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Biomedical subjects

M A Hoffman

Publications and source records attributed to M A Hoffman.

At least 37 records · Page 2Linked to original sources

Determination by capillary zone electrophoresis of mercaptopurine and thioguanine concentration in capsules for paediatric patients.

OBJECTIVE: Mercaptopurine monohydrate and thioguanine are two antineoplastic agents that inhibit purine metabolism. They are given by mouth in the treatment of acute leukaemias, usually for the maintenance of remission. In order to quantify these two antimetabolites into capsules for paediatric patients prepared in the pharmacy department, a capillary zone electrophoresis method (CZE) was developed. METHOD: The equipment and reagents used included: a P/ACE 5000 capillary electrophoresis system, a 37 cm x 75 microm silica capillary, a 22.2 mM borate buffer (pH 9.0), 5 s high pressure injections, direct UV detection at 280 nm, run 20 kV. Hypoxanthine was used as an internal standard. RESULTS: All compounds were separated in less than 3 min using a constant voltage of 20 kV. At a theoretical concentration of 100 microg/ml, the accuracy (average percentage of recovery = 98.9%, RSD = 0.45%, n = 6 for mercaptopurine and average percentage of recovery = 101.7%, RSD = 0.20%, n = 6 for thioguanine), the repeatability (RSD = 0.84%, n = 6 for mercaptopurine and RSD = 0.75%, n = 6 for thioguanine), the reproducibility (RSD = 0.58%, n = 18 for mercaptopurine and RSD = 1.55%, n = 18 for thioguanine) and the linearity of detection (range 50-150% of the studied concentration, r > 0.999 for mercaptopurine and r > 0.998 for thioguanine) were satisfactory. The capsule excipients did not interfere with quantification of the mercaptopurine or thioguanine peak. CONCLUSION: The two antineoplastic agents could be assayed rapidly by the same capillary zone electrophoretic method with acceptable accuracy and precision. This method is suitable for routine control of capsules prepared for paediatric patients.

Antimetabolites, Antineoplastic↗

Stability of methacholine chloride in isotonic sodium chloride using a capillary electrophoresis assay.

OBJECTIVE: To investigate the stability of methacholine chloride in 0.9% sodium chloride solutions. METHOD: Methacholine powder was mixed with diluent to a final concentration of 5 and 10 mg/ml. Duplicates of each admixture were divided and stored in glass vials at 25 degrees C, 4 degrees C and -20 degrees C for 12 months. At appropriate times intervals, samples were removed from solutions and analysed. Methacholine concentrations were measured using a high performance capillary electrophoresis assay. RESULTS: No colour or other visual changes were seen in any sample. However, an additional peak was observed in some samples. CONCLUSION: Methacholine chloride solutions 5 mg/ml were stable in isotonic sodium chloride after refrigeration or freezing over a period of one year; methacholine chloride solutions 10 mg/ml were stable for one year after freezing. The solutions stored at ambient temperature were stable for 35 days and for less than 14 days, respectively, for the 5 and the 10 mg/ml solutions.

Bronchoconstrictor Agents↗

Notable multicultural training in APA-approved counseling psychology and school psychology programs.

On the basis of the initial work of M.R. Rogers, J. Martin, and L. Druckman (1994) regarding exemplary multicultural training occurring at school psychology programs, the authors examined salient aspects of 5 American Psychological Association (APA)-approved counseling psychology and 5 APA-approved school psychology programs nominated for their reputation for multicultural training. Twenty-two percent of the program faculty represented a racial-ethnic minority group, at least 2 faculty members per program were involved in multicultural teaching, and 90% of the programs offered a multicultural course. Program faculty at the notable programs were actively involved in relevant research, routinely made presentations at national conferences regarding their scholarship, regularly participated in campuswide multicultural committees, and generally reported their university training environment to be supportive of multicultural issues.

Counseling↗

Dynamic balance testing with electrically evoked perturbation: a test of reliability.

OBJECTIVE: To investigate the reliability of a newly developed perturbation protocol for assessing dynamic balance. DESIGN: Each subject was tested in two experimental balance conditions, static and dynamic. The dependent variables for the static condition were sway area (SA), sway path length (SPL), sagittal sway standard deviation (SSD), and lateral sway standard deviation (LaSD). During the dynamic condition trials a stimulus was delivered to the tibial nerves of both legs to perturb the subjects. The subjects were instructed to return to the pre-perturbation level of steadiness as soon as possible after the stimulation. The dependent variables for the dynamic condition were dynamic phase duration (DPD), sway path mean (SPM), linear sway standard deviation (LiSD), and sagittal sway standard deviation (SSD). SETTING: The motor control laboratory of a university department of kinesiology. PATIENTS: Ten subjects from a population-based sample of healthy adults. MAIN OUTCOME MEASURE: An intraclass reliability estimate for all dependent measures in the static and dynamic conditions. RESULTS: In the static condition, the variables SA, SPL, SSD, and LaSD had reliabilities of .94, .98, .86, and .92, respectively, and in the dynamic condition the reliability estimates for DPD. SPM, LiSD, and SSD were .90, .71, .80, and .92, respectively. CONCLUSIONS: The results indicate the current technique provides a means of objectively measuring a subject's ability to regain static postural stability following electrically induced perturbation.

