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A Kaufman

Publications and source records attributed to A Kaufman.

At least 55 records · Page 3Linked to original sources
PubMed1995

Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle.

Several reports have shown that individual mitochondrial DNA (mtDNA) deletions accumulate with age. However, the overall extent of somatic mtDNA damage with age remains unclear. We have utilized full-length PCR to concurrently screen for multiple mtDNA rearrangements in total DNA extracted from skeletal muscle derived from physiologically normal individuals (n = 35). This revealed that both the number and variety of mtDNA rearrangements increases dramatically between young and old individuals (P < 0.0001). We further examined the mtDNA from both the younger and older subjects by Southern blot analysis and observed an age-related increase in mtDNA(s) comparable in size to mtDNA products unique to patients with known mtDNA deletions. These data imply that a wide spectrum of mtDNA rearrangements accumulate in old individuals, which correlates with the marked age related decrease in OXPHOS capacity observed in post-mitotic tissues.

Adult↗
PubMed1995

Leber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation.

A novel point mutation in the ND6 subunit of complex I at position 14,459 of the mitochondrial DNA (MTND6*LDY T14459A) was identified as a candidate mutation for the highly tissue-specific disease. Leber's hereditary optic neuropathy plus dystonia. Since the MTND6*LDYT14459A mutation was identified in a single family, other pedigrees with the mutation are needed to confirm its association with the disease. Clinical, biochemical, and genetic characterization is reported in two additional pedigrees. Leber's hereditary optic neuropathy developed in two family members in one pedigree. The daughter had clinically silent basal ganglia lesions. In a second pedigree, a single individual presented with childhood-onset generalized dystonia and bilateral basal ganglia lesions. Patient groups that included individuals with Leigh's disease, dystonia plus complex neurodegeneration, and Leber's hereditary optic neuropathy did not harbor the MTND6*LDYT14459A mutation, suggesting that this mutation displays a high degree of tissue specificity, thus producing a narrow phenotypic range. These results confirm the association of the MTND6*LDYT14459A mutation with Leber's hereditary optic neuropathy and/or dystonia. As the first genetic abnormality that has been identified to cause generalized dystonia, this mutation suggests that nuclear DNA or mitochondrial DNA mutations in oxidative phosphorylation genes are important considerations in the pathogenesis of dystonia.

Adolescent↗
PubMed1995

Renal amino acid transport in adults with oxidative phosphorylation diseases.

The clinical manifestations of mitochondrial DNA (mtDNA) mutations depend on a variety of factors including ratios of normal to abnormal mtDNA and tissue-specific differences in ATP production by oxidative phosphorylation (OXPHOS). In order to investigate the effects of OXPHOS defects on renal tubule function, we characterized sodium-coupled transport processes in six individuals with OXPHOS diseases. Pathogenic mtDNA mutations were identified in five of these individuals. Sodium coupled transport processes were evaluated by determining fractional excretions of amino acids, glucose, lactate, urate, and phosphate in patients and controls. Four of the six individuals had high fractional excretions of neutral amino acids, indicating abnormal renal tubule reabsorbtion of these amino acids. Abnormalities in fractional excretions of lactate, glucose, urate, and phosphate were less pronounced. These results demonstrate that sodium-coupled transport processes in the kidney are sensitive to OXPHOS impairment. When abnormalities in these processes are encountered, an OXPHOS disease should be included in the differential diagnosis.

Adenosine Triphosphate↗
PubMed1995

Mitochondrial encephalomyopathy associated with a single nucleotide pair deletion in the mitochondrial tRNALeu(UUR) gene.

The investigation of pathogenic mitochondrial DNA (mtDNA) mutations has revealed a complex relation between patient genotype and phenotype. For unknown reasons, some mtDNA mutations produce specific clinical manifestations such as chronic progressive external ophthalmoplegia; myoclonic epilepsy and ragged-red fiber disease (MERRF); and mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). To enhance our understanding of the association between genotype and phenotype, we investigated a patient with mitochondrial encephalomyopathy and severe cerebral calcifications for a mtDNA mutation. There was a deletion of one of three T:A nucleotide pairs in the tRNALeu(UUR) gene of the mtDNA involving positions 3271 to 3273. Pedigree analysis suggested that this mutation may have occurred spontaneously in the proband. This analysis represents the smallest mtDNA deletion observed to date and is the first deletion identified within a mitochondrial tRNA. This observation emphasizes the importance of delineating the precise mutation responsible for an oxidative phosphorylation disease for patient diagnosis as well as for genetic counseling of maternal lineage relatives.

Adult↗
PubMed1995

Oxidative phosphorylation diseases and cerebellar ataxia.

Oxidative phosphorylation (OXPHOS) diseases can be caused by mutations in nuclear genes or mitochondrial DNA (mtDNA) genes. mtDNA mutations include complex mtDNA rearrangements in which large segments of mtDNA are duplicated or deleted and point mutations in which single nucleotide substitutions occur within transfer RNA (tRNA) genes, ribosomal RNA (rRNA) genes, or mitochondrial genes encoding OXPHOS polypeptides. Although over 30 pathogenic mtDNA point mutations and over 60 different types of mtDNA deletions are known (Shoffner and Wallace, 1995; Wallace et al., 1994), only a subset of these mutations are associated with cerebellar ataxia. This review focuses on the clinical, biochemical, and genetic features of OXPHOS diseases caused by mtDNA mutations in which ataxia is a common manifestation.

Adult↗
PubMed1994

Teaching and learning methods for new generalist physicians.

