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Biomedical subjects

D M Jacobs

Publications and source records attributed to D M Jacobs.

At least 37 records · Page 2Linked to original sources

Is match ethics an oxymoron?

BACKGROUND: Graduate medical education has undergone economic and structural changes-changes that have placed increasing pressure on medical students and programs to match effectively. This study documents the experiences, perceptions, and ethical dilemmas of medical students with the 1998 match process. METHODS: Surveyed were 437 senior students from three medical schools. Students were questioned about: interviewing practices, communication with programs, commitments made, ethical dilemmas faced, and the match process itself. Data were analyzed using Student's t test, the chi-square test, and descriptive statistics. RESULTS: In all, 314 (72%) students responded. Programs expect postinterview communication from students (57%). Students perceive that programs are making "informal" commitments (43%), lying to them (33%), and encouraging their unethical behavior in order to match (21%). Ethical dilemmas are related to requests for informal commitments. CONCLUSIONS: The NRMP's ruling that denounces prematch commitments is being broken by students and programs alike, resulting in the promotion of unprofessional behavior and gamesmanship.

Career Choice↗

Effect of literacy on neuropsychological test performance in nondemented, education-matched elders.

The current investigation compared neuropsychological test performance among nondemented literate and illiterate elders. The sample included participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and did not have history of Parkinson's disease, stroke, or head injury. Literacy level was determined by self-report. MANOVAs revealed a significant overall effect for literacy status (literate vs. illiterate) on neuropsychological test performance when groups were matched on years of education. The overall effect of literacy status remained significant after restricting the analyses to elders with no formal education, and after controlling for the effects of language of test administration. Specifically, illiterates obtained lower scores on measures of naming, comprehension, verbal abstraction, orientation, and figure matching and recognition. However tests of verbal list delayed recall, nonverbal abstraction, and category fluency were unaffected by literacy status, suggesting that these measures can be used to accurately detect cognitive decline among illiterate elders in this sample. Differences in organization of visuospatial information, lack of previous exposure to stimuli, and difficulties with interpretation of the logical functions of language are possible factors that contribute to our findings.

Aged↗

Human replication protein A: global fold of the N-terminal RPA-70 domain reveals a basic cleft and flexible C-terminal linker.

Human Replication Protein A (hsRPA) is required for multiple cellular processes in DNA metabolism including DNA repair, replication and recombination. It binds single-stranded DNA with high affinity and interacts specifically with multiple proteins. hsRPA forms a heterotrimeric complex composed of 70-, 32- and 14-kDa subunits (henceforth RPA70, RPA32, and RPA14). The N-terminal 168 residues of RPA70 form a structurally distinct domain that stimulates DNA polymerase alpha activity, interacts with several transcriptional activators including tumor suppressor p53, and during the cell cycle it signals escape from the DNA damage induced G2/M checkpoint. We have solved the global fold of the fragment corresponding to this domain (RPA70 delta 169) and we find residues 8-108 of the N-terminal domain are structured. The remaining C-terminal residues are unstructured and may form a flexible linker to the DNA-binding domain of RPA70. The globular region forms a five-stranded anti-parallel beta-barrel. The ends of the barrel are capped by short helices. Two loops on one side of the barrel form a large basic cleft which is a likely site for binding the acidic motifs of transcriptional activators. Many lethal or conditional lethal yeast point mutants map to this cleft, whereas no mutations with severe phenotype have been found in the linker region.

Amino Acid Sequence↗

Risk factors and patterns of injury in snowmobile crashes.

OBJECTIVE: To evaluate risk factors for snowmobile injury and patterns of injury. METHODS: We performed a retrospective analysis of patients with snowmobile injury at three trauma centers. Data were collected from trauma databases and patients charts from January 1988 through April 1996; we obtained statistics from the Minnesota Department of Natural Resources for comparison purposes. RESULTS: There were 274 patients identified. The average age was 29 years (SD 12, range 1.6-77). The male:female ratio was 6.6:1. Helmets were used in 35%, not used in 10%, and not reported in 55%. Ethanol consumption was reported in 44% of patients. The average speed of the snowmobile at the time of the accident, when reported, was 47 mph/75 kph (n = 103, range 10-100 mph/16-166 kph). Of these patients, 26% (n = 27) reported a speed in excess of the legal limit (55 mph/88 kph). Accidents were more common in the afternoon and evening hours, and most accidents were caused by the snowmobile striking terrain or man-made objects. Mortality rate was 3.6% for this patient group (10 of 274). The average injury severity score (ISS) was 15 (SD 11). The average Glasgow Coma Score (GCS) was 14. The average number of patients who went to the intensive care unit and the total lengths of stay were 2 +/- 5 and 8 +/- 9 days, respectively. Neither GCS nor ISS correlated with reported speed. The frequencies of different types of injuries are as follows: fractures of upper and lower extremities (n = 184), serious head injury (n = 92), facial fractures or soft tissue injury to head or neck (n = 88), thoracic injury (n = 80), spine injuries (n = 50), intraabdominal injuries (n = 41), and pelvic fractures (n = 31). CONCLUSIONS: Snowmobile injuries are related to ethanol use and the high speed attained by the newer generation of snowmobiles. Extremity fractures were a common component of snowmobile injury in this series, and rates of such injuries are similar to rates injuries in motorcycle accidents in states with helmet laws. Efforts at prevention of snowmobile injuries should be targeted at rider education and enforcement of alcohol restrictions.

