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Biomedical subjects

R Schwartz

Publications and source records attributed to R Schwartz.

At least 37 records · Page 2Linked to original sources
PubMed2000

Pharmacology and therapeutic use of trastuzumab in breast cancer.

The development, pharmacology, safety, efficacy, and dosage and administration of trastuzumab are reviewed. The discovery of HER2 gene amplification in up to 30% of women with breast cancer led to the development of trastuzumab, a humanized recombinant monoclonal antibody directed against the HER2-receptor protein on breast cancer cells. In large, multicenter trials of trastuzumab as a single agent or in combination with chemotherapy as first-line or second-line therapy for metastatic breast cancer (MBC), response rates have ranged from 12% to 23% for single-agent trastuzumab and from 25% to 62% for trastuzumab plus chemotherapy. Trastuzumab increased time to disease progression and survival time when administered in combination with chemotherapy. The National Comprehensive Cancer Network guidelines for the treatment of breast cancer now include trastuzumab and paclitaxel as an option for patients with MBC or recurrent breast cancer in which the HER2-receptor protein is overexpressed. Trastuzumab is administered weekly, with an initial i.v. dose of 4 mg/kg followed by weekly doses of 2 mg/kg. Most clinical trials continued treatment until disease progression occurred. Adverse effects include infusion-related reactions manifested by fever and chills, exacerbation of chemotherapy-induced gastrointestinal toxicity and myelosuppression, and cardiotoxicity. Trastuzumab, either as a single agent or in combination with chemotherapy, can be an effective therapeutic option for MBC patients who overexpress the HER2-receptor protein and has changed the standard of care.

Antibodies, Monoclonal↗
PubMed2000

"Local rules" theory applied to polyomavirus polymorphic capsid assemblies.

The papovaviruses are nonenveloped dsDNA viruses whose capsids are characterized by a non-quasi-equivalent bonding pattern in which 72 pentameric capsomeres occupy positions having either five or six neighboring capsomeres. The local rules theory of Berger et al. (1994, Proc. Natl. Acad. Sci. USA, 91, 7732-7736), previously developed to explain aspects of icosahedral capsid assembly, has been applied to the papovavirus geometry. Local rules describe capsid symmetry patterns in terms of the local interactions of assembly units, such as coat proteins or capsomeres. Polymorphic assemblies, including T = 1 icosahedral, dodecahedral, spiral, and tubular structures of the polyomavirus VP1 protein, can be induced by specific mutations or changes in the solvent conditions during in vitro assembly of the recombinant coat protein. Local rules models were developed to model the wild-type capsid and several polymorphic assemblies. Some assemblies corresponded to structures modeled by small deviations from wild-type local rules. We conclude that aspects of polyomavirus assembly are consistent with local rules models, although they do not explain all polymorphisms. These results may provide insights into the nature of papovavirus assembly, constraints on assembly pathways, and strategies for disrupting assembly.

Capsid↗
PubMed2000

The prevalence of celiac disease in at-risk groups of children in the United States.

OBJECTIVE: In contrast to its prevalence in Europe, celiac disease (CD) is considered rare in the United States. We aimed to determine the prevalence of CD in children presenting with symptoms or conditions associated with CD. STUDY DESIGN: Individuals aged 6 months to 20 years were screened for IgG and IgA antigliadin (AGA-IgG and AGA-IgA) and antiendomysium (EMA) antibodies. Those with only elevated AGA-IgG were screened for selective IgA deficiency. Patients with elevated EMA, or AGA-IgG elevation and selective IgA deficiency, were advised to undergo small intestinal biopsy. RESULTS: A total of 1200 individuals were studied; 34 were EMA positive-26 (19 EMA positive) consented to biopsy and 21 had CD, giving a prevalence of 1 in 57 (21/1200). Including the 15 EMA positive patients who refused a biopsy, the prevalence of CD in this study could be as high as 1 in 33 (36/1200). CONCLUSIONS: CD is not rare in the United States and may be as common as in Europe. AGA and EMA are useful for identifying patients who should undergo a small intestinal biopsy.

