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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 577 records · Page 32Linked to original sources
PubMed1996

Race and gender differences in the association of Lp(a) with carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study.

The association of lipoprotein(a) [Lp(a)] with preclinical atherosclerotic disease is not well established in any race group, particularly African Americans. This report examined the association of Lp(a) with preclinical extracranial carotid atherosclerosis in middle-aged black and white participants in the Atherosclerosis Risk in Communities (ARIC) Study. Study participants (15 124: 2417 black women, 1522 black men, 5907 white women, and 5278 white men) who were 45 to 64 years old at baseline were examined during the period 1987 to 1989. Carotid intimal-medial far-wall thickness was determined by B-mode ultrasonography and expressed as the overall wall thickness mean at six sites to approximate atherosclerosis in the carotid system. Lp(a) was measured as its total protein component, Lp(a) protein, by a double-antibody ELISA for apolipoprotein(a) detection. Mean Lp(a) protein levels were higher in blacks than whites (169.1 and 147.0 microgram/mL in black women and black men, respectively, compared with 86.6 and 75.1 micrograms/mL in white women and white men). Mean carotid wall thickness (in millimeters) varied by race and gender: 0.798 in white men, 0.779 in black men, 0.718 in black women and 0.695 in white women. Multivariable-adjusted Lp(a) protein was independently associated with wall thickness (in millimeters) in white men and black men; among women, however, this association appeared to be stronger when smoking and diabetes were present. A 100-microgram/mL difference in Lp(a) protein was associated with 0.049- and 0.043-mm higher wall thickness values in black men and white men, respectively. Among white women who smoked, the difference in wall thickness was 0.051 mm compared with 0.032 mm for former/never smokers and 0.21 mm in black female diabetics compared with 0.031 mm in black female nondiabetics. These results suggest that Lp(a) is associated with preclinical carotid atherosclerosis in both blacks and whites, but that this association may be affected by the presence of other cardiovascular risk factors, particularly in women.

Age Factors↗
PubMed1996

The effects of extracting upper second permanent molars on lower second permanent molar position.

There is some controversy over whether the extraction of upper second permanent molars as part of orthodontic treatment leads to the over eruption of unopposed lower second permenent molars. A study was established to investigate the presence of any over-eruption in a group of subjects who had upper second permanent molars extracted as part of a previous course of orthodontic treatment. These subjects (the experimental group) were compared with a control group of subjects, matched for age and sex. Upper and lower impressions were taken, and the vertical positions of the posterior teeth were objectively assessed from the study models using the travelling microscope. Measurements from the study models showed that the distal aspect of the lower second permanent molar had over erupted in the experimental group when compared to the control (P < 0.001 right, P < 0.05 left). The degree of over-eruption was influenced on the mesial aspect by the distal position of the upper first permanent molar (P < 0.01), but the distal aspect was not. Eruption of the upper third molar did not affect the over-eruption of the lower second permanent molar in the experimental group. The majority of upper third molars had erupted at least 3 years since the upper second molars had been extracted, but the majority had erupted into an unfavourable contact position with the first permanent molar.

Adult↗
PubMed1996

Phase I trial of ZD1694, a new folate-based thymidylate synthase inhibitor, in patients with solid tumors.

PURPOSE: To perform a phase I clinical and pharmacologic study of ZD1694 (Tomudex, Alderley Park, United Kingdom), a new folate-based thymidylate synthase (TS) inhibitor, in patients with advanced malignancy. PATIENTS AND METHODS: From February 1991 to January 1993, 61 patients with a range of solid tumor received 161 courses of ZD1694 given as a single 15-minute intravenous infusion every 3 weeks, at escalating doses from 0.1 to 3.5 mg/m2. Pharmacokinetic (PK) analysis was performed with the first two courses of treatment. There were 33 men and 28 women with a median age of 53 years (range, 21 to 73). Fifty-five patients (90%) had previously received chemotherapy. RESULTS: Reversible liver toxicity and dose-related gastrointestinal (GI) and bone marrow toxicity occurred at > or = 1.6 mg/m2. Liver function usually returned to normal with repeated treatment, but GI and bone marrow toxicities generally became more severe. No renal toxicity was observed. The maximum-tolerated dose (MTD) was 3.5 mg/m2, at which, in addition to antiproliferative toxicities, four of six patients (67%) developed severe malaise that consisted of anorexia, nausea, and asthenia, with rapidly decreasing performance status that limited re-treatment. Abnormal liver function was also seen in four patients (67%). At 3.0 mg/m2, grades III and IV diarrhea were seen in six of 23 patients (26%) and grade IV myelosuppression in two others. Liver toxicity was self-limiting and not associated with severe malaise. Two patients had a partial response to treatment. PK analysis showed that plasma elimination was triexponential, with pronounced variability in the mean terminal half-life (t1/2gamma) for a given dose ranging from 8.2 to 105 hours. There was a linear relationship between dose and both the area under the concentration-time curve (AUC) and maximum concentration (Cmax), but no clear association between these parameters and response or toxicity. CONCLUSION: The dose of ZD1694 recommended for phase II trials is 3.0 mg/m2.

