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Biomedical subjects

S Abramson

Publications and source records attributed to S Abramson.

At least 19 recordsLinked to original sources

Can the procedure for prolapsing hemorrhoids (PPH) be done twice? Results of a porcine model.

BACKGROUND: The procedure for prolapsing hemorrhoids (PPH) is a new surgical method for the treatment of symptomatic hemorrhoids. In cases of recurrent prolapse, the performance of a second PPH may result in a ring of mucosa and submucosa between the two circular staple lines. In this study, we used a porcine model to assess whether PPH can be safely performed twice. METHODS: Five adult pigs underwent two PPH procedures in one session, leaving a ring of approximately 1 cm of mucosa between the two staple lines. One month later, the pigs were examined under anesthesia. The anal canal was assessed using the following four methods: (a) clinical examination, (b) evaluation of mucosal blood perfusion at different levels of the anal canal via a laser Doppler flow detector, (c) measurement of concentrations of hydroxyproline and collagen to check for fibrosis, and (d) histopathological examination. RESULTS: At the completion of the study period, all five pigs showed no clinical evidence of anorectal dysfunction. On examination under anesthesia 1 month after surgery, there was no evidence of anal stenosis in any of the pigs. The mean mucosal blood flow between the two staple lines did not differ significantly from the flow measured proximally and distally (394 vs 363 and 339 flow units, respectively; p = NS). The collagen levels, based on hydroxyproline concentration, were 81 mcg/mg between the staple lines, compared to 82 and 79 proximally and distally, respectively ( p = NS). There was no significant difference in degree of fibrosis, as assessed histopathologically, between specimens taken from the ring between the staple lines and specimens taken from the area external to the staple lines. CONCLUSIONS: The results of this porcine model suggest that a second synchronous PPH is feasible. A controlled experience involving human subjects is required to determine the safety and usefulness of this technique in cases of metachronous application for recurrent or residual hemorrhoids.

Animals↗

N7: a novel multi-modality therapy of high risk neuroblastoma (NB) in children diagnosed over 1 year of age.

BACKGROUND: The N7 protocol for poor-risk neuroblastoma uses dose-intensive chemotherapy (as in N6 protocol [Kushner et al.: J Clin Oncol 12:2607-2613, 1994] but with lower dosing of vincristine) for induction, surgical resection and 2100 cGy hyperfractionated radiotherapy for local control, and for consolidation, targeted radioimmunotherapy with 131I-labeled anti-GD2 3F8 monoclonal antibody and immunotherapy with unlabeled/unmodified 3F8 (400 mg/m2). PROCEDURE: The chemotherapy consists of: cyclophosphamide 70 mg/kg/d x 2 and a 72-hr infusion of doxorubicin 75 mg/m2 plus vincristine 2 mg/m2, for courses 1, 2, 4, and 6; and cisplatin 50 mg/m2/d x 4 and etoposide 200 mg/m2/d x 3, for courses 3, 5, and 7. 131I-3F8 is dosed at 20 mCi/kg, which is myeloablative and therefore necessitates stem-cell support. RESULTS: Of the first 24 consecutive previously untreated patients more than 1 year old at diagnosis, 22 were stage 4 and two were unresectable stage 3 with MYCN amplification. Chemotherapy achieved CR/VGPR in 21 of 24 patients. Twenty patients to date have completed treatment with 131I-3F8, and 15 patients have completed all treatment. With a median follow-up of 19 months, 18 of 24 patients remain progression-free. CONCLUSIONS: Major toxicities were grade 4 myelosuppression and mucositis during chemotherapy, and self-limited pain and urticaria during antibody treatment. Late effects include hearing deficits and hypothyroidism.

Antibodies, Monoclonal↗

Effect of site and source of energy supplementation on milk yield in dairy cows.

The effect of infusing similar energy equivalents of starch into the rumen, or starch or oil into the abomasum was studied in four midlactation cows in a 4 x 4 Latin square design experiment; controls were ruminally infused with water. Cows were fitted with cannulas in the rumen, abomasum, and ileum, and nutrient digestion in the rumen and small intestine was evaluated with Cr as a digesta marker. Ruminal infusions of starch, or abomasal infusions of starch or oil, were associated with a decrease in voluntary feed organic matter intake. Overall energy intake was reduced in oil-infused, but not in starch-infused cows. Nonstructural carbohydrate digestibility in the rumen and in the small intestine was similar among treatments. In abomasally infused cows 3.4 kg/d of nonstructural carbohydrates was apparently digested in the small intestine. Milk production was reduced in oil-infused cows, but the efficiency of milk energy and protein yield was unaffected by treatments. Plasma glucose, insulin, and IGF-1 concentration, mammary glucose extraction rate, rumen ammonia and plasma urea, and arterial and mammary extraction rate of amino acids were all similar among treatments. Large quantities of starch can be digested in the rumen or small intestine of dairy cows. There appear to be no metabolic advantage to increasing the supply of starch to the rumen or the abomasum of mid-lactation dairy cows maintained on highly concentrated diets and exhibiting a positive energy balance.

