Recreational use of aminorex and pulmonary hypertension

Pulmonary hypertension has been associated with ingestion of the appetite suppressant aminorex. A similar compound, 4-methyl-aminorex (street names, "U-4-E-uh" [pronounced euphoria] or "ice"), is a "designer" drug with central stimulant activity. This drug was discovered on the property of three individuals with diagnoses of pulmonary hypertension. The association between "recreational" aminorex manufacture and ingestion and the development of pulmonary hypertension is described.     

Patterns of anomalous pulmonary venous connection/drainage in hypoplastic left heart syndrome: diagnostic role of Doppler color flow mapping and surgical implications.

Differentiation between anomalous connection and anomalous drainage of the pulmonary veins in hypoplastic left heart syndrome is important before either the Norwood procedure or heart transplantation is performed. To determine the prevalence of echocardiographically detected anomalous connection or drainage, or both, of pulmonary veins in patients with this syndrome, preoperative two-dimensional echocardiographic and Doppler color flow mapping studies of 317 patients who underwent the stage I Norwood procedure were reviewed. The term "connection" was used to describe the precise anatomic attachment of the pulmonary veins and the term "drainage" to describe the physiologic end point of pulmonary venous flow. Twenty patients (6.3%) had anomalous connection or drainage, or both, of the pulmonary veins by preoperative echocardiographic and Doppler examination. The subcostal and suprasternal scans best showed the anatomic details of the pulmonary veins. All these patterns were confirmed intraoperatively and could be grouped as follows: 1) partial anomalous connection and drainage (two patients); 2) total anomalous connection and drainage (eight patients); 3) normal connection with total anomalous drainage (eight patients); and 4) normal connection with partial anomalous drainage (two patients). The advantage of adding Doppler color flow mapping to two-dimensional echocardiography and conventional Doppler study was clearly demonstrated in the detection of small accessory vertical veins, their course and the presence or absence of obstruction. Doppler color flow mapping was especially helpful in detecting anomalous drainage of the right pulmonary veins to the right of the superior attachment of the septum primum.     

Prognostic value of normal coronary angiography

Coronary angiography is the "gold standard" for coronary artery disease (CAD). It is considered either normal or subnormal without any lesion (endocoronary echography often demonstrates atheroma), or in presence of a < 50% stenosis. Nevertheless, the risk of plaque rupture is not well correlated with the degree stenosis. Despite the frequent presence of non-significant atheroma, is a normal coronarography really of a good prognosis? Between January and September 1997, 136 of 600 (22.6%) angiographies were considered as normal. The indications were: "CAD suspicion" (n = 77), "preoperative angiography of valvulopathy" (n = 38), and "angioplasty control" (n = 22). The arteries were strictly normal for 86 patients (63%) and a < 50% stenosis was found in 50 patients (37%); 108 patients (80.1%) were followed for 18 +/- 3 months: eight non coronary deaths were reported: four postoperative deaths in "valvular group", two pulmonary embolisms and two pulmonary neoplasm's in "CAD suspicion group". No myocardial infarction was reported and one unstable angina was documented. Despite the frequency of non-significant atheroma, an acute coronary syndrome exceptionally complicates a "normal" coronarography.     

"Masked" pulmonary venous obstruction in patients with isomerism of the right atrial appendages: an overstated association

Isomerism of the right atrial appendages is associated with anomalies of pulmonary venous return, which may be obstructive. The associated pulmonary arterial obstruction, however, has been reported to "mask" the pulmonary venous obstruction, with resultant pulmonary edema following augmentation of the flow of blood to the lungs. We postulated that the frequency of "masked" pulmonary venous obstruction has been over-reported in the literature. To ascertain the true situation, we evaluated the frequency of "masked" pulmonary venous obstruction in a large, unselected, group of patients with isomerism of the right atrial appendages. We evaluated the clinical, anatomic, and radiographic data of 65 newborns seen with this syndrome since 1970. Development of pulmonary venous obstruction, both before and after systemic-to-pulmonary shunting and/or infusion of prostaglandin E1, was determined and correlated to clinical and radiographic findings. Of the 65 patients, 19 (29%) were ultimately diagnosed with pulmonary venous obstruction. The pulmonary veins themselves connected in infradiaphragmatic fashion in 10 patients, supracardiac in 3, to the atriums directly in 1, and in mixed fashion in the other 5. Pulmonary venous obstruction was readily apparent in 15 of the 19, as demonstrated by pulmonary edema on initial chest radiography. The remaining four cases ultimately diagnosed with pulmonary venous obstruction received augmentation of pulmonary blood flow with resultant pulmonary edema. Of these four severely cyanosed patients, pulmonary vascular markings on the initial chest radiograph had been normal in one but increased in three. Due to the presence of these clinical markers, they do not truly represent "masked" pulmonary venous obstruction. Except for two patients with minimally obstructed pulmonary arterial blood flow, 44 patients without pulmonary venous obstruction had normal or decreased pulmonary vascular markings at presentation. Of these 44, 14 received infusions of prostaglandin E1, with none developing pulmonary edema. We conclude that pulmonary venous obstruction is usually readily apparent at time of presentation in patients with right isomerism, and that "masked" pulmonary venous is a very rare event which has been over-emphasized in the literature. Careful evaluation of clinical and radiographic findings at time of presentation can correctly identify pulmonary venous obstruction in such patients.     

