Search PubMed⌕ Search

Biomedical subjects

K Brady

Publications and source records attributed to K Brady.

At least 73 records · Page 4Linked to original sources

Mechanical factors in the etiology of premature rupture of the membranes.

The physiologic cascade that results in PROM is cyclic and probably can be entered at many points--through the production of collagenases, peroxidases, phospholipases, or prostaglandins. It can be initiated or exacerbated by bacteria. In addition, PROM is the result of direct bacterial insults or host-mediated autodestruction in response to bacterial presence or challenge. It may be affected by physical properties and stresses that are mechanical. This review of the mechanical factors that support normal chorioamnion membranes may provide an understanding of where the support can be eroded, thus leading to PROM. With this basic overview of the pathophysiology contributing to PROM, the clinician can justify clinical decisions better, depending on the patient's presentation and gestational age. The judicious use of various tocolytic agents, antimicrobial agents, and/or corticosteroids singly or in combination is predicated on the effect each of these iatrogenically administered agents will have on the mother and fetus. As more investigations are done, we will gain greater insight into the mechanical factors involved in causing PROM.

Bacterial Infections↗

Calcium pyrophosphate dihydrate deposition disease: morphological and microanalytical features.

The light microscopic and polarization appearances of calcium pyrophosphate dihydrate crystal deposits in tissues are reviewed. In routine sections haematoxylinophilic crystalline deposits with a feathery or brush-like pattern are typical of calcium pyrophosphate dihydrate. Short rhomboidal crystals showing positive birefringence are seen on polarization; X-ray microanalytical and infrared spectroscopic data support the specificity of these appearances. The appearances of the crystal deposits in decalcified specimens are also described. We include six cases of calcium pyrophosphate dihydrate deposition within periarticular bone; to the best of our knowledge this has not previously been described.

Aged↗

Randomised double-blind trial of bromovinyldeoxyuridine (BVDU) and trifluorothymidine (TFT) in dendritic corneal ulceration.

The results of a randomised double-blind clinical trial of 0.1% bromovinyldeoxyuridine (BVDU) and 1% trifluorothymidine (TFT) in 60 patients with corneal dendritic ulceration are presented. There was no significant difference between BVDU and TFT in terms of numbers of ulcers healed (p = 0.61), mean healing time (p = 0.065), and cumulative healing rate (p = 0.058). No serious side effects were observed, though transient stinging was recorded in five patients receiving TFT and in three patients receiving BVDU. One patient in the group treated with TFT developed a punctate epitheliopathy.

Adolescent↗

Substance abuse in an inpatient psychiatric sample.

The relationship between psychoactive drug abuse and psychopathology is complex. There have been few systematic explorations of substance abuse in psychiatric populations since the recent epidemic of cocaine abuse. To update and further explore the relationship between psychiatric illness and substance abuse, 100 consecutively admitted patients to an inpatient psychiatry unit were administered a drug and alcohol use/abuse questionnaire. Sixty-four percent endorsed current or past problems with substance abuse and 29% met DSM-III-R criteria for substance abuse in the 30 days prior to admission. For the major diagnostic categories, there were no significant differences between groups in percentages of patients with substance abuse disorders. There was a trend (p less than or equal to .2) toward an increased number of lifetime psychiatric hospitalizations in the substance-abusing group. Alcohol was the most common drug of choice followed by stimulants, cannabis, and sedative hypnotics. Differences in drug choices between diagnostic categories are discussed. Forty-three percent of urine drug screens obtained were positive, and of those with positive urine drug screens, 42% denied drug use upon admission. Only 40% of patients with current or past substance abuse problems had received treatment for their chemical dependency. In our sample, while substance abuse was very prevalent, it was underreported and undertreated.

Adult↗

Bromovinyldeoxyuridine (BVDU) and trifluorothymidine (TFT) in dendritic corneal ulceration: a double blind controlled study.

Fifty patients with corneal dendritic ulceration were randomly entered into a double blind clinical trial comparing BVDU eyedrops with TFT eyedrops. Of those receiving TFT 100% healed in a mean time of 6.7 days, while 92% of those receiving BVDU healed in a mean time of 8.7 days. There was no statistical difference between the two groups in terms of numbers healed, but BVDU was significantly slower in terms of days to heal. After a mean follow-up period of 7.5 months there has been one recurrence in each group.

Administration, Topical↗

Screening for illicit drug use in a military obstetric population.

