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PubMed2000

Future directions of research in statistical genetics.

From a global perspective, two external developments are having dramatic effects upon the field of statistical genetics: improved genetic data, for example, human DNA sequence, and new technologies, for example, microarray technology. Meiotic mapping techniques will have to be adapted to benefit from the improved data, for example, allelic association studies have to be extended to multiple markers to profit from the new genetic map of SNP markers. Changing technology has led to ever-increasing knowledge about gene function which has enabled novel gene mapping strategies which we refer to as functional mapping. Functional mapping has great potential for mapping complex disease genes since it uses pathway fractions to intermediate between genotype and phenotype information. Methods used in whole-genome gene expression studies are used to illustrate concepts of functional mapping.

Biomedical Technology↗
PubMed1995

Cardiac-cardiovascular reflexes induced by hydrogen peroxide in cats.

We have shown previously that reactive oxygen species stimulate abdominal sympathetic afferents to cause reflex cardiovascular activation. Because myocardial ischemia and reperfusion also generate reactive oxygen species, we investigated the possibility that cardiovascular reflexes could be induced by topical application of H2O2 to the anterior or posterior ventricular surface in cats anesthetized with alpha-chloralose. Mean arterial pressure (MAP), heart rate (HR), left ventricular (LV) pressure, aortic flow (AF), and first derivative of LV pressure at 40 mmHg developed pressure (LV dP/dt40) were monitored. H2O2 (44 and 130 mumol) significantly increased MAP but not HR or LV dP/dt40 in intact cats (n = 8). Application of H2O2 (44 mumol) significantly increased MAP (129 +/- 9 to 152 +/- 10 mmHg), HR (240 +/- 11 to 245 +/- 10 beats/min), AF (191 +/- 13 to 212 +/- 17 ml/min), total peripheral resistance (0.68 +/- 0.13 to 0.73 +/- 0.04 peripheral resistance units), and LV dP/dt40 (2,666 +/- 145 to 3,012 +/- 205 mmHg/s) after bilateral cervical vagotomy (n = 6). These H2O2-induced excitatory responses were abolished after bilateral T1-T4 ganglionectomy. In six additional cats, H2O2 (44 mumol) significantly decreased MAP (114 +/- 5 to 102 +/- 5 mmHg), HR (207 +/- 7 to 190 +/- 7 beats/min), and LV dP/dt40 (2,776 +/- 168 to 2,600 +/- 153 mmHg/s) after sympathectomy. These depressor responses were eliminated after vagotomy. The magnitude of the cardiovascular reflexes was increased or decreased in a dose-dependent fashion in vagotomized or sympathectomized cats, respectively, over a range of 440 nmol to 44 mumol H2O2. Application of H2O2 to the anterior or posterior ventricular surface resulted in similar pressor or depressor reflexes. Dimethylthiourea and deferoxamine abolished pressor or depressor responses evoked by H2O2 in both vagotomized (n = 8) and sympathectomized (n = 8) cats. We conclude that reactive oxygen species, particularly the hydroxyl radical, can participate in activating cardiac afferents responsible for reflex cardiovascular responses during myocardial ischemia and reperfusion. An inhibitory reflex is transmitted through vagal afferents, whereas an excitatory reflex is conducted by sympathetic cardiac afferents.

Animals↗
PubMed1978

High dose medroxyprogesterone-acetate treatment in advanced mammary carcinoma. A phase II investigation.

In a phase II investigation of high dose medroxyprogesterone treatment of advanced and previously with other methods heavily treated patient with mammary carcinoma, 7 of 25 patients had a partial remission with a median duration of 5 + months. In a further 7 patients the disease became stationary. As measured by Karnofsky's scale, a median improvement of 20 points was obtained in these 14 patients. In 4 of 15 patients who had not responded to Tamoxifen treatment, a partial remission occurred following MAP therapy. The patients tolerated MAP well.

Adult↗
PubMed1998

As others see us, Part 2. Goals and the annual report: a system for performance evaluation.

This systematic approach to an annual performance report can show that laboratory professionals are active outside the physical laboratory as a vital part of the healthcare team. The annual report also provides an opportunity to show the many dimensions of clinical laboratory science and presents evidence of the multifaceted role of the laboratory manager. The annual report shows that employees can be self-directed and creative in goal setting and in achieving goals. In addition, the annual report is helpful should a laboratorian decide to apply for a promotion or other position. Also, the annual report documents a track record and demonstrates abilities and qualifications to prospective employers for expanded careers outside the laboratory. But most importantly, the annual report can be used as a road map for insight into professional growth and development.

Annual Reports as Topic↗
PubMed2005

Hughes technique, amniotic membrane allograft, and topical chemotherapy in conjunctival melanoma with eyelid involvement.