Pulmonary disease associated with L-tryptophan-induced eosinophilic myalgia syndrome. Clinical and pathologic features

Tablets and capsules containing the essential amino acid L-tryptophan are currently being investigated as a cause of the newly recognized eosinophilia/myalgia syndrome. In the five histologically documented cases reported herein, L-tryptophan ingestion was associated with prominent pulmonary complications. All patients were women ranging from 34 to 65 years, and all presented with respiratory symptoms that began after one to nine months of L-tryptophan therapy. Peripheral eosinophilia was present in four patients as were bilateral interstitial infiltrates on chest roentgenograms. One patient had a normal chest roentgenogram. Lung biopsies were done in all patients and biopsy specimens showed a vasculitis and perivasculitis associated with a mild chronic interstitial pneumonitis and eosinophilia. Three patients had clinical and/or histologic evidence of pulmonary hypertension, and one had a follicular bronchiolitis. Four patients recovered promptly with steroid therapy and discontinuation of L-tryptophan therapy, and one patient has had minimal symptomatic improvement.     

Intermediate syndrome of platelet dysfunction

We studied eight patients with intermittent bleeding episodes usually following trauma and associated with the ingestion of medicine known to interfere with platelet function. All patients had a normal or minimally prolonged baseline bleeding time. All had a normal platelet count, glass bead retention test, and platelet serotonin content and a variable pattern of abnormalities in prothrombin consumption and platelet factor 3 availability. However, all showed abnormal platelet aggregation reactions using epinephrine, adenosine diphosphate, and collagen. Following the administration of 975 mg aspirin, our patients' bleeding times became prolonged to a greater extent than the bleeding times of normal controls (range 13 to greater than 20 min). Review of the literature showed approximately 5% of "normal" controls had findings similar to those we report. We believe we are describing a group of individuals with an intermediate form of platelet dysfunction. Although their bleeding diathesis is not as severe as that of patients with platelet dysfunction syndromes previoulsy described, they do bleed significantly when subjected to trauma following the ingestion of drugs such as aspirin. We propose that this defect is common and should be screened for. The aspirin tolerance test is a simple test for detecting these patients.     

Different Response of Gastric Inhibitory Polypeptide to Glucose and Fat from Duodenum and Jejunum

Gastric inhibitory polypeptide (GIP), insulin, and blood glucose after ingestion of glucose or fat were examined in patients after gastrectomy with esophagojejunostomy or esophagoduodenostomy. After a glucose load patients without duodenal passage had significantly higher glucose and significantly smaller insulin levels than patients with duodenal passage. The fasting levels of serum immunoreactive GIP were moderately elevated and reached significantly higher levels after oral glucose ingestion in both gastrectomized groups as compared with normal subjects. In patients with preserved duodenal passage serum IR-GIP levels peaked earlier and were significantly higher than in patients without duodenal passage. In contrast to the finding after oral glucose ingestion, the IR-GIP response to an oral fat load was nearly twofold greater in patients without duodenal passage than in patients with duodenal continence. Thus, glucose-induced GIP release is mainly of duodenal and fat-induced GIP release mainly of jejunal origin. This suggests the existence of two types of GIP cells.     

