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Biomedical subjects

R Goldberg

Publications and source records attributed to R Goldberg.

At least 37 records · Page 2Linked to original sources

Differential localization of arabinan and galactan side chains of rhamnogalacturonan 1 in cambial derivatives.

The development of pectin structural features during the differentiation of cambial derivatives was investigated in aspen (Populus tremula L. x P. tremuloides Michx.) using biochemical and immunocytochemical methods. Comparisons were also made between active and resting tissues. Active tissues, in particular cambial cells and phloem derivatives, were characterized by a high pectin content. Use of antibodies raised against arabinan side chains of rhamnogalacturonan 1 (LM6), as well as biochemical analysis, revealed an obvious decrease from the cortex to the differentiating xylem. Galactan side chains, detected with LM5 antibodies, were present mainly in the cambial zone and enlarging xylem cells. In contrast, they were totally absent from sieve-tube cell walls. Image analysis of LM5 immunogold labelling in the cambial zone showed a clustered distribution of galactan epitopes in the radial walls, a distribution which might result from the association of two different periodic processes, namely the exocytosis of galactan and wall expansion. Cessation of cambial activity was characterized by cell wall thickening accompanied by a sharp decrease in the relative amount of pectin and a lowering of the degree of methylesterification. The data provide evidence that the walls of phloem and xylem cells differ in their pectin composition even at a very early stage of commitment. These differences offer useful tools for identifying the initial cells among their immediate neighbours.

Cell Wall↗

Crohn's disease: a rare cause of upper airway obstruction.

Although uncommon, lesions of Crohn's disease can involve the hypopharynx and lower respiratory tract. We describe a patient with partial airway obstruction secondary to Crohn's disease of the hypopharynx and larynx. This entity should be considered in the differential diagnosis of patients presenting to the Emergency Department with upper airway obstruction.

Adult↗

Missed opportunities to impact fast response to AMI symptoms.

The potential for reducing cardiovascular disease mortality rates lies both in prevention and treatment. The earlier treatment is administered, the greater the benefit. Thus, duration of time from onset of symptoms of acute myocardial infarction to administration of treatment is important. One major factor contributing to failure to receive efficacious therapy is the delay time from acute myocardial infarction (AMI) symptom onset to hospital arrival. This paper examines the relationship of several factors with regard to intentions to seek care promptly for symptoms of AMI. A random-digit dialed telephone survey (n = 1294) was conducted in 20 communities located in 10 states. People who said they would wait until they were very sure that symptoms were a heart attack were older, reported their insurance did not pay for ambulance services, and reported less confidence in knowing signs and symptoms in themselves. When acknowledging symptoms of a heart attack, African-Americans and people with more than a high school education reported intention to act quickly. No measures of personal health history, nor interaction with primary care physicians or cardiologists were significantly related to intention to act fast. The study confirms the importance of attribution and perceived self-confidence in symptom recognition in care seeking. The lack of significant role of health history (i.e. those with chronic conditions or risk factors) and clinician contact highlights missed opportunities for health care providers to educate and encourage patients about their risk and appropriate action.

Adult↗

High-dose chemotherapy and stem cell transplantation for patients with stage IV breast cancer without clinically evident disease: correlation of CD34+ selection to clinical outcome.

Forty-five patients with metastatic breast cancer without clinically evident disease were treated with thiotepa 750 mg/m2, mitoxantrone 40 mg/m2 and carboplatin 1000 mg/m2 followed by stem cell transplantation to determine the safety and efficacy of CD34+ selection of peripheral blood stem cells. Of these, 15 patients' (group I) stem cells were processed through Baxter Isolex 300 device for CD34+ selection, whereas 30 patients (group II) received unmanipulated stem cells. Toxicity, progression-free survival and survival were compared between these two groups. There was no difference in transfusion requirements, white cell count and platelet recovery and non-hematologic toxicity between the two groups. The survival of patients in group I was 27 months compared to 38 months in group II (P = 0.8). The progression-free survival was 12 months and 13.5 months for group I and group II patients, respectively (P = 0.6). Our results indicate that while there is no adverse effect, there is also no significant advantage of CD34+ selection in terms of progression-free survival and survival in patients with metastatic breast cancer without clinically evident disease. Bone Marrow Transplantation (2000).

