Failure rate of frontal versus parietal approaches for proximal catheter placement in ventriculoperitoneal shunts: revisited.

Early studies on ventriculoperitoneal shunt malfunctions demonstrated that proximal catheter obstruction was the most common cause for shunt malfunction and choroid plexus was the primary culprit for catheter obstruction. Subsequently, several studies were performed using stereotactic and endoscopic guidance systems to assist with optimal placement of proximal shunt catheters. Surgeons collectively agree that optimum placement of the proximal catheter tip is away from choroid plexus in the frontal horn. To achieve this catheter placement, neurosurgeons typically choose a frontal or parietal approach. Two previous studies comparing parietal and frontal shunt failure rates in the pediatric population have different conclusions. Thus, we decided to compare proximal catheter failure rates of frontal versus parietal approaches on 117 patients (ages ranging from 1 month to 80 years) who had undergone ventriculoperitoneal shunt placement at our institution. Statistical analysis demonstrated a significantly higher malfunction rate in the patients less than 3 years of age and a lower overall malfunction rate in patients shunted for normal pressure hydrocephalus. Surprisingly, there was no significant difference between the two surgical approaches. Thus, we concluded after reviewing the literature, that regardless of the initial surgical approach, the most important variable in shunt malfunction appears to be the final destination of the catheter tip in relation to the choroid plexus.

Cord serum lipid and apolipoprotein levels in preterm infants with the neonatal respiratory distress syndrome.

OBJECTIVE: The purpose of this study was to evaluate the effects of birth weight on cord serum lipid and apolipoprotein levels in preterm infants with and without respiratory distress syndrome (RDS). METHODS: Cord serum lipid and apolipoprotein levels were evaluated in preterm infants (39 with RDS and 68 controls without RDS). Based on morbidity and mortality risk, RDS and non-RDS infants were separated into four birth weight groups (2,000-2,499 g, 1,500-1,999 g, 1,000-1,499 g, < 1,000 g) and evaluated for effects of birth weight on cord serum levels. RESULTS: RDS infants with birth weight of 2,000-2,499 g had significantly higher levels of cholesterol, triglyceride, total fatty acids and apolipoprotein A-I, but not arachidonic acid, than controls. RDS infants weighing 1,000-1,999 g had lower total fatty acids and apolipoprotein B levels, including arachidonic acid, than non-RDS infants. Cord serum lipid and apolipoprotein levels were significantly elevated in large (2,000-2,499 g) RDS infants, but lower levels were found in smaller (1,000-1,999 g) RDS infants. CONCLUSIONS: Cord serum arachidonic acid and apolipoprotein levels found in RDS infants suggest that lipid transport across the placenta may be abnormal. Inadequate total fatty acid supplies in utero could interfere with normal fetal growth and maturation, leading to development of neonatal RDS as one manifestation of risk for postnatal morbidity and mortality.

Evaluation of aminotransferase elevations in a bodybuilder using anabolic steroids: hepatitis or rhabdomyolysis?

The use of anabolic steroids among competitive athletes, particularly bodybuilders, is widespread. Numerous reports have noted "hepatic" dysfunction secondary to anabolic steroid use based on elevated serum aminotransferase levels. The authors' objective was to assess whether primary care physicians accurately distinguish between anabolic steroid-induced hepatotoxicity and serum aminotransferase elevations that are secondary to acute rhabdomyolysis resulting from intense resistance training. Surveys were sent to physicians listed as practicing family medicine or sports medicine in the yellow pages of seven metropolitan areas. Physicians were asked to provide a differential diagnosis for a 28-year-old, anabolic steroid-using male bodybuilder with an abnormal serum chemistry profile. The blood chemistries showed elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatine kinase (CK) levels, and normal gamma-glutamyltransferase (GGT) levels. In the physician survey (n = 84 responses), 56% failed to mention muscle damage or muscle disease as a potential diagnosis, despite the markedly elevated CK level of the patient. Sixty-three percent indicated liver disease as their primary diagnosis despite normal GGT levels. Prior reports of anabolic steroid-induced hepatotoxicity that were based on aminotransferase elevations may have overstated the role of anabolic steroids. Correspondingly, the medical community may have been led to emphasize anabolic steroid-induced hepatotoxicity and disregard muscle damage when interpreting elevated aminotransferase levels. Therefore, when evaluating enzyme elevations in patients who use anabolic steroids, physicians should consider the CK and GGT levels as essential elements in distinguishing muscle damage from liver damage.

Apolipoprotein D in the aging brain and in Alzheimer's dementia.

