial area were significantly greater with MRB than with RASB. The difference between groups remained significant after adjustment for the decrease in ambulatory BP. In patients with resistant hypertension, MRB-based treatment decreased both BP and LVMI more efficiently than a strategy based on dual RASB.

[Double blind study of the efficacy and safety of the fixed dose combination of enalapril 10 mg/nitrendipine 20 mg versus the increase of amlopidine dose in essential hypertensive patients not controlled with amlodipine 5 mg].

Combined therapy or dose-tiration are acceptable second-line therapeutic options after a first treatment failure. This double blind clinical trial compared the fixed dose combination of enalapril 10 mg/nitrendipine 20 mg (E/N) with amlopidine 10 mg (A) in 323 hypertensive patients not previously controlled with amlodipine 5 mg. After 6 weeks of treatment, the E/N and A groups had similar percentages of blood pressure normalization (55% versus 60.2%; p = 0.4588). The adverse events related with the treatment were significantly less frequent with E/N than with a (19.8% versus 37%; p = 0.0029), especially due to a lower incidence of malleolar edema in E/N (11.1% versus 33.6%; p < 0.0001). Combining the efficacy and tolerability data, treatment with E/N permitted control of blood pressure of 2.8 patients per every patient with adverse events, while this rate for A was 1.6 to 1.

Does furosemide alter the hemodynamic response to rapid intravascular transfusion of the anemic fetal lamb?

The purpose of this study was to define the hemodynamic response to rapid intravascular transfusion of the anemic fetal lamb and to determine whether furosemide alters that response. Sixteen experiments were performed in nine chronically instrumented gravid ewes between 0.8 and 0.9 of timed gestation. On day 1 of each experiment, each fetus was subjected to hemorrhage (40 ml/kg of estimated fetal weight) over 1 hour. On day 2, plasma was withdrawn from the stored fetal blood until the hematocrit was approximately 70%, and the packed red blood cells were returned to the fetus intravenously over 10 minutes. Each fetus received either furosemide (2 mg/kg) or control saline solution intravenously at time zero and again at 5 minutes. The order of experiments was randomly determined for each animal. Hemorrhage resulted in a similar decrease in fetal hematocrit in the two groups. The mean +/- SEM fetal hematocrit before hemorrhage was 38 +/- 3% in the furosemide group (n = 8) and 36 +/- 2% in the control group (n = 8). On day 2, the mean +/- SEM fetal hematocrit before transfusion was 28 +/- 2% in the furosemide group and 25 +/- 1% in the control group. There was no significant difference between groups in the fetal hemodynamic response to transfusion. At the end of the transfusion, the fetal central venous pressure had increased from 4.9 +/- 0.5 to 6.2 +/- 0.5 mm Hg in the furosemide group (p = 0.01) and from 3.9 +/- 0.2 to 5.8 +/- 0.3 mm Hg in the control group (p = 0.0001). Fetal mean arterial pressure increased from 42 +/- 1 to 50 +/- 1 mm Hg in the furosemide group (p = 0.0001) and from 40 +/- 1 to 46 +/- 1 mm Hg in the control group (p = 0.0007). Fetal heart rate decreased from 187 +/- 2 to 169 +/- 5 beats/min in the furosemide group (p = 0.004) and from 188 +/- 4 to 170 +/- 5 beats/min in the control group (p = 0.0008). Transfusion did not significantly change fetal pH in either group. At 120 minutes, the fetal PO2 had increased from 17 +/- 1 to 19 +/- 1 mm Hg in the furosemide group (p = 0.03) and from 19 +/- 1 to 21 +/- 2 mm Hg in the control group (p = 0.05). We conclude that rapid transfusion of the anemic fetal lamb resulted in modest increases in fetal central venous pressure and mean arterial pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Frusemide/amiloride combination ('Frumil') in heart failure: an open, multi-centre study in general practice.

A total of 95 patients seen in general practice with oedema associated with heart failure took part in an open study of the efficacy and tolerability of a combination tablet containing 40 mg frusemide and 5 mg amiloride. The study was of 3-months' duration and patients received a dosage of 1 to 2 tablets once daily. Efficacy was assessed by physicians' scores for ankle, leg and lumbosacral oedema and pulmonary crepitations, body weight and physicians' global clinical impression. In addition, patients recorded their symptom severity in study diaries during the first 7 days of therapy, and the day before each trial visit. On the basis of the physicians' overall impression of response to therapy, 89 (93.7%) of the patients were graded as 'excellent', 'good' or 'adequate' responders. Improvement in severity scores for oedema, crepitations and body weight also followed this pattern, although certain symptoms were mild or absent in some patients at recruitment. Nine patients were withdrawn from the study, 4 due to drug-related adverse effects. There was no evidence of any consistent change in serum potassium levels or other clinical chemistry, liver function tests or haematology during the study.

Clevidipine

Cleviprex is administered intravenously and should be titrated to achieve the desired blood pressure reduction. Blood pressure and heart rate should be monitored continually during infusion. Cleviprex is a single use product that should not be diluted and should not be administered in the same line as other medications. Once the stopper is punctured, Cleviprex should be used within 12 hours and any unused portion remaining in the vial should be discarded. Change IV lines in accordance with hospital protocol. An IV infusion at 1–2 mg/hour is recommended for initiation and should be titrated by doubling the dose every 90 seconds. As the blood pressure approaches goal, the infusion rate should be increased in smaller increments and titrated less frequently. The maximum infusion rate for Cleviprex is 32 mg/hour. Most patients in clinical trials were treated with doses of 16 mg/hour or less.

Neurology_Adams

In the past, when effective treatment was not available, the outcome was often fatal. Lowering of the blood pressure with antihypertensive drugs may reverse the picture in a day or two. The same can be accomplished by administering magnesium sulfate in the eclamptic woman. However, antihypertensive drugs must be used cautiously; a safe target is a pressure of 150/100 mm Hg or a 20 percent reduction in mean pressure. One may use intravenous sodium nitroprusside, 0.5 to 0.8 mg/kg/min; a calcium channel blocker such as nifedipine, 10 to 20 mg sublingually; or intravenous beta-adrenergic blockers (labetalol, 20 to 40 mg intravenously followed by an infusion at 2 mg/min, or esmolol are favored). Longer-acting antihypertensive agents, such as ACE inhibitors and calcium channel blockers, must follow these. If there is already evidence of brain edema and increased intracranial pressure, dexamethasone, 4 to 6 mg every 6 h, is sometimes added, but its effect, and the use of hyperosmolar

Randomized, controlled, parallel-group comparison of ambulatory and clinic blood pressure responses to amlodipine or enalapril during and after treatment in adult chinese patients with hypertension.

