Biomedical subjects
Publications and source records attributed to E Cook.
Vaginal cancer is infrequent, but the morbidity associated with treatment is high. Delays in diagnosis account for presentations in advanced stages. Screening is probably not warranted given the low incidence, but inspection of the vagina should be performed at the time of Pap smear screening. No molecular markers are currently promising. Chemoprevention with retinoids may be feasible.
Cervical cancer remains an important health problem for women worldwide, despite its decline in countries where organized screening programs are in place. The morbidity of treatment and the mortality for advanced lesions are high, a frustrating situation because the cervix is accessible and a good screening test, the Pap smear, exists. HPV is an important risk factor, and the molecular evidence for its role is overwhelming. Molecular markers may soon help us decide which lesions are at highest risk of progression to invasion and which invasive lesions are likely to recur. Chemoprevention of precursor lesions is promising. An HPV vaccine could be effective in eradicating this cancer.
OBJECTIVE: This article reviews, discusses, and elaborates considerations and recommendations summarized by the biological research working group at the May 1993 NIMH conference on ethical issues in mental health research on children and adolescents. METHOD: Notes from the conference were summarized and supplemented by a computer search of relevant literature. Drafts were circulated for comment to national and international experts, some of whom joined as coauthors. RESULTS: Issues addressed include possible overprotection by policy makers and institutional review boards arising out of the recognition of children's special vulnerability without equal recognition of their need for research; the definition of minimal risk, which has often been equated with no risk in the case of children; assessment of the risk-benefit ratio; procedures for minimization of risk, such as improved technology, "piggybacking" onto clinical tests, and age-appropriate preparation; the difficulty of justifying risk for normal controls; age-graded consent; special considerations about neuroimaging; "coercive" inducement, both material and psychological; disposition of unexpected or unwanted knowledge about individuals, including the subject's right not to know and parent's right not to tell; and socioeconomic status and cultural/ethnic equity. CONCLUSIONS: The working group adopted a position of advocacy for children's right to research access while recognizing that this advocacy must be tempered by thoughtful protections for child and adolescent subjects.
Guinea pig lung mast cells can be isolated and purified to high purity. This has given us the opportunity to study in greater detail mediator release from these cells. Both immunologic (ovalbumin sensitized) and nonimmunologic (calcium ionophore, CaI) stimuli caused a dose-dependent release of histamine and pLT from monodispersed lung cells and highly purified lung mast cells. Examination of the time release curve for pLT revealed a 5-min lag in the release of this mediator and a peak release at 60 min after challenge with antigen. Verification of pLT release was obtained by use of the 5-lipoxygenase inhibitor A64077 (Zileuton). Pretreatment of lung mast cells with the 5-lipoxygenase inhibitor prevented release of pLT by either antigen or CaI but had no appreciable effect on histamine release (HR). The pulmonary mast cell appears to be an important contributor to pLT release in the guinea pig lung.
The primary objective of this study was to compare the antihypertensive efficacy and safety of intravenously administered nicardipine with that of intravenous nitroprusside (SNP) in patients with severe hypertension. The study was conducted in 121 patients with severe hypertension (diastolic blood pressure [BP] > 120 mm Hg, or systolic BP > 200 mm Hg). Patients were randomized to receive intravenous nicardipine or SNP. Drugs were administered according to a predetermined dosing schedule for a 10 to 12 h period. Sixty-one patients were randomized to intravenous nicardipine and 60 to SNP. Pretreatment BP values for the nicardipine and SNP groups were 217/128 mm Hg and 219/128 mm Hg, respectively. Therapeutic response (diastolic BP < 100 mm Hg, or a decrease of > 15 mm Hg; systolic BP < 180 mm Hg, or a decrease of > 20 mm Hg) was achieved in 98% (60/61) of patients treated with nicardipine and 93% (56/60) of patients treated with SNP. The mean decreases in systolic and diastolic BP were 61 mm Hg and 40 mm Hg after 4 h of nicardipine, and 59 mm Hg and 38 mm Hg after 4 h of SNP. The mean increases in heart rate also were similar in both groups (nicardipine, 12 beats/min; SNP 10 beats/min). The mean numbers of dose adjustments per hour required to maintain the BP reductions were lower (P < .01) in the nicardipine-treated patients (0.5 +/- 0.1 times per hour) than in the SNP-treated patients (1.5 +/- 0.2 times per hour).(ABSTRACT TRUNCATED AT 250 WORDS)
A prospective study of 199 patients over a two year period, 1 Jun 90 to 31 May 92 at the Louise Margaret Maternity Wing, Cambridge Military Hospital, Aldershot was undertaken to audit the uptake of an offer of conservative management of prolonged pregnancy to women at 42 weeks gestation. The labour outcomes of patients opting for conservative or induction management plans were recorded and the increased workload introduced to the Ultrasound Unit measured. Of the 91/199 (45.7%) patients who chose to be managed conservatively, 20 (22.0%) developed an abnormal result of a test of fetal surveillance, 16 (17.6%) were electively delivered because of an abnormal result. There were no significant differences in labour performance or neonatal outcome between those women opting for conservative management or induction of labour. 201 new ultrasound scans were booked, 129 were performed (0.4 scans/week/1000 deliveries).
