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D Martinez

Publications and source records attributed to D Martinez.

At least 37 records · Page 2Linked to original sources
PubMed2001

Properties of St I and St II, two isotoxins isolated from Stichodactyla helianthus: a comparison.

Sticholysins I and II are two highly hemolytic polypeptides purified from the Caribbean Sea anemone Stichodactyla helianthus. Their high sequence homology (93%) indicates that they correspond to isoforms of the same hemolysin. The spectroscopic measurements show a close similarity in the secondary structure content, conformation and stability of both toxins. Exposure of the toxins to high pHs (>11), a free radical source (AAPH), urea or temperature produce permanent changes in the toxin that lead to a significant loss of HA. It is significant to note that this loss of hemolytic activity occurs when other indicators, probably with the only exception of near-UV CD spectra, barely detect changes in the protein structure. This emphasizes the sensitivity of the protein function to changes in the macromolecule conformation. The most noticeable difference between both toxins is the considerably higher activity of St II, both measured in terms of erythrocyte internal K(+) exit or hemolysis; which is related to enthalpic factors. This difference is not due to an incomplete association of St I to the membrane. We consider then that the different pore forming capacity of both toxins in erythrocytes can be explained in terms of the difference in charge of the N-terminal fragment, than can considerably reduce the St I insertion rate in the membrane probably due to the negatively charged outer leaflet of the red blood cell, without a significant reduction of its capacity to bind to the cell membrane. This electrostatic effect, together with a slightly more relaxed structure in St II, could explain the higher pore forming capacity of St II in the red blood cell membrane.

Amidines↗
PubMed2001

Differential occupancy of somatodendritic and postsynaptic 5HT(1A) receptors by pindolol: a dose-occupancy study with [11C]WAY 100635 and positron emission tomography in humans.

Augmentation of selective serotonin reuptake inhibitors (SSRIs) therapy by the 5-HT(1A) receptor agent pindolol may reduce the delay between initiation of antidepressant treatment and clinical response. This hypothesis is based on the ability of pindolol to block 5-HT(1A) autoreceptors in the dorsal raphe nuclei (DRN) and to potentiate the increase in 5-HT transmission induced by SSRIs. However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT(1A) receptors during treatment with pindolol controlled release (CR) in nine healthy volunteers with Positron Emission Tomography and [11C]WAY 100635. Subjects were studied four times: at baseline, following one week of pindolol CR 7.5 mg/day (4 and 10 hrs post dose), and following one dose of pindolol CR 30 mg(4 hrs post dose). Occupancy of the DRN was 40 +/- 29% on scan 2, 38 +/- 26% on scan 3, and 64 +/- 15% on scan 4. The average occupancy in all other regions was significantly lower at each doses (18 +/- 5% on scan 2, 12 +/- 3% on scan 3, and 42 +/- 4% on scan 4). These results suggest that the blockade in the DRN reached in clinical studies (7.5 mg/day) might be too low and variable to consistently augment the therapeutic effect of SSRIs. However, these data indicate that pindolol exhibits in vivo selectivity for the DRN 5-HT(1A) autoreceptors. As DRN selectivity is desirable for potentiation of 5-HT function, this observation represents an important proof of concept for the development of 5-HT(1A) agents in this application.

Adult↗
PubMed2001

The variable number of tandem repeats polymorphism of the dopamine transporter gene is not associated with significant change in dopamine transporter phenotype in humans.

A 40 base polymorphism of a variable number of tandem repeats (VNTR) has been described in the 3' untranslated region of the gene (SLC6A3) coding for the dopamine transporter (DAT). Despite being located in the untranslated region of the gene, this polymorphism has been associated with clinical phenotypes associated with dysregulation of dopamine transmission, such as attention deficit hyperactivity disorder and cocaine-induced paranoia. To examine the neurochemical phenotype associated with this polymorphism, we compared amphetamine-induced dopamine release (measured as displacement of the radiotracer [123I]IBZM) and DAT expression (measured with [123I]beta-CIT) in the striatum with Single Photon Computerized Emission Tomography (SPECT). Our sample included 59 subjects, 31 healthy controls and 29 patients with schizophrenia. No significant association was found between VNTR polymorphism and amphetamine-induced dopamine release or DAT density in the total sample, nor when each diagnostic group was considered separately. Thus, we did not replicate the findings of two previous studies, which had suggested that the 9 repeat allele was associated with either an increased or decreased DAT expression, albeit in different patient populations.

Adult↗
PubMed2001

Magnetic resonance and cranial ultrasound characteristics of periventricular white matter abnormalities in newborn infants.

