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Biomedical subjects

J Bass

Publications and source records attributed to J Bass.

At least 37 records · Page 2Linked to original sources

Poor outcome of gastrointestinal perforations associated with childhood abdominal non-Hodgkin's lymphoma.

BACKGROUND/PURPOSE: With modern chemotherapeutic protocols and advances in medical care, the outcome of intraabdominal non-Hodgkin's lymphoma (NHL) in children can be excellent for limited disease. Advanced disease, however, is associated with increased tumor aggression and requires more rigorous adjuvant therapy. Hence, complications early in the course of the disease process or its management often lead to a poor outcome. Perforation of the gastrointestinal tract, either iatrogenic, tumor related or chemotherapeutically induced is one such complication and may result significant morbidity and mortality. METHODS: The authors reviewed their experience with this disease, and present two cases of children with abdominal NHL, which poignantly demonstrate these points. Results and a review of the literature are then discussed. RESULTS: Fifteen cases of abdominal NHL were examined with an overall mortality rate of 40%. This increased to 100% in the presence of perforation. In two cases, inadvertent entry into the bowel occurred at the time of laparotomy for tumor biopsy. In the first case, intestinal wall was included in the biopsy specimen; in the second, laparotomy unmasked an already sealed-off perforation secondary to tumor invasion. Sepsis ensued in both cases. In the first, this resulted in repeated delays in chemotherapy, and the child succumbed to the disease. In the second, chemotherapy was continued, and although the small bowel leak was controlled, the initial insult hampered marrow recovery and host defenses, resulting in fatal sepsis. CONCLUSIONS: These data and other reported cases in the literature indicate that intestinal perforation associated with abdominal lymphomas in children portends an extremely poor prognosis. All attempts to avoid this complication should be made, including avoiding direct tumor biopsy whenever possible.

Antineoplastic Combined Chemotherapy Protocols↗

Use of a state data bank to measure incidence and prevalence of a chronic disease: end-stage renal failure.

The Western Australian Health Services Research Linked Database was used to examine trends in the incidence rate and prevalence of end-stage renal failure and to describe treatment patterns in these patients. Linked hospital morbidity and mortality records from 1980 to 1994 were selected if a record had a principal diagnosis or procedure of chronic renal failure, dialysis, or renal transplantation. Patient records were grouped according to the stage of care (predialysis, dialysis, transplant, or death). A total of 1, 046 patients with a principal diagnosis or procedure that met our criteria for end-stage renal failure was admitted to the hospital from 1985 to 1994. Trends in the incidence rate and prevalence of end-stage renal failure by sex and race, patterns of care, indices of comorbidity, and waiting time to transplantation were calculated. Results showed that both the incidence rate and prevalence of end-stage renal failure increased from 1986 to 1994, most noticeably in the aboriginal population. Rates of renal failure in 1994 were 15 times greater in aborigines than in nonaborigines. Of the hospital patients, 73.5% received dialysis three times a week. Complications associated with dialysis treatment were the most common cause of comorbid hospitalization. The mean waiting time to transplantation was 503 days for those who had a transplant and 6.3 years for all patients. The escalating numbers of patients undergoing renal dialysis, the high cost of maintaining them on dialysis, and the additional use of hospital services for comorbid conditions highlight the need to develop programs to prevent the occurrence of renal failure, particularly in the aboriginal population.

Adult↗

Growth factors controlling muscle development.

