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Biomedical subjects

J Diaz

Publications and source records attributed to J Diaz.

At least 37 records · Page 2Linked to original sources

Evidence for joint genetic control of insulin sensitivity and systolic blood pressure in hispanic families with a hypertensive proband.

BACKGROUND: The clustering of hypertension, insulin resistance, and obesity remains unexplained. We tested for genetic and nongenetic influences on the association among these traits in Hispanic families with hypertension. METHODS AND RESULTS: Blood pressure and body mass index (BMI) were measured in 331 members of 73 Hispanic families in which an index case (proband) had hypertension. Insulin sensitivity (S(I)) was measured by euglycemic clamp in 287 probands and their spouses (parents' generation) or their adult offspring. Correlation analysis examined relationships among traits within and between generations. Path analysis estimated genetic and nongenetic contributions to variability in systolic blood pressure (SBP), S(I), and the correlation between them. In the offspring, there was a significant correlation between individuals for each trait, as well as significant correlations within and between individuals for all possible pairs of traits. Between generations, SBP, S(I), and BMI in parents correlated with the same traits in their offspring; BMI in parents correlated with S(I) and SBP in offspring; and S(I) in parents correlated with SBP in offspring. Path analysis estimated that among offspring, genetic effects unrelated to BMI accounted for 60.8% of the variation in SBP, 36.8% of the variation in S(I), and 31.5% of the correlation between SBP and S(I) after adjustment for age and sex. Heritable effects related to BMI accounted for an additional 14.0% of variation in SBP, 26.8% of variation in S(I), and 56.3% of variation in their correlation. CONCLUSIONS: Clustering of hypertension and insulin resistance in Hispanic Americans is accounted for in part by heritable factors both associated with and independent of BMI.

Adolescent↗

Assessing the acceptability, service delivery requirements, and use-effectiveness of the diaphragm in Colombia, Philippines, and Turkey.

The diaphragm is not available in many countries, despite the recommendations of numerous authors that it has important advantages as a woman-controlled method that offers some protection against sexually transmitted diseases, and one that is safe and free of side effects. An interagency team collaborated to introduce the diaphragm in Colombia, the Philippines, and Turkey, using the same protocol to assess the acceptability, service delivery requirements and use-effectiveness of the method. Eighteen public and private sector service delivery sites were involved and a total of 550 women were enrolled in the study. Provider training aimed to improve the quality of care with which all methods were delivered and included counseling about sexuality and reproductive health risks. The cumulative 12-month pregnancy rate of 10.1 (SE 1.7) per 100 woman-years is on the low end of previous studies of the diaphragm, and the 12-month continuation rate (57.2 [SE 2.4] per 100) compares favorably with that for oral contraceptives and the intrauterine device. Focus group discussions conducted with clients and providers indicated that the method was an important alternative for some women, particularly those who had experienced health problems with other methods or were unable to negotiate condom use with their partners. Provider biases diminished as they observed the strategic niche that the diaphragm filled for their clients. While providing the diaphragm requires training and good client-provider interaction, the requirements are consistent with those called for in the Programme of Action of the International Conference on Population and Development (ICPD, 1994). With proper attention to quality of care, the diaphragm can be successfully offered in resource-poor settings.

Adolescent↗

The effect of chronic cocaine administration on hemodynamic stability and neurohumoral mediators during isoflurane anesthesia and shock in rats.

BACKGROUND: The aim of this investigation was to determine whether chronic cocaine administration altered endogenous vasoconstrictor secretion in response to hypotension from isoflurane anesthesia and blood loss in rats. METHODS: Rats received continuous intravenous infusions of saline (n=11), or cocaine 6 mg kg(-1) d(-1) (n=13) or 18 mg kg(-1) d(-1) (n=12) for 13 days. On day 14, rats were anesthetized with intraperitoneal ketamine and xylazine and a femoral artery catheter and a tracheotomy performed to allow lung ventilation (PaCO2, 30-40 mmHg). After baseline parameters were noted, isoflurane was introduced to end-tidal concentrations of 0.7% for 10 min (1/2 MAC), 1.4% for 10 min (MAC) and again 0.7% for 10 min (1/2 MAC-2) when 5 ml of blood was withdrawn (SHOCK). Blood samples were drawn to assess arterial blood gas indices at various time points as well as plasma epinephrine, angiotensin II and vasopressin at MAC, 1/2 MAC-2 and SHOCK. RESULTS: Rats administered cocaine had higher oxygen extraction, required higher minute ventilation and had lower PaO2 values than rats administered saline despite similar body temperatures and hematocrits. Isoflurane administration resulted in significant dose dependent but similar blood pressure decreases in all study groups. Plasma epinephrine, angiotensin II and vasopressin concentrations were not different in saline or cocaine treated animals at any time point. CONCLUSION: These data suggest that chronic cocaine treatment in rats does not impair endogenous vasoconstrictor secretion nor alter the heart rate and blood pressure response to isoflurane and blood loss.

