Biomedical subjects

N Shah

Publications and source records attributed to N Shah.

At least 73 records · Page 4Linked to original sources

PubMed2001

Characterization of reentrant circuit in macroreentrant right atrial tachycardia after surgical repair of congenital heart disease: isolated channels between scars allow "focal" ablation.

BACKGROUND: The purpose of this study was to characterize the circuit of macroreentrant right atrial tachycardia (MacroAT) in patients after surgical repair of congenital heart disease (SR-CHD). METHODS AND RESULTS: Sixteen patients with atrial tachycardia (AT) after SR-CHD were studied (atrial septal defect in 6, tetralogy of Fallot in 4, and Fontan procedure in 6). Electroanatomic right atrial maps were obtained during 15 MacroATs in 13 patients, focal AT in 1 patient, and atrial pacing in 2 patients without stable AT. A large area of low bipolar voltage (</=0.5 mV) involved most of the free wall in all patients and contained 2 to 7 dense scars or lines of double potentials, forming 29 narrow channels (width </=2.7 cm) between scars in all but 1 patient, who had a single scar and only focal AT. All 15 MacroATs were propagated through narrow channels. Ablation within the channel eliminated all 15 MacroATs with 1 to 3 (median 1) radiofrequency applications. Ablation was performed in 9 other channels identified during MacroAT (5 patients) and in 5 channels identified during atrial pacing (2 patients). Conduction block was obtained across 28 of 29 channels. After ablation, reproducible sustained right AT was not induced in any patient. During follow-up (median 13.5 months), new MacroATs, atrial fibrillation, or palpitations occurred in 3 of 16 patients. CONCLUSIONS: MacroAT after SR-CHD requires a large area of low voltage containing >/=2 scars forming narrow channels. Ablation within the channels eliminates MacroAT.

Adult↗

PubMed2001

Effect of serial passage on gene expression in MC3T3-E1 preosteoblastic cells: a microarray study.

The osteoblastic function of mouse preosteoblastic MC3T3-E1 cells, as measured by alkaline phosphatase activity and osteocalcin secretion, decreases after serial passage. To uncover genes responsible for decreased osteoblastic function in high-passage cells, we have studied passage-dependent change of gene expression in MC3T3-E1 cells. Changes in the expression pattern of 2000 selected genes were examined simultaneously by comparing mRNA levels between MC3T3-E1 cells at passage 20 and passage 60 using the cDNA microarray analysis. Significant changes in the steady-state abundance of 27 mRNAs were observed in response to different passage numbers, including 17 known genes, 4 ESTs with homology to known genes, and 6 genes with no previously described function or homology. Northern blot analysis was used to verify and quantify the expression of selected genes, and revealed a significant higher level of up- and down-regulation compared to microarray data. These results indicate the existence of a significant change in gene expression in osteoblastic cells undergoing serial passages. Such changes might be responsible for a reduction in bone regeneration in older osteoblasts. Potential roles of selected genes in bone aging are discussed.

Aging↗

PubMed2001

Sources of absorption and scattering contrast for near-infrared optical mammography.

RATIONALE AND OBJECTIVES: Near-infrared (NIR) diffuse optical spectroscopy and imaging may enhance existing technologies for breast cancer screening, diagnosis, and treatment. NIR techniques are based on sensitive, quantitative measurements of functional contrast between healthy and diseased tissue. In this study, the authors quantified the origins of this contrast in healthy breasts. MATERIALS AND METHODS: A seven-wavelength frequency-domain photon migration probe was used to perform noninvasive NIR measurements in the breasts of 28 healthy women, both pre- and postmenopausal, aged 18-64 years. A diffusive model of light transport quantified oxygenated and deoxygenated hemoglobin, water, and lipid by their absorption signatures. Changes in the measured light-scattering spectra were quantified by means of a "scatter power" parameter. RESULTS: Substantial quantitative differences were observed in both absorption and scattering spectra of breast as a function of subject age. These physiologic changes were consistent with long-term hormone-dependent transformations that occur in breast. Instrument response was not adversely affected by subject age or menopausal status. CONCLUSION: These measurements provide new insight into endogenous optical absorption and scattering contrast mechanisms and have important implications for the development of optical mammography. NIR spectroscopy yields quantitative functional information that cannot be obtained with other noninvasive radiologic techniques.