The enlarged muscles of certain breeds of cattle, such as the Belgian Blue, have been shown to result from a marked increase in the number of normal sized muscle fibers. Originally insulin-like growth factors (IGFs) were implicated in this myofiber hyperplasia, as IGFs have been shown to stimulate myoblast proliferation as well as maintain fiber differentiation. Recently it has been reported that mice lacking a myostatin gene, a member of the TGFbeta superfamily, have enhanced skeletal mass resulting from increased muscle fiber number and size. Mutations in this gene have been found in double-muscled cattle, indicating that myostatin is an inhibitor of muscle growth. Myostatin is expressed early in gestation and then maintained to adulthood in certain muscles. Myostatin expression in bovine muscle is highest during gestation when muscle fibers are forming and some of the myogenic regulatory factors have elevated expression over the same period as myostatin. Molecular expression of the IGF axis does not differ between Belgian Blue and normal muscled cattle, and IGF-II mRNA is increased throughout formation of secondary fibers in both breeds. However, myostatin and MyoD expression in muscle differ between normal and hypertrophied muscle cattle breeds. This evidence strongly suggests that lack of myostatin is associated with an increase in fiber number which then results in a marked increase in potential muscle mass in double-muscled cattle.

Amino Acid Sequence↗

Violence prevention and young adolescents' participation in community youth service.

PURPOSE: To examine whether participation in a school-sponsored community youth service program reduces self-reported violent behaviors among young urban adolescents. METHODS: A total of 972 seventh- and eighth-grade students at two large, urban, public middle schools were surveyed at baseline and at 6-month follow-up. One school was assigned to interventions and the other served as a control. All students at the intervention school received the Reach for Health classroom curriculum that included a 10-lesson unit focusing on violence prevention. In addition, approximately half the students were randomly assigned by classroom to participate in the Reach for Health Community Youth Service program (CYS). Under the guidance of teachers and community nurses, these students spent several hours each week providing service in local health care agencies. Regression analyses were used to assess the influence of treatment condition on violent behavior outcomes. RESULTS: Comparing students in the curriculum-only and curriculum-plus-CYS interventions to the control group, there is a statistically significant interaction (p < .03) among grade, CYS participation, and violence at follow-up. Eighth-grade CYS students reported significantly less violence at follow-up than students in the control school, taking into account baseline level of risk behavior, gender, ethnicity, and social desirability (p < .04). There was no significant difference between controls and students in the curriculum-only condition. Comparing students in the CYS intervention to the curriculum-only condition within the intervention school, the grade by intervention interaction again is significant (p < .05). Eighth-grade CYS students-who received the broadest CYS experience-reported less violence at follow-up than their curriculum-only counterparts. CONCLUSION: When delivered with sufficient intensity, school programs which couple community service with classroom health instruction can have a measurable impact on violent behaviors of a population of young adolescents at high risk for being both the perpetrators and victims of peer violence. Community service programs may be an effective supplement to curricular interventions and a valuable part of multicomponent violence prevention programs.

Adolescent↗

Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia.

The genetic lesion underlying familial British dementia (FBD), an autosomal dominant neurodegenerative disorder, is a T-A transversion at the termination codon of the BRI gene. The mutant gene encodes BRI-L, the precursor of ABri peptides that accumulate in amyloid deposits in FBD brain. We now report that both BRI-L and its wild-type counterpart, BRI, were constitutively processed by the proprotein convertase, furin, resulting in the secretion of carboxyl-terminal peptides that encompass all or part of ABri. Elevated levels of peptides were generated from the mutant BRI precursor. Electron microscopic studies revealed that synthetic ABri peptides assembled into irregular, short fibrils. Collectively, our results support the view that enhanced furin-mediated processing of mutant BRI generates fibrillogenic peptides that initiate the pathogenesis of FBD.

Adaptor Proteins, Signal Transducing↗

Retrograde esophageal balloon dilatation for caustic stricture in an outpatient clinic setting.

Caustic injury to the esophagus, with resultant esophageal stricture, is a challenge for the surgeon. These strictures require multiple esophageal dilatations, which are usually performed under general anesthesia and frequently under fluoroscopic control. Because of the risks of multiple general anesthetics and frequent radiation, a technique is described for retrograde esophageal balloon dilatation in an outpatient clinic setting without a general anesthetic or fluoroscopic control.

Ambulatory Care↗

Folding of insulin receptor monomers is facilitated by the molecular chaperones calnexin and calreticulin and impaired by rapid dimerization.