Anesthesia↗

Localized amyloid deposition in trigger finger.

Trigger finger is due to degeneration and thickening of the proximal portion (A1 pulley) of the flexor tendon sheath, which causes constriction of the flexor tendon. This study reports the presence of localized amyloid deposition in the tendon sheath of 11 of 47 cases (23%) of idiopathic primary trigger finger. Amyloid deposits were only found in patients aged over 46 years old and were present around cells and at sites of mucinous and fibrinoid degeneration which contained highly sulphated glycosaminoglycans. The pathogenic significance of these deposits is uncertain but their small size and presence only in middle-aged and elderly adults suggests that they represent a form of age-associated amyloid deposition.

Adult↗

Autologous Schwann cells drive regeneration through a 6-cm autogenous venous nerve conduit.

Peripheral nerve regeneration is a complex series of events, involving bi-directional interactions between regenerating axons and Schwann cells. These authors have demonstrated in their laboratory that nerves will regenerate through a 3-cm autogenous venous nerve conduit (AVNC) in an animal model and, with Dr. David Chiu, a similar distance in the human. They have shown that the upper limit of nerve regeneration in an empty AVNC was 3 cm, with no evidence of nerve growth at the 6-cm mark (no-growth model). Most recently, they have demonstrated rapid growth at 1 month in a 3-cm AVNC filled with Schwann cells, compared to poor-to-no-regrowth at 1 month in controls. While, in theory, Schwann-cell-derived growth factor should be sufficient to supplant the requirement for Schwann cells, in practice, therapies with growth factors have failed in clinical trials, with some resulting in severe morbidity and mortality for the subjects. The present study showed excellent nerve regeneration through a 6-cm AVNC with the addition of autologous Schwann cells, breaking the barrier in the previous no-growth model. In the first stage, autologous Schwann cells were harvested from the contralateral peroneal nerve of the rabbit and expanded in culture. The Schwann cells were purified to >99 percent homogeneity using differential adhesion and antibody-compliment-mediated cytolysis. In the second stage, 6 cm of gluteal vein were harvested and used as a conduit that was filled with either Matrigel or a slurry of Matrigel and 10(6)/ml autologous Schwann cells (n=6 control and 6 experimental animals). The non-donor side peroneal was exposed and transected, leaving a gap of 6 cm. The filled gluteal vein graft (AVNC) was then anastomosed to the proximal and distal peroneal nerve stumps, and the rabbits were allowed to recover. Four months postoperatively, the animals were subjected to transcardiac perfusion with EM grade fixative. The grafts were analyzed at the light and electronmicroscopic levels, and showed excellent growth of nerve at 6 cm, the distal end of the AVNC.

Animals↗

Prospective comparison of admission computed tomographic scan and plain films of the upper cervical spine in trauma patients with altered mental status.

OBJECTIVE: The accurate evaluation of patients with multiple injuries is logistically complex and time sensitive, and must be cost-effective. We hypothesize that computed tomographic (CT) scan of the upper cervical spine (occiput to C3 [Co-C3]) would add little to the initial evaluation of patients with multiple injuries who have altered mental status. METHODS: The study consisted of a prospective, unblinded, consecutive series. Patients met entry criteria if they had sustained a blunt mechanism of injury and had an altered mental status requiring CT scan of two or more body systems. All patients received CT scan of Co-C3 with 2-mm cuts and subsequent reconstructions as well as five-view cervical spine plain films. Cervical spine injury was defined as any radiographically identified fracture or subluxation that required treatment. Patients were excluded if they died or were cleared clinically before plain film series were obtained. CT scan of Co-C3 and cervical spine films were reviewed by two different attending radiologists. RESULTS: Of the 2,690 consecutive admissions between December 1998 and November 1999, 1,356 patients met entry criteria. Seventy patients (5.2%) had a total of 95 injuries to the upper cervical spine. CT scan of Co-C3 identified 67 of 70 patients and plain films identified 38 of 70 patients with injuries to the upper cervical spine. Twelve patients (17%) had neurologic deficits attributable to Co-C3 injuries. Three patients had false-negative CT scans of Co-C3, and one patient was quadriplegic. There were 32 patients with false-negative plain films, including four patients with motor deficits (one with quadriplegia). Use of the guidelines developed by the Eastern Association for the Surgery of Trauma identified all patients with upper cervical spine injuries; to date, no patient in the study group was readmitted or has initiated a lawsuit for missed injury of the upper cervical spine. CONCLUSION: CT scan of Co-C3 was superior to plain films in the early identification of upper cervical spine injury. Plain films failed to identify 45% of upper cervical spine injuries; four of these missed injuries resulted in motor deficits. Our study supports the practice guidelines developed by the Eastern Association for the Surgery of Trauma for clearance of the upper cervical spine in patients with altered mental status, as all patients with injuries were identified using these guidelines.

