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Biomedical subjects

J M Kaufman

Publications and source records attributed to J M Kaufman.

At least 19 recordsLinked to original sources

[How to evaluate osteoporosis: bone densitometry and biochemical tests].

The use of bone densitometry, by dual energy x-ray absorptiometry, allows the identification, at an early stage, of subjects who will, 15-20 years later, present a fracture event. Furthermore, this technique is the most appropriate to confirm the efficacy of preventive or curative therapeutic approaches of osteoporosis. A balanced utilisation of biochemical tests is mandatory to exclude a secondary cause of osteoporosis, to help in the choice of the most appropriate therapeutic strategy and to evaluate the early response of patients to the administered drugs.

Absorptiometry, Photon

[Postmenopausal osteoporosis in women].

Postmenopausal osteoporosis is now considered a major public health problem in aging women, due to the burden related to the consequent fractures. Over recent years, several pharmacological approaches were developed for the prevention and treatment of osteoporosis. Besides regular physical exercise and calcium rich diet, calcium supplementation can be suggested to both genders, after seventy years as well as systematic vitamin D supplementation in order to cope with the frequent lack observed in our country. Hormone replacement therapy is the first choice in prevention of postmenopausal osteoporosis. Based on a careful evaluation of the needs of a postmenopausal woman as well as on the risk/benefit ratio derived from her individual risk factors, selective estrogen receptor modulators (raloxifene) or second generation bisphosphonates (alendronate) can be considered as alternative to estrogens. Due to its prohibitive cost, nasal calcitonin should be only considered for very specific cases. In osteoporosis confirmed by bone densitometry or by occurrence of fractures, bisphosphonate (alendronate) reduces subsequent fracture rate. Fluoride salts can, in some cases, improve spinal symptomatic osteoporosis. The use of etidronate, a molecule from the past, should be avoided as much as possible and, at any rate, strictly restricted to its legal indication including women with several vertebral crush fractures and severely decreased bone mineral density.

Aged

The Multi Unit Activity analyzer: a Windows based hardware-software system for low cost, high speed analog to digital data conversion, data acquisition and window discrimination.

The Multi Unit Activity analyzer is a hardware-software package for multi-purpose, two-channel data acquisition, with a computer dependent maximal digitizing frequency selectable from 1 to 27,000 s(-1) on both channels simultaneously. The hardware is connected to an IBM compatible PC through one of the serial ports (standard RS 232 interface). Software was developed to view digitized signals and record or read them on or from the harddisk. The program can also perform amplitude based window discrimination on the raw signal, on-line or during replay. The system is used for recording and analyzing multi unit activity from neuronal tissue in our electrophysiology lab but it can be applied in a variety of other settings. Basic programming routines are available that allow customized data acquisition.

Analog-Digital Conversion

Immediate salvage procedure for infected penile prosthesis.

PURPOSE: The most devastating complication after the insertion of a penile prosthesis is the development of infection. The standard approach involves removing the entire device, treating intensively with antibiotics and attempting to reinsert a prosthesis at a later date, often with a suboptimal result. Based on the encouraging results of others, during the last 24 months we have used in 2 separate private urological practices a salvage procedure for treatment of infected inflatable penile prostheses. MATERIALS AND METHODS: The protocol used in 7 men with an infected inflatable penile prosthesis included removal of all device components, a 7-step vigorous intraoperative irrigation with 4 different solutions, including vancomycin, immediate reimplantation of a new inflatable penile prosthesis and postoperative outpatient antibiotics with oral ciprofloxacin or intravenous vancomycin or cefazolin. RESULTS: Of the 7 men 6 have experienced excellent results with no infection, minimal morbidity and preservation of penile length. The only failure occurred in a poorly controlled diabetic who required multiple revisions and may have had latent infection for months before it became apparent. CONCLUSIONS: We believe that an immediate salvage procedure for an infected inflatable penile prosthesis is an effective treatment for this difficult complication.

Adult

Declining gonadal function in elderly men.