The purpose of this study was to define the time course and the extent of recovery of muscle weight and tension in the extensor digitorum longus (EDL) muscle following partial denervation in nine-week-old male rats (300 to 325 g). The L4 nerve underwent unilateral sectioning while the opposite side served as a sham-operated control. The muscle weight and tension of the control and the partially denervated group were examined at two (n = 15), eight (n = 15), 12 (n = 15), and 16 (n = 15) weeks after L4 nerve sectioning. The partially denervated muscle weights as a percentage of respective controls were 58.6%, 56.1%, 68.4%, and 61.9% at two, eight, 12, and 16 weeks after L4 nerve sectioning. There was no significant difference (p > 0.05) between these percentages at the respective time intervals. The tetanic tensions compared with their respective matched controls were 14.5%, 32.8%, 50.0%, and 32.4% at these respective time intervals (p < 0.05). The muscle weight (MW) and muscle weight/body weight (MW/BW) of the partially denervated side as a percentage of its contralateral control remained unchanged throughout the duration of the experiment. The twitch tension (Pt), tetanic tension (Po), Pt/Po, and the Po/MW of the partially denervated muscle relative to its matched control increased between the second and the eighth week post-partial denervation (p < 0.05). After the eighth week post-L4 nerve sectioning, there was no further increase in these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
This four-center, 20-week, open-label study evaluated transdermal clonidine as an adjunct to enalapril 10 mg daily and demonstrated patterns of compliance. Seventy-four mildly to moderately hypertensive patients (mean seated blood pressure, 150/101 mm Hg) received enalapril 10 mg once daily as initial monotherapy. In 66 patients, the seated diastolic blood pressure remained greater than or equal to 90 mm Hg at the trough blood levels of enalapril. Transdermal clonidine (3.5 cm2, 7.0 cm2, or 10.5 cm2, equivalent to 0.1 mg, 0.2 mg, and 0.3 mg clonidine/day, respectively) then was added as needed to achieve blood pressure control. Forty-eight patients achieved diastolic blood pressures less than 90 mm Hg on concomitant therapy; 44 patients completed 8 weeks of maintenance dosing with a mean blood pressure of 134/85 mm Hg. Oral compliance, as measured by an electronic device that was actuated each time the medication vial was opened, varied from 48 to 140%. Compliance with the transdermal clonidine regimen was excellent; the patch was worn as directed during 96% of the patient-weeks of therapy. The authors conclude that blood pressure can be controlled by a combination of transdermal clonidine and enalapril in patients that do not adequately respond to enalapril monotherapy. Patients poorly complying with oral regimens may be candidates for a trial of transdermal clonidine monotherapy.
Explore the source record for details and available documents.
Nicardipine hydrochloride was administered intravenously to two groups of hypertensive patients: one group of 37 patients with mild to moderate hypertension and one group of 20 patients with severe hypertension. In the first group, doses of 0.5, 1, 2, and 4 mg/hr, as well as placebo, were infused for 48 hours in a double-blind fashion. Blood pressure and heart rate were monitored for this period and for the 24 hours after the infusion was discontinued. Significant decrements in blood pressure were noted with all doses; 4 mg/hr produced lowering that was greater than all other doses; 1 and 2 mg/hr produced lowering that was greater than 0.5 mg/hr but that were not different from each other. Excellent correlation of blood pressure reduction and plasma level was observed and linear kinetics existed. In the severe hypertensive patients, 1, 2, 4, 5, and 8 mg/hr were infused to established minimal and ineffective doses. One milligram per hour was an ineffective dose; 4, 5, and 8 mg/hr all produced significant reductions over the course of the study that were undistinguishable from each other. Two milligrams per hour produced modest reductions in blood pressure. Blood pressure reduction also correlated with plasma levels in the severe hypertensive group.