Absorption↗

PubMed2001

Neurophysiological regulation and target-tissue impact of the pulsatile mode of growth hormone secretion in the human.

Neuroendocrine axes function as an ensemble of regulatory loci which communicate and maintain homeostasis via time-delayed blood-borne signals. The growth hormone (GH)-insulin-like growth factor I (IGF-I) feedback axis sustains a vividly pulsatile mode of interglandular signalling. Pulsatility is driven jointly by hypothalamic GH-releasing hormone (GHRH) and GH-releasing peptide (GHRP), and modulated by somatostatinergic restraint. Paradoxically, intermittent somatostatin inputs also facilitate somatotrope-cell responses to recurrent secretagogue stimuli, thereby amplifying pulsatile GH secretion. A concurrent low basal (8-12% of normal total) rate of GH release is controlled positively by GHRH and GHRP and negatively by somatostatin. Sex-steroid hormones (such as oestradiol and aromatizable androgen) and normal female and male puberty augment GH secretory-burst mass 1.8- to 3.5-fold, whereas ageing, relative obesity, physical inactivity, hypogonadism, and hypopituitarism mute the amplitude/mass of pulsatile GH output. An abrupt rise in circulating GH concentration stimulates rapid internalization of the GH receptor in peripheral target tissues, and evokes second-messenger nuclear signalling via the STAT 5b pathway. Discrete GH peaks stimulate linear (skeletal) growth and drive muscle IGF-I gene expression more effectually than basal (time-invariant) GH exposure. A brief pulse of GH can saturate the plasma GH-binding protein system and achieve prolonged plasma GH concentrations by convolution with peripheral distribution and clearance mechanisms. A single burst of GH secretion also feeds back after a short latency on central nervous system (CNS) regulatory centres via specific brain GH receptors to activate somatostatinergic and reciprocally subdue GHRH outflow. This autoregulatory loop probably contributes to the time-dependent physiologically pulsatile dynamics of the GH axis. More slowly varying systemic IGF-I concentrations may also damp GH secretory pulse amplitude by delayed negative-feedback actions. According to this simplified construct, GH pulsatility emerges due to time-ordered multivalent interfaces among GHRH/GHRP feedforward and somatostatin, GH and IGF-I feedback signals. Resultant GH pulses trigger tissue-specific gene expression, thereby promoting skeletal and muscular growth, metabolic and body compositional adaptations, and CNS reactions that jointly maintain health and homeostasis.

Aging↗

PubMed2001

Transseptal left heart catheterization for cardiac ablation procedures.

UNLABELLED: Transseptal left heart catheterization has been performed as an alternative to the retrograde approach since 1958. However, this procedure can result in life-threatening complications, some of which may occur because of insufficient anatomical landmarks. Accordingly, we sought to assess the safety and efficacy of a new transseptal left heart catheterization technique designed for ablation procedures. Specifically, we examined whether electrode catheters could be used as anatomical landmarks, permitting identification of the aortic root and other critical structures. RESULTS: One hundred and eight consecutive patients underwent transseptal left heart catheterization under biplane fluoroscopy during catheter ablation. Electrode catheters positioned in the right atrial appendage, His bundle region, and coronary sinus were used as anatomical landmarks to guide the transseptal unit to the fossa ovalis. The angles of the right anterior and left anterior oblique projections were selected in each patient based on the orientation of the His bundle and coronary sinus catheters. Transseptal left heart catheterization was successfully performed in all patients without complications. In contrast to previous reports, the direction of the needle at the successful puncture site in the last 96 patients varied substantially: 2 o'clock in 13 patients (13 %); 3 o'clock in 43 patients (45 %); and 4 o'clock in 40 patients (42 %). CONCLUSION: The use of electrode catheters as anatomical landmarks and biplane fluoroscopy facilitates transseptal catheterization. This approach can be used safely during catheter ablation procedures.

