Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Program on the Surgical Control of the Hyperlipidemias.

BACKGROUND: In 1990, when the Program on the Surgical Control of the Hyperlipidemias (POSCH) reported its in-trial results strongly supporting the conclusion that effective lipid modification reduces progression of atherosclerosis, the differences for the end points of overall mortality and mortality from atherosclerotic coronary heart disease (ACHD) did not reach statistical significance. METHODS: The Program on the Surgical Control of the Hyperlipidemias recruited men and women with a single documented myocardial infarction between the ages of 30 and 64 years who had a plasma cholesterol level higher than 5.69 mmol/L (220 mg/dL) or higher than 5.17 mmol/L (200 mg/dL) if the low-density lipoprotein cholesterol level was in excess of 3.62 mmol/L (140 mg/dL). Between 1975 and 1983, 838 patients were randomized: 417 to the diet control group and 421 to the diet plus partial ileal bypass intervention group. Mean patient follow-up for this 5-year posttrial report was 14.7 years (range, 12.2-20 years). RESULTS: At 5 years after the trial, statistical significance was obtained for differences in overall mortality (P = .049) and mortality from ACHD (P = .03). Other POSCH end points included overall mortality (left ventricular ejection fraction > or =50%) (P = .01), mortality from ACHD (left ventricular ejection fraction > or =50%) (P = .05), mortality from ACHD and confirmed nonfatal myocardial infarction (P<.001), confirmed nonfatal myocardial infarction (P<.001), mortality from ACHD, confirmed and suspected myocardial infarction and unstable angina (P<.001), incidence of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (P<.001), and onset of clinical peripheral vascular disease (P = .02). There were no statistically significant differences between groups for cerebrovascular events, mortality from non-ACHD, and cancer. All POSCH patients have been available for follow-up. CONCLUSION: At 5 years after the trial, all POSCH mortality and atherosclerosis end points, including overall mortality and mortality from ACHD, demonstrated statistically significant differences between the study groups.

The study of brain function impairment in fetal alcohol syndrome: some fruitful directions for research.

Fetal alcohol syndrome (FAS) is the most prevalent known preventable health hazard to the human fetus by a noxious agent. It is associated with impairments of the central nervous system that are expressed in the forms of mental retardation of varying severity, learning disabilities, attentional deficits and an increased vulnerability to stress. Results of psychophysiological studies of the effects of ethanol on the central nervous system are reviewed, with the aim of exploring how conclusions derived from them can serve as testable hypotheses in FAS research. The experimental methods used in such studies are examined for their applicability to FAS research. It is concluded that FAS research effort will benefit from the inclusion of psychophysiological studies.

Effects of rate of repetitive stimulus presentation on the visual evoked brain potentials of young adults with Down's syndrome.

Visual evoked brain potentials (VEP) to repeated stimuli of several interstimulus intervals (ISI) were recorded from young adults with Down's syndrome (DS). The following results were obtained: (i) An ISI effect previously observed in normals: VEP amplitudes increased with increase in ISI; some ISI effect on latency was also observed; (ii) VEP amplitudes of DS subjects were larger than VEP amplitudes of normals; (iii) VEP peak latencies of DS subjects were longer than VEP peak latencies obtained from normals; (iv) ISI had a more pronounced effect on VEP amplitudes of DS than normal subjects. These results are discussed with respect to CNS differences and issues of attention and information processing.

The effects of neuroleptics on attention in adolescent schizophrenics.

In contrast to studies of adult psychiatric patients, there was no striking difference between vigilance task performance by 11 newly diagnosed, previously untreated adolescent schizophrenics and that of 58 nonpsychotic adolescent comparison subjects. Neuroleptic treatment failed to improve the performance of the schizophrenic subjects. Sedation, a frequent side effect, was associated with significant prolongation of reaction time and an increase in error rate. Attentional characteristics of adolescent schizophrenics appear to resemble those of other disturbed children. Their response to neuroleptics appears to be limited and the deleterious effects of sedation on attention may well outweigh any clinical benefit attributable to sedation. Findings are discussed in terms of methodology and age-related characteristics.