The purpose of our investigation was to determine the prevalence of illicit drug use within our socioeconomically heterogeneous obstetric population, in order to assess the need for institution of universal screening. Five hundred consecutive new obstetric registrants had urine collected for routine culture. Following removal of a small aliquot of urine for culture, the samples were sent to the Armed Forces Institute of Pathology, Division of Forensic Toxicology. Each specimen was screened for the presence of alcohol, cocaine metabolites, cannabinoids, opiates, and amphetamines using fluorescent polarization immunoassay techniques. All positive screening tests were confirmed by gas chromatography mass spectrometry. Thirty samples were either lost in processing or of insufficient quantity to test. Five of the 470 samples (1.06%) tested were positive. One subject was taking prescription narcotics, so the correlated prevalence was 0.85%. Three tested positive for tetrahydrocannabinol and two for opiates. Analysis of our data demonstrates that our obstetric population has a significantly lower prevalence of illicit drug use than other populations reported previously (P less than .01). We recommend that each institution providing obstetric services determine its specific prevalence of illicit drug use.

Cross-Sectional Studies↗

Maternal and neonatal effects of outlet forceps delivery compared with spontaneous vaginal delivery in term pregnancies.

Previous retrospective studies have suggested that the prophylactic use of outlet forceps has a beneficial impact on the neonate because it shortens the second stage of labor and decreases the incidence of neonatal hypoxia. The purpose of this study was to compare the immediate maternal and neonatal effects of outlet forceps delivery (N = 165) with spontaneous vaginal delivery (N = 168) in term parturients. Subjects were randomized to the study or control group immediately before delivery. There were 88 nulliparas and 77 multiparas in the forceps delivery group and 90 and 78, respectively, who delivered spontaneously, a nonsignificant difference. There were no significant differences in gestational age, parity, infant birth weight, length of the first and second stages of labor, use of conduction (continuous epidural) anesthesia, decrease in hematocrit values, Apgar scores, or umbilical arterial pH values between the forceps and spontaneous delivery groups. Seventeen infants in the forceps group and 16 in the control group had cephalhematoma, facial bruising, subconjunctival hemorrhage, or scalp abrasion (not significant). No neonate had fractures, nerve palsies, or intracranial hemorrhage (determined by cranial ultrasound). In the nulliparous population, significant differences were found in the use of episiotomy (93 versus 78%) and the incidence of deep perineal lacerations (24 versus 10%) with forceps compared with spontaneous delivery, respectively (P less than .05). No significant differences between the groups were found in multiparas. We conclude that the use of outlet forceps in patients with uncomplicated labor has no immediate effect on the neonate. Furthermore, outlet forceps delivery does not significantly shorten the second stage of labor and is associated with an increased incidence of maternal perineal trauma.

Delivery, Obstetric↗

Cord blood acid-base values in breech-presenting infants born vaginally.

The purposes of our investigation were to establish normal umbilical cord blood acid-base values for breech-presenting fetuses born vaginally and to compare our findings with values from cephalic-presenting fetuses delivered vaginally (control group). Our study population consisted of 30 term fetuses with frank breech presentation who fulfilled selective criteria for trial of labor and subsequently had uncomplicated vaginal breech deliveries. The mean (+/- SD) gestational age of the study group was 38 weeks, 5 days (+/- 1 week, 4 days); the mean birth weight was 3178 +/- 321 g and the median 1- and 5-minute Apgar scores were 7 (range 2-9) and 8 (range 7-9), respectively. Thirteen infants had assisted breech deliveries and 17 had assisted breech deliveries with forceps applied to the aftercoming head. We obtained umbilical arterial and venous blood samples for acid-base analysis from both the study and control infants. The results for the study group were: umbilical venous pH 7.32, PCO2 37.88 mmHg, PO2 22.88 mmHg, HCO3 25.92 mmol/L, and base deficit -4.90; umbilical arterial pH 7.23, PCO2 51.20 mmHg, PO2 18.85 mmHg, HCO3 19.42 mmol/L, and base deficit -5.86. Comparison of the subjects' umbilical cord blood acid-base values with those of controls demonstrated a statistically lower cord arterial pH (P = .0001) and a higher arterial PCO2 (P = .028). We conclude that umbilical cord arterial blood acid-base values of the breech-presenting fetus born vaginally without complications differ from established normative umbilical cord blood gas values based on data obtained from uncomplicated cephalic-presenting fetuses delivered vaginally.

Acid-Base Equilibrium↗

The association of antiphospholipid antibodies with pregnancies complicated by fetal growth restriction.

