Outcome for children after failed transplant for primary haemophagocytic lymphohistiocytosis.

Primary haemophagocytic lymphohistiocytosis is a rare disorder of childhood, which is usually fatal without allogeneic stem cell transplantation (SCT). For children who lack a matched family or closely matched unrelated donor, SCT using haploidentical parental stem cells has been used, but is associated with an increased risk of graft failure. The most appropriate subsequent management for those children who survive after graft rejection is currently unclear. We report the outcome for three such children. After a period of disease quiescence lasting 4 months to 8 years, disease recurrence and subsequent death occurred in each case. Accordingly, a second SCT is recommended.

An outbreak of erysipelas in 2-day-old poults.

Systemic erysipelas infection was seen in 2-to-4-day-old poults from three separate ranches owned by the same company. The affected poults were all from the same breeder source; poults from other breeder sources were seemingly unaffected. Mortality increased on days 2 and 3, ranging from 2% to 8.5%. Birds submitted were dehydrated and very weak, with one half of the poults submitted having died during transport to the lab. Gross lesions included swollen, congested livers and spleens, as well as hemorrhagic breast muscle in one case. Toes were swollen and reddish-purple in color. The poults had been toe-trimmed during hatchery processing using a commercial microwave. Histologically, periportal inflammation with heterophilic infiltration in the liver was noted. Spleens showed hyalinization of arteries, lymphoid depletion, and necrosis. Toe joints showed purulent synovitis and cellulitis. Gram stains done on impression smears of liver and spleen showed rare to moderate numbers of small gram-positive rods. Erysipelothrix rhusiopathiae was isolated from 18 of 22 livers cultured, five of six toe joints cultured, and from the yolk sac in two birds.

[The French state and immigration: problems involved in implementing a public policy]. / L'etat francais et l'immigration: problemes de mise en oeuvre d'une politique publique.

The author uses the example of France to examine why it is so difficult for a liberal democratic state to control immigration. He examines the political process in France, particularly the capacity of the government to intervene in matters of social and economic activity. Even though France is seen as a strong, centralized state with the capacity to intervene when it needs to do so, the author concludes that "economic and social conditions are found to play a much greater role in channeling migratory flows than the 'actions' of the state, as expressed in public policy." (SUMMARY IN ENG)

Migration and international relations: cooperation and control in the European Community.

"In this article I have developed a political-economic framework for understanding international migration in postwar Europe and the United States." The author begins by reviewing four theories of international relations and gives a short critique of their main assumptions. He "finds that international migration reveals a contradiction between the main economic purpose of the postwar international order--to promote exchange--and the national perquisites of sovereignty and citizenship."

The effects of benazepril, a new angiotensin-converting enzyme inhibitor, in mild to moderate essential hypertension: a multicenter study.

Benazepril hydrochloride is a new angiotensin-converting enzyme inhibitor. In a multicenter study, 206 patients with mild to moderate hypertension were randomized to receive benazepril at a dose of 2, 5, 10, or 20 mg, hydrochlorothiazide, 25 mg, or placebo once daily for 4 weeks. The 20 mg dosage of benazepril lowered blood pressure to a degree equal to that of 25 mg hydrochlorothiazide: -12.2/7.7 mm Hg and -13.4/-7.5 mm Hg, respectively. Hydrochlorothiazide proved to be more effective in black subjects. At lower dosage levels of benazepril (2, 5, and 10 mg), blood pressure reduction was not significantly different from that with placebo. In those patients who failed to achieve goal diastolic blood pressure of less than 90 mm Hg with monotherapy after 4 weeks, the addition of open-label hydrochlorothiazide (25 mg/day) to benazepril, hydrochlorothiazide, or placebo produced a substantial additional decrease in blood pressure over a 2-week period. No definite adverse effects on hematologic measurements, serum biochemistry test results, or urinalyses were noted. Subjective adverse experiences were common in all groups but except in three or possibly four instances were not considered causally related to the study drug.

A comparison of the efficacy and safety of a beta-blocker, a calcium channel blocker, and a converting enzyme inhibitor in hypertensive blacks.

