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Biomedical subjects

J Fernandes

Publications and source records attributed to J Fernandes.

At least 37 records · Page 2Linked to original sources
PubMed1999

In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: prevention of osteoarthritis progression.

The goal of this study was to determine the efficacy of local IL-1Ra gene therapy by intra-articular plasmid injections on structural changes in the meniscectomy rabbit model of osteoarthritis. A partial meniscectomy of the right knee was performed on the rabbits through a medial parapatellar incision. The rabbits were then divided into four experimental groups. Group 1 received no treatment. Group 2 received three consecutive intra-articular injections at 24-hour intervals of 0.9% saline containing a lipid, gammaAP-DLRIE/DOPE, and a DNA plasmid, VR1012. Group 3 received three consecutive injections of saline containing 1000 microg of canine IL-1Ra plasmid and lipid. The injections were given starting 4 weeks post-surgery. Rabbits from Group 1 were killed 4 weeks post-surgery, and all other rabbits 8 weeks post-surgery. The severity of macroscopic and microscopic changes on cartilage on the medial and femoral condyles and tibial plateaus and synovium were graded separately. Specimens were also processed for immunohistochemical staining using a rabbit polyclonal antibody against canine IL-1Ra. The level of canine IL-1Ra in synovial fluid was determined using enzyme-linked immunosorbent assay. The presence of the DNA plasmid in the synovium was tested by polymerase chain reaction. A significant reduction in the width of osteophytes and size of macroscopic lesions (P < 0.04) was observed, and was dependent on the amount of IL-1Ra plasmid injected. A significant reduction was also noted in the severity of histologic cartilage lesions (P < 0.01) in the group that received the highest dosage (1000 microg) of IL-1Ra plasmid. IL-1Ra was detected in synovial fluid by enzyme-linked immunosorbent assay and by immunohistochemical staining in the synovium and cartilage of rabbits that received injections containing the IL-1Ra plasmid. Polymerase chain reaction analysis of synovial DNA revealed the presence of the cloned cDNA dog IL-1Ra up to 4 weeks after the first intra-articular injection. This study demonstrates that direct in vivo transfer of the IL-1Ra gene into osteoarthritis knee cells using intra-articular injections of a plasmid vector and lipids can significantly reduce the progression of experimental osteoarthritis. This avenue may therefore represent a promising future treatment for osteoarthritis.

Animals↗
PubMed1999

Generalizing from a controlled trial: the effects of patient preference versus randomization on the outcome of inpatient versus outpatient chronic pain management.

Patients accepting randomization in a randomized controlled trial (RCT) may not be representative of the clinical population from which they are drawn, calling into question the generalizability of study findings. Comparison of randomized and non-randomized inpatient and outpatient samples at baseline and in treatment outcomes up to one year was made to determine whether the findings of the RCT generalized to non-randomized patients in the same treatment program. One hundred and twenty one patients with intractable pain, randomized between inpatient, outpatient and waiting list control, were compared with 128 who elected for either inpatient or outpatient treatment. Treatment was a group-based multidisciplinary cognitive-behavioral treatment program aimed at enabling patients to return to more normal function despite persistent pain, delivered to mixed groups of randomized and elective patients, and outcome was measured by physical performance, pain impact on function, mood, and drug use. Agreement to randomization was a function of travelling distance from home to hospital. Non-randomized patients largely resembled their randomized counterparts before and after treatment. In order to indicate the clinical significance of results, analyses were conducted using numbers needed to treat (NNTs). NNTs estimate the number of patients required in the treatment condition for one of them to achieve the specified outcome who would not have achieved it in the comparison condition. Across a range of measures at one month follow-up, comparison of inpatients with outpatients gave NNTs between 2.3 and 7.5, and comparison of inpatients with waiting list controls gave NNTs between 2.3 and 3.6. At one year inpatients showed greater likelihood than outpatients of maintaining these treatment gains.

Adult↗
PubMed1999

Effect of nimesulide on glucocorticoid receptor activity in human synovial fibroblasts.