Ageing in men is accompanied by a progressive decline of gonadal function with, in particular, a decline of total and free testosterone (T) plasma levels resulting in a significant proportion of elderly men over age 60 years presenting with subnormal T levels compared with the levels in young adults. A great interindividual variation in T levels is observed in elderly men, a variability explained in part by physiological variables and differences in life style, while associated acute or chronic diseases may accentuate the age-related decline of T levels. The progressive decrease of plasma T levels has been shown to result from both primary testicular changes and altered neuroendocrine regulation of Leydig cell function. At present, little is known about the clinical relevance of the relative hypoandrogenism of elderly men and there is an urgent need for more longitudinal studies, which may clarify a possible role of decreased T levels in the modulation of the clinical consequences of ageing in men. In view of the lack of relevant controlled clinical trials having careful assessment of the risks and benefits of androgen replacement therapy in elderly men, this treatment should be reserved for selected patients with clinically and biochemically manifest hypogonadism, after careful screening for contraindications.

Aged

201Tl scintigraphy does not allow visualization of the thyroid in euthyroid and hyperthyroid patients treated with amiodarone.

A retrospective study was performed to evaluate the usefulness of thallium scintigraphy for visualization of thyroid morphology and function. Moreover, applying absolute quantitation, we wished to confirm the qualitatively reduced 99Tc(m) uptake reported by Wiersinga et al. in both euthyroid and hyperthyroid patients treated with amiodarone. Over a period of 2 years (1995-96), 10 patients (group A; 2 females, 8 males, mean age 68.6 years, range 61-74 years) receiving amiodarone treatment for cardiac arrhythmias for at least 4 months were referred for exploration of either hyperthyroidism (n = 4) or for exclusion of parathyroid adenoma (n = 6). During the same period, 17 patients (group B; 10 females, 7 males, mean age 62 years, range 19-91 years) referred for Tc-Tl subtraction scintigraphy, and in whom follow-up revealed no thyroid or parathyroid pathology, were used as controls. In all patients, thyroid status was assessed by thyroid function tests. 201Tl and 99Tc(m) uptake was calculated as a percentage of the injected dose, taking account of net injected counts and background and isotope decay correction. Original images were scored using a 2-point scoring system (0 = poor, 1 = fair or good). Uptake of both 99Tc(m) and 201Tl was significantly reduced in group A (99Tc[m]: 0.16 +/- 0.21%; 201Tl: 0.30 +/- 0.21%; mean +/- S.D.) compared to group B (99Tc[m]: 1.58 +/- 1.07%; 201Tl: 0.72 +/- 0.37%) (P < 0.005). The mean relative reduction in 99Tc(m) uptake was more pronounced (90% decrease) than that of 201Tl (58% decrease). In group A, the 99Tc(m) and 201Tl image quality was poor in 10 of 10 and 8 of 10 patients respectively. In group B, the 99Tc(m) and 201Tl image quality was poor in 3 of 17 and 4 of 17 patients respectively. The decreased uptake of 201Tl may reflect the inhibitory effect of iodides on adenyl cyclase and its stimulation by TSH. In conclusion, the data presented confirm the qualitatively reduced pertechnetate uptake reported by Wiersinga et al. Furthermore, 201Tl uptake by the thyroid in euthyroid or hyperthyroid patients treated with amiodarone is also reduced. Although quantitatively less pronounced, it does not allow proper visualization of the thyroid.

Adult

Oral alendronate induces progressive increases in bone mass of the spine, hip, and total body over 3 years in postmenopausal women with osteoporosis.

To determine the effects of long-term daily oral alendronate sodium (ALN) on bone mass in postmenopausal women with osteoporosis, 19 centers enrolled 516 postmenopausal women aged 45-80 years with spine bone mineral density (BMD) at least 2.5 SD below the mean for young premenopausal women in a 3-year, double-blind, placebo-controlled study. Subjects were randomly allocated to one of four treatment groups: placebo; alendronate, 5 or 10 mg/day for 3 years; or alendronate, 20 mg/day for 2 years followed by 5 mg/day for the 3rd year. All patients received 500 mg/day of supplemental calcium to ensure adequate calcium intake. BMD was measured by dual-energy X-ray absorptiometry at several skeletal sites. Nonsignificant mean decreases in BMD of the spine, femoral neck, and trochanter of 0.6, 0.7, and 0.4%, respectively, occurred in the placebo group at 3 years. Relative to placebo-treated patients, spine BMD increased by 5.4%, 7.4%, and 8.4% in the 5, 10, and 20/5 mg ALN groups, respectively. Increases at the femoral neck were 3.5%, 5.5%, and 4.3%, and those at the trochanter were 5.1%, 7.2%, and 7.2%, respectively. Thus, efficacy of 10 and 20/5 mg ALN was similar, whereas the 5 mg dose was less effective. BMD continued to increase over the entire 3-year study duration in the ALN-treated groups and, compared with the other dosage groups, 10 mg ALN produced the largest gains in BMD during the 3rd year. Changes in biochemical markers of bone turnover and mineral homeostasis confirmed the effect of ALN to decrease bone turnover to a new steady-state level. The safety and tolerability of ALN were comparable with those of placebo. In summary, 10 mg daily oral ALN given for 3 years significantly and progressively increases bone mass and is a generally well-tolerated treatment for osteoporosis in postmenopausal women.

