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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 649 records · Page 36Linked to original sources

Decreased beta 2-adrenoceptor density and decreased isoproterenol induced c-AMP increase in juvenile type I diabetes mellitus: an additional cause of severe hypoglycaemia in childhood diabetes?

Little is known about the receptor and post receptor mechanisms of sympathoadrenal signal transmission in type I diabetes mellitus. Therefore, we examined the maximum binding of granulocyte beta 2-adrenoceptors and the in vitro c-AMP accumulation in lymphocytes of 24 children and adolescents with diabetes mellitus and 14 similarly aged healthy subjects. The number of high affinity beta 2-adrenoceptors on granulocytes correlated significantly with unstimulated (r = 0.6, P < 0.004) and with isoproterenol stimulated c-AMP values in lymphocytes (r = 0.68, P < 0.0007) showing the proportional changes of beta 2-adrenoceptors and c-AMP in two different cells. The number of beta 2-adrenoceptors on granulocytes was significantly reduced in diabetic as compared to healthy children (median 1397, range 599-3405 vs. 2205, 825-3200 beta 2-adrenoceptors per granulocyte, P = 0.014). Moreover, the percentage in vitro stimulation of c-AMP by isoproterenol in lymphocytes was significantly reduced in diabetic children as compared to healthy individuals (120%, 39%-278% vs. 225%, 66%-500%, P = 0.012). These results indicate a decreased sympathoadrenergic signal transmission in peripheral blood cells as a model for the liver probably contributing to severe hypoglycaemia in diabetic children.

Adolescent↗

Effects of acute treadmill exercise and delayed access to food on food selection in rats.

Total energy intake and macronutrient self-selection were examined in rats following forced exercise (2 h treadmill, 15 m/min) or after a similar period of food deprivation without exercise. Acute exercise was realized at the end of the daytime. Return to the home cage for food access after exercise or after the same period of fasting was delayed for 0, 30, and 90 min. It has been shown that rats decreased body weight after all exercise situations. Food intake after deprivation was decreased in the first 3 h but was not modified over 24 h. The 24-h energy intake after exercise was identically reduced in the three situations. Carbohydrate and protein intakes were significantly reduced just after exercise. Protein decrease persisted all through the night and, to a lesser extent, during the following nycthemere. Fat decrease appeared later and was significant in the last part of the night. Increasing the delay to food access after exercise did not modify the total energy intake, but it significantly reduced carbohydrate intake. Those results show that exercise has a longer influence on food intake and, specifically, on macronutrient selection, than just food deprivation. Various hypotheses regarding central (cerebral neurotransmitters) and peripheral factors could be evoked in order to explain these modifications in the self-selected diet after an acute exercise.

Animals↗

Time sampling observation procedure for studying drug effects: interaction between d-amphetamine and selective dopamine receptor antagonists in the rat.

A rapid time sampling observation procedure combined with two forms of automatic activity assessment is described. The methods are illustrated by examination of the behavioral effects of d-amphetamine, administered to rats either alone or in combination with antagonists selective for D1 or D2 dopamine (DA) receptors. Low doses of d-amphetamine (0.5-4.0 mg/kg) increased photocell counts, rearing, ambulation, and various forms of sniffing. Similar effects were observed in the first 30 min following administration of 8.0 mg/kg d-amphetamine. However, animals exhibited licking, intense sniffing down, and repetitive head and limb movements in the following 30 min; minimal ambulation, rearing, and sniffing up were observed. The "traditional" total photocell count measure did not differentiate between these time-dependent changes in locomotion. On the other hand, latch counts-where subjects had to move between the beams to register a count-adequately demonstrated this change in locomotion. The selective D1 receptor antagonist SCH23390 and selective D2 antagonist raclopride dose dependently inhibited the behavioral changes produced by 1.5 mg/kg d-amphetamine. Higher doses of SCH23390, but not raclopride, produced a behavioral pattern indistinguishable from that observed in control sessions. Both DA antagonists equipotently blocked the intense sniffing down and repetitive head/body movements produced by 8.0 mg/kg d-amphetamine. A narrow intermediate range of doses of SCH23390 reduced the incidences of these behaviors and produced levels of locomotion and sniffing straight that were significantly higher than those observed in control session. This form of behavioral activation was not observed with raclopride. Therefore, this observation procedure revealed subtle differences between the inhibitory effects of SCH23390 and raclopride on d-amphetamine-induced behavioral changes.