Few studies have examined the relative efficacy and tolerability of antihypertensive drug classes in Chinese populations. This study compared the efficacy, tolerability, and duration of antihypertensive effect of amlodipine besylate and enalapril in Chinese patients with hypertension, including elderly patients with isolated systolic hypertension. This randomized, double-blind, double-dummy, parallel-group dose-titration study was conducted at the Department of Medicine and Therapeutics, Chinese University of Hong Kong. Chinese patients aged 18 to 80 years with primary hypertension were enrolled. After a 4-week placebo run-in period, patients were randomly assigned to receive active oral, once-daily treatment with amlodipine (5 mg) or with enalapril (5 mg) for 14 weeks. Treatment doses were titrated at weeks 4 and 8 if necessary according to blood pressure (BP) response and if the dose had been tolerated. Patients also underwent 24-hour ambulatory BP monitoring (ABPM) at the end of the placebo run-in, after the first and last doses of active treatment, and 48 hours after discontinuation of treatment to determine the duration of drug action and to mimic the effect of 2 missed doses. Eighty patients were recruited for the study (26 men, 54 women; mean [SD] age, 60.5 [11.6] years) (40 patients per group). Thirty-seven patients in each group completed the active treatment phase. Baseline trough BPs were similar: 167.7 (15.0)/94.6 (9.7) mm Hg in the amlodipine group and 168.6 (11.9)/93.4 (9.5) mm Hg in the enalapril group. After 14 weeks of treatment, amlodipine (mean [SD] final dose, 6.3 [2.3] mg) produced greater reductions than enalapril (mean [SD] final dose, 13.3 [6.6] mg) in trough BP (-20.8 [13.2]/-9.2 [9.0] vs -5.5 [14.9]/-3.2 [10.6] mm Hg, respectively; P < or = 0.01). Most of the effect of amlodipine persisted for 72 hours after the last dose (-18.9 [14.6]/-11.1 [11.7] mm Hg), but enalapril had no significant antihypertensive effect at 72 hours (-1.3 [12.3]/-1.8 [9.1] mm Hg). Similar observations were found with ABPM recordings. Cough was reported in 5 patients (12.5%) and 13 patients (32.5%) in the amlodipine and enalapril groups, respectively, but was thought to be treatment related in only 6 patients (15.0%), all in the enalapril group. One of the patients in the enalapril group withdrew from the study because of cough, and 1 patient in the amlodipine group withdrew because of ankle edema.

[Effect of long-term treatment with enalapril, losartan and their combination on the quality of life of patients with congestive heart failure].

To study the effect a combination of enalapril and losartan on life quality in patients with congestive heart failure (HF). One hundred and eighty six patients with NYHA functional classes II to IV HF were examined. The study inclusion criteria were as follows: a left ventricular (LV) end-diastolic volume of > 160 ml, a LV ejection fraction of < 35%, sinus rhythm, a cardiothoracic index of > 0.55, no history data on prior treatment with an angiotensin-converting enzyme inhibitor (ACEI) and/or an AT1-antagonist, a patient's written free-will consent to participate in the study. The exclusion criteria were as follows: pacemaker migration, an artificial pacemaker, high-degree block, atrial fibrillation, cerebral circulatory disorders. All the patients were divided into 4 groups and received basic therapy with cardicet, 60-120 mg/day, aspirin, 250 mg/day, furosemide, 80-440 mg/week, and digoxin, 0.25-0.5 mg/day. Group 1 comprised 60 patients who refused therapy with ACEI and/or AT1-antagonist despite that they had indications for their use and they had been convinced many times. In Group 2 (n = 82) enalapril, an ACEI, was added to the basic therapy. Its initial dose of 2.5 mg/day was given once and slowly incremented to the therapeutical one (10-20 mg/day). Group 3 patients (n = 56) on the basic therapy were additionally treated with the AT1-antagonist losartan in a daily dose of 25-50 mg. They were started on 12.5 mg a day. In group 4 the basic therapy was added by a combination of enalapril and losartan in the same doses. The follow-up was 48 weeks. The efficiency of the treatments was controlled by the personal questionnaires SF-36, Life with Heart Failure, by evaluating the magnitude of clinical HF manifestations and by estimating the total life quality inxed. The data were analyzed by assuming that all the patients received the treatments. As compared with the conventional therapy and the use of each drug alone, a combination of the ACEI enalapril and the AT1-antagonist losartan promotes a more significant increase in the satisfaction of the patients with their vital activity, in the critical rate of their self-assessment of the "internal picture" of disease, and leads to a greater improvement of the quality of their life as a whole. The ICAE-AT1-antagonist combination exerts a positive impact on life quality in patients with heart failure.

Gantacurium chloride

Adverse effects Histamine release—hypotension, reflex tachycardia and cutaneous flushing Gantacurium chloride is not associated with histamine release when administered as a rapid bolus (<5 seconds administration time) at doses up to and including 0.45 mg/kg (≤2.5xED95) according to one small study in healthy human volunteers. At 0.54 mg/kg (just under 3xED95 dose), one of four volunteers experienced histamine release with associated hypotension (30% maximum decrease in blood pressure and 13% maximum increase in heart rate) but no cutaneous flushing. At the highest administered dose of 0.72 mg/kg, three of four volunteers experienced histamine release with associated hypotension (17% to 34% maximum decrease in blood pressure and 16% to 25% increase in heart rate) and cutaneous flushing. These effects were transient and lasted no more than two minutes and did not require any adjunctive treatment to address the changes in blood pressure or heart rate.

Antihypertensive monotherapy with nitrendipine in general practice.

Efficacy and feasibility of antihypertensive monotherapy with the calcium antagonist nitrendipine were investigated in a 6-week open trial in 768 patients with mild to moderate essential hypertension from 191 practicing internists and general practitioners. Previous antihypertensive therapy (n = 501) was withheld for 1 week and therapy then started with nitrendipine 20 mg q.d. If diastolic blood pressure before tablet intake in the morning stayed above 90 mm Hg or fell less than 10 mm Hg, the dose could be doubled to the maximum dose of 20 mg b.i.d. Alternatively, if blood pressure control was good, the dose could be halved to 10 mg q.d. One hundred thirty-four patients discontinued therapy prematurely because of unwanted effects mostly characteristic with dihydropyridines (headaches, flushes, and ankle edema) and mostly within the first 3 weeks. In 72% of the remaining 634 patients, the goal blood pressure was achieved by nitrendipine monotherapy (10 mg q.d. in 8%, 20 mg q.d. in 87%, and 20 mg b.i.d. in 5%) and diastolic blood pressure was between 90 and 95 mm Hg in another 3%. Reductions of blood pressure did not result in changes of heart rate or weight. Nitrendipine was effective in patients of all age groups but patients older than 65 years showed a significantly greater fall of systolic and mean arterial pressure than middle aged or young patients. Nitrendipine's efficacy under conditions of general practice and the high proportion of patients responding to once daily administration appear well suited for first-line therapy of uncomplicated hypertension. The incidence of side effects might have been smaller if therapy had started with a smaller dose.

