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Biomedical subjects

L Freeman

Publications and source records attributed to L Freeman.

At least 19 recordsLinked to original sources

The effects of Neotrofin on septodentate sprouting after unilateral entorhinal cortex lesions in rats.

PURPOSE: Recent research on the purine derivative of hypoxanthine Neotrofin (4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid; AIT-082) has indicated that Neotrofin treatment elevates the mRNA levels of various neurotrophic factors, including nerve growth factor (NGF), in the CNS. Several previous studies have indicated that NGF may regulate septodentate sprouting after entorhinal cortex lesions in rats. Thus, the objective of this investigation was to determine whether Neotrofin treatment would enhance lesion-induced septodentate sprouting from 4 to 15 days postlesion. METHODS: Sham-operated rats or rats with EC lesions were injected (i.p.) with either Neotrofin (30 mg/kg) or saline (0.9%) immediately after surgery and every day thereafter until the end of the treatment regimen. Septodentate sprouting, as indicated by intensity of acetylcholinesterase (AChE) label in the dentate gyrus, was assessed with optical densitometry. RESULTS: We observed that Neotrofin elevated the AChE-label in the outer molecular layer of the ventral dentate gyrus at 4 days postlesion and of the dorsal dentate gyrus at 15 days postlesion. CONCLUSIONS: Neotrofin appears to have exerted limited stimulatory effects on lesion-induced sprouting by a cholinergic pathway.

Alzheimer Disease↗

A fall prevention program for the home environment.

Falls are the leading cause of injury, death, and disability among people older than 65. When elders fall, they sustain such injuries as hip, spine, hand, and/or pelvic fractures. The prognosis after such a fall is poor--only half of older adults hospitalized for hip fractures are able to return home or live independently again. Even without injury, falls cause a loss of confidence that results in reduced physical activity, increased dependency, and social withdrawal. As a home care agency dealing with a geriatric population, our goal was to develop a user-friendly fall prevention program that would promote multidisciplinary assessment and intervention. We have developed a preventive approach through which clinicians and patients can collaborate on preventing falls in the home and maintaining our patients' first priority: quality of life.

Accidental Falls↗

Evaluation of ambulatory and self-initiated blood pressure monitors by pregnant and postpartum women.

OBJECTIVE: To investigate the acceptability of an ambulatory blood pressure (ABP) monitor (SpaceLabs 90207) and a self-initiated blood pressure monitor (Omron HEM-705CP) to pregnant women. METHODS: Acceptability of the SpaceLabs 90207 and Omron HEM- 705CP monitors was evaluated, using a modified British Hypertension Device assessment form, by () healthy, pregnant women at <15 weeks (n = 120), 35-37 weeks (n = 81), and 5-9 weeks postpartum (n = 86); and () women with preeclampsia (n = 52). MAIN OUTCOME MEASURES: A monitor was acceptable if a woman graded the overall impression as "good" or "very good." RESULTS: Healthy women at <15 and 35-37 weeks' gestation and preeclamptic women reported the SpaceLabs 90207 monitor caused discomfort in 54%, 52%, and 60%, interfered with activities in 38%, 40%, and 23%, and disturbed sleep in 62%, 52% and 31%, respectively. Fewer than 12% in any group reported these problems with the Omron HEM-705CP monitor. In the 78 women who evaluated both monitors at 35-37 weeks, the SpaceLabs 90207 and Omron HEM-705CP were acceptable to 78% and 95% of healthy women, respectively (p = 0.005). Women with preeclampsia rated the Space-Labs 90207 as "bad" or "fair" (14%), "good" (58%), and "very good" (28%) compared with "bad" or "fair" (8%), "good" (28%), and "very good" (64%) for the Omron HEM-705CP monitor (p = 0.009). CONCLUSIONS: Pregnant women found the less intensive blood pressure monitoring with the Omron HEM-705CP more acceptable than the 24-h ABP monitoring with the SpaceLabs 90207. If accurate self-initiated blood pressure devices become available, pregnant women would prefer this method of home blood pressure monitoring.

Blood Pressure Monitoring, Ambulatory↗

Inherited infantile dilated cardiomyopathy in dogs: genetic, clinical, biochemical, and morphologic findings.

Dilated cardiomyopathy, a lethal disease characterized by left ventricular dilation and systolic dysfunction, is relatively common in humans and other mammals. Idiopathic dilated cardiomyopathy (IDCM) is a primary myocardial disease of unknown cause and can be a familial disorder. This report describes autosomal recessive IDCM in dogs. It occurs in Portuguese Water Dog (PWD) pups and is manifested by acute, vague clinical signs and sudden death. Affected pups have progressive reduction of fractional shortening that can be demonstrated by echocardiography prior to the development of clinical signs. Furthermore, these pups have low plasma taurine levels when consuming certain diets. Affected pups had dilation of the left ventricle and alterations in the sarcomere appearance, while immunohistochemical and biochemical studies demonstrate an increase in desmin, a cytoskeleton protein. The clinical and morphologic findings of IDCM in PWDs are distinct from those reported in adult IDCM. Finally, the clinical and echocardiographic manifestations were reversible in some pups following oral taurine supplementation for 2 months. These results suggest that IDCM in PWDs is correlated with low plasma taurine levels.