Blood pressure and pulse changes in hyperactive children treated with imipramine and methylphenidate.

The authors found significant increases in systolic and diastolic blood pressure and pulse rate in hyperactive children treated with imipramine. Methylphenidate-treated children showed significant weight loss but no significant changes in blood pressure or pulse. The authors recommend caution in the use of imipramine and suggest the need for further study to determine short- and long-term effects of imipramine on blood pressure.

Clinical comparison of thiothixene and thioridazine in schizophrenic adolescents.

Of 21 schizophrenic adolescents given thiothixene or thioridazine, many responded poorly or experienced sedation. Because sedation necessitates dose reductions, which limit therapeutic response, for schizophrenic adolescents high-potency neuroleptics may be preferable to the more sedating low-potency drugs.

Subgroup analyses of the major clinical endpoints in the Program on the Surgical Control of the Hyperlipidemias (POSCH): overall mortality, atherosclerotic coronary heart disease (ACHD) mortality, and ACHD mortality or myocardial infarction.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a secondary atherosclerosis intervention trial employing partial ileal bypass surgery as the intervention modality. For this report, we analyzed 105 subgroups in 35 variables in POSCH, chosen predominantly for their potential relationship to the risk of atherosclerotic coronary heart disease (ACHD). We defined potential differential effects as those with: (1) an absolute z-value > or = 2.0 for the subgroup, if the absolute z-value for the overall effect was < 2.0; and (2) an absolute z-value > or = 3.0 for the subgroup and a relative risk < or = 0.5, if the absolute z-value for the overall effect was > or = 2.0. For each of three major POSCH endpoints of overall mortality, ACHD mortality and ACHD mortality or confirmed nonfatal myocardial infarction, we found seven subgroups with a differential risk reduction in the surgery group as compared to the control group. Allowing for identical subgroups for more than one endpoint, there were 13 individual subgroups with differential effects. Of these, seven demonstrated internal consistency across endpoints, and five of these seven displaced external consistency with known ACHD risk factors and for biological plausibility: triglyceride concentration > or = 200 mg/dl; cigarette smoking; overt or borderline diabetes mellitus; a Minnesota ECG Q-QS code of 1-1; and obesity. A greater risk reduction, in comparison to the overall treatment effect, by the reduction of a single risk factor, hypercholesterolemia, in patients with at least two major ACHD risk factors was a provocative and an hypothesis-generating outcome of this analysis. The clinical implications of this finding may lead to more aggressive cholesterol intervention in patients with multiple ACHD risk factors.

Program on the Surgical Control of the Hyperlipidemias (POSCH): design and methodology. POSCH Group.

The Program on the Surgical Control of the Hyperlipidemias (POSCH) is a prospective, randomized, controlled, multi-center, secondary, atherosclerosis intervention trial. POSCH addresses the therapeutic arm of the lipid-atherosclerosis theory, i.e. whether lowering of plasma cholesterol is directly related to a reduction in atherosclerosis risk. In this trial, lipid modification is accomplished by the partial ileal bypass operation. Between 1975 and 1983, 838 patients were randomized into this study. All patients were between 30 and 64 years of age, had survived one and only one electrocardiogram and enzyme-documented myocardial infarction, and had a total plasma cholesterol of at least 220 mg/dl or a low density lipoprotein (LDL)-cholesterol of at least 140 mg/dl if the total plasma cholesterol was between 200 and 219 mg/dl after a minimum of 6 weeks of dietary fat and cholesterol restriction. The primary response variable in POSCH is overall mortality. Secondary endpoints include fatal and non-fatal myocardial infarctions, serial electrocardiographic changes, and, most importantly, sequential coronary arteriography changes. The minimum follow-up is currently planned to be 7 years. Study analyses will be made primarily on the "intention to treat" basis. This paper is the first detailed presentation of POSCH design and methodology. Included are descriptions of study design, implementation, and data collection, including data processing, quality assurance/quality surveillance, and patient safety monitoring. POSCH seeks to demonstrate a significant reduction in overall mortality by lipid modification and to validate the use of coronary arteriographic change as a surrogate endpoint for change in coronary heart disease risk.