Abomasum↗

Effect of pneumoperitoneal pressure on tumor dissemination and tumor recurrence at port-site and midline incisions.

Over the past several years numerous cases of port site tumor recurrence after laparoscopic resection of a cancerous tissue have been reported. Possible mechanisms for tumor seeding include tumor removal, contaminated instruments, pneumoperitoneum, and aerosolization of tumor cells. This experiment examined the relationship among trocar contamination, aerosolization, and tumor recurrence with increasing pneumoperitoneal pressure using a hamster model. Increased pneumoperitoneal pressure significantly increased both instrument contamination and tumor recurrence at midline and port site incisions. Interestingly, increasing pneumoperitoneal pressure had no significant effect on the number of aerosolized tumor cells. The results reaffirm that the use of a reduced pneumoperitoneum or gasless laparoscopy may significantly lower port site tumor recurrence.

Animals↗

Hypercoagulability: clinical assessment and treatment.

This review emphasizes pathophysiology, clinical features, assessment, and therapy for hypercoagulability. Risk factors that further increase clotting include obesity, recent surgery, pregnancy, and cancer. Clinical examples of coagulation abnormalities may occur from single or multiple abnormalities and include both inherited and acquired defects. Laboratory testing undertaken at the time of acute thrombosis is often inaccurate or difficult to interpret. Individuals are best tested when they are not taking anticoagulants. Treatment of patients with either inherited or acquired abnormalities usually requires heparin compounds followed by warfarin, but the length of therapy has not yet been settled. Asymptomatic individuals with underlying hypercoagulability may not require treatment except in clot-promoting situations such as trauma, pregnancy, recent surgery, or use of venous access devices. The detection of one abnormality may no longer suffice because multiple defects can be found frequently. In patients with clotting and underlying risk factors, such as malignancy, pregnancy, estrogens, or surgery, an assessment for hypercoagulability should be considered.

Antiphospholipid Syndrome↗

On Five- vs Six-membered Diacetal Formation from Threitol and the Intermediacy of Unusually Stable Protonated Species(1).

The long known, but hitherto poorly understood, thermodynamically controlled diacetalation of rac-threitol with alkylaldehydes provided bicyclic, cis-tetraoxadecalin (TOD) ("66") and bi(dioxolanyl) (BDO) ("55") products, shown to be formed in acid-concentration and temperature-dependent ratio. The configurational and conformational isomeric diacetals obtained in four such reactions of substituted aldehydes (RCHO, R = CH(3), CH(2)Cl, CH(2)Br, CO(2)CH(3)) with rac-threitol were isolated and characterized. A variable acid-concentration analysis of the equilibrium mixture of products in one such case (R = CH(2)Br) was performed and provided equilibrium constants and, hence, free-energy differences among these products and their relatively stable protonated intermediates. The latter were rationalized by the unusually high proton-affinity calculated for the cis-TOD ("66") form.

Journal Article↗

Local control with multimodality therapy for stage 4 neuroblastoma.

PURPOSE: To evaluate the efficacy of 21 Gy hyperfractionated radiotherapy for local control in conjunction with surgery and intensive systemic therapy for patients with Stage 4 neuroblastoma. METHODS AND MATERIALS: After achieving a partial or complete remission, 47 children, ages 1-10 years, with Stage 4 neuroblastoma were treated on four consecutive institutional protocols (N4-N7) with dose-intensive multi-agent chemotherapy, maximal surgical debulking, and hyperfractionated radiotherapy (1.5 Gy twice a day to 21 Gy). Radiotherapy fields encompassed the initial tumor volume and regional lymph nodes plus a 3-cm margin. This was followed by consolidation with either autologous bone marrow transplantation (N4 and N5) or immunotherapy (N6 and N7). RESULTS: Forty-five of 47 patients had a complete response to surgery and chemotherapy prior to radiotherapy. Five-year actuarial rates of local control, progression-free survival, and overall survival were 84%, 40%, and 45%, respectively. Among 26 patients who relapsed, 1 failed only at the primary site, 22 developed distant metastases exclusively, and 3 had both local and distant failures. There were no acute complications of radiotherapy. CONCLUSION: Hyperfractionated radiotherapy to 21 Gy, in conjunction with dose-intensive systemic therapy and aggressive surgical resection, is well tolerated and is associated with durable local control for most patients with Stage 4 neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer.

