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Biomedical subjects

M Williams

Publications and source records attributed to M Williams.

At least 415 records · Page 23Linked to original sources
PubMed1994

Vulvar application of lidocaine for pain relief in spontaneous vaginal delivery.

OBJECTIVE: To evaluate the effect of topical perineal lidocaine on immediate postpartum perineal pain. METHODS: Two hundred three volunteers randomly received either 2% lidocaine jelly or chlorhexidine gluconate topically to the perineum during the second stage of labor in a double-blind study. A four-point analogue pain scale was used to rate perineal pain 30 minutes after delivery. Parametric data were evaluated with the unpaired Student t test. Nonparametric data were analyzed using Mann-Whitney, Pearson chi 2, and Mantel-haenzel tests, and forward stepwise logistic regression. RESULTS: Women receiving topical lidocaine reported less overall perceived pain (48%, P < .05) and less moderate to severe pain (52%, odds ratio 1.83, P < .04) at delivery than those receiving placebo (33 and 67%, respectively). The incidence of perineal lacerations was similar in the two groups. A logistic regression found topical lidocaine and multiparity as significant correlates of diminished peripartum pain (P < .007). CONCLUSIONS: Topical application of 2% lidocaine gel was associated with decreased pain perception in the immediate postpartum interval. If confirmed by other investigators, this technique may offer improved analgesia while minimizing the injection route with local analgesia.

Administration, Topical↗
PubMed1994

Combination therapy with nucleoside analogs and alkylating agents.

The nucleoside analog, 2'-deoxycoformycin (dCF), and the alkylating agents, chlorambucil (CLB) and cyclophosphamide, are effective agents in the treatment of chronic B cell leukemias and lymphomas. The cyclophosphamide analog, 4-hydroperoxycyclophosphamide (4-HC), generates the same active metabolite as cyclophosphamide in cells and has been used extensively for bone marrow purging in vitro. We have observed that deoxyadenosine (dAdo) plus dCF (dAdo/dCF) inhibit the repair of x-irradiation-induced and bleomycin-induced DNA damage in vitro, and that this results in either synergistic or additive cytotoxicity, respectively. In the present study we examined whether dAdo/dCF, can enhance the antitumor activity of CLB and 4-HC in chronic lymphocytic leukemia (CLL) cells in vitro. CLL cells were treated with CLB for 6 hr and then with dAdo/dCF for 18 hr and cytotoxicity was measured by the MTT assay. Synergy was observed between CLB and dAdo/dCF in CLL cells from 2 patients, with synergy increasing as the CLB dose was raised. In contrast, similar treatment of human bone marrow cells resulted in little or no synergistic cell kill. Treatment of CLL cells from 2 patients with 4-HC for 30 min followed by dAdo/dCF for 18 hr resulted in little synergistic cytotoxicity, although this drug combination did produce an additive cell kill. Thus, combination therapy with nucleoside analogs and alkylating agents may be useful for improving treatment of CLL.

Alkylating Agents↗
PubMed1993

A familial hypertrophic cardiomyopathy locus maps to chromosome 15q2.

We report that a gene responsible for familial hypertrophic cardiomyopathy (FHC) in a kindred with a mild degree of cardiac hypertrophy maps to chromosome 15q2. The gene encoding cardiac actin, located on chromosome 15q, was analyzed and excluded as a candidate for FHC at this locus. Two additional families with typical FHC were studied and the disorder in one also maps to the chromosome 15q2 locus. The maximum combined multipoint logarithm of odds score in the two linked families is 6.02. Although these two kindreds reside in the same country, we believe that their disorder is caused by independent mutations in the 15q2 locus because of the clinical and genotypic differences between affected individuals. Mutations in at least four loci can cause FHC: chromosomes 14q1 (beta cardiac myosin heavy chain gene), 1q3, and 15q2 and another unidentified locus, suggesting substantial genetic heterogeneity.

Adolescent↗
PubMed1993

Purification and properties of LR1, an inducible DNA binding protein from mammalian B lymphocytes.