Familial multiple bilateral pneumothorax associated with Marfan syndrome.

Three members of one family, a father and two sons, inflicted with Marfan syndrome, suffered multiple bilateral episodes of spontaneous pneumothorax that required repeated drainage procedures. The youngest patient also had an episode of unilateral expansion pulmonary edema; he underwent sequential pleural abrasions. Familial pneumothorax is very uncommon, and its association with Marfan syndrome is an exception.

Bronchogenic carcinoma associated with upper aerodigestive cancers.

Of 1,450 patients with upper airway cancers, 189 (13%) had additional cancers. There were 60 cases in which lung cancer occurred after upper airway cancer and a single case in which it preceded upper airway cancer. The occurrence of upper airway plus lung cancer in 61 patients was referred to as multiple airway cancers. The overall incidence of multiple airway cancers was 4.1%, or 1:112 patient-years at risk. The highest incidence of lung cancer was 1:70 patient-years, and this was associated with laryngeal cancer. The mean diagnostic interval between upper airway and lung cancers was 6.1 (0 to 23) years, including nine cases (14.8%) in which the two were synchronous. Triple endoscopy revealed occult lung cancer only once. The use of mediastinoscopy (n = 9) and other surgical staging procedures (n = 9) was limited, because previous treatment of upper airway cancers made such procedures impractical and also because interpretation of findings would have been difficult. Past reports have indicated that lung cancer in association with upper airway cancer is almost invariably squamous cell and almost always develops in men. By contrast, among our 61 patients, the incidence of adenocarcinomas was 24%, and 16 patients or 26% were women. Among patients whose records could be evaluated in this regard, symptoms were present in 27 of 55 (49%); the cancers were in Stage III at presentation in 51%. Outcome was related to symptomatology and to lung cancer stage. The median survivals for symptomatic and asymptomatic patients were 6 and 25 months, respectively (p less than 0.001); the median survivals for patients with Stage I, II, and III lesions were 26, 9, and 6 months, respectively (p less than 0.05). Post-thoracotomy management after surgical-radiation therapy of upper airway cancers (n = 22) was inordinately challenging because of preexisting impairment of the upper airways. We have reached the following conclusions: Patients with upper airway cancer are at high risk for lung cancer of all cell types. When multiple airway cancers occur together, the prognosis is poor; nonetheless, cure of each cancer can be achieved if it is completely and adequately treated. When multiple airway cancers occur synchronously, the more life-threatening cancer should be treated first. When the option exists, the lung cancer should be treated before the upper airway cancer to avoid the impact of previous irradiation and/or surgical treatment of the upper airway cancer upon post-thoracotomy management.

Chondrosarcoma of the bronchus.

A primary chondrosarcoma of the right main bronchus was removed by pneumonectomy in a 74-year-old woman. The presenting symptoms were dyspnea and cough with a lung mass evident for 18 months. She is well and free of tumor 16 months later. Only eight established cases of primary chondrosarcoma arising from the lung, and four originating from the tracheobronchial tree have been previously described. The long preoperative history and the outcome so far confirm the relatively less aggressive character of the tracheobronchial as compared to the lung subdivision of primary pulmonary chondrosarcoma.

Castleman's disease. An uncommon computed tomographic feature.

A case of localized intrathoracic Castleman tumor demonstrated, on CT scan, calcifications in a circumferential distribution. The prevalence of calcifications in Castleman's disease and the differential diagnosis of the above unusual CT findings are discussed.

Penetrating thoracic wounds caused by plastic bullets.