Animals↗

Reconstitution of a voltage-activated calcium conducting cation channel from brain microsomes.

Many aspects of nerve cell function are controlled by cytosolic Ca2+. Intracellular organelles can sequester the cation and release it in a regulated fashion through specific ion channels including ryanodine-sensitive and inositol trisphosphate (InsP3)-activated intraneuronal Ca2+ channels. We have now used the planar bilayer technique to characterize a distinct high-conductance Ca2+ channel from brain microsomal membranes, which was not found in synaptic plasma membranes. Channel conductance in 50 mM CaCl2 is approximately 100 pS. The channel is permeable to Ca2+, Ba2+, K+ and Cs+, but it is not ideally cation-selective (PCs+:PCl- = 4:1). It opens in bursts in a steeply voltage-dependent manner, with maximal activation around zero mV. Channel activity is unaffected by caffeine or ryanodine (both of which modify the gating of ryanodine-sensitive Ca2+ channels), or by InsP3 or heparin (which act on InsP3-sensitive Ca2+ channels). omega-conotoxin GVIA, ruthenium red, amiloride and procaine all block the channel, the latter two by interacting with one or more negatively-charged binding sites in the voltage gradient within the channel pore. We suggest the channel may have a role in intracellular Ca(2+)-signalling, possibly linked to the operation of intracellular Ca2+ stores.

Amiloride↗

T cell responses to myelin basic protein in experimental autoimmune encephalomyelitis-resistant BALB/c mice.

In strains of mice that are susceptible to experimental autoimmune encephalomyelitis (EAE), cloned CD4+ T cells reactive with autologous myelin basic protein (MBP) have been shown to cause disease when transferred to naive syngeneic recipients. Recent reports indicate that under particular experimental conditions, 'resistant' strains of mice can also develop EAE, although cloned cells have not been isolated and characterized. An analysis of the characteristics of a panel of MBP-specific T cells and the antigen presenting capability of CNS-derived cells obtained from the resistant strain BALB/c is presented here. The data demonstrate that immunization of EAE-resistant BALB/c mice results in the activation of a heterogeneous group of T cells reactive with autologous MBP. Both peripheral antigen presenting cells, as well as microglia isolated from brains of BALB/c mice, are capable of stimulating these cloned MBP-specific T cells to proliferate. When optimally activated in vitro and then injected in vivo into syngeneic BALB/c recipients, three clones studied induced severe cachexia, resulting in loss of up to 35% of body weight before death. Two of the clones also induced clinical and histological EAE, while the third induced only occasional histological evidence of disease. Differences in epitope recognition, T cell receptor usage, cytokine profiles or regulatory mechanisms of self tolerance, may play important roles in preventing potentially destructive autoimmune reactions by these T cells capable of recognizing autologous myelin in the central nervous system.

Animals↗

[Anesthesia in the management of pyloric stenosis. Evaluation of the combination of propofol-halogenated anesthetics].

This study was aimed at evaluating haemodynamic changes during an anaesthetic sequence for full stomach, using propofol as induction agent and volatile anaesthetics for maintenance of anaesthesia in infants scheduled for surgical cure of hypertrophic pyloric stenosis. After correction of preoperative blood electrolyte and metabolic disturbances with appropriate i.v. hydrating solutions, anaesthesia was induced with propofol and suxamethonium. Infants were divided in two groups according to the volatile anaesthetic agent used for maintenance of anaesthesia after tracheal intubation: halothane (n = 16) or isoflurane (n = 15). The two groups were identical regarding weight (4.28 +/- 0.6 vs 4.14 +/- 0.76 kg), age (1.6 +/- 0.9 vs 1.5 +/- 0.6 months), preinduction heart rate (155 +/- 22 vs 151 +/- 22 b.min-1) and systolic-diastolic arterial pressure (96 +/- 18/58 +/- 12 vs 105 +/- 16/67 +/- 15 mmHg). Propofol and suxamethonium doses were identical, 3.9 +/- 1 mg.kg-1 and 1.3 +/- 0.6 mg.kg-1 respectively in halothane group, vs 4.3 +/- 0.8 mg.kg-1 and 1.3 +/- 0.4 mg.kg-1 in isoflurane group. Heart rate did not change after induction of anaesthesia, while arterial blood pressure decreased significantly (p < 0.001). However, blood pressure remained within the normal range for age throughout the procedure. Mean duration of surgery was shorter in halothane group (64 +/- 16 vs 79 +/- 17 min, p < 0.05), however time-interval from the end of surgery to tracheal extubation (12 +/- 6 vs 15 +/- 8 min) was short and identical in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

[Dopexamine: a new dopaminergic agonist].