LR1 is a lipopolysaccharide-inducible B cell-specific DNA binding activity, with sites in the immunoglobulin heavy chain enhancer and switch regions. We describe the purification of this 106-kDa protein from nuclear extracts of PD31 murine pre-B cells, using three chromatographic steps. The DNA binding activity of LR1 is dependent upon phosphorylation, and we show that LR1 is post-translationally modified by N-acetylglucosamine addition. The importance of regulatory modification to LR1 DNA binding activity is apparent from the chromatographic pattern on the anion exchange resin Mono Q: while the LR1 polypeptide elutes over a broad salt range from the column, DNA binding activity is confined to a narrow peak eluting at the highest salt.

Acetylglucosamine↗
PubMed1993

Receptor-based assays.

Recombinant DNA technology has expanded the potential of the targeted screening approach in drug discovery. The use of cloned and expressed receptors as targets for the evaluation of novel compounds can significantly simplify the structure affinity/activity process. However, the patenting of cloned receptors, as well as species differences in receptor pharmacology, especially with respect to human tissues, may limit their use in drug screening. Improved technologies to measure the functional aspects of the receptor-ligand interaction offer the potential to further enhance the targeted screening approach. A greater strategic focus is required to access chemically and biologically diverse ligand sources.

Animals↗
PubMed1993

Direct evidence for competition between local and global mechanisms of two-dimensional orientation illusions.

Orientation illusions induced by two-dimensional stimuli, such as square outline frames or plaids, have been more or less adequately accounted for in terms of repulsion of the vertical test stimulus from the axis of symmetry nearest vertical of the inducing stimulus, whether that axis is real or virtual. Recently, data have been obtained which directly suggest a more complex mechanism: one in which the observed illusion is the sum of all effects--complementary and antagonistic--induced by all axes flanking vertical which are sufficiently close to vertical to exert a significant effect. Experiments are reported in which this latter hypothesis was directly tested by using nonorthogonal plaid component gratings and varying the real-axis orientations while a virtual plaid axis remained fixed in orientation at 10 degrees from vertical. The data indicate that the real component gratings modulate the virtual-axis effect.

Adult↗
PubMed1993

A linkage map of human chromosome 15 with an average resolution of 2 cM and containing 55 polymorphic microsatellites.

We have constructed a 2.0 centiMorgan (cM) resolution genetic linkage map for chromosome 15q that contains 55 polymorphic satellites and 3 RFLPs that have placed on the map with odds for order of at least 1,000:1. Genotypes from 67 polymorphic loci (64 polymorphic microsatellites) were used to construct the map. Nine genes are included in the 1,000:1 map and 37 markers have heterozygosities of at least 70%. The sex-equal map length is 128 cM and the largest genetic interval is 11 cM (15.5 cM on the female map). The female and male map lengths are 150 cM and 106 cM, respectively. The map was constructed with 'MultiMap' and is based on the CEPH reference pedigrees and includes over 12,000 new genotypes. A sub-set of 12 markers spanning the length of the linkage map were genotyped in a somatic cell hybrid panel with breakpoints that divided 15q into five segments. Cytogenetic placement agreed with the linkage positions for each of the microsatellites tested with the exception of one (ACTC) which failed to give consistent results. Ten spontaneous new mutations were identified from a subset of 42 polymorphic microsatellites (out of a total of 20,420 transmissions), giving an apparent observed spontaneous mutation rate of 5 x 10(-4) per locus. An integrated map of chromosome 15q was also constructed with the microsatellite markers described here and previously genotyped RFLP-based markers. The sex average map spans 144.7 cM with an average distance between unique map locations of 3.5 cM and a maximum intermarker distance of 11.5 cM. These genetic linkage maps can be considered baseline maps for 15q which will be useful for physical mapping and the localization of disease genes and other genes of interest.

Base Sequence↗
PubMed1993

Sperm numbers and distribution within the human fallopian tube around ovulation.