Nicardipine is an investigational dihydropyridine calcium-channel blocker. In the present study, 21 patients with severe hypertension were treated with oral nicardipine, alone or in combination with beta-blockers and diuretics for 4-5 weeks, following initial control of their blood pressure with intravenous nicardipine. Each of the 21 patients had a satisfactory response to intravenous nicardipine which was administered as an infusion following initial blood pressure lowering. At 1 h prior to discontinuation of the intravenous treatment, oral nicardipine therapy was begun as a 40 mg dose. Oral nicardipine, 40 mg t.i.d., was continued for the remainder of hospitalization and for a 4-5-week outpatient follow-up period. The dose of oral nicardipine was downtitrated and additional antihypertensive drugs, beta-adrenergic blocking agents and/or diuretics, were added to maintain blood pressure in an acceptable range. Compared to baseline, mean supine systolic blood pressure was lowered significantly (p less than 0.001) by 57 mmHg at the end of intravenous maintenance and by 50 mmHg at the end of oral treatment. Likewise, significant (p less than 0.001) decreases in diastolic blood pressure of 43 and 32 mmHg, respectively, were observed for the same time periods. At the end of oral treatment, 6 patients remained on nicardipine monotherapy, 8 patients were on two-drug therapy and 7 patients required three-drug therapy. Side-effects were mild except for a moderate headache reported in one patient during intravenous treatment. From these observations we conclude that oral nicardipine is a useful new agent for initial, single treatment of chronic severe hypertension, although a significant number of patients eventually need additional antihypertensive therapy.
A 1610-bp DNA duplex coding for human tissue-type plasminogen activator has been chemically synthesized using the phosphoramidite procedure, adapted for a custom-built gene synthesizer. The synthesizer, which was designed for both simplicity and speed, permits the rapid construction of relatively large genes and compares favorably in speed with alternative cDNA isolation procedures. The plasminogen activator gene has been expressed in mammalian cells and shown to produce authentic protein by an immuno-activity assay.
Explore the source record for details and available documents.
On the basis of Lang's (1979) theory of emotional imagery three experiments were conducted to investigate the relationship between slow cortical potentials (SP) and emotional imagery. According to the assumptions of Lang's theory and our model (Rockstroh et al., 1982) of SP-function imagery ability should be related to a person's capacity to generate and suppress preparatory activity in cortical networks "on demand." In order to test this hypothesis subjects in Experiment I were trained to regulate right- versus left-hemispheric SP-differentiation within an instrumental learning paradigm. Thirty-four subjects were reinforced for achieving maximal SP-differences between electrode locations C3-C4 over a 6 s interval across 120 trials. Success in the SP-regulation task correlated significantly (r = .37) with the capacity for vivid imagery as measured with the Questionnaire for Mental Imagery (QMI). In Experiment II instructions to imagine right- versus left-hand movements were introduced successively over 5 sessions of SP-self-regulation. Imagery clearly modified right- versus left-hand EMG-differentiation but had no influence on cortical SP-differentiation. Experiment III tested the influence of already achieved SP-regulation at the vertex on the perceived vividness of emotional images introduced after the SP-biofeedback training. Again, clear effects of imagery content on autonomic variables (HR, SCR) were found. However, SP-amplitude and SP-polarity had no effect on perceived vividness, arousal or emotional content. It may be concluded from the results of Experiment II and III that SPs either are not the crucial parameter to represent the cortical efferent outflow component of imagery, or that the dual task of SP-self-regulation and imagery prevented covariations to show up. Experiment I, on the other hand, points toward a positive relation of imagery-ability as a trait-variable and brain-self-regulation abilities.