Adolescent↗
PubMed2000

Effects of diabetic pregnancy on the fetus and newborn.

Diabetes in pregnancy is unique because of the diversity of problems that can affect the embryo/fetus beginning with conception. Considerable effort has been devoted to understanding the basic developmental biology from observing young embryos in vitro or in vivo. Maternal glucose control has been identified as an important event. The preponderance of evidence indicates that rigid glucose control will minimize the incidence of anomalies incurred before 9 weeks of pregnancy. Later events are related to fetal hyperinsulinemia. These include fetal macrosomia, respiratory distress syndrome, neonatal hypoglycemia, neonatal hypocalcemia, and neonatal hypomagnesemia. Control of maternal metabolism can have a significant impact on each of the above. Finally, the long-term effects of maternal diabetes are as diverse as the pathogenetic events during pregnancy. Surprisingly, there is a significant transmission rate of 2% of type I diabetes if the mother has insulin-dependent diabetic mother, whereas the rate is 6% for the father. The Diabetes in Early Pregnancy Study showed that good maternal control was associated with normal neurodevelopmental outcome.

Blood Glucose↗
PubMed2000

Potentially reversible cognitive impairment in patients presenting to a memory disorders clinic.

This paper aims to describe a memory disorders clinic (MDC) for the assessment of patients presenting with early cognitive impairment, to examine the predictive utility of laboratory tests conducted on patients with early memory complaints, and, to investigate the potential reversibility of cognitive impairment in 80 consecutive patients presenting to an MDC. Abnormal laboratory results did not significantly correlate with diagnosis at presentation, with presence or absence of cognitive impairment at presentation or at one year follow up, or with cognitive outcome. Thorough assessment of a person presenting with memory impairment is mandatory. We suggest that a routine battery of laboratory investigations be replaced with selected investigations based on clinical indicators only. The term 'reversible dementia' is a misnomer, and we recommend instead the use of 'potentially reversible cognitive impairment'. We argue that the term 'dementia' should only be used to describe cognitive impairment in cases of irreversible degenerative brain disease.

Adult↗
PubMed2000

Effects of a single and double commercial athletic mouthpiece on expiratory peak flow: a pilot study.

Utilizing an Assess Peak Flow Meter, six healthy subjects with no lung disease volunteered to have their expiratory peak flow measured under the following five conditions: 1. Biting on the oral tube of the peak flow meter and lip-sealing the tube; 2. Using a custom built diaphragm allowing the subject to lip-seal the tube of the peak flow meter without biting on it; 3. Using orange wood blocks of known dimension bilaterally on the posterior occlusion, and a custom built diaphragm allowing the subject to lip-seal the oral tube of the peak flow meter without biting on it; 4. Using a commercial single (maxillary) athletic mouthpiece and a custom built diaphragm allowing the subject to lip-seal the oral tube of the peak flow meter without biting on it; and 5. Using a commercial double (maxillary and mandibular) athletic mouthpiece and a custom built diaphragm allowing the subject to lip-seal the oral tube of the peak flow meter without biting on it. Expiratory peak flow measurements were virtually the same whether the subjects bit and lip-sealed on the oral tube of the peak flow meter, used the custom diaphragm and lip-sealed without biting on the oral tube of the peak flow meter, or bit on the orange wood blocks while using the custom diaphragm and lip-sealing without biting on the oral tube. There was significant deterioration (p < .0001) in expiratory peak flow volume when either the single or double commercial athletic mouthpieces were employed.

Adult↗
PubMed2000

Discovery of novel antifungal (1,3)-beta-D-glucan synthase inhibitors.