Adolescent↗

Wheat germ supplement reduces cyst and trophozoite passage in people with giardiasis.

The protozoan parasite Giardia lamblia is a major cause of waterborne enteric disease worldwide. Lectins are proteins that bind to carbohydrate (sugar) moieties. Potential targets for lectins are found on the surface of most single-celled organisms. Modest concentrations of wheat germ agglutinin (WGA) have been shown to inhibit G. lamblia excystation and trophozoite growth in vitro and can reduce cyst passage in mice infected with the closely related protozoan parasite, G. muris. Commercial preparations of wheat germ (WG) contain 13-53 microg of WGA per gram. We performed a double-masked, placebo-controlled study of dietary supplementation with WG in 63 subjects with giardiasis in Montreal and Lima (25 asymptomatic patients passing cysts; 38 patients with symptoms). Asymptomatic subjects received WG (2 g, 3 times a day) or placebo (cornstarch, 2 g, 3 times a day) for 10 days, followed by metronidazole (250 mg 3 times a day) for 7 days. Symptomatic subjects received metronidazole (250 mg 3 times a day) plus either WG or placebo for 7 days. Stool specimens were collected every day (Montreal) or every other day (Lima) for 10 days and on Day 35 for microscopic examination and coproantigen determination. Subjects kept a diary of symptoms for 10 days after recruitment. In asymptomatic subjects, both cyst passage and coproantigen levels were reduced by approximately 50% in those taking WG compared with the placebo group (P < 0.01 and P = 0.06, respectively). In symptomatic subjects, cyst passage and coproantigen levels fell precipitously in response to metronidazole therapy, and there were no clinically important differences between those receiving supplemental WG or placebo. However, symptoms appear to have resolved more rapidly in the subjects taking WG in addition to metronidazole. The WG supplement was well tolerated in both symptomatic and asymptomatic subjects. These data suggest that components of WG, possibly WGA, either alone or in combination with antiprotozoal agents, can influence the course of human giardiasis.

Adult↗

Late-onset mitochondrial DNA depletion: DNA copy number, multiple deletions, and compensation.

Through a report of 4 late-onset cases with mitochondrial DNA (mtDNA) depletion, we address the specificity of the clinical entities associated with a very low residual amount of mtDNA. Three of the patients met the diagnostic criteria of Kearns Sayre syndrome, which has never been associated with mtDNA depletion. The fourth patient had an isolated skeletal myopathy. Deleted mtDNA molecules were found by long-range polymerase chain reaction (PCR) only in the Kearns Sayre syndromes, which strengthens the clinical differences between the two types of patients. All patients had extremely low residual amounts of mtDNA as shown by Southern blot analysis. Using an original method based on competitive PCR, we were able to measure the number of mtDNA copies per diploid genome. These results demonstrated the severity of the depletion in the patients by comparison not only to normal controls but also to patients with mtDNA disorders. Despite the severity of the depletion, in situ hybridization using two mtDNA transcripts revealed a normal steady-state level of transcription. Such compensation provides clues to the striking contrast between the severity of mtDNA depletion and the late onset and slowly progressive disease.

Age of Onset↗

Dopamine D3 receptors expressed by all mesencephalic dopamine neurons.

A polyclonal antibody was generated using synthetic peptides designed in a specific sequence of the rat D(3) receptor (D(3)R). Using transfected cells expressing recombinant D(3)R, but not D(2) receptor, this antibody labeled 45-80 kDa species in Western blot analysis, immunoprecipitated a soluble fraction of [(125)I]iodosulpride binding, and generated immunofluorescence, mainly in the cytoplasmic perinuclear region of the cells. In rat brain, the distribution of immunoreactivity matched that of D(3)R binding, revealed using [(125)I]R(+)trans-7-hydroxy-2-[N-propyl-N-(3'-iodo-2'-propenyl)amino] tetralin ([(125)I]7-trans-OH-PIPAT), with dense signals in the islands of Calleja and mammillary bodies, and moderate to low signals in the shell of nucleus accumbens (AccSh), frontoparietal cortex, substantia nigra (SN), ventral tegmental area (VTA) and lobules 9 and 10 of the cerebellum. Very low or no signals could be detected in other rat brain regions, including dorsal striatum, or in D(3)R-deficient mouse brain. Labeling of perikarya of AccSh and SN/VTA appeared with a characteristic punctuate distribution, mostly at the plasma membrane where it was not associated with synaptic boutons, as revealed by synaptophysin immunoreactivity. In SN/VTA, D(3)R immunoreactivity was found on afferent terminals, arising from AccSh, in which destruction of intrinsic neurons by kainate infusions produced a loss of D(3)R binding in both AccSh and SN/VTA. D(3)R-immunoreactivity was also found in all tyrosine hydroxylase (TH)-positive neurons observed in SN, VTA and A8 retrorubral fields, where it could represent D(3) autoreceptors controlling dopamine neuron activities, in agreement with the elevated dopamine extracellular levels in projection areas of these neurons found in D(3)R-deficient mice.