Many complex membrane proteins undergo subunit folding and assembly in the ER before transport to the cell surface. Receptors for insulin and insulin-like growth factor I, both integral membrane proteins and members of the family of receptor tyrosine kinases (RTKs), are unusual in that they require homodimerization before export from the ER. To better understand chaperone mechanisms in endogenous membrane protein assembly in living cells, we have examined the folding, assembly, and transport of the human insulin receptor (HIR), a dimeric RTK. Using pulse-chase labeling and nonreducing SDS-PAGE analysis, we have explored the molecular basis of several sequential maturation steps during receptor biosynthesis. Under normal growth conditions, newly synthesized receptor monomers undergo disulfide bond formation while associated with the homologous chaperones calnexin (Cnx) and calreticulin (Crt). An inhibitor of glucose trimming, castanospermine (CST), abolished binding to Cnx/Crt but also unexpectedly accelerated receptor homodimerization resulting in misfolded oligomeric proreceptors whose processing was delayed and cell surface expression was also decreased by approximately 30%. Prematurely-dimerized receptors were retained in the ER and more avidly associated with the heat shock protein of 70 kD homologue binding protein. In CST-treated cells, receptor misfolding followed disordered oligomerization. Together, these studies demonstrate a chaperone function for Cnx/Crt in HIR folding in vivo and also provide evidence that folding efficiency and homodimerization are counterbalanced.

Animals↗

Catheter closure of moderate- to large-sized patent ductus arteriosus using the new Amplatzer duct occluder: immediate and short-term results.

OBJECTIVES: The aim of this study was to assess the immediate and short-term results of anterograde catheter closure of a moderate- to large-sized patent ductus arteriosus (PDA) using the new self-expandable, respositionable Amplatzer duct occluder (ADO) device. BACKGROUND: Transcatheter closure of a PDA using devices or coils is technically challenging and may be accompanied by a 38% incidence of residual shunts. METHODS: Twenty-four patients (6 male, 18 female) underwent attempted transcatheter closure of a PDA using the ADO at a median age of 3.8 years (range 0.4 to 48) and a median weight of 15.5 kg (range 6 to 70). The mean PDA diameter at its narrowest segment was 3.7+/-1.5 mm. A 6F long sheath was used for delivery of the ADO. Follow-up evaluation was performed with color flow mapping of the main pulmonary artery within 24 h and at 1 and 3 months after closure. RESULTS: Twenty three of the 24 patients had successful device placement. Angiography showed that 7 patients had complete immediate closure, 14 had a trace shunt (foaming through the device with no jet), and 2 had a small residual shunt (with a jet). Within 24 h, color Doppler revealed complete closure in all patients. The unsuccessful attempt was during an initial trial with a prototype that has been modified. The median fluoroscopy time was 13.5 min (range 6.3 to 47). All patients were discharged home the next day. There were no complications. Of the 23 patients, 21 completed the 1-month follow-up, all (95% confidence interval [CI] 86% to 100%) with complete closure, and 18 of 23 patients completed the 3-month follow-up, also all (95% CI 83% to 100%) with complete closure. CONCLUSIONS: Anterograde transcatheter closure using the new ADO is an effective therapy for patients with a PDA diameter up to 6 mm. Further clinical trials are underway.

Alloys↗

Alanine scanning mutagenesis of insulin.

Alanine scanning mutagenesis has been used to identify specific side chains of insulin which strongly influence binding to the insulin receptor. A total of 21 new insulin analog constructs were made, and in addition 7 high pressure liquid chromatography-purified analogs were tested, covering alanine substitutions in positions B1, B2, B3, B4, B8, B9, B10, B11, B12, B13, B16, B17, B18, B20, B21, B22, B26, A4, A8, A9, A12, A13, A14, A15, A16, A17, A19, and A21. Binding data on the analogs revealed that the alanine mutations that were most disruptive for binding were at positions TyrA19, GlyB8, LeuB11, and GluB13, resulting in decreases in affinity of 1,000-, 33-, 14-, and 8-fold, respectively, relative to wild-type insulin. In contrast, alanine substitutions at positions GlyB20, ArgB22, and SerA9 resulted in an increase in affinity for the insulin receptor. The most striking finding is that B20Ala insulin retains high affinity binding to the receptor. GlyB20 is conserved in insulins from different species, and in the structure of the B-chain it appears to be essential for the shift from the alpha-helix B8-B19 to the beta-turn B20-B22. Thus, replacing GlyB20 with alanine most likely modifies the structure of the B-chain in this region, but this structural change appears to enhance binding to the insulin receptor.

