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Biomedical subjects

J Gonzales

Publications and source records attributed to J Gonzales.

At least 37 records · Page 2Linked to original sources

Magnesium transport induced ex vivo by a pharmacological dose of insulin is impaired in non-insulin-dependent diabetes mellitus.

Diabetes mellitus may be associated with magnesium depletion, which in turn may contribute to metabolic complications of diabetes including vascular disease and osteoporosis. Intracellular depletion is thought to be due to osmotically induced renal magnesium loss; however, impaired ability of insulin to increase intracellular magnesium during insulin deficiency or insulin resistance could also play a role. Magnesium deficiency per se has also been reported to result in insulin resistance. In order to determine if magnesium transport is altered in non-insulin-dependent diabetes mellitus (NIDDM), we measured intracellular Mg(2+) in circulating lymphocytes obtained from nine normal subjects and seven patients with NIDDM. Ionized intracellular Mg(2+) was determined by fluorescent spectroscopy using Mg-fura-2. A 30 min incubation of insulin with lymphocytes obtained from normal subjects resulted in an increase in Mg(2+) of 8.6 +/- 3.6 percent (mean +/- SEM) at 100 mu U/ml which reached a plateau at approximately 250 mu U/ml (11.0 +/- 1.7 percent). The mean lymphocyte Mg(2+) in the patients (0.198 +/- 0.011 mM) was not significantly lower than normal (0.218 +/- 0.017). Insulin (500 mU/ml) added acutely during the fluorescence reading caused a rapid 31 +/- 3.9 percent rise in intracellular Mg(2+) in the normal subjects, which was significantly greater than the 18 +/- 1.6 percent rise observed in the NIDDM subjects (P < 0.01). The effect of magnesium deficiency was also studied in 3 normal subjects experimentally Mg deficient for 3 weeks. The mean lymphocyte Mg(2+) fell from 0.198 +/- 0.009 mM pre-diet to 0.153 +/- 0.006 mM post-diet. and the insulin-induced rise in Mg(2+) fell from 27.2 percent pre-magnesium depletion to 12.7 percent post-magnesium depletion. These data suggest that insulin resistance and magnesium depletion may result in a vicious cycle of worsening insulin resistance and decrease in intracellular Mg(2+) which may limit the role of magnesium in vital cellular processes.

Adult↗

Glucocorticoid and cAMP increase fatty acid synthetase mRNA in human fetal lung explants.

During late fetal development, synthesis of surfactant phospholipid requires a large supply of fatty acid precursor. Fatty acid synthetase is a regulatory enzyme for de novo fatty acid synthesis in lung as well as other lipogenic tissues. In this study, we report hormonal induction of FAS mRNA in human fetal lung explants (16-23 week gestation) cultured up to 7 days in Waymouth's medium (no serum) supplemented with dexamethasone (Dex, 10 nM) or agents that increase cAMP (8-Br-cAMP, 0.1 mM; isobutylmethylxanthine, 0.1 mM; forskolin, 0.01 mM; PGE1, 0.01 mM). Exposure of explants to Dex or cAMP agents increased FAS mRNA content by 6 h and maximal stimulation occurred at 72 h for Dex (approx. 3-fold increase) and 24 h for cAMP (approx. 2-fold increase). In the presence of both Dex and cAMP there was a synergistic increase in FAS mRNA content at all times (approx. 11-fold increase at 72 h). Induction of FAS mRNA was specific for steroids with glucocorticoid activity, reversible on removal of hormone, and was half-maximal at 2-3 nM Dex consistent with receptor mediation. Actinomycin D blocked induction by Dex but not by cAMP suggesting a transcriptional effect by glucocorticoid but not by cAMP. T3, which increases phosphatidylcholine synthesis, did not induce FAS mRNA. The findings indicate that both glucocorticoid and cAMP increase FAS gene expression consistent with an important role for FAS in regulating the supply of fatty acid for surfactant phospholipid synthesis.

Cyclic AMP↗

A comparison of reflection and transmission ultrasonic techniques for measurement of cancellous bone elasticity.

A reflection ultrasonic technique, which offers several advantages over transmission ultrasonic techniques, has been described for elastic property measurement of bone. Ultrasonic velocities from specimens of cancellous bone were compared using a reflection ultrasound technique and the more traditional transmission ultrasonic technique. The two techniques were found to yield velocities which were reasonably well correlated (r2 = 0.74). However, a statistical difference was found between the line of identity and the regression between transmission and reflection velocities (due to an offset in the intercept). In spite of differences in intercept between velocities measured by the two techniques, significant correlation was found between the two methods, suggesting that the reflection technique can measure wave velocities meaningful to bone elasticity.