A double-blind, positively controlled, forced dose titration study comparing the efficacy and safety of atenolol, captopril, and verapamil sustained release as single agents in the treatment of black patients with mild to moderate hypertension (diastolic blood pressure, 95 to 114 mm Hg) was conducted. A total of 394 patients were randomized to one of the three therapies. Mean blood pressures during a 2- to 4-week placebo treatment period (baseline) ranged from 100.4 to 100.7 mm Hg diastolic and 151.7 to 152.5 mm Hg systolic for the three groups. Of the patients, 355 (of whom 345 had assessable data) completed the first treatment period, which consisted of therapy with either 50 mg/d of atenolol, 25 mg every 12 hours of captopril, or 240 mg/d of verapamil sustained release. During the second 4-week treatment period, which 319 patients completed (307 assessable), half of the patients had their antihypertensive medication increased and the other half continued the same dose. Goal blood pressure was defined as a supine diastolic pressure of less than 90 mm Hg or a 10-mm Hg or greater drop in supine diastolic blood pressure from pretreatment levels. Atenolol, captopril, and verapamil sustained release therapy was associated with goal blood pressure achievement during the first treatment period 55.1%, 43.8%, and 65.2% of the time, respectively, and during the second treatment period 59.6%, 57.1%, and 73.0% of the time. Side effects were minimal and comparable for all three drugs.

Immigration and the French state: problems of policy implementation.

"Why is it so difficult for a liberal-democratic state to regulate immigration? Although control of a territory is part and parcel of the definition of state sovereignty, labor-importing countries have found it increasingly difficult to regulate the flow of noncitizens across their borders. This article seeks to address the difficulties of regulating immigration by focusing on the policy-making process and the interaction of politics and markets in France, one of the principal countries of immigration."

[Immigrants or citizens: immigration policy in France and in the United States]. / Migrants ou citoyens: la politique de l'immigration en France et aux Etats-Unis.

PIP: Treatment of migrants and foreigners by a government can reveal not only the functioning of the political system but the philosophic values on which the system is founded. This article compares French and American immigration policy and explores the extent to which French immigration policy is more "statist" or Jacobin while American immigration policy is more "liberal" or pluralist. Immigration is an explosive problem for all democratic governments. 4 questions are involved, that of the sovereignty of the state over its citizens; that of citizenship, not only regarding the juridical definition of citizen but also assimilation, ethnicity, race, and political socialization; that of employment, which has been the most important determinant of migration policies in the industrialized countries after World War II; and that of humanitarian considerations, which have become more significant in the 1980s. Comparison of immigration policies must focus on issues of citizenship and employment and on humanitarian aspects. France and the US have had more difficulty in formulating and applying migration policies with national objectives than have any of the other liberal democracies. This work seeks to explain this similarity as well as divergences in the migration policies of France and the US by examining: 1) institutional differences between the 2 political systems and how they affect the state's capacity to control immigration; 2) the way in which the political and juridical culture influence relationships between problems of citizenship and use of foreign manpower; and 3) immigration policies as they have been applied in the 2 countries in the postwar period. The entire issue of immigration has become more politicized in France than in the US, partly because of the statist and administrative approach to it in France. The federal nature of the US political system, the stability of the party system, and the pluralist approach to legislation have fragmented the issue of immigration to a large extent. Despite significant differences in French and American political systems and cultures, both societies retain a fundamentally liberal attitude toward their foreign populations. The Jacobin ideal of equality before the law held by many French citizens and the liberal ideal of equality of opportunity at the heart of recent American political development explain the openness and attraction of the 2 countries for foreigners.^ieng

Potassium restoration in hypertensive patients made hypokalemic by hydrochlorothiazide.