Apolipoprotein D (apoD) levels were examined in the temporal cortex as well as an assessment of the location of apoD positive cells within the brain by immunohistochemical and biochemical methods in young control (YC), aged control (AC), and Alzheimer's demented (AD) probands. Scattered apoD positive astrocytes and oligodendrocytes were found throughout the white matter by immunohistochemistry. ApoD immunoreactivity was also observed in the cerebellar oligodendrocytes of the YC group. There was faint positive apoD staining in scattered cortical astrocytes and a few neurons in the same group. In contrast, some of the AC and all of the AD probands had intense and frequent apoD immunostained cortical astrocytes and pyramidal neurons. The cortical senile plaques and neurofibrillary tangles were apoD immunonegative. No quantitative differences were found between the cortical apoD levels in the AC and AD groups, determined by immunoblotting. ApoD detected in the brain tissue was different in molecular weight (29 kDal) from that seen in CSF or in the serum (32 kDal). Our results indicate apoD is present in the human brain, especially in glial cells, and has increased abundance in the elderly and AD subjects.

Middle cerebral artery blood flow velocity in elite power athletes during maximal weight-lifting.

Cerebral blood flow velocity (CBFV) has been shown to significantly increase during dynamic exercise (running) secondary to increases in cardiac output. Static exercise (weight-lifting) induces supraphysiological arterial pressures up to 450/380 mmHg, and thus may alter CBFV. Catastrophic brain injuries such as stroke, cerebral hemorrhage, subarachnoid hemorrhage, retinal hemorrhage and retinal detachment have been associated with weight-lifting. A recent study has shown that intra-ocular pressure (IOP), which is an indirect measure of intracranial pressure, elevates to pathophysiologic levels during weight-lifting. Recent CBFV studies instituting Valsalva have demonstrated decreases in CBFV from 21%-52%. To date, no studies have examined CBFV during maximal weight-lifting to elucidate the cerebrovascular responses to extreme pressure alterations. We recruited nine elite power athletes, including a multi-world record holder in powerlifting, for a transcranial Doppler study of middle cerebral artery blood flow velocity at rest and during maximal weight-lifting. All subjects' resting blood flow velocities were within normal ranges (mean 64.4 +/- 9.5 cm sec2). Blood flow velocities were significantly (p < 0.0001) decreased in all subjects during maximal lifting (mean 48.4 +/- 10.1 cm sec2). Linear regression analysis demonstrated a significant inverse linear relationship in the net change of blood velocities from rest to maximal lift for each subject (r = 0.8585, p < 0.001). This study demonstrates that blood flow velocities are significantly decreased during heavy resistance training. The drop in CBFV during weight-lifting was significantly less than previous Valsalva studies, which likely reveals the cardiovascular, baroreflex, and cerebrovascular system adaptations occurring in these elite power athletes.

Evaluation of serum-lipid-related cardiovascular risk factors in Alzheimer's disease.

There is now sufficient evidence to suggest that cardiovascular pathology and altered lipid metabolism contribute to the development of late-onset Alzheimer's disease (AD). In the present study, 24 AD patients and 15 controls were assessed for cardiovascular risk based on serum lipid and lipid oxidation parameters. The AD patients appeared to have a more favorable cardiovascular risk profile than the controls based on high-density lipoprotein cholesterol (HDL-C) values. The levels of thiobarbituric-acid-reactive substances and the activity of the enzyme paraoxonase (PON) following copper oxidation indicate that female patients may have better protection against serum and perhaps tissue oxidants than males with AD. While the higher HDL-C values indicate lower cardiovascular risk, additional data on oxidized lipid parameters suggest a lower level of protection against serum oxidants in male AD probands. CopyrightCopyright 1999S.KargerAG,Basel

Pressure-overload-induced sliding hiatal hernia in power athletes.

Sliding hiatal hernias are a common condition thought to occur with increasing age secondary to a degenerative process. The incidence of sliding hiatal hernias in the general population is 0.5%. Although the prevalence in the Western world is thought to be significantly higher, with approximately 60% of geriatric patients in North America having a hiatal hernia on radiologic studies. Thus, the primary etiology of the sliding hiatal hernia is thought to be degeneration of the phrenoesophageal ligament. Most hiatal hernias occurring in young adults are idiopathic. There has been speculation of a stress-induced hiatal hernia from repeated episodes of elevated intra-abdominal pressure, and to date there is one report of a pressure-overload-induced hiatal hernia occurring in an elite body builder. The prevalence of hiatal hernia in young male power athletes has yet to be examined. Therefore, we examined eight male elite power athletes and seven male non-weightlifters, matched for age, via fluoroscopy with barium swallow to test the hypothesis that pressure overload can induce hiatal hernias in young adults.