This study examined the life satisfaction of 58 elderly American Indians and its relationship to selected external and internal environmental factors. Elderly Indians were 51-85 years of age and resided on two midwestern reservations. Data were collected through use of the Life Satisfaction Index Z-scale (LSI-Z), the Oars Multi-dimensional Functional Assessment Questionnaire (OARS) and a semi-structured interview schedule. Findings indicated that life satisfaction tended to be high. Six internal environmental variables explained 40% of the variance in life satisfaction scores. A higher correlation was found between self-perception of life satisfaction and mental health than objective ratings on these two variables. This study suggests that variables associated with the internal environment may be useful as indicators of life satisfaction in elderly reservation American Indians and that subjective measures of life satisfaction may be more predictive of mental health than objective measures.
By use of the opiate antagonist naloxone, we have examined the hormonal and metabolic responses to opiate-receptor blockade under basal conditions and during insulin-induced hypoglycemia in normal dogs. Naloxone treatment had no measurable effect on glucose concentration, turnover, and norepinephrine levels, but stimulated plasma epinephrine, glucagon, and cortisol and inhibited insulin release. Insulin (7 mU X kg-1 X min-1) decreased plasma glucose to 42 +/- 4 mg/dl due to an initial decrease in glucose production and an increase in glucose disappearance. Glucose production then increased, and plasma glucose plateaued. After 50 min of insulin infusion, epinephrine levels increased 26-fold (P less than 0.05), norepinephrine and glucagon 3-fold (P less than 0.02), and cortisol 4-fold (P less than 0.01). Similarly, plasma beta-endorphin and adrenocorticotropin (ACTH) were elevated (6-fold, P less than 0.01, and 16-fold, P less than 0.05, respectively). When naloxone was given during insulin-induced hypoglycemia, there was earlier release of epinephrine, glucagon, beta-endorphin, ACTH, and cortisol as well as a greater release of glucagon (P less than 0.001) and cortisol (P less than 0.0001). This resulted in a greater increase in glucose production (P less than 0.01), thus lessening the insulin-induced hypoglycemic excursion. In conclusion, in the dog, endogenous opiates may play a small role in the regulation of basal insulin and glucagon release and can inhibit the pituitary-adrenal axis under basal conditions and during hypoglycemia. Thus increased glucose production in response to insulin-induced hypoglycemia is consistent with the excessive response of counterregulatory hormones during opiate-receptor blockade.
Lipoteichoic acid (LTA) was prepared from type III group B streptococci and administered by topical oral application or intravenous or intratracheal injection in weanling and adult white New Zealand rabbits. Tritiated [3H]LTA in tissues and body fluids was measured by scintillation spectrometry. Five minutes to 120 h after intravenous injection of 10 mg (17 x 10(6) dpm) of [3H]LTA, none was present in blood. Combined urine and fecal excretion peaked at 24 h and decreased over 5 days. There was no effect on collagen-induced platelet aggregation. [3H]LTA concentrations were greatest in colon, bone, stomach, and skin 1 day after intravenous injection. After a 5-mg oral dose (8.5 x 10(6) dpm) in an adult animal, fecal excretion peaked at 24 h and decreased after 4 days. No systemic absorption was noted. No [3H]LTA was found in any of seven tissues examined at autopsy 3 days after 1 to 5 mg/kg oral doses in weanling animals with normal or traumatized buccal mucosa. No effect was noted on platelet aggregation or serum complement, there was no increase in the incidence of nephrocalcinosis and the buccal mucosa remained histologically normal. Intratracheal injection of 0.5 to 2.5 mg/kg of LTA resulted in no tachypnea or alteration in blood gases. All animals remained healthy after LTA administration. The absence of toxicity and absorption in animals suggests that studies could be performed in humans to evaluate the safety and efficacy of oral LTA.
A 43-bp DNA duplex coding for poly(arginine) [poly(arg)] has been synthesised by modified phosphotriester procedures. It has been inserted into the Bg/II and BamHI restriction sites of a cloned synthetic beta-urogastrone (Uro) gene, under the control of the trp promoter. Subsequent induction with 3 beta-indole acrylic acid produces beta-Uro with a C-terminal poly(arg) fusion. The raised isoelectric point of this polypeptide fusion facilitates rapid purification by cation exchange chromatography. The C-terminal poly(arg) tail can be readily removed by treatment with carboxypeptidase B.