Alanine↗

Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer.

PURPOSE: We report the local control and survival of two Phase I dose escalation trials of combined preoperative 5-fluorouracil (5-FU), low-dose leucovorin (LV), and radiation therapy followed by postoperative LV/5-FU for the treatment of patients with locally advanced and unresectable rectal cancer. METHODS AND MATERIALS: A total of 36 patients (30 primary and 6 recurrent) received two monthly cycles of LV/5-FU (bolus daily x 5). Radiation therapy (50.40 Gy) began on day 1 in the 25 patients who received concurrent treatment and on day 8 in the 11 patients who received sequential treatment. Postoperatively, patients received a median of four monthly cycles of LV/5-FU. RESULTS: The resectability rate with negative margins was 97%. The complete response rate was 11% pathologic and 14% clinical for a total of 25%. The 4-year actuarial disease-free survival was 67% and the overall survival was 76%. The crude local failure rate was 14% and the 4-year actuarial local failure rate was 30%. Crude local failure was lower in the four patients who had a pathologic complete response (0%) compared with those who either did not have a pathologic complete response (16%) or who had a clinical complete response (20%). CONCLUSION: Our preliminary data with the low-dose LV regimen reveal encouraging downstaging, local control, and survival rates. Additional follow-up is needed to determine the 5-year results. The benefit of downstaging on local control is greatest in patients who achieve a pathologic complete response.

Adult↗

Dysplastic nitrergic neurons in the rectum of a patient with rectal ectasia.

We present a histochemical study of resected colon from a 13-year-old boy diagnosed with rectal ectasia. Laminar preparations and sectioned tissue of rectum were assayed histochemically for nitric oxide (NO) synthase activity by reducing nitro blue tetrazolium salt in the presence of the cofactor NADPH. Tissue preparations displayed intensely labelled neurons and fibers throughout the gut wall. Laminar preparations of Meissner's plexus showed a hyperplasia of ganglia and NO-related neurons throughout the length of the resected rectum compared with normal bowel. Sectioned tissue of the Auerbach's plexus demonstrated a normal number of ganglia and NO-related neurons. As well, the ectatic bowel showed a proliferation of nerve fibers in keeping with the degree of circular smooth muscle hypertrophy. This proliferation may represent a reactive phenomenon secondary to the functional obstruction. The NO histochemical technique may form the basis of further investigations in defining the cause of this functional obstruction.

Adolescent↗

Cardiovascular function in children following bone marrow transplant: a cross-sectional study.

