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Biomedical subjects

E Lambert

Publications and source records attributed to E Lambert.

At least 19 recordsLinked to original sources

[Acute cardiovascular complications of cocaine. About two case reports].

Concerning any socioprofessional category, some addictive drugs like cocaine are responsible for many complications. The authors relate two case reports of young patients who suffered from cardiovascular accidents due to this drug. The first one was diagnosed with an ischemic stroke caused by carotid artery dissection and a leg distal vascular obliteration, the second one with a myocardial infarction with transient left ventricular dysfunction. Through these two case reports, the authors take stock of the pathophysiological and therapeutic knowledge of cardiovascular accidents after cocaine intake.

Adult↗

[Anaesthesia and amiodarone-associated hyperthyroidism].

Amiodarone can induce severe hyperthyroidism that justifies its withdrawal and initiation of antithyroid drugs. Impossibility to stop amiodarone, failure to control hyperthyroidism and unfavourable evolution can lead to thyroidectomy. Cardiac manifestations, persistence of hyperthyroidism and interactions between amiodarone and anaesthetic or haemodynamic drugs may contraindicate anaesthesia. We report nine consecutive cases of amiodarone-associated hyperthyroidism that prompted us to perform thyroidectomy under general anaesthesia. The features and anaesthetic data of patients were noted. The antithyroid medical treatment failed in all patients. After thyroidectomy, evolution was favourable in all nine cases, without any intra or postoperative complication, in spite of the extent of hyperthyroidism and the severity of the associated cardiac problems. Despite potential high risks, thyroidectomy for amiodarone-induced hyperthyroidism does not seem to increase morbidity or mortality and allows a quick return to euthyroidism and reintroduction of amiodarone.

Adult↗

Bone mineral density and lifetime physical activity in South African women.

We investigated the relation between lifetime physical activity and bone mineral density (BMD) in South African women using data collected in a case-control study of breast cancer in relation to BMD. Subjects (n = 144) were of black African or mixed ancestral origin, and <60 years of age (mean age 42.6 +/- 8.9 years). Cases had newly diagnosed breast cancer (n = 62) and controls were referred for conditions unrelated to BMD or breast cancer (n = 82). Physical activity data consisting of household, occupational and leisure-time activity, and activity for transport, were collected via questionnaire at 4 life stages (epochs), viz. 14-21, 22-34, 35-50, and 50+ years of age. Total energy (MET hrs) and peak strain scores were calculated. Lumbar spine and total proximal femur BMD were measured using dual-energy x-ray absorptiometry. BMD measures were similar between groups, therefore data were combined. BMD measures were unrelated to total lifetime physical activity. However, the major determinants of total proximal femur BMD included age, transport activity including walking and bicycling between the ages of 14 and 21 years, and current weight (adjusted r2 = 0.33, P < 0.0001). The major determinants of lumbar spine BMD included age, household energy expenditure between the ages of 14 and 21 years, and current weight (adjusted r2 = 0.23, P < 0.0001). Total peak bone strain score for activities between 14-21 years of age was also significantly correlated with lumbar spine BMD ( r = 0.18, P < 0.05). Intraclass correlation coefficients to assess tracking of activity through epochs 1, 2, and 3 were high for total energy expenditure (0.96; 95%CI: 0.94-0.97), household (0.98; 95%CI: 0.97-0.99) and occupational activity (0.78; 95%CI: 0.71-0.84) and activity for transport (0.92; 95%CI: 0.89-0.94). These data suggest that walking or activities resulting in impact loading at a young age are associated with higher BMD in later years. In addition, our findings suggest tracking of physical activity over time.

Absorptiometry, Photon↗

[Clinical and biological surveillance of envenomed patients].