Thoracic penetrating injuries caused by a new plastic bullet were studied to determine the nature of the wounds and the appropriate management. Twenty-six casualties from the Israeli-Palestinian conflict (Intifada) were included. The organs most commonly involved were lung (n = 21), bony chest wall (n = 9), heart (n = 3), and diaphragm. Bleeding was at least moderate in 20 patients, amounting in all patients to an average of 975 ml. Thoracotomy was required in 11 patients (42%) mainly because of cardiac injury (n = 3) and aortic or other arterial bleeding (n = 3). Simple oversewing of severed organs (n = 8) or ligation of bleeding vessels (n = 3) was satisfactory. Two patients died (7.7% mortality); one after major liver resection; the other was dead on arrival. We conclude that plastic bullets have a linear course unless displaced by the bony chest wall, when they tend to fragment and cause simple fractures. Fired from a presumed range of at least 70 m, plastic bullets behave like low-velocity missiles, and tissue destruction is minimal. Management should be similar to that of civilian thoracic penetrating trauma.

Pulmonary carcinoid: presentation, diagnosis, and outcome in 142 cases in Israel and review of 640 cases from the literature.

OBJECTIVE: To determine the characteristic features and outcome of pulmonary carcinoid tumors in Israel. METHODS: Retrospective analysis of the clinicopathologic data and outcome of patients from four major hospitals in Israel in the last 20 years. RESULTS: There were 142 cases of pulmonary carcinoid tumors: typical (n = 128) and atypical (n = 14). We calculated an annual incidence of about 2.3 to 2.8 cases per 1 million population. The ratio of female to male patients was 1.6:1. The prevalence of smoking was similar to the general population in patients with typical carcinoids and twice as high in the atypical group. Bronchial obstruction was the cause of most of the presenting symptoms and signs and included obstructive pneumonitis, pleuritic pain, atelectasis, and dyspnea (41%). Carcinoid syndrome was extremely rare and occurred in only one patient with metastatic disease. Most of the tumors (68%) arose in the major bronchi. Diagnosis was made using fiberoptic bronchoscopy in 52% of patients without evidence of endobronchial hemorrhage. Nodal involvement and distant metastases occurred in 57% and 21%, respectively, in the atypical group, and 10% and 3%, respectively, in the typical group. The treatment of choice was surgical: lobectomy (56%) or pneumonectomy (16%). The respective 5-year survival rates for patients with typical and atypical tumors were 89% and 75% (not significant), and the 10-year survival rates were 82% and 56% (p < 0.05). A review of large series from the literature is presented. CONCLUSION: Pulmonary carcinoid is an uncommon tumor in the Israeli population. With early diagnosis and aggressive surgical therapy, long-term prognosis is excellent.

Percutaneous core needle biopsy in the diagnosis of mediastinal tumors.

OBJECTIVE: to determine the contribution of percutaneous core cutting needle biopsy (PCNB) in the diagnosis of mediastinal tumors. DESIGN: retrospective review of 70 patients with mediastinal lesions who underwent CT-guided PCNB between 1988 and 1996. RESULTS: PCNB provided adequate material in 62/70 cases, giving a total sample rate of 88.6%. Of these 62 patients, 57 were diagnosed correctly by PCNB whereas 5/62 were misdiagnosed as nonspecific inflammation, providing an overall sensitivity of 91.9%. PCNB established a specific histologic diagnosis in 90.3% of the patients, mainly in cases of lymphoma, bronchogenic carcinoma, and thymoma. Pneumothorax was the most commonly encountered complication (11%). Hemoptysis (30-50 ml) occurred in only one (1.6%) of the patients. CONCLUSION: CT guided PCNB is an easy and safe procedure which can provide a precise diagnosis in the majority of mediastinal tumors and can obviate the need for exploratory thoracic surgery in cases which are medically treatable or non-resectable.

The Program on the Surgical Control of the Hyperlipidemias: a status report.