Accidents↗

Wound management in perforated appendicitis.

Open wound management after perforated appendicitis was common practice but, recently, primary closure has been advocated to reduce costs and morbidity. Hospital records from 319 adults who underwent appendectomy from 1993 to 1996 were reviewed to identify surgical wound infections (SWIs) and examine risk factors. Information about age, length of stay (LOS), operative time, white blood cell count, and antibiotic administration were obtained. Perforation was either noted at operation or identified microscopically by the pathologist. If primary wound closure was performed, patients with acute appendicitis and perforation had a 4-fold higher readmission rate, a 5-fold increase in SWI, and twice the LOS compared with patients with acute appendicitis without perforation. Patients with grossly perforated acute appendicitis had no difference in LOS if the wound was treated open or closed primarily. No patient with microscopic perforation and primary wound closure developed SWI. Primary wound closure after acute appendicitis was safe in the absence of clinical perforation. In the presence of clinical appendiceal perforation the wound should be left open.

Acute Disease↗

Initial experience with laparoscopic live donor nephrectomy.

BACKGROUND: Advances in laparoscopic instruments and video technology have made laparoscopic donor nephrectomy (LDN) feasible. We report our initial experience with this technique. METHODS: A retrospective review of 30 open donor nephrectomies and our first 30 LDNs was performed to assess donor and recipient outcome and resource usage. RESULTS: LDN was successfully completed in 26 donors (87%). The increased operative time and costs were balanced by less postoperative pain, earlier discharge, earlier return to normal activity and work, fewer incision problems, and less personal financial loss. Recipient outcome was not affected. CONCLUSION: LDN is technically feasible and safe, and recipient graft outcomes are equivalent. Convalescence is shortened, and there is less personal financial loss. LDN offers significant benefit to the donor and may result in increased organ donation.

Adult↗

Civilian rectal trauma: a changing perspective.

BACKGROUND: Recently the Organ Injury Scaling Committee of the American Association for the Surgery of Trauma developed a Rectal Injury Scaling System (RISS). Little data exist regarding its clinical utility. METHODS: We retrospectively reviewed 45 patients with rectal injuries to assess the impact of the RISS on patient management and outcome. We compared RISS grade I patients (group I, partial-thickness injury) with patients with grades 2, 3, and 4 injuries (group II, full-thickness injury). RESULTS: Group II underwent distal rectal washout and repair of the injury twice as often and had a significantly higher rate of diversion of the fecal stream. This was associated with a 3-fold increase in complications. The only complications in group I were in patients managed with diversion of the fecal stream and distal rectal washout. CONCLUSIONS: Our data suggest that aggressive surgical management for RISS grade I injury may not be necessary. Implementation of therapy based on the RISS may improve outcomes of civilian rectal trauma.

Adolescent↗

Assessment of the relationship between timing of fixation of the fracture and secondary brain injury in patients with multiple trauma.

BACKGROUND: It has been suggested that early fixation of a fracture is deleterious to eventual neurologic outcome. We undertook this study to determine whether the timing of fracture fixation is correlated to neurologic outcome. METHODS: We retrospectively reviewed patients with severe head and orthopedic injuries requiring fracture fixation. Patients were divided into two groups: early fracture fixation (< 24 hours after injury) and late fracture fixation (> 24 hours after injury). RESULTS: One hundred twenty-three patients met entry criteria. During fracture fixation, the early group had a significant 2-, 3-, and 2-fold increase in crystalloid, blood infusion, and blood loss, respectively. There was no difference in oxygen saturation and systolic blood pressure or episodes of cranial hypertension or hypoperfusion. There was no difference in outcomes as measured by in-hospital complications, stay in the intensive care unit or hospital, mortality rates, hospital discharge or follow-up Glasgow Coma Scores, or long-term orthopedic or neurologic results. CONCLUSIONS: Patients undergoing fracture fixation with severe head injury mandate monitoring of intracranial pressure and perfusion and tailored fluid resuscitation to meet specific organ end points. Integrating end organ perfusion and pressure with meticulous fluid status during the definitive repair phase may reduce the exposure to secondary brain injury in patients undergoing early fracture fixation.