The association of antiphospholipid antibodies with fetal growth restriction is often cited, but the published evidence for this is based on few patients and comes primarily from patient histories, not study groups. In this prospective study, we evaluated a subgroup of our population with fetuses whose estimated weights at ultrasound were at or below the tenth percentile for gestational age. Plasma and serum testing was performed to determine the presence of antiphospholipid antibodies, specifically lupus anticoagulant and anticardiolipin antibodies, respectively. From March 1990 through March 1991, 55 women were followed for suspected fetal growth restriction. Intensive monitoring of the fetal condition and modification of the mother's activity were recommended, resulting in 100% compliance. Despite this, 37 newborns were confirmed by birth weight to be at or below the tenth percentile, and all were below the 45th percentile. Fifteen of 55 women (27%) were positive for anticardiolipin antibodies, as were nine of 37 (24%) with correctly diagnosed fetal growth restriction. Five of 15 women whose newborns had ponderal indexes below the tenth percentile tested positive for anticardiolipin antibodies. None of the women had a positive lupus anticoagulant test. The prevalence of anticardiolipin antibodies in this study group was significantly higher than in our general population. We conclude that there is a statistically significant association between the presence of circulating maternal anticardiolipin antibodies and fetal growth restriction.

Autoantibodies↗

Use of a standard preparatory diet for the oral glucose tolerance test. Is it necessary?

A prospective investigation was performed to evaluate the necessity of a diet containing greater than or equal to 150 g/d of carbohydrate for three days before the oral glucose tolerance test (OGTT). Thirty-seven obstetric patients who had a value of greater than or equal to 135 mg/dL on the one-hour, 50-g oral glucose screening test underwent a subsequent OGTT. The patients were alternately assigned to one of two groups. Nineteen of 37 (51%) were asked to precede the OGTT with a three-day diet containing greater than 150 g/d of carbohydrate. Those patients were then asked not to alter their normal dietary pattern and to repeat the OGTT in one to two weeks (group I). Eighteen of 37 (49%) followed the testing scheme in reverse order (group II). There were no significant differences in mean fasting or in one-, two- or three-hour plasma glucose values at either testing period between groups I and II. There were no significant differences between groups I and II in the number of patients who had an abnormal OGTT at the initial or repeat testing period. Dietary preparation for the OGTT is not necessary, and patients can be scheduled for the test when convenient.

Adult↗

Pulmonary function of preeclamptic women receiving intravenous magnesium sulfate seizure prophylaxis.

Pulmonary function was studied in ten preeclamptic women in labor (mean gestational age 38.1 +/- 0.9 weeks measured from the last menstrual period) receiving continuous intravenous (IV) infusions of magnesium sulfate. Baseline maximal inspiratory pressure, maximal expiratory pressure, functional vital capacity, and forced expiratory volume at 1 second were measured immediately before a 6-g IV loading dose of magnesium sulfate and 2 hours after the initiation of a continuous 2-g/hour infusion of magnesium sulfate. Serum magnesium levels were measured at the same time pulmonary function tests were performed. All values are reported as the mean +/- standard deviation. The maximal inspiratory pressure, an indicator of generalized respiratory muscle weakness, decreased from a baseline value of 26.2 +/- 7.7 to 19.4 +/- 6.3 cm H2O (P less than .05). The maximal expiratory pressure, an indicator of expiratory muscle strength, decreased from a baseline value of 30.6 +/- 9.2 to 25.2 +/- 7.1 cm H2O (P less than .005). The functional vital capacity decreased from a baseline value of 3.37 +/- 0.49 to 3.19 +/- 0.73 L, and the forced expiratory volume at 1 second decreased from a baseline value of 2.61 +/- 0.58 to 2.36 +/- 0.68 L at 2 hours (P less than .05). The mean serum magnesium level was 1.7 +/- 0.2 mg/dL before the administration of the IV loading dose and 4.51 +/- 0.67 mg/dL 2 hours after initiation of the continuous infusion. Our results demonstrate a significant decrease in pulmonary function tests in term preeclamptic patients receiving magnesium sulfate for seizure prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Structure of chymotrypsin-trifluoromethyl ketone inhibitor complexes: comparison of slowly and rapidly equilibrating inhibitors.