Among 447 hypertensive patients, most with a history of diuretic-induced hypokalemia, 252 developed diuretic-induced hypokalemia while receiving hydrochlorothiazide, 50 mg/d. In a randomized study we evaluated the efficacy of three drug regimens in restoring potassium levels while maintaining blood pressure control: hydrochlorothiazide (50 mg/d) plus potassium supplement (20 mmol/d); hydrochlorothiazide (50 mg/d) plus potassium supplement (40 mmol/d); or hydrochlorothiazide (50 mg/d) with triamterene (75 mg/d) in one combination tablet. In all groups, mean serum levels of potassium rose within 1 week and showed no further change thereafter. However, the hydrochlorothiazide/triamterene and hydrochlorothiazide plus 40 mmol of potassium regimens were significantly more effective in restoring serum potassium levels than was the hydrochlorothiazide plus 20 mmol of potassium regimen. A significant increase in magnesium levels was observed only in the group treated with the hydrochlorothiazide/triamterene combination. Each regimen provided continued control of mild to moderate hypertension.

Thiazide treatment of systemic hypertension: effects on serum magnesium and ventricular ectopic activity.

Clinical and investigational evidence has proved an association between thiazide-induced electrolyte imbalances and ventricular arrhythmias. It is hypothesized that this increases the potential for sudden unexplained death. Elderly hypertensive patients are at particular risk because of their tendency to have significantly depressed serum magnesium levels, which decrease even further when treated with thiazide diuretics. Potassium supplementation does not effectively restore electrolyte balance unless accompanied by magnesium. Therefore, concomitant administration of potassium and magnesium supplementation appears to be an approach to reducing the risk of arrhythmias and death in thiazide-treated hypertensive patients.

Electrolyte disarray and cardiovascular disease.

Thiazide diuretics have frequently been recommended as initial therapy in patients with mild to moderate hypertension. However, their undesirable metabolic consequences have been suspected of contributing to increases in cardiovascular morbidity and mortality. Even at low doses, there is a definite decrease in both potassium and magnesium levels. The degree of decrease in potassium and magnesium levels has been shown to be directly related to the hydrochlorothiazide dosage. Many investigators have now reported an increase in ventricular ectopy associated with diuretic-induced hypokalemia. Whereas there is no single study that conclusively proves that thiazide therapy results in malignant arrhythmias and an increased risk of sudden death, the circumstantial evidence is strong. Although sodium restriction is critical to potassium restoration, it rarely works alone. Potassium chloride supplementation can be effective in restoring potassium but not magnesium. Potassium-sparing diuretic combinations can both prevent and treat hypokalemia and hypomagnesemia, possibly reducing the risk of potentially lethal arrhythmias and sudden death.

Comparison of equal-weight oral dosages of verapamil hydrochloride and diltiazem hydrochloride in patients with mild to moderate hypertension.

The clinical efficacy, safety, and tolerability of oral verapamil and diltiazem, at total daily dosages of equal weight, were evaluated in a placebo-controlled, double-blind crossover study. Thirty-six ambulatory patients with chronic, stable, mild to moderate hypertension (supine diastolic blood pressure of 94-116 mm Hg) received a dosage of either verapamil or diltiazem 80 mg t.i.d. as the hydrochloride salt for one week after an antihypertensive-drug washout period. Each then received 120 mg of the same drug t.i.d. for one week. After another two-week washout period, the patients were crossed over to the other drug. Each patient had a 12-lead electrocardiogram and measurement of supine and standing blood pressure weekly. In the 32 patients completing the study, low-dose verapamil reduced supine diastolic blood pressure (DBP) from a mean of 101.5 +/- 5.2 to 95.3 +/- 9.5 mm Hg; high dose verapamil reduced DBP to 90.9 +/- 7.4 mm Hg. Standing DBP was reduced to a similar degree. Diltiazem showed an almost identical effect: Supine DBP was reduced from a mean of 101.7 +/- 5.3 to 94.0 +/- 10.1 mm Hg with the low dose and to 91.0 +/- 8.6 mm Hg with the high dose, with similar effects on standing DBP. The high dose of both drugs significantly increased the QTc interval, and both doses of diltiazem significantly increased the PR interval compared with baseline. Both drugs exhibited consistent efficacy with minimal adverse effects. The electrophysiologic safety profile of verapamil was superior to that of diltiazem.

Serum magnesium and potassium levels in hypertensive patients after a therapeutic switch from hydrochlorothiazide plus a potassium supplement to maxzide.

