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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 271 records · Page 15Linked to original sources
PubMed1994

The use of benzodiazepines among regular amphetamine users.

The relationship between benzodiazepine and regular amphetamine use was examined in a sample of 301 regular amphetamine users. Benzodiazepine use was widespread, with 37% of subjects having used them in the month preceding interview, and 55% in the preceding 6 months. Injectors of amphetamines were more likely to have ever used, and to be currently using, benzodiazepines. Comparisons of benzodiazepine users with other subjects indicated that benzodiazepine users had higher levels of polydrug use and psychopathology, as well as poorer health and social functioning than non-users. The odds of benzodiazepine using injectors having injected with a borrowed used needle in the preceding month were 3.8 times of those of non-benzodiazepine-using injectors. These results are consistent with studies of other groups of illicit drug users, such as heroin users, in indicating that benzodiazepine use is associated with greater levels of risk and psycho-social dysfunction.

Adolescent↗
PubMed1994

The half-life of c-myc mRNA in growing and serum-stimulated cells: influence of the coding and 3' untranslated regions and role of ribosome translocation.

c-myc mRNA contains at least two discrete sequence elements that account for its short half-life, one in the 3' untranslated region and the other in the carboxy-terminal coding region (coding-region determinant). To investigate the function of each determinant, one or both were fused in frame to portions of a gene encoding long-lived beta-globin mRNA. Each chimeric gene was stably transfected into HeLa and NIH 3T3 cells and was transcribed from a constitutive cytomegalovirus promoter or from a serum-regulated c-fos promoter, respectively. The steady-state levels of the chimeric mRNAs in exponentially growing HeLa cells were compared, and their half-lives were measured by two independent methods: (i) in actinomycin D-treated HeLa cells and (ii) after serum addition to starved 3T3 cells. By each method, mRNAs containing either instability determinant were less stable than beta-globin mRNA. mRNA containing only the c-myc 3' untranslated region was not significantly more stable than mRNA with both determinants. In a cell-free mRNA decay system containing polysomes from transfected HeLa cells, mRNA containing the coding-region determinant was destabilized by addition of a specific RNA competitor, whereas mRNA containing only the 3' untranslated region was unaffected. When a stop codon was inserted upstream of the coding-region determinant, the chimeric mRNA was stabilized approximately twofold. These and other data suggest that degradation involving the coding-region determinant occurs most efficiently when ribosomes are translating the determinant.

3T3 Cells↗
PubMed1994

Attitudes of women to fetal tissue research.

The use of human fetal tissue for scientific research has enormous potential but is subject to government legislation. In the United Kingdom the Polkinghorne Committee's guidelines were accepted by the Department of Health in 1990. These guidelines set out to protect women undergoing termination of pregnancy from exploitation but in so doing may significantly restrict potential research. Although the committee took evidence from a wide variety of experts they did not seek the views of the general public. We asked 108 women about to have a therapeutic abortion; 167 women who had had a pregnancy terminated in the past, and 419 women who had never had an abortion, their views on research using human fetal tissue. Regardless of their past experiences the women were overwhelmingly in favour of research using fetal tissue (94 per cent). They made little distinction between basic research and research with obvious clinical relevance and supported the concept of using transplanted fetal tissue for the treatment of adult disease such as Parkinsonism. Women about to undergo an abortion were significantly more likely (p < 0.001) to approve of all types of research including that aimed at improving methods of abortion and research using live fetuses in utero.

Aborted Fetus↗
PubMed1994

ANG II receptor blockade prevents ventricular hypertrophy and ANF gene expression with pressure overload in mice.