Elotuzumab

Dosage and administration In combination with lenalidomide and dexamethasone The package insert advises that intravenous administration with 10 mg/kg every week for the first 2 cycles (each cycle is 28 days) and every 2 weeks thereafter, with the appropriate doses of lenalidomide and low dose dexamethasone is acceptable for treatment. For additional information on dosing dexamethasone and/or lenalidomide, refer to the package inserts. In combination with pomalidomide and dexamethasone Elotuzumab is recommended through intravenous administration at 10 mg/kg each week for the first 2 cycles (each cycle is 28 days). At the start of cycle 3, administer 20 mg/kg every 4 weeks, while administering the recommended dose of pomalidomide and low dose dexamethasone. For additional information on dosing dexamethasone and/or dexamethasone, refer to the package inserts.

Continuous infusion of furosemide in the treatment of patients with congestive heart failure and diuretic resistance.

To assess the value of treatment with continuous intravenous infusion of furosemide (F) in patients with refractory congestive heart failure. Open uncontrolled dose-response study. Patients with congestive heart failure (those with New York Heart Association (NYHA) classes III and IV with an assessed amount of oedema of more than 5 kg and diuretic resistance were included [n = 10]). Diuretic resistance was defined as: failure to lose weight and/or inappropriate urinary sodium excretion (50 mmol 24 h-1) despite bed rest for a period of 2-3 days, salt and water restriction, orally and intravenously administered furosemide in a dose of 250 mg day-1, digoxin, and when possible an ACE inhibitor. Included patients were treated with continuous F infusion at a delivery rate of 20 mg-1 over 24 h. The infusion rate was gradually heightened up to a maximum dose of 160 mg h-1. Daily physical examination, history of side-effects, determination of serum electrolytes and 24-h electrolyte excretion during treatment with furosemide. Weight loss (mean +/- SD; 12.5 +/- 5 kg) and relief of symptoms was achieved in all patients. Mean (+/- SD) 24-h sodium output rose from 19 +/- 16 mmol 24 h-1 (n = 10) on oral therapy with 250 mg F to 137 +/- 85 mmol 24 h-1 (n = 8) during 80 mg h-1 and to 268 +/- 124 mmol 24 h-1 (n = 3) on the maximal dose of 160 mg h-1. Continuous infusion of F under careful monitoring of the patient is a safe, controllable and efficient treatment in patients with severe congestive heart failure and diuretic resistance.

Adjunctive sympathoplegic therapy to ACE inhibition in Blacks with congestive heart failure: a comparison of alpha-1 with beta-1 blockade on exercise tolerance and cardiac sympathovagal reflex activity.

Congestive heart failure (CHF) is characterized by an initial compensatory, but subsequently deleterious, activation of both the renin-angiotensin (RAS) and the sympathetic nervous system (SNS). Incomplete suppression of the SNS may contribute to the residual mortality during optimal ACE inhibitor therapy in CHF. Carvedilol, a mixed alpha and beta-blocker with antioxidant properties, and other pure beta-adrenoceptor blockers reduce morbidity and mortality in Caucasians with CHF. However, beta-blocker monotherapy is of poor efficacy in Blacks with essential hypertension or in the treatment of glaucoma. The efficacy of beta-blockers in the treatment of African Americans with congestive heart failure is a controversial issue with conflicting findings. The aims of the present study were to examine and compare the cardiovascular, autonomic, and clinical effects of additional alpha-1, or beta-1 blockade in ACE-inhibitor treated Black patients with moderate to severe CHF. Twenty-eight Nigerian patients with chronic CHF stabilized on digoxin and diuretics, were randomized to 3 groups of similar demographics according to a single blind, parallel group design. The patients were aged 53 +/- 6 years, and comprised 14 men and 14 women, with a mean cardiothoracic ratio of 0.66 +/- 0.03, and ejection fraction of 0.38 +/- 0.10, 60% hypertensive etiology. Group 1 patients received 5 mg enalapril alone, group 2 received 5 mg enalapril + 1 mg prazosin, and group 3 received 5 mg enalapril + 50 mg atenolol. All medication was taken daily for 4 weeks. Blood pressure, heart rate, pressure rate product, 6-minute walk test, NYHA class, and cardiac autonomic reflexes were measured at baseline and again at 2 and 4 weeks of treatment. Two-way repeated measures ANOVA, and a one-way ANOVA were used in data analysis. The 3 treatments caused significant (P<.001 ANOVA) and similar improvements for the NYHA class (-1.0 to -1.6), and increased the 6-minute distance covered (+130 m to +205 m). Although no treatment differences were observed, a trend suggesting a greater improvement with enalapril + atenolol became apparent. By the fourth week, the sympathoplegic treatments, enalapril + atenolol, and enalapril + prazosin, caused significant reductions in the pressure rate product (-3726 +/- 1885 mm Hg x beats/min; -3498 +/- 396 mm Hg beats/min, respectively), (compared to enalapril alone (-1349 +/- 894 mm Hg x beats/min) (P<.001 ANOVA). During the Valsalva maneuver, the phase IV bradycardia were significantly greater after treatment with enalapril + atenolol (944 +/- 66 msec) or with enalapril + prazosin (825 +/- 48 msec), compared to enalapril alone (760 +/- 45 msec) (P<.001 ANOVA). The phase II Valsalva tachycardia were similar between treatments. The respiratory sinus arrhythmia ratio increased significantly (P<.005 ANOVA) and equally on all treatments. However, the pressor and chronotropic responses to forearm isometric handgrip increased significantly on the enalapril + prazosin combination (P<.02), compared to the other treatments. Our findings demonstrated not only the safety of providing additional therapy with alpha-1 or beta-1 receptor blockade concurrent with ACE inhibition in Blacks with CHF, but also the resultant improvement in exercise tolerance and NYHA class. Compared to using ACE inhibition alone, the combined therapies caused a marked reduction in the pressure rate product, an index of myocardial oxygen consumption, and a greater enhancement of cardiac parasympathetic activity. Selective beta-1 blockade caused a greater enhancement of central baroreceptor vagal activity compared to alpha-1 blockade. Conversely, the pressor and chronotropic abnormalities during forearm isometric handgrip in CHF, were normalized by alpha-1, but not beta-1, blockade. Thus, the combined reflex cardiac vagal augmentation following selective beta-1 blockade, and the hemodynamic effects of alpha-1 antagonism with concurrent ACE inhibition, may be of major therapeutic and prognostic benefit in Blacks with non-ischemic (hypertensive) CHF stabilized on digoxin and diuretics.