Animals↗

How many embryos should be transferred in in vitro fertilization? A prospective randomized study.

OBJECTIVE: To maintain the rate of pregnancy, while suppressing high rank multiple pregnancies by limiting the number of fresh embryos transferred after IVF, in a population selected for potential success. DESIGN: A prospective, randomized study. SETTING: Département de Gynécologie Obstétrique, Centre Hospitalo Universitaire, Paris VI, France. PATIENTS: There were two groups of 28 couples. Women were < or = 35 years of age, with > or = 70% cleavage rate and at least four morphologically regular embryos. INTERVENTION: On the day of ET, either four fresh embryos were transferred (group 1) or two fresh embryos were transferred and two were frozen for later transfer (group 2). MAIN OUTCOME: Pregnancy rate and multiple pregnancy. RESULTS: The pregnancy rate was the same in the two groups with one-third of the high rank pregnancies in group 1 and no pregnancies in group 2. CONCLUSION: Only two fresh embryos need to be transferred in this selected population.

Adult↗

[Streptomycin was born fifty years ago].

The discovery of streptomycin by Waksman in 1943 marked the beginning of true chemotherapy in all forms of tuberculosis. The possibility to reverse the lethal course of tuberculous meningitis in children constituted a hope verged on enthusiasm. But after encouraged results, skepticism arose: cases of resistance of BK to streptomycin were reported and other observations noted severe sequelae when administration had begun too late. Successes due to drug were often weakened by side effects like cochlear and vestibular deficiencies. All those reservations came in addition to the great price of streptomycin, difficulties of its supply and doubts upon long term prognosis for cared patients. Finally streptomycin won. In the following years, new drugs more and more efficient against tuberculosis were used, instead of streptomycin which some enthusiastic people had nevertheless thought only able to eradicate the "white plague". Today, morbidity and mortality from tuberculosis remain dramatic, partly accelerated by the AIDS epidemic and increased by high frequency of cases with BK resistance to all drugs ... except streptomycin. What a long story, full of hopes, for this antibiotic which, during the first clinical trials, saved from certain death ... a child became the author of the present paper!

Drug Therapy↗

Neonatal screening for maple syrup urine disease by an enzyme-mediated colorimetric method.

A microplate-based, enzyme-mediated, colorimetric method using L-leucine dehydrogenase (EC 1.4.1.9) has been developed for the determination of the combined branched-chain amino acids in plasma and blood-spot specimens. The test exhibits acceptable precision and fits into a new concept according to which the different parameters of neonatal screening programs for metabolic disorders, such as phenylalanine (phenylketonuria), galactose/galactose-1-phosphate (galactosemia) and branched-chain amino acids (maple syrup urine disease) can be measured in the same blood-spot eluate by use of different specific NAD(H)-dependent enzymes.

Amino Acid Oxidoreductases↗

Clinical, serologic, and immunogenetic studies in childhood-onset systemic lupus erythematosus.

OBJECTIVE: To determine the frequency of systemic lupus erythematosus (SLE)-associated clinical manifestations, autoantibodies, and HLA class II alleles in a large cohort of patients with childhood-onset SLE. METHODS: Eighty children with SLE onset before age 18 (27 before age 11) were studied for the frequency of renal, neuropsychiatric, and hematologic complications as well as for anti-native DNA, Ro, La, Sm, and U1 RNP autoantibodies. HLA-DR, DQ, and DP alleles were determined by oligotyping. The results were compared with findings in 213 adults with SLE onset at or after age 18 years. RESULTS: Renal involvement was more frequent in those with childhood-onset SLE, especially those with onset before age 11 (82%, compared with 53% in adults). Anti-U1 RNP was more common in American blacks with SLE onset before age 18. HLA-DRB1*0301, DQA1*0501, DQB1*0201 was more common in Caucasians and DRB1*1503, DRB5*0101, DQA1*0102, DQB1*0602 in American blacks, regardless of age at SLE onset. Anti-Sm autoantibodies were most highly associated with HLA-DQA1*0102 and DQB1*0602. CONCLUSION: While childhood-onset SLE shares many immunogenetic and serologic similarities to adult-onset disease, important clinical differences nevertheless exist in children with this disease.