Adult↗

Prevalence and correlates of diabetes in national schizophrenia samples.

People with schizophrenia may be at increased risk for Type II diabetes because of the side effects of antipsychotic medication, poorer overall physical health, less healthy lifestyles, and poorer health care. The present study uses data bases collected by the Schizophrenia Patient Outcomes Research Team (PORT) to assess the prevalence and demographic and clinical correlates of diabetes within large populations of persons receiving treatment for schizophrenia. In the Schizophrenia PORT, Medicaid and Medicare data from 1991 and more recent interview data were collected regarding the comorbidity of schizophrenia and diabetes: prevalence, quality of life, physical health, and services utilization and costs. The study found that rates of diagnosed diabetes exceeded general population statistics well before the widespread use of the new antipsychotic drugs. Risk factors for diabetes were similar to those observed in the general population. The linkage of diabetes to poor physical health, medical morbidity, and increased service use and cost requires attention. This study of diabetes in the early 1990s suggests that even before the widespread use of the atypical antipsychotic drugs, diabetes was a major problem for persons with schizophrenia.

Adult↗

Age and sex differences in presentation of symptoms among patients with acute coronary disease: the REACT Trial. Rapid Early Action for Coronary Treatment.

BACKGROUND: There are few data on possible age and sex differences in presentation of symptoms for patients with acute coronary disease. OBJECTIVE: To investigate demographic differences in presentation of symptoms at the time of hospital presentation for acute myocardial infarction (AMI) and unstable angina. METHODS: The medical records of patients who presented with chest pain and who also had diagnoses of AMI (n = 889) or unstable angina (n = 893) on discharge from 43 hospitals were reviewed as part of data collection activities of the Rapid Early Action for Coronary Treatment trial based in 10 pair-matched communities throughout the USA. RESULTS: Dyspnea (49%), arm pain (46%), sweating (35%), and nausea (33%) were commonly reported by men and women of all ages in addition to the presenting complaint of chest pain. After we had controlled for various characteristics through regression modeling, older persons with AMI were significantly less likely than were younger persons to complain of arm pain and sweating, and men were significantly less likely to report vomiting than were women. Among persons with unstable angina, arm pain and sweating were reported significantly less often by elderly patients. Nausea and back, neck, and jaw pain were more common complaints of women. CONCLUSIONS: Results of this study suggest that there are differences between symptoms at presentation of men and women, and those in various age groups, hospitalized with acute coronary disease. Clinicians should be aware of these differences when diagnosing and managing patients suspected to have coronary heart disease.

Adult↗

Treatment of obstructive sleep apnea, other than with continuous positive airway pressure.

Treatment, other than with continuous positive airway pressure, for patients with obstructive sleep apnea remains an active area of investigation. The long-established behavior modification approaches (eg, weight loss and avoidance of alcohol and sedatives) are applicable to many patients, though unlikely to be curative. Oral appliances and surgical techniques are used, although treatment success is hindered by the site-specific nature of the therapies. These treatments are traditionally used for the patient with mild sleep apnea, but more recent studies are questioning their possible benefits in a moderate-to-severe apnea patient population. Surgical techniques range from uvulopalatopharyngoplasty and more extensive skeletal modifications (maxillomandibular advancement), to laser-assisted uvulopalatoplasty and newer minimally invasive techniques. Preoperative evaluation, patient selection, and measures of success vary somewhat between publications, making comparison of treatments and their application to the individual patient challenging.

Humans↗

Radial distribution pattern of pectin methylesterases across the cambial region of hybrid aspen at activity and dormancy.