Hypertension in the elderly: a study of a combination of atenolol, hydrochlorothiazide and amiloride hydrochloride.

The anti-hypertensive effects of atenolol (Tenormin) 50 mg, a potassium-sparing diuretic (half-strength Moduretic) comprising hydrochlorothiazide 25 mg plus 2.5 mg amiloride hydrochloride, and the 'free' combination of atenolol and diuretic were compared in elderly hypertensive patients aged 60-79 years. After a four-week run-in period on placebo, patients were randomly assigned, in a double-blind manner, to atenolol or diuretic treatment, each for four weeks. Thereafter patients were given the 'free' combination for a further four weeks and this treatment was continued for six months. Blood pressure and heart rate were measured after the patient had rested for five minutes supine and after two minutes standing. These blood pressure measurements were made at least 24 hours after the preceding dose using a Random Zero sphygmomanometer. Results from 26 of the 27 patients entered into the study showed an advantage for combination therapy combined with either atenolol or diuretic treatment alone. No significant difference was found between treatments in the frequency of supraventricular and ventricular ectopic beats occurring in six patients who underwent 24-hour ambulatory ECG monitoring. However, ectopic activity was reduced in some patients during beta-blocker treatment. Few adverse effects occurred with any treatment. Three patients withdrew during the placebo period and three withdrew while taking active treatment. This study has shown that the combination of atenolol, hydrochlorothiazide and amiloride hydrochloride is an effective, safe, well-tolerated antihypertensive drug regimen when used once daily in elderly hypertensive patients.


In healthy adults there may be palpable inguinal nodes up to 2 centimeters that can be considered normal. A complementary study of these normal lymph nodes is not warranted.

A 24-year-old woman consults after noticing inguinal lymphadenopathy. The interrogation does not reveal the presence of any local discomfort or data suggestive of sexually transmitted infection. The examination revealed two lymphadenopathies, one in each groin, 1 cm in diameter, soft, mobile, non-painful. There are no skin lesions on the lower limbs, anus or perineum. Which test do you consider essential?

A lues serology since it is most likely a Treponema pallidum infection.

A gynecological examination to rule out ovarian cancer.

By the clinical characteristics it seems to be normal lymph nodes and complementary explorations should not be done.

A Paul-Bunnell test should be performed in order to rule out infectious mononucleosis.

Inguinal lymphadenopathy

Inguinal lymphadenopathy causes swollen lymph nodes in the groin area. It can be a symptom of infective or neoplastic processes. Infective aetiologies include Tuberculosis, HIV, non-specific or reactive lymphadenopathy to recent lower limb infection or groin infections. Another notable infectious cause is Lymphogranuloma venereum, which is a sexually transmitted infection of the lymphatic system. Neoplastic aetiologies include lymphoma, leukaemia and metastatic disease from primary tumours in the lower limb, external genitalia or perianal region and melanoma. References Further reading Inflammations Diseases of veins, lymphatic vessels and lymph nodes

Genital ulcer

Overview A genital ulcer may be located on the vulva, penis, perianal region, or anus. Globally, the incidence of genital ulcers is estimated to be approximately 20 million cases annually. The most likely cause of a genital ulcer varies depending on the characteristics of a population and location. The most common cause of genital ulcers in the United States is herpes simplex infections, with syphilis the second most common cause, and chancroid the third. These common causes of genital ulcer disease (HSV-1, HSV-2 and treponema pallidum) can all be efficiently transmitted through oral sex. Important signs associated with genital ulcers that may assist in the diagnosis of the cause of the genital ulcer may include the presence of tender or non-tender enlarged lymph nodes in the groin area, a painful or non-painful genital ulcer, or the presence of vesicular lesions, which are small, painful, elevated blisters.

[A chancre instead of cancer].

Syphilis (lues) is a sexually transmitted infection caused by the spirochete Treponema pallidum. In adolescents, the diagnosis of primary syphilis can be made promptly by taking a sexual medical history and inspecting the glans penis. A 17-year-old male was referred to the paediatric oncology centre for additional diagnostics due to inguinal lymphadenopathy, with a strong suspicion of a malignant lymphoma. None of the physicians took a sexual medical history or investigated the glans penis, as a result of which essential information was lacking. The combination of inguinal lymphadenopathy and the ultrasound findings for the inguinal region made the physicians only consider a malignancy. However, it actually concerned a reactive lymphadenopathy associated with primary syphilis. This case demonstrates that a full medical history and thorough physical examination can prevent the need for costly and invasive diagnostics.

Inguinal lymph nodes

Clinical significance The presence of swollen inguinal lymph nodes is an important clinical sign because lymphadenopathy (swelling) may indicate an infection, or spread as a metastasis from cancers, such as anal cancer and vulvar cancer. Inguinal lymph nodes may normally be up to 2 cm. The cut-off value for normal sized inguinal nodes is up to 10 mm. Additional images References Lymphatic organ anatomy

Anatomy, Abdomen and Pelvis: Inguinal Lymph Node -- Clinical Significance -- Lymphadenopathy

Swollen lymph nodes usually indicate infection from bacteria or viruses. Swollen inguinal lymph nodes could indicate an infection of areas of the lower body. One of the more concerning causes of inguinal lymphadenopathy is sexually transmitted infections. Sexually transmitted infections that commonly presents with inguinal lymphadenopathy are lymphogranuloma venereum, secondary syphilis, and chancroid caused by Chlamydia trachomatis (L1-L3), Treponema pallidum , and Haemophilus ducreyi , respectively. Lymphogranuloma venereum

