Javier Villanueva-Meyer

Frontal lobe degeneration Clinical, neuropsychological, and SPECT characteristics

The clinical, neuropsychological, and cerebral blood flow characteristics of eight patients with frontal lobe degeneration (FLD) were studied. Social withdrawal and behavioral disinhibition were the earliest and most common clinical presentations, and psychiatric symptoms typically preceded the onset of dementia by several years. Neuropsychological testing showed selective impairment of frontal and memory tasks with relative sparing of attention, language, and visuospatial skills. Single-photon emission computerized tomography demonstrated frontal and temporal hypoperfusion with relative sparing of parietal and occipital blood flow. Previous studies suggest that the neuropathologic findings in patients with FLD are varied; some demonstrate frontal gliosis, neuronal loss, and Pick bodies while others show only gliosis and neuronal loss.

Colonic motility and transit in health and ulcerative colitis

Preprandial and postprandial colonic motility and transit (scintigraphy), with respect to the splenic flexure, were studied in 10 patients with ulcerative colitis and in 9 healthy subjects. The healthy subjects had a postprandial increase in intraluminal pressure that was significantly (P less than 0.03) greater in the descending colon than in other regions of the colon. In ulcerative colitis, the pressure was decreased in all regions compared with healthy subjects, with no significant pressure gradient among different regions. In normal subjects, transit was quiescent during fasting; eating stimulated both antegrade and retrograde transit. In ulcerative colitis, transit was variable before as well as after the meal. Both healthy subjects and patients with ulcerative colitis had more rapid emptying from the splenic flexure into the sigmoid than into the transverse colon. More frequent, low-amplitude, postprandial propagating contractions occurred in ulcerative colitis (P less than 0.05) than in healthy subjects. Propagating contractions were always antegrade and caused a rapid movement of the tracer into the sigmoid. In conclusion, ulcerative colitis is characterized by (a) decreased contractility, (b) increased low-amplitude propagating contractions, and (c) variable transit. These disturbances may accentuate the diarrhea in ulcerative colitis.

Association Between Postprandial Changes in Colonic Intraluminal Pressure and Transit

The aim of this study was to correlate the movement of colonic luminal contents with the changes in intraluminal pressure. Studies were performed in 9 healthy volunteers. Intraluminal pressure was measured with perfused catheter ports in the transverse, splenic flexure, descending, and sigmoid colon. Movement of the luminal contents was measured by following the movement of technetium 99m-ethylenetriamine-pentaacetic acid that was instilled as a bolus in the splenic flexure. During fasting there was very little change in pressure or in the movement of intraluminal contents. After eating a 1000-kcal meal, the tracer moved from the splenic flexure into the transverse colon and the sigmoid colon. Nonpropagating colonic motor activity increased in all colonic segments immediately after eating the meal (p less than 0.05). The increase in motility was significantly greater in the descending colon than in the transverse and sigmoid colon (p less than 0.05). In one-half of the subjects propagating contractions occurred postprandially. The movement of the intraluminal tracer occurred during both types of motility. The nonpropagating contractions were associated with a gradual movement of the luminal contents. The direction of the movement of the contents was determined by the differences in pressure in the different segments of the colon. The propagating contractions were associated with a rapid movement of intraluminal contents. These studies suggest that (a) colonic motility and transit are quiescent during fasting and (b) the transverse colon acts as a mixing and storage area, as retrograde transit into the transverse colon is the characteristic postprandial pattern.

Effect of eating on colonic motility and transit in patients with functional diarrhea

The aim of this study was to correlate colonic motility with transit in 8 patients with functional diarrhea compared to 12 healthy subjects. Intraluminal pressure was measured with perfused catheter ports in the transverse colon, splenic flexure, and descending and sigmoid colons. Transit of the luminal contents was measured by following the movement of 99mTC-diethylenetriaminepentaacetic acid instilled as a bolus in the splenic flexure. In patients with diarrhea, the intraluminal marker moved in and out of the transverse and sigmoid colon regions of interest during fasting, unlike healthy subjects, in whom the marker remained in the splenic flexure. After eating, radioactivity immediately increased in both the transverse and sigmoid colons in healthy subjects. In the patients with diarrhea, eating did not alter the marker movement into the different regions of the colon compared with fasting. Within 100 minutes of eating, the intraluminal marker almost disappeared from the regions of interest in patients with diarrhea. Postprandial colonic nonpropagating contractions increased in each region of the colon in healthy subjects; there was only a small postprandial increase in colonic motility in patients with diarrhea. However, the numbers of fasting and postprandial propagating contractions were increased in patients with diarrhea compared with healthy subjects (P less than 0.02). Each propagating contraction moved more tracer in patients with diarrhea than in healthy subjects (P less than 0.05). These studies suggest that (a) in patients with diarrhea, the fluctuation of marker in both transverse and sigmoid colons during the fasting and postprandial periods is associated with decreased nonsegmenting contractions and frequent propagating contractions; and (b) in healthy subjects, the intraluminal marker moved after eating because of a pressure gradient caused by nonpropagating contractions.