Adolescent↗

Measurement of intrinsic bone quality in vivo by reflection ultrasound: correction of impaired quality with slow-release sodium fluoride and calcium citrate.

The intrinsic (material) quality of cancellous and cortical bone was evaluated in vivo from the measurement of reflection ultrasound velocities in the ulna. In cancellous bone, the reflection ultrasound velocity was inversely correlated with age in normal women (r = -0.48, p = 0.001), with a significantly lower mean value in 32 normal postmenopausal women than in 14 premenopausal women (3124 versus 3341 m/s, p < 0.0001). In 32 untreated osteoporotic women the cancellous bone velocity was lower than in normal postmenopausal subjects (2906 versus 3124 m/s, p = 0.0001). Following treatment with slow-release sodium fluoride plus calcium citrate (mean 2.4 years in 33 osteoporotic patients with no fracture during treatment), the cancellous bone velocity was significantly higher than in untreated osteoporotic women (3082 versus 2906 m/s, p = 0.0002) and was not significantly different from that in normal postmenopausal women. The cortical bone velocity displayed similar trends, but the changes did not attain statistical significance. The measurements were repeated approximately 9 months later in 9 untreated and in 20 treated patients; in 5 additional patients, the measurements were made both before and after 9 months of treatment with slow-release sodium fluoride and calcium citrate. The cancellous bone velocity increased significantly (p = 0.046) in these patients, from 3008 m/s before treatment to 3112 m/s after the first 9 months of treatment. The velocity rose significantly from 3037 to 3167 m/s (p = 0.017) in patients treated for a short time (12-30 months at first measurement), but it did not change in untreated patients or those treated for more than 30 months. Thus, the material quality of cancellous bone decreases with normal aging and is reduced further with the osteoporotic process. This impaired quality may be corrected by treatment with slow-release sodium fluoride plus calcium citrate.

Analysis of Variance↗

Gastro-duodenal injury associated with intake of 100-325 mg aspirin daily.

During the year 1991, 43 patients with upper gastrointestinal bleeding and one with severe epigastric pain associated with intake of non-steroidal anti-inflammatory drugs were admitted for emergency endoscopy to our unit. Fourteen patients (33%) had been treated with 100-325 mg aspirin daily, 11 of them for at least one year. The mean age of this group was 71. Only two patients had a previous history of peptic ulcer. Five patients used anticoagulants or antiplatelet drugs concomitantly with aspirin. The endoscopic diagnosis of the sources of bleeding was erosive gastritis in eight patients, gastric ulcer in four, duodenal ulcer in five and oesophageal ulcer in one. Our results support findings by other groups, showing that doses of aspirin as low as 75 mg daily should be used in the management of elderly patients with thrombo-embolic disease.

Acute Disease↗

Lack of deleterious effect of slow-release sodium fluoride treatment on cortical bone histology and quality in osteoporotic patients.

We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

Adult↗

Variable effects of human and canine polymorphonuclear leucocytes on vascular smooth muscle tone.

OBJECTIVE: Previous studies have shown variable effects of human and canine polymorphonuclear leucocytes (neutrophils) on vascular tone. The aim of this study was to identify whether these variations in neutrophil function are due to species differences. METHODS: Canine and human arterial rings (with and without endothelium) were contracted with the thromboxane A2 analogue U46619, and then exposed to isolated neutrophils. RESULTS: Human neutrophils caused a significant relaxation of the human mammary arterial rings, and the relaxation was unaffected by the cyclo-oxygenase inhibitor indomethacin, enhanced by superoxide dismutase (SOD), and inhibited by oxyhaemoglobin. The relaxant effect of human neutrophils was also diminished upon pretreatment with NG-monomethyl-l-arginine (L-NMMA), indicating that the vasorelaxant material released by the neutrophils was nitric oxide (NO). Human neutrophils also relaxed canine femoral arterial rings, and the relaxant effect was potentiated by SOD and inhibited by pretreatment with oxyhaemoglobin or L-NMMA, confirming that the vasorelaxation was via release of NO. Canine neutrophils, on the other hand, caused an endothelium dependent contraction of autologous femoral arterial rings. This vasoconstriction was not affected by indomethacin, SOD, oxyhaemoglobin, or L-NMMA. However, treatment of canine neutrophils with the 5-lipoxygenase inhibitor piriprost attenuated (p < 0.02) their contractile effect on vascular rings, suggesting that neutrophil generated 5-lipoxygenase products were probably responsible for smooth muscle contraction. Presence of the leukotriene C4 and D4 receptor antagonist FPL 55,712 totally blocked the contractile effects of canine neutrophils, indicating that femoral arterial ring contraction was mediated by peptido-leukotrienes. CONCLUSIONS: The endothelium dependent nature of the canine neutrophil induced contraction suggests that the 5-lipoxygenase product leukotriene A4 is taken up by endothelial cells for conversion to peptido-leukotrienes. Since SOD had no effect and FPL 55,712 totally blocked the vasoconstrictor effects of canine neutrophils, it appears that the vasoconstrictor effects of the latter are mediated primarily through peptido-leukotrienes. In contrast, the vasorelaxation by human neutrophils is mediated through release of NO.