Adult↗

Cognitive function in nondemented older women who took estrogen after menopause.

Investigations of the effects of estrogen replacement on cognitive function in healthy older women have yielded disparate results. We evaluated the relationship between a history of estrogen use and cognitive test performance in 727 women participating in a large community-based study. Participants were followed longitudinally for an average of 2.5 years. Estrogen use history was obtained at baseline. Standardized tests of memory, language, and abstract reasoning were administered at baseline and at follow-up. Results indicate that women who had used estrogen replacement scored significantly higher on cognitive testing at baseline than nonusers, and their performance on verbal memory improved slightly over time. The effect of estrogen on cognition was independent of age, education, ethnicity, and APOE genotype. Results suggest that estrogen replacement therapy may help to maintain cognitive function in nondemented postmenopausal women.

Aged↗

Cognitive test performance among nondemented elderly African Americans and whites.

We examined the neuropsychological test performance of a randomly selected community sample of English-speaking non-Hispanic African American and white elders in northern Manhattan. All participants were diagnosed as nondemented by a neurologist, whose assessment was made independent of neuropsychological test scores. African American elders obtained significantly lower scores on measures of verbal and nonverbal learning and memory, abstract reasoning, language, and visuospatial skill than whites. After using a stratified random sampling technique to match groups on years of education, many of the discrepancies became nonsignificant; however, significant ethnic group differences on measures of figure memory, verbal abstraction, category fluency, and visuospatial skill remained. Discrepancies in test performance of education-matched African Americans and whites could not be accounted for by occupational attainment or history of medical conditions such as hypertension and diabetes. These findings emphasize the importance of using culturally appropriate norms when evaluating ethnically diverse elderly for dementia.

Aged↗

Prospective comparative study of the evolution of probable Alzheimer's disease and Parkinson's disease dementia.

No previous comparison of test performance in probable Alzheimer's disease (pAD) and Parkinson's disease (PD) dementia has provided information about potential differences in the dementing process. This study compared the evolution of cognitive changes associated with these dementias. Generalized estimating equations (GEE) applied to regression analyses with repeated measures were used to evaluate cognitive changes over 1 to 3 years prior to the point when dementia was diagnosed in 40 matched pairs of patients with incident pAD and PD dementia. Both groups' performance declined on the Short Blessed, Selective Reminding Test (SRT; total recall, long-term retrieval, and delayed recall), Boston Naming Test, Category Fluency, and Similarities. The decline on naming and SRT delayed recall was more rapid in the PD dementia group, suggesting that these performance deficits emerge earlier in the development of pAD. The PD dementia group performed worse on Category Fluency throughout the follow-up period, suggesting either that dementia is overlaid on this preexisting performance deficit or that this type of executive deficit is an early manifestation of dementia in PD. The pAD group performed more poorly throughout the follow-up period on SRT delayed recognition, consistent with a pAD-specific encoding deficit. We conclude that while pAD and PD dementia are similar in many respects, differences in their evolution support previous observation of unique features in the 2 dementias and suggest different underlying pathologies.

Aged↗

Normative data for a brief neuropsychological battery administered to English- and Spanish-speaking community-dwelling elders.

The use of neuropsychological tests in non-English-speaking populations and among those with less education has been limited because most tests have been standardized for English-speaking populations with relatively high levels of education. In effort to establish norms, a battery of neuropsychological tests was administered, in either English or Spanish, to 995 normal elders with a wide range of educational attainment, residing in the community of Washington Heights-Inwood in northern Manhattan. Results indicate that age, education, and language all influence test performance and should be considered when evaluating neuropsychological measures.

Aged↗

Predicting time to nursing home care and death in individuals with Alzheimer disease.

OBJECTIVE: To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies. DESIGN: Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed. SETTING: Three AD research centers. PATIENTS: All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit. INTERVENTION: Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features. MAIN OUTCOME MEASURES: (1) Requiring the equivalent of nursing home placement and (2) death. RESULTS: Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted. Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients. When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients. CONCLUSIONS: The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.

Age of Onset↗

The course of psychopathologic features in mild to moderate Alzheimer disease.