InternalMed_Harrison

Diagnosis Although most genital ulcerations cannot be diagnosed confidently on clinical grounds alone, clinical findings (Table 163-7) FIGURE 163-5 Chancroid: multiple, painful, punched-out ulcers with undermined borders on the labia occurring after autoinoculation. Sexually Transmitted Infections: Overview and Clinical Approach FIGURE 163-6 Genital herpes. A relatively mild, superficial ulcer is typically seen in episodic outbreaks. (Courtesy of Michael Remington, University of Washington Virology Research Clinic.) FIGURE 163-7 Lymphogranuloma venereum (LGV): striking ten-der lymphadenopathy occurring at the femoral and inguinal lymph nodes, separated by a groove made by Poupart’s ligament. This “sign-of-the-groove” is not considered specific for LGV; for example, lym-phomas may present with this sign. InITIAL MAnAgEMEnT of gEnITAL oR PERIAnAL uLCER

Lymphogranuloma venereum

The secondary stage most often occurs 10–30 days later, but can present up to six months later. The infection spreads to the lymph nodes through lymphatic drainage pathways. The most frequent presenting clinical manifestation of LGV among males whose primary exposure was genital is unilateral (in two-thirds of cases) lymphadenitis and lymphangitis, often with tender inguinal and/or femoral lymphadenopathy because of the drainage pathway for their likely infected areas. Lymphangitis of the dorsal penis may also occur and resembles a string or cord. If the route was anal sex, the infected person may experience lymphadenitis and lymphangitis noted above. They may instead develop proctitis, inflammation limited to the rectum (the distal 10–12 cm) that may be associated with anorectal pain, tenesmus, and rectal discharge, or proctocolitis, inflammation of the colonic mucosa extending to 12 cm above the anus and associated with symptoms of proctitis plus diarrhea or abdominal cramps.

Gynecology_Novak

Several clinical presentations are highly suggestive of specific diagnoses: 1. A painless and minimally tender ulcer, not accompanied by inguinal lymphadenopathy, is likely to be syphilis, especially if the ulcer is indurated. A nontreponemal rapid plasma reagin (RPR) test, or venereal disease research laboratory (VDRL) test, and a confirmatory treponemal test—ﬂuorescent treponemal antibody absorption (FTA ABS) or microhemagglutinin–T. pallidum (MHA TP)—should be used to diagnose syphilis presumptively. Some laboratories screen samples with treponemal enzyme immunoassay (EIA) tests, the results of which should be confirmed with nontreponemal tests. The results of nontreponemal tests usually correlate with disease activity and should be reported quantitatively. 2.

Anatomy, Abdomen and Pelvis: Female External Genitalia -- Clinical Significance -- Sexually Transmitted Infections

Treponema pallidum : Syphilis infections result from Treponema pallidum . This infection usually manifests as a painless chancre in the primary stage. If the disease is left untreated, it will progress to the secondary stage. In the secondary stage, it manifests as fever, widespread maculopapular skin rashes involving the palms and soles,  widespread lymphadenopathy (epitrochlear node is pathognomic), and genital lesions similar to genital warts (condylomata lata- has a rounder surface when compared with condylomata acuminata). If there is still no treatment during the secondary stage, the infection will progress into the tertiary stage. The tertiary stage causes necrotic lesions called Gummas, neurological symptoms such as tabes dorsalis, Argyll Robertson pupils, and general paresis, cardiac symptoms such as aortitis. The treatment of syphilis is with the use of penicillin.

InternalMed_Harrison

Source: From RM Ballard, in KK Holmes et al (eds): Sexually Transmitted Diseases, 4th ed. New York, McGraw-Hill, 2008. HSV-1 from HSV-2 has prognostic implications, because the latter causes more frequent genital recurrences. Painless, nontender, indurated ulcers with firm, nontender inguinal adenopathy suggest primary syphilis. If results of dark-field examination and a rapid serologic test for syphilis are initially negative, presumptive therapy should be provided on the basis of the individual’s risk. For example, with increasing rates of syphilis among MSM in the United States, most experts would not withhold therapy for this infection pending watchful waiting and/or subsequent detection of seroconversion. Repeated serologic testing for syphilis 1 or 2 weeks after treatment of seronegative primary syphilis usually demonstrates seroconversion.

Lymphogranuloma venereum

Diagnosis The diagnosis usually is made serologically (through complement fixation) and by exclusion of other causes of inguinal lymphadenopathy or genital ulcers. Serologic testing has a sensitivity of 80% after two weeks. Serologic testing may not be specific for serotype (has some cross reactivity with other chlamydia species) and can suggest LGV from other forms because of their difference in dilution, 1:64 more likely to be LGV and lower than 1:16 is likely to be other chlamydia forms (emedicine). For identification of serotypes, culture is often used. Culture is difficult. Requiring a special medium, cycloheximide-treated McCoy or HeLa cells, and yields are still only 30-50%. DFA, or direct fluorescent antibody test, PCR of likely infected areas and pus, are also sometimes used. DFA test for the L-type serovar of C. trachomatis is the most sensitive and specific test, but is not readily available.

InternalMed_Harrison

Demonstration of H. ducreyi by culture (or by PCR, where available) is most useful when ulcers are painful and purulent, especially if inguinal lymphadenopathy with fluctuance or overlying erythema is noted; if chancroid is prevalent in the community; or if the patient has recently had a sexual exposure elsewhere in a chancroid-endemic area (e.g., a developing country). Enlarged, fluctuant lymph nodes should be aspirated for culture or PCR to detect H. ducreyi as well as for Gram’s staining and culture to rule out the presence of other pyogenic bacteria.

Syphilis is a bacterial infection caused by the spirochete Treponema pallidum. Clinical presentation of secondary syphilis can present with diffuse lymphadenopathy along with fever, skin rashes, and condylomata lata. [7] Chancroid

InternalMed_Harrison

Lymphadenopathy may be an incidental finding in patients being examined for various reasons, or it may be a presenting sign or symptom of the patient’s illness. The physician must eventually decide whether the lymphadenopathy is a normal finding or one that requires further study, up to and including biopsy. Soft, flat, submandibular nodes (<1 cm) are often palpable in healthy children and young adults; healthy adults may have palpable inguinal nodes of up to 2 cm, which are considered normal. Further evaluation of these normal nodes is not warranted. In contrast, if the physician believes the node(s) to be abnormal, then pursuit of a more precise diagnosis is needed. APPROACH TO THE PATIENT:

InternalMed_Harrison

Approach to the Patient with an Infectious Disease regions (e.g., popliteal, inguinal, epitrochlear, axillary, multiple cervical regions), with notation of the location, size (normal, <1 cm), presence or absence of tenderness, and consistency (soft, firm, or shotty) and of whether the nodes are matted (i.e., connected and moving together). Of note, palpable epitrochlear nodes are always pathologic. Of patients presenting with lymphadenopathy, 75% have localized findings, and the remaining 25% have generalized lymphadenopathy (i.e., that involving more than one anatomic region). Localized lymphadenopathy in the head and neck region is found in 55% of patients, inguinal lymphadenopathy in 14%, and axillary lymphadenopathy in 5%. Determining whether the patient has generalized versus localized lymphadenopathy can help narrow the differential diagnosis, as various infections present differently.