Cardiopulmonary hemodynamics in systemic sclerosis and response to nifedipine and captopril

PURPOSE: This prospective study was performed to evaluate the response of the cardiopulmonary vasculature to two vasodilators in patients with systemic sclerosis and either minimal or no central hemodynamic abnormalities. PATIENTS AND METHODS: Twenty patients with systemic sclerosis, Raynaud's phenomenon (19 of 20 patients), and clinically normal cardiac function underwent right heart catheterization. Rest and exercise hemodynamic measurements, including cardiac output by thermodilution, were performed before and after oral administration of nifedipine 20 mg and captopril 25 mg. RESULTS: Half of the patients had normal hemodynamics (Group A); the other half (Group B) had abnormal baseline elevations in pulmonary vascular resistance and four of them showed "borderline" pulmonary arterial hypertension. Group A, with significantly shorter disease duration compared with Group B, responded poorly to nifedipine and captopril. However, Group B had significant decreases in pulmonary vascular resistance (from 148 +/- 20 to normal levels of 94 +/- 21 dynes.second.cm-5) and pulmonary mean pressure in response to nifedipine treatment but not to captopril. CONCLUSION: These observations show a short-term beneficial effect of nifedipine in the cardiopulmonary vasculature of patients with systemic sclerosis and suggest that a potentially reversible vasoconstrictive element is included in the vascular lesion of this disorder.     

Different response of gastric inhibitory polypeptide to glucose and fat from duodenum and jejunum

Gastric inhibitory polypeptide (GIP), insulin, and blood glucose after ingestion of glucose or fat were examined in patients after gastrectomy with esophagojejunostomy or esophagoduodenostomy. After a glucose load patients without duodenal passage had significantly higher glucose and significantly smaller insulin levels than patients with duodenal passage. The fasting levels of serum immunoreactive GIP were moderately elevated and reached significantly higher levels after oral glucose ingestion in both gastrectomized groups as compared with normal subjects. In patients with preserved duodenal passage serum IR-GIP levels peaked earlier and were significantly higher than in patients without duodenal passage. In contrast to the finding after oral glucose ingestion, the IR-GIP response to an oral fat load was nearly twofold greater in patients without duodenal passage than in patients with duodenal continence. Thus, glucose-induced GIP release is mainly of duodenal and fat-induced GIP release mainly of jejunal origin. This suggests the existence of two types of GIP cells.     

Insulin production rate,hepatic insulin retention and splanchnic carbohydrate metabolism after oral glucose ingestion in hyperinsulinaemic Type 2 (non-insulin-dependent) diabetes mellitus

Summary To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143±4% ideal body weight; mean±SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, -hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57±0.28 pmol.kg^-1. min^-1) than in healthy control subjects (1.68±0.17 pmol.kg^-1. min^-1; p<0.01). After ingestion of 25 g glucose, the cumulative insulin production rate exceeded normal values (p < 0.05), but was below normal with 100 g glucose (p < 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54±3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p < 0.005). Splanchnic output of pyruvate (p < 0.025), lactate (p < 0.01), and -hydroxybutyrate (p < 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.     

Recombinant DNA risk assessment studies in humans: efficacy of poorly mobilizable plasmids in biologic containment

Recombinant DNA risk assessment studies quantitated the mobilizability of "safe" plasmid pBR325, in comparison with readily mobilizable plasmid pJBK5 (chloramphenicol and tetracycline resistant). Of 15 volunteers who became colonized after ingestion of 5 X 10(10) Escherichia coli HS-4, a normal human flora strain containing pJBK5 and daily oral tetracycline, nine manifested transfer of pJBK5 to normal flora by means of triparental mating. In contrast, none of 12 other volunteers cocolonized with HS-4 bearing "safe" pBR325 and normal flora showed transfer (P = 0.001), despite ingestion of tetracycline. To accomplish transfer directly, E coli HS-4 containing both pBR325 and a derepressed, conjugative plasmid (F-amp) was fed to two groups of volunteers. Transfer of pBR325 to normal flora occurred in 13 of 18 volunteers taking daily tetracycline but in none of eight who did not (P less than 0.002). Nor were transconjugants detected, despite tetracycline ingestion, in five volunteers who ingested and excreted E coli K12 (pBR325 plus F-amp).     

THE EFFECT OF ALCOHOL,BARBITURATE, AND DIAZEPAM ON HYPOTHALAMIC/PITUITARY/ADRENAL FUNCTION IN CHRONIC ALCOHOLICS

Investigations of hypothalamic/pituitary/adrenal function in chronic alcoholics by measurement of plasma-" cortisol " responses to various stimuli revealed several pronounced differences from normal. In acutely withdrawn alcoholics the 9 A.M. plasma-" cortisol" level was higher than normal after about 12 hours without alcohol and fell after the ingestion of moderate amounts of alcohol, instead of rising as it did in normal healthy patients. In acutely withdrawn alcoholics, amylo-barbitone, like alcohol, caused a significant fall in plasma-" cortisol " levels between 9 A.M. and midday, whereas diazepam, in sufficient amounts to allay anxiety and produce subjective improvement, or placebo had no significant effect on the plasma-" cortisol" level.     