OBJECTIVE: To characterize the range of abnormalities within the periventricular white matter (PVWM) in a cohort of newborns using magnetic resonance (MR) brain imaging and to compare the focal MR abnormalities with the cranial ultrasound (CUS) findings. METHODS: Retrospective study of MR brain and CUS findings of infants born in the 18-month period 1998-1999. PVWM abnormalities were identified by MR and focal lesions were characterized by size, number and distribution using a grading scale. Correspondence with CUS findings was assessed. RESULTS: 175 MR examinations corresponding to n = 105 preterm infants, (median GA 28, range 23-36 weeks) and n = 25 term infants (median GA 39, range 37-42 weeks) were analysed for PVWM abnormalities. In the preterm group, MR demonstrated a normal PVWM in n = 76, focal areas of altered signal intensity (SI) in PVWM in n = 26 and venous infarction in n = 3. In the term group, MR demonstrated a normal PVWM in n = 15, focal areas of altered SI in PVWM in n = 4, oedematous PVWM in n = 2 and a middle cerebral artery infarction in n = 4. All infants with normal MR had normal CUS findings. A focal PVWM SI abnormality detectable on MR corresponded with an abnormality on CUS in only n = 10/30. CONCLUSIONS: MR appears considerably more sensitive than CUS in demonstrating the existence and extent of focal PVWM lesions in newborn infants. Satisfactory correspondence between the two imaging investigations is obtained only for cystic PVWM lesions.

Brain Ischemia↗
PubMed2001

Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D(2) receptor parameter measurements in ventral striatum.

Dopamine transmission in the ventral striatum (VST), a structure which includes the nucleus accumbens, ventral caudate, and ventral putamen, plays a critical role in the pathophysiology of psychotic states and in the reinforcing effects of virtually all drugs of abuse. The aim of this study was to assess the accuracy and precision of measurements of D(2) receptor availability in the VST obtained with positron emission tomography on the high-resolution ECAT EXACT HR+ scanner (Siemens Medical Systems, Knoxville, TN, U.S.A.). A method was developed for identification of the boundaries of the VST on coregistered high-resolution magnetic resonance imaging scans. Specific-to-nonspecific partition coefficient (V(3)") and binding potential (BP) of [(11)C]raclopride were measured twice in 10 subjects, using the bolus plus constant infusion method. [(11)C]Raclopride V(3)" in the VST (1.86 +/- 0.29) was significantly lower than in the dorsal caudate (DCA, 2.33 +/- 0.28) and dorsal putamen (DPU, 2.99 +/- 0.26), an observation consistent with postmortem studies. The reproducibility of V(3)" and BP were appropriate and similar in VST (V(3)" test-retest variability of 8.2% +/- 6.2%, intraclass correlation coefficient = 0.83), DCA (7.7% +/- 5.1%, 0.77), DPU (6.0% +/- 4.1%, 0.71), and striatum as a whole (6.3% +/- 4.1%, 0.78). Partial volume effects analysis revealed that activities in the VST were significantly contaminated by counts spilling over from the adjacent DCA and DPU: 70% +/- 5% of the specific binding measured in the VST originated from D(2) receptors located in the VST, whereas 12% +/- 3% and 18% +/- 3% were contributed by D(2) receptors in the DCA and DPU, respectively. Thus, accuracy of D(2) receptor measurement is improved by correction for partial voluming effects. The demonstration of an appropriate accuracy and precision of D(2) receptor measurement with [(11)C]raclopride in the VST is the first critical step toward the use of this ligand in the study of synaptic dopamine transmission at D(2) receptors in the VST using endogenous competition techniques.

Adult↗
PubMed2001

Acute nicotine poisoning associated with a traditional remedy for eczema.

We present a case of severe acute nicotine poisoning in an 8 year old boy with moderate eczema after topical application of a traditional remedy from a book published in Bangladesh. Symptoms consistent with nicotine poisoning developed within 30 minutes of application of the remedy. The child subsequently improved with supportive care and was discharged after five days with no neurological sequelae. Diagnosis of nicotine poisoning was not initially made due to difficulty in obtaining an accurate history via an interpreter from the parents who did not speak English. Samples taken 12 hours after application of the remedy showed a serum nicotine of 89 microgram/l, serum cotinine of 1430 microgram/l, urine nicotine of 1120 microgram/l, and a urine cotinine of 6960 microgram/l confirming acute nicotine poisoning.

Administration, Cutaneous↗
PubMed2001

Imaging neurochemical endophenotypes: promises and pitfalls.