Sexually Transmitted Infections -- History and Physical -- Granuloma Inguinale

Females and males: Signs and symptoms: Patients will present with highly vascularized lesions over the genitals and perineum that tend to be painless. [37] [38] It can cause severe scarring. Physical Exam: Typical findings include ulcer-like lesions that are beefy red, consistent with high vascularization that bleeds easily with manipulation. Subcutaneous granulomas may be present, but lymphadenopathy is uncommon. The lesions tend to be relatively large and irregular. It is often found to be associated with secondary infections. Four main lesions can be seen on examination: 1. Ulcerovegetative: large painless ulcer on the patient's physical exam. 2. Nodular: soft and erythematous that tend to ulcerate throughout the infectious process. 3. Cicatricial: dry ulcerations that tend to transition into plaques. 4. Hypertrophic: lesions are thick and painless. [37] [39]

InternalMed_Harrison

node is an enlarged left supraclavicular node infiltrated with metastatic cancer from a gastrointestinal primary. Metastases to supraclavicular nodes also occur from lung, breast, testis, or ovarian cancers. Tuberculosis, sarcoidosis, and toxoplasmosis are nonneoplastic causes of supraclavicular adenopathy. Axillary adenopathy is usually due to injuries or localized infections of the ipsilateral upper extremity. Malignant causes include melanoma or lymphoma and, in women, breast cancer. Inguinal lymphadenopathy is usually secondary to infections or trauma of the lower extremities and may accompany sexually transmitted diseases such as lymphogranuloma venereum, primary syphilis, genital herpes, or chancroid. These nodes may also be involved by lymphomas and metastatic cancer from primary lesions of the rectum, genitalia, or lower extremities (melanoma).

Yaws

Serological tests cannot distinguish yaws from the closely related syphilis; no test distinguishing yaws from syphilis is widely available. The two genomes differ by about 0.2%. PCR and DNA sequencing can distinguish the two. There are also no common blood tests which distinguish among the four treponematoses: syphilis (Treponema pallidum pallidum), yaws (Treponema pallidum pertenue), bejel (Treponema pallidum endemicum), and pinta (Treponema carateum). Haemophilus ducreyi infections can cause skin conditions that mimic primary yaws. People infected with Haemophilus ducreyi lesions may or may not also have latent yaws, and thus may or may not test positive on serological tests. This was discovered in the mid 2010s. It seems that a recently diverged strain of Haemophilus ducreyi has evolved from being a sexually transmitted infection to being a skin ulcer pathogen that looks like yaws. Yaws has been reported in nonendemic countries.

Sexually Transmitted Infections -- History and Physical -- Lymphogranuloma venereum (LGV)

Females and males: Signs and symptoms: Patients will present with painful lymphadenopathy localized to the inguinal area. Patients may note the initial presentation of a pustule that gradually progresses to large painful ulceration. [41] Men tend to present with early or acute stages, while women typically present much later. [19] Physical Exam: Lymphogranuloma venereum presents with two stages: Primary phase is a small painless papule/pustule that will ulcerate and can be visualized throughout the affected genital area. During the secondary phase, patients present with unilateral lymphadenopathy that is fluctuant with palpation or may be suppurative in a presentation known as buboes. [38] Buboes tend to rupture in the acute phase and progress to a thickened mass. [42]

Glandular fever and pulmonary artery thrombosis in a paraplegic patient, who had undergone splenectomy for splenic trauma sustained along with spinal cord injury: misdiagnosed initially as urine infection and later as lymphoma when CT scan revealed enlarged lymph nodes: a case report.

A 36-year-old male sustained fracture of first lumbar vertebra, splenic tear and paraplegia in a motorcycle accident in 2001; splenectomy was performed. In 2008, he presented with temperature and feeling rough. With a diagnosis of urine infection, he was prescribed ciprofloxacin, followed by trimethoprim, amoxicillin, and gentamicin, as temperature did not subside. White cell count was 21.2 x 109/L; lymphocytes were 13.05 x 109/L (1.00 - 4.00). Therefore, computerised tomography (CT) of chest and abdomen was performed. Thrombus was present in pulmonary arteries bilaterally involving the lobar and segmental branches. Enlarged lymph nodes were seen in axillae, chest, abdomen and inguinal regions. Radiological diagnosis was lymphoma. Cell marker showed an excess of large granular lymphocytes and activated lymphocytes. The Glandular Fever Slide Test was positive. Subsequently, Paul Bunnell test was also positive. Epstein Barr virus serology was consistent with recent Epstein Barr virus infection. Antibiotic was omitted; enoxaparin was prescribed for pulmonary artery thrombosis. Learning points from this case: (1) Although routine administration of antibiotic to a spinal cord injury patient with pyrexia may be acceptable in outpatient setting, other possibilities such as infection by multi-drug resistant organism, viral infection, venous or, arterial thrombosis should be considered if a patient does not respond promptly to antibacterial therapy. (2) When full blood count showed lymphocytosis (comprising > 50% of white blood cells) with atypical morphology, lymphocyte surface markers, Paul Bunnell test, and Epstein Barr virus serology should be performed. These tests would have led to a diagnosis of infectious mononucleosis, and abdominal imaging studies could have been avoided. (3) Lymphoid hyperplasia is the hallmark of infectious mononucleosis; therefore, we should have suspected glandular fever rather than lymphoma when CT scan revealed enlarged lymph nodes in abdomen, mediastinum, axillae and inguinal regions in this patient, who had lymphocytosis with atypical morphology. (4) A soft tissue mass, situated inferior to left hemidiaphragm in this asplenic patient, was misinterpreted as lymph nodes; review of CT led to the correct diagnosis of splenunculus. (5) Acute infection with Epstein Barr virus may lead to transient induction of anti-phospholipid antibodies, which can cause vascular thrombosis. (6) This case illustrates the value of reviewing test results and discussion with senior doctors, as these measures help to recognize medical errors and improve patient care.