Animals↗

Complete genomic sequence of the human ABCA1 gene: analysis of the human and mouse ATP-binding cassette A promoter.

The ABCA1 gene, a member of the ATP-binding cassette A (ABCA1) transporter superfamily, encodes a membrane protein that facilitates the cellular efflux of cholesterol and phospholipids. Mutations in ABCA1 lead to familial high density lipoprotein deficiency and Tangier disease. We report the complete human ABCA1 gene sequence, including 1,453 bp of the promoter, 146,581 bp of introns and exons, and 1 kb of the 3' flanking region. The ABCA1 gene spans 149 kb and comprises 50 exons. Sixty-two repetitive Alu sequences were identified in introns 1-49. The transcription start site is 315 bp upstream of a newly identified initiation methionine codon and encodes an ORF of 6,783 bp. Thus, the ABCA1 protein is comprised of 2,261 aa. Analysis of the 1,453 bp 5' upstream of the transcriptional start site reveals multiple binding sites for transcription factors with roles in lipid metabolism. Comparative analysis of the mouse and human ABCA1 promoter sequences identified specific regulatory elements, which are evolutionarily conserved. The human ABCA1 promoter fragment -200 to -80 bp that contains binding motifs for SP1, SP3, E-box, and AP1 modulates cellular cholesterol and cAMP regulation of ABCA1 gene expression. These combined findings provide insights into ABCA1-mediated regulation of cellular cholesterol metabolism and will facilitate the identification of new pharmacologic agents for the treatment of atherosclerosis in humans.

ATP Binding Cassette Transporter 1↗

The condensin complex governs chromosome condensation and mitotic transmission of rDNA.

We have characterized five genes encoding condensin components in Saccharomyces cerevisiae. All genes are essential for cell viability and encode proteins that form a complex in vivo. We characterized new mutant alleles of the genes encoding the core subunits of this complex, smc2-8 and smc4-1. Both SMC2 and SMC4 are essential for chromosome transmission in anaphase. Mutations in these genes cause defects in establishing condensation of unique (chromosome VIII arm) and repetitive (rDNA) regions of the genome but do not impair sister chromatid cohesion. In vivo localization of Smc4p fused to green fluorescent protein showed that, unexpectedly, in S. cerevisiae the condensin complex concentrates in the rDNA region at the G2/M phase of the cell cycle. rDNA segregation in mitosis is delayed and/or stalled in smc2 and smc4 mutants, compared with separation of pericentromeric and distal arm regions. Mitotic transmission of chromosome III carrying the rDNA translocation is impaired in smc2 and smc4 mutants. Thus, the condensin complex in S. cerevisiae has a specialized function in mitotic segregation of the rDNA locus. Chromatin immunoprecipitation (ChIP) analysis revealed that condensin is physically associated with rDNA in vivo. Thus, the rDNA array is the first identified set of DNA sequences specifically bound by condensin in vivo. The biological role of higher-order chromosome structure in S. cerevisiae is discussed.

Adenosine Triphosphatases↗

Management of bladder problems in patients with multiple sclerosis.

Bladder problems are a common feature in patients with multiple sclerosis (MS). Many patients experience distressing symptoms such as frequency, urgency and incontinence, unaware of the range of treatments which are available to either overcome or manage their bladder problems. While patients with MS may experience many types of bladder dysfunction, certain types of problem are more common in this patient group. These problems can be grouped under the headings of storage, emptying or combined dysfunction. Community nurses are well-placed to offer methods of containment by providing first-line treatment as well as identifying which patients need to be referred to other members of the multidisciplinary team.

Adult↗

Serial laparoscopic biopsies of liver and spleen from Schistosoma-infected baboons (Papio spp.).

PURPOSE: To obtain large, serial biopsy samples from the liver and spleen by using laparoscopy. Large samples were needed for measurement of inflammatory mediators during various stages of schistosomiasis. METHODS: Each of the seven female baboons (Papio sp.) underwent as many as three laparoscopies, for a total of 19 laparoscopic procedures. This process permitted sampling of the liver, spleen, and mesenteric lymph nodes before and at 6 and 9 weeks after infection with Schistosoma mansoni. All surgery was performed through three trocar sites. Postoperative care included preemptive analgesia. After surgery, we monitored the animals' appetite and measured the core body temperature and activity by using implanted radiofrequency transmitters. RESULTS: We obtained samples of the liver and splenic biopsies during all 19 laparoscopic procedures. The mean weight of the liver biopsies was 3.7 g and that of the spleen samples was 5.3 g. We encountered small adhesions during 5 of the 12 reoperations. Eating and activity rapidly returned after surgery. CONCLUSIONS: Laparoscopy permitted collection of large, serial biopsies with apparently limited stress to the animals. Laparoscopy can be used for biopsies in studies to characterize disease response, confirm normal organ histology prior to drug toxicity studies, determine target-organ drug concentrations in pharmacokinetic studies, and measure drug residues. This refinement likely will reduce required animal numbers by decreasing the effect of surgery compared to that of the experimental conditions, enhance animal well-being, and permit repeated measurements in an animal that serves as its own control.