A large number of polymorphisms in genes coding for neurotransmitter receptors and transporters have been associated with neuropsychiatric conditions, although few of these associations have been consistently replicated. These proteins are critical targets of psychoactive drugs and the clarification of the functional significance of these polymorphisms might offer important leads for drug development and therapeutic applications. Brain imaging techniques such as single photon emission computed tomography (SPECT) and positron emission tomography (PET) provide the means to monitor the expression and function of many of these proteins in the living human brain. This paper reviews brain imaging studies designed to evaluate the significance of polymorphisms in genes coding for important drug targets (e.g., the serotonin transporter [SERT], the dopamine transporter [DAT] and the dopamine D(2) receptor) in terms of expression or function. These studies illustrate the unique opportunities, as well as the pitfalls, generated by combining genetic analysis with brain imaging studies.

Brain Chemistry↗
PubMed2001

Popliteal artery injury associated with knee dislocations.

Since the Vietnam War experience we have known that there is a high association between knee dislocations and popliteal artery injuries. In an effort to improve the quality of care we asked whether every patient with a knee dislocation needs an arteriogram. This is a retrospective chart review of all injured patients who presented to Louisiana State University Health Science Center with knee dislocations between January 1, 1993 and March 31, 1998. Twenty-one patients met the study criteria. There were no deaths in this series. Twelve patients presented with normal palpable pulses. Nine of these 12 patients underwent an arteriogram. There was only one abnormal arteriogram (intimal defect) in this group. None of the patients who presented with normal pulses were operated on. There were no in-hospital complications from this nonoperative management. In the group of patients with either diminished pulses or no pulses arteriograms were performed on all patients. Fifty-five per cent of these arteriograms were abnormal, and one-third of these patients (two) were taken to the operating room for repair. In the group of patients who present with knee dislocations and normal peripheral vascular examination arteriograms are not helpful.

Adolescent↗
PubMed2001

Cerebral maturation in premature infants: quantitative assessment using MR imaging.

BACKGROUND AND PURPOSE: The assessment of whether brain development is at an appropriate level for age has become an integral part of clinical MR reporting, although few studies have quantitatively defined the developmental changes occurring in premature infants. We have developed a simple scoring system to assess four parameters of cerebral maturation--myelination, cortical folding, glial cell migration, and germinal matrix distribution--to determine the total maturation score (TMS). The aim of this study was to validate this scoring system in a large population of preterm infants across a range of gestational ages. METHODS: A retrospective analysis was conducted of MR images acquired over a 3-year period with an identical imaging protocol. Infants born more than 14 days before the imaging examination and those with a clinical or radiologic history suggestive of neuroabnormality were excluded from the study. The TMS was derived by consensus. Interobserver agreement was evaluated by using the Bland-Altman plot. RESULTS: Images from 134 infants (23-41 weeks' gestational age) were evaluated. The TMS was significantly related to the postmenstrual age of the infant, with the mean TMS for each age group increasing with advancing postmenstrual age. Interobserver agreement was found to be high (mean difference in score = 0.07, SD = 0.56). CONCLUSION: This scoring system provides a standardized method for assessing cerebral maturation in the premature infant. The TMS is easy to calculate from standard MR images, is reproducible, and can help detect changes occurring within a postnatal age of a few weeks.

Brain↗
PubMed2000

Increased anterior cingulate and caudate activity in bipolar mania.

BACKGROUND: Executive control of cognition, emotion, and behavior are disrupted in the manic state of bipolar disorder. Whereas frontal systems are implicated in such dysfunction, the localization of functional brain abnormalities in the manic state is not well understood. METHODS: We utilized a high-sensitivity H(2)(15)0 positron emission tomography technique to investigate regions of increased brain activity in mania, compared to euthymia, in bipolar disorder. RESULTS: The principal findings were manic state-related increased activity in left dorsal anterior cingulate, and left head of caudate. CONCLUSIONS: The findings suggest that the manic state of bipolar disorder may be associated with heightened activity in a frontal cortical-subcortical neural system that includes the anterior cingulate and caudate.

Adult↗
PubMed2000

Pindolol augmentation of antidepressant treatment: recent contributions from brain imaging studies.

