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Biomedical subjects

C Havel

Publications and source records attributed to C Havel.

8 recordsLinked to original sources
PubMed2004

Vasopressors for shock.

BACKGROUND: Besides reversing the underlying cause, the first line treatment for the symptoms of shock is usually the administration of intravenous fluids. If this method is not successful, vasopressors such as dopamine, dobutamine, adrenaline, noradrenaline and vasopressin are recommended. It is unclear if there is a vasopressor of choice, either for the treatment of particular forms of shock or for the treatment of shock in general. OBJECTIVES: To assess the efficacy of vasopressors for circulatory shock in critically ill patients. Our main aim was to assess whether particular vasopressors reduce overall mortality. We also intended to identify whether the choice of vasopressor influences outcomes such as length-of-stay in the intensive care unit and health-related quality of life. SEARCH STRATEGY: We searched MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, PASCAL BioMed, CINAHL, BIOSIS, and PsychINFO:all from inception to November 2003; for randomized controlled trials. We also asked experts in the field and searched meta-registries for ongoing trials. SELECTION CRITERIA: We included randomized controlled trials comparing various vasopressors, vasopressors with placebo or vasopressors with intravenous fluids for the treatment of any kind of circulatory failure (shock). Mortality was the main outcome. DATA COLLECTION AND ANALYSIS: Two reviewers abstracted data independently. Disagreement between two reviewers was discussed and resolved with a third reviewer. We used random effects models for combining quantitative data. MAIN RESULTS: We identified eight randomized controlled trials. Reporting of methodological details was for many items not satisfactory: only two studies reported allocation concealment, and two that the outcome assessor was blind to the intervention. Two studies compared norepinephrine plus dobutamine with epinephrine alone in patients with septic shock (52 patients, relative risk of death 0.98, 95% confidence interval 0.57 to 1.67). Three studies compared norepinephrine with dopamine in patients with septic shock (62 patients, relative risk 0.88, 0.57 to 1.36). Two studies compared vasopressin with placebo in patients with septic shock (58 patients, relative risk 1.04, 0.06 to 19.33). One study compared terlipressin with norepinephrine in patients with refractory hypotension after general anaesthesia but there were no deaths (20 patients). REVIEWERS' CONCLUSIONS: The current available evidence is not suited to inform clinical practice. We were unable to determine whether a particular vasopressor is superior to other agents in the treatment of states of shock.

Humans↗
PubMed2001

Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome.

BACKGROUND: Moderate elevation of brain temperature, when present during or after ischemia, may markedly worsen the resulting injury. OBJECTIVE: To evaluate the impact of body temperature on neurologic outcome after successful cardiopulmonary resuscitation. METHODS: In patients who experienced a witnessed cardiac arrest of presumed cardiac cause, the temperature was recorded on admission to the emergency department and after 2, 4, 6, 12, 18, 24, 36, and 48 hours. The lowest temperature within 4 hours and the highest temperature during the first 48 hours after restoration of spontaneous circulation were recorded and correlated to the best-achieved cerebral performance categories' score within 6 months. RESULTS: Over 43 months, of 698 patients, 151 were included. The median age was 60 years (interquartile range, 53-69 years); the estimated median no-flow duration was 5 minutes (interquartile range, 0-10 minutes), and the estimated median low-flow duration was 14.5 minutes (interquartile range, 3-25 minutes). Forty-two patients (28%) underwent bystander-administered basic life support. Within 6 months, 74 patients (49%) had a favorable functional neurologic recovery, and a total of 86 patients (57%) survived until 6 months after the event. The temperature on admission showed no statistically significant difference (P =.39). Patients with a favorable neurologic recovery showed a higher lowest temperature within 4 hours (35.8 degrees C [35.0 degrees C-36.1 degrees C] vs 35.2 degrees C [34.5 degrees C-35.7 degrees C]; P =.002) and a lower highest temperature during the first 48 hours after restoration of spontaneous circulation (37.7 degrees C [36.9 degrees C-38.6 degrees C] vs 38.3 degrees C [37.8 degrees C-38.9 degrees C]; P<.001) (data are given as the median [interquartile range]). For each degree Celsius higher than 37 degrees C, the risk of an unfavorable neurologic recovery increases, with an odds ratio of 2.26 (95% confidence interval, 1.24-4.12). CONCLUSION: Hyperthermia is a potential factor for an unfavorable functional neurologic recovery after successful cardiopulmonary resuscitation.