Biochemical microanalysis combined with tangential cryosectioning was used to visualize the distribution of pectin methylesterases (PMEs) across the cambial region in active and dormant hybrid aspen (Populus tremula L. x Populus tremuloides Michx). These novel techniques allowed us to relate activity and isoforms of PMEs to specific tissues and developmental stages of the stem to get more information on the physiological function of PMEs in cambial growth. Isoelectrofocusing analysis revealed numerous isoforms that were differentially distributed according to the tissue-type and to the cambial stage. A neutral isoform was found to be distributed ubiquitously across the stem of both active and dormant trees, which suggests that it is a housekeeping isoform involved in the maintenance of the cell wall integrity throughout the stem. In addition, two distinct isoforms having different isoelectric points were found to be related to the differentiation of cambial derivatives. A basic isoform appears to be a physiological marker of the dormant stage involved in the cessation of meristematic radial growth, whereas an acidic isoform is functionally related to the immediate expansion of the cambial daughter cells that occurs bilaterally on each side of the cambium at the active stage.

Carboxylic Ester Hydrolases↗

Sleep medicine practices, training, and attitudes: a wake-up call for pulmonologists.

STUDY OBJECTIVES: To determine attitudes and knowledge about sleep medicine among chest physicians. DESIGN: : Interactive survey of self-selected respondents. SETTING: Interactive session at the 1998 American College of Chest Physicians (ACCP) annual meeting. PARTICIPANTS: Approximately 60 chest physicians. INTERVENTIONS: Interactive questions about the knowledge, training, attitudes, and practice of sleep medicine. MEASUREMENTS AND RESULTS: Response rates demonstrated that 65% of respondents directed or were on the staff of a sleep laboratory, 18% had American Board of Sleep Medicine (ABSM) certification, and only 3% had completed formal sleep medicine training, and performance on test questions about sleep-disordered breathing was better than that on questions about "nonpulmonary" sleep disorders. We polled approximately 60 participants in an interactive session called "Issues in Sleep Medicine Education and Practice" at the ACCP annual meeting in October 1998. The group was well-credentialed, with about one third of participants being board-certified in pulmonary medicine and critical care medicine, and about 17% having passed the ABSM examination. About two thirds of the group spent < or = 25% of their time in the practice of sleep medicine, but > 30% directed sleep laboratories. Respondents thought that sleep training was better addressed in pulmonary fellowship training than in medical school or other postgraduate training experiences. Forty-three percent of the group had received training in sleep medicine as part of a pulmonary fellowship. About half of the sample thought that formal training should be required for eligibility to take the ABSM examination. When presented with two "nonpulmonary" sleep disorder cases, this well-trained and self-selected group did not perform very well. The findings suggest that pulmonologists are actively involved in the practice of sleep medicine and that they both need and desire formal training in sleep disorders during pulmonary fellowship training. CONCLUSIONS: Participants were actively involved in the practice of sleep medicine, most had trained informally, and performance on questions about nonpulmonary sleep disorders was not good.

Adult↗

Oxaliplatin in colorectal cancer: current studies.

One of the more promising chemotherapeutic agents for patients with metastatic colorectal cancer is oxaliplatin (Eloxatin), a third-generation platinum derivative with a unique mechanism of action. Preclinical studies corroborated by results from early trials suggested that oxaliplatin could be particularly advantageous when used in combination with fluorouracil (5-FU)/leucovorin. In addition, early studies of oxaliplatin as monotherapy showed clear activity similar in magnitude to that observed with other active agents. When administered as neoadjuvant therapy in patients with unresectable liver metastases, the responses were substantial enough for some patients to undergo potentially curative hepatic resection. These trials also demonstrated a reasonable safety profile for oxaliplatin. In light of the accumulating data on the use of oxaliplatin in advanced colorectal cancer, the North Central Cancer Treatment Group (NCCTG) and other cooperative groups developed trials to further define the specific therapeutic roles and optimal regimens of oxaliplatin combined with 5-FU and leucovorin, as well as other agents. A number of studies are underway in the United States, including the three-arm NCCTG N9741 trial in patients with previously untreated metastatic colorectal cancer, the NCCTG N9841 trial in patients who progressed on 5-FU/leucovorin, and the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 adjuvant trial for stage II and III colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Concomitant human immunodeficiency virus protease inhibitor therapy markedly reduces tacrolimus metabolism and increases blood levels.