This study aimed to determine the number and distribution of spermatozoa within the human Fallopian tubes around ovulation. Parous women, undergoing total abdominal hysterectomy for menorrhagia, were inseminated with either partner's semen (3/10) or donor semen (7/10). Approximately 18 h later both Fallopian tubes were ligatured into ampullary, isthmic and intramural regions. These were removed and assessed for sperm content by flushing, scanning electron microscopy (SEM) or homogenization. A median of 251 spermatozoa were recovered (range, 79-1386). The number of spermatozoa within each tube was not significantly different. The ovulatory ampulla contained a significantly (P < or = 0.01) larger percentage of spermatozoa than the non-ovulatory ampulla. The number of motile spermatozoa inseminated was not significantly correlated to the number of spermatozoa recovered, but a trend was identified. The time between the onset of the luteinizing hormone surge and hysterectomy was significantly correlated (P < or = 0.01) to the number of spermatozoa within the intramural regions, but not to the tubal sperm distribution. Spermatozoa were not observed, by SEM, bound to the tubal epithelium. These data suggest that, after artificial insemination at least, sperm access to the human Fallopian tube may be controlled, but that ovulation does not affect the redistribution of spermatozoa between tubal regions and that the isthmus does not appear to act specifically as a sperm reservoir.

Adult↗
PubMed1993

Uterine flushing: a method to recover spermatozoa and leukocytes.

The process of sperm transport from the cervix, where a leukocytic reaction is initiated, through the uterus to gain access to the site of fertilization is very poorly understood. This preliminary study was designed to utilize a uterine flushing technique to determine firstly, the number of spermatozoa that can be recovered from the uterine cavity at 4 h post-insemination, around the time of ovulation, and secondly, to establish whether the spermatozoa initiate a leukocytic response while present. Uterine flushing was carried out in 10 potentially fertile women at 4 h post-insemination with donor semen, 24-36 h after the onset of the luteinizing hormone (LH) surge. The flush fluid was analysed for the numbers of spermatozoa and leukocytes present. In 8/10 women spermatozoa were retrieved from the uterus, in consistently low numbers (median 46, range 3-415). In 5/5 women leukocytes were recovered (median, 2.75 x 10(8)/l, range 2.0 x 10(8)-12.7 x 10(8)/l) from an origin other than peripheral blood contamination. These results suggest firstly that the flushing technique was a consistent method for retrieving spermatozoa and leukocytes from the uterine cavity, secondly that only low numbers of spermatozoa can be retrieved on flushing and thirdly that the leukocytic reaction to spermatozoa extends to the uterine cavity.

Female↗
PubMed1993

The effects of inhaled interferon gamma in normal human airways.

Recent studies suggest that cytokines such as recombinant interferon-gamma (rIFN-gamma) may play a role in the treatment of certain respiratory conditions associated with infection and inflammation. This study was designed to determine if rIFN-gamma could be delivered effectively in a group of normal human volunteers. The effectiveness of the inhaled delivery system was demonstrated by the recovery of free IFN-gamma in bronchoalveolar lavage (BAL) fluid and macrophage (M phi) expression of IP-10, an IFN-gamma-inducible molecule, after therapy but not at baseline. IL-1 beta, but not IL-8, gene transcripts also showed evidence for up-regulation after rIFN-gamma therapy. Compared with baseline, inhaled rIFN-gamma did not significantly alter clinical symptom scores, spirometry, morning peak expiratory flow rate (PEFR), or the response to methacholine. Of interest, the evening PEFR increased significantly (p = 0.02), from 568 +/- 36 L/min at baseline to 584 +/- 33 L/min after inhaled rIFN-gamma. Although there was no significant change in total white cell count in BAL fluid, the cellular composition did demonstrate a significant decrease in percentage of alveolar M phi (p = 0.02) and an increase in percentage of lymphocytes (p = 0.02) after rIFN-gamma. There were no histologic differences seen in bronchial biopsy specimens, and there was no evidence for up-regulation of ICAM-1 or HLA-DR expression after rIFN-gamma. We conclude that, in normal persons, rIFN-gamma can be effectively delivered by inhalation. Future trials using inhaled rIFN-gamma appear to be warranted for certain pulmonary diseases.