The Program on Surgical Control of the Hyperlipidemias (POSCH) is a multicentered secondary coronary heart disease intervention trial utilizing maximal plasma lipid reduction as achieved by the partial ileal bypass operation. With over 500 patients recruited into this trial at present, the 4-year sequential lipid changes are statistically highly significant and include an approximate 30% plasma total cholesterol and 40% low density lipoprotein (LDL)-cholesterol reduction, with a slight increase in the high density lipoprotein (HDL)-cholesterol and a marked increase in the HDL-cholesterol:LDL-cholesterol ratio of about 75% or higher. A definitive answer to the lipid-atherosclerosis theory corollary--whether a decrease in the plasma cholesterol engenders a reduction in the incidence or severity of atherosclerotic cardiovascular disease--can be expected from these marked lipid changes in POSCH.

Ruptured mycotic aneurysm: a complication of parenteral drug abuse.

Mycotic aneurysms occurred in five narcotics addicts treated between 1969 and 1975. Fever, localized tenderness, swelling, loss of distal pulses, and leukocytosis were common findings. The aneurysms were located in the femoral (two patients), brachial (two), and superior mesenteric arteries (one). They occurred at the site of arterial injection in three patients. In one patient with subacute bacterial endocarditis, an aneurysm of the superior mesenteric artery developed. In one patient, the pathogenesis was uncertain. All patients had rupture of the arterial wall, with hemorrhage contained by adjacent muscle or soft tissue. Four patients were treated by ligation and debridement. One, with preexisting ischemia, required amputation below the knee. One patient underwent repair with autogenous artery. Recurrent hemorrhage necessitated ligation of the artery. In all patients, extensive sepsis and tissue necrosis precluded repair with prosthetic material. All patients survived, without evident of ischemia.

Traumatic diaphragmatic hernia.

The records of 36 patients with traumatic diaphragmatic hernia (TDH) were reviewed. In 14, acute hernias were diagnosed, but the diagnosis was made one month to 15 years after injury in 22 patients with chronic hernia. Seven acute TDHs were due to blunt and seven to penetrating trauma. Four chronic TDHs were due to blunt and 18 to penetrating trauma. Chest pain, abdominal pain, or dyspnea occurred in each acute case and in 18 of 22 chronic cases. Plain chest roentgenograms were abnormal in 33 of 36 cases. Pleural effusion or abnormal diaphragmatic contour were common abnormal findings. Supradiaphragmatic bowel, pathognomonic of TDH, was evident in seven acute and eight chronic hernias. Celiotomy was routinely employed in acute hernias, celiotomy or thoracotomy in chronic hernias. There were three deaths, two with associated CNS injury and one with chronic pulmonary disease.

Management of major arteriovenous fistulas by arteriographic techniques.

Five patients with major symptomatic arteriovenous fistulas were treated between July 1976 and December 1977. In two patients the fistulas were due to trauma; in two others, malignant neoplasms; and in one patient, congenital angiodysplasia. The anatomic location or extent of each arteriovenous fistula would have made direct surgical access to the fistula sites difficult; therefore, it was elected to use arteriographic embolization techniques to attempt definitve obliteration of the fistulas. Wool-tufted wire coli emboli were used in three patients and gelatin sponge-autologous blood clot was used in two patients. These were precisely embolized to the fistula site by superselective catheterization of the feeding artery. Complete obliteration of the fistulas was achieved in each case with no morbidity. Follow-up clinical and ateriographic examination confirmed persistence of fistula closure.

Hepatic trauma.

Two hundred thirty-three patients were operated on for hepatic trauma during a two-year period. There were 101 patients with stab wounds, 90 with gunshot wounds, and 42 with blunt trauma. There were 56 isolated liver injuries. Three hundred seventy-five associated injuries occurred among the remaining 177 patients. The majority of patients required only drainage. "Liver sutures" were employed in 66 patients. Only 18 patients required débridement, resection, or packing. Twenty-eight patients (12%) died. Perioperatively, 13 patients died of hemorrhage from the hepatic wound and from the associated major vascular injuries that were present in eight of the 13 cases. The remaining deaths were not primarily a consequence of the hepatic wound. Control of hemorrhage remains the dominant consideration in the treatment of major hepatic wounds.