We present the case of a patient with hepatitis C-induced cirrhosis and concomitant human immunodeficiency virus infection who underwent orthotopic liver transplantation. The patient developed severe, prolonged tacrolimus toxicity in the presence of human immunodeficiency virus protease inhibitors. At various times, the patient received saquinavir, ritonavir, and nelfinavir in conjunction with tacrolimus. In each instance, the tacrolimus concentration rose to toxic levels. We hypothesize that the protease inhibitors' competition for binding to cytochrome P450 isoenzyme system CYP3A induced extreme prolongation of tacrolimus metabolism. After stabilization of the patient, reinstitution of treatment with nelfinavir resulted in a >95% reduction in tacrolimus dosing from 4 mg twice per day to 0.5 mg once every 3-5 days.

Aryl Hydrocarbon Hydroxylases↗

Design and synthesis of thiol containing inhibitors of matrix metalloproteinases.

A series of thiol containing derivatives was prepared. Several of these compounds were found to inhibit matrix metalloproteinases 1, 3, and 9 with selectivity towards 3 and 9. Compounds 15, 20, and 22 were administered to rats orally at 75 mumol/kg. Drug levels of compounds 20 and 22 in the plasma were found to exceed the IC50 values for MMP 3 and 9 four hours after administration.

Animals↗

Antibody titers to hepatitis B surface antigen among vaccinated emergency physicians: three years' experience with a wellness booth.

STUDY OBJECTIVE: To determine antibody titers to hepatitis B surface antigen (anti-HBsAg) among previously vaccinated emergency physicians and to assess the degree of compliance with Centers for Disease Control and Prevention (CDC) postvaccination guidelines. METHODS: A descriptive analysis was performed of anti-HBsAg titer determinations and vaccination surveys among a self-selected group of emergency physicians attending the annual scientific assembly of the American College of Emergency Physicians in 1995, 1996, or 1997. RESULTS: Of 943 participants, titer levels were found to be protective in 768 (81%), borderline in 45 (5%), and nonreactive in 130 (14%). A total of 337 participants (36%) had not obtained postvaccination titer determinations, as advised by the CDC. More than 50% reported an occupational exposure to blood products within the previous 2 years. CONCLUSION: Despite their high risk for exposure to blood products, many previously vaccinated emergency physicians were not in compliance with CDC postvaccination guidelines.

Centers for Disease Control and Prevention, U.S.↗

A common breakpoint on 11q23 in carriers of the constitutional t(11;22) translocation.

Structural chromosomal rearrangements occur commonly in the general population. Individuals that carry a balanced translocation are at risk of having unbalanced offspring; therefore, the frequency of translocations in couples with recurrent spontaneous abortions is higher than that in the general population. The constitutional t(11;22) translocation is the most common recurrent non-Robertsonian translocation in humans and may serve as a model to determine the mechanism that causes recurrent meiotic translocations. We previously localized the t(11;22) translocation breakpoint to a region on 22q11 within a low-copy repeat, termed "LCR22." To define the breakpoint on 11q23 and to ascertain whether this region shares homology with LCR22 sequences, we performed haplotype analysis on patients with der(22) syndrome. We found that the breakpoint on 11q23 occurred between two genetic markers, D11S1340 and APOC3-tetra, both being present within a single bacterial-artificial-chromosome clone. To determine whether the breakpoint occurred within the same region among a larger set of carriers, we performed FISH mapping studies. The breakpoints were all within the same clone, suggesting that this region may harbor sequences that are prone to breakage. We narrowed the breakpoint interval, in both derivative chromosomes from two unrelated carriers, to a 190-bp, AT-rich repeat, which indicates that this repeat may mediate recombination events on chromosome 11. Interestingly, the LCR22s harbor AT-rich repeats, suggesting that this sequence motif may mediate recombination events in nonhomologous chromosomes during meiosis.

Animals↗

A common molecular basis for rearrangement disorders on chromosome 22q11.