Preclinical studies suggest that augmentation of selective serotonin (5-HT) reuptake inhibitors by the 5-HT(1A) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response, an effect largely mediated by blockade of 5-HT(1A) autoreceptors in the dorsal raphe nuclei. Although some controlled clinical trials suggest that pindolol might reduce latency to selective serotonin reuptake inhibitor response in acute depressive episodes, the effect is moderate and highly variable. Recent positron emission tomography studies investigating the occupancy of 5-HT(1A) receptors in humans by pindolol have shown that at the dose used most often in clinical trials the occupancy is low and variable, which might explain the inconsistent clinical results. Positron emission tomography studies also suggest that pindolol might be more potent at blocking 5-HT(1A) autoreceptors than at blocking postsynaptic receptors, a property that may be useful in this pharmacologic strategy. Thus, the positron emission tomography data support the potential of pindolol to augment the antidepressant response of selective serotonin reuptake inhibitors, but also imply that this potential has not been fully evaluated. Here we review the clinical trials, the positron emission tomography studies, and the possible mechanisms of pindolol augmentation. It is also suggested that positron emission tomography may be used to define therapeutic dosing early on in the process of clinical evaluation of new treatment strategies.

Animals↗
PubMed2000

Positron emission tomography study of pindolol occupancy of 5-HT(1A) receptors in humans: preliminary analyses.

Preclinical studies in rodents suggest that augmentation of serotonin reuptake inhibitors (SSRIs) therapy by the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response. This hypothesis is based on the ability of pindolol to potentiate the increase in serotonin (5-HT) transmission induced by SSRIs, an effect achieved by blockade of the 5-HT(1A) autoreceptors in the dorsal raphe nuclei (DRN). However, placebo-controlled clinical studies of pindolol augmentation of antidepressant therapy have reported inconsistent results. Here, we evaluated the occupancy of 5-HT(1A) receptors following treatment with controlled release pindolol in nine healthy volunteers with positron-emission tomography (PET). Each subject was studied four times: at baseline (scan 1), following 1 week of oral administration of pindolol CR (7.5 mg/day) at peak level, 4 h after the dose (scan 2), and at 10 h following the dose (scan 3), and following one dose of pindolol CR (30 mg) (at peak level, 4 h) (scan 4). Pindolol occupancy of 5-HT(1A) receptors was evaluated in the DRN and cortical regions as the decrease in binding potential (BP) of the radiolabelled selective 5-HT(1A) antagonist [carbonyl-(11)C]WAY-100635 or [carbonyl-(11)C] N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridyl)cyclohexa necarboxamide abbreviated as [(11)C]WAY-100635. Pindolol dose-dependently decreased [(11)C]WAY-100635 BP. Combining all the regions, occupancy was 20 +/- 8% at scan 2, 14 +/- 8% at scan 3, and 44 +/- 8% at scan 4. The results of this study suggest that at doses used in clinical studies of augmentation of the SSRI effect by pindolol (2.5 mg t.i.d.), the occupancy of 5-HT(1A) receptors is moderate and highly variable between subjects. This factor might explain the variable results obtained in clinical studies. On the other hand, at each dose tested, pindolol occupancy of 5-HT(1A) receptors was higher in the DRN compared to cortical regions, demonstrating a significant in vivo selectivity for DRN 5-HT(1A) autoreceptors relative to cortico-limbic postsynaptic receptors. This selectivity is necessary for the potentiation of 5-HT transmission, and this finding represents an important proof of concept in the development of 5-HT(1A) agents for this application. Early evaluation of new drugs with PET imaging will enable rapid screening of compounds based on DRN selectivity and more appropriate determination of doses for clinical trials.

Adult↗
PubMed2000

The subjective assessment of echogenic fetal bowel.

OBJECTIVES: To assess the subjective interpretation of the echogenicity of fetal bowel compared to bone from antenatal ultrasound images taken during examinations conducted between 17 and 22 weeks of gestation. METHODS: Eighty-seven women attending for their antenatal scan were selected in a random prospective manner over a 9-month period. Images of the fetal bowel were taken and evaluated by 10 sonographers, one consultant obstetrician and one consultant radiologist. Images from a further 13 fetuses, in which the subjective assessment of echogenic bowel was made, were also included. All ultrasound images were acquired on a dedicated ultrasound scanner, with a standard transducer, thermal paper printer and single operator using standardized equipment settings and reproducible image sections. Questionnaires with 100 sets of images of fetal bowel were distributed to the participants. Performance was assessed by means of percentage agreement and levels of chance corrected agreement (Kappa). RESULTS: The subjective assessment of fetal bowel echogenicity is very variable. Intra- and inter-observer variation discrepancies in the assessment of bowel echogenicity compared to bone were demonstrated between the sonographers. Good agreement was identified between the consultants with good to almost perfect intra-observer agreement. Overall, only moderate agreement was observed between the sonographers and the consultants. CONCLUSIONS: The lack of agreement demonstrated between sonographers when evaluating the echogenicity of fetal bowel should be addressed if this ultrasound marker is to be incorporated into routine fetal screening programs.