Administration, Oral

The N-methyl-D-aspartate-mediated inhibitory control of gonadotropin-releasing hormone release in the hypothalamus of the adult male guinea pig is expressed through opioidergic systems.

Previously, we reported on a dual role of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission in the control of GnRH secretion from the medial basal hypothalamus (MBH) of the adult male guinea pig, with a predominantly inhibitory action in the intact animal, which is reversed to a facilitatory role by orchidectomy. In the present study we examined the hypothesis that endogenous opioids are involved in the NMDA receptor-mediated inhibition of GnRH release. A static incubation system was used to test the effects of excitatory amino acid agonists and an excitatory amino acid antagonist, alone or in the presence of either the opiate agonist morphine or the mu-receptor antagonist naloxone, on in vitro GnRH release from the isolated MBH of intact, orchidectomized, or sham-operated guinea pigs. GnRH output from the MBH of intact guinea pigs was markedly suppressed in the presence of the NMDA-specific receptor agonist, N-methyl-D,L-aspartic acid (NMA; 50 mM), whereas NMDA-specific receptor blockade with D,L-amino-5-phosphonovaleric acid (AP-5; 1 mM) resulted in a pronounced facilitation of GnRH release, as did exposure to the non-NMDA-specific receptor agonist, kainic acid (50 mM). Opioidergic blockade with naloxone (1 mM) caused a reversal of the responses to NMA and AP-5, with exposure to these compounds this time resulting in clear facilitation and inhibition, respectively. The stimulatory action of kainic acid, on the other hand, remained unaffected by the presence of naloxone. Morphine inhibited basal GnRH output and also annulled the stimulatory effect of AP-5 on GnRH secretion. The results obtained from MBHs of sham-operated guinea pigs were identical to those seen for the intact animals, with naloxone effectively increasing baseline GnRH release and reversing the inhibitory effect of NMA and stimulatory action of AP-5 on GnRH secretion to a facilitation and inhibition, respectively. On the other hand, NMA caused a marked stimulation, whereas AP-5 produced a significant inhibition of GnRH release from the MBHs of orchidectomized guinea pigs; neither of these effects was altered by the presence of naloxone, which, moreover, had only a marginal effect on basal GnRH output in this group of animals. In conclusion, our present data provide evidence to support the view that the primary inhibitory action of NMDA receptor-mediated neurotransmission on GnRH release in the MBH of the intact male guinea pig is the result of activation of opioidergic systems and that a marked reduction of opioid tone after orchidectomy brings a facilitatory NMDA receptor-mediated system to the fore. On the other hand, non-NMDA-specific kainate receptor-mediated facilitation of GnRH, previously shown to be unaffected by gonadal status, appears to be also independent from opioidergic modulation.

2-Amino-5-phosphonovalerate

Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males.