Animals↗

Coherent bremsstrahlung in the alpha + p system at 50 MeV/nucleon

Photons originating from coherent bremsstrahlung have been measured over a large dynamic range for the reaction of 200 MeV alpha particles with protons. At low photon energies the bremsstrahlung spectrum exhibits the classical behavior with an approximate 1/E(gamma) shape. At higher photon energies there is a pronounced contribution from capture into the unbound ground state and first excited state of 5Li. These results allow one, for the first time, to test theoretical models for a consistent description of bremsstrahlung and radiative capture in a complex system. Calculations predict both features qualitatively but fail to account for their relative importance.

Journal Article↗

Acceptability and performance of the levonorgestrel-releasing intrauterine system (Mirena) in Campinas, Brazil.

The objectives of this study were to evaluate the acceptability of the LNG-IUS Mirena(R), when offered as an additional option in a free choice context, and to evaluate the possibility of using this method in women with increased bleeding wanting an IUD and in copper IUD users requesting removal of the device for bleeding problems. A total of 256 women chose Mirena and were accepted into the study during the enrollment period. This represents 23.3% of all new acceptors of contraceptive methods in the clinic during the same period. Discontinuations were fairly evenly distributed among expulsion, bleeding changes, pain, and personal reasons. Bleeding changes were decreased bleeding, oligomenorrhea or amenorrhea. Comparing the performance in the group of women who chose the LNG-IUS as a first option with those having heavy bleeding, the only difference found was a higher expulsion rate in the group with bleeding problems. No pregnancies occurred and continuation rate was slightly over 75% in the total sample and in both groups. The characteristics of the LNG-IUS (Mirena) allow predicting that this method can effectively contribute to the increase in contraceptive options when introduced to family planning programs in Brazil.

Brazil↗

Possible implications of the dopamine D(3) receptor in schizophrenia and in antipsychotic drug actions.

The D(3) receptor may represent an important target for antipsychotic drugs which all bind with high affinity and do not induce upon repeated administration either tolerance or receptor upregulation. The D(3) receptor is localized in brain areas, namely the nucleus accumbens and cerebral cortex, implicated in neural circuits believed to display defective functioning in schizophrenia. Overexpression of the D(3) receptor, which accounts for the behavioral sensitization to levodopa in a rodent model of Parkinson's disease, might also be responsible for the sensitization to dopamine agonists observed in schizophrenia. The appearance of the D(3) receptor during brain development, early in proliferating neuroepithelia and later in neurons from limbic areas, suggests further studies to assess its participation in the neurodevelopmental disorders of schizophrenia. Finally, meta-analysis of approximately 30 studies comprising over 2500 patients indicate that a polymorphism in the coding sequence of the D(3) receptor is associated with a small but significant enhancement of vulnerability to the disease.

Animals↗

Selective increase of dopamine D3 receptor gene expression as a common effect of chronic antidepressant treatments.

The mesolimbic dopaminergic system is a neuroanatomical key structure for reward and motivation upon which previous studies indicated that antidepressant drugs exert a stimulatory influence, via still unknown neurobiological mechanisms. Here we examined the effects of chronic administration of antidepressants of several classes (amitriptyline, desipramine, imipramine, fluoxetine and tranylcypromine) and repeated electroconvulsive shock treatments (ECT) on dopamine D3 receptor expression in the shell of the nucleus accumbens, a major projection area of the mesolimbic dopaminergic system. Short-term drug treatments had variable effects on D3 receptor mRNA expression. In contrast, treatments for 21 days (with all drugs except fluoxetine) significantly increased D3 receptor mRNA expression in the shell of nucleus accumbens; D3 receptor binding was also significantly increased by amitriptyline or fluoxetine after a 42-day treatment. ECT for 10 days increased D3 receptor mRNA and binding in the shell of nucleus accumbens. D1 receptor and D2 receptor mRNAs were increased by imipramine and amitriptyline, but not by the other treatments. The time-course of altered D3 receptor expression, in line with the delayed clinical efficiency of antidepressant treatment, and the fact that various antidepressant drugs and ECT treatments eventually produced the same effects, suggest that increased expression of the D3 receptor in the shell of nucleus accumbens is a common neurobiological mechanism of antidepressant treatments, resulting in enhanced responsiveness to the mesolimbic dopaminergic system.

Amitriptyline↗