Faced with an envenomation, the problem is to take sufficiently rapidly the decision to administer the only effective treatment--immunotherapy--, to know which antivenom to choose and how long to administrate it. If the snake is not identified, symptoms and initial development give information on the type of venom. It is convenient to classify the symptoms according to four clinical types: i) the cobra syndrome with a potentially fatal evolution within two to ten hours and which resembles an Elapid bite, ii) the viper syndrome associating bleeding and inflammation, which can be due either to a viper, pit viper or, in Australia, to Elapids, iii) disturbance of blood circulating functions and iv) disturbance of other live functions. Between the third to the half of snakebite victims present no envenomation. Severe envenomations must be monitored in an intensive care unit, with experience in emergency management and monitoring of patients with major life-threatening conditions. Throughout the world, snakebites induce more than 100,000 deaths every year. Schematically, the emergency may be considered in terms of seconds for blood circulation disorders, minutes for respiratory paralysis, and hours for the coagulopathy.

Algorithms↗

Impact of the renin-angiotensin system on cerebral perfusion following subarachnoid haemorrhage in the rat.

1. This study investigated the effects of blocking the AT1 angiotensin receptors with irbesartan, either peripherally or centrally, on systemic blood pressure, intracranial pressure and cerebral perfusion pressure following experimental subarachnoid haemorrhage (SAH) in urethane-anaesthetized rats. Sympathetic nervous activation was determined by measuring plasma noradrenaline levels. 2. In untreated animals, SAH induced a sustained increased in intracranial pressure from 2.1 +/- 0.3 to 16 +/- 2 mmHg (3 h, P < 0.001). Cerebral perfusion pressure was reduced by 20 % (P < 0.001), this reduction being maintained for 3 h. Sympathetic activation was evident in the high level of plasma noradrenaline measured 3 h post-SAH (751 +/- 104 vs. 405 +/- 33 pg ml(-1), P < 0.05). 3. Acute peripheral pretreatment with irbesartan (3 mg kg(-1), I.V.) prevented the rise in plasma noradrenaline and further aggravated the decrease in cerebral perfusion pressure by producing transient systemic hypotension (blood pressure was 85 +/- 6 mmHg at 2 h post-SAH vs. 100 +/- 3 mmHg, P < 0.01). 4. Intracisternal pretreatment with irbesartan (0.035 mg) did not prevent the rise in plasma noradrenaline post-SAH but enhanced the rise in intracranial pressure by 75 % compared with untreated animals. 5. This study demonstrates that peripheral endogenous angiotensin II interacts with the sympathetic nervous system in order to maintain an adequate cerebral perfusion following SAH. Endogenous angiotensin II in the brain seems to exert a protective effect by counteracting the elevation in intracranial pressure that occurs following experimental SAH.

Angiotensin II↗

Noradrenaline synthesis, release and vesicular transport in the rat brain following subarachnoid haemorrhage.

The present study was designed to estimate the release of noradrenaline, and to evaluate the efficiency of noradrenaline vesicular transport, as indicated from measures of dihydroxyphenylglycol (DHPG), and synthesis in the medulla and hypothalamus following subarachnoid haemorrhage in rats. Subarachnoid haemorrhage was induced by the injection of homologous blood into the cisterna magna (n = 11). Sham operated animals served as controls (n = 11). Three days following subarachnoid haemorrhage, medulla and hypothalamus were dissected and placed in an in vitro superfusion system. Exposure to K(+) (50 mM) for 2 min served as a stimulus for the release of the neurotransmitter noradrenaline, its precursor (dihydroxyphenylalanine [DOPA]) and intraneuronal metabolite, DHPG. Basal noradrenaline overflow from both the medulla and hypothalamus were similar in the two groups of rats but basal DOPA overflow from the medulla was significantly reduced in the subarachnoid haemorrhage animals (0.97 +/- 0.15 vs. 1.97 +/- 0.38 pg/10 min/mg, p < 0.01). Administration of K(+) induced the release of noradrenaline, the response from the medulla in the subarachnoid haemorrhage group being attenuated (p < 0.01) compared with the sham operated animals (174% and 240%, respectively). K(+) induced a similar release of noradrenaline from the hypothalamus in both groups of rats (239% in sham animals and 283% in the subarachnoid haemorrhage group). The overflow of DHPG from both the hypothalamus and medulla was similar in both groups of animals. Our results suggest that the diminution in noradrenaline release from the medulla occurs as a result of a reduction in the rate of noradrenaline synthesis and release.