Animals↗

Colposcopic and histologic findings and human papillomavirus (HPV) DNA test variability in young women positive for HPV DNA.

The purpose of this study was to determine the prevalence of human papillomavirus (HPV)-related disease in women positive for HPV DNA by using a commercially available DNA detection kit and to compare these results to HPV DNA variability observed in repeated sampling. Young women attending family planning clinics who were positive for HPV DNA on routine screening were asked to return for a repeat HPV DNA test, cytology, colposcopy, and biopsy if indicated. Of the 78 women examined, 35% had biopsy-verified low-grade dysplasia of the cervix, and 64% had evidence of HPV-related disease somewhere in the anogenital area. Fifty percent of the women had a negative test on repeat sampling, but there was no association between DNA persistence at the second visit and colposcopic/histologic findings. In conclusion, the minority of women positive for HPV DNA have latent infection. In addition, variability in detection is common and unrelated to the presence of HPV-related disease.

Adolescent↗

Natural history of anal cytologic abnormalities and papillomavirus infection among homosexual men with group IV HIV disease.

Previous studies have demonstrated a high prevalence of anal cytologic abnormalities as well as anal human papillomavirus (HPV) infection among homosexual men with group IV HIV disease. However, the natural history of these changes in this population has not yet been studied. To this end, 37 homosexual men with group IV HIV disease attending an outpatient HIV clinic were followed at approximately 9-month intervals for an average of 17 months, using anal cytology, anoscopy, anal biopsy, and anal HPV DNA hybridization. During the study, the proportion of the 37 subjects with anal cytologic abnormalities increased from 27 to 65%. The proportion of subjects with any grade of anal intraepithelial neoplasia rose from 8 to 32%, with high-grade anal intraepithelial neoplasia increasing from 0 to 16%. The proportion of subjects with anal HPV infection increased from 60 to 89%, and infection with multiple HPV types was noted in at least 48%. We conclude that a large proportion of homosexual men with group IV HIV disease develop anal cytologic abnormalities, including anal intraepithelial neoplasia, over a short period of time. Together with a rapidly increasing incidence of anal cancer among single, never-married men in the San Francisco Bay area, these results suggest that these men may be at significant risk of development of anal cancer.

Adult↗

Gamete and zygote intrafallopian transfers and related techniques.

Until recently, most authors reported superior results (ie, higher implantation and pregnancy rates) with gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) compared with results using in vitro fertilization-embryo transfer (IVF-ET). According to these investigators, the advantages of tubal over uterine transfer are related mainly to a stable tubal environment and a more appropriate arrival time of the embryo into the uterine cavity. However, more recently, the use of IVF-ET has been increasingly extended to etiologies other than tubal infertility. Indeed, the recent simplification of this technique and the achievement of pregnancy rates comparable to those obtained with tubal transfers have seriously questioned the value of ZIFT and any other type of tubal embryo transfer. As discussed in this review, the results obtained with various transfer procedures in nontubal infertility must still prove ZIFT to be a more effective procedure than IVF-ET. Efforts to develop transcervical methods of transfer to the tube have not translated into higher pregnancy rates than those with IVF-ET. On the other hand, laboratory conditions appear to affect embryos in ways not corrected by the tubal milieu. Negative effects of laboratory conditions on embryos are confirmed by differences in results between GIFT and ZIFT that are accentuated with age. The results obtained with GIFT in patients 40 years of age and older seem to emphasize not only the high compliance of the endometrial receptivity but also the relevance of the biologic potential of the embryos in the process of implantation at this age.

Adult↗

Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer.