Fibroblasts from human synovial membranes were cultured with nimesulide, naproxen or dexamethasone. Nimesulide, but not naproxen, showed effects on the glucocorticoid system that may contribute importantly to its anti-inflammatory activity. Nimesulide at therapeutically relevant concentrations induced the intracellular phosphorylation and activation of glucocorticoid receptors, and activated their binding to the target genes. Naproxen or dexamethasone markedly reduced the number of glucocorticoid receptor binding sites, in contrast to nimesulide, which had no significant effect.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

[The persistence of the left vena cava superior and the absence of the right vena cava superior: the implications in the implantation of a definitive pacemaker].

Persistent left superior vena cava and associated absence of the right superior vena cava is exceedingly rare. The authors present a case, diagnosed when a DDD pacemaker system was being implanted, and point out its rarity, possibility of diagnosis by non invasive methods and technical implications in transvenous electrode implantation.

Aged↗
PubMed1998

Increased serum cholesterol in healthy human methane producers is confounded by age.

It has been theorized that colonic production and absorption of short-chain fatty acids (SCFA) is different in methane producers (MP) compared with nonproducers (MNP). Because colonic SCFA may influence systemic lipid metabolism, blood lipids may differ in MP and MNP. To compare serum lipids and SCFA in fasting MP and MNP, we measured breath gases, serum lipids and SCFA in 167 healthy subjects and excluded subjects with abnormal blood lipids. The 66 MP were significantly older than the 63 MNP (49.5 +/- 16.0 vs. 39.6 +/- 17.0 y, P = 0.0009), and breath methane concentrations were weakly correlated with age in MP (r = 0.268, P = 0.03). Mean serum cholesterol was significantly higher in MP compared with MNP, but the differences were not significant after adjusting for age. No significant differences were observed in serum SCFA between the two groups. This study has shown that breath methane increases with age, which may be due to age-related increases in transit time and carbohydrate malabsorption. These results provide no conclusive link between colonic events and serum lipids in MP because, with age, methane production increased as did serum cholesterol. More research is required before any definite conclusions can be drawn.

Adult↗
PubMed1998

Poverty, psychological disorder and disability in primary care attenders in Goa, India.

BACKGROUND: This study examined the association of common mental disorders in primary health clinic attenders with indicators of poverty and disability in Goa, India. METHOD: Adult attenders (n = 303) in two primary health clinics were recruited. RESULTS: There were 141 (46.5%) cases of common mental disorder. The following were associated with common mental disorder: female gender; inability to buy food due to lack of money; and being in debt. Cases scored significantly higher on all measures of disability. Primary health clinic staff recognised a third of the morbidity but used multiple oral drugs, injectable vitamins and benzodiazepines to treat common mental disorders. CONCLUSIONS: Poverty is closely associated with common mental disorder which in turn is associated with deprivation and despair. Primary mental health care priorities in low-income countries need to shift from psychotic disorders which often need specialist care to common mental disorders. Health policy and development agencies need to acknowledge the intimate association of female gender and poverty with these disorders.

Adolescent↗
PubMed1997

Brazilian multicentric study of psychiatric morbidity. Methodological features and prevalence estimates.

BACKGROUND: Psychiatric morbidity studies in developing countries have used diagnostic procedures of low reliability, without a clinical definition of caseness, producing descriptive data with limited application for mental health planning. METHOD: A two-stage cross-sectional design (with a sample size of 6476) was conducted to estimate the prevalence of DSM-III psychiatric diagnoses in three metropolitan areas of Brazil (Brasília, São Paulo and Porto Alegre). All subjects were screened for the presence of psychopathology with a 44-item instrument (the QMPA) and a subsample was selected for a psychiatric interview. RESULTS: Age-adjusted prevalence of cases potentially in need of care ranged from 19% (São Paulo) to 34% (Brasília and Porto Alegre). Anxiety disorders comprised the highest prevalences (up to 18%). Alcoholism yielded the most consistent prevalence levels, around 8% in all sites. Depression showed great variation between areas: from less than 3% (São Paulo and Brasília) to 10% (Porto Alegre). CONCLUSIONS: Overall prevalences were high in comparison with previous studies conducted in Brazil. A female excess of non-psychotic disorders (anxiety, phobias, somatisation and depression) and a male excess for alcoholism were consistently found.

Age Factors↗
PubMed1996

Muscle organizers in Drosophila: the role of persistent larval fibers in adult flight muscle development.