Sexual health clinic

In a private room or space, the patient will partially undress. The clinician may inspect the patient's: Throat and lymph nodes of the neck for inflammation Pubic hair for lice Lymph nodes of the groin for swelling Genitals, anus, and surrounding areas for sores and warts The clinician may swab the patient's: Throat to test for gonorrhea and possibly chlamydia Cheek, inside, to diagnose HIV Sores of the genitals, anus, and surrounding areas to test for herpes Urethra to test for gonorrhea and possibly chlamydia Vagina to test for chlamydia and possibly gonorrhea Cervix to test for cervical intraepithelial neoplasia (a Pap test) Rectum to test for gonorrhea and possibly chlamydia The clinician may take small blood samples by pricking a finger or from a vein to test for HIV, syphilis, and possibly herpes and hepatitis C.

Unusual Manifestations of Secondary Syphilis: Case Presentations.

Dear Editor, Syphilis is an infection caused by Treponema pallidum. Without treatment, it goes through the following stages: primary, secondary, latent, and tertiary (1). The clinical picture of secondary syphilis is very variable (2,3). We present two rare cases of secondary syphilis, one with nodular lesions initially considered to be lymphoma and second with periostitis, which was initially interpreted as an osteoma. To date, only 15 cases with nodular lesions and 10 cases with periostitis in secondary syphilis have been reported in the literature. The first patient was a 59 year old man who presented in a private practice with nodular lesions on the face and axillary and inguinal folds (Figure 1, a, b). The initial diagnostic consideration was lymphoma. A biopsy specimen was taken, and the histopathological features revealed epidermal hyperplasia with papillomatosis, minimal spongiosis with many neutrophils and with a marked inflammatory infiltrate in dermis, consisting of lymphocytes, plasma cells, and neutrophils; the diagnosis of interfaced dermatitis was established (Figure 1, d, e). After one month, the patient presented to our clinic with numerous nodular lesions, some of them painful, located on the trunk and intertriginous folds, including the intergluteal cleft - the lesions in this area being suggestive of condylomata lata (Figure 1, c). The diagnosis of secondary syphilis was taken into consideration, and screening serum tests were performed and found reactive: a Venereal Diseases Research Laboratory (VDRL) titer of 1:64 and Treponema pallidum Hemaglutination Assay (TPHA) titer of 1:80. Hepatitis and anti-human immunodeficiency virus (HIV) antibodies serology was negative. The biopsy was repeated and showed the same histopathological changes. In addition, Warthin-Starry staining was performed, revealing the presence of some spiral micro-organisms in the dermis corresponding to Treponema pallidum (Figure 1, f). A diagnosis of secondary syphilis was established, and the patient was treated with benzathine penicillin G 2.4 million units by intramuscular injection once a week for 2 consecutive weeks. The skin lesions regressed within 1 month, and serological tests showed a VDRL titer of 1:8 3 months after treatment. The second patient was a homosexual male, 35 years old, diagnosed with HIV infection, stage B2. He presented with bone pain in the calves and forearms, with insidious onset. He also presented with an associated erythematous maculo-papular rash on the trunk and limbs and generalized lymphadenopathy (Figure 2, a, b). The tibial crest and radius were sensitive to palpation. A right leg radiography was performed, raising suspicion of osteoid osteoma. The CT scan excluded the diagnosis of osteoma; taking into account the epidemiological context, the diagnosis of syphilis was suspected. The diagnosis was confirmed by leg ultrasound examination (2D US) which showed thickening of the compact tibial bone associated with subperiosteal destructive and proliferative changes (Figure 2, c, d) and by serology for syphilis: the VDRL titer was 1:32 and the TPHA titer was 1:80. The patient was treated with benzathine penicillin 2.4 million units, once a week, for 2 consecutive weeks, with clinical improvement. Syphilis continues to be a serious public health problem worldwide, even if it is a controllable disease due to diagnostic tests and effective and accessible treatment. According to the World Health Organization in 2008, the estimated number of new cases of sexually transmitted diseases in adults with syphilis is 10.6 million cases (4). The cases presented in this paper were characterized by unusual manifestations, requiring good collaboration between the dermatologist and other specialties. In the first case, the diagnosis of secondary syphilis was confirmed by positive serological, clinical, and histopathological findings. The main differential diagnosis of nodular syphilis includes lymphoma, sarcoidosis, Kaposi's sarcoma, atypical mycobacteriosis, deep fungal infections, leprosy, tuberculosis, leishmaniasis, and lymphomatoid papulosis (5). Another important differential diagnosis is between secondary and tertiary syphilis, especially when ulcerating nodules are present. Tertiary syphilis is characterized by unilateral, deep ulcerating nodules with necrotizing granulomas (6). Bone involvement during syphilis is mainly represented by polyarthritis, synovitis, osteitis, and periostitis (7,8). Syphilitic periostitis is characterized by localized or diffuse pain, particularly during the night, which is relieved by movement. The skull, the shoulder girdle, and the long bones are the most common sites of involvement (9). In conclusion, we presented two different cases of secondary syphilis that contribute to the clinical experience of rare cases presented in the literature, raising the awareness of dermatologists and other specialists about less specific clinical aspects of syphilis.

InternalMed_Harrison

adenopathy that is sometimes mistaken for malignancy; syphilis, LGV, HSV infection, and chancroid involving the anus can produce inguinal adenopathy because anal lymphatics drain to inguinal lymph nodes.

Cervical lymphadenopathy

Cervical lymphadenopathy is a sign or a symptom, not a diagnosis. The causes are varied, and may be inflammatory, degenerative, or neoplastic. In adults, healthy lymph nodes can be palpable (able to be felt), in the axilla, neck and groin. In children up to the age of 12 cervical nodes up to 1 cm in size may be palpable and this may not signify any disease. If nodes heal by resolution or scarring after being inflamed, they may remain palpable thereafter. In children, most palpable cervical lymphadenopathy is reactive or infective. In individuals over the age of 50, metastatic enlargement from cancers (most commonly squamous cell carcinomas) of the aerodigestive tract should be considered. Classification Cervical lymphadenopathy can be thought of as local where only the cervical lymph nodes are affected, or general where all the lymph nodes of the body are affected. Causes

Lymphogranuloma Venereum -- Differential Diagnosis

Sexually transmitted infections are the first to consider in the differential diagnosis of LGV. The exclusion of diseases which cause genital ulceration and inguinal adenopathy including herpes simplex, syphilis, chancroid, herpes, and granuloma inguinale will help narrow the diagnosis. HIV and lymphoma can also cause generalized lymphadenopathy. Dermatological conditions and trauma which can cause genital ulcerations should also be in the differential diagnosis.