Adult↗

Stability of refrigerated and frozen solutions of tropisetron in either polyvinylchloride or polyolefin infusion bags.

OBJECTIVE: To investigate the stability of 50 microg/ml tropisetron in 0.9% sodium chloride or 5% dextrose injections on storage in either 100 ml polyvinylchloride (Tuliflex) or polyolefin (Clear-flex) infusion bags, at +4 degrees C and -20 degrees C. METHOD: A stability-indicating high-performance liquid chromatography (HPLC) assay was used to measure residual drug at day 0 (D0), D8, D15, D30, D60 and D90 for each bag. Samples were tested for pH at D0, D60 and D90. Frozen samples were thawed in a microwave oven according to a validated procedure before analysis. RESULTS: In 0.9% sodium chloride and 5% dextrose, no degradation products were observed in any of the chromatograms. No admixtures, at any time, contained less than 98.2% of the initial concentration. Only minor changes (-0.12 unit) in pH occurred over the storage period. No colour or other visual changes were seen in any sample. CONCLUSION: Tropisetron (50 microg/ml) in either 0.9% sodium chloride or 5% dextrose is chemically stable in polyvinylchloride or polyolefin bags for at least 3 months when stored in a refrigerator or in a frozen state.

Drug Stability↗

An infectious clone of human parainfluenza virus type 3.

A full-length clone of the human parainfluenza virus type 3 (HPIV-3) genome (called pHPIV-3) was constructed, and recombinant, infectious HPIV-3 was generated by transfecting pHPIV-3 and support plasmids encoding the HPIV-3 NP, P, and L proteins into HeLa cells infected with a vaccinia virus recombinant which expresses T7 RNA polymerase. T7 RNA polymerase promoters on the transfected plasmids direct the synthesis of transcripts encoding the NP, P, and L proteins and a full-length, positive-sense copy of the HPIV-3 genome. Generation of virus was dependent on transfection of pHPIV-3 and the HPIV-3 P- and L-encoding plasmids. However, a plasmid encoding the NP protein was not required since NP was expressed from pHPIV-3. Recovered virus was neutralized by anti-HPIV-3 antisera and shown to contain specific base substitutions characteristic of pHPIV-3. Recombination was shown to occur during recovery, as viruses with two distinct genotypes and phenotypes were isolated. The ability to produce infectious HPIV-3 engineered to contain specific alterations within the HPIV-3 genes and cis-acting elements expedites the study of all aspects of the virus replication cycle. Additionally, analysis of mutations may lead to the identification of attenuating genotypes, a key step in the development of a live virus vaccine.

Cloning, Molecular↗

Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up.

PURPOSE: To analyze initial and long-term outcomes after treatment of patients with active hairy-cell leukemia (HCL) with a single cycle of cladribine (2-CdA). PATIENTS AND METHODS: Forty-nine patients with active HCL were treated with 2-CdA by continuous intravenous infusion at 0.1 mg/kg/d for a total of 7 days at the Long Island Jewish Medical Center between September 1990 and August 1992. Here we report on all patients followed-up until April 1996. RESULTS: At 3 months after treatment, complete response (CR) occurred in 37 patients (76%) and partial response (PR) occurred in 12 patients (24%), for an overall response rate of 100% (95% confidence interval, 94% to 100%). At a median follow-up of 55 months, the relapse-free survival is 80% and overall survival is 95%. Ten patients (20%) have relapsed. Of the 26 patients in whom lymphocyte phenotyping was performed, four were found to have a CD25-negative phenotype. All four of these patients had PRs only and all relapsed. Eight patients have been re-treated with 2-CdA, and all achieved at least a partial remission; two of these have already relapsed with remission durations of less than 1 year. Five second malignancies have occurred in four patients. CONCLUSION: With a median follow-up of more than 4 years, 39 patients (80%) continue in remission. Only two deaths have occurred. A CD25-negative phenotype may predict for a poorer response to 2-CdA. Patients who relapse may be re-treated with 2-CdA, but subsequent remissions may be of shorter duration. There has not been a markedly increased incidence of second malignancies or late opportunistic infections.

Adult↗

Exploring attitudes of white dental students regarding willingness to treat people with HIV.

