Precurved catheters for transbrachial coronary arteriography

A series of precurved catheters has been designed for use in coronary arteriography through the brachial artery. They facilitate entry of the coronary arteries, especially the left, from abnormal aortas. Their use has reduced the necessity for flushing the sinus of Valsalva as a method for viewing the coronary arteries, improved the quality of films obtained in difficult cases, and reduced fluoroscopic manipulation.     

Age-related bone loss: old bone, new facts

The human skeleton serves several functions for the body: support, locomotion, protection of vital organs, and housing of bone marrow. Bone remodeling is the result of the interactions of multiple elements, including osteoblasts, osteoclasts, hormones, growth factors, and cytokines, the end result being the maintenance of the bone architecture and to maintain systemic calcium homeostasis. In early life, a careful balance exists between bone formation by osteoblasts and bone resorption by osteoclasts. With aging, the process of coupled bone formation is affected by the reduction of osteoblast differentiation, activity, and life span which is further potentiated in the perimenopausal years with hormone deprivation and increased osteoclast activity. Age-related bone loss is thus not only a consequence of hormone deprivation, but also the result of changes in bone formation and cell-cell interactions with a unique pathophysiology. In this review, we describe the cellular and metabolic changes associated with aging bone and present recent evidence regarding cell differentiation within the bone marrow. We also consider the mechanism of programmed cell death, apoptosis, as being an important determinant of aging in bone as well as describe possible future interventions to prolong the life span of osteoblasts.     

Alcohol and fatty acid stimulation of neurotensin release from rat small intestine

We have previously reported that neurotensin (NT) is released from the small intestine and elevated in the hepatic-portal circulation in response to the perfusion of the small intestine with a micellar solution of oleic acid. In order to determine the minimum acyl chain length and whether the presence of a carboxylic acid is necessary for the stimulation of NT release, the small intestine of anesthetized rats was perfused with test solutions of fatty acids of 2-, 4-, 8-, or 18-carbons or fatty alcohols of 2-, 4-, or 8-carbons at a concentration of 1 mM prepared in 2.4 mM taurodeoxycholate in 0.9% NaCl. Blood samples, collected from the superior mesenteric vein immediately before the start of the test perfusion and at 15-min intervals thereafter, were extracted immediately and radioimmunoassayed for NT-like immunoreactivity (NTLI) with a C-terminal-directed antiserum. Perfusions of fatty acids with 4 or more carbons and alcohols of 2 or more carbons resulted in a significant elevation (P less than 0.05) in plasma levels of NTLI above the values obtained before the onset of perfusion. Perfusions with ethanol resulted in a value of 4.3 +/- 0.03 mg/dl (SEM) in blood from the superior mesenteric vein while there was no increase in ethanol levels in the peripheral circulation. Perfusion with taurodeoxycholate and 0.9% NaCl alone had no significant effect on plasma levels of the NTLI. In order to characterize the chemical nature of the elevated NTLI, plasma samples from animals perfused with test solution were collected, extracted, pooled, and subjected to HPLC. NT and its N-terminal metabolite, NT(1-8), were quantitated. NT was defined as material having the same retention time as synthetic NT standard and having comparable measurements using N- and C-terminal-directed antisera. Perfusions of fatty acids of four or more carbons and alcohols of two or more carbons resulted in a 2- to 4-fold increase of both NT and NT(1-8) levels in plasma. It is particularly interesting that perfusion with ethanol (2-carbons) causes an elevation in plasma NT, because perfusion with acetic acid (2-carbons) does not increase NTLI. The fact that perfusion of ethanol is effective in releasing intestinal NT suggests that NT may mediate some of the biological effects observed after the consumption of alcohol.     