Lymphadenopathy

Lymph node enlargement is recognized as a common sign of infectious, autoimmune, or malignant disease. Examples may include: Reactive: acute infection (e.g., bacterial, or viral), or chronic infections (tuberculous lymphadenitis, cat-scratch disease). The most distinctive sign of bubonic plague is extreme swelling of one or more lymph nodes that bulge out of the skin as "buboes." The buboes often become necrotic and may even rupture. Infectious mononucleosis is an acute viral infection usually caused by Epstein-Barr virus and may be characterized by a marked enlargement of the cervical lymph nodes. It is also a sign of cutaneous anthrax and Human African trypanosomiasis Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy (Piringer-Kuchinka lymphadenopathy). Plasma cell variant of Castleman's disease - associated with HHV-8 infection and HIV infection

[Inguinal lymphogranuloma venereum in a man having sex with men: perhaps an example of the missing link to explain the transmission of the recently identified anorectal epidemic].

A 38-year-old man who had sex with men, presented at the outpatient department for Sexually Transmitted Diseases in Amsterdam with a painful, red, fluctuating swelling in the left groin and general discomfort. He had been sexually active in the population of men who have sex with men, in which an anorectal lymphogranuloma venereum (LGV) epidemic has recently been discovered. Unlike other cases where there was anorectal involvement, this patient was the first case of LGV with the classical inguinal presentation although he had not visited the tropics where the inguinal form of LGV occurs as an STD. Routine investigation using PCR on material from urethra and rectum and from the urine, repeatedly failed to detect LGV. However, PCR on pus aspirated from the enlarged lymph node demonstrated Chlamydia trachomatis serovar type L2. Treatment with doxycycline 100 mg twice daily was started. This case illustrates that routine analysis from urethra and rectum and of urine may fail to detect LGV. Furthermore, this case of a patient who probably had LGV initially in the urethra may be the missing link in explaining the route of transmission of the anorectal LGV epidemic.

InternalMed_Harrison

The presentation of chancroid does not usually include all of the typical clinical features and is sometimes atypical. Multiple ulcers can coalesce to form giant ulcers. Ulcers can appear and then resolve, with inguinal adenitis (Fig. 182-2) and suppuration following 1–3 weeks later; this clinical picture can be confused with that of lymphogranuloma venereum (Chap. 213). Multiple small ulcers can resemble folliculitis. Other differential diagnostic considerations include the various infections causing genital ulceration, such as primary syphilis, secondary syphilis (condyloma latum), genital herpes, and donovanosis. In rare cases, chancroid lesions become secondarily infected with bacteria; the result is extensive inflammation. FIGURE 182-2 Chancroid with characteristic penile ulcers and associated left inguinal adenitis (bubo).

Primary syphilis of the oropharynx: an unusual location of a chancre.

A 33-year-old man presented with a two-week history of an asymptomatic ulcer of the oropharynx and submandibular lymph nodes swelling. Laboratory examinations were normal, but serological tests revealed positivity for rapid plasma reagin, Treponema pallidum haemagglutination assay and anti-T. pallidum IgM antibodies. Since the patient denied any homosexual relationship, a biopsy of the lesion was performed, which confirmed primary syphilis. The patient received an intramuscular injection of Benzathine Penicillin G (2.4 MU) with complete resolution of the lesion. Extragenital chancres occur in at least 5% of patients with primary syphilis, and the oral mucosa is the most frequent location as a consequence of orogenital/oroanal contact with an infectious lesion. Because of their transient nature, these oral ulcerations are often underestimated by the patient or by any unsuspecting clinician. Health professionals should consider the recent sexual history of their patients and should be prepared to recognise oral and systemic manifestations of sexually transmitted infections.

Oropharyngeal lesions and cervical lymphadenopathy: syphilis is a differential diagnosis that is still relevant.

Syphilis (lues), a chronic infectious disease caused by Treponema pallidum, has been increasing in incidence during the last few years. Therefore, while clinically it is often not suspected, syphilis is increasingly becoming a differential diagnosis in routine pathology. To report our experience with five cases of cervical lymphadenopathy and/or oropharyngeal lesions, clinically thought to be lymphomas, lymph node metastases or carcinoma, in which we made the mostly clinically unsuspected diagnosis of syphilis. Fine needle aspiration of enlarged cervical lymph nodes was evaluated by cytology and flow cytometry (fluorescence-activated cell sorting analysis), and biopsies were examined by using histology. In addition, all materials were also subjected to immunostaining, silver staining and molecular (PCR) testing. Fine needle aspiration cytology revealed follicular hyperplasia in two cases and granulomatous lymphadenitis in one case. In three patients, concomitant biopsy of co-existing oropharyngeal lesions revealed histological findings compatible with syphilis. T pallidum was detected in all cytological and histological samples by immunohistochemistry/immunocytochemistry and PCR. Subsequently, a diagnosis of syphilis was confirmed clinically and by serology. Syphilitic lymphadenitis is still a relevant differential diagnosis of cervical lymphadenopathy, and it is clinically often not suspected. Co-existing oropharyngeal lesions should alert the physician to this differential diagnosis; and lesions with compatible morphology should be tested with immunohistochemistry and immunocytochemistry and/or molecular analysis to confirm the diagnosis of syphilis.

Chancroid

About half of infected men have only a single ulcer. Women frequently have four or more ulcers, with fewer symptoms. The ulcers are typically confined to the genital region most of the time. The initial ulcer may be mistaken as a "hard" chancre, the typical sore of primary syphilis, as opposed to the "soft chancre" of chancroid. Approximately one-third of the infected individuals will develop enlargements of the inguinal lymph nodes, the nodes located in the fold between the leg and the lower abdomen. Half of those who develop swelling of the inguinal lymph nodes will progress to a point where the nodes rupture through the skin, producing draining abscesses. The swollen lymph nodes and abscesses are often referred to as buboes.

Sézary disease

Generalized erythroderma– redness of the skin Lymphadenopathy – swollen, enlarged lymph nodes Atypical T-cells – malignant lymphocytes known as "Sézary cells" seen in the peripheral blood with typical cerebriform nuclei (brain-shaped, convoluted nuclei) Hepatosplenomegaly– enlarged liver and spleen Palmoplantar keratoderma – thickening of the palms of the hands, and soles of the feet Diagnosis Those who have Sézary disease often present with skin lesions that do not heal with normal medication. A blood test generally reveals any change in the levels of lymphocytes in the blood, which is often associated with a cutaneous T-cell lymphoma. Finally, a biopsy of a skin lesion can be performed to rule out any other causes.