Adolescent↗

PubMed2001

Accuracy of outpatient endometrial biopsy in the diagnosis of endometrial hyperplasia.

BACKGROUND: To determine the accuracy of outpatient endometrial biopsy in diagnosing endometrial hyperplasia in women with abnormal uterine bleeding. DESIGN: Systematic quantitative review of published medical literature. DATA SOURCES: Relevant papers were identified through electronic scanning of MEDLINE (1980-1999) and EMBASE (1980-1999), manual searching of bibliography of known primary and review articles and contact with manufacturers. REVIEW METHODS: Studies were selected if accuracy of outpatient endometrial biopsy, in women with abnormal pre or postmenopausal uterine bleeding, was estimated compared to a reference standard, which was endometrial histology obtained by tissue sampling under anesthesia. Quality assessment and data extraction were performed in duplicate. Diagnostic accuracy was determined by pooled likelihood ratios (LR) for positive and negative test results for endometrial hyperplasia. RESULTS: There were 881 subjects in 8 diagnostic evaluations reported in 6 primary studies. Postmenopausal women represented 25% of the participants studied. There were 43 patients in whom outpatient sampling was inadequate. A positive test result on outpatient biopsy diagnosed endometrial hyperplasia with a pooled LR of 12.0 (95% CI 7.8-18.6) while a negative test result had a pooled LR of 0.2 (95% CI 0.1-0.3). With a positive test result, the posttest probability of endometrial hyperplasia was 57.7% (95% CI 41.1%-72.7%) while it was 2.2% (95% CI 0.9%-4.1%) with a negative test. CONCLUSION: Outpatient endometrial biopsy has modest accuracy in diagnosing endometrial hyperplasia. Therefore, additional endometrial assessment should be undertaken, especially if symptoms persist or intrauterine structural abnormalities are suspected.

Ambulatory Care↗

PubMed2001

Vesico-ureteric reflux in adults with neuropathic bladders treated with Polydimethylsiloxane (Macroplastique).

OBJECTIVE: To establish the efficacy of Macroplastique in treating vesico-ureteric reflux (VUR) in adults with neuropathic bladder dysfunction. PATIENTS AND METHODS: Fifteen patients (12 male and three female), age range 19 to 80 years (mean age 38) were included in this study. Diagnosis was confirmed by videourodynamics. In seven patients reflux was present bilaterally. Twenty-two refluxing ureters were treated. Twelve patients had detrusor hyper-reflexia, two had areflexic bladders and one had loss of bladder wall compliance. According to the International Grading System, 10 ureters had grade IV reflux, five had grade III reflux, five had grade II reflux, and two had grade I reflux. Macroplastique (0.5-1.5 ml) was injected submucosally under each ureteric orifice to convert the opening to a slit like shape. The patients were followed up from 9 to 68 months. RESULTS: VUR was completely resolved in 72.7% (16) ureters following a single injection and in a further 4.5% (1) ureter following a second injection. 9.1% (2) ureters were improved and treatment failed in 13.7% (3) ureters. Two patients showed a recurrence of reflux 1 and 4 years after primary injection and subsequently had a curative second injection. Most of the patients in whom VUR was cured or improved showed a reduction in laboratory proven urinary infection rates. CONCLUSION: Macroplastique produced an excellent result (86% with complete resolution or improvement of reflux) in treating VUR in adult neuropathic bladders. This is comparable to larger studies carried out on the paediatric population. This is an easy procedure, which avoids major surgery and can be performed as a day case. In cases of failure or recurrence, repeat injection or open surgery can be undertaken without any added complications.

