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Biomedical subjects

J Hannah

Publications and source records attributed to J Hannah.

At least 19 recordsLinked to original sources

Effects of obesity and body fat distribution on lipids and lipoproteins in nondiabetic American Indians: The Strong Heart Study.

OBJECTIVES: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. RESEARCH METHODS AND PROCEDURES: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/ lipoproteins. RESULTS: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m2) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m2), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = -0.24, p < 0.001). There was a significant but weak relation with apoAI (r = -0.14, p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14, p < 0.001) and negatively related to HDL cholesterol (r = -0.23, p < 0.001) and apoAI (r = -0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = -0.35, p < 0.001) and apoAI (r = -0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = -0.36, p < 0.001). In both women and men there was an inverted U-shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (-1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (-0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. DISCUSSION: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.

Adipose Tissue↗

Long-term calorie restriction reduces energy expenditure in aging monkeys.

Calorie restriction to produce stable long-term adult body weight for approximately 10 years prevents obesity and diabetes in middle-aged rhesus monkeys. To determine whether this dietary regimen also alters energy metabolism, the doubly labeled water method was used to measure total daily energy expenditure. Six adult male rhesus monkeys, which had been calorie-restricted for more than 10 years, were compared to 8 control adult monkeys, which had been fed ad libitum for their entire lives. The calorie-restricted monkeys weighed less than the ad-libitum fed monkeys and had a lower lean body mass and lower fat mass. Total daily energy expenditure was lower in the calorie-restricted than in the ad-libitum fed monkeys, even when corrected for differences in body size using body weight (563 +/- 64 vs 780 +/- 53 kcal/d; p < .04), surface area (547 +/- 67 vs 793 +/- 56 kcal/d; p < .05), or lean body mass (535 +/- 66 vs 801 +/- 54 kcal/d; p < .02) as covariates. Thyroxine (T4) was reduced and the free thyroxine index was suggestively lower in the calorie-restricted monkeys whereas triiodothyronine (T3) was not significantly different. Activity in calorie-restricted monkeys was similar to that of a weight-matched younger adult comparison group. We conclude that the process of preventing obesity by long-term caloric restriction causes a significant and sustained long-term reduction in energy expenditure, even when corrected for lean body mass.

Adipose Tissue↗

Intubation via the LMA using a Cook retrograde intubation kit.

PURPOSE: We report two cases of difficult intubation where a laryngeal mask airway (LMA) was used and changed to a conventional endotracheal tube using a retrograde intubation set. CLINICAL FINDINGS: In two patients, following induction of anaesthesia, the trachea could not be intubated in the conventional fashion with a blade. In both patients an LMA was inserted to achieve an airway. In both patients intubation with a conventional endotracheal tube was required. A Cook Retrograde Intubation Kit and fibreoptic bronchoscope were used to change the LMA to conventional endotracheal tube without problems. CONCLUSION: The Cook retrograde intubation allows an LMA to be replaced with an endotracheal tube with an ID greater than 6 mm with a #3 or 7 mm with a #5 LMA. This technique places an exchange stylet into the airway which is superior to a conventional guidewire. This method allows the airway to be maintained until the LMA is exchanged with an endotracheal tube. Anaesthesia may be maintained and the airway instrumented without difficulty using this technique.

Adult↗

Dietary fish oil decreases low-density-lipoprotein clearance in nonhuman primates.

To assess whether fish oil-induced alterations in low-density-lipoprotein (LDL) composition have distinct and important effects on LDL metabolism, we evaluated LDL kinetic behavior in cynomolgus macaques fed an atherogenic diet supplemented with either fish oil (1.6 g n-3 fatty acids; n = 10) or olive oil (n = 9) for > or = 6 mo. LDL from monkeys supplemented with fish oil or olive oil was isolated, labeled with either 125I or 131I, and simultaneously reinjected so that each monkey received its own (autologous injection) and donor (homologous injection) LDL. For LDL injected autologously (monkeys that received their own LDL), the LDL fractional clearance rate (FCR) was reduced in fish oil-supplemented monkeys compared with the olive oil-supplemented controls (0.42 +/- 0.03 compared with 0.56 +/- 0.05 pools/d, P = 0.04). The cholesteryl ester content of fish oil LDL increased compared with olive oil LDL (43 +/- 2% and 36 +/- 3%, respectively, P = 0.03), and the LDL cholesteryl ester content was strongly correlated with autologous LDL clearance (r = -0.76, P = 0.0001). Compared with olive oil LDL, fish oil LDL had a reduced dissociation constant (KD) for binding to the LDL receptor in vitro (KD for fish oil LDL compared with olive oil LDL: 13.9 +/- 1.8 and 7.4 +/- 1.0 mg LDL protein/L, P = 0.03). When both fish oil LDL and olive oil LDL were simultaneously injected into fish oil-supplemented monkeys, the FCR of fish oil LDL was decreased compared with olive oil LDL (0.42 +/- 0.03 and 0.52 +/- 0.04 pools/d, P = 0.006). These data suggest that dietary supplementation with fish oil decreases LDL clearance, and that this effect is mediated, at least in part, by altering LDL structure and reducing the affinity of LDL for its receptor.