Adult↗
PubMed1996

MK-0677, a potent, novel, orally active growth hormone (GH) secretagogue: GH, insulin-like growth factor I, and other hormonal responses in beagles.

MK-0677, a spiroindoline sulfonamide, is a novel, orally active GH secretagogue. The effects of MK-0677 on serum GH and other hormones after oral and iv single dose administrations in beagles were evaluated. After oral administration in a balanced eight-dog crossover study, treatment with MK-0677 significantly increased peak GH concentrations, with a 5.3-fold increase (mean +/- SEM, 10.5 +/- 1.9 ng/ml) at the 0.25 mg/kg dose, a 9.0-fold increase (18.0 +/- 3.3 ng/ml) at the 0.50 mg/kg dose, and a 15.8-fold increase (31.6 +/- 5.8 ng/ml) at the 1.0 mg/kg dose. Total GH release, expressed as the area under the curve, showed similar significant increases over the effect of the water placebo. A single oral 1 mg/kg dose in three dogs induced a mean GH peak of 27.6 +/- 1.5 ng/ml at 120 min, and GH levels remained elevated up to 360 min after treatment. Insulin-like growth factor I (IGF-I) levels were significantly increased by 30% at 480 min after treatment. Cortisol levels were increased 2.4-fold over pretreatment levels. After i.v. administration, compared to the saline control group which had a mean (+/- SEM) serum GH peak of 3.8 +/- 0.7 ng/ml, MK-0677 at 0.25 mg/kg significantly increased (P < 0.05) peak GH concentrations 20.4-fold (77.4 +/- 13.7 ng/ml). Total GH release, expressed as the area under the curve, showed a similar increase. The mean peak GH level was recorded 10 min after treatment, with GH levels elevated up to 180 min after treatment. IGF-I levels were significantly elevated by 25% 360 min after the administration of MK-0677. Cortisol levels were increased 2.3-fold over pretreatment levels. Insulin and glucose levels were higher, LH and PRL levels were unaltered, and T4 levels were marginally lower; the levels of each of these hormones remained within the normal ranges for dogs throughout the experiment. In summary, MK-0677 is a potent GH secretagogue that induces an immediate, large, long lasting increase in GH levels when administered orally or i.v. In contrast to GH-releasing peptide-6 and benzolactam secretagogues, GH levels were elevated up to 360 min after treatment, and this was associated with a significant increase in IGF-I levels. Cortisol levels were increased; however, the increases were modest compared to those in GH.

Administration, Oral↗
PubMed1996

Nitric oxide regulation of corticotropin-releasing hormone release from the human perfused placenta in vitro.

We have investigated the regulatory role of nitric oxide (NO) in corticotropin-releasing hormone (CRH) release from the human perfused placental lobule in vitro. The effects of the NO donor sodium nitroprusside, the NO synthase inhibitor N omega-nitro-L-arginine, and the NO substrate L-arginine on human (h) placental CRH secretion have been studied. Single lobules of term placentae were bilaterally perfused with Krebs solution (5 mL/min; 95% O2-5% CO2; 37 C; pH 7.3). Fetal and maternal perfusates were collected at 4 C every 30 min for 3 h. CRH immunoreactivity (CRH-IR) in perfusates was measured by RIA using the 41-residue synthetic CRH as standard, 125I-labeled Tyr-hCRH as tracer, and a rabbit anti-CRH antibody Y2BO. The sensitivity of the assay was 0.13 pmol/L. Under basal conditions, human perfused placentae in vitro continuously secreted CRH-IR, which diluted in parallel to a synthetic hCRH-(1-41) standard curve. Size-exclusion chromatography of placental perfusates using a Sephadex G-50 column indicated that placental CRH-IR predominately coeluted with hCRH-(1-41) standard. Basal maternal perfusate CRH-IR levels (27 +/- 4 pmol/L) released from perfused placental lobules were nearly 10-fold greater than fetal perfusate CRH-IR levels (3.4 +/- 0.7 pmol/L; P < 0.05). Infusion of sodium nitroprusside (30-100 mumol/L) into the maternal and fetal placental circulations inhibited CRH-IR release into maternal perfusate in a concentration-dependent manner, but did not inhibit CRH-IR release into the fetal perfusate. N omega-nitro-L-arginine (100 mumol/L) increased placental CRH-IR secretion into fetal perfusate, and this effect was reversed by the infusion of L-arginine (100 mumol/L), which also reduced release below basal levels. In contrast, maternal perfusate CRH-IR levels were not affected by N omega-nitro-L-arginine or L-arginine. These results indicate that the human perfused placenta in vitro releases a substance of similar mol wt and hCRH-IR. Moreover, modulators of the NO signaling pathway differentially affect placental secretion of CRH-IR into the maternal and fetal perfusates. These data are consistent with the involvement of NO in the regulation of placental CRH release during pregnancy.

Adolescent↗
PubMed1996

Adrenocorticotropin causes vasodilatation in the human fetal-placental circulation.

During human pregnancy, ACTH is produced by both the placenta and fetal pituitary. ACTH has been shown to cause vasodilatation in the adrenal cortex in vitro. In this context we have investigated the vasoactive effects of ACTH in the human fetal-placental circulation. Single lobules of term human placentas were bilaterally perfused in vitro with Krebs solution (maternal and fetal, 5 mL/min; 95% O2-5% CO2; 37 C; pH 7.3), and changes in fetal placental arterial perfusion pressure (FAP) were measured. ACTH (40-4000 pmol/L; n = 5) caused a dose-dependent reduction of both KC1 and PGF2alpha-induced increases in FAP in the fetal placental circulation. The reductions were of a similar magnitude in the presence of either constrictor agent. ACTH was 187.4 (95% confidence limits, 162.7-215.9) times more potent than prostacyclin (PGI2; 1.2-1180 nmol/L; n = 6), which is a known vasodilator of the fetal-placental circulation. The threshold concentrations for ACTH and PGI2 were 40 pmol/L and 1.2 nmol/L, respectively. ACTH-induced reductions in PGF2alpha-induced increases in FAP in the fetal placental circulation were not inhibited by the nitric oxide synthase inhibitor, N omega-nitro-L-arginine (100 micromol/L; n = 5), the cyclooxygenase inhibitor indomethacin (3 micromol/L; n = 5), or a guanylate cyclase inhibitor LY83583(1 micromol/L; n = 5). The inhibitory effect of ACTH was attenuated by the antagonist, ACTH-(7-38) (240 pmol/L; n = 4), and a polyclonal ACTH antiserum (1:1000 dilution; n = 4). We have demonstrated that ACTH causes a reduction in fetal placental vascular resistance in the human fetal-placental circulation in vitro. The mechanism by which it exerts these effects has not been defined, but neither nitric oxide nor PG-mediated pathways appear to be involved.

Adrenocorticotropic Hormone↗
PubMed1996

Association of the mitochondrial 8344 MERRF mutation with maternally inherited spinocerebellar degeneration and Leigh disease.

We report previously undescribed or atypical clinical and biochemical manifestations of the mitochondrial DNA MERRF mutation at nucleotide 8344 in members of a multigenerational family with maternally inherited, highly variable neurodegenerative disorder. The more profound neurologic abnormalities include Leigh disease, spinocerebellar degeneration, and atypical Charcot-Marie-Tooth disease.

Adult↗
PubMed1996

Color Doppler imaging and transrectal sonography of the prostatic fossa after radical prostatectomy: early experience.

OBJECTIVE: Our objective was to determine if the addition of color Doppler imaging (CDI) during transrectal sonography can improve the detection of residual or recurrent prostatic cancer after radical prostatectomy. MATERIALS AND METHODS: Thirty patients who had undergone radical prostatectomy for prostatic cancer were evaluated with transrectal sonography and transrectal sonography with CDI. Twenty-three of these 30 patients were evaluated for suspicion of local tumor recurrence. The remaining seven patients were not suspected of harboring recurrent tumor and served as controls. Transrectal sonography and CDI-directed needle biopsies of the vesicourethral anastomosis (four-quadrant) and perianastomotic soft tissues were obtained in the 23 patients suspected of recurrent tumor. The ability of transrectal sonography to detect local tumor recurrence was compared with transrectal sonography with CDI. RESULTS: Fourteen of 23 patients (61%) had positive transrectal sonography or transrectal sonography and CDI-directed biopsies. Transrectal sonography alone detected grayscale abnormalities in 11 of 23 patients (48%), of whom 10 (43%) had positive transrectal sonography-directed biopsies. CDI during transrectal sonography showed hypervascularity in 12 of 23 patients (52%). Biopsies of these hypervascular regions were positive in all 12 patients (100%). Hypervascularity was detected in 10 of 11 (91%) gray-scale abnormalities initially detected with transrectal sonography alone. CDI during transrectal sonography detected two patients with hypervascular areas without associated gray-scale findings. Both patients had positive biopsies of their hypervascular sites. Transrectal sonography had a sensitivity and specificity of 71% and 89%, respectively, with positive and negative predictive values of 91% and 67%, respectively. CDI during transrectal sonography had a sensitivity and specificity of 86% and 100%, respectively, with positive and negative predictive values of 100% and 82%, respectively. CONCLUSION: CDI used during transrectal sonography improves the detection of early recurrent or residual prostatic cancer compared with transrectal sonography alone. Although most gray-scale abnormalities that are recurrent tumor show hypervascularity, CDI can detect additional tumor recurrences not identifiable with transrectal sonography alone.