Adult↗
PubMed2000

Measurement of striatal and extrastriatal dopamine D1 receptor binding potential with [11C]NNC 112 in humans: validation and reproducibility.

To evaluate the postulated role of extrastriatal D1 receptors in human cognition and psychopathology requires an accurate and reliable method for quantification of these receptors in the living human brain. [11C]NNC 112 is a promising novel radiotracer for positron emission tomography imaging of the D1 receptor. The goal of this study was to develop and evaluate methods to derive D1 receptor parameters in striatal and extrastriatal regions of the human brain with [11C]NNC 112. Six healthy volunteers were studied twice. Two methods of analysis (kinetic and graphical) were applied to 12 regions (neocortical, limbic, and subcortical regions) to derive four outcome measures: total distribution volume, distribution volume ratio, binding potential (BP), and specific-to-nonspecific equilibrium partition coefficient (k3/k4). Both kinetic and graphic analyses provided BP and k3/k4 values in good agreement with the known distribution of D1 receptors (striatum > limbic regions = neocortical regions > thalamus). The identifiability of outcome measures derived by kinetic analysis was excellent. Time-stability analysis indicated that 90 minutes of data collection generated stable outcome measures. Derivation of BP and k3/k4 by kinetic analysis was highly reliable, with intraclass correlation coefficients (ICCs) of 0.90+/-0.06 (mean +/- SD of 12 regions) and 0.84+/-0.11, respectively. The reliability of these parameters derived by graphical analysis was lower, with ICCs of 0.72+/-0.17 and 0.58+/-0.21, respectively. Noise analysis revealed a noise-dependent bias in the graphical but not the kinetic analysis. In conclusion, kinetic analysis of [11C]NNC 112 uptake provides an appropriate method with which to derive D1 receptor parameters in regions with both high (striatal) and low (extrastriatal) D1 receptor density.

Adult↗
PubMed2000

Hyperechogenic fetal bowel: a prospective analysis of sixty consecutive cases.

A two year prospective analysis of all second trimester fetuses (16-22 weeks of gestation) with hyperechogenic bowel was undertaken. Hyperechogenic fetal bowel (sonographic echogenicity similar to or greater than that of surrounding fetal bone) was diagnosed using strict criteria. Outcome of affected fetuses was ascertained from hospital records, health care workers and autopsy reports, up to six months of age. Sixty consecutive fetuses were identified, of which 48 (80%) were liveborn. Six pregnancies were terminated, four ended with an intrauterine fetal death and two died at birth. The incidence of cystic fibrosis and aneuploidy were each 5%, and there were no cases of congenital infection. Intrauterine growth retardation was recorded in six fetuses (10%), four of whom died perinatally. Eighty-two percent of fetuses (28/34) with isolated hyperechogenic bowel had a normal outcome.

Abortion, Induced↗
PubMed2000

Quantitative comparison of intrabrain diffusion in adults and preterm and term neonates and infants.

OBJECTIVE: Quantitative measurements of mean water diffusivity (D(av)) were made in human neonates, infants, and adults to assess changes in brain tissue that occur with maturation. SUBJECTS AND METHODS: Values of D(av) were obtained by calculating the average of the diffusion measurements made with diffusion-sensitizing gradients placed along three orthogonal directions. The mean diffusivity, a rotationally invariant determination of apparent diffusion coefficient, was measured in five healthy prematurely born neonates and infants, in 10 healthy term neonates and infants, and in five adults. RESULTS: Values of D(av) were found to decrease with maturation in most parts of the brain. In prematurely born neonates and infants with a postmenstrual age (postgestastional age + postnatal age) under 36 weeks, the average value of D(av) in frontal white matter was 1.90 x 10(-3) mm2 sec(-1). The corresponding value was measured as 1.62 x 10(-3) mm2 sec(-1) in neonates and infants born at term with a postnatal age of no more than 43 days and 0.79 x 10(-3) mm2 sec(-1) in the adult brain. CONCLUSION: Values of D(av) are known to decrease in neonates and young infants in the period immediately after ischemic insult. This decrease and the associated increase in signal intensity seen on diffusion-weighted imaging have been used to monitor ischemic brain injury in neonates and infants. Therefore, the decrease in D(av) that occurs with maturation, which we report in this study, must be considered if quantitative diffusion measurements are used to assess ischemic neonatal brain injury.

Adult↗