PURPOSE: Membrane-type matrix metalloproteinases are recently described proteolytic enzymes belonging to the matrix metalloproteinase family. Initial studies have indicated that membrane-type matrix metalloproteinases are involved in tumor invasion and metastasis. Membrane-type 1 matrix metalloproteinase is the first membrane-type matrix metalloproteinase to be described. The aim of this study was to investigate the expression of membrane-type 1 matrix metalloproteinase mRNA in colorectal cancer. METHODS: Samples were collected from surgical specimens of patients with colorectal adenocarcinoma and were immediately frozen in liquid nitrogen and stored at -80 degrees C until processed. Both normal and cancer tissue was taken from each patient. TNM stage, tumor differentiation, mucin production, and vascular invasion were assessed. Northern blotting was used to quantify membrane-type 1 matrix metalloproteinase mRNA levels in the samples using a membrane-type 1 matrix metalloproteinase cDNA clone. X-ray film images were digitized and densitometry was used to quantify bands. All samples were normalized against 18S rRNA levels. Results are expressed as the ratio of cancer to normal tissue levels. Statistical analysis was performed using analysis of variance, with P < 0.05 accepted as the level of significance. RESULTS: A total of 32 samples were prospectively analyzed. The correlation between TNM stage and increased expression of membrane-type 1 matrix metalloproteinase mRNA in cancer tissue over normal tissue is expressed in the mean ratio of cancer to normal tissue expression for Stages I through IV, respectively: 1.4 +/- 0.2 (12 patients); 4.1 +/- 2.6 (8 patients); 3.4 +/- 3 (7 patients); and 4.5 +/- 5 (5 patients). Stage I is significantly different from Stages II and IV (P < 0.05). These preliminary results show an overall increasing trend in membrane-type 1 matrix metalloproteinase expression with increasing tumor stage. However, there was no correlation between membrane-type 1 matrix metalloproteinase expression and mucin production, degree of tumor differentiation, or vascular invasion. CONCLUSION: Preliminary results indicate that membrane-type 1 matrix metalloproteinase levels correlate with increasing tumor stage.

Adenocarcinoma↗

Treatment of the alcohol intoxications: ethylene glycol, methanol and isopropanol.

Intoxications with ethylene glycol, methanol, and isopropanol are among the most common ingestions, in the treatment of which a nephrologist plays an important role. These three substances have the ideal characteristics for intervention by hemodialysis, and the three parent compounds and their metabolites are readily dialyzable. Two of the three substances, ethylene glycol and methanol, are metabolized to more toxic substances, so that an early treatment strategy that removes the parent compound or blocks its metabolism can prevent the development of many of the adverse events that are often seen in these ingestions. Fomepizole, an inhibitor of alcohol dehydrogenase, slows the metabolism of these substances and is now approved by the US Food and Drug Administration for use in ethylene glycol intoxication. The present review addresses recent advances in the diagnosis and treatment of intoxication with ethylene glycol, methanol and isopropanol.

2-Propanol↗

Personal exercise habits and counseling practices of primary care physicians: a national survey.

OBJECTIVE: Regular physical activity can reduce the incidence and prevalence of many chronic diseases. A vast majority of Americans cite their physician as their primary source of information regarding healthy lifestyle decisions. This study was designed to obtain information about the personal exercise behavior and counseling practices of primary care physicians, to evaluate the relationship between their personal and professional exercise practices, and to determine whether physician specialty is associated with these practices. DESIGN: A cross-sectional survey was mailed to a randomly selected sample of primary care physicians in the United States. A questionnaire was used to obtain detailed information on the personal exercise habits, counseling practices, and barriers to counseling of these physicians, regarding both aerobic exercise and strength training. PARTICIPANTS: 298 primary care physicians, comprising 84 family practitioners, 79 pediatricians, 58 geriatricians, and 77 internists. MAIN OUTCOME MEASURES: Frequency of physician exercise, exercise counseling, and relationship between these practices. RESULTS: Physicians who perform aerobic exercise regularly are more likely to counsel their patients on the benefits of these exercises, as are physicians who perform strength training. Pediatricians and geriatricians counsel fewer patients about aerobic exercise than family practitioners and internists. Counseling regarding strength training is less common in all physician groups surveyed, and lowest among pediatricians, of whom 50% did not advise these exercises for any of their patients. Inadequate time was noted by 61% and inadequate knowledge and/or experience by 16% of respondents as the major barriers to counseling regarding aerobic exercise. CONCLUSION: Physicians who exercise are more likely to counsel their patients to exercise. Inadequate time and knowledge/experience regarding exercise are the most common barriers to counseling identified. These findings suggest strategies that might increase physician exercise counseling behavior.