Determinations of serum magnesium and potassium levels and blood pressure were made in 40 hypertensive patients in whom daily therapy with 50 mg of hydrochlorothiazide plus potassium supplements was switched to a once-daily regimen of 50 mg of hydrochlorothiazide plus 75 mg of triamterene (Maxzide). Patients showed no clinically significant changes in blood pressure or in serum magnesium or serum potassium values following the switch. It is concluded that therapy in patients receiving hydrochlorothiazide and up to 60 meq of potassium can be safely switched to Maxzide without adversely affecting serum magnesium levels, serum potassium levels, or blood pressure control.

Magnesium depletion, diuretics, and arrhythmias.

Increasing information on the potentially serious risks of potassium and magnesium depletion associated with diuretic therapy demands a clinical focus on understanding the factors involved and on methods for preventing these electrolyte deficiencies. Data suggest that serum potassium and magnesium levels may be normal in the presence of tissue depletion, but decreases in serum levels are almost always associated with tissue and whole-body depletion of these electrolytes in patients in whom such depletion cannot be risked. Ventricular ectopy has also been associated with depletion of potassium and magnesium, which may explain the increased risk of sudden unexpected death in hypertensive patients. Any clinician who treats hypertension or congestive heart failure must consider whether to replete potassium and magnesium in patients already receiving diuretic therapy, or, better still, consider how to prevent depletion of these electrolytes in patients in whom such depletion cannot be risked. If prevention is selected, the clinician must then evaluate the data on available diuretic combinations for efficacy in electrolyte conservation, bioavailability, and dosage convenience. The combination of triamterene and hydrochlorothiazide (Maxzide, 75 mg triamterene/50 mg hydrochlorothiazide) has demonstrated electrolyte conservation, with bioavailability and dosage convenience.

Thiazide treatment of hypertension. Effects of thiazide diuretics on serum potassium, magnesium, and ventricular ectopy.

Thiazide diuretics are considered to be the cornerstone of contemporary antihypertensive therapy and are generally recommended as the initial treatment for patients with mild to moderate, uncomplicated hypertension. Hypokalemia and hypomagnesemia are two metabolic alterations that are associated with long-term thiazide therapy. Thirty-five patients (20 with low renin status and 15 with normal renin status) with mild to moderate essential hypertension were treated with hydrochlorothiazide in a dose-titration experiment after a four-week lead-in period. The initial daily dose was 12.5 mg; this was increased at four-week intervals to 25 mg, 37.5 mg, and 50 mg daily. The endpoint dose of this titration was that dose at which the patient's blood pressure normalized, or the dose of 50 mg, if that dose was reached. Patients were maintained on their endpoint dose of hydrochlorothiazide for 24 weeks of continuous thiazide monotherapy beyond the dose titration. The serum potassium and serum magnesium levels during the control period were 4.4 +/- 0.2 mmol/liter and 2.30 +/- 0.08 mg/dl, respectively. During dose titration, each incremental increase of hydrochlorothiazide produced a decrease in blood pressure and a stepwise decrease in serum potassium and magnesium levels. A previously reported study involving 38 patients with mild to moderate hypertension (22 with low renin status and 16 with normal renin status) used similar methods to study higher-dose thiazide therapy. An initial dose of 50 mg daily of hydrochlorothiazide was administered; this was increased at four-week intervals to 100 mg, 150 mg, and 200 mg. The serum potassium and serum magnesium levels during the control period were 4.5 +/- 0.2 mmol/liter and 2.1 +/- 0.18 mg/dl, respectively. In the hypertensive patients with normal renin status, doses of hydrochlorothiazide greater than 50 mg did not result in further blood pressure lowering effects; however, the undesirable effects of hypokalemia and hypomagnesemia continued to be manifested and increased at higher doses of hydrochlorothiazide. Thirty-eight patients who had previously experienced hypokalemia, palpitations, or cardiac arrhythmia were placed on hydroclorothiazide therapy for one to three months and were monitored for arrhythmias after treadmill exercise. The occurrence of premature ventricular contractions correlated significantly with the decrease in serum potassium (r = 0.73, p less than 0.001) and serum magnesium (r = 0.68, p less than 0.001) levels during hydrochlorothiazide therapy and with the product of the change of the two cations (r = 0.81, p less than 0.001).