There is increasing evidence that the renin-angiotensin system may play a important role in cardiac hypertrophy. To assess the role of angiotensin II in the induction of cardiac hypertrophy, three groups of adult mice were subjected to left ventricular pressure overload by transverse aortic constriction (TAC). For the next 7 days the groups received either the specific angiotensin II subtype 1 receptor (AT1) antagonist (losartan, 1.05 g/l; n = 17), an angiotensin enzyme inhibitor (captopril, 2 g/l; n = 17), or no treatment (n = 22) administered in the drinking water and compared with three similarly treated sham-operated groups (n = 7 each). TAC resulted in a significant increase in heart weight-to-body weight ratio (0.634 +/- 0.087 vs. 0.525 +/- 0.039, g/g x 100, P < 0.05), which was prevented by losartan (0.506 +/- 0.069, g/g x 100, P < 0.0001) despite similar hemodynamic load (proximal systolic pressure 146 +/- 31 vs. 136 +/- 32 mmHg, untreated vs. losartan, P = NS). Proximal systolic pressure was positively correlated with the development of ventricular hypertrophy. In the presence of AT1-receptor blockade, the increase in heart weight-to-body weight ratio at any given systolic pressure was significantly attenuated compared with untreated TAC mice. The increase in heart weight-to-body weight ratio was also significantly attenuated by captopril compared with untreated banded controls (0.542 +/- 0.091, g/g x 100, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗
PubMed1994

Force-frequency relations during heart failure in pigs.

In isolated cardiac muscle from patients with severe heart failure (HF) the force-frequency relation (FFR) is often negative, but the characteristics of the FFR under basal conditions and its responsiveness to adrenergic stimulation have not been studied in the intact, failing heart. Severe HF was produced in pigs (n = 6) by continuous rapid left ventricular (LV) pacing (225 beats/min). In the conscious resting state, high-fidelity LV pressure and its maximum first derivative (LV dP/dtmax) were obtained over a range of atrial pacing rates (100-225 beats/min) before (control) and after HF. Before HF, the relationship between increased heart rate and LV dP/dtmax (a measure of the FFR) was flat, but during dobutamine infusion the FFR showed a significant positive slope (P < 0.003). After HF, the basal FFR was depressed, but the slope of the FFR was not increased by dobutamine. After HF, responses of dP/dtmax to slowing of HR by a specific sinus node inhibitor confirmed the absence of a negative basal FFR. In conclusion, the basal LV FFR in conscious pigs with severe HF was not negative. Unlike the normal heart, in HF beta-adrenergic receptor stimulation did not amplify the FFR, a phenomenon that could play an important role in the impaired response to exercise in patients with HF.

Animals↗
PubMed1994

Heart rate and force-frequency effects on diastolic function of the left ventricle in exercising dogs.

BACKGROUND: Previous studies from our laboratory have shown pronounced augmentation of the force-frequency relation on myocardial contraction during exercise, but the influence of this effect on diastole has not been investigated. METHODS AND RESULTS: Accordingly, the effect of changing heart rate on left ventricular (LV) relaxation, filling dynamics, and pressure-volume relations during exercise was studied in eight conscious dogs. The exercise heart rate was slowed from 208 +/- 21 (SD) to 163 +/- 11 beats per minute by injection of a specific sinus node inhibitor (UL-FS 49, or zatebradine, 0.6 mg/kg) during continuous exercise. Heart rate was then abruptly restored to the predrug level by atrial pacing during continued exercise. LV volume was calculated by use of implanted ultrasonic crystals, and LV pressure was determine with an implanted micromanometer. Comparing conditions after pacing back to a heart rate of 210 beats per minute with those obtained when the heart rate was slowed by atrial pacing, LV dP/dtmax was increased by 27% at the higher rate (P < .01), despite a marked decrease in LV end-diastolic pressure (24 +/- 4 versus 10 +/- 5 mm Hg, P < .01) and the time constant of isovolumic LV pressure decay (tau) was significantly shortened (19 +/- 5 versus 14 +/- 4 milliseconds, P < .01). The peak rapid filling rate in early diastole (PFR) was not significantly changed by increasing the heart rate, since it was maintained at the slower rate. During exercise, at the slowed heart rate the early portion of the diastolic pressure-volume curve was significantly shifted upward and to the right compared with that at the physiological heart rate, but the late portion of the curve was unchanged. CONCLUSIONS: These data indicate that the negative inotropic effect of the force-frequency relation when heart rate was slowed during exercise caused pronounced impairment of LV relaxation and early filling dynamics. Conversely, an important component of the pronounced improvement of diastolic ventricular function during normal exercise was shown to result from exercise-induced enhancement of the positive inotropic effects of the force-frequency relation on myocardial contraction and relaxation.

Animals↗
PubMed1994

Extended supracricoid partial laryngectomy with tracheocricohyoidoepiglottopexy.

Extended supracricoid partial laryngectomy with tracheocricohyoidoepiglottopexy (TCHEP) was studied as an alternative to total laryngectomy in 16 patients with glottic carcinoma presenting a 10-15 mm of anterior subglottic extent. The technique of the procedure is described. Results were analyzed for tumor free margins, tracheostomy decannulation, oral alimentation, phonation and disease free interval. The 3-year survival and local control rate were 68% and 86.7%, respectively. Our preliminary data suggest that the TCHEP procedure is a viable alternative to total laryngectomy for patients presenting with varying degrees of carcinoma extension below the free edge of the true vocal cords.

Adult↗
PubMed1994

Discrimination of auditory temporal patterns.

Two same-different discrimination experiments were performed for click patterns having a total duration of about 4 sec and interclick intervals of n x 250 msec, with n a random integer. In Experiment 1, the influence of the physical click group structure on discrimination performance was investigated. In Experiment 2, the effect of the strength of an induced internal clock on discrimination performance was measured. Performance was poor if the group structure of clicks was maintained during a change in click pattern and also if the induced internal clock strength was low. The performance of about 70% of the subjects improved significantly if either a change in click grouping structure occurred or a strong internal clock could be induced. These results cannot be accounted for with simple models based on single-interval duration discrimination or between-pattern correlation statistics.

Attention↗
PubMed1994

Penetrating injuries of the popliteal artery: the Baragwanath experience.

This study describes the management of 43 patients with penetrating injury of the popliteal artery. Of these patients, 33 (76.5%) had bullet wounds, four patients (9.5%) pellet wounds and 6 (14%) knife wounds. Patients with 'hard' signs of arterial injury underwent exploration without preoperative angiograms. There were no negative explorations. Patients with only 'soft' signs of arterial injury underwent preoperative angiograms. Of this group, 75% had positive angiograms and underwent exploration. There were no false-positive or false-negative preoperative angiograms in the group of patients with 'soft' signs in this study. Definitive orthopaedic management of associated fractures followed vascular reconstruction. There was no difference in the short-term patency of autologous saphenous vein graft as against PTFE grafts. Fasciotomy was performed on patients who had arterial and venous injury or presented late. Overall amputation rate was 14% and for bullet injuries 18%.

Adolescent↗
PubMed1994

HIV in general practice.

Jim's story illustrates many issues. The importance of the GP in any chronic condition is highlighted. In Jim's case he was never actually sick. All his visits were for monitoring, counselling, preventive medicine and co-ordinating other health care workers. There is a fine line between performing these vital functions and 'over-medicalising' a well person. All areas of Jim's life were touched by his diagnosis--work, recreation, relationships and sex--all had to be included in his overall management. I had to face my own difficulties in dealing with the potential tragedy of Jim's situation and maintain a personal detachment. An obvious friendship had developed between us and I too dreaded every blood count and new symptom in case it was a sign of deterioration. My discomfort was made worse by my inexperience with HIV and I had to struggle to keep ahead of Jim with regard to information about new medication and research findings. Jim experienced the usual grief reactions and emotional responses that anyone with bad news must work through. In his situation his lack of support from family or lover left him particularly vulnerable. His dealing with the diagnosis was made that much harder as he saw his partner and friends dying from the same condition. In summary, Jim was a well man who was given a result that changed his life. The principles of his management were the same for every other medical condition in that mind and body, work and play are all important for good care.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Natural cytotoxicity in breast cancer patients receiving neoadjuvant chemotherapy: effects of L-arginine supplementation.

Certain cytotoxic drugs have been shown to suppress host anti-cancer defence mechanisms. The amino acid L-arginine can significantly enhance natural killer (NK) and lymphokine-activated killer (LAK) cell cytotoxicity in patients with locally advanced breast cancer. In this study, the effect of L-arginine supplementation on natural cytotoxicity was determined in patients with breast cancer receiving CHOP chemotherapy. This cytotoxic regimen caused a transient immunosuppression, maximal on day 14 of each cycle (P < 0.001); this was not cumulative during the four cycles of treatment. Those patients receiving L-arginine supplementation (30 g/day for 3 days prior to each course of chemotherapy) had a smaller and delayed onset of immunosuppression (day 14), compared with those patients who had CHOP only (day 9). L-Arginine was able to repeatedly stimulate NK and LAK cell cytotoxicity in patients who were receiving CHOP chemotherapy (P < 0.003). In conclusion, further studies are required to determine the optimal use of chemotherapeutic agents, alone or in combination with immunostimulators, to avoid inhibition of host anti-cancer defence mechanisms.

Adult↗
PubMed1994

Promotion of corneal allograft survival with leflunomide.

PURPOSE: The efficacy of the antirejection drug leflunomide was evaluated in a rat model of penetrating keratoplasty. METHODS: Corneal grafts from inbred Lewis rats were transplanted orthotopically to inbred Wistar-Furth (WF) recipients. WF rats received either Leflunomide (HWA 486), the active metabolite of leflunomide (A77-1726A), or cyclosporin A, administered orally beginning 2 days before transplantation and continuing for 30 days thereafter. Graft survival was assessed clinically three times per week, and mean survival times were determined. RESULTS: Oral administration of either leflunomide or the salt of its active metabolite resulted in a significant prolongation of graft survival time. Moreover, almost one third of the grafts survived for an additional 3 weeks, even after drug treatment was discontinued. CONCLUSION: The results indicate that leflunomide holds considerable promise as an antirejection drug for use in recipients of corneal transplants in whom cyclosporin A and steroids are contraindicated.

Administration, Oral↗
PubMed1993

Left ventricular function after coronary artery reperfusion.

Left ventricular dysfunction and dilation after reperfusion relate to the amount of infarcted and dysfunctional myocardium and will continue to be important determinants of morbidity and mortality. There is marked heterogeneity in the anatomic and pathophysiologic presentation of patients with acute myocardial infarction prior to thrombolysis, and many of these individual settings resemble those in animal species with various degrees of collateral formation. Three major determinants of infarct size are responsible for this heterogeneity and include the risk area, the duration of the coronary occlusion, and the level of the residual coronary blood flow via collaterals or a partially patent artery. All 3 of these determinants will influence the initial and late results of reperfusion therapy on infarct size and ventricular function. However, in addition to late or unsuccessful thrombolysis, there are other important factors determining outcome: inadequate reflow, residual coronary stenosis, and coronary reocclusion, factors that can be associated with late progressive left ventricular dilation and dysfunction. The risk factors for left ventricular dysfunction and dilation after reperfusion can now be identified, and such patients should undergo coronary angiography prior to hospital discharge and, if appropriate, revascularization of the infarct-related artery (and perhaps other vessels). In other patients, if serial studies reveal progressive left ventricular failure and dilation late after reperfusion, despite therapy with an angiotensin-converting enzyme (ACE) inhibitor, and if repeat coronary angiography identifies significant coronary stenoses and areas of hibernating or stunned myocardium, revascularization may limit progression of dilation and improve left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Outcome after acute myocardial infarction in patients with prior coronary artery bypass surgery.

Little is known concerning the influence of remote prior coronary artery bypass grafting (CABG) on the outcome of patients with acute myocardial infarction (AMI). Therefore, this study evaluated 2,494 patients with AMI of whom 219 (8.8%) had a history of CABG a mean of 7.1 +/- 3.7 years before the index AMI. Compared with all other patients, those with a history of CABG had an increased prevalence of a history of prior AMI (153 [70%] vs 547 [24%]), congestive heart failure (48 [22%] vs 236 [10%]), and angina pectoris (165 [75%] vs 787 [35%]), all p < 0.001. There was no difference in age, but patients with prior CABG were more often men (192 [88%] vs 1,702 [75%], p < 0.001). During the hospitalization for AMI, patients with prior CABG had more recurrent ischemic pain (100 [46%] vs 732 [32%, p < 0.001]), and more frequently developed non-Q-wave AMI (72 [33%] vs 514 [23%], p < 0.01). In-hospital mortality did not differ among patients with or without prior CABG (15 [7%] vs 195 [9%]). At hospital discharge, more patients with prior CABG had complex ventricular ectopic activity on 24-hour ambulatory electrocardiographic monitoring (48 of 74 [65%] vs 327 of 797 [41%], p < 0.0001), and radionuclide ejection fraction < 0.45 (53 of 99 [54%] vs 430 of 1,024 [42%], p < 0.01). Among patients undergoing coronary angiography during the first 2 months, multivessel coronary artery disease was more prevalent among patients with prior CABG (78 of 107 [73%] vs 508 of 959 [53%], p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1993