Anabolic steroid-induced hepatotoxicity: is it overstated?

OBJECTIVE: There have been numerous reports of hepatic dysfunction secondary to anabolic steroid use based on elevated levels of serum aminotransferases. This study was conducted to distinguish between serum aminotransaminase elevations secondary to intense resistance training and anabolic steroid-induced hepatotoxicity in elite bodybuilders. DESIGN: This was a case-control study of serum chemistry profiles from bodybuilders using and not using anabolic steroids with comparisons to a cohort of medical students and patients with hepatitis. PARTICIPANTS: The participants were bodybuilders taking self-directed regimens of anabolic steroids (n = 15) and bodybuilders not taking steroids (n = 10). Blood chemistry profiles from patients with viral hepatitis (n = 49) and exercising and nonexercising medical students (592) were used as controls. MAIN OUTCOME MEASURES: The focus in blood chemistry profiles was aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltranspeptidase (GGT), and creatine kinase (CK) levels. RESULTS: In both groups of bodybuilders, CK, AST, and ALT were elevated, whereas GGT remained in the normal range. In contrast, patients with hepatitis had elevations of all three enzymes: ALT, AST, and GGT. Creatine kinase (CK) was elevated in all exercising groups. Patients with hepatitis were the only group in which a correlation was found between aminotransferases and GGT. CONCLUSION: Prior reports of anabolic steroid-induced hepatotoxicity based on elevated aminotransferase levels may have been overstated, because no exercising subjects, including steroid users, demonstrated hepatic dysfunction based on GGT levels. Such reports may have misled the medical community to emphasize steroid-induced hepatotoxicity when interpreting elevated aminotransferase levels and disregard muscle damage. For these reasons, when evaluating hepatic function in cases of anabolic steroid therapy or abuse, CK and GGT levels should be considered in addition to ALT and AST levels as essential elements of the assessment.

Intra-ocular pressure changes during maximal isometric contraction: does this reflect intra-cranial pressure or retinal venous pressure?

Recent publications have suggested that intra-ocular pressure (IOP) may be an indirect assessment of intra-cranial pressure (ICP). Both IOP and ICP have similar physiologic pressure ranges and similar responses to changes in intra-abdominal, intra-thoracic and aortic pressure. Previous studies have demonstrated the relationships between retinal arterial pressure and aortic pressure, intra-ocular pressure and retinal venous pressure, intra-cranial pressure and retinal venous pressure. Power athletes routinely utilize the Valsalva maneuver during weightlifting. In fact there are reports of stroke, cerebral hemorrhage, subarachnoid hemorrhage, conjunctival, foveal and retinal hemorrhage, retinal detachment, hiatal hernia and pneumothorax associated with weightlifting. These events are thought to occur secondary to the extreme pressure elevations that occur in the intra-abdominal, intra-thoracic, intra-cranial, intra-ocular and vascular compartments. To date no human studies have examined the IOP changes that may occur with heavy resistance exercise. Therefore, we recruited power athletes (n = 11), who had participated in prior studies, from the local metropolitan area. The athletes had blood pressure status, drug screening and medical histories performed during previous investigations. Intra-ocular pressure was measured by noncontact tonometry at rest and during maximal isometric contraction. All subjects resting IOP were within normal ranges (mean 13 +/- 2.8 mmHg). Intra-ocular pressures were significantly (p < 0.0001) elevated in each subject during maximal contraction (mean 28 +/- 9.3 mmHg). One subject's IOP reached 46 mmHg during maximal contraction. Linear regression analysis demonstrated a significant linear relationship (r = 0.62, p < 0.0001) in the net change of IOP from rest to maximal contraction for each subject. This study demonstrates that IOP elevates to pathophysiologic levels during resistance exercise. The findings of conjunctival hemorrhages in two subjects further supports IOP being reflective of retinal venous pressure. The enormous pressures generated by power athletes during weightlifting leads to elevations in ICP which obstruct venous outflow leading to hemorrhage and elevations in IOP. The question remains as to whether these intermittent bursts of elevated IOP can lead to long-term pathological sequelae.

Lp(a) and LDL2: differences in fatty acid composition and collagen lattice contraction activity.