Aged↗
PubMed2001

Different patterns of angioedema in patients with and without angiotensin-converting enzyme inhibitor therapy.

BACKGROUND: There is convincing evidence for a causal relationship between angiotensin converting enzyme inhibitor (ACEI) therapy and angioedema, but the clinical features of the patients remain unclear. The aim of the study was to compare patterns of angioedema in patients under ACEI therapy and those without ACEI therapy. METHODS: One hundred and seventeen consecutive patients with angioedema treated in the emergency department of a 2000-bed tertiary care university hospital were included. A retrospective cohort study was performed, the exposure being ACEI therapy. The pattern of location of angioedema was the primary outcome measure. RESULTS: Of 117 patients with angioedema, 25 (21%) received ACEI therapy. In a multivariate logistic regression model, angioedema of the cheeks, eyelids or nose was independently negatively associated with ACEI therapy [adjusted odds ratio 0.13 (95% confidence interval 0.03 to 0.49), p = 0.003]. Higher age was also significantly associated with ACEI therapy [adjusted odds ratio 1.85 (95% confidence interval 1.23 to 2.80), p = 0.003]. Furthermore, a trend towards an independent negative association between a history of allergies and angioedema under ACEI therapy was seen. CONCLUSION: Patients with angioedema under ACE inhibitor therapy differ significantly from those receiving no ACEI therapy in terms of patterns of angioedema and age. The applicability of this observation as a tool for deciding whether to continue or terminate ACEI therapy requires prospective evaluation.

Age Factors↗
PubMed2001

Therapeutic hypothermia after cardiac arrest.

This review discusses the mechanisms of neurologic damage during and after global cerebral ischemia caused by cardiac arrest. The different pathways of membrane destruction by radicals, free fatty acids, excitatory amino acids (neurotransmitters), calcium, glucose metabolism, and oxygen availability and demand in relation to metabolic rate are briefly discussed. The main focus of this review paper, however, lies in therapeutic (resuscitative) hypothermia after cardiac arrest. Two pioneering studies of the 1950s and four recent publications (in part preliminary results of ongoing studies) in humans are discussed in detail. The conclusions are as follows: (1) hypothermia holds promise as the only specific brain therapy after cardiac arrest so far; (2) hyperthermia is not tolerable after successful resuscitation; and (3) if the ongoing European multicenter trial of hypothermia after cardiac arrest finds a significant benefit to mild hypothermia, withholding hypothermia may be ethically hard to defend.

Brain Ischemia↗
PubMed1993

The mitotic feedback control gene MAD2 encodes the alpha-subunit of a prenyltransferase.

The mad2-1 mutation inactivates the cell-cycle feedback control that prevents budding yeast cells from leaving mitosis until spindle assembly is complete. The gene product of MAD2 shows significant sequence similarity to the alpha-subunit of prenyltransferases. Here we isolate a new temperature-sensitive mad2 mutant, mad2-2ts, and find that Mad2p is required for the membrane association of Ypt1p and Sec4p, two prenylated small GTP-binding proteins involved in protein trafficking. Extracts from mad2-2ts mutant cells fail to geranylgeranylate a number of substrates at the non-permissive temperature. mad2-2ts is synthetically lethal with bet2-1, a mutation in the gene that encodes for the beta-subunit of the Ypt1p and Sec4p geranylgeranyl transferase. Therefore MAD2 and BET2 gene products may physically interact to form a geranylgeranyl transferase complex. In addition, the difference between the phenotypes of mad2-1 and mad2-2ts suggests that MAD2 has distinct roles in protein transport and the mitotic feedback control.