Regional 133Xenon cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment

We previously reported increased regional cerebral cortical uptake and decreased caudate nucleus uptake of 99mTc-HMPAO in patients with obsessive-compulsive disorder(OCD) before treatment compared to matched normal controls. In the present study, we determined whether or not these changes persisted during treatment. Single-photon emission computed tomography was used to measure regional cerebral blood flow (rCBF) by 133Xe inhalation and cerebral uptake of 99mTc-HMPAO in eight adult male OCD patients before and during treatment with chlomipramine, and in eight age-matched normal male controls. With 133Xe, there were no significant differences in rCBF between patients with OCD and their matched controls, and no significant differences in rCBF in the patients before and during treatment. Significantly increased HMPAO uptake in the orbital frontal cortex, posterofrontal cortex, and high dorsal parietal cortex bilaterally occurred in the OCD patients before treatment compared to their matched controls, and there were significant reductions of HMPAO uptake, into the normal range, in all these areas in the patients during treatment. Significantly reduced HMPAO uptake in the caudate nucleus bilaterally occurred in the patients before treatment compared to their matched controls, and these reductions persisted during treatment. This study provides additional support for the involvement of both the orbital frontal cortex and the caudate nuclei in the pathophysiology of OCD.

Comparison of thallium-201 and technetium-99m hexakis 2-methoxyisobutyl isonitrile single-photon emission computed tomography for estimating the extent of myocardial ischemia and infarction in coronary artery disease

Single-photon emission computed tomography (SPECT) using thallium-201 (Tl-201) was compared with technetium-99m hexakis 2-methoxyisobutyl isonitrile (Tc-99m MIBI) in 24 patients with coronary artery diseaes. Patients exercised to the same work load as each isotope was studied. Normal and hypoperfused left ventricular mass was determined with an automated method. Estimated total left ventricular mass was similar for both stress/redistribution Tl-201 and stress/rest Tc-99m MIBI images. The mean estimated defect size in the redistribution Tl-201 images was 32 +/- 34.7 vs 33 +/- 38.4 g in the resting Tc-99m MIBI studies (difference not significant). The individual determinations of defect mass were highly correlated (r = 0.93; p less than 0.0001). Estimated defect size in the stress Tl-201 images (52 +/- 46.2 g) was significantly larger than the exercise Tc-99m MIBI estimates of defect mass (42 +/- 39.9 g; p less than 0.05). A linear correlation existed between stress thallium and technetium estimates of defect size (r = 0.85) but 15 of 24 Tc-99m MIBI defects were smaller than the Tl-201 defects. Partial redistribution of Tc-99m MIBI could explain the discordance. Stress Tc-99m MIBI SPECT defect size determined by visual interpretation or by the use of isocount analysis may be smaller than what is seen with stress Tl-201 SPECT.

Recovery of Testicular Blood Flow Following Ligation of Testicular Vessels

To determine whether initial ligation of the testicular vessels of the high undescended testis followed by a delayed secondary orchiopexy is a viable alternative to the classical Fowler-Stephens procedure, a series of preliminary experiments were conducted in the rat in which testicular blood flow was measured by the 133xenon washout technique before, and 1 hour and 30 days after ligation of the vessels. In addition, testicular histology, and testis and sex-accessory tissue weights were measured in 6 control, 6 sham operated and 6 testicular vessel ligated rats 54 days after vessel ligation. The data demonstrate that ligation and division of the testicular blood vessels produce an 80 per cent decrease in testicular blood flow 1 hour after ligation of the vessels. However, 30 days later testis blood flow returns to the control and pre-treatment value. There were no significant changes in testis or sex-accessory tissue weights 54 days after vessel ligation. Histologically, 4 of the surgically operated testes demonstrated necrosis of less than 25 per cent of the seminiferous tubules while 1 testis demonstrated more than 75 per cent necrosis. The rest of the tubules in all 6 testes demonstrated normal spermatogenesis. From this study we conclude that initial testicular vessel ligation produces an immediate decrease in testicular blood flow but with time the collateral vessels are able to compensate and return the testis blood flow to its normal pre-treatment value. These preliminary observations lend support for the concept that initial ligation of the testicular vessels followed by a delayed secondary orchiopexy in patients with a high undescended testis may be a possible alternative to the classical Fowler-Stephens approach.

Control of Oxidative Reactions of Hemoglobin in the Design of Blood Substitutes: Role of the Ascorbate–Glutathione Antioxidant System

Uncontrolled oxidative reactions of hemoglobin (Hb) are still the main unresolved problem for Hb-based blood substitute developers. Spontaneous oxidation of acellular ferrous Hb into a nonfunctional ferric Hb generates superoxide anion. Hydrogen peroxide, formed after superoxide anion dismutation, may react with ferrous/ferric Hb to produce toxic ferryl Hb, fluorescent heme degradation products, and/or protein-based free radicals. In the presence of free iron released from heme, superoxide anion and hydrogen peroxide might react via the Haber-Weiss and Fenton reactions to generate the hydroxyl radical. These highly reactive oxygen and heme species may not only be involved in shifting the cellular redox balance to the oxidized state that facilitates signal transduction and pro-inflammatory gene expression, but could also be involved in cellular and organ injury, and generation of vasoactive compounds such as isoprostanes and angiotensins. It is believed that these toxic species may be formed after administration of Hb-based blood substitutes, particularly in ischemic patients with a diminished ability to control oxidative reactions. Although varieties of antioxidant strategies have been suggested, this in vitro study examined the ability of the ascorbate-glutathione antioxidant system in preventing Hb oxidation and formation of its ferryl intermediate. The results suggest that although ascorbate is effective in reducing the formation of ferryl Hb, glutathione protects heme against excessive oxidation. Ascorbate without glutathione failed to protect the red blood cell membranes against Hb/hydