Effects of l-amphetamine sulfate on cognitive function in multiple sclerosis patients.

We evaluated the effects of the levo (l) enantiomer of amphetamine sulfate on cognitive function in multiple sclerosis (MS) patients. Using a counterbalanced within-subjects design, 19 MS patients received four single-dose administrations of placebo, 15 mg, 30 mg, or 45 mg of l-amphetamine. Neuropsychological tests measuring processing speed and memory served as the primary outcomes. Performance on tests of processing speed were improved following the 45 mg condition and the largest effects were observed on the Symbol Digit Modalities Test, which measures visual processing speed and working memory. While episodic memory test effects were in the expected direction, the findings were not statistically significant. These preliminary findings show promise for the use of l-amphetamine for the symptomatic treatment of slowed mental processing in MS. Further placebo-controlled trials are needed to confirm these findings.

Dual cell seeding and the use of zymogen tissue plasminogen activator to improve cell retention on polytetrafluoroethylene grafts.

OBJECTIVE: The purpose of this study was to enhance the retention of seeded endothelial cells (EC) on prosthetic vascular grafts. Dual-layer EC and smooth muscle cell (SMC) seeding and gene transfer of a zymogen tissue plasminogen activator gene (tPA) into seeded EC were studied. METHODS: Polytetrafluoroethylene (PTFE) grafts were precoated with fibronectin, seeded with SMC followed by EC a day later, and then, 24 hours later, exposed to an in vitro flow system for 1 hour. Cell retention rates were determined for grafts seeded with EC only, a dual layer of EC on top of SMC, EC transduced with wild-type tPA, and EC transduced with zymogen tPA. RESULTS: Seeding efficiency of PTFE pretreated with fibronectin was 260 +/- 8 cell/mm(2). After exposure to flow, only 39% +/- 14% of the EC were retained when EC were seeded alone, whereas 73% +/- 22% of EC remained on grafts when EC were seeded on top of SMC (P <.001, n = 10). The enzyme activity of a mutant zymogen tPA in absence of fibrin was 14 +/- 1 IU/mL, which is 3.6-fold lower than that in the presence of fibrin (50 +/- 19 IU/mL), whereas fibrin has no effect on the wild-type tPA activity. EC expressing a high level of wild-type tPA had a lower retention rate (37%) when compared with normal EC (45%). EC expressing the mutant zymogen tPA had an improved retention rate (54%, P =.001, n = 10) in absence of fibrin, whereas its retention rate was reduced to 43% when the cells were exposed to fibrin. CONCLUSION: SMC seeded between EC and PTFE improves EC retention in vitro. Transduction of zymogen tPA increases thrombolytic ability of seeded cells with less adverse impact on cell retention than wild-type tPA.

Lesiones vasculares abdominales. El desafío del cirujano traumatológico / Abdominal vascular lesions. A challenge for the trauma surgeon

Introducción. Las lesiones vasculares abdominales presentan los mayores índices de mortalidad y morbilidad de entre todas las lesiones que puede sufrir un enfermo traumático. Método. Revisión de la clínica, diagnóstico, vías de abordaje y tratamiento de los pacientes con lesiones vasculares intraabdominales, basada en la experiencia en el tratamiento de 302 enfermos. Resultados. Las heridas penetrantes abdominales constituyen entre el 90 y el 95 por ciento de las lesiones que afectan a los vasos abdominales. La lesión abdominal multiorgánica es frecuente. Los hallazgos clínicos compatibles con hemoperitoneo o peritonitis y la ausencia de pulsos femorales son tributarios de laparotomía. En los pacientes que presentan paro cardiorrespiratorio se debe realizar una toracotomía de urgencia para el masaje cardíaco abierto y el pinzamiento aórtico. La mortalidad global es del 54 por ciento y la exsanguinación representa el 85 por ciento de la misma. El síndrome compartimental en el abdomen y en las extremidades, así como el círculo vicioso de la acidosis, la hipotermia y la coagulopatía, son las principales complicaciones. Conclusiones. Las lesiones vasculares abdominales presentan una alta mortalidad y morbilidad. El conocimiento anatómico del retroperitoneo y de las vías de abordaje de los vasos, así como una exploración clínica adecuada, ayudarán a disminuir las complicaciones y la mortalidad de estos pacientes (AU)

The Texas Medication Algorithm Project Patient and Family Education Program: a consumer-guided initiative.

Educating patients with mental illness and their families about the illness and its treatment is essential to successful medication (disease) management. Specifically, education provides patients and families with the background they need to participate in treatment planning and implementation as full "partners" with clinicians. Thus, education increases the probability that appropriate and accurate treatment decisions will be made and that a treatment regimen will be followed. The Texas Medication Algorithm Project (TMAP) has incorporated these concepts into its philosophy of care and accordingly created a Patient and Family Education Program (PFEP) to complement the utilization of medication algorithms for the treatment of schizophrenic, bipolar, and major depressive disorders. This article describes how a team of mental health consumers, advocates, and professionals developed and implemented the PFEP. In keeping with the TMAP philosophy of care, consumers were true partners in the program's development and implementation. They not only created several components of the program and incorporated the consumer perspective, but they also served as program trainers and advocates. Initially, PFEP provides basic and subsequently more in-depth information about the illness and its treatment, including such topics as symptom monitoring and management and self-advocacy with one's treatment team. It includes written, pictorial, videotaped, and other media used in a phased manner by clinicians and consumer educators, in either individual or group formats.

Vascular smooth muscle cell apoptosis in aneurysmal, occlusive, and normal human aortas.

PURPOSE: Apoptosis is a physiologic mechanism of cell death that regulates mass and architecture in many tissues. Apoptosis has been described as a feature in human vascular atherosclerosis and large vessel structural integrity. We examined the extent of vascular smooth muscle cell (VSMC) apoptosis in aneurysmal, occlusive, and normal human aortic tissue. METHODS: Tissue samples of aneurysmal, occlusive, and normal human infrarenal aorta were evaluated. DNA fragmentation detection methods, immunohistochemistry, and DNA electrophoresis determined VSMC density, VSMC apoptosis, and apoptosis markers. Apoptotic cells and VSMC nuclei were counted with the use of computer-generated image analysis. Aortic subtypes were compared statistically by analysis of variance. RESULTS: Seventeen aneurysmal, ten occlusive, and five normal human aortas were evaluated. By alpha(1)-actin immunostaining, VSMC density was least in aneurysmal aortas (271.8 +/- 13.5 cells/high-power field [HPF]) compared with occlusive aorta (278.2 +/- 39.4 cells/HPF) and normal aortas (291.0 +/- 25.4 cells/HPF; P = not significant). Presence of apoptotic VSMCs was demonstrated by terminal deoxynucleotidyl transferase fragment end labeling and propidium iodide nuclear staining. VSMC apoptosis was greatest within aneurysmal aortas with 11.7 +/- 1.5 cells/HPF compared with occlusive aortas with 3.3 +/- 0. 8 cells/HPF (P <.05) and normal aortas with 3.75 +/- 4.6 cells/HPF (P <.05). Significant differences in apoptosis markers, p53 or bcl-2, could not be demonstrated by immunohistochemistry or DNA electrophoresis in aortic subtypes. CONCLUSION: Apoptosis of VSMCs is increased and VSMC density is decreased within the medial layer of aneurysmal aortic tissue. Structural degeneration of aortic tissue at the cellular level contributes to aneurysmal formation.

Combined carotid endarterectomy and coronary artery bypass grafting in asymptomatic carotid artery stenosis.

The role of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) in patients with severe asymptomatic carotid artery disease and concurrent symptomatic coronary artery disease is controversial. The objective of this report is to investigate the safety of combined CEA/CABG. The medical records of 30 patients who underwent combined CEA/CABG for coexistent asymptomatic carotid and symptomatic coronary artery occlusive disease were reviewed. All patients were scheduled for either elective or urgent myocardial revascularization due to their symptomatic coronary artery disease. Color-flow duplex scanning identified internal carotid artery stenosis of 80 to 99 per cent in 28 patients (93%) and 50 to 79 per cent in 2 patients (7%). Seventeen patients (57%) were male. The mean age was 64 +/- 10 years (range, 42-84 years). Contralateral internal carotid artery occlusion was present in four patients. Severe left main coronary artery disease was present in 12 patients (40%) and 7 patients (23%) had an ejection fraction of less than 50 per cent. There were no perioperative deaths or strokes. One patient suffered a myocardial infarction on postoperative day 1. This study demonstrates the safety of combined CEA/CABG for coexistent coronary and asymptomatic carotid disease. Using this surgical approach for critical coexistent disease may minimize the incidence of perioperative cerebrovascular complications in patients undergoing CABG.

Extended resection for locally advanced colorectal carcinoma.

BACKGROUND: The purpose of this study was to determine the therapeutic benefit of multivisceral resection (MVR) in patients with locally advanced colorectal carcinomas. METHODS: The study population was composed of 118 patients whose resection of the primary lesion included one or more adhesed adjacent secondary organs or structures (ASOS). Tumors were staged as B3 (T4,N0) and as C3 (T4,N1-3). Adhesions were classified as invasive (B3+,C3+) or inflammatory (B3-, C3-). RESULTS: Sixty-four patients were staged B3 and 54 C3. Eighty-one were classified B3+/C3+. Fifty-nine percent of patients had ASOS resected, 29% had two resected, and the remaining 12% had three or four resected. Actuarial 5-year survival rates were 62% and 38% (p = 0.017) for B3 and C3 lesions, respectively. The 5-year survival rates were 78% for patients with B3- tumors and 58% for those with B3+ tumors (p = 0.043), and 34% for patients with C3+ tumors and 64% for those with C3- tumors (p = NS). The 5-year survival rates were 71% for patients with B3-/C3- tumors and 47% for those with B3+/C3+ tumors (p = NS). The 5-year survival rates after resection of one ASOS, two ASOS, and three or four ASOS were 52%, 55%, and 38%, respectively (P = NS). CONCLUSIONS: There is no statistically significant difference in the 5-year survival rates when multiple ASOS are resected; therefore, an aggressive surgical approach is warranted.

Simultaneous correction of malrotation and gastroesophageal reflux in infants.

Gastroesophageal reflux (GER) is often associated with gastrointestinal malrotation in infants. Primary correction of the malrotation, reserving a secondary antireflux procedure for those patients with persistent symptoms of GER, is most commonly practiced. This decision is based on the notion that an antireflux procedure may be unnecessary and is associated with added morbidity. We retrospectively reviewed 12 infants with GER and malrotation. All infants had symptoms attributed to GER and/or malrotation. A control group of seven infants with malrotation only was included for comparison of operative duration and postoperative recovery. Infants who received concurrent Ladd and Nissen procedures (Group 1, n=8) had immediate resolution of symptoms. Infants treated by Ladd procedure alone (Group 2, n=4), had persistent symptoms, despite postoperative medical therapy. A subsequent antireflux procedure was necessary. Comparison of operative times showed that a simultaneous procedure added, on average, 35 minutes to the Ladd procedure. Postoperative feeding and hospital stay were comparable between Group 1 and the control group. In contrast, Group 2 patients had longer hospitalizations due to ineffective medical therapy for persistent GER. No significant morbidity was noted. We recommend comprehensive surgical treatment with concurrent Ladd and Nissen procedures. This approach provides expedient and effective treatment of GER and malrotation, with minimal increase in operative time and no increase in morbidity .

Operative treatment of gastroesophageal reflux in low birth weight infants.

Operative correction of symptomatic gastroesophageal reflux (GER) has been used frequently and successfully in both children and larger infants for many years. In contrast, surgical repair of GER has been applied relatively sparingly in very small infants because of perceived technical and postoperative difficulties. We retrospectively reviewed our experience with Nissen fundoplications performed for symptomatic GER in low birth weight (LBW) infants ( < or = 2500 grams the time of surgery). Twenty-one consecutive cases from 1988 to 1993 were evaluated. At the time of surgery, the average age was 9.1 weeks and the average weight was 2100 grams (range, 1220 to 2500 grams). All infants had failed a trial of medical management. Follow-up from 1 month to 5 years showed no intraoperative complications and resolution of symptoms in 91 per cent of our patients. Technical factors found to enhance the success of the operative repairs included appropriately sized dilators, division of the short gastric vessels, and a loose 360-degree wrap. With suitable technique, the surgical management of symptomatic GER can be performed safely in small infants.

Interactions of dietary methionine, lead and lindane in rats.