The increasing incidence of life-threatening fungal infections has driven the search for new, broad-spectrum fungicidal agents that can be used for treatment and prophylaxis in immunocompromised patients. Natural-product inhibitors of cell wall (1,3)-beta-D-glucan synthase such as lipopeptide pneumocandins and echinocandins as well as the glycolipid papulacandins have been evaluated as potential therapeutics for the last two decades. As a result, MK-0991 (caspofungin acetate; Cancidas), a semisynthetic analogue of pneumocandin B(o), is being developed as a broad-spectrum parenteral agent for the treatment of aspergillosis and candidiasis. This and other lipopeptide antifungal agents have limited oral bioavailability. Thus, we have sought new chemical structures with the mode of action of lipopeptide antifungal agents but with the potential for oral absorption. Results of natural-product screening by a series of newly developed methods has led to the identification of four acidic terpenoid (1,3)-beta-D-glucan synthase inhibitors. Of the four compounds, the in vitro antifungal activity of one, enfumafungin, is comparable to that of L-733560, a close analogue of MK-0991. Like the lipopeptides, enfumafungin specifically inhibits glucan synthesis in whole cells and in (1,3)-beta-D-glucan synthase assays, alters the morphologies of yeasts and molds, and produces a unique response in Saccharomyces cerevisiae strains with point mutations in FKS1, the gene which encodes the large subunit of glucan synthase.

Antifungal Agents↗
PubMed2000

Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds.

The definition of clinically significant hypoglycemia remains one of the most confused and contentious issues in contemporary neonatology. In this article, some of the reasons for these contentions are discussed. Pragmatic recommendations for operational thresholds, ie, blood glucose levels at which clinical interventions should be considered, are offered in light of current knowledge to aid health care providers in neonatal medicine. Future areas of research to resolve some of these issues are also presented.

Adaptation, Physiological↗
PubMed2000

The economic implications of self-care: the effect of lifestyle, functional adaptations, and medical self-care among a national sample of Medicare beneficiaries.

OBJECTIVES: Self-care includes actions taken by individuals to promote or ensure their health, to recover from diseases or injuries, or to manage their effects. This study measured associations between self-care practices (lifestyle practices, adaptations to functional limitations, and medical self-care) and Medicare expenditures among a national sample of adults 65 years and older. METHODS: Regression models of Medicare use and expenditures were estimated by using the National Survey of Self-Care and Aging and Medicare claims for 4 years following a baseline interview. RESULTS: Lifestyle factors (swimming and walking) and functional adaptations (general home modifications) were associated with reductions in monthly Medicare expenditures over a 12-month follow-up period. Expenditure reductions were found over the 48-month follow-up period for participation in active sports, gardening, and medical self-care. Practices associated with increases in expenditures included smoking, physical exercise (possibly of a more strenuous nature), and specific home modifications. CONCLUSIONS: Certain self-care practices appear to have significant implications for Medicare expenditures and presumptively for the health status of older adults. Such practices should be encouraged among older adults as a matter of national health policy.

Activities of Daily Living↗
PubMed2000

Access site management after aortic valvuloplasty using a suture mediated closure device: clinical experience in 4 cases.

Management of the femoral access site following percutaneous balloon aortic valvuloplasty is often associated with significant vascular morbidity. In an effort to reduce vascular complications, a novel method of suture mediated closure device deployment was employed in four patients that underwent aortic valvuloplasty at our institution. Delivery of the sutures to the access site took place prior to the intervention in all patients. This pre-close technique allowed the sutures to be placed utilizing the 10 French (Fr) closure device prior to expanding the access site to a 14 Fr size. This was done to facilitate adequate tissue capture, thereby assuring successful hemostasis following sheath removal. The technique was successful in all patients and none of the patients suffered vascular complications. This new access site management method was successful in achieving hemostasis and provided improved patient recovery in this small group of patients as compared to our usual experience.

Aged↗
PubMed2000

Mammography utilization in a skilled nursing facility.

OBJECTIVE: To examine mammography utilization and subsequent clinical decisions in a skilled nursing facility in women aged 75 years and older with no history of breast cancer. METHODS: This study was a retrospective medical chart review of 95 women living in a skilled nursing facility aged 75 years and older who did not have a history of breast cancer. RESULTS: One-hundred seventy-nine mammograms were performed on 95 patients with an average of 1.9 mammograms per patient. Forty-five percent of the women had some evidence of abnormal results requiring further investigation. DISCUSSION: Determining the utility of screening mammography in long-term care populations is essential to the development of appropriate guidelines. Future research should further explore the influence of patient preferences and psychological burden.