Animals↗

Acute and chronic alterations in blood pressure variability following experimental subarachnoid haemorrhage.

This study examined the role of the renin-angiotensin and vasopressin systems on systolic blood pressure (SBP) variability following subarachnoid haemorrhage (SAH) in conscious rats. Animals received no treatment, the angiotensin II AT1 receptor antagonist, losartan, or the vascular vasopressin receptor antagonist, AVPX. SAH resulted in a transient sympathetic activation as estimated from the increase in the mid-frequency oscillations of SBP (3.2 +/- 0.8 mm Hg2, 3 hours after the injury vs. 1.3 +/- 0.3 mm Hg2 in control conditions, p < 0.01). On the second and fourth day following SAH, a marked elevation in the low-frequency component of SBP was observed (7.1 +/- 1.0 mm Hg2 on day 2 vs. 2.6 +/- 0.3 mm Hg2 in control conditions, p < 0.001 and 6.3 +/- 1.1 mm Hg2 on day 4 vs. 2.6 +/- 0.3 mm Hg2 in control conditions, p < 0.01). Pre-treatment with losartan prevented the acute rise in the mid-frequency oscillations in SBP and partially reduced the low-frequency component observed at 2 and 4 days. Administration of AVPX on the second and fourth day following SAH normalised the elevated low-frequency oscillations in SBP. This study indicates that the modifications in SBP variability observed in the early and delayed stage after subarachnoid haemorrhage involve angiotensin II. Vasopressin seems to be implicated in the delayed development of low-frequency fluctuations of SBP.

Animals↗

Subarachnoid haemorrhage-induced sympathoexcitation in rats is reversed by bosentan or sodium nitroprusside.

1. The roles played by nitric oxide (NO) and endothelin (ET) in the genesis of sympathetic nervous activation following experimental subarachnoid haemorrhage was investigated using spectral analysis of blood pressure rhythms. 2. Subarachnoid haemorrhage was induced in conscious rats by injecting 0.3 mL homologous blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. Three hours after the insult and after sympathetic activation was evident, animals received either an acute injection of the ET antagonist bosentan (5 mg/kg, i.v.; n = 7), an infusion of the NO donor sodium nitroprusside (SNP; 18 microg/h; n = 7) or no treatment (n = 7). 3. Three hours following the induction of subarachnoid haemorrhage, the mid-frequency components of systolic blood pressure were markedly elevated, indicating a pronounced sympathoexcitation. However, blood pressure and heart rate levels remained unchanged at this time. In the absence of treatment, the mid-frequency components of blood pressure remained elevated for a subsequent 2 h. Treatment with a non-hypotensive dose of SNP reversed the sympathoexcitation within 1 h. Treatment with bosentan was also effective in reducing the mid-frequency oscillations in blood pressure associated with subarachnoid haemorrhage. 4. Our results indicate that subarachnoid haemorrhage is associated with an acute activation of the sympathetic nervous system. The degree of sympathoexcitation can be reversed by the use of either bosentan or SNP.

Animals↗

Subarachnoid hemorrhage induced sympathoexcitation arises due to changes in endothelin and/or nitric oxide activity.