Adult↗

PubMed2001

Intranasal tooth as a complication of cleft lip and alveolus in a four year old child: case report and literature review.

Ectopic position of teeth is not rare. The presence of teeth have been reported in ovaries, testes, anterior mediastinum, and pre-sacral regions. In the maxillofacial region, teeth have been found in maxillary sinus, mandibular condyle, coronoid process, chin, nose, and even orbit. Approximately 50 cases of a tooth in the nasal cavity have been reported in literature. However, an intranasal tooth in cases of cleft lip and palate is comparatively rare. Intranasal teeth can cause problems such as nasal obstruction, chronic rhinorrhea and speech problems. Sometimes however, they are totally symptom-free. We present here an interesting case of an intranasal tooth in a four year-old-boy, who was operated on for cleft lip and alveolus at 6 months of age. The intranasal tooth did not cause any symptoms. The tooth was extracted under general anaesthesia when it was found to be very loosely attached to the nasal mucosa. The case is discussed in the light of relevant literature on intranasal teeth in cases of cleft lip and palate.

Child, Preschool↗

PubMed2001

Highly active antiretroviral therapy associated with improved anemia among HIV-infected women.

Anemia is common during human immunodeficiency virus (HIV) infection and is associated with increased mortality. We conducted a study to examine the impact of highly active antiretroviral therapy (HAART) on anemia in a multicenter cohort of HIV-positive women, the Human Immunodeficiency Virus Epidemiology Research (HER) Study. Among women receiving HAART (n = 188), non-HAART monotherapy or combination antiretroviral therapy (ART) (n = 111), or who had no reported treatment (n = 62), the prevalence of anemia (hemoglobin, <120 g/L) at baseline was 38.3, 36.9, and 43.6%, respectively (p = 0.58) and at 1-year follow-up was 26.1%, 36.9%, 45.2%, respectively (p = 0.01); mean hemoglobin at baseline was 125 +/- 16, 122 +/- 16, and 122 +/- 18 g/L, respectively (p = 0.29) and at 1-year follow-up was 128 +/- 14, 123 +/- 16, and 119 +/- 20 g/L, respectively (p < 0.0001). Adjusted linear regression models showed that HAART was associated with an increase of hemoglobin of 0.20 g/L per month (p = 0.007). After 1 year of treatment, HAART was associated with a 32% reduction in anemia among HIV-infected women (p = 0.01), whereas there was no significant change in the prevalence of anemia among those on non-HAART ART or those who had no reported treatment. HAART is associated with a large reduction in anemia among HIV-infected women.

Adult↗

PubMed2001

Fas-mediated apoptosis of neutrophils in sera of patients with infection.

In the presence of infection, neutropenia is considered to be a marker of poor prognosis; conversely, neutrophilia may not be a determinant of a better prognosis. Since apoptotic neutrophils are compromised functionally, we evaluated the effect of infection on neutrophil apoptosis. The rate of apoptosis was greater for neutrophils isolated from patients with infection than for healthy controls. Escherichia coli did not directly modulate the rate of neutrophil apoptosis. However, sera from infected patients promoted (P < 0.001) neutrophil apoptosis. Interestingly, the sera of patients with different types of infection (gram negative, gram positive, or culture negative) exerted a more or less identical response on neutrophil apoptosis. Sera of infected patients showed a fivefold greater content of FasL compared to controls. Moreover, anti-FasL antibody partly attenuated the infected-serum-induced neutrophil apoptosis. In in vitro studies, E. coli enhanced monocyte FasL expression. Moreover, conditioned media prepared from activated macrophages from control mice showed enhanced apoptosis of human as well as mouse neutrophils. On the contrary, conditioned media prepared from activated macrophages isolated from FasL-deficient mice induced only a mild degree of neutrophil apoptosis. These results suggest that neutrophils in patients with infection undergo apoptosis at an accelerated rate. Infection not only promoted monocyte expression of FasL but also increased FasL content of the serum. Because the functional status of apoptotic cells is compromised, a significant number of neutrophils may not be participating in the body's defense. Since neutrophils play the most important role in innate immunity, their compromised status in the presence of infection may transfer the host defense burden from an innate response to acquired immunity. The present study provides some insight into the lack of correlation between neutrophilia and the outcome of infection.

Adult↗

PubMed2001

GLI-2 modulates retroviral gene expression.

GLI proteins are involved in the development of mice, humans, zebrafish, Caenorhabditis elegans, Xenopus, and Drosophila. While these zinc finger-containing proteins bind to TG-rich promoter elements and are known to regulate gene expression in C. elegans and Drosophila, mechanistic understanding of how regulation is mediated through naturally occurring transcriptional promoters is lacking. One isoform of human GLI-2 appears to be identical to a factor previously called Tax helper protein (THP), thus named due to its ability to interact with a TG-rich element in the human T-lymphotropic virus type 1 (HTLV-1) enhancer thought to mediate transcriptional stimulation by the Tax protein of HTLV-1. We now demonstrate that, working through its TG-rich binding site and adjacent elements, GLI-2/THP actually suppresses gene expression driven by the HTLV-1 promoter. GLI-2/THP has no effect on the HTLV-2 promoter, activates expression from the promoters of human immunodeficiency virus types 1 and (HIV-1 and -2), and stimulates HIV-1 replication. Both effective suppression and activation of gene expression and viral replication require the first of the five zinc fingers, which is not necessary for DNA binding, to be intact. Thus, not only can GLI-2/THP either activate or suppress gene expression, depending on the promoter, but the same domain (first zinc finger) mediates both effects. These findings suggest a role for GLI-2 in retroviral gene regulation and shed further light on the mechanisms by which GLI proteins regulate naturally occurring promoters.

Animals↗

PubMed2001

Diagnosis of human papillomavirus infection by dry vaginal swabs in military women.

OBJECTIVE: Human papillomavirus (HPV) assays are likely to be used with increasing frequency in clinical management of women with abnormal Papanicolaou smears and in cervical cancer screening. Our objective was to simplify the method of collection of female genital tract specimens. The utility of vaginal dry swabs for HPV diagnosis was evaluated. METHODS: Specimens for cytology and for HPV identification were collected by a clinician from 189 female soldiers attending a military clinic. Three methods of specimen collection for HPV identification were compared: a vaginal dry swab (v-DRY), and vaginal and cervical swabs placed into specimen transport medium (v-STM and c-STM). Swabs were shipped to a STD laboratory for processing. Specific HPV types were identified by a consensus primer based PCR based method. Results from 165 women were evaluable. RESULTS: HPV prevalence by the three methods was similar and ranged from 44.8% to 50.9%. 53 (32.1%) women were HPV positive and 60 (36.4%) women were HPV negative by all three collection methods. With respect to the risk categories of specific HPV types, there was greater agreement between the results from the two vaginal (v-DRY and v-STM) samples (kappa values of 0.69-0.81) than between the cervical (c-STM) and either of the vaginal samples (kappa values of 0.37-0.55). The HPV yield from c-STM was somewhat greater than that from the vaginal specimens but the correlation between cytological abnormalities and HPV was high for all three methods. CONCLUSION: A dry vaginal swab may be an acceptable method of specimen collection for HPV diagnosis.

Adolescent↗

PubMed2001

Short-term estradiol supplementation augments growth hormone (GH) secretory responsiveness to dose-varying GH-releasing peptide infusions in healthy postmenopausal women.