Transient neonatal tricuspid regurgitation: a Doppler echocardiographic study of three cases.

Three patients with normal hearts and no pulmonary abnormality had neonatal tricuspid regurgitation causing cardiorespiratory distress and cyanosis. The signs of tricuspid regurgitation resolved over a few weeks. In the acute phase echocardiography showed gross dilatation of the right atrium and ventricle. The interatrial septum bulged into the left atrium during the whole cardiac cycle. Doppler echocardiography showed clinically significant tricuspid regurgitation, a right to left shunt through the foramen ovale, reduced flow through the pulmonary valve, and in two patients ductal flow into the pulmonary artery. In one patient tricuspid regurgitation was so great that it impeded the opening of the pulmonary valve and produced functional "atresia" of the pulmonary valve. The presence of regurgitant blood flow through the pulmonary valve showed that the "atresia" was functional rather than organic. Doppler echocardiographic study is useful in distinguishing functional neonatal tricuspid regurgitation from structural abnormality of the tricuspid valve.     

Manometry during Food Ingestion Aids in the Diagnosis of Diffuse Esophageal Spasm

It has been shown that food ingestion can provoke esophageal motor abnormalities in patients with otherwise normal manometry. Such motor abnormalities are usually nonspecific in character. We now report water swallow and food ingestion data on 12 patients with a history of dysphagia and/or chest pain who satisfied strict manometric diagnostic requirements for diffuse esophageal spasm. Three of these patients had normal water swallow manometry, yet, during food ingestion, showed manometric evidence of diffuse esophageal spasm. In the other nine patients, the occurrence of nonperistaltic contractions was greater, and there was a greater incidence of nonperistaltic contractions of 100 mm Hg or more after ingestion of food. We conclude that food ingestion increases the diagnostic yield of manometric testing for diffuse esophageal spasm and, not infrequently, magnifies an abnormality seen during standard water-swallow testing.     

Transient neonatal tricuspid regurgitation: a Doppler echocardiographic study of three cases

Three patients with normal hearts and no pulmonary abnormality had neonatal tricuspid regurgitation causing cardiorespiratory distress and cyanosis. The signs of tricuspid regurgitation resolved over a few weeks. In the acute phase echocardiography showed gross dilatation of the right atrium and ventricle. The interatrial septum bulged into the left atrium during the whole cardiac cycle. Doppler echocardiography showed clinically significant tricuspid regurgitation, a right to left shunt through the foramen ovale, reduced flow through the pulmonary valve, and in two patients ductal flow into the pulmonary artery. In one patient tricuspid regurgitation was so great that it impeded the opening of the pulmonary valve and produced functional "atresia" of the pulmonary valve. The presence of regurgitant blood flow through the pulmonary valve showed that the "atresia" was functional rather than organic. Doppler echocardiographic study is useful in distinguishing functional neonatal tricuspid regurgitation from structural abnormality of the tricuspid valve.     

Functional assessment of the Fontan operation: combined M-mode, two-dimensional and Doppler echocardiographic studies

Combined M-mode, two-dimensional and Doppler echocardiographic studies were used to assess the postoperative status of 33 patients who had undergone the modified Fontan procedure. Twenty-four patients had surgical repair with use of a simple direct right atrium to pulmonary artery anastomosis. The remaining patients had repair with use of a prosthesis or associated Glenn shunt. Twenty-seven patients were studied early in the postoperative period (2 months or less) and the remaining patients were studied up to 6 years postoperatively. A total of 36 examinations were performed. Of the 33 patients, 13 had tricuspid atresia, 12 had double inlet left ventricle with hypoplastic right ventricular outlet chamber and 8 had complex lesions with atrioventricular canal, double outlet right ventricle or a hypoplastic ventricle. Postoperative assessment by M-mode and two-dimensional echocardiography demonstrated normal or mildly reduced ventricular function (ejection fraction greater than 40%) in 22 patients. In 24 patients, a "normal" flow pattern was observed in the pulmonary artery by pulsed Doppler echocardiography, with predominant diastolic flow and accentuation by atrial systole somewhat similar to the venous flow pattern observed in the superior vena cava. "Abnormal" flow patterns (disorganized systolic flow, absence of atrial waves and little or no increase with inspiration) were observed in nine patients with reduced ventricular function or residual shunt. Continuous wave Doppler study also demonstrated mild dynamic subaortic obstruction in two patients. Combined pulsed and continuous wave studies showed atrioventricular valve insufficiency in 10 patients. Follow-up studies revealed a satisfactory clinical course in most patients. Three patients died approximately 4 to 8 months after their Fontan operation.     

