PubMed Health⌕ Search

Biomedical subjects

S Khoury

Publications and source records attributed to S Khoury.

At least 19 recordsLinked to original sources
PubMed1992

Ambulatory blood pressure monitoring in a nonacademic setting. Effects of age and sex.

Twenty-four-hour ambulatory blood pressure measurements (ABPM) are likely to eliminate the stress of visits and observer bias in office blood pressure (BP) recordings, allow consideration of the circadian variability in BP, and correlate well with target organ damage. To define the prevalence of "white coat" hypertension in a rural community to a nonacademic setting, and to assess age and sex related differences, we studied 131 patients who had more than two prior office diastolic BP measurements greater than 90 mm Hg and less than 115 mm Hg. Blood pressure was measured every 10 to 60 min for 24 h using the SpaceLabs 90207 device. Office BP readings were higher than ABPM in the group as a whole, in individual age groups, and in both sexes. The differences were more pronounced at night. Average differences between office and ambulatory BP ranged between 14.4 +/- 1.7/2.9 +/- 2.0 (ABPM at 10:00), and 33.8 +/- 2.3/22.8 +/- 1.5 mm Hg (systolic/diastolic +/- SE) (ABPM at 01:00). The nighttime drop in systolic BP was not apparent in subjects more than 65 years old. Women had a proportionately higher mean office BP than men (115.0 +/- 0.9 office v 110.2 +/- 1.3 mm Hg ABPM in women and 112.3 +/- 0.9 v 104.3 +/- 1.1 mm Hg in men) (P = .013), and the elderly did not display the relationship between ambulatory and office mean BP seen in younger subjects (r = 0.15, P = .30 v r = 0.36, P = .0004, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

Future directions in the management of benign prostatic hyperplasia.

A meeting of the International Consultation on Benign Prostatic Hyperplasia (BPH) in June 1991 provided an update on the management of PBH. It is recognised that the development of complications in what may be regarded as a relatively well tolerated disease may necessitate surgical intervention. Current treatment is directed towards circumventing or ameliorating the complications of BPH and perhaps to find minimally invasive or non-invasive alternatives to surgery that could eliminate this modality altogether. Anticipated changes in the management of BPH include establishment of an improved scoring system and response criteria; implementation of stenting techniques, physical modalities such as hyperthermia and laser therapy to replace transurethral resection of the prostate; development of more specific alpha blockers with fewer adverse effects; and administration of hormonal therapy, possibly as an eventual preventative of BPH. The 1991 International Consultation on Benign Prostatic Hyperplasia (BPH), which took place in Paris, France, under the joint sponsorship or the World Health Organization and the major international and national societies of urology, provided an excellent opportunity to review current knowledge on the subject of BPH and to explore future trends in its management. Most of the information included in this report is drawn from the conclusions of the consultation participants.

Adrenergic alpha-Antagonists↗
PubMed1992

MIDAS: hypertension and atherosclerosis. A trial of the effects of antihypertensive drug treatment on atherosclerosis. MIDAS Research Group.

Although clinical trials of the efficacy of antihypertensive treatment have demonstrated impressive reductions in the incidence of stroke, the reduction in coronary artery disease mortality has been less impressive. It may be that the antihypertensive drugs used in these trials induced metabolic disturbances, or produced inadequate regression of left ventricular hypertrophy, thus blunting the reduction in risk of coronary artery disease expected with blood pressure-lowering. Isradipine, a dihydropyridine calcium antagonist known to be an effective antihypertensive agent, has also displayed pronounced antiatherogenic effects in animals. Thus, a reasonable hypothesis could be that isradipine not only reduces the level of blood pressure, but also may have a positive effect on the evolution of atherosclerotic plaque in coronary and carotid arteries, thereby leading to prevention of clinical sequelae of atherosclerosis. On this basis, a 3-year clinical trial is being carried out in the United States--the Multicenter Isradipine/Diuretic Atherosclerosis Study (MIDAS)--to establish the efficacy of isradipine in inhibiting atherogenesis and retarding the progression of atherosclerosis in carotid arteries of hypertensive patients. The primary end point of the study is intima-media thickness and the extent of atherosclerotic plaque in the carotid arteries, as measured by B-mode ultrasonography.

Antihypertensive Agents↗
PubMed1991

Phase II study of fotemustine in recurrent supratentorial malignant gliomas.