A 59-year-old woman presented with a pigmented mass in the inferior tarsal conjunctiva of the left eye with an associated diffuse, multifocal pigmentation involving largely the inferior half of the bulbar conjunctiva, fornix, and eyelid skin. Histopathologic examination of map biopsies disclosed conjunctival melanoma from primary acquired melanosis. Surgical excision of the inferior bulbar conjunctiva, fornix, and lower eyelid with histopathologic free margins was performed. Adjuvant cryotherapy was applied. The bulbar conjunctiva and lower fornix were reconstructed with an amniotic membrane allograft. Lower eyelid reconstruction was accomplished by use of the Hughes technique. Topical mitomycin C (0.04%) was applied after surgery. After 2 years of follow-up, no tumor recurrence has been detected and the eyelid and conjunctival defect have been satisfactorily corrected. This combined surgical procedure using amniotic membrane allograft and a composite tarsoconjunctival flap is shown to be useful in the treatment of an advanced conjunctival neoplasia with extensive eyelid involvement.

Administration, Topical↗
PubMed2003

Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac.

The purpose of this study was to evaluate the ability of the nonsteroidal anti-inflammatory drug nepafenac to prevent development of mitogen-induced pan-retinal edema following topical ocular application in the rabbit. Anesthetized Dutch Belted rabbits were injected intravitreally (30 microg/20 microL) with the mitogen concanavalin A to induce posterior segment inflammation and thickening (edema) of the retina. The Heidelberg Retina Tomograph was used to generate edema maps using custom software. Blood-retinal barrier breakdown was assessed by determining the protein concentration in vitreous humor, whereas analysis of PGE2 in vitreous humor was performed by radioimmunoassay. Inhibition of concanavalin A-induced retinal edema was assessed 72 h after initiation of topical treatment with nepafenac (0.1-1.0%, w/v), dexamethasone (0.1%), VOLTAREN (0.1%), or ACULAR (0.5%). Concanavalin A elicited marked increases in vitreal protein and PGE2 synthesis at 72 h postinjection. Retinal thickness was also increased by 32%, concomitant with the inflammatory response. Topical application of 0.5% nepafenac produced 65% reduction in retinal edema which was correlated with 62% inhibition of blood-retinal barrier breakdown. In a subsequent study, 0.5% nepafenac significantly inhibited (46%) blood-retinal barrier breakdown concomitant with near total suppression of PGE2 synthesis (96%). Neither Voltaren nor Acular inhibited accumulation of these markers of inflammation in the vitreous when tested in parallel. This study demonstrates that nepafenac exhibits superior pharmacodynamic properties in the posterior segment following topical ocular dosing, suggesting a unique therapeutic potential for a variety of conditions associated with retinal edema.

Administration, Topical↗
PubMed2002

Surgical approaches to malignant melanoma. Practical guidelines.

Practical guidelines for the surgical approach to malignant melanoma are discussed in detail. Topics include diagnosis and proper biopsy technique; the appropriate preoperative metastatic workup; width of excision margins; treatment of the regional lymph nodes including cutaneous lymphoscintigraphy, intraoperative lymphatic mapping, and sentinel lymphadenectomy; postoperative follow-up schedules; management of local recurrence including surgical resection, isolated limb perfusion, intralesional therapy, adjuvant immunotherapy; management of special clinical situations including subungal melanoma, plantar melanoma, melanoma on the face, melanoma in pregnancy, and the treatment of lesions of uncertain diagnosis.

Biopsy, Needle↗
PubMed1983

Comparison of intravenous and topical lidocaine in attenuating the cardiovascular responses to endotracheal intubation.

We administered lidocaine intravenously or topically to the larynx to compare the cardiovascular response to intubation between the two techniques and to determine if these responses were related to blood levels of lidocaine. Sixteen patients were randomly selected into group A (100 mg intravenous lidocaine) or group B (160 mg topical lidocaine). Neither method was completely effective in abolishing hypertension and tachycardia on intubation. The increase in pulse rate (PR) was more significant than the rise in mean arterial pressure (MAP) and was of longer duration. Significant increases in MAP were evident for less than two minutes in group A and less than three minutes in group B. Significant increases in PR were observed for approximately four minutes in group A and six minutes in group B. The average lidocaine blood level in group A was approximately 20 times that in group B at the time of intubation. The more prolonged and more significant increase in PR observed in group B indicates that intravenous administration of lidocaine may be superior to topical administration.

Administration, Topical↗
PubMed1999

Functional MRI of cerebral activation during encoding and retrieval of words.