Primary aldosteronism: computerized tomography in preoperative evaluation.

We reviewed the value of computerized tomography (CT) in the preoperative evaluation of 34 patients with primary aldosteronism. All 34 patients entered a standard protocol including saline suppression testing, abdominal CT scanning, and adrenal venous sampling. Surgical pathologic findings, biochemical determinations, and clinical response to adrenalectomy were the criteria used to evaluate 68 adrenals in 34 patients. Of 36 diseased glands 17 were correctly identified by CT (48%). Of the 32 normal glands, 29 were identified correctly by CT (91%). Thus, CT is not sensitive (0.48), but very specific (0.91) in Conn's syndrome. Our patients were divided into two groups: group 1 were those scanned between 1977 and 1980, group 2 were those scanned from 1981 to 1983 with a high-resolution GE-8800 scanner. CT results in group 2 showed no significant improvement in specificity (0.92), but improvement in sensitivity (0.58) over group 1 (specificity 0.90, sensitivity 0.42). Furthermore, CT is less sensitive in patients with smaller tumors than in those with larger tumors.

The prediction of anatomical morphology of primary aldosteronism using serum 18-hydroxycorticosterone levels.

Serum 18-hydroxycorticosterone, aldosterone, and potassium were measured under basal conditions in 34 patients with documented primary aldosteronism, 10 patients with essential hypertension, and 9 normal subjects. The results revealed that 22 of 23 patients with aldosterone-producing adenomas had 18-hydroxycorticosterone levels greater than 100 ng/dl, and all 9 patients with idiopathic adrenal hyperplasia had plasma levels less than 100 ng/dl. Two patients with unusual macromicronodular hyperplasia of the adrenal glands had levels greater than 100 ng/dl. We found a significant relationship between serum potassium and the ratio of 18-hydroxycorticosterone to aldosterone in patients with idiopathic adrenal hyperplasia, but not in those with an aldosterone-producing adenoma. We conclude that measurement of serum 18-hydroxycorticosterone is a useful predictor of the etiology of primary aldosteronism.

Potassium and magnesium abnormalities: diuretics and arrhythmias in hypertension.

Thiazide diuretics are widely accepted as the cornerstone of antihypertensive treatment programs. Hypokalemia is a commonly encountered metabolic consequence of long-term thiazide therapy but the effect of thiazide on serum magnesium is less well known. Thirty-eight patients (22 low renin, 16 normal renin) with moderate diastolic hypertension were treated with hydrochlorothiazide administered twice a day. The initial daily dose was 50 mg; this was increased at four week intervals to 50 mg, 100 mg, 150 mg, and 200 mg. Dose escalation was discontinued when either normalization blood pressure was attained or the 200 mg dose level was reached. Patients were then maintained with their hydrochlorothiazide dose for 24 weeks of continuous thiazide monotherapy. The serum potassium during the control period was 4.5 +/- 0.2 mmol/liter. During dose escalation and long-term maintenance therapy, the serum potassium and magnesium levels fell in a step wise, dose-dependent fashion. In another 38-patient study, the effects of hydrochlorothiazide therapy (100 mg daily) on the occurrence of premature ventricular contractions were observed during rest as well as during static and dynamic exercise. During rest 0.6 +/- 0.08 premature ventricular contractions per minute (mean +/- SEM) were observed, and during dynamic exercise 0.8 +/- 0.15 premature ventricular contractions per minute. During hydrochlorothiazide therapy (50 or 100 mg per day) premature ventricular contractions per minute were 1.4 and 5.7, respectively. The occurrence of premature ventricular contractions correlated significantly with the decrease observed in serum potassium (r = 0.71, p less than 0.001) and in serum magnesium (r = 0.68, p less than 0.001). Thiazide therapy appears to cause both potassium and magnesium depletion, and decreases in both correlate well with the appearance of ventricular ectopic depolarizations.