This paper describes teaching and learning methods that can be used to build the competencies needed by the generalist physician. Supervised patient care, problem-based learning, and ongoing feedback through standardized patients all have proven efficacy in several domains. Computer-based learning has much to offer as a supplement to clinical teaching. New learning experiences in continuous improvement promise to cover areas that are not often reached by traditional methods, especially those of cost-effectiveness and quality of care. The authors review each method's principles, relationship to generalist competencies, examples of effective applications, and challenges to successful implementation. Where possible, they summarize what is known about the relationships of learning and teaching methods to career choices in generalism.

Adult↗
PubMed1994

Innovative generalist programs: academic health care centers respond to the shortage of generalist physicians.

Academic health care centers increasingly are exploring innovative ways to increase the supply of generalist physicians. The authors review successful innovations at representative academic health centers in the areas of recruitment and admissions, undergraduate medical education, residency training, and practice support. Lessons learned focus on those areas that have demonstrated improvements in the number and quality of physicians trained in family practice, general pediatrics, and general internal medicine. Successful recruitment of generalism-oriented applicants requires identification and tracking of rural, minority, and other special groups of students at the high school and college levels. Academic health care centers that provide early, sustained, community-based, ambulatory experiences for medical students and residents encourage trainees to maintain and choose generalist careers. Finally, academic health care centers that link with community providers and with state government encourage the retention of generalist physicians through continuing education and teaching networks.

Academic Medical Centers↗
PubMed1993

Sinusitis and atopy in human immunodeficiency virus infection.

Sinusitis is increased in patients with human immunodeficiency virus (HIV) infection. To determine the underlying mechanism(s), 37 HIV-positive patients were evaluated. HIV-negative controls included 21 with rhinosinusitis, 32 with atopy, and 16 without sinusitis. Twenty-two HIV-positive patients (59%) had sinusitis; 14 of them had AIDS. There was a significant association between sinusitis severity and stage of HIV infection (P < .05). IgE levels were higher in the HIV-positive patients, increased with disease progression, and were strongly correlated with sinusitis severity (P < .01). Of HIV-positive patients, 72% exhibited more than two positive skin tests compared with 24% of HIV-negative rhinosinusitis patients and 12.5% of controls (P < .05). Sinusitis is common in HIV-positive patients, especially those with AIDS. HIV causes an allergic diathesis with increased IgE levels and allergic reactivity. There is a significant correlation between IgE levels and sinusitis severity, suggesting sinusitis is part of this acquired atopic state.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Pure red cell aplasia and hepatitis A.

A patient with pure red cell aplasia associated with hepatitis A showed a dramatic and rapid recovery after initiation of oral prednisone therapy. The response to corticosteroid therapy suggests an immune etiology for this life-threatening disorder.

Female↗
PubMed1993

Pneumocystis carinii pneumonia presenting as asthma: increased bronchial hyperresponsiveness in Pneumocystis carinii pneumonia.

Two male patients presented with clinical and laboratory findings consistent with typical bronchial asthma and subsequently developed Pneumocystis carinii pneumonia (PCP). Only on subsequent questioning did both admit to homosexuality and behavior associated with a high risk of HIV-infection. In order to determine how frequently reversible airway obstruction is seen in patients with PCP, we measured peak expiratory flow rates (PEFR) before and after bronchodilator administration in 37 of these patients. Initial PEFR measurements revealed a significant decrease in PEFR (< 80% predicted) in 84%, with 54% of these exhibiting a significant bronchodilator response (> or = 15% increase). For comparison, peak flow measurements were made in a control group of 31 HIV-infected patients without acute PCP, divided between those with asymptomatic HIV-infection, AIDS-related complex (ARC), and AIDS, (including patients with previous PCP). Only 23% of these individuals had low PEFR, and only 3% exhibited bronchodilator responses. In order to confirm the existence of bronchial hyperreactivity in patients with PCP, another 16 patients with PCP were tested by methacholine bronchial challenge and 50% were found to have positive responses. These findings suggest that both reversible airway obstruction and airway hyperreactivity are found in association with acute PCP and that as a result some patients with PCP may present with symptoms of asthma. It is important for physicians to have a high degree of suspicion to avoid missing a diagnosis of PCP in a patient presenting with apparent asthma.

AIDS-Related Complex↗
PubMed1992

Health of the public. The academic response. Health of the Public Mission Statement Working Group.

Aging of the population, increasing prevalence of chronic and disabling illnesses with multiple social and behavioral risk factors, concern about quality of care, and escalating costs of medical care require fundamental changes in the way that academic health centers discharge their mission. This article describes a newly developed "Mission Statement" for academic health centers that wish to contribute positively to the health of the populations that they serve. A shift toward addressing the needs of the public may produce increasing institutional strength, long-run stability, and enhanced productivity, as well as higher quality, more cost-effective care for patients. Seventeen centers in the Health of the Public Program are currently conducting activities that implement the described mission elements. The goals and objectives described herein create a foundation for change, with more balanced institutional goals, and could turn an emerging confrontation between academe and its public into an opportunity for both.

Academic Medical Centers↗
PubMed1991

Comparison of adolescent health care provided at a school-based clinic and at a hospital-based pediatric clinic.

Adolescents are an underserved population lacking adequate access to health care. School-based clinics have been promoted as one strategy to improve both access and care. We studied the degree to which such clinics provide services that either differ from or complement conventional health care service. Six categories of primary diagnoses were collected from adolescent visits to a high school clinic and from a nearby hospital-based pediatric clinic, both serving an indigent, predominantly Hispanic, inner-city community. Comparison of patterns of clinic utilization showed that the school-based clinic received significantly more visits for counseling and health care maintenance, while the pediatric clinic received more visits for acute and chronic illnesses. The school-based clinic appeared to improve access to health care for adolescents by allowing confidential visits for issues less easily addressed at more conventional health care sites.

Adolescent↗