The chromosome 22q11 region is susceptible to rearrangements that are associated with congenital anomaly disorders and malignant tumors. Three congenital anomaly disorders, cat-eye syndrome, der() syndrome and velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS) are associated with tetrasomy, trisomy or monosomy, respectively, for part of chromosome 22q11. VCFS/DGS is the most common syndrome associated with 22q11 rearrangements. In order to determine whether there are particular regions on 22q11 that are prone to rearrangements, the deletion end-points in a large number of VCFS/DGS patients were defined by haplotype analysis. Most VCFS/DGS patients have a similar 3 Mb deletion, some have a nested distal deletion breakpoint resulting in a 1.5 Mb deletion and a few rare patients have unique deletions or translocations. The high prevalence of the disorder in the population and the fact that most cases occur sporadically suggest that sequences at or near the breakpoints confer susceptibility to chromosome rearrangements. To investigate this hypothesis, we developed hamster-human somatic hybrid cell lines from VCFS/DGS patients with all three classes of deletions and we now show that the breakpoints occur within similar low copy repeats, termed LCR22s. To support this idea further, we identified a family that carries an interstitial duplication of the same 3 Mb region that is deleted in VCFS/DGS patients. We present models to explain how the LCR22s can mediate different homologous recombination events, thereby generating a number of rearrangements that are associated with congenital anomaly disorders. We identified five additional copies of the LCR22 on 22q11 that may mediate other rearrangements leading to disease.

Chromosome Aberrations↗

Sleep problems in emergency department patients with injuries.

OBJECTIVES: To assess trauma patients' frequency of sleep problems, to evaluate their injuries in the context of their sleep habits, and to determine how often ED health care workers (HCWs) inquire about sleep complaints. METHODS: This was a prospective observational study of patients evaluated in the ED for unintentional trauma. Patients answered a "sleep survey" that was reviewed for the amount and timing of sleep in the preinjury period and for indications of a sleep problem. Preinjury sleep characteristics were compared with the individual's usual habits, and the group's sleep features were compared with "normal" sleep and the prevalence of sleep problems in historical controls. RESULTS: Seventy patients were surveyed. Mechanisms and types of injury included motor vehicle collisions (MVCs), falls, lacerations, bruises, sprains, and fractures. The mean total sleep time in the preinjury period (6.9 hours) was significantly shorter than that obtained during usual weekday and weekend sleep. Twenty-four patients (34.3%) were at high risk for a sleep problem. Few patients thought a sleep problem contributed to the injury. No other ED HCW asked about the patient's sleep habits. CONCLUSIONS: Acute sleep deprivation in the preinjury period, and chronic sleep deprivation with a variety of other sleep problems are found in this patient population. Despite the association of sleep problems and certain types of injury (e.g., MVC), ED HCWs do not inquire about sleep in their initial ED evaluations. This important issue may be overlooked in trauma risk assessment and prevention.

Adolescent↗

Repeatable battery for the assessment of neuropsychological status as a screening test in schizophrenia, II: convergent/discriminant validity and diagnostic group comparisons.

OBJECTIVE: In a companion article in this issue of the Journal, the authors presented data suggesting that the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is sensitive to the types of impairments observed in schizophrenia, correlates highly with standard measures of intelligence and memory, and is related to employment status in a group of patients with schizophrenia drawn from a tertiary care research center. The objectives of the current study were 1) to determine if evidence of the convergent validity of the RBANS could be replicated in a diagnostically heterogeneous sample drawn from a public mental health system, 2) to examine the relationship of the RBANS to a broad neuropsychological battery, and 3) to compare the performance of patients with schizophrenia and patients with bipolar disorder on a neuropsychological battery and the RBANS. METHOD: The RBANS and a standard neuropsychological battery, including the WAIS-III and Wechsler Memory Scale, 3rd ed. (WMS-III), were given to 150 patients drawn from a larger study of vocational rehabilitation. RESULTS: Correlations of RBANS total scores with WAIS-III and WMS-III variables were highly similar across study groups. The RBANS correlated highly with a composite z score derived from 22 standard measures of IQ, memory, language, motor, attention, and executive function. Principal component analyses of the neuropsychological battery resulted in a six-factor solution: the RBANS correlated most highly with a general ability factor and had limited correlations with measures of motor performance, vigilance, and executive function. Patients with schizophrenia demonstrated greater deficits on the neuropsychological battery and the RBANS than patients with bipolar disorder. CONCLUSIONS: These data suggest that the RBANS is a useful screening instrument for assessing the severity of cognitive impairment in psychiatric populations.

Adult↗