Attitude to Health↗

Impact in the emergency department of unenhanced CT on diagnostic confidence and therapeutic efficacy in patients with suspected renal colic: a prospective survey. 2000 ARRS President's Award. American Roentgen Ray Society.

OBJECTIVE: Our objective was to evaluate the impact of unenhanced CT on clinician diagnostic confidence and therapeutic efficacy in emergency department patients with clinically suspected renal colic. SUBJECTS AND METHODS: Questionnaires were completed on 93 patients who were referred to the radiology department with clinically suspected renal colic. We prospectively surveyed the clinician's diagnostic confidence and treatment plan before and after unenhanced abdominal and pelvic CT. RESULTS: Fifty-six patients (60%) had positive findings for calculi, 20 patients (22%) had normal findings, and alternative diagnoses were found in 17 patients (18%). The clinician's diagnostic certainty of stones before CT was variable with the largest frequencies at 41-60% (n = 30) and 71-90% (n = 35). The diagnostic certainty of stones after CT showed movement toward either less than or equal to 10% (n = 25) or greater than or equal to 91% (n = 51). The mean change in diagnostic confidence was 34%. Fifty-seven patients (61%) had a change in treatment plan. Specifically, the need for urology consultation as the initial treatment plan was reduced from 24 patients to one patient. Plans for admissions suggested before CT (n = 11) were nearly cut in half (n = 6) after imaging. Lastly, seven patients who would have initially been discharged were admitted to the hospital after imaging. CONCLUSION: CT significantly increased emergency department clinician diagnostic confidence and altered initial treatment decisions in patients with suspected renal colic. Most often, CT confirmed a ureteral stone and allowed appropriate discharge or urologic intervention. In a smaller subset of patients, CT established a significant alternative diagnosis that allowed the prompt initiation of appropriate treatment.

Adult↗

A multicenter, randomized, double-blind, placebo-controlled trial of high-dose intravenous immunoglobulin for oral corticosteroid-dependent asthma.

To determine the efficacy of high doses of intravenous gammaglobulin (IVIG) for the treatment of severe, steroid-dependent asthma in patients between 6 and 68 years of age, a randomized, double-blind, placebo-controlled multicenter clinical trial was conducted in private and university hospitals in the United States. Patients were randomized to one of three treatment arms: 2 g IVIG/kg/month (16 patients); 1 g IVIG/kg/month (9 patients); or 2 g iv albumin (placebo)/kg/month (15 patients). The treatment consisted of seven monthly infusions followed by a posttreatment observation period. The primary outcome measurement was mean daily prednisone-equivalent dose requirements, determined during the observation month preceding initiation of treatment and compared to the month preceding the seventh infusion. Secondary clinical endpoints measured were pulmonary function, frequency of emergency room visits or hospitalizations, and number of days absent from school or work. When adjusted for body weight, the mean dose requirements fell by 33, 39, and 33% in the placebo, IVIG (1 g/kg), and IVIG (2 g/kg) treatment arms, respectively. The differences between therapies were not statistically different (P = 0.9728). The mean percentage-of-predicted FEV1 fell in all three treatment groups during the treatment period but there was no significant difference between treatment groups (P = 0.8291). There was also no significant difference in the percentage of subjects requiring emergency room visits or hospitalizations or missing days of work/school, among the three treatment groups. The trial was terminated prematurely after interim analysis determined the adverse experience rate was different between the three groups. Three patients, all randomized to the 2-g/kg IVIG dose group, were hospitalized with symptoms consistent with aseptic meningitis. In summary, in this randomized, double-blind, placebo-controlled multicenter study, high doses of IVIG did not demonstrate a clinically or statistically significant advantage over placebo (albumin) infusions for the treatment of corticosteroid-dependent asthma. Subgroup analysis failed to identify markers predicting responsiveness. High-dose IVIG can also be associated with a significant incidence of serious adverse events.

Administration, Oral↗

Anticoagulation in continuous renal replacement therapy.

Continuous renal replacement therapies (CRRTs) allow for gradual solute and fluid removal. In very sick patients with acute renal failure, they may be better tolerated than hemodialysis. The major drawback to CRRTs is the need for anticoagulation to maintain filter patency. The patients who are likely to benefit from CRRTs are also at higher risk for bleeding from systemic anticoagulation. The most commonly used form of anticoagulation for CRRTs, low-dose heparin, causes bleeding in 10-50% of patients. Regional anticoagulation using protamine may reduce the risk of bleeding, but it is difficult to use. Low molecular weight heparin and prostacyclin both may partially reduce bleeding, but are difficult to dose. Regional anticoagulation with citrate is easy to use and has been shown to prolong filter life without systemic anticoagulation. It is the anticoagulant of choice for most patients on CRRT.

Anticoagulants↗