The peptidyl trifluoromethyl ketones Ac-Phe-CF3 (1) and Ac-Leu-Phe-CF3 (2) are inhibitors of chymotrypsin. They differ in Ki (20 and 2 microM, respectively) as well as in their kinetics of association with chymotrypsin in that 1 is rapidly equilibrating, with an association rate too fast to be observed by steady-state techniques, while 2 is "slow binding", as defined by Morrison and Walsh [Morrison, J. F., & Walsh, C. T. (1988) Adv. Enzymol. Relat. Areas Mol. Biol. 61, 202], with a second-order association rate constant of 750 M-1 s-1 at pH 7.0 [Imperiali, B., & Abeles, R. (1986) Biochemistry 25, 3760]. The crystallographic structures of the complexes of gamma-chymotrypsin with inhibitors 1 and 2 have been determined in order to establish whether structural or conformational differences can be found which account for different kinetic and thermodynamic properties of the two inhibitors. In both complexes, the active-site Ser 195 hydroxyl forms a covalent hemiketal adduct with the trifluoromethyl ketone moiety of the inhibitor. In both complexes, the trifluoromethyl group is partially immobilized, but differences are observed in the degree of interaction of fluorine atoms with the active-site His 57 imidazole ring, with amide nitrogen NH 193, and with other portions of the inhibitor molecule. The enhanced potency of Ac-Leu-Phe-CF3 relative to Ac-Phe-CF3 is accounted for by van der Waals interactions of the leucine side chain of the inhibitor with His 57 and Ile 99 side chains and by a hydrogen bond of the acetyl terminus with amide NH 216 of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Inhibition of chymotrypsin by peptidyl trifluoromethyl ketones: determinants of slow-binding kinetics.

A series of seven peptidyl trifluoromethyl ketone (TFK) inhibitors of chymotrypsin have been prepared which differ at the P1 and P2 subsites. Inhibition equilibria and kinetics of association and dissociation with chymotrypsin have been measured. The association rate of Ac-Phe-CF3 was measured at enzyme concentrations between 8 nM and 117 microM in order to examine the relation between the ketone/hydrate equilibrium of trifluoromethyl ketones and the "slow binding" by these inhibitors. The association rate decreases at high enzyme concentrations, indicating that TFK ketone is the reactive species and that conversion of TFK hydrate to ketone becomes rate limiting under these conditions. Inhibitors with hydrophobic side chains at P2 bind more tightly but more slowly to chymotrypsin, indicating that formation of van der Waals contacts between the P2 side chain and the His 57 and Ile 99 side chains of chymotrypsin is a relatively slow process. Inhibitor properties were compared to the Michaelis-Menten kinetic constants of a homologous series of peptide methyl ester and peptide amide substrates. Plots of log Ki vs log (kcat/Km) are linear with slopes of 0.65 +/- 0.2, indicating that these inhibitors are able to utilize 65% of the total binding energy between chymotrypsin and its hydrolytic transition state.

Acetylation↗

Vaginal breech delivery: a five-year prospective evaluation of a protocol using computed tomographic pelvimetry.

In 1983 a protocol was established at our institution that used computed tomographic pelvimetry to evaluate patients presenting with a singleton term frank breech fetus for an attempt at vaginal delivery. The criteria for a trial of labor were singleton fetus, term gestation (37 to 42 weeks' gestation from the first day of the last menstrual period), frank breech presentation, estimated fetal weight 2000 to 4000 gm, non-extended fetal head, and adequate computed tomographic pelvimetry. Two digital radiographs and a tomographic cross-section were taken of each patient, i.e., an anteroposterior view, a lateral view, and an axial section through the femoral head at the level of the fovea capitalis. Adequate pelvimetry was defined as: anteroposterior diameter of the inlet greater than or equal to 10.0 cm, transverse diameter of the inlet greater than or equal to 11.5 cm, transverse (interspinous) diameter of the midpelvis greater than or equal to 9.5 cm, and posterior sagittal diameter of the midpelvis greater than or equal to 4.0 cm. The purpose of this prospective analysis was to determine the obstetric and perinatal outcome of those breech fetuses that were evaluated with these criteria during the study period of January 1984 through July 1989. During this period the incidence of breech deliveries at our institution was 2.71% (394/14,542). Of these 394 breech deliveries, 122 patients underwent computed tomographic pelvimetry. Eighty-five patients had adequate pelvimetry, fulfilling the protocol criteria, and formed the study group. Eighty-one percent (69/85) of the study group had successful vaginal deliveries (group 1). Nineteen percent (16/85) required cesarean delivery after a trial of labor (group 2) (10 with fetal distress and six with arrested labor disorders). Of the 37 patients who had inadequate computed tomographic pelvimetry and underwent cesarean delivery without a trial of labor (group 3), 54% (20/37) had an extended fetal head, 21.6% (8/37) had an inadequate transverse diameter of the inlet, 13.5% (5/37) had an inadequate midpelvic posterior sagittal measurement, and 10.8% (4/37) had an inadequate interspinous diameter. Perinatal outcome including Apgar scores, cord gases, length of hospital stay, neonatal complications, was evaluated. No difference in infant complications was noted between the group delivered vaginally and the groups delivered abdominally. The only maternal complications in our study group were chorioamnionitis, endomyometritis, and postpartum anemia. There were no significant differences in the incidence of chorioamnionitis among the three groups of patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