BACKGROUND: The onset and course of the psychopathologic features of Alzheimer disease have not been established in prospective, longitudinal studies. METHODS: Two hundred thirty-five patients with early, probable Alzheimer disease were recruited at 3 sites and observed naturalistically for up to 5 years. At 6-month intervals, the Columbia University Scale for Psychopathology in Alzheimer's Disease was administered. Markov analyses were used to predict the probability of a specific symptom developing or being maintained at the next visit. For each symptom category, the maximum frequency of occurrence at 4 consecutive points (duration, 2 years) was calculated. RESULTS: Misidentification, wandering or agitation, and physical aggression increased during follow-up. At any visit, the likelihood of a new symptom developing was greatest for behavioral disturbance, intermediate for paranoid delusions and hallucinations, and least for depressed mood with vegetative features. Wandering or agitation occurred at 3 or more of 4 consecutive visits (duration, 2 years) in the majority of patients, paranoid delusions and hallucinations were intermediate in their degree of persistence, and depressed mood with vegetative signs rarely persisted. CONCLUSIONS: Behavioral disturbance, particularly agitation, is common and persistent in patients with Alzheimer disease. Psychotic symptoms are less common and show moderate persistence over time. Depressed mood with vegetative signs is uncommon and rarely persists. These findings suggest leads about the optimal treatment duration for specific subtypes of psychopathologic features.

Aged↗

Pathological correlates of extrapyramidal signs in Alzheimer's disease.

Extrapyramidal signs frequently accompany Alzheimer's disease (AD), but the pathological substrate remains unknown. Clinical and postmortem information from patients with AD, Parkinson's disease, or progressive supranuclear palsy and control subjects seen at a large tertiary medical center between 1989 and 1994 was examined. AD patients who had taken neuroleptics and AD brains that also contained Lewy bodies were excluded. The presence of extrapyramidal signs was determined using the Unified Parkinson's Disease Rating Scale. Sections of basal ganglia, subthalamic nucleus, and substantia nigra were examined for neurofibrillary tangles and neuropil threads and the nigra for neuronal numbers. Patients with AD (with or without extrapyramidal signs) did not show neuronal loss in the nigra compared to control subjects, while both Parkinson's disease and progressive supranuclear palsy brains showed marked depletion. The number of neurofibrillary tangles and neuropil threads was increased in AD (with or without extrapyramidal signs) nigra compared to control tissue, and also in progressive supranuclear palsy nigra, but not Parkinson's disease nigra. The numbers of nigral neurofibrillary tangles and neuropil threads were positively related to extrapyramidal signs in AD. There were no correlations between tangles and threads in the basal ganglia or subthalamic nucleus and extrapyramidal signs in AD. Thus, extrapyramidal signs in AD correlate best with tangle pathology in the nigra and do not require the concomitant presence of Lewy bodies.

Aged↗

The absence of an apolipoprotein epsilon4 allele is associated with a more aggressive form of Alzheimer's disease.

We investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE epsilon4 allele. The rate of decline in modified Mini-Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE epsilon4 alleles compared with patients with other genotypes. Compared with patients without an APOE epsilon4 allele, the risk of mortality was also decreased in patients with at least one epsilon4 allele (RR = 0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE epsilon4 is associated with a less aggressive form of AD.

Age of Onset↗

A randomized trial comparing cyclosporine induction with sequential therapy in renal transplant recipients.

Calcium antagonists may reduce the nephrotoxicity of cyclosporine (CsA), allowing CsA to be introduced immediately after renal transplantation and thereby obviating the need for sequential induction therapy with a monoclonal or polyclonal antibody. To test this hypothesis, in a pilot feasibility trial 100 cadaveric or one-haplotype-mismatched living-related renal transplant recipients were randomized to either (1) sequential therapy with anti-thymocyte globulin (ATG) (ATGAM; Upjohn, Kalamazoo, MI) 20 mg/kg/d for 7 to 14 days until renal function was established and CsA (Sandimmune; Sandoz, East Hanover, NJ) was started, or (2) CsA 8 mg/kg/d begun immediately before surgery with diltiazem (Cardizem; Marion Merrell Dow, Kansas City, MO) 60 mg sustained release twice daily. Acute rejection episodes during the first 90 days were not different with ATG versus CsA induction (42% v 28%; P = 0.142 by chi-square analysis). Graft failures (10% v 16%; P = 0.372) and the incidence of delayed graft function (28% v 34%; P = 0.516) were also similar with ATG compared with CsA. ATG caused lower platelet counts (138 +/- 59 x 10(3) v 197 +/- 75 x 10(3) at 7 days; P < 0.001) and lower white blood cell counts (9.6 +/- 4.6 x 10(3) v 12.3 +/- 4.9 x 10(3) at 7 days; P = 0.003). Diltiazem reduced the dose of CsA required to maintain target blood levels (479 +/- 189 mg/d v 576 +/- 178 mg/d at 14 days; P = 0.015). There were no statistically significant differences between the groups in serum creatinine levels at days 1, 3, 5, 7, 14, 28, 60, or 90. The results of this pilot feasibility trial suggest that prophylactic treatment with CsA and diltiazem may be equally effective and less toxic than ATG induction after renal transplantation.

Adult↗