Long-term effects of exercise on psychological functioning in older men and women

The purpose of this study was to determine the psychological, behavioral, and cognitive changes associated with up to 14 months of aerobic exercise training. For the first 4 months of the study, 101 older (greater than 60 years) men and women were randomly assigned to one of three conditions: Aerobic exercise, Yoga, or a Waiting List control group. Before and following the intervention, all subjects completed a comprehensive assessment battery, including measures of mood and cognitive functioning. A semi-crossover design was employed such that, following completion of the second assessment, all subjects completed 4 months of aerobic exercise and underwent a third assessment. Subjects were given the option of participating in 6 additional months of supervised aerobic exercise (14 months total), and all subjects, regardless of their exercise status, completed a fourth assessment. Results indicated that subjects experienced a 10-15% improvement in aerobic capacity. In general, there were relatively few improvements in cognitive performance associated with aerobic exercise, although subjects who maintained their exercise participation for 14 months experienced improvements in some psychiatric symptoms. However, the healthy subjects in this study were functioning at a relatively high level to begin with, and exercise training may produce greater improvements among elderly with concomitant physical or emotional impairments.     

Determinants of Intima-Media Thickness in the Young: The ALSPAC Study

ObjectivesThis study characterized the determinants of carotid intima-media thickness (cIMT) in a large (n > 4,000) longitudinal cohort of healthy young people age 9 to 21 years.BackgroundGreater cIMT is commonly used in the young as a marker of subclinical atherosclerosis, but its evolution at this age is still poorly understood.MethodsAssociations between cardiovascular risk factors and cIMT were investigated in both longitudinal (ages 9 to 17 years) and cross-sectional (ages 17 and 21 years) analyses, with the latter also related to other measures of carotid structure and stress. Additional use of ultra-high frequency ultrasound in the radial artery at age 21 years allowed investigation of the distinct layers (i.e., intima or media) that may underlie observed differences.ResultsFat-free mass (FFM) and systolic blood pressure were the only modifiable risk factors positively associated with cIMT (e.g., mean difference in cIMT per 1-SD increase in FFM at age 17: 0.007 mm: 95% confidence interval [CI]: 0.004 to 0.010; p < 0.001), whereas fat mass was negatively associated with cIMT (difference: ?0.0032; 95% CI: 0.004 to ?0.001; p = 0.001). Similar results were obtained when investigating cumulative exposure to these factors throughout adolescence. An increase in cIMT maintained circumferential wall stress in the face of increased mean arterial pressure when increases in body mass were attributable to increased FFM, but not fat mass. Risk factor?associated differences in the radial artery occurred in the media alone, and there was little evidence of a relationship between intimal thickness and any risk factor.ConclusionsSubtle changes in cIMT in the young may predominantly involve the media and represent physiological adaptations as opposed to subclinical atherosclerosis. Other vascular measures may be more appropriate for the identification of arterial disease before adulthood.     

Potential applications of GH secretagogs in the evaluation and treatment of the age-related decline in growth hormone secretion

The two classes of GH secretagogs—GH-releasing hormone (GHRH) and the GH-releasing peptides and their analogs (GHRP’s)—retain their ability to endogenous GH secretion in healthy and frail elderly subjects. They have very limited utility in assessment of the state of the GH/IGF-I axis except to confirm an intact pituitary, but they are attractive potential alternatives to GH as therapeutic agents. There is wide interest in the possibility that elevating GH and IGF-I might increase muscle mass, physical strength and performance, and possibly sleep and cognition in aging. The GH secretagogs, like GH, can produce a sustained stimulation of this axis; in contrast to GH, they preserve feedback regulation at the pituitary level and stimulate a near-physiologic pulsatile pattern of GH release. GHRP’s and their nonpeptide analogs are also active when given orally, a significant practical advantage. Short-tern treatment studies have shown that GHRH and the GHRP’s can enhance GH secretion and elevate IGF-I and IGFBP-3 levels; that GHRH may promote sleep; and that these agents are generally well tolerated. Longer-term studies, assessing effects upon body composition and physical and psychological function are underway. Prepared for presentation at “Assessment of the Growth Hormone/IGF-I Axis in Aging,” Bethesda, MD, April 14, 1997.     