Pulmonary vascular obstruction in the adult respiratory distress syndrome

Pulmonary vascular obstruction is most likely to occur in patients with the severest form of ARDS. Obstruction has been ascribed to fibrin thrombosis and to activation of the blood coagulation system, both well-documented in ARDS. The obstruction has been postulated to occur in two stages during post-traumatic ARDS: an initial transient pulmonary vasoconstriction, attributable to platelet and leukocyte aggregation and the release of vasoactive substances; and, two to five days post injury, a more malignant "delayed microembolism" stage, attributable to the development of protein-rich edema and fibrin deposition in the lungs. Bedside balloon occlusion pulmonary angiography, in a single exposure, allows identification of intraluminal filling defects and occlusions of arteries greater than or equal to 1.0 mm in diameter, irregularity and decreased filling of side branch arteries 0.5 to 1.0 mm in diameter, and decreased filling of the pulmonary microvascular background. Plain radiography findings correlate poorly with angiography results, but the mortality rate of patients who exhibit angiographic evidence of obstruction is twice as high as it is in patients with normal angiography.     

Permeability pulmonary edema following lung resection

The etiology of edema associated with pulmonary resection was investigated in five patients during the immediate postoperative period. Three patients received pneumonectomy while two patients had one lobe resected. All patients suffered from severe respiratory distress and had x-ray evidence of diffuse interstitial pulmonary edema within 12 hours of surgery. Hemodynamic data were obtained with radial and pulmonary artery catheters. Edema fluid was obtained along with blood samples for simultaneous determination of protein and albumin content. All patients studied had normal or high cardiac output, normal cardiac filling pressures, and edema fluid protein to serum protein ratio of 0.6 or greater suggestive of permeability changes contributing to edema fluid accumulation. Calculated shunt fraction exceeded 25 percent in all patients. Pulmonary edema has been noted in patients following pulmonary resection in the early postoperative period. In patients reviewed here, two factors appeared to be significant. First is an increase in pulmonary capillary pressure associated with passage of a normal to high cardiac output in a reduced volume pulmonary vascular bed. The second factor, as demonstrated by protein content in the edema fluid, is injury to the alveolar capillary membrane.     

Defective lung macrophages in pulmonary alveolar proteinosis.

Lung macrophages obtained by segmental lavage from three patients with pulmonary alveolar proteinosis were studied in vitro. The macrophages exhibited morphologic abnormalities including excessive lipid accumulation and giant secondary lysosome formation. These cells survived poorly in tissue culture, showed impaired chemotactic activity, and had decreased adhesiveness to glass. They phagocytized normally but had substantially decreased capacity to kill ingested Candida pseudotropicalis. Evidence was obtained that the macrophage defect was acquired and probably related to ingestion of the proteinaceous alveolar fluid. Peripheral blood monocyte function was normal in one patient and morphologic abnormalities were produced in normal monocyte-derived macrophages cultured with proteinaceous lavage material. These studies suggest that the lung macrophage in alveolar proteinosis is a defective cell as a consequence of an abnormal pulmonary environment.     

Pulmonary atresia with ventricular septal defect. Selection of patients for systemic-to-pulmonary artery shunt based on echocardiography.

From January 1987 to December 1988, in 22 infants with PAVSD, the diagnostic results obtained with echocardiography (two-dimensional, Doppler, and color) were prospectively compared to the angiocardiographic findings. We classified into group 1 patients with confluent and good-sized pulmonary (greater than or equal to 3 mm) arteries, single ductus arteriosus, and normal pulmonary venous connections ("favorable pattern"). The other patients with PAVSD were classified into group 2 ("unfavorable pattern"). The intracardiac anatomy, the morphology of the pulmonary arteries, and the pattern of pulmonary blood supply and pulmonary venous connection were correctly identified with echocardiography in all but one patient, who was erroneously considered to be in group 2. No false-positive of the "favorable pattern" (group 1) was detected. Echocardiography is an effective tool in infants with PAVSD, in order to discriminate cases with "favorable" and "unfavorable" patterns of pulmonary arteries, pulmonary blood supply, and pulmonary veins. The first group with the "favorable pattern" may be considered for systemic-to-pulmonary shunt surgery without angiocardiography. Based on this experience from January to December 1989, four patients with this "favorable pattern" underwent a successful systemic-to-pulmonary artery shunt with an echocardiographic diagnosis alone.