OBJECTIVE: The demonstration of the effectiveness of endothelin antagonists and nitric oxide donors in managing vasospasm following subarachnoid hemorrhage is encouraging. Whether such drugs can modify the sympathoexcitation that accompanies this condition remains unknown and was the basis for the present report. METHODS: Subarachnoid hemorrhage was induced in conscious rats by injecting blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. We combined measurements of arterial plasma catecholamines with the spectral analysis of blood pressure variability in order to examine sympathetic nervous activation following subarachnoid hemorrhage. Experiments were performed in untreated animals and in rats following pretreatment with either bosentan or sodium nitroprusside. RESULTS: Indicative of a pronounced sympathoexcitation, the 0.2-0.6 Hz frequency components of blood pressure were markedly elevated following subarachnoid hemorrhage (2.5 +/- 0.5 vs. 8.9 +/- 2.6 mmHg2, P < 0.01). Parallel changes in plasma norepinephrine concentration were observed (1.0 +/- 0.2 vs. 2.4 +/- 0.4 nmol/l, P < 0.01). The subarachnoid injection of saline did not modify blood pressure variability or plasma norepinephrine concentrations. Pretreatment with either bosentan or sodium nitroprusside completely prevented the subarachnoid hemorrhage induced sympathoexcitation. CONCLUSIONS: Experimental subarachnoid hemorrhage is associated with a pronounced activation of the sympathetic nervous system. It would appear that this sympathoexcitation has its roots ensconced in either the release of endothelin or an impairment in nitric oxide mediated vasodilation.

Animals↗

Decreased resting metabolic rate in ballet dancers with menstrual irregularity.

We studied 21 ballet dancers aged 19.4 +/- 1.4 years, hypothesizing that undernutrition was a major factor in menstrual irregularity in this population. Menstrual history was determined by questionnaire. Eight dancers had always been regular (R). Thirteen subjects had a history of menstrual irregularity (HI). Of these, 2 were currently regularly menstruating, 3 had short cycles, 6 were oligomenorrheic, and 2 were amenorrheic. Subjects completed a weighed dietary record and an Eating Attitudes Test (EAT). The following physiological parameters were measured: body composition by anthropometry, resting metabolic rate (RMR) by open-circuit indirect calorimetry, and serum thyroid hormone concentrations by radioimmunoassay. R subjects had significantly higher RMR than HI subjects. Also, HI subjects had lower RMR than predicted by fat-free mass, compared to the R subjects. Neither reported energy intake nor serum thyroid hormone concentrations were different between R and HI subjects. EAT scores varied and were not different between groups. We concluded that in ballet dancers, low RMR is more strongly associated with menstrual irregularity than is current reported energy intake or serum thyroid hormone concentrations.

Adolescent↗

Duration of protective activity of cerebrospinal fluid shunt catheters impregnated with antimicrobial agents to prevent bacterial catheter-related infection.

This study determined the protective effect of antibacterial processing of cerebrospinal fluid (CSF) shunt catheters against infection with staphylococci, which is an important complication following CSF shunt placement for hydrocephalus. Also examined is the effect of a conditioning film such as that seen on the luminal surface of shunts used in posthemorrhagic hydrocephalus. Conventional preventative measures, including antimicrobial prophylaxis, confer a temporary or unproven benefit. The authors have therefore developed a process for impregnation of CSF shunts with rifampicin and clindamycin, and this has been shown previously to achieve the target duration of 28 days of protective activity in vitro. The present study demonstrates the limit of the period of protection and the efficacy of the processing against a wide range of staphylococci, particularly in the presence of a plasma protein conditioning film. Five strains of Staphylococcus aureus and 17 coagulase-negative staphylococci, all clinical isolates, were inoculated into the shunts at 2-week intervals until failure of antimicrobial protection occurred. The results showed that the process protected against all strains for between 42 and 56 days and that the conditioning film did not diminish the protection. Catheters processed by this method show promise of significant reductions in the incidence of CSF shunt infections.

Catheterization↗

Cloning and sequencing a novel metallothionein I isoform expressed in human reticulocytes.

Total RNA from human reticulocytes was purified and reverse-transcribed into cDNA using an oligo-dT primer. This cDNA was used as a template for a polymerase chain reaction (PCR) with a primer specific for the N-terminal sequence of mammalian metallothioneins (MT) and a universal primer. A single amplified fragment was thus generated which when cloned and sequenced revealed two distinct MT cDNAs of almost identical molecular weights. One sequence was identical to that previously reported for human MT II and the other encoded a novel MT I isoform (MT IR). The DNA sequence of MT 1R is distinct from those documented for other MT I isoforms.