Administration, Inhalation↗
PubMed1993

Novel preservation solution permits 24-hour preservation in rat and baboon cardiac transplant models.

BACKGROUND: Cardiac preservation for transplantation disrupts normal vascular homeostatic mechanisms. Hypoxia and reoxygenation increase endothelial cell permeability, induce procoagulant activity, and alter endothelial cell/leukocyte interactions, with a parallel reduction in endothelial cAMP and nitric oxide levels. Because hypoxia/reoxygenation simulates a significant component of the global ischemia/reperfusion of cardiac transplantation, we hypothesized that preservation failure may be related to these perturbations. This work focuses on repleting the intercellular/intracellular second messengers nitric oxide/cGMP and cAMP in the donor heart to enhance cardiac preservation for transplantation. METHODS AND RESULTS: A heterotopic rat heart transplant model was used to compare lactated Ringer's (LR) and University of Wisconsin (UW) solutions to a novel storage solution (Columbia University solution, CU), which contains a cAMP analogue (dibutyryl cAMP) and nitroglycerin (to enhance nitric oxide-related mechanisms). By 24 to 28 hours of preservation, no LR hearts survived (n = 9), 35% of UW hearts survived (n = 20), and 88% of CU-preserved hearts survived (n = 8; P < .05) versus LR or UW). The viability of preserved hearts was explored by determining whether CU preservation enabled myocytes to maintain resting membrane potentials and preserve their ability to generate an action potential in response to a field stimulus. Of 24 sites explored with a microelectrode in UW-preserved hearts, only 4% were able to generate an action potential, compared with 75% of 36 sites in CU-preserved hearts (P < .001), with corresponding preservation of resting membrane potential in the CU-preserved hearts (-13 mV for UW versus -54 mV for CU, P < .001). Orthotopic baboon cardiac transplantation performed after 24-hour simple hypothermic preservation demonstrated that no UW-preserved heart (n = 4) survived the perioperative period; in contrast, four of five hearts stored for 24 hours in CU solution sustained the recipient with minimal inotropic support, and two animals survived long-term. CONCLUSIONS: Sustaining higher levels of intercellular/intracellular second messengers cAMP and nitric oxide/cGMP provides a new approach to enhancing cardiac preservation.

Adenosine↗
PubMed1993

Helmet slippage during visual tracking: the effect of voluntary head movements.

The influence of visual tracking on head movement and on the head/helmet system was investigated for two different helmets (a motorcycle helmet and a flying helmet) under static laboratory conditions. Subjects visually refixated between pairs of illuminated targets located at various horizontal (up to 160 degrees) and vertical (up to 90 degrees) distances apart while head position and helmet slippage were measured in azimuth, pitch, roll, X, Y, and Z using a double magnetic coil system. Results showed that for both helmets, root mean square (RMS) head movement increased with refixation distance, especially in the main axis of refixation, and that RMS helmet slippage can be a function of RMS head motion. Further, large individual differences in the degree of head motion were found. These findings may have implications for designers and investigators of helmet-mounted avionics.

Accommodation, Ocular↗
PubMed1993

Evaluation of a new dentinal bonding system.

The purpose of this study was to compare the in vitro microleakage of a new dentinal bonding system, not yet released in the United States, to the microleakage of two first-generation bonding agents. Simulated Class V cavities were prepared in freshly extracted bovine incisors and restored with the appropriate composite resin-bonding agent combination. Restorations were thermocycled and examined for microleakage at 24 hours and 60 days. Comparison of the materials revealed no statistically significant difference in microleakage scores at the gingival or incisal margins after 24 hours. However, the first-generation bonding agents exhibited significantly more microleakage at the gingival margin than did the new bonding system after 60 days. No significant increase in microleakage was measured at the incisal margin for any of the materials after 60 days. In contrast, all materials exhibited a significant increase in leakage at the gingival margin after 60 days. No correlation between microleakage and polymerization shrinkage or coefficients of thermal expansion of the composite resins could be established.

Animals↗