Identification and biochemical characterization of a heart-muscle cell transforming growth factor beta-1 receptor.

Binding of human-recombinant transforming growth factor-beta 1 (TGF-beta 1) to the neonatal rat heart-muscle cell (cardiomyocyte) was characterized as a potential element in the cardioprotective pharmacology of this growth factor. The cardiomyocytes were found to express a single class of specific, high-affinity TGF-beta 1 binding sites. Ligand binding to these sites was rapid, saturable, selective, and reversible, characteristics of a receptor-mediated process. Scatchard and iterative non-linear least-squares regression analyses demonstrated that the cardiomyocyte TGF-beta 1 receptor had a Kd < or = 40 pM, a Bmax of approximately 3.4 fmol/10(6) cells, and a density of approximately 2000 binding sites/cell. Binding was selective for TGF-beta 1 as compared with other TGF-beta isoforms (i.e. TGF-beta 2 and -beta 3) and nonrelated cytokines (e.g. acidic fibroblast growth factor). Affinity-binding experiments to probe the molecular nature of the specific binding revealed three types of cardiomyocyte TGF-beta 1 binding proteins, the most prominent of which corresponded to the high-molecular-mass proteoglycan observed in nonmuscle cell types. These data raise the possibility that the known pharmacological effects of TGF-beta 1 on heart muscle may be direct actions via specific receptor-mediated events.

Affinity Labels↗
PubMed1993

Individual purified core and linker histones induce histone H4 mRNA destabilization in vitro.

The replication-dependent histone genes encode mRNAs that are expressed during S phase. When DNA synthesis ceases, histone mRNAs are rapidly degraded via the activation of a specific mRNA destabilization process. It has been proposed that this process is autoregulated by histone proteins and is triggered by an increase in the abundance of cytoplasmic histones that accompanies the cessation of DNA synthesis. Consistent with this proposal, all four core histones, in conjunction with cytosol, specifically trigger a 3-4-fold destabilization of polysome-associated histone mRNA in cell-free extracts. Here, we show that each individual purified core histone or purified linker histone H1 can autoregulate (destabilize) histone mRNA in vitro. Three basic polypeptides, protamines, poly-L-lysine, and poly-L-arginine, accelerate an early step in the decay pathway but do not fully autoregulate the mRNA. These data suggest that histones function by overcoming a holdup point at an early step in histone mRNA degradation and that unique properties of histones, aside from their basic domains, are necessary to trigger autoregulation.

Animals↗
PubMed1993

Identification and molecular characterization of a high-affinity cardiomyocyte transforming growth factor-beta 2 receptor.

Rat neonatal heart muscle cells (cardiomyocytes) were found to express a high-affinity surface receptor for transforming growth factor-beta 2 (TGF-beta 2). Specific binding was rapid, saturable, ligand-selective, and reversible. Equilibrium binding analyses revealed that the cardiomyocyte had one class of specific binding sites with a Kd < or = 26 pM TGF-beta 2, a Bmax of approximately 9 fmol/10(6) cells, and approximately 5,000 binding sites/cardiomyocyte. Binding was selective for TGF-beta 2 in comparison to other TGF-beta isoforms and to unrelated growth factors. Affinity-binding experiments revealed three types of cardiomyocyte TGF-beta 2 binding proteins, the most prominent of which corresponded to the high-molecular mass proteoglycan. These data raise the possibility that the anti-ischemic cardioprotective effects of TGF-beta may reflect receptor-mediated signal transduction at the cardiomyocyte level.

Affinity Labels↗