Treatment of hypertension associated with renal arterial occlusive disease

Renal artery stenosis is a common cause of diastolic hypertension. Recent development of arterial reconstructive technics provides the opportunity to cure most patients with renovascular hypertension and to salvage the involved kidney or kidneys.

Resectional therapy provides a second type of treatment when definitive arterial reconstruction is impossible.

Patch graft angioplasty and renal artery bypass are the two most satisfactory technical means of renal revascularization.

Selection of patients with renal artery stenosis for revascularization is primarily a matter of exclusion. Specific contraindications include cerebrovascular insufficiency and coronary artery disease. Eighty per cent of 140 patients having renal revascularization procedures were cured of hypertension.     

Course of virologic breakthroughs under long-term lamivudine in HBeAg-negative precore mutant HBV liver disease

We studied the course of virologic breakthroughs detected by a quantitative polymerase chain reaction (PCR) assay in 32 of 78 patients with hepatitis B e antigen (HBeAg)-negative precore mutant hepatitis B virus (HBV) chronic liver disease under long-term lamivudine monotherapy. Serum HBV DNA levels were measured every 3 months and on every biochemical breakthrough. YMDD mutants were detected in 30 of the 32 patients with virologic breakthroughs. Among these 32 patients, biochemical remission rate was 44% at 6 months, 21% at 12 months, and 0% at 24 months after the onset of virologic breakthrough. Development of biochemical breakthroughs was associated with a significant increase of serum HBV DNA levels, which exceeded 100,000 copies/mL in 19 of 20 patients (95%) with biochemical breakthroughs and in only 1 of 8 patients (12.5%) remaining in biochemical remission for at least 6 months after the onset of virologic breakthrough (P <.001). Alanine aminotransferase (ALT) level peaked within 0 to 3 months after the onset of biochemical breakthrough and decreased at 6 months but remained abnormal in all but 2 patients. Follow-up liver histologic lesions in patients with biochemical breakthroughs did not differ from baseline findings, although they were significantly improved in patients remaining in virologic and biochemical remission. In conclusion, the frequent emergence of viral resistance under long-term lamivudine monotherapy in HBeAg-negative precore mutant HBV chronic liver disease is followed by increasing viremia levels culminating in the development of biochemical breakthroughs in most cases. ALT activity peaks close to the onset of biochemical breakthrough, decreasing thereafter but remaining persistently abnormal with fluctuating levels.     

Use of nonvolume-reduced (unmanipulated after thawing) umbilical cord blood stem cells for allogeneic transplantation results in safe engraftment

Volume reduction of umbilical cord blood (UCB) units before infusion is standard in most transplant centers. We examined 26 patients who underwent transplantation from May 1997 to December 2001 with unmanipulated (n=18) or volume-reduced (n=8) UCB units for engraftment. Of 18 unmanipulated UCBT patients, 16 achieved ANC >500/mm(3), a median of 26 days (range, 16-104) post-UCBT; two died before engraftment on days +2 and +14. Of 18 unmanipulated UCBT patients, 10 achieved platelet recovery, a median of 60.5 days (range, 41-144) post-UCBT; eight patients died before platelet recovery +2 to +255 days post-UCBT. These results are similar to several reported studies and our series utilizing volume-reduced UCB units for UCBT. At a median follow-up of 29.5 months, the 100-day and 3-year overall survivals of unmanipulated UCBT were 61.1% (95% CI, 38.6-83.6) and 48.6% (95% CI, 24.8-72.4) and of volume-reduced UCBT were 60% (95% CI, 24.4-95.6) and 22.5% (95% CI, 0-58.7). There was no serious toxicity from UCB infusion using unmanipulated UCB units. We conclude that unmanipulated UCB units may be infused safely into UCBT patients with adequate engraftment and survival.