The effects of dietary methionine on lead and lindane toxicities in rats were studied in two experiments. Rats were fed methionine-deficient (60% of requirement) or methionine-sufficient soy protein-based diets with lead acetate added (10,000 mg/kg Pb) and treated with a single dose of lindane (25% of LD50 or 88 mg/kg, p.o.) in both experiments. In experiment I, all rats were fed ad libitum. In experiment II, rats fed the methionine-sufficient diet were pair-fed to rats fed the methionine-deficient diet. In experiments I and II, the methionine-sufficient and the methionine-deficient rats had decreased final body weights, increased liver weights, decreased hematocrits, and no changes in glutathione S-transferase activity when compared to a control group. Lead + lindane treatments increased liver glutathione levels in the methionine-sufficient and methionine-deficient rats in both experiments. However, in experiment II (pair-feeding), the methionine-sufficient rats had a much greater level of liver glutathione than the methionine-deficient rats. The methionine status of the animals seems to be an important factor in determining the liver glutathione level of pair-fed rats treated with lead + lindane.

Radiation measurements aboard Spacelab 1.

The radiation environment inside Spacelab 1 was measured by a set of passive radiation detectors distributed throughout the volume inside the module, in the access tunnel, and outside on the pallet. Measurements of the low-LET (linear energy transfer) component obtained from the thermoluminescence detectors ranged from 102 to 190 millirads, yielding an average low-LET dose rate of 11.2 millirads per day inside the module, about twice the low-LET dose rate measured on previous flights of the space shuttle. Because of the higher inclination of the orbit (57 degrees versus 28.5 degrees for previous shuttle flights), substantial fluxes of highly ionizing HZE particles (high charge and energy galactic cosmic rays were observed, yielding an overall average mission dose-equivalent of about 150 millirems, more than three times higher than measured on previous shuttle missions.

Lymphocyte studies in a patient with chronic polyradiculoneuropathy.

We studied immunologic abnormalities in one patient with chronic polyradiculoneuropathy and the effects of immune suppression and plasmapheresis on the clinical course and immune abnormalities. Increased helper T cells and B cells with deficiency of T suppressor cells to B-cell but not to T-cell targets were detected. The patient's blood lymphocytes, but not the controls' lymphocytes, proliferated in vitro on culturing them with P2 antigen in the presence of the patient's CSF. Plasmapheresis combined with corticosteroid and azathioprine reversed the majority of immune abnormalities to normal but did not decrease the patient's lymphocyte-P2 proliferative response; nor did it improve clinical status.

Comparison of the diagnostic value of serum pancreatic isoamylase and immunoreactive trypsin measurement in patients with cystic fibrosis.

We have measured serum immunoreactive trypsin (IRT) and serum pancreatic isoamylase (PIA) activities using commercially available kits in 37 cystic fibrosis (CF) patients and 46 hospital controls of similar age range. Immunoreactive trypsin was more often abnormal than PIA (26/37 v 18/37 abnormal respectively); IRT will be particularly useful as an additional diagnostic test in older children, in whom interpretation of the sweat test may be difficult, as 14/15 CF patients aged over 10 years had abnormal IRT results. Less than half of our patients who were aged between one and nine years had abnormal IRT activity, limiting the value of the test, though a low activity would still support the diagnosis of CF. Comparison with faecal fat estimations in 31 patients suggests that neither IRT nor PIA can be used as a non-invasive test of pancreatic function in order to identify those few CF patients who do not require pancreatic enzyme supplements.

Rat serum stimulates serotonin N-acetyltransferase activity in pineal monolayer cultures.

The effects of rat serum on serotonin N-acetyltransferase (NAT) activity and indole synthesis in monolayer cultures of neonatal rat pineal glands was examined. The addition of 5% rat serum to these cultures resulted in stimulation of NAT activity equal to that obtained with optimal concentrations of the adrenergic agonist norepinephrine (NE). Rat serum also increased the synthesis of both N-acetylserotonin and melatonin from tryptophan. Stimulation of NAT activity by rat serum was partially blocked by metoprolol and propranolol, but not by phentolamine or butoxamine. The serum factor responsible for the stimulation was stable to both freezing and boiling. No significant amounts of epinephrine, norepinephrine, or dopamine were detected in the serum.