Lp(a) and LDL2 were used for detailed fatty acid analyses and tested in an in vitro model for promotion of fibroblast-mediated collagen lattice contraction to determine possible compositional and functional differences between these two apoB-containing lipoprotein species. Autologous Lp(a) was more saturated with respect to fatty acid composition than LDL2 in triglyceride and cholesterol ester lipid classes and had differences in the fatty acid content of phospholipids. Functionally, LDL2 promoted rapid fibroblast-mediated contraction while Lp(a) was significantly less active in promoting rapid contraction on a protein per weight basis. These studies suggest a synthetic route for Lp(a) diverging from the majority of other apoB-containing lipoproteins and significant activity of LDL2 in a collagen lattice contraction system.

Lp(a) and LDL2: differences in fatty acid composition and collagen lattice contraction activity.

Lp(a) and LDL2 were used for detailed fatty acid analyses and tested in an in vitro model for promotion of fibroblast-mediated collagen lattice contraction to determine possible compositional and functional differences between these two apoB-containing lipoprotein species. Autologous Lp(a) was more saturated with respect to fatty acid composition than LDL2 in triglyceride and cholesterol ester lipid classes and had differences in the fatty acid content of phospholipids. Functionally, LDL2 promoted rapid fibroblast-mediated contraction while Lp(a) was significantly less active in promoting rapid contraction on a protein per weight basis. These studies suggest a synthetic route for Lp(a) diverging from the majority of other apoB-containing lipoproteins and significant activity of LDL2 in a collagen lattice contraction system.

Functional characterization of T7 and T8 of human apolipoprotein (a).

Lipoprotein (a) [Lp(a)], a risk factor for coronary artery disease, is a LDL-like particle with apolipoprotein (a) [apo(a)] covalently linked to apolipoprotein B (apoB). Apo(a) has many repeats of kringle 4-like domain, classified as type 1 through type 10 (T1-T10). Deletion analysis was performed to define the functional modules of human apo(a). We found that T7 has an affinity for cell surfaces and is required for Lp(a) formation. Cell surface binding was inhibited by L-proline, KI = 4.7 +/- 3.6 mM (n=3). We also found that T8 has an affinity for subendothelial extracellular matrix (ECM). ECM binding was inhibited modestly by L-proline (KI = 6.1 +/- 1.9 mM, n=3), and more effectively by L-lysine (KI = 2.7 +/- 1.0 mM, n=3) and its analogue, 6-aminohexanoic acid (KI = 0.35 +/- 0.13 mM, n=3). These data point to T7 and T8 as important functional modules of apo(a).

Left ventricular wall thickening does occur in elite power athletes with or without anabolic steroid Use.

Reports on the occurrence of left ventricular wall thickening in resistance-trained athletes have rejected the possibility for this physiological adaptation to occur without concomitant anabolic steroid abuse. Others have concluded short bursts of arterial hypertension that occur with maximal weight lifting are not sufficient to induce left ventricular wall thickening, and left ventricular wall thickness >/=13 mm should not be found in pure resistance-trained athletes. Therefore, we examined 4 elite resistance-trained athletes by two-dimensional echocardiography. In addition, we retrospectively examined the individual left ventricular dimensions of 13 bodybuilders from our previous echocardiographic studies. All 4 elite resistance-trained athletes had left ventricular wall thicknesses beyond 13 mm. One of the elite bodybuilders has the largest left ventricular wall thickness (16 mm) ever reported in a power athlete. Retrospectively, 43% of the drug-free bodybuilders and 100% of the steroid users had left ventricular wall thickness beyond the normal range of 11 mm. In addition, 1 drug-free subject and 3 steroid users were beyond the critical mark of 13 mm. No subjects demonstrated diastolic dysfunction. In contrast to previous reports, we have demonstrated that left ventricular wall thicknesses >/=13 mm can be found routinely in elite resistance-trained athletes. The use of anabolic steroids concomitant with intensive resistance exercise does appear to augment left ventricular size without dysfunction. Anabolic steroids may accelerate left ventricular wall thickening indirectly by increasing strength, thus augmenting the pressor response.

Aortic valve thickening associated with power training: is it pressure overload?

This is a first report of aortic valve thickening secondary to intermittent hypertensive episodes experienced with weight lifting.

Can pressure overload cause sliding hiatal hernia? A case report and review of the literature.

We describe a hiatal hernia of moderate size in a 31-year-old competitive bodybuilder to raise the question of whether such hernias are more likely in young elite resistance-trained athletes as a consequence of attempts to increase intra-abdominal pressure and thus decrease the strain on the lumbar spine.

Effect of probucol therapy on plasma fatty acid composition during postprandial lipemia in hypertriglyceridemia.