38 adults with recurrent supratentorial malignant gliomas, including glioblastoma multiforme (21), anaplastic astrocytomas (9), probably transformed low-grade astrocytomas (6), pinealoblastoma (1) and non-metastatic tumour of unknown histology (1), were treated with fotemustine 100 mg/m2 intravenously every week for 3 consecutive weeks followed by a 5-week rest period. Maintenance treatment consisted of one infusion every 3 weeks. Patients were divided into three groups according to treatment effect. 10 objective responses (26%) with a median time without progression of 32.7 weeks, 18 stabilisations (47%) and 10 failures (26%) were observed. Pathological findings of the initial primary tumour and neurological functional status were unequally distributed in these groups. Haematological and liver toxicities were mild, delayed, transient and reversible. Thrombocytopenia and leukopenia were more frequent (30%) in patients treated with prior chemotherapy. Fotemustine is a well tolerated active drug in recurrent malignant gliomas with an original and short treatment schedule.

Adolescent↗
PubMed1991

Mechanisms of hypertension in diabetes.

Hypertension in insulin resistance states is generally attributed to hyperinsulinemia, with resulting increases in renal sodium retention and/or sympathetic nervous system activity. However, recent data from our laboratory suggest that cellular insulin resistance, rather than hyperinsulinemia per se, may lead to hypertension. The basic tenet proposed in this review is that the common mechanism involved in the development of hypertension in both type I and type II diabetes mellitus is a deficiency of insulin at the cellular level. Recent observations suggest that impaired cellular response to insulin predisposes to increased vascular smooth muscle (VSM) tone (the hallmark of hypertension in the diabetic state). For example, recently reported studies from our laboratory demonstrate that insulin in physiological doses attenuates the vascular contractile response to phenylephrine, serotonin, and potassium chloride. Thus, insulin appears to normally modulate (attenuate) VSM contractile responses to vasoactive factors, and insulin resistance should accordingly be associated with enhanced vascular reactivity. Abnormal VSM cell calcium [Ca2+]i homeostasis may be the nexus between insulin resistance and increased VSM tone. The genetically obese, hyperinsulinemic, insulin-resistant Zucker rat demonstrates increased vascular reactivity, reduced membrane Ca2(+)-ATPase activity, increased cellular Ca2+ levels, and a marked impairment in vascular smooth muscle Ca2+ efflux compared to lean controls. Insulin stimulates membrane Ca-ATPase, blocks Ca2+ currents, and Ca2(+)-driven action potentials. Thus, an insulin-resistant state as exists in the Zucker rat may be associated with increased Ca2+ influx through voltage-dependent sarcolemmal Ca2+ channels and/or decreased production or activation of the VSM cell Ca-ATPase pump.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1991

Diabetes and hypertension: a review.

The basic mechanisms that initiate and sustain hypertension in type 2 diabetics are poorly understood. Contributing factors discussed in this review include obesity, insulin resistance, hyperinsulinemia, genetic factors, and abnormalities of cellular cation homeostasis. Also discussed are the features of hypertension in type 2 diabetic individuals that are reminiscent of the hemodynamic abnormalities characterizing hypertension in the elderly, including increased vascular reactivity and increased atherosclerotic vascular disease. This article reviews mechanisms by which hyperinsulinemia, insulin resistance, or both may lead to hypertension.

Antihypertensive Agents↗
PubMed1991

World Health Organization Consensus Committee recommendations concerning the diagnosis of BPH.

The expert committees, which met in Paris in June 1991 under the patronage of WHO to establish a consensus concerning BPH, adopted the recommendations summarised in this report. Despite certain criticisms which can be made, these recommendations offer the advantage of simplicity and uniformity, thereby constituting a "universal language". This will facilitate comparison of patients and therapeutic results, both in everyday practice and in the course of clinical trials. These recommendations will be periodically re-evaluated in the light of clinical experience and technological progress.

Clinical Protocols↗
PubMed1991

Therapeutic approach to hypertension in the elderly.

Hypertension is an important risk factor for cardiovascular disease in the elderly. This article addresses the factors that increasingly influence hypertension as age increases. In addition, the initial therapeutic approach to the elderly hypertensive patient should generally consist of a reduction in salt and caloric intake and increased exercise. Drug therapy should be initiated with lower doses of medication with special concern about orthostatic hypotension. The drug regimen should be made as simple as possible and be carefully explained to the patient. With these considerations in mind, hypertension in the geriatric patient can be effectively managed.

Age Factors↗
PubMed1989

The long-term antihypertensive effects of prazosin and atenolol.

The efficacy and tolerability of the alpha-blocker prazosin was compared with that of atenolol, a beta-blocker, in the long-term treatment of uncomplicated, essential hypertension. Twelve patients were randomly assigned to prazosin treatment and 15 to treatment with atenolol. Drug therapy was titrated to reduce diastolic blood pressure by 10 mm Hg or to below 89 mm Hg, whichever was lower. If monotherapy with either study drug failed to do this, hydrochlorothiazide was added to the regimen. Once blood pressure control was established, patients received maintenance therapy at that dosage and were followed for up to 12 months. Blood pressure, side effects, and plasma lipid levels were monitored during this period. Seventy-five percent of patients receiving prazosin monotherapy attained blood pressure goals, compared with 60 percent of patients given atenolol monotherapy. With the addition of low-dose hydrochlorothiazide, those patients not having an adequate response to monotherapy attained blood pressure control. Blood pressure reductions were maintained without dosage adjustment throughout the maintenance period; patient acceptance was good, and there was no evidence of tolerance. Treatment with atenolol produced slight increases in plasma triglyceride levels and little change in total or low-density lipoprotein cholesterol. In contrast, patients treated with prazosin demonstrated no adverse effects with regard to lipid levels. Although a higher percentage of patients reached goal blood pressure with prazosin monotherapy than with atenolol, the response rates were comparable when hydrochlorothiazide was added to the regimens.

Atenolol↗
PubMed1988

Increased luteinizing hormone pulse frequency during sleep in early to midpubertal boys: effects of testosterone infusion.

Gonadotropin secretion is pulsatile in prepubertal and early pubertal boys, and the onset of puberty is characterized by a sleep-associated rise in LH pulse amplitude. To determine whether an augmentation in LH pulse frequency as well as amplitude occurs at the onset of puberty, we studied gonadotropin secretion in 21 early to midpubertal boys. Blood samples were taken every 20 min (every 15 min in 4 boys) for LH determinations. A 2-fold increase in LH pulse frequency occurred during the nighttime sampling period (2200-0400 h) compared to that in the hours when the boys were awake (1000-2200 h). The maximum frequency (0.7 pulses/h) occurred between 2400 and 0200 h. The mean plasma LH concentration increased during the night from 2.3 +/- 0.2 (+/- SE) mIU/mL (2.3 +/- 0.2 IU/L) between 2000-2200 h to a maximum of 6.2 +/- 0.4 (6.2 +/- 0.4 IU/L) between 0200-0400 h. The mean plasma LH decreased to 5.5 +/- 0.4 mIU/mL (5.5 +/- 0.4 IU/L) between 0400-0600 h and to 4.2 +/- 0.5 (4.2 +/- 0.5 IU/L) between 0600-0800 h. Plasma testosterone rose during the night to a mean maximum value of 2.4 +/- 0.5 (+/- SE) ng/mL (8.3 +/- 1.7 nmol/L). This finding suggested that the rise in testosterone might play a role in decreasing LH secretion during the later hours of sleep (after 0400 h). To address this question and to study further the effects of testosterone in early puberty, we measured plasma LH concentrations every 10 min from 2000-0800 h in 8 early to mid-pubertal boys before and during short term testosterone administration. Saline or testosterone at a concentration of 9.33 micrograms/mL (32 mumol/L) was infused at a rate of 10 mL/h from 2100-1200 h to shift the nighttime testosterone rise 3 h earlier than would occur spontaneously. Blood samples were obtained every 10 min for LH and every 30 min for testosterone determinations from 2000-0800 h. Pituitary responsiveness was assessed by administering sequential doses of synthetic GnRH (25 and 250 ng/kg) at 1000 and 1200 h, respectively. The nighttime increase in LH pulse frequency and mean plasma LH concentration occurred between 2300 and 0200 h despite testosterone infusion. However, testosterone infusion was associated with significantly lower mean plasma LH concentrations from 0200-0800 h compared to those on the night of the saline infusion. Pituitary responsiveness to synthetic GnRH was unaltered by testosterone administration.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Gonadotrophin responses to GnRH pulses in hypogonadotrophic hypogonadism: LH responsiveness is maintained in the presence of luteal phase concentrations of oestrogen and progesterone.