Animals↗

Immunogenicity of synthetic HIV-1 gp120 V3-loop peptide-conjugate immunogens.

A successful prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine must elicit an immune response that will prevent establishment of the persistent viral infection. The only response shown to be effective in this regard is virus-neutralizing antibody directed against the viral gp120 hypervariable V3-loop region. Conjugate immunogens, containing cyclic peptides representing the V3 determinant covalently bound to a carrier protein, were capable of eliciting virus-neutralizing antibodies. The consistency of the response was related to peptide size. The smaller cyclic peptides, expressing relatively conserved sequences from the V3-loop apex, were poor inducers of neutralizing activity. In contrast, the largest cyclic peptides mediated neutralizing responses that were similar to those observed and previously reported for intact gp120 immunogens. A cyclic synthetic peptide expressing most of the prototypic HIV-1 MN variant V3 determinant warrants further study as a potentially effective vaccine immunogen.

AIDS Vaccines↗

Extrarenal angiomyolipomas of the perinephric space.

We describe 2 cases of extrarenal angiomyolipoma of the perinephric space. All other cases of extrarenal angiomyolipoma of the retroperitoneum are reviewed and the clinical relevance of this unusual pathological entity is discussed.

Adult↗

Food intake and meal patterns in rhesus monkeys: significance of chronic hyperinsulinemia.

To investigate the role of plasma insulin on food intake, we have examined the effect of naturally occurring chronic hyperinsulinemia on the feeding behavior of male rhesus monkeys. Two groups of monkeys, a group with normal fasting insulin concentrations (52.4 +/- 2.2 microU/ml) (mean +/- SE) and a hyperinsulinemic group (148.6 +/- 14.5 microU/ml), were selected to be similar in weight, 13.0 +/- 1.0 and 15.3 +/- 0.5 kg, respectively, prior to study. Food intake and feeding patterns were recorded and analyzed. No differences in either daily caloric intake, 815.2 +/- 27.4 versus 890.0 +/- 64.2 kcal (p less than 0.32), or feeding patterns were found. The number of meals taken per day did not differ between the two groups, 8.7 +/- 1.7 versus 6.7 +/- 1.1 (p less than 0.35), nor did meal size differ, 129 +/- 16.5 versus 110.5 +/- 16.3 (p less than 0.45). We conclude that chronic endogenous hyperinsulinemia as it occurs naturally in some obese rhesus monkeys has no significant effect on daily feeding behavior.

Animals↗

Prognosis of patients with stage D1 prostate carcinoma following radical prostatectomy with and without early endocrine therapy.

Early endocrine therapy after radical retropubic prostatectomy was compared to radical prostatectomy alone (nonearly endocrine therapy) for the treatment of carcinoma of the prostate with lymph node metastases. Our retrospective analysis demonstrated that the 2 cohorts were similar with respect to patient age, Gleason sum score, seminal vesicle invasion, lymph node involvement, tumor volume and pathological stage of the primary tumor. The cause-specific survival of the entire group was 84% at 60 months and 78% at 98 months. The cause-specific curves for the early and nonearly endocrine therapy group were not significantly different (p less than 0.194), although the estimated 9-year survival rates were 91 and 71%, respectively. Survival free of disease was significantly prolonged in the early endocrine therapy group (p less than 0.030), with a 9-year estimated rate free of disease of 67% versus 32% in the nonearly endocrine therapy group. Followup prostate specific antigen serum levels were analyzed and the value as a progression marker is discussed. These data suggest that a radical operation plus early endocrine therapy is effective palliation in selected patients with low volume lymph node metastases, producing clinical survival free of disease in most patients.

Antineoplastic Agents↗

Significance of histological prognostic indicators in patients with carcinoma of the prostate.

The relationship between histological prognostic indicators and their relative significance in prognosis were studied in 139 patients who underwent radical prostatectomy. The estimated progression rates at 5 and 8 years were 14 and 52% respectively for patients with high grade tumours, 25 and 50% for those with capsular penetration, 31 and 58% for patients with seminal vesicle invasion and 23 and 55% for those with lymph node metastases. Each of the 4 parameters yielded an approximately equal increased risk of disease progression at 5 and 8 years. The occurrence of 2 or more risk factors in the same patient did not result in a statistically increased risk of progression at 5 and 8 years. The effect of capsular involvement on progression was directly related to the extent of invasion. The progression rate at 8 years was 3% for patients with mild involvement, 19% for those with extensive invasion and 50% for those with capsular penetration.

Adult↗

Giant-cell tumor of the sphenoid bone: case report and review of the literature.