Aged↗
PubMed1999

Necessity versus sufficiency: the role of input in language acquisition.

There is data which indicates that the critical/sensitive period(s) for language development begins in the 6th month of fetal life and may be most susceptible to impairment during the first 2 years of life. There are observations which would indicate that the linguistic abilities which develop are dependent upon the amount of linguistic information available to the infant and are not dependent upon any particular receptive sensory mode. The challenge for the cochlear implant is to be able to transmit sufficient linguistic information--flux of information--during this period so that the resultant language is optimal. Language must be the primary outcome measure of the cochlear implant in the infant and young child.

Child, Preschool↗
PubMed1999

Multi-component apparent diffusion coefficients in human brain.

The signal decay with increasing b-factor at fixed echo time from brain tissue in vivo has been measured using a line scan Stejskal-Tanner spin echo diffusion approach in eight healthy adult volunteers. The use of a 175 ms echo time and maximum gradient strengths of 10 mT/m allowed 64 b-factors to be sampled, ranging from 5 to 6000 s/ mm2, a maximum some three times larger than that typically used for diffusion imaging. The signal decay with b-factor over this extended range showed a decidedly non-exponential behavior well-suited to biexponential modeling. Statistical analyses of the fitted biexponential parameters from over 125 brain voxels (15 x 15 x 1 mm3 volume) per volunteer yielded a mean volume fraction of 0.74 which decayed with a typical apparent diffusion coefficient around 1.4 microm2/ms. The remaining fraction had an apparent diffusion coefficient of approximately 0.25 microm2/ms. Simple models which might explain the non-exponential behavior, such as intra- and extracellular water compartmentation with slow exchange, appear inadequate for a complete description. For typical diffusion imaging with b-factors below 2000 s/mm2, the standard model of monoexponential signal decay with b-factor, apparent diffusion coefficient values around 0.7 microm2/ms, and a sensitivity to diffusion gradient direction may appear appropriate. Over a more extended but readily accessible b-factor range, however, the complexity of brain signal decay with b-factor increases, offering a greater parametrization of the water diffusion process for tissue characterization.

Adult↗
PubMed1999

Laparoscopic pancreatic surgery.

BACKGROUND: Potential applications for laparoscopic surgery in pancreatic disease include (1) staging of pancreatic malignancies; (2) palliation of pancreatic malignancies; (3) pancreatic resections for benign and malignant disease; and (4) pancreatic drainage procedures. METHODS: A review of the literature is presented. In addition, original data on a series of 5 laparoscopic pancreatic distal resections and 10 laparoscopic cystogastrostomies are presented. RESULTS AND CONCLUSIONS: Laparoscopy may have a role in the staging of patients with pancreatic malignancies; however, with high-quality preoperative imaging, the percentage of patients who will benefit from laparoscopy may be as low as 5%. For palliation, both cholecystoenterostomy and choledochoenterostomy can be performed laparoscopically. The former is technically straightforward but has a higher failure rate; the latter is technically difficult and currently not suitable for widespread adoption. Laparoscopic gastroenterostomy is a straightforward means of palliating gastrointestinal obstruction. Patients appear to benefit from laparoscopic distal pancreatic resection but not from laparoscopic pancreaticoduodenectomy. Patients appear to benefit from laparoscopic pseudocyst decompression.

Humans↗
PubMed1999

Study on steroidal oximinoethers: synthesis and stereostructure by NMR spectroscopy.

The condensation of O-substituted hydroxylamines with conjugated 3-oxo-4-en steroids results in a mixture of syn-anti configurations. Syn-anti ratios are influenced by sterical hindrance between the oximino substituents (e.g. O-benzyl) and the steroidal skeleton. Stereostructures and isomeric ratios were proved by detailed 1H and 13C NMR studies and also by using 2D-COSY, 2D-HSC, DEPT, 2D-COLOC and DNOE measurements.

Ethers↗