OBJECTIVE: To determine the effect of probucol (PR) on fatty acid composition of plasma lipids in patients with hypertriglyceridemia during the fasting and postprandial states. DESIGN: Open-label, single-center, 6-week treatment, baseline-controlled trial. SETTING: Outpatient clinical research center. PATIENTS: Six patients with established hypertriglyceridemia and no complicating medical conditions. INTERVENTION: Step 1 American Heart Association diet and no lipid-lowering medications for at least 4 weeks. Lead to a baseline standarized meal ingestion with postprandial blood samplings. After 6 weeks of treatment with 500-mg of PR twice daily and diet, the meal tests were repeated. MEASUREMENTS: The clinical status, 3-day food records, postprandial blood samplings (0, 2, 4, 6, and 8 hours) for lipid and fatty acids in whole plasma, triglyceride (TG), phospholipid (PL), and cholesteryl ester (CE) fractions. RESULTS: PR had the following effects: (1) In plasma, cholesterol, high-density lipoprotein cholesterol, apolipoprotein (Apo) A1, and ApoB were decreased postprandially. ApoC111 ratio (heparin-treated plasma versus precipitate) was decreased in the fasting state. (2) The saturated/unsaturated (S/U) fatty acid ratios in the PL, TG, and CE fractions were elevated postprandially and increased in CE in the fasting state. In the PL fraction it was due to an increase in the percentage of myristic, palmitic, stearic, and oleic acids and a decrease in linolenic, eicosatrienoic, and arachidonic acids. In the TG and CE fractions the changes were not due to any particular patterns of fatty acids. The ratio of arachidonic/eicosatrienoic acid was decreased postprandially in PL and CE fractions. The ratio of eicosatrienoic/linoleic acid was decreased in PL and increased in CE fractions. (3) The S/U ratio in the lipoprotein (Lp) B and LP(a) lipid components decreased in PL and CE. Lp(a) was more saturated with respect to fatty acids than LpB. CONCLUSION: PR treatment for 6 weeks increased postprandial S/U fatty acid ratios. This was due to a combination of an increase in saturated and monounsaturated levels and a decrease in polyunsaturated levels. The effect was most notable in the PL fraction. In those systems dependent on the pattern of fatty acids, the fatty acid compositional change could modify biological responses in clinically important ways during lipid-lowering therapy. The change toward saturation of fatty acids in the postprandial state may contribute to the antioxidant properties of probucol.

Probing the structure of the ligand binding cavity of lipocalins by fluorescence spectroscopy.

The lipocalin superfamily constitutes a phylogenetically conserved group of more than 40 proteins that function in the binding and transport of a variety of physiologically important ligands. Members of this family subserve diverse functions as carriers of retinoids (retinol binding protein), odorants (odorant binding proteins), chromophores (insecticyanin, INS), pheromones (aphrodisin) and sterols (apolipoprotein D, apoD). Despite the pivotal importance of the ligand binding function of these proteins, a suitable approach for characterizing the molecular determinants of such binding has not been available. In studies using three homogeneously purified lipocalins INS, beta-lactoglobulin (BLG) and human apoD, we find that the fluorescence reporter BIS (1,1'-bi(4-anilino) naphthalene-5,5'-disulfonic acid) is an ideal candidate for use in rapid kinetic experiments and in fluorescence resonance energy transfer (FRET). These methods require only small amounts of reagents and yield molecular coordinates of the ligand binding cavity of lipocalins in solution that are in remarkably close agreement to those obtained from crystallographic work with solids. Extremely fast ligand binding dynamics is indicated.

Neuroendocrine-associated behavioral patterns in the male Asian elephant (Elephas maximus).

Steroid-responsive behaviors have been reported in various species; however, the reports thus far on the male Asian elephant (bull) during musth are few in number and most have been conducted on single captive animals for short time periods. The purpose of this investigation was to perform a longitudinal study on steroid-responsive behavior in 3 male Asian elephants from a captive herd of 11 male Asian elephants in Nepal. Male Asian elephants were 18, 25, and 43 years old. The animals had serum collected for 11 months and were observed on a daily basis for aggressive behavior according to the Species Survival Plan (SSP) collection protocol on SSP data sheets. Testosterone (T) and dihydrotestosterone (DHT) were measured in each animal by radioimmunoassay. Testosterone levels rose during musth 26-fold compared to nonmusth, and DHT was elevated 12-fold in musth. Maximal aggressive behavior episodes occurred during peak elevations of T and DHT, with correlation coefficients of 0.82 and 0.89, respectively. Therefore, we suggest that the aggressive episodes are dependent on elevated circulating androgens acting on androgen-responsive neural tissues.