Analgesics, Opioid↗

Patterns of attendance and treatment at an emergency dental clinic: a three year follow-up.

OBJECTIVES: Patterns of attendance at the Dublin Dental Hospital's Accident and Emergency Clinic in 1996 were compared with figures from 1993 to look for changes, especially in the light of changing provision of public funding for dental treatment for medical card holders and dependants. METHODS: An audit of patient clinical records for one month in 1996 was compared to previously published data relating to 1993. RESULTS: While patient numbers were similar in the two time periods (718 in 1993 versus 708 in 1996), the proportion of attendances by medical card holders or their dependants dropped from 48 per cent to 36 per cent. The proportion of non urgent treatments had also dropped over the three years. CONCLUSIONS: Changes in the provision of publicly funded dental treatment for medical card holders and dependants has reduced the proportion of such patients attending the clinic. However, their places have been taken by other patients.

Adolescent↗

Pulmonary embolism in a 13-year-old boy.

Pulmonary embolism and thromboembolic disease are uncommon entities in the pediatric population. The importance of risk factor assessment is paramount to considering the diagnosis in children. Clinical presentations are similar to those in adults; however, children may present with minimal objective findings on preliminary ancillary testing that would make one consider pulmonary embolus as a diagnosis. This report involves a 13-year-old boy with a well-defined risk factor for thromboembolism who presented with a classic history and without hypoxemia.

Adolescent↗

The efficacy of diagnostic laparoscopic ultrasound.

Precise staging of malignant disease is required to define the optimum therapeutic strategy. In spite of technical advances, the sensitivity of conventional imaging techniques is usually limited to defining lesions of at least 1 cm in size. Laparoscopy is a sensitive technique that is very valuable for visual inspection of the abdominal cavity and the identification of small surface lesions. However, non-superficial lesions may escape detection due to the lack of tactile sensitivity. As an adjunct to laparoscopy, this study, utilizing a young swine model, has analyzed the detectability of intra-abdominal lymph nodes by laparoscopic ultrasound (LU). Lymph nodes in and around the hepatoduodenal ligament, examined and measured by LU, were resected by subsequent open laparotomy in eight young, mixed-breed swine. The numbers and sizes of lymph nodes detected by LU and resected at laparotomy were compared and analyzed statistically. Forty-six lymph nodes were resected by laparotomy, while LU failed to detect 3 small nodes (sensitivity, 43/46 = 93.5%). The sizes of lymph nodes in the LU group correlated strongly with the sizes actually measured in the laparotomy group (r = 0.936, P < 0.001). Twenty-six small lymph nodes, which conventional extracorporeal imaging might have failed to diagnose, were detected accurately by LU (r = 0.877, P < 0.001). This new technology may not only be effective for staging intra-abdominal malignant disease, but adds the benefit of obtaining tissue samples under direct vision using minimally invasive techniques.

Abdomen↗

Functional domains for assembly of histones H3 and H4 into the chromatin of Xenopus embryos.

Histones H3 and H4 have a well defined structural role in the nucleosome and an established role in the regulation of transcription. We have made use of a microinjection strategy using Xenopus embryos to define the minimal structural components of H3 and H4 necessary for nucleosome assembly into metazoan chromosomes in vivo. We find that both the N-terminal tail of H4, including all sites of acetylation, and the C-terminal alpha-helix of the H4 histone fold domain are dispensable for chromatin assembly. The N-terminal tail and an N-terminal alpha-helix of H3 are also dispensable for chromatin assembly. However, the remainder of the H3 and H4 histone folds are essential for incorporation of these proteins into chromatin. We suggest that elements of the histone fold domain maintain both nucleosomal integrity and have distinct functions essential for cell viability.

Acetylation↗

Verapamil therapy for persistent antral spasms in a child.

Little is known about the use of calcium channel blockers in children with gastric motility disorders. We report the case of an 11-year-old child who was hospitalized after 3 weeks of persistent vomiting, abdominal pain, and a 12-lb weight loss. When his symptoms failed to improve with traditional treatment, verapamil therapy was begun. Within 24 hours, his symptoms totally resolved.

Abdominal Pain↗

Incidence of head injury: lasting effects among college students and working adults in the general population.

224 (21%) of 1067 persons in a nonclinical population surveyed had one or more head injuries resulting in unconsciousness. They had a total of 306 head injuries with 113 (31%) of them resulting in lasting neurological effects. Both in a pilot project and in the main study, headache was the most commonly reported of an array of symptoms that are essentially a postconcussion syndrome.

Adolescent↗