This descriptive field study examines the willingness of ninety white dental students to provide care to people with Human Immunodeficiency Virus disease (HIV disease). This study suggests that perceived clinical ability, attitudes toward gay men, and white racial attitudes account for white dental students' willingness to provide dental care to patients with HIV disease. Likewise, this study suggests that white dental students' perception of risk of occupational infection with HIV is uniquely predicted by the same variables. A hierarchical regression found that in white dental students, racial attitudes were significant predictors of willingness to treat persons with HIV disease beyond the significant contributions of perceived clinical competence and attitudes toward gay men. In terms of perceptions of occupational risk, results of the hierarchical regression were that both perceived clinical competence and attitudes toward gay men were significant predictors. Thus, the results of this study show that attitudes regarding cultural diversity can influence clinical intentions.

Adult↗

Orthotopic liver transplantation for inflammatory myofibroblastic tumor of the liver hilum.

Inflammatory myofibroblastic tumor is a rare gastrointestinal neoplasm. The authors report the case of a 5-year-old girl who initially presented with gastric outlet obstruction secondary to an inflammatory myofibroblastic tumor along the lesser gastric curvature. A subtotal gastrectomy and wedge resection of a left hepatic lobe nodule were performed. Obstructive jaundice developed one month postoperatively. Computerized tomography, percutaneous transhepatic cholangiography, and selective celiac and mesenteric arteriography showed a mass that involved the left hepatic lobe, with concomitant high-grade biliary obstruction and portal venous encasement. Percutaneous biliary drainage was performed. During laparotomy, the tumor was found to be unresectable, and the patient was referred to the Liver Transplant Service at The Children's Hospital of Philadelphia. A total hepatectomy with temporary portocaval shunt was performed, leaving the inferior vena cava in situ. At the back table, an ex vivo left trisegmentectomy was performed, followed by reimplantation of the posterior segment of the right hepatic lobe. The reimplanted liver segment functioned poorly, and completion hepatectomy with portocaval shunt was performed 24 hours postoperatively, because of severe coagulopathy, intraabdominal bleeding, and hemodynamic instability. The patient's condition stabilized, and she was listed for urgent liver transplantation. The anhepatic state was managed with intermittent plasmapheresis. She had transplantation 72 hours later, and was discharged from the hospital 3 weeks postoperatively after an uneventful recovery. She remains disease-free and has normal liver function 8 months after transplantation.

Child, Preschool↗

Breakdown of gastric staple line as a complication of the uncut Collis-Nissen fundoplication in children.

Uncut Collis-Nissen fundoplication for complicated gastroesophageal reflux was performed in 102 children (46 girls; age 5.6 +/- 4.2 years). Five patients developed intractable emesis postoperatively (average 11 +/- 5 months after surgery) and were found to have two independent luminal openings at the gastroesophageal junction seen on upper endoscopy but not demonstrable on upper GI. The defect was presumed to occur from breakdown of the original staple line on the lesser gastric curve. The condition was successfully repaired in all patients by including a new staple line and rewrapping of the stomach. Practitioners should be aware of this previously unreported complication post uncut Collis-Nissen fundoplication and that this condition may not be excluded by a normal upper GI study.

Child↗

Revertant analysis of J-K mutations in the encephalomyocarditis virus internal ribosomal entry site detects an altered leader protein.

The internal ribosomal entry site (IRES) of picornaviruses consists of various sequence and structural elements that collectively impart translational function to the genome. By engineering substitution and deletion mutations into the J-K elements of the encephalomyocarditis virus IRES, translationally defective viruses with small-plaque phenotypes were generated. From these, 60 larger-plaque revertant viruses were isolated and characterized, and their sequences were compared with a structural model of the IRES. The data provide confirming evidence for the existence of helix J3 within stem J but suggest that helix J1 is 3 bp longer than previously estimated. They also suggest that previously modeled stems L and M should be replaced by an alternative structure. One reversion mutation was mapped to the leader protein coding region. This change of leader amino acid 20 from Pro to Ser increased the viral plaque size dramatically but did not alter the cell-free translational activity of the mutated, parental IRES.

Animals↗

Attributions and responses to the Arab-Israeli conflict: a developmental analysis.

This study assessed the causes ascribed by Israeli children and youth for the Arab-Israeli conflict and the relation of these attributions to their expectations and emotions. The results highlight basic contingencies between the form of attribution and the character of emotional response and future expectation, with marked developmental variations in both the strength and manner of this association. Overall, the findings suggest the utility of Bizman and Hoffman's attributional model as a heuristic for understanding children's perception and response to conflict, but underscore the need for developmental adaptation. Particular attention is drawn to the developing concept of mutuality and its implication for the application of attributional analyses in the young.

Adolescent↗

Acute promyelocytic leukemia and pregnancy. A case report.