The aims of the present study were to identify the cerebral structures associated with encoding and retrieval of verbal material. To circumvent the inherent disadvantages of the conventional block designs used in functional magnetic resonance imaging (MRI), an event-related design compared activation related to randomly intermixed old and new words during recognition. To support the validity of results, both nonparametric analyses in regions of interest (ROI) and statistical parametric mapping (SPM 96) were used. Twelve healthy volunteers, ages 22-35 years, performed three tasks: intentional encoding of words, recognition of old (previously learned) words, and discrimination between words and nonwords, a task to control for visual input and motor output during recognition. Echo-planar magnetic resonance imaging of blood-level, oxygen-dependent, task-related changes was used to compare cerebral activity under active and resting conditions as well as to detect event-related activity within blocks of trials. Comparable results were obtained following nonparametric statistical analysis of selected ROI and SPM. Encoding of words was associated with increased activity in the left inferior frontal gyrus, including Broca's area and in the left parietal association cortex. Event-related data analysis revealed activation of the right medial frontal gyrus, the right anterior cingulate gyrus, and parietal association cortices during recognition of previously presented words. In the lexical decision task, words in comparison with nonwords were associated with activation of the left parietal association cortex. The right medial frontal gyrus, the right anterior cingulate gyrus, and the right parietal association cortex are likely to be involved in episodic memory functions during recognition of previously presented verbal material. The comparison of event-related activation occurring within one trial block instead of among several trial blocks may significantly improve the performance of memory studies.

Adult↗
PubMedDate not supplied

XLMR genes: update 1992.

Up to now, we have identified 77 X-linked conditions in which mental retardation is the primary or a major component manifestation. These conditions were subdivided into 2 categories, designated respectively "X-linked mental retardation syndromes" and "Non-specific X-linked mental retardation". Forty genes have been regionally mapped onto the X chromosome. However, in several instances the data were derived from a single family and most lod scores were less than 3.0.

Chromosome Mapping↗
PubMed2003

Mapping of MRX81 in Xp11.2-Xq12 suggests the presence of a new gene involved in nonspecific X-linked mental retardation.

X-linked nonspecific mental retardation (MRX) accounts for approximately 25% of mental retardation in males. A number of MRX loci have been mapped on the X chromosome, reflecting the complexity of gene action in central nervous system (CNS) specification and function. Eleven MRX genes have been identified, but many other causative loci remain to be refined to the single gene level. In 21 MRX families, the causative gene is located in the pericentromeric region; and we report here the identification by linkage analysis of a further such locus, MRX81. The new MRX locus was identified by two- and multi-point parametric analysis carried out on a large Italian family. Tight linkage of MRX81 to DNA markers ALAS2, DXS991, and DXS7132 was observed with a maximum LOD score of 3.43. Haplotype construction delineates an MRX81 critical region of 8 cM, the smallest MRX pericentromeric interval so far described, between DXS1039 and DXS1216, and placing it in Xp11.2-Xq12. So far, automated sequencing of two candidates in the region, the MRX gene oligophrenin (OPHN1) and the brain-specific ephrinB1 (EFNB1) gene, in DNA from affected males excluded their candidacy for MRX81, suggesting a novel disease gene.

5-Aminolevulinate Synthetase↗
PubMed2004

Cyto- and chemoarchitecture of the cerebral cortex of the Australian echidna (Tachyglossus aculeatus). I. Areal organization.

We have examined the topography of the cerebral cortex of the Australian echidna (Tachyglossus aculeatus), using Nissl and myelin staining, immunoreactivity for parvalbumin, calbindin, and nonphosphorylated neurofilament protein (SMI-32 antibody), and histochemistry for acetylcholinesterase (AChE) and NADPH diaphorase. Myelinated fibers terminating in layer IV of the cortex were abundant in the primary sensory cortical areas (areas S1, R, and PV of somatosensory cortex; primary visual cortex) as well as the frontal cortex. Parvalbumin immunoreactivity was particularly intense in the neuropil and somata of somatosensory regions (S1, R, and PV areas) but was poor in motor cortex. Immunoreactivity with the SMI-32 antibody was largely confined to a single sublayer of layer V pyramidal neurons in discrete subregions of the somatosensory, visual, and auditory cortices, as well as a large field in the frontal cortex (Fr1). Surprisingly, SMI-32 neurons were absent from the motor cortex. In AChE preparations, S1, R, V1, and A regions displayed intense reactivity in supragranular layers. Our findings indicate that there is substantial regional differentiation in the expanded frontal cortex of this monotreme. Although we agree with many of the boundaries identified by previous authors in this unusual mammal (Abbie [1940] J. Comp. Neurol. 72:429-467), we present an updated nomenclature for cortical areas that more accurately reflects findings from functional and chemoarchitectural studies.

Acetylcholinesterase↗