In many organisms muscle formation depends on specialized cells that prefigure the pattern of the musculature and serve as templates for myoblast organization and fusion. These include muscle pioneers in insects and muscle organizing cells in leech. In Drosophila, muscle founder cells have been proposed to play a similar role in organizing larval muscle development during embryogenesis. During metamorphosis in Drosophila, following histolysis of most of the larval musculature, there is a second round of myogenesis that gives rise to the adult muscles. It is not known whether muscle founder cells organize the development of these muscles. However, in the thorax specific larval muscle fibers do not histolyze at the onset of metamorphosis, but instead serve as templates for the formation of a subset of adult muscles, the dorsal longitudinal flight muscles (DLMs). Because these persistent larval muscle fibers appear to be functioning in many respects like muscle founder cells, we investigated whether they were necessary for DLM development by using a microbeam laser to ablate them singly and in combination. We found that, in the absence of the larval muscle fibers, DLMs nonetheless develop. Our results show that the persistent larval muscle fibers are not required to initiate myoblast fusion, to determine DLM identity, to locate the DLMs in the thorax, or to specify the total DLM fiber volume. However, they are required to regulate the number of DLM fibers generated. Thus, while the persistent larval muscle fibers are not obligatory for DLM fiber formation and differentiation, they are necessary to ensure the development of the correct number of fibers.

Actins↗
PubMed1996

X-linked liver glycogenosis type II (XLG II) is caused by mutations in PHKA2, the gene encoding the liver alpha subunit of phosphorylase kinase.

X-linked liver glycogenosis type II (XLG II) is a recently described X-linked liver glycogen storage disease, mainly characterized by enlarged liver and growth retardation. These clinical symptoms are very similar to those of XLG I. In contrast to XLG I patients, however, XLG II patients do not show an in vitro enzymatic deficiency of phosphorylase kinase (PHK). Recently, mutations were identified in the gene encoding the liver alpha subunit of PHK (PHKA2) in XLG I patients. We have now studied the PHKA2 gene of four unrelated XLG II patients and identified four different mutations in the open reading frame, including a deletion of three nucleotides, an insertion of six nucleotides and two missense mutations. These results indicate that XLG II is due to mutations in PHKA2. In contrast to XLG I, XLG II is caused by mutations that lead to minor structural abnormalities in the primary structure of the liver alpha subunit of PHK. These mutations are found in a conserved RXX(X)T motif, resembling known phosphorylation sites that might be involved in the regulation of PHK. These findings might explain why the in vitro PHK enzymatic activity is not deficient in XLG II, whereas it is in XLG I.

Amino Acid Sequence↗
PubMed1996

Serum acetate:propionate ratio is related to serum cholesterol in men but not women.

Acetic and propionic acids, produced by colonic fermentation of unabsorbed carbohydrates, may influence systemic lipid metabolism. To determine whether the ratio of the concentrations of acetate to propionate in peripheral serum of fasting humans was related to serum cholesterol, we studied 62 men [age 45 +/- 17 y (mean +/- SD), range 19-74 y; body mass index 25.0 +/- 2.8 kg/m2] and 69 women [43 +/- 18 y, (range, 18-77 y); body mass index 23.0 +/- 3.1 kg/m2] with normal serum lipid concentrations. The concentrations of serum acetate, propionate and butyrate (means +/- SD) were similar in men (98 +/- 33, 3.8 +/- 1.5 and 2.3 +/- 1.5 micromol/L, respectively) and women (92 +/- 38, 3.9 +/- 1.9 and 2.3 +/- 1.6 micromol/L). There were significant positive relationships between the serum acetate:propionate ratio and total cholesterol (r = 0.466, P = 0.0002) and LDL cholesterol (r = 0.384, P = 0.0023) in men, but in women the relationships were not significant (R = 0.174, P = 0.15 and r = 0.135, P = 0.27, respectively). The relationships in men remained significant after adjustment for age and body mass index. These data support the hypothesis that, at least in men, colonic short-chain fatty acids influence systemic lipid metabolism. The relationships among the factors influencing colonic short-chain fatty acid production, the enterohepatic circulation of endogenous estrogens, dietary phytoestrogens and blood lipids in women, however, need further clarification.

Acetates↗
PubMed1996

[Clinical and neuropathological aspects of Wernicke-Korsakoff syndrome].