Dopexamine hydrochloride is a new synthetic catecholamine for intravenous use in low cardiac output states with co-existing raised systemic or pulmonary vascular resistance. Dopamine has been commonly used since several years in these situations. The drawbacks of dopamine include a vasoconstrictive effect with high infusion rates, and a marked tendency for ventricular ectopy due to the potent beta-1 adrenergic stimulation. Dopexamine hydrochloride has interesting vasodilator properties, with marked intrinsic agonist activity at beta-2 adrenoreceptors and a lesser agonist activity at dopaminergic receptors (DA1 and DA2). Its mild inotropic activity arises primarily from baroreceptor reflex stimulation with a possible contribution from direct stimulation of myocardial beta 2-adrenoreceptors. Dopexamine hydrochloride is responsible for an inhibition of neuronal re-uptake of catecholamines (uptake-1), producing an indirect stimulation of cardiac beta 1-receptors. This catecholamine has no effect at alpha 1 and alpha 2-adrenoreceptors, and only very weak and clinically insignificant beta 1-adrenoreceptor agonist activity. Dopexamine hydrochloride improves cardiac performance by a marked vasodilation and a mild inotropic activity. The specific activity at dopaminergic receptors increases cerebral, myocardial, splanchnic and renal blood flows. These haemodynamic effects are associated with an increase in diuresis and natriuresis. These benefits are achieved without side effects such as an increased myocardial oxygen consumption, although induced tachycardia may be responsible for chest pain/anginae pain in patients with ischaemic heart disease. In clinical practice, dopexamine hydrochloride is easy to use; the short plasma half-life (6 minutes in healthy volunteers and 11 minutes in patients with low cardiac output) allows a rapid return to pretreatment status at discontinuation of the infusion. Preliminary studies have shown that dopexamine hydrochloride can produce beneficial effects in patients with acute heart failure or with compromised left ventricular function following cardiac surgery. The drug has also been assessed in patients with septic shock, most often in association with dopamine or norepinephrine. In these patients, dopexamine produces a dose-related increase in cardiac index, stroke volume, heart rate and a decrease in systemic vascular resistance. Its use in this indication must be cautious, particularly in patients with hypotension or decreased venous return. Comparative therapeutic trials are clearly required to establish the efficiency and tolerance of dopexamine hydrochloride in comparison with dopamine and dobutamine, before its place in therapy can fully be defined.

Adrenergic Agonists↗

[Computer-assisted intravenous anesthesia: value, method and use].

Total intravenous anaesthesia (TIVA) is becoming increasingly popular among anaesthetists. It has several advantages, namely each component of the anaesthetic protocol can be independently controlled, and the operating room remains unpolluted with nitrous oxide or volatile anaesthetic agents. TIVA aims to maintain a constant blood concentration of each anaesthetic agent. This means that infusion rates need to be repeatedly altered. A computer calculates theoretical blood concentrations of agent according to a pharmacokinetic model, and drives an infusion device. Only a few programmes have been developed by research teams. No commercial device is available as yet. However, there are several syringe pumps and volumetric pumps which are accurate enough for use in TIVA and which may be controlled by computer. Clinical studies have shown the benefits of TIVA: greater haemodynamic stability, decreased drug consumption, more rapid recovery, and a lesser need for postoperative ventilatory support. The most appropriate agents are propofol and etomidate as hypnotics, alfentanil and sufentanil for opioids, vecuronium and atracurium as muscle relaxants. Etomidate is not recommended for prolonged infusions, because of the risk of adrenocortical suppression. TIVA seems to be attractive for neurosurgery, thoracic surgery, day case surgery, endoscopic procedures, and anaesthesia in remote locations. Unfortunately, it is an expensive technique. Moreover, there is considerable interpatient variability of the drug concentration required for a same clinical effect. Two methods are proposed to decrease this variability: population pharmacokinetic models and Bayesian forecasting. Closed loop systems are still research tools. It is concluded that computer-driven anaesthesia is the equivalent to the vaporizer for volatile agents. However, further clinical studies are needed to determine whether the advantages of this technique outweigh its disadvantages.