Several aspects of the regulation of androgen secretion and plasma levels in males remain controversial. Among these, we cite the problem of whether the age-related decrease in testosterone (T) levels is an intrinsic aging phenomenon or is a sequel of previous illness, the mechanisms underlying the increase in sex hormone-binding globulin (SHBG)-binding capacity in aging men and the supranormal capacity observed immediately after a weight-reducing diet, and the role of insulin in the age-associated decrease in dehydroepiandrosterone (sulfate) [DHEA (DHEAS)] levels. To gain further insight into these issues, we investigated the influence of age, smoking, body mass index (BMI), serum albumin, insulin, GH, and insulin-like growth factor I (IGF-I) levels, respectively, on androgen levels and SHBG-binding capacity in a nonobese healthy population (n = 250) as well as in an obese population (n = 50) before and after weight loss. The influence of GH supplementation on SHBG, DHEAS, DHEA, and insulin levels was studied in a small group of men (n = 8) with isolated GH deficiency. In nonobese healthy men, age was inversely correlated with serum levels of all androgens studied (although total T levels stayed relatively stable until age 55 yr) as well as with albumin, GH, and IGF-I levels and positively correlated with BMI, insulin levels, and SHBG-binding capacity. Nevertheless, SHBG levels were significantly negatively correlated with insulin levels (P < 0.001) as well as with mean 24-h GH and IGF-I levels. Among possible confounding factors affecting (free) T [(FT)] levels in healthy men, smoking appeared to be accompanied by higher (F)T levels than those in nonsmokers. BMI increased with age, but although BMI was negatively correlated with T, FT, and SHBG, respectively, the age-dependent decrease in T levels persisted after correction for BMI. Data not corrected for BMI may, nevertheless, overestimate the age-associated decrease in T levels. The albumin concentration decreased with age, and if FT is the feedback regulator of plasma T levels, albumin concentration might be a codeterminant (although, evidently, less important than SHBG) of T levels and contribute to the age-associated decrease in T levels. In any case, albumin concentration is a codeterminant of DHEAS concentration. T, DHEA, and DHEAS levels were significantly correlated, but this correlation disappeared after controlling for age; hence, there is no evidence for an adrenal-gonadal interaction in men. In obese men, T, FT, and SHBG levels were significantly lower than those in the nonobese men and inversely correlated with BMI; DHEAS levels were slightly lower than those in the nonobese controls, but no significant correlation between DHEA or DHEAS, and insulin levels was observed. After a weight-reducing, protein-rich diet, resulting in a mean weight loss of +/- 15 kg, SHBG-binding capacity increased to normal values notwithstanding the fact that the subjects were still obese and that the insulin levels remained higher than those in the nonobese controls. Considering that after weight loss, GH and IGF-I levels remained lower than those in the nonobese controls, that adult men with isolated GH deficiency presented with higher SHBG levels than normal controls, which decreased to normal levels during GH substitution, and that elderly men have elevated SHBG levels notwithstanding high insulin levels, we suggest that the low GH and/or IGF-I levels might play a role in the elevated SHBG levels observed in both elderly males and obese men after a weight-reducing diet. As weight loss did not influence DHEAS levels notwithstanding an important decrease in insulin levels, our data do not support a role of insulin in the regulation of plasma DHEAS levels.

Adult

Influence of the arterial blood pressure and nonhemodynamic factors on regional arterial wall properties in moderate essential hypertension.

Structural and functional abnormalities may occur at the left ventricle and in different large arteries in essential hypertension. Noninvasive high resolution pulsed doppler echo-tracking technique allows calculation of regional arterial wall properties, which might be determined by either hemodynamic or non-hemodynamic factors. Therefore we aimed to study regional arterial wall properties in three different vascular territories and examined whether hemodynamic and non-hemodynamic parameters were significantly associated to a specific vascular territory. In 30 patients (mean age 47 +/- 2 years) with newly diagnosed and untreated essential arterial hypertension, arterial wall properties were determined at the carotid (common, external and internal), femoral, and brachial artery using a noninvasive ultrasound wall movement detector system. The study parameters were arterial diameter, relative diameter change, arterial distensibility (DC) and cross-sectional compliance (CC) coefficient. On the day of the experiments office blood pressure (BP) was measured as well as an ambulatory 24 h BP profile performed on an outpatient basis. Blood samples were taken on the day of the vascular examination for the determination of plasma renin activity (PRA), aldosterone, intact (1-84) parathyroid hormone (PTH), insulin and plasma noradrenaline and adrenaline. Among the studied vascular territories, only DC and CC of the common carotid artery were significantly (P < 0.01) correlated with office and ambulatory systolic BP. Intact PTH was significantly correlated with the diameter (r = 0.61, P = 0.005) and DC (r = -0.53, P = 0.01) of the internal carotid artery. Noradrenaline was inversely correlated with DC of the femoral artery (r = - 0.55, P < 0.01). All correlations remained significant after adjustment for age and body mass index as confounding variables. In conclusion, in mild to moderate arterial essential hypertension there is a heterogeneity of vascular wall properties and their relationship to BP and humoral factors between brachial, femoral and carotid (common, external and internal) arteries. Our findings might renew interest in the old concept of the 'circulatory paradox'.

Adult

Role of calcium and vitamin D in the prevention and the treatment of postmenopausal osteoporosis: an overview.