Sixty-three patients who had undergone a BMT at age < or = 18 years were evaluated cross-sectionally to determine cardiac function as well as the long-term prevalence, types, severity, and risk factors of cardiac abnormalities. Patients were > or = 1 year post-BMT and were evaluated by history, resting ECG, echocardiography (ECHO), exercise treadmill test, chest X-ray, pulmonary function tests and review of past cardiac studies. Patients were assigned a New York Heart Association (NYHA) class based on an activity and cardiac symptoms questionnaire. Pretransplant preparative regimens included high-dose cyclophosphamide (CY) and total body/lymphoid irradiation (n = 38), CY in combination with other chemotherapy (n = 22), and other drug combinations (n = 3). Forty patients (63.5%) had received prior anthracyclines (median 307 mg/m2). Patients' ages ranged from 1.9 to 32 years (median 10.9 years) with median follow-up of 3.3 years (range 1-16.3 years). Twenty-six patients (41.3%) had a cardiac abnormality detected at follow-up. In 21 patients the abnormal finding had not been present at the pre-BMT evaluation. Ten patients (16.4%) had resting ECG abnormalities. Left ventricular ejection fraction (LVEF) by ECHO was mildly decreased to 50-54% in three patients and markedly decreased to 40% in one patient. Only one patient (1.7%) developed a mildly abnormal shortening fraction of 27%. All patients with ECHO abnormalities were asymptomatic. Twenty-three of 31 patients > or = 9 years of age (74%) who underwent a treadmill exercise test had a borderline or abnormal response to exercise. There was no correlation between demographic factors, previous therapy, preparative regimen or length of follow-up with the post-BMT ECG, ECHO and treadmill abnormalities. Overall, eight patients (12.7%) were symptomatic and NYHA class II or III, and all had abnormal exercise tests. The presence of symptoms and NYHA class were predictors for oxygen consumption during exercise (P = 0.03 and 0.02, respectively) and tended to predict overall treadmill results also. Late cardiac abnormalities do occur following BMT in childhood and thus, there is a clear need for continued, serial long-term cardiac evaluation in transplant survivors. Evaluations should include exercise stress testing to detect inadequate cardiac output as well as oxygen consumption during exercise.

Adolescent↗

Reducing pain after inguinal hernia repair in children: caudal anesthesia versus ketorolac tromethamine.

BACKGROUND: The optimal method to achieve analgesia after inguinal hernia repair in children is unknown. This study compared the analgesic efficacy, adverse events, and the costs associated with supplementation of local anesthesia (infiltration of the wound) with either intravenous ketorolac or caudal analgesia in children having inguinal hernia repair. METHODS: With parental consent and institutional review board approval, children aged 2-6 yr having elective, outpatient inguinal hernia repair were studied in this randomized, single-blinded investigation. Anesthesia was induced by inhalation with nitrous oxide and halothane or intravenously with propofol. Anesthesia was maintained with nitrous oxide and halothane. Patients were randomly assigned to receive caudal analgesia (1 ml/kg 0.20% bupivacaine with 1/200,000 epinephrine) or intravenous ketorolac (1 mg/kg) immediately after induction of anesthesia. Both groups received field blocks with 0.25% bupivacaine administered by the surgeon under direct vision during operation. Patients were assessed for 24 h. In-hospital pain was assessed using a behavior-based pain score. Parents assessed pain with a visual linear analog pain scale with anchors of 0 (no pain) and 100 (worst pain imaginable). RESULTS: The authors studied 164 children, with 84 patients in the ketorolac group. The groups had similar demographic data. In-hospital analgesic requirements and pain scores were almost identical in both groups. Pain at home was significantly less in the ketorolac group, with visual linear analog pain scale scores of 10 (0-80) compared with 20 (0-80) (median [range]) for ketorolac versus caudal (P = 0.002 by the Mann-Whitney U test). The ketorolac group also had a lower incidence of vomiting, ambulated more rapidly, and micturated earlier (P < 0.05). CONCLUSION: The use of intravenous ketorolac to supplement local anesthesia infiltrated by the surgeon during pediatric inguinal hernia repair is superior to supplementation with caudal analgesia.

Anesthesia, Caudal↗

Defining total corporate health and safety costs--significance and impact. Review and recommendations.

This is the first in a series of studies designed to assist directors of occupational health and safety services in defining, measuring, predicting, and integrating total health and safety costs into useful management information. This study was structured to review recent literature on health and safety costs and to categorize costs as either direct or indirect. This delineation should aid in defining total health and safety costs, delineating priority areas for interventions to reduce costs, and evaluating the effectiveness of health and safety programs. The significance of such efforts is underscored by the reported direct health care costs for the nation's work force of over $418 billion, and indirect costs, using the lower range of estimates for such costs, of over $837 billion. Reducing the total costs of over $1.256 trillion would have major impacts on corporate productivity and competitiveness, as well as on availability of health care programs for employees. Recommendations for follow-up activities to define costs and evaluate intervention programs are provided.