We report the case of a 23-year-old man with a giant-cell tumor of the sphenoid bone. The radiologic manifestations consisted of an expansile mass arising from the sphenoid bone with extension into the cranial cavity and the nasopharynx. The findings with computed tomography and magnetic resonance imaging best reflected respectively the osseous and soft-tissue extent of the disease.

Adult↗

Prognostic significance of the DNA content of renal carcinoma.

DNA analysis was performed on fresh frozen samples of the primary tumor in 32 patients with renal carcinoma (13 with apparently localized disease and 19 with metastases at presentation). A comparison of ploidy with staging and standard histologic variables was performed. None of the patients who presented without metastases died of disease during the follow-up period. Eleven of 13 patients of this group had a diploid/near diploid pattern, and metastases developed in only one patient. Patients with metastatic disease and a diploid/near diploid DNA content had a significantly better survival rate than those with aneuploid primary tumors. Statistical analysis showed that grade and ploidy contributed significant but independent prognostic information. We concluded that DNA content is a useful prognostic factor in renal carcinoma.

Adult↗

Oncocytic carcinoid of the kidney associated with periodic Cushing's syndrome.

An oncocytic carcinoid of the kidney producing a periodic Cushing's syndrome in an adolescent is described. The tumor displayed gross, histologic, and ultrastructural features similar to renal oncocytoma, another unusual renal neoplasm. A review of renal carcinoids and possible associations between oncocytic change and periodic hormone production are discussed.

ACTH Syndrome, Ectopic↗

Synthesis and antiherpetic activity of (+/-)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine and related compounds.

A series of analogues of acyclovir and ganciclovir were prepared in which conformational constraints were imposed by incorporation of a cyclopropane ring or unsaturation into the side chain. In addition, several related base-modified compounds were synthesized. These acyclonucleosides were evaluated for enzymatic phosphorylation and DNA polymerase inhibition in a staggered assay and for inhibitory activity against herpes simplex virus types 1 and 2 in vitro. Certain of the guanine or 8-azaguanine derivatives were good substrates for the viral thymidine kinase and were further converted to triphosphate, but none was a potent inhibitor of the viral DNA polymerase. Nevertheless, one member of this group, (+/-)-9-[[(Z)-2-(hydroxymethyl)cyclopropyl]methyl]guanine (3a), displayed significant antiherpetic activity in vitro, superior to that of the corresponding cis olefin 4a. Another group, typified by (+/-)-9-[[(E)-2-(hydroxymethyl)cyclopropyl]methyl]adenine (17b), possessed modest antiviral activity despite an apparent inability to be enzymatically phosphorylated. The relationship of side-chain conformation and flexibility to biological activity in this series is discussed.

Acyclovir↗

Relationship of DNA content to conventional prognostic factors in clinically localised carcinoma of the prostate.

One hundred and nine patients treated by total prostatectomy for apparently localised carcinoma were analysed to investigate the prognostic significance of capsular invasion and penetration, seminal vesicle invasion, lymph node metastases, grade as assessed by the Gleason and MD Anderson Hospital (MDAH) systems and DNA content measured by flow cytometry of nuclear material extracted from paraffin embedded tumour. Comparison of DNA content was made with 36 benign prostates. Mean follow-up/survival was 60.7 months, at which time 21 patients had evidence of recurrence or had died. Only 5 patients had local recurrence. Tumour grade, as assessed by both the Gleason Sum Score and the MDAH system, correlated with anatomical extent and was the most important determinant of time to recurrence. Fifty-nine tumours were diploid, 44 tetraploid and 6 aneuploid. One of 36 benign prostates showed aneuploidy. Ploidy did not correlate with the anatomical extent of the tumour or with grade. Tetraploid tumours recurred earlier than diploid tumours. None of 6 aneuploid tumours have recurred, although only 3 have been followed beyond 5 years. Multivariate analysis showed that after accounting for grade, none of the other variables, including ploidy, contributed any additional significant prognostic information. Although the results must be regarded as preliminary, in view of the small number of patients with recurrence, they suggest that DNA content offers limited prognostic information in clinically localised prostate cancer.

Aged↗

Staging of localized prostate cancer: a clinical-pathologic correlation.

Sixty consecutive patients were staged clinically by digital rectal examination, acid phosphatase and bone scan prior to radical retropubic prostatectomy and pelvic lymphadenectomy. Twenty-one patients also had magnetic resonance imaging (MRI) and computerized tomography (CT) of the pelvic. The surgical specimens were step-sectioned for pathologic staging. Understaging was documented in 0% of A2 patients, 27% of B1 patients and 67% of B2 patients. Capsular invasion was found in 12% of B1 and 52% of B2 patients, while seminal vesicle extension was documented in 18% of B1 and 52% of B2 patients. Lymph node metastases occurred in 3% of B1 and 29% of B2 patients. Clinical staging error was related to tumor size, tumor grade and history of prior TURP or radiotherapy. Neither CT scan nor MRI improved the accuracy of the digital rectal examination.

Carcinoma↗