Amino Acid Sequence↗

Estimating lumbar bone mineral density from routine radiographs of the lumbar spine.

To evaluate the information content of lateral lumbar films with respect to bone mineral content, we compared reading criteria with values obtained by quantitative computed tomography (CT) of L1 at baseline and after 5 years. The highest correlations with mineral content were found for the criteria "overall assessment of the vertebra", "vertebral bone density versus soft tissue", and "amount of trabeculations". These three reading criteria yielded higher correlations with CT scores in subjects with lower body mass index. Changes in mineral content over the 5-year period could not be read adequately, the average difference representing only a loss of about 10% in the study subjects. We conclude that a rough estimate of bone density can be obtained from lateral radiographs which, in the presence of eventual risk factors for osteoporosis, may serve as an additional indication to timely bone densitometry with methods which allow precise short-term follow-up measurements.

Aged↗

Perforin and granzyme A expression identifying cytolytic lymphocytes in rheumatoid arthritis.

Lymphocytes from the synovial fluid of patients with rheumatoid arthritis were examined for the expression of granzyme A and perforin. Previous studies have demonstrated that the expression of these proteins, which are implicated as mediators of cytotoxicity, can be used to identify putative cytolytic lymphocytes in vivo. Twenty-two synovial fluid samples were analyzed by in situ hybridization and immunohistochemistry. In six patients receiving low doses of immunosuppressant, a population of granzyme A- and perforin-expressing lymphocytes could be identified. In contrast, lymphocytes from patients who were receiving high doses of immunosuppressant did not contain any granzyme A- or perforin-expressing lymphocytes. Synovial fluid lymphocytes from patients with osteoarthritis did not express either marker. The expression of these markers demonstrates the presence of potentially functional cytolytic lymphocytes, expressing proteins required to mediate killing, in the synovial fluid of patients with rheumatoid arthritis. This suggests that cytolytic lymphocytes may be involved in the pathogenesis of rheumatoid arthritis.

Arthritis, Rheumatoid↗

Resistance circumvention strategies tested in clinical leukaemia specimens using the MTT colorimetric assay.

We have used a 4-day MTT colorimetric assay to study drug sensitivity of leucocytes from leukaemia patients and from normal donors. Response to Adriamycin, vincristine, aclacinomycin A, 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2), and melphalan has been determined, together with the effects of the resistance modifiers verapamil, cyclosporin A, and ethacrynic acid. Sensitivity of chronic lymphoblastic leukemia (CLL) lymphocytes to vincristine was much greater than that of normal lymphocytes or of leucocytes from myeloid leukaemia patients. These cells were also more sensitive to melphalan. Verapamil and cyclosporin A at clinically achievable doses of 1 microgram/ml produced significant chemosensitisation in normal and leukaemic specimens, but the sensitisation ratio was greater than or equal to 2 only in a minority of specimens, except in the case of sensitisation to vincristine seen in the majority of CLL specimens. Sensitisation was generally greater in the more chemo-resistant specimens. The ratio of sensitivities of cells to Adriamycin compared with aclacinomycin A was greatest in the more Adriamycin-resistant specimens which supports the idea that cross-resistance between these agents may not be great. This was not, however, true for the ratio of Adriamycin/MX2 sensitivity. Use of the MTT assay may allow the identification of patients who would benefit from treatment with resistance modifiers or with 'low-resistance' anthracyclines.

Antineoplastic Agents↗

Selective toxicity of ethacrynic acid towards lymphocytes of chronic lymphocytic leukemia in vitro.

We have used the MTT colorimetric assay to determine the sensitivity to ethacrynic acid of lymphocytes from normal donors and of peripheral blood cells from leukaemia patients. Whereas normal lymphocytes and cells from acute or chronic myeloid leukaemia showed similar sensitivities (median inhibitory dose, ID50 = 20-22 microM), lymphocytes from chronic lymphocytic leukaemia patients were much more sensitive (ID50 = 6 microM). This result was found irrespective of the assay duration.

Cell Survival↗