Analgesics, Opioid↗

Targeted delivery of a heme oxygenase inhibitor with a lyophilized liposomal tin mesoporphyrin formulation.

Tin mesoporphyrin (SnMP) is a competitive inhibitor of heme oxygenase being examined clinically for the treatment of hyperbilirubinemia. Since liposomes have been shown to target SnMP to the spleen and increase its efficacy (S. A. Landaw, G. S. Drummond, and A. Kappas, Pediatrics 84, 1091-1096, 1989), we began investigating the feasibility of the preparation and scaleup of a liposomal SnMP formulation for clinical use. SnMP liposomes were prepared by high-pressure homogenization of a suspension of SnMP and egg phosphatidylcholine (1:20, w/w) in lactose-phosphate buffer, resulting in SnMP liposomes that were less than 200 nm in diameter and had encapsulation efficiencies of up to 90% at pH 5. The SnMP liposomes could be sterile filtered and lyophilized in a 1-day cycle with retention of the encapsulation efficiency and particle size. Following injection into rats, the distribution of liposomal SnMP to spleen at 2 and 6 hr after dosing was 5-20 times higher than for aqueous SnMP. Lyophilized SnMP liposomes were also more effective than aqueous SnMP in decreasing bilirubin production in bile-cannulated rats. The results suggest the potential for producing a safe, sterile, and effective lyophilized formulation of SnMP liposomes for targeting of heme oxygenase inhibitors to the spleen.

Animals↗

DIP: a member of the MIP family of membrane proteins that is expressed in mature seeds and dark-grown seedlings of Antirrhinum majus.

DiP, a gene from Antirrhinum majus, which encodes a protein with striking homology to other integral membrane proteins, was cloned. The gene was specifically expressed in mature seeds and during seedling germination, particularly in cotyledons of seedlings grown in the dark. The deduced product, called DiP, for dark intrinsic protein, shows strong homology with the MIP family of channel transporters which include; the bovine major intrinsic protein (MIP), the Escherichia coli glycerol facilitator (GIpF), the peribacteroid nodulin-26 (Nod26), and the tonoplast protein from kidney bean (TIP). DiP is most similar to other plant members of this family, and in particular to the tobacco protein TobRB7 which is expressed specifically in roots. However, the expression pattern of diP suggests that its product is functionally more similar to the tonoplast intrinsic protein from kidney bean since it is most highly expressed in the cotyledons of germinating seedlings, before the cells undergo expansion growth and become photosynthetic.

Amino Acid Sequence↗

Expression of myb-related genes in the moss, Physcomitrella patens.

Three cDNA clones encoding proteins containing a myb-related DNA binding domain have been isolated from a cDNA library prepared from protonemal tissue of the moss, Physcomitrella patens. The three cDNA clones between them encode two different classes of myb-like proteins, termed Pp1 and Pp2, that, outside of the myb domain, show no regions of significant homology. Acidic domains, capable of forming alpha-helical structures, are present in the carboxy-termini of the derived amino acid sequences from Pp1 and Pp2cDNAs suggesting that, like other myb genes, these proteins probably function as transcriptional activators. In contrast to other plants, where extensive myb-related gene families are present in the genome, a relatively small family is present in P. patens. Analyses of transcript levels during development of P. patens showed that maximum levels of transcription of the two genes occurred in young wild-type protonemal tissue that correlated with the time of maximum mitotic index. A decline in the expression of both genes occurs with increasing age of the wild-type tissue. Aberrant levels of expression of the two genes were observed in developmental mutants of P. patens which, as well as carrying specific morphological mutations, have greatly retarded protonemal growth rates. Transformation of wild-type P. patens with antisense constructs derived from Pp1 and Pp2 cDNA clones led to a dramatically reduced frequency of transformants when the expression of the reporter gene within the constructs was selected. Taken together, the data strongly suggest that expression of Pp1 and Pp2 is essential for cell growth during normal gametophytic development of P. patens.

Amino Acid Sequence↗

Effect of bolus doses of midazolam on intracranial pressure and cerebral perfusion pressure in patients with severe head injury.