Biopsy↗
PubMed1996

Long-term follow-up of older patients with iron deficiency anemia after a negative GI evaluation.

OBJECTIVE: To determine the clinical outcome of a cohort of patients over the age of 50 yr with iron deficiency anemia in whom a source was not identified during a prior GI evaluation. METHODS: A cohort of 69 patients (43 men, 26 women) with a mean age of 68 yr (range 50-89 yr) who previously had a negative GI evaluation for documented iron deficiency anemia was followed for an average of 39 months (range 2-89 months). RESULTS: In 49 patients (71%), the iron deficiency anemia resolved. All remained stable during the follow-up period except five patients in whom iron deficiency recurred (from 18 months to 5 yr later). Subsequent GI evaluations were negative, and iron deficiency resolved with iron supplementation in all five patients. In 16 patients (23%), a mild chronic anemia persisted during the follow-up period. None of these patients required transfusions, and 12 of the 16 had concomitant medical illnesses that likely contributed to an anemia of chronic disease. Only four patients (6%) had a persistent anemia severe enough to require intermittent transfusions. However, in three of these patients, the anemia was likely secondary to chronic disease (chronic renal failure in two patients, metastatic carcinoma in one patient). Therefore, only one patient (1%) had consistent iron deficiency anemia severe enough to require intermittent transfusions, which was found to be secondary to duodenal angiodysplasia during a subsequent GI evaluation. CONCLUSION: The prognosis of iron deficiency anemia in older patients after a negative GI evaluation is favorable. The anemia resolves and remains stable in the majority of patients after iron replacement. Subsequent GI evaluations should be reserved for those patients whose anemia is refractory to iron replacement and in whom there are not concomitant medical illnesses contributing to an anemia of chronic disease.

Aged↗
PubMed1996

Young black males and trauma: predisposing factors to presentation in an urban trauma unit.

Young black males are disproportionately represented as patients in trauma units. Unemployment, low educational level, and family composition may predispose young black males to trauma unit admission. To test this hypothesis, 300 males between the ages of 18 and 40 admitted to the Cook County Hospital Trauma Unit were surveyed with respect to demographic data, family composition, educational level, and employment background. The majority of patients were black (87%) and unemployed (68%). The most common diagnoses were penetrating trauma (53.2%) and assault (33.5%). Highest unemployment and lowest educational levels were found among patients who were victims of penetrating trauma or assault. Sixty-six percent reported the presence of an adult male in the household while growing up, and 93% reported the consistent presence of their biological mother. There was a significant correlation between race, trauma mechanism, unemployment, low educational level, and family composition. Recognition and amelioration of the economic and educational inequities that may exist in this population might reduce the incidence of trauma significantly.

Adolescent↗
PubMed1996

The management of HIV-positive pregnant women.

The chance of a baby born to an HIV-positive mother being HIV positive itself is 1 in 6. HIV infection cannot be diagnosed in utero. A diagnosis of HIV infection may not be excluded until the baby is 15 months old. There is no sound evidence that pregnancy worsens maternal HIV disease. The options of caesarean section and vaginal delivery are discussed but the decision does not need to be made until after 36 weeks. The risk of transmitting the virus in breastmilk should always be discussed and the mother advised to bottle feed. The prescribing of zidovudine needs full and informed explanation.

Aftercare↗
PubMed1996

The effect of urinary tract reconstruction on neurologically impaired women previously treated with an indwelling urethral catheter.