Costs and Cost Analysis↗

Minimum criteria for reporting child abuse from health care settings.

We evaluated how consistently clinicians of two hospitals reported child abuse and neglect, and the utility of specific, operational criteria for assessing hospital clinicians' compliance with the child abuse reporting laws. To evaluate clinicians' compliance, we audited the medical records of 85 children who had been reported to a child protective service (CPS) agency by clinicians at either of two hospitals and who had been seen at that hospital at least once before the index report of abuse. The time elapsed from first hospital visit to index abuse report among the 85 children averaged 4.3 years. In the children's records, we identified 28 earlier reports to the CPS agency and four episodes that met criteria we developed but that had not been reported. Thus, application of specific criteria resulted in the finding that 28 (88 percent) of 32 suspected abuse episodes were actually reported to the CPS agency (95 percent confidence interval: 76 to 99 percent). In a second phase of the study, we compared the content of 45 reported episodes of child abuse (4) index reports and four earlier reports) to the criteria in order to evaluate their utility. Thirty-five episodes (78 percent) met one of the criteria. Review of the remaining 10 episodes led to the development of one new criterion. We conclude that, although it has been estimated that hospital personnel nationwide report to CPS agencies only 69 percent of the child abuse cases they identify, clinicians at the hospitals we studied reported 88 percent of documented episodes of suspected abuse. We also conclude that specific, operational criteria can help in the assessment of hospital clinicians' compliance with their obligation to report child abuse and neglect.

Child↗

Health surveillance: effective components of a successful program.

1. Using the nursing process, the occupational health nurse plays a key role in the health surveillance of workers at risk for exposure to chemical, biological, or physical hazards. 2. To implement and manage a successful occupational surveillance program, the occupational health nurse must be familiar with walk through procedures, test selection and interpretation issues, toxicology and epidemiology concepts and budgeting processes. 3. Employee education and program evaluation are integral and ongoing components of a comprehensive occupational health surveillance program. Anticipation of legal and ethical problems is also critical during the design, implementation, and evaluation of the program. 4. Quality data collection and management aid the occupational health nurse in decision making and accurate and timely record keeping.

Data Collection↗

Fusion of insulin receptor ectodomains to immunoglobulin constant domains reproduces high-affinity insulin binding in vitro.

A unique feature of the insulin receptor is that it is dimeric in the absence of ligand. Dimerization of two adjacent transmembrane domain (TMD) alpha helices has been shown to be critical in receptor kinase activation. Moreover, previous work has suggested that the TMD is involved in stabilizing the high-affinity binding site; soluble receptors expressed after simple truncation at the ectodomain-TMD junction have reduced affinity for insulin. To further examine this issue, we have replaced the TMD and intracellular domain of the soluble human insulin receptor (HIRs) with constant domains from immunoglobulin Fc and lambda subunits (HIRs-Fc and HIRs-lambda). Studies of receptor biosynthesis and binding characteristics were performed following transient transfection of receptor cDNAs into human embryonal kidney 293 cells. Each hybrid receptor was initially synthesized as a single chain proreceptor, followed by cleavage into alpha- and beta-Fc or beta-lambda subunits. The majority of secreted protein appeared in the cell medium as fully processed heterotetramer. Fc fragments released from HIRs-Fc by papain digestion and analyzed by nonreducing SDS-polyacrylamide gel electrophoresis were dimeric. Furthermore, dissociation constants for both chimeras were similar to those for the full-length holoreceptor (wild-type receptor, Kd1 = 200 pM and Kd2 = 2 nM; HIRs-Fc, Kd1 = 200 pM and Kd2 = 40 nM; and HIRs-lambda, Kd1 = 200 pM and Kd2 = 5 nM). These results extend previous observations that dimerization of the membrane-proximal ectodomain is necessary to maintain an intact high-affinity insulin-binding site.

Animals↗