We have studied the effects of bolus doses of midazolam 0.15 mg kg-1 i.v. on intracranial pressure (ICP), mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) in 12 patients with severe head injury (Glasgow Coma Scale score < or = 6). The study was performed in patients aged 17-44 yr who were sedated (phenoperidine 20 micrograms kg-1 h-1) and paralysed (vecuronium 2 mg h-1). Midazolam reduced MAP from 89.0 mmHg to 75.0 mmHg (P < 0.0001), while CPP decreased from 71.0 mmHg to 55.8 mmHg (P < 0.0001). During the study, CPP decreased to less than 50 mmHg in four patients. Midazolam induced small, non-significant changes in ICP. However, when control ICP was less than 18 mmHg (n = 7 patients), an increase in ICP was observed. The remaining five patients (control ICP > or = 18 mmHg) exhibited a slight decrease in ICP. These findings suggest that bolus administration of midazolam should be performed with great caution in patients with severe head injury, especially when ICP is less than 18 mmHg.

Adolescent↗

Post-ejection wall thickening as a marker of successful short term hibernation.

OBJECTIVE: Short term hibernating myocardium is characterised by a decrease in contractile function in proportion to the reduced blood flow, the recovery of creatine phosphate despite ongoing ischaemia, a recruitable inotropic reserve, and the absence of necrosis. During acute myocardial ischaemia systolic wall thickening decreases and post-ejection wall thickening develops. The extent of post-ejection thickening during severe ischaemia correlates with the recovery of contractile function during reperfusion. Whether the extent of post-ejection wall thickening can also distinguish short term hibernating myocardium from more severely ischaemic, infarcting myocardium and thus predict the amount of viable tissue was tested in 13 anaesthetised pigs. METHODS: The left anterior descending coronary artery (LAD) was cannulated and perfused at constant flow. After control measurements of regional myocardial blood flow (with radiolabelled microspheres) and wall thickening (sonomicrometry), coronary inflow was reduced to produce a reduction in regional contractile function by 60-100%. After 85 minutes of ischaemia, dobutamine was infused into the LAD for five minutes to determine the extent of inotropic reserve. Transmural biopsies were taken to measure regional myocardial creatine phosphate content and infarct size was determined after two hours of reperfusion by staining with triphenyl tetrazolium chloride. RESULTS: The extent of post-ejection wall thickening after 85-90 minutes of ischaemia correlated with the myocardial creatine phosphate content (r = 0.812, n = 11, p < 0.01) and the extent of the dobutamine recruitable inotropic reserve (r = 0.783, n = 7, p < 0.05). A negative correlation existed between the extent of post-ejection wall thickening and % infarct size (r = -0.699, n = 10, p < 0.05 for the transmural piece of tissue containing the ultrasonic crystals; r = -0.743, n = 10, p < 0.05 for the area of the left ventricle at risk). Finally, post-ejection wall thickening after 85-90 minutes of ischaemia correlated with the recovery of contractile function at 30 minutes reperfusion (r = 0.657, n = 10, p < 0.05). CONCLUSION: The extent of post-ejection wall thickening may indicate the amount of viable tissue after 85-90 minutes of low flow ischaemia. The greater the post-ejection wall thickening, the more myocardium is successfully hibernating.

Animals↗

A non-comparative study of the efficacy and tolerance of cefepime in combination with amikacin in the treatment of severe infections in patients in intensive care.

Patients in intensive care units (ICUs) are at increased risk of developing nosocomial infections. This is of special concern in the immunocompromised patient, particularly with regard to multiresistant pathogens. We evaluated the effectiveness of cefepime 2 g bd in combination with amikacin 7.5 mg/kg bd for the treatment of severe bacterial infection in 118 ICU patients, including 113 patients with nosocomial lower respiratory tract infections (LRTI) (mean age, 51 years). Ninety-six per cent (108/113) of the LRTI patients required respiratory assistance and 12% (14/113) had associated septicaemia/bacteraemia. Eighty-four per cent (95/113) had clinical signs of sepsis and 35% (39/113) had features of septic shock. The mean Simplified Acute Physiologic Score (SAPS) was 12 at inclusion. Seventy-nine patients with LRTI were clinically and bacteriologically evaluable. The causative pathogens were representative of those usually isolated in ICUs: Staphylococcus aureus (19%); Pseudomonas aeruginosa (14%); and Klebsiella, Enterobacter and Serratia spp. (17%). The clinical cure rate was 86% (68/79) while the pathogen eradication rate was 91% (107/117). Of the patients with associated septicaemia/bacteraemia, 89% (8/9) of the pathogens were eliminated. Cefepime-amikacin combination therapy was well tolerated; two patients discontinued treatment due to rashes. Combination therapy with cefepime 2 g bd and amikacin 7.5 mg/kg bd appears safe and effective for the treatment of nosocomial pneumonia in patients hospitalized in ICUs. Further comparative controlled studies are justified.