PURPOSE: We investigated the changes in sexuality and quality of life that evolve after lower urinary tract reconstruction in neurologically impaired women previously treated with an indwelling urethral catheter. MATERIALS AND METHODS: A total of 18 neurologically impaired women treated with an indwelling urethral catheter underwent bladder reconstruction. Pubovaginal sling urethral compression was required to restore perineal dryness in 13 patients and was the only operation required in conjunction with intermittent catheterization in 3. Eight patients underwent ileocystostomy, that is creation of a "bladder chimney," and 4 underwent augmentation cystoplasty with creation of a continent catheterizable stoma. In 3 patients ileocystoplasty alone with intermittent urethral catheterization was performed. All patients were followed 6 to 40 months (mean 18) after reconstructive surgery using a 9-part questionnaire to score numerically the effect of surgical reconstruction on sexuality and quality of life issues. RESULTS: On a scale of 0 (worst) to 5 (best) mean score for self-esteem improved from 1 preoperatively to 4 postoperatively, self-image from 1 to 4, sexual desire from 2 to 4 and ability to cope with disability from 1 to 4, respectively. In 4 of the 15 women who were sexually active preoperatively the frequency of sexual intercourse doubled from a mean of 3 to 6 times per month, respectively, and all 4 women reported improved sexual satisfaction. All 13 patients with pelvic pain and 5 with symptoms of autonomic dysreflexia noticed significant improvement if not complete resolution of the symptoms. CONCLUSIONS: Neurogenic lower urinary tract dysfunction treated with an indwelling urethral catheter is detrimental to sexuality and quality of life in neurologically impaired women. Urinary tract reconstruction restores not only quality of life but also sexuality by improving self-image, self-esteem and the ability to cope. Indwelling catheterization as a method of long-term urinary treatment should be avoided in women.

Adult↗
PubMed1996

Serological profiles of hepatitis B carrier patients in Singapore with special reference to the frequency and significance of concurrent presence of HBsAg and anti-HBs.

Hepatitis B serological markers were investigated in 1,132 consecutive Singaporean HBV carriers. Hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were found concurrently in 234 carriers (234/1132 or 21%). Serum anti-HBs levels were more than 10 mIU/mL in 80 of these carriers (80/234 or 34%). There were no difference in HBeAg positive status, as well as HBV-DNA positive status in concurrent HBsAg/anti-HBs carriers compared to carriers without anti-HBs. Our results suggested that concurrent HBsAg and anti-HBs is a common serologic pattern in Singaporean HBV carriers.

Adolescent↗
PubMed1995

Cervical cancer survival in a high risk urban population.

BACKGROUND: Cervical cancer remains an important public health problem, particularly for the urban minority population. To the authors' knowledge, determinants of cervical cancer survival have not been studied in this high risk population. METHODS: This study included all 158 women diagnosed and treated for invasive cervical cancer from January 1, 1986, through December 31, 1992, at the Grady Memorial Hospital and Clinics (Atlanta, GA). Medical records were abstracted to determine age at diagnosis, race, International Federation of Gynecology and Obstetrics (FIGO) clinical stage, treatment, and survival. Pathologic material was reviewed to confirm the diagnosis. RESULTS: Most patients (80%) were African American, and the stage distribution was similar for African American and white patients. Sixty-six (42%) had FIGO Stage I disease; 50%, Stage II or III; and 8%, Stage IV. Four-year actuarial survival differed significantly according to clinical stage (Ia = 94%, Ib = 79%, II = 39%, III = 26%, IV = 0%). Overall survival was lower for patients with glandular carcinomas than for those with squamous cell carcinomas (26% vs. 55%, P = 0.09). This difference was almost entirely due to increased mortality in patients with Stage Ib adenocarcinomas (53% vs. 88% for squamous cell carcinoma, Stage Ib, P = 0.03). CONCLUSIONS: The major prognostic markers for cervical cancer survival in this high risk patient population were clinical stage and histology, factors identical to those identified for other populations.

Black or African American↗
PubMed1995

Type 1 collagen synthesis by skin fibroblasts from 17 patients with osteogenesis imperfecta type III.

The aim of this study was to look for osteogenesis imperfecta (O.I.) specific features in collagen synthesised by skin fibroblast cultures obtained from patients with severe progressive deforming O.I. type III. Results from 17 O.I. type III cultures were contrasted with results from 6 relatives, 3 unrelated controls, 6 O.I. type II, 7 O.I. type IV and 7 O.I. type I cultures. Biosynthesised radiolabelled collagen types I and III were extracted and separated by gel electrophoresis as intact alpha chains or as cyanogen bromide digested peptides. Various abnormalities of type I collagen synthesis were detected in cultures from 13/17 O.I. type III patients. In conclusion, synthesised collagen abnormalities were detected in cells from most O.I. type III patients studied and were O.I.-specific, not O.I. type III-specific at the individual level. However, the frequency of detection of these features was partially specific to the O.I. type III phenotype.

Adolescent↗