Calcium-Binding Proteins↗
PubMed1986

Isopentenoid synthesis in isolated embryonic Drosophila cells. Possible regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity by shunted mevalonate carbon.

Our previous studies (Watson, J. A., Havel, C. M., Lobos, D. V., Baker, F. C., and Morrow, C. J. (1985) J. Biol. Chem. 260, 14083-14091) suggested that a matabolite, distal to isopentenyl 1-pyrophospate (IPP), served as a regulatory signal for sterol-independent modulation of Kc cell 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. This report summarizes efforts to localize the potential source of the post-IPP regulatory signal molecule. We found no direct correlation between mevalonate-mediated suppression of Kc cell HMG-CoA reductase activity and the rates of [1-14C]-, [3-14C]-, [5-14C]-, or [5-3H]mevalonate incorporation into either carbon dioxide, neutral lipids, water, or water-soluble isopentenoid pyrophosphate esters. [1-14C]Mevalonate's rate of conversion to 14CO2 (a measure of total isopentenyl 1-pyrophosphate synthesis) was minimally 5-fold greater than that for neutral isopentenoid lipid synthesis (measured with either [5-3H]-, [3-14C]-, or [5-14C]mevalonate). However, [5-3H]mevalonate's rate of conversion into [3H]H2O (measure of shunted mevalonate carbon) was equivalent or greater than that measured for neutral isopentenoid lipid synthesis. [5-14C]Mevalonate radioactivity was incorporated into macromolecules and n-fatty acids. Kc cell extracts (100,000 X g supernatant fluid) readily oxidized alcohols with the following activity sequence: geraniol = nerol greater than farnesol = dimethylallyl alcohol greater than geranylgeraniol, isopentenyl alcohol, and allyl alcohol. Oxidation required NAD, and ethanol was not a substrate. We conclude that (a) Kc cells shunted a significant fraction (greater than or equal to 40%) of their post-IPP carbon to prenols for oxidative catabolism and (b) that shunted mevalonate carbon may play a significant role in the mevalonate-mediated regulation of Kc cell HMG-CoA reductase activity.

Alcohols↗
PubMed1979

Regulation of cholesterol synthesis in primary rat hepatocyte culture cells. Possible regulatory site at sterol demethylation.

Primary rat hepatocyte culture cells were used to study the acute regulation of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity in response to 25-hydroxycholesterol, 3 beta,5 alpha,6 beta-cholestantriol, and mevalonolactone. All three effectors caused a rapid suppression of HMG-CoA reductase activity. 25-Hydroxycholesterol also caused an increase in the ratio of newly synthesized methyl sterols to newly synthesized C27-sterols. Furthermore, in 25-hydroxycholesterol-treated cells, the relative contribution of delta 24-sterol precursors to the nonsaponifiable lipid fraction increased. Di- and trimethyl-diene sterols were the dominant methyl sterols synthesized in the presence of 25-hydroxycholesterol. 3 beta,5 alpha,6 beta-Cholestrantriol (50 microM) also caused a very strong (97%) suppression of sterol demethylation; 4,4-dimethylmonoene sterols were more prominent (23%) in cells treated with 3 beta,5 alpha,6 beta-cholestrantriol, than in cells treated with 25-hydroxycholesterol (2%). The rates of both unesterified and esterified sterol synthesis increased as a function of exogenous mevalonolactone concentration. C27-sterol synthesis was saturated at a concentration of (R)-mevalonolactone which produced only a 33% suppression of HMG-CoA reductase activity. However, there was a direct relationship between the accumulation of methyl sterols and the decrease in HMG-CoA reductase activity. With the aid of triparanol, it was demonstrated that the suppression of HMG-CoA reductase activity by mevalonolactone was linked with the ability of the cells to convert squalene-2,3-epoxide into sterols. The results described in the present article support an important and perhaps necessary relationship between the rate of methyl sterol conversion of C27-sterols and the suppression or inhibition of HMG-Coa reductase in primary hepatocyte culture cells.

Acetates↗