Adolescent↗

Sufentanil increases intracranial pressure in patients with head trauma.

BACKGROUND: Sufentanil is an intravenous opioid often used as a component of anesthesia during neurosurgical procedures. However, the effects of sufentanil on intracranial pressure in patients with diminished intracranial compliance are not well established, and remain controversial. METHODS: Ten patients with head trauma, in each of whom the trachea was intubated, were studied for the effects of sufentanil on intracranial pressure (ICP) and on cerebral perfusion pressure (CPP). In all patients, ICP monitoring was instituted before the study. Sedation was obtained using a propofol infusion, and paralysis was achieved with vecuronium. After obtaining control of ICP (between 15 and 25 mmHg) hemodynamic values and blood gas tensions (PaCO2 between 30 and 35 mmHg), the level of sedation was deepened with an intravenous injection of sufentanil (1 microgram/kg over 6 min), followed by an infusion of 0.005 microgram.kg-1min-1. Mean arterial pressure (MAP), ICP (fiberoptic intracranial pressure monitor), and end-tidal CO2 were continuously measured and recorded at 1-min intervals throughout the 30-min study period. RESULTS: Sufentanil injection was associated with a statistically significant increase in ICP of 9 +/- 7 mmHg (+ 53%), which peaked at 5 min. Then ICP gradually decreased and returned to baseline after 15 min. This was accompanied by a significant decrease in MAP (24% decrease) and, thus, CPP (38% decrease). After 5 min, MAP and CPP gradually increased, but remained significantly decreased throughout the study. CONCLUSIONS: The results of the current study indicate that caution should be exercised in the administration of sufentanil bolus to patients with abnormal intracranial elastance, particularly if ICP is significantly increased.

Adolescent↗

Transposon-induced inversion in Antirrhinum modifies nivea gene expression to give a novel flower color pattern under the control of cycloidearadialis.

The nivea (niv) gene of Antirrhinum majus encodes chalcone synthase, an enzyme involved in synthesis of anthocyanin pigments. The nivrec:98 allele contains a single copy of the transposon Tam3 inserted at the niv locus. A large chromosomal rearrangement derived from this mutant has been shown to be flanked by two copies of Tam3. In this study, we compared sequences involved in this rearrangement with their progenitor sequences and concluded that the rearrangement is an inversion resulting from an aberrant transposition occurring shortly after replication of Tam3 that left both copies of Tam3 active after the rearrangement. Excision of Tam3 from its position adjacent to the niv coding region resulted in a novel distribution of anthocyanin pigment in the flower tube, caused by the interaction of the new sequences with the remnant of the niv promoter. The new sequences upstream of niv serve both to enhance niv transcription and to redirect the pattern of gene expression, placing niv under the control of the gene cycloidearadialis, which determines the morphogenetic polarity of the flower.

Alleles↗

Subtypes of early age onset alcoholism.

Forty-three adolescents qualifying for a DSM-III-R diagnosis of alcohol abuse/dependence were classified according to the internalizing-externalizing behavior dimension. Two clusters were identified. The majority of subjects clustered into a group characterized by behavioral dyscontrol and hypophoria (history of suicide attempts) (cluster 2), whereas the other group was primarily featured by negative affect (cluster 1). Cluster 2 subjects demonstrated more severe alcohol and drug use-related problems, behavioral disturbances, and general psychopathology; lower prevalence of depressive disorders; and less severe anxiety disorders. These results, implicating two variants of adolescent alcohol abuse/dependence, suggest the need to tailor differential treatments to adolescents with alcohol abuse/dependence based on personality characteristics and clinical presentation.

Adolescent↗

Strain identification of Mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology.

DNA fingerprinting of Mycobacterium tuberculosis has been shown to be a powerful epidemiologic tool. We propose a standardized technique which exploits variability in both the number and genomic position of IS6110 to generate strain-specific patterns. General use of this technique will permit comparison of results between different laboratories. Such comparisons will facilitate investigations into the international transmission of tuberculosis and may identify specific strains with unique properties such as high infectivity, virulence, or drug resistance.

Base Sequence↗