Estrogen is a prominent stimulus to GH secretion throughout the human life span, albeit via neuroendocrine mechanisms that are incompletely defined. Here, we test the hypothesis that estradiol replacement in postmenopausal women enhances the responsiveness of the hypothalamo-pituitary unit to the GH-releasing effect of GH-releasing peptide-2 (GHRP-2). GHRP-2 is a potent and selective synthetic hexapeptide capable of activating an endogenous GHRP receptor/effector pathway, for which a (3)Ser-octanoylated 28-amino acid ligand was cloned recently. To examine this postulate, we studied 10 healthy estrogen-withdrawn postmenopausal women, who were given oral placebo or estrogen supplementation [1 mg micronized 17 beta-estradiol (E(2)) twice daily for 7-15 days] in a patient-blinded, prospective, randomized, and within-subject cross-over design. The GH-releasing actions of five semilogarithmically increasing doses of GHRP-2 (absolute range, 0.03-3 microg/kg by bolus iv infusion) vs. saline were evaluated by frequent blood sampling on separate days in the morning while fasting. Serum GH concentrations were determined in blood sampled every 10 min using an ultrasensitive chemiluminescence assay and analyzed by multiparameter deconvolution to calculate the summed mass of GH secreted during the 2-h interval after bolus GHRP-2 infusion. Logarithmically transformed secretory responses were compared across the different dosages of infused GHRP-2 by two-way repeated measures ANOVA. Estradiol replacement increased the global mean (+/-SEM) serum E(2) concentration from 15 +/- 0.8 to 470 +/- 17 pg/mL (55 +/- 2.9 to 1725 +/- 62 pmol/L; P = 0.004) and lowered insulin-like growth factor I levels by approximately 27% (P = 0.087). Administration of E(2) elevated the geometric mean basal (saline-infused) GH secretory burst mass by 2.1-fold (95% confidence interval, 1.4- to 3.1-fold) compared with placebo ingestion (geometric mean ratios; P < 0.001). E(2) exposure enhanced the efficacy of the highest GHRP-2 dose tested (3 microg/kg) by 2.1-fold (1.3- to 3.3-fold; P = 0.010). Compared with the effect of placebo and saline, E(2) combined with the highest dose of GHRP-2 stimulated GH secretory burst mass by a total of 31-fold (24- to 41-fold; P < 0.001). Random coefficient regression analysis of the relationship between the logarithm of GHRP-2 dose and GH secretory burst mass revealed that E(2) significantly augmented the amount of GH secreted per unit GHRP-2 dose (E(2), 16.6 +/- 1.8 slope units; placebo, 10.1 +/- 1.4 slope units; P = 0.03). Although the global mean endogenous GH half-life did not differ between the E(2) and placebo sessions (E(2), 18 +/- 0.6 min; placebo, 17 +/- 0.5 min), GH half-life varied directly with dose of GHRP-2 (and, hence, the mean serum GH concentration) in both the E(2) and placebo sessions (test of zero slope hypothesis, P = 0.0018). The deconvolved GH secretory burst peaked within 8-13 min of the bolus iv injection of GHRP-2, and this latency was not altered by E(2). Based on a mixed effects analysis of covariance model, GHRP-2 dose and E(2), but not the plasma insulin-like growth factor I concentration, determined the magnitude of the GH secretory response (P < 0.001). We conclude that short-term oral E(2) repletion in postmenopausal women selectively augments GH secretory pulse mass, enhances the steepness of the GHRP-2 dose-GH secretory response relationship (greater sensitivity), and heightens the maximal GH secretory response to the highest dose of GHRP-2 tested (greater efficacy). These data point to a facilitative interaction between E(2) and the GHRP receptor/effector pathway in driving the mass of GH secreted per burst.

Aged↗

PubMed2001

Short-term estradiol replacement in postmenopausal women selectively mutes somatostatin's dose-dependent inhibition of fasting growth hormone secretion.