Alcohol abuse is one of most serious problems in public health and the Wernicke-Korsakoff syndrome one of the gravest consequences of alcoholism. The pathology is often undiagnosed in its less evident presentations, therefore an accurate diagnostic approach is a critical step in planning treatment. Besides new pharmacological proposals, treatment is based on the restoration of thiamine, although this is insufficient to prevent the psychological decline of a great number of patients. The cognitive impact of the pathology is derived from the interaction of alcoholic neurotoxicity, thiamine deficiency and personal susceptibility. In this article the history, epidemiology, clinical and neuropathological features of the Wernicke-Korsakoff syndrome, as well as some aspects of its treatment and prognosis, are described.

Alcohol Amnestic Disorder↗
PubMed1995

Nutrition assessment and counseling practices: attitudes and interests of primary care physicians.

This survey examined the nutrition-related practices and office services of primary care physicians, and their preferred nutrition topics and educational methods. Respondents were 960 physicians from across the United States who were members of the Society of General Internal Medicine. A four-page mailed questionnaire with 21 items queried background information, nutrition-related clinical practices and office support systems, perceived self-efficacy for nutrition assessment and counseling, and nutrition-related educational preferences. Two-thirds of the respondents said they personally provided nutrition counseling. They reported moderate self-efficacy for nutrition counseling and lower confidence for using specific relapse prevention strategies. Greatest interest in further education related to chronic disease prevention and nutrition for the elderly, provided in convenient formats for practicing physicians.

Attitude of Health Personnel↗
PubMed1995

Neuromuscular development in Drosophila: insights from embryos and pupae.

During embryogenesis, Drosophila melanogaster generates a set of muscles and motoneurons that are restructured during pupal metamorphosis to give rise to an adult motor system. The study of neuromuscular development in embryos and pupae has recently revealed important insights into the cellular and molecular mechanisms controlling both muscle patterning and the establishment of synaptic connections.

Animals↗
PubMed1995

Positive methane-producing status associated with increased serum cholesterol in subjects with impaired glucose tolerance.

OBJECTIVE: To determine if those who produce methane (i.e., have presence of methane in breath) have higher serum cholesterol than those who do not produce methane in subjects with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS: We measured breath gases and fasting serum total and high-density lipoprotein (HDL) cholesterol and triglyceride (TG) levels in 21 subjects with IGT. RESULTS: The 11 methane-producers were well matched to the 10 non-methane-producers for age, sex, and body mass index. Methane-producers had higher fasting serum total (6.5 +/- 0.3 vs. 5.5 +/- 0.2 mmol/l; P < 0.02) and low-density lipoprotein (4.3 +/- 0.3 vs. 3.4 +/- 0.2 mmol/l; P < 0.05) cholesterol concentrations with no difference in TG or HDL levels. CONCLUSIONS: The results suggest that in subjects with IGT, positive methane-producing status may be associated with increased serum cholesterol levels.

Blood Glucose↗
PubMed1995

24-hour blood pressure profile early after renal transplantation.

Renal transplant patients are often found to have high blood pressure. We studied 12 cyclosporine-treated patients 8-10 days after kidney transplantation by 24-hour ambulatory blood pressure monitoring, and once again at 35-40 days after kidney transplantation. The patients were found to have high mean blood pressure values at 8-10 days after transplantation, with a significant (p < 0.05) decrease at 35-40 days after transplantation (154.2 +/- 4.9/94.4 +/- 2.8 and 142.2 +/- 4.0/88.6 +/- 2.7 mmHg, respectively). A significant (p < 0.05) decrease in blood pressure values was also noted in the second series of measurements, when compared to the first series, in the day-time systolic and in the night-time systolic and diastolic blood pressure values, but not in the day-time diastolic blood pressure values. An abnormal day/night pattern of blood pressure ("non-dipper") was found in these patients in both occasions, with a difference between average blood pressure values during day- and night-time of 1.3/3.0 (systolic/diastolic) and 5.7/7.6 mm Hg at 8-10 and 35-40 days after transplantation, respectively. This tendency towards attenuation of the "non-dipper" pattern occurred in association with the decrease in body weight and of the dose of immunosuppressive drugs. As hemodynamic factors may play a role in both the short and the long-term function and viability of kidney transplant grafts, the high blood pressure and the "non-dipper" pattern of blood pressure found early after kidney transplantation may require a special therapeutic approach.

Adult↗