When discussing the use of calcium and vitamin D in the prevention and the treatment of osteoporosis one can make a distinction between the use as dietary supplementation to correct or prevent deficiencies, and the pharmacologic use of higher doses, whether or not in association with other drugs. However, in practical terms it is not always possible to clearly make this distinction. Available evidence suggests that increasing the calcium intake can favourably affect the build-up of bone mass in adolescence. In this population, the daily consumption of calcium in the diet should, optimally, be at least 1200 mg/day. In view of the lack of data pertaining to the effect on the final peak bone mass, there is at present time no basis for the systematic administration of calcium supplements to healthy children and adolescents. Calcium supplementation, aiming at a total calcium intake of at least 1500 mg/day, has a partial protective effect on postmenopausal bone loss, this effect being documented mainly in women more than 5 years after menopause. In the present state of our knowledge, there is no established role for vitamin D supplementation in the prevention of postmenopausal osteoporosis, except in elderly patients presenting with a higher risk for relative vitamin D deficiency and with low calcium intake. The results of a controlled trial suggest that in institutionalised elderly patients, systematic administration of calcium and vitamin D supplements can substantially reduce the risk of hip fracture. In the treatment of established postmenopausal osteoporosis, calcium supplementation has only a role as a general adjuvant therapeutic measure and as a specific complement to the treatment with other active compounds. There are indications that treatment alpha-calcidol or calcitriol has a positive effect on the evolution of bone mass, but awaiting further confirmation of a favourable effect on the incidence of osteoporotic fractures, treatment with these drugs remains experimental.

Adolescent

Renin-angiotensin-aldosterone system, RR interval, and blood pressure variability during postural changes in borderline arterial hypertension.

This study aimed to examine the changes in RR interval and blood pressure (BP) variability and humoral factors during postural changes in borderline arterial hypertension. Twenty-nine patients (44 +/- 3 year; BP, 145 +/- 3/84 +/- 3 mm Hg) with borderline hypertension and a control group of 38 subjects (35 +/- 2 year; BP, 123 +/- 3/70 +/- 2 mm Hg) underwent power spectrum analysis of RR interval and BP (low frequency (LF), 0.05 to 0.15 Hz; high frequency (HF), 0.15 to 0.40 Hz) in the supine and standing positions. Concentrations of plasma renin activity, angiotensin II, and aldosterone in supine and standing positions had been determined in the hypertensive group. Borderline hypertensives are characterized by higher oscillations of systolic and diastolic BP, but not of RR interval in the supine position versus the control group. Low frequency and HF components of systolic and diastolic BP expressed as absolute data are also significantly higher in borderline hypertensives. Moreover, standing tended to increase the LF/HF ratio of both RR interval and BP variability compared to controls. The standing position was able to further activate the LF but not the HF component of BP variability. In borderline hypertension renin release during postural changes correlated well with the decrease in the power of the HF vagal component of RR interval variability (r = -0.70, P < .001) and with the increase of the LF component of diastolic blood pressure variability (r = 0.43, P = .03). In conclusion, our results indicate that in borderline arterial hypertension, LF and HF oscillations of BP are already significantly increased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Renin-angiotensin-aldosterone system, RR-interval and blood pressure variability during postural changes after myocardial infarction.

Low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.40 Hz) components of heart rate variability have been used to evaluate the autonomic nervous system. The sympathico-vagal balance as well as the renin-angiotensin-aldosterone (RAA) axis are disturbed in the post-acute phase of acute myocardial infarction (AMI). This study examined the relationship between the RAA-axis and spectral indices of the RR-interval and blood pressure (BP) variabilities during postural manoeuvres in the post-AMI period. Power spectral analysis of the RR-interval and BP variability was computed from non-invasive beat-to-beat BP measurements 10-12 days post-AMI, using Fast-Fourier transforms. Concomitantly, hormonal changes of the RAA-axis were determined and data were further correlated with the left ventricular ejection fraction. When the patient moved from the lying to the supine position all RAA-axis parameters significantly increased. Both LF and HF components of total RR-interval variability decreased upon standing, while the LF component of systolic and diastolic BP variability increased and HF components remained constant. In the upright position, plasma renin activity (P<0.01) and angiotensin II (borderline) were inversely related with the LF component of systolic BP. The aldosterone level was dissociated from plasma renin activity and angiotensin II. The left ventricular ejection fraction was inversely correlated (P<0.05) with systolic and diastolic BP variabilities and their LF and HF powers. These results suggest that the renin-angiotensin II system in the post-acute phase of AMI patients treated with aspirin and beta-blocking agents is correlated with cardiovascular autoregulation during postural manoeuvres.

Autonomic Nervous System