LH pulse secretion changes during the menstrual cycle from a rapid regular pattern in the follicular phase to a slower and irregular pattern in the luteal phase. To determine whether the irregular LH pulse pattern in the luteal phase reflects altered GnRH secretion or altered pituitary responsiveness to GnRH, we gave low dose GnRH pulses (25 ng/kg i.v.) every 2 h or every hour for 10 or 12 d to three women with isolated GnRH deficiency. After 4 d of GnRH alone, oestradiol (E2) was given and after 6 d progesterone (P) was added to mimic the hormonal milieu of the luteal phase. LH and FSH were measured every 4 h throughout and also every 20 min for 6 or 12 h, before and after GnRH alone (day 0 and day 4), after E2 (day 6), and after E2 + P (day 10 and day 12). Both GnRH pulse frequencies resulted in a rapid increase in plasma FSH to peaks on day 4 (every 2 h) and day 2 and 3 (every hour). FSH concentrations then declined as plasma E2 rose to 50-80 pg/ml reflecting the selective inhibitory effect of E2 on FSH release. Plasma LH was also increased after the hourly GnRH injections and this regimen was associated with a more rapid rise in E2 reflecting follicular maturation. In contrast to the differences in mean hormone concentrations, administration of GnRH at both frequencies resulted in sustained one-on-one responsiveness of LH that was maintained in the presence of both oestrogen and progesterone at mid-luteal phase concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

The frequency of gonadotropin-releasing hormone secretion regulates expression of alpha and luteinizing hormone beta-subunit messenger ribonucleic acids in male rats.

The influence of GnRH pulse frequency on LH subunit mRNA concentrations was examined in castrate, testosterone-replaced male rats. GnRH pulses (25 ng/pulse) or saline to controls, were given via a carotid cannula at intervals of 7.5-240 min for 48 h. alpha and LH beta mRNA concentrations were 109 +/- 23 and 30 +/- 5 pg cDNA bound/100 micrograms pituitary DNA, respectively, in saline controls. GnRH pulse intervals of 15, 30, and 60 min resulted in elevated alpha and LH beta mRNAs (P less than 0.01) and maximum responses (4-fold, alpha; 3-fold, LH beta) were seen after the 30-min pulses. Acute LH release to the last GnRH pulse was seen after the 15-, 30-, and 60-min pulse intervals. In contrast, LH subunit mRNAs were not increased and acute LH release was markedly impaired after the rapid (7.5 min) or slower (120 and 240 min) pulse intervals. Equalization of total GnRH dose/48 h using the 7.5- and 240-min intervals did not increase LH subunit mRNAs to levels produced by the optimal 30-min interval. These data indicate that the frequency of the pulsatile GnRH stimulus regulates expression of alpha and LH beta mRNAs in male rats. Further, GnRH pulse frequencies that increase subunit mRNA concentrations are associated with continuing LH responsiveness to GnRH.

Animals↗
PubMed1986

Gonadotropin-releasing hormone differentially regulates expression of the genes for luteinizing hormone alpha and beta subunits in male rats.

Gonadotropin-releasing hormone (GnRH) and gonadal steroids regulate synthesis and release of luteinizing hormone (LH). GnRH is secreted intermittently by the hypothalamus, producing pulsatile LH release, and a pulsatile GnRH stimulus is required to maintain LH secretion. We report the regulatory effects of GnRH pulse injections on pituitary concentrations of LH alpha and beta subunit mRNAs in a castrated/testosterone-replaced male rat model. Replacement with physiologic amounts of testosterone decreased concentrations of both LH subunit mRNAs. GnRH pulse injections (10-250 ng per pulse given every 30 min for 48 hr) increased both mRNA concentrations, but the dose response patterns were markedly different. alpha subunit mRNA was increased by all GnRH doses but not the levels seen after castration alone. In contrast, LH beta subunit mRNA concentrations showed a marked dependence on GnRH dose. Maximal responses, to values similar to those in castrates, occurred after 25-ng GnRH pulses, and larger doses produced a smaller increase in LH beta subunit mRNA. Both the acute LH secretory response to GnRH and the number of GnRH receptors followed a pattern similar to the LH beta subunit mRNA concentration and were maximal after the 25-ng GnRH dose. These results show that GnRH can differentially regulate LH subunit mRNAs and suggest that concentrations of LH beta subunit mRNA may be a limiting factor in GnRH-stimulated LH release.

Animals↗