Forty anal paraffin-embedded tissue specimens from 24 subjects were studied for the presence of human papillomavirus (HPV) types 6, 11, 16, 18, 31, and 33, herpes simplex virus (HSV), Epstein-Barr virus, and cytomegalovirus DNA by using the polymerase chain reaction. These tissues ranged from histologically normal to invasive squamous cell carcinoma. HPV DNA was detected in the invasive anal cancer tissues of 11 of 13 subjects. HPV types were segregated by histopathological severity, with HPV 16 associated exclusively with high grade anal intraepithelial neoplasia and invasive cancer. HPV types 6 and 11 were associated with condyloma and low grade anal intraepithelial neoplasia. HPV DNA in situ hybridization studies confirmed the presence of HPV DNA in the invasive cancer tissues of 6 of 12 subjects. HPV DNA in these tissues was highly focal and primarily associated with invasive cell nests that demonstrated the greatest degree of squamous differentiation. HSV DNA was detected only in association with advanced disease, being found in the cancer tissues of 5 of 13 subjects, and in 3 of 4 subjects with high grade anal intraepithelial neoplasia, but was not detected by in situ hybridization. Epstein-Barr virus and cytomegalovirus DNA were not detected in the 40 tissue specimens. We conclude that HPV infection may play an important role in the pathogenesis of anal cancer. The association between HSV infection and high grade anal disease suggests that HSV infection may also play a role in disease progression.

Adult↗

Assessment by reflection ultrasound method of the effect of intermittent slow-release sodium fluoride-calcium citrate therapy on material strength of bone.

It has been suggested that fluoride therapy, while increasing bone mass, produces bone with inferior mechanical properties. In the present report this hypothesis was tested using a novel reflection ultrasound technique. Transiliac crest bone biopsies were obtained from 16 patients with osteoporosis and vertebral compression fractures (12 women and 4 men, mean age 56 years) before and after approximately 2 years of intermittent slow-release sodium fluoride therapy (25 mg twice a day) combined with continuous calcium citrate supplementation. Samples were analyzed by a reflection ultrasound method, which analyzes ultrasound velocity with a sample site resolution of 200 microns and thus provides a measure of the mechanical property of single trabeculae (material). For the group, mean fractional change in velocity increased 6.1 +/- 2.3% (SEM) from a mean value of 3303 +/- 80 to 3484 +/- 55 m/s (p = 0.028). A total of 13 patients (81%) demonstrated higher velocities after treatment. Thus reflection ultrasound analysis of bone appears to provide a sensitive means of assessing changes in the material property of bone. Furthermore, these results suggest that the treatment regimen utilized in these patients improves strength of bone at the material or trabecular level largely independently of change in bone mass. The combination therapy also increased spinal (L2-L4) bone density for the group as assessed by dual-photon absorptiometry (5.3 +/- 2.0%). There was no significant correlation between the change in ultrasound velocity and bone density (r = 0.0026, p = 0.996).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Measurement of mechanical properties of bone material in vitro by ultrasound reflection: methodology and comparison with ultrasound transmission.

An ultrasound reflection technique was designed and implemented to study the mechanical properties of bone material. The technique uses the fact that an ultrasound beam produced in water undergoes total internal reflection off a bone sample at a critical angle formally related to the velocity of a pressure wave in bone. When the plane of scattering is rotated around the normal to the sample surface, the critical angle varies with a periodic dependence dictated by the intrinsic symmetry of the bone structure at the point being examined. Most current measurements of sound velocity are made using transmission techniques. A double-blind intercomparison between this technique and a transmission technique, which was previously validated against tensile mechanical testing, was performed for samples of isotropic materials and of human cortical bone. Strong correlations were found for both sets of samples. For the isotropic materials the velocities were approximately equal, but for bone they were on average 11% higher in reflection than in transmission. This was the result both of the higher frequency employed in reflection (3.5 rather than 2.25 MHz) and of the different effects of sample imperfections on the two measurements. In particular, the reflection technique used in this work studied the surface of the sample, but the ultrasound beam in the transmission method propagated through its interior. In assessing the mechanical properties of bone specimens by ultrasound, the reflection technique samples a discrete bone surface element and the transmission method analyzes the entire volume of the specimen. Thus the reflection technique may yield a measure of the mechanical property of bone trabeculae that is largely unaffected by the mass of the entire specimen, but mass and the structural density of the specimen affect the transmission method.

Biomechanical Phenomena↗