How estradiol stimulates pulsatile GH secretion in the human is not well understood. Here, we test the clinical hypothesis that estradiol stimulates GH secretion, in part, by opposing somatostatin's inhibition of GH release. To this end, 13 estrogen-withdrawn postmenopausal women received placebo or 1 mg micronized estradiol-17beta orally, twice daily for 14 days, in a prospectively randomized, patient-blinded, within-subject cross-over design. For each intervention, the dose-dependent suppressive actions of somatostatin were evaluated by infusing 0 (saline), 3, 10, 30, 100, or 300 microg/1.73 m(2).h somatostatin-14 continuously, iv, for 3 h, on separate mornings, in the fasting state, 48 h apart. Blood was sampled at 10-min intervals for 2 h before, for 3 h concurrently with, and for 1 h after each infusion. Serum GH concentrations were quantitated in an ultrasensitive chemiluminescence-based assay (detection threshold, 0.005 microg/L). In the estrogen-deficient milieu, constant iv somatostatin infusions inhibited steady-state serum GH concentrations (valley mean during the last 60 min of the infusion interval) in a dose-dependent manner (P < 10(-4) interventional effect). Maximally effective doses of somatostatin reduced the latter by 89 +/- 6.1% (mean +/- SEM) below the subject-specific preinfusion baseline. Estrogen administration increased the serum estradiol concentration from 12 +/- 1 to 245 +/- 35 pg/mL [42 +/- 4 to 920 +/- 110 pmol/L] (P < 10(-4)); decreased serum concentrations of LH (P = 0.018), FSH (P < 10(-4)), and insulin-like growth factor-I (P = 0.003); and elevated the fasting (6-h mean) serum GH concentration from 0.41 +/- 0.07 to 0.87 +/- 0.27 (P = 0.011). Estradiol supplementation did not alter somatostatin's maximal suppression of GH by 89 +/- 4.7% (P < 10(-4) below subject-specific preinfusion baseline), thus signifying unchanging somatostatin efficacy. In contrast, estradiol replacement significantly elevated the half-maximally inhibitory dose of infused somatostatin by 13.5-fold, from 0.43 (0.38-0.48, 95% group statistical confidence intervals) (placebo) to 6.0 (5.2-7.0) (estradiol) microg/1.73 m(2)/h (P < 10(-4)), denoting muting of somatostatin's inhibitory potency. The latter inference was confirmed by a concomitant 4-fold decrease in the exponential steepness of the somatostatin inhibitory dose-response function; viz., mean 1.42 (1.49 to 1.33) (placebo) vs. 0.34 (0.62 to 0.26) (estradiol) slope units (P < 10(-4)). The foregoing effects were specific, because estrogen did not alter somatostatin's dose-dependent enhancement (P < 10(-4)) of the orderliness of GH release patterns, as quantitated via the approximate entropy regularity statistic. In summary, short-term replacement of estradiol to midfollicular phase levels in postmenopausal women selectively reduces the potency, but not the efficacy, of somatostatin's dose-dependent inhibition of GH release. Estrogen supplementation does not modify somatostatin's reciprocal enhancement of the quantifiable orderliness (approximate entropy) of the GH secretory process. Accordingly, we postulate that estradiol can facilitate pulsatile GH secretion, in part, by opposing the repressive actions of somatostatin.

Cross-Over Studies↗

PubMed2001

Geriatric oral health issues in India.

An overview of the demographics and oral health status of the elderly population of India is presented. India is a vast country with a population of one billion people. Of this, people older than 60 years constitute 7.6%, which in actual number is 76 million. There are several factors that affect the oral health of elderly. The dentist:population ratio is 1:27,000 in urban areas and 1:300,000 in rural areas, whereas 80% of the elderly population reside in rural India. Forty per cent of the elderly live below the poverty line and 73% are illiterate. Ninety per cent of the elderly have no social security and the dependency ratio is 12.26. Incidence of oral cancer, which is considered an old-age disease, is highest in India, 13.5% of all body cancers are oral cancers. Preventive dental care is almost nonexistent to the rural masses and very limited in urban areas. Above all, there is no orientation of dental graduates towards the special needs of the geriatric population. Recommendations include: the establishment of Continuing Dental Education programmes on geriatric oral care; inclusion of a geriatric component in undergraduate and postgraduate curricula; initiation of a diploma, certificate and degree courses in geriatric dentistry; research on various aspects of ageing and age-related oral health problems; provision of preventive and curative treatment for various oral diseases to the elderly.