An evaluation of immunohistologic stains for immunoglobulin light chains in bone marrow biopsies in benign and malignant plasma cell proliferations.

Bone marrow specimens from 226 patients with a variety of benign and malignant plasma cell proliferations were studied to assess the reliability of immunohistologic studies in their evaluation. The clonality of the bone marrow plasma cells was compared with results of serum and urine electrophoreses. Discordance was observed most frequently in cases in which a paraprotein was demonstrated, but no monoclonality was detected by immunoperoxidase (16 cases). Of these 16 cases, 9 had 5% or less bone marrow plasma cells. In only one case was the light chain class of the bone marrow plasma cells different from that of the paraprotein. If discordant cases with 5% or less plasma cells are eliminated, the overall concordance was 97%. The authors' findings indicate that immunohistologic studies for immunoglobulin light chains in Zenker-fixed decalcified bone marrow biopsy sections are reliable in the evaluation of patients with plasma cell proliferations when the marrow contains more than 5% plasma cells.

Biopsy↗

Cocaine abuse among schizophrenic patients.

Initial studies have indicated that stimulant abuse is prevalent among schizophrenic persons. To assess the phenomenon of cocaine abuse by patients with schizophrenia, 17 male cocaine-abusing schizophrenic patients were compared with 22 male schizophrenic patients who did not use cocaine. The cocaine-abusing subjects had been hospitalized more frequently, were more likely to be of the paranoid subtype, and were more likely to be depressed at the time of interview. It appears that cocaine abuse may influence both the psychopathologic presentation of schizophrenic patients and the intensity of care that they require.

Adult↗

Plasma fibronectin concentrations during normal term labor.

We measured plasma concentrations of fibronectin in 30 normal parturients in early labor and at the time of delivery, using a rapid immunoturbidimetric assay. We compared these values with those of 30 healthy nonpregnant control women. The mean plasma concentrations of fibronectin in women in early labor and at delivery were 400 +/- 104 and 410 +/- 147 micrograms/mL, respectively (not significant). Both of these values were higher than the mean fibronectin concentration in controls, 283 +/- 81 micrograms/mL (P less than .0001). We conclude that plasma concentrations of fibronectin are higher in pregnant women than in nonpregnant controls and that they remain relatively constant during uncomplicated term labor.

Adolescent↗

pH dependence of the inhibition of chymotrypsin by a peptidyl trifluoromethyl ketone.

The effects of pH on the kinetics of association and dissociation of chymotrypsin and the dipeptidyl trifluoromethyl ketone (TFK) N-acetyl-L-leucyl-L-phenylalanyltrifluoromethane (1) were examined through the pH range 4-9.5. The pH dependence of the association rate (kon) is similar to that of kcat/Km for ester and peptide substrates and is dependent on two pK's at 7.0 and 8.9. We assign these pK's to the active site His and to the amino group of the N-terminal isoleucine residue. Ki for the complex of 1 and chymotrypsin has a pH dependence very similar to that of kon, and we conclude that the same ionizable groups which determine the pH dependence of kon are involved. The dissociation constant of the enzyme-inhibitor complex (koff) shows no pH dependence between pH 4 and pH 9.5. The data indicate that the inhibitor reacts with a form of the enzyme in which His 57 is unprotonated, and the resulting complex contains no groups which ionize between pH 4 and pH 9.5. This is consistent with conclusions previously reached from NMR data (Liang & Abeles, 1987). These experiments led to the conclusion that 1 reacts with chymotrypsin to form a tetrahedral complex in which His 57 is protonated (pK greater than 9.5) and the OH group of serine 195 has added to the carbonyl group of 1 to form an ionized hemiketal (pK less than 4.9). The pK of His 57 is increased by greater than 3 units over that in the free enzyme, and the pK of the hemiketal decreased by greater than 4 units compared to the pK in solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