BACKGROUND: Acute promyelocytic leukemia (APL) is an uncommon form of acute myeloid leukemia usually associated with disseminated intravascular coagulation (DIC). Pregnancy in patients with APL requires special consideration to maximize the probability of survival of both mother and fetus. METHODS: A patient with APL diagnosed during pregnancy who developed DIC is described. Obstetric and oncologic management of this difficult patient is discussed, and a pertinent literature review of pregnancy in APL is presented. RESULTS: Of 23 pregnancies in patients with APL reported in the literature (including the present patient), 19 yielded live births, including 8 of 12 who received chemotherapy during late pregnancy and all 3 patients who received all-trans-retinoic acid (ATRA) during late pregnancy. Chemotherapy or ATRA induced complete remission in 72% of treated patients. CONCLUSIONS: Proper management of pregnant patients with APL usually results in a live birth and complete remission of the mother's leukemia, despite the potentially devastating consequences of DIC, which is present at diagnosis in most patients.

Adult↗

The effects of vision and task complexity on Hoffmann reflex gain.

Previous research demonstrates modulation of the Hoffmann reflex amplitude and gain during changes in environmental conditions. H-reflex gain (defined in this study as the ratio of H-reflex amplitude to average soleus background EMG) is considered a functional measure of reflex modulation. In this study the effects of manipulating visual input and surface stability were to investigated in 17 subjects under four experimental conditions: (1) vision-stable surface, (2) no vision-stable surface, (3) vision-unstable surface, and (4) no vision-unstable surface. In each condition, subjects performed fifteen trials of a single leg stance for 7 s. The H-reflex was electrically elicited at the end of each trial by delivering a 1 ms square wave stimulation to the tibial nerve in the popliteal online for each trial (sampling rate = 2 kHz). An analysis of variance revealed significant decreases in H-reflex gain for the visual (F1.16 = 4.71, P < 0.05) and, surface conditions (F1.16 = 7.67, P < 0.05), however there was no interaction (F1.16 = 0.48, P < 0.05), between these variables. These results suggest that supraspinal mechanisms, possibly presynaptic inhibition, modulate H-reflex gain across environmental conditions. We conclude that visual and possibly cutaneous inputs were responsible for driving presynaptic inhibition and thus decreasing H-reflex gain.

Analysis of Variance↗

Leukemic meningitis in B-cell prolymphocytic leukemia. A clinical, pathologic, and ultrastructural case study and a review of the literature.

BACKGROUND: Leukemic meningitis is rare in B-chronic lymphocytic leukemia (CLL) and B-prolymphocytic leukemia (PLL); a MEDLINE search for reports published 1960 and after disclosed only nine prior reports. A patient with stable Rai Stage II CLL/PL developed mental status changes. Lumbar puncture revealed a lymphocytic pleocytosis with prolymphocytes containing intracytoplasmic inclusions. METHODS: The patient's cerebrospinal fluid lymphocyte population was analyzed by immunophenotyping and electron microscopy. RESULTS: The studies revealed a clonal population of B prolymphocytes, with typical immunophenotypic and ultrastructural characteristics. The patient was treated with intrathecal chemotherapy with eventual resolution of the cerebrospinal fluid pleocytosis and return to his normal neurologic status. Prior studies also have revealed the efficacy of intrathecal chemotherapy. CONCLUSION: Leukemic meningitis in CLL or PLL is responsive to treatment with intrathecal chemotherapy.

Aged↗

Mutational analysis of the J-K stem-loop region of the encephalomyocarditis virus IRES.

Cap-independent translation of encephalomyocarditis virus (EMCV) RNA is controlled by a segment of the 5' untranslated region termed the internal ribosomal entry site, or IRES. The IRES contains a series of stem-loop structural elements. The J and K stems (EMCV bases 682 to 795), near the center of the IRES, are well conserved among all cardio-, aphtho-, and hepatoviruses. We have examined the biological roles of these elements by constructing mutations within the J-K sequences of EMCV and testing the mutations for activity in translation, translation competition, UV cross-linking, and viral infectivity assays. Mutations near the helical junction of J and K proved severely detrimental to both cellular translation and cell-free translation of downstream cistrons. The same mutations reduced the ability of the IRES to compete for cellular factors in competition assays and reduced the infectivity of viral genomes carrying these lesions. A mutation in the terminal loop of J gave similar results. In contrast, mutations within the terminal loop of K had minimal impact on in vitro translation activity and IRES competitive ability. However, in vivo analysis of the K-loop mutations revealed deficiencies during cellular translation and further showed markedly reduced infectivity in HeLa cells. UV cross-linking experiments identified a 49-kDa protein which interacts strongly with the J-K region, but the identity of this protein and its contribution to IRES activity are unclear.

Base Sequence↗