Aged↗

PubMed2001

Effect of flurbiprofen on hind-limb suspension-induced bone loss.

BACKGROUND: Prostaglandins, specifically prostaglandin E2 (PGE2), may be involved in the bone loss that occurs in microgravity. Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), has been shown to increase periosteal apposition rate in rats, and may inhibit bone loss by decreasing PGE2 concentrations. METHODS: A hind-limb suspension (HLS) technique was used to determine if FBP could attenuate the bone demineralization that occurs with decreased load-bearing activity. Rats were assigned to either the HLS group or the ground-based (control) group. Both of these groups were then divided into drug-treated and control subgroups (n = 10). Rats in the drug group received FBP 2 mg x kg(-1) x d(-1) subcutaneously. Study data were collected at 2 and 4 wk. The left femur of each animal was used for densitometry, and the right tibia was processed for histomorphometry. Mechanical properties of the left femur were assessed by three-point bending. RESULTS: After 2 wk, the FBP-treated rats in both the HLS and ground-based groups had 6% less bone mineral density (BMD) than did controls (p < 0.05). FBP was not effective in protecting bone from the early stages of disuse osteopenia. At 4 wk, BMD in the ground-based group was not significantly different between control and drug animals. However, in the HLS group, BMD was 11% greater in the FBP-treated group than in the control group (p < 0.05). FBP did not significantly affect the mechanical properties of bone at either 2 or 4 wk. CONCLUSION: FBP may not only affect bone demineralization by interacting with existing osteoclasts, but may also interfere with the signaling, activation, and recruitment of osteoclasts that occur after skeletal unloading.

Animals↗

PubMed2000

Gonadal hormone levels in injection drug users.

Levels of serum sex hormones, particularly testosterone, luteinizing hormone, and follicle-stimulating hormone, have been shown to change in various disease states. Hypogonadism has been well-documented in patients with HIV infection. As HIV infection and injection drug use are closely linked, we examined whether injection drug users (IDU's) exhibit hormone abnormalities. We evaluated men participating in the ALIVE study (AIDS Linked to Intravenous Experiences), a large cohort study conducted in Baltimore, MD. We found that 20% of 40 IDU subjects (20 HIV+, 20 HIV-) with a mean age 41.5+/-0.9, had low serum total testosterone concentration. We were unable to detect a direct correlation between drug use and hormone levels. Further study is needed on the hormonal milieu of the IDU patient.

Adult↗

PubMed2000

Randomized, controlled trials, observational studies, and the hierarchy of research designs.

BACKGROUND: In the hierarchy of research designs, the results of randomized, controlled trials are considered to be evidence of the highest grade, whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects. We used published meta-analyses to identify randomized clinical trials and observational studies that examined the same clinical topics. We then compared the results of the original reports according to the type of research design. METHODS: A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of randomized, controlled trials and meta-analyses of either cohort or case-control studies that assessed the same intervention. For each of five topics, summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual randomized, controlled trials and the individual observational studies. RESULTS: For the five clinical topics and 99 reports evaluated, the average results of the observational studies were remarkably similar to those of the randomized, controlled trials. For example, analysis of 13 randomized, controlled trials of the effectiveness of bacille Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 (95 percent confidence interval, 0.34 to 0.70) among vaccinated patients, as compared with an odds ratio of 0.50 (95 percent confidence interval, 0.39 to 0.65) from 10 case-control studies. In addition, the range of the point estimates for the effect of vaccination was wider for the randomized, controlled trials (0.20 to 1.56) than for the observational studies (0.17 to 0.84). CONCLUSIONS: The results of well-designed observational studies (with either a cohort or a case-control design) do not systematically overestimate the magnitude of the effects of treatment as compared with those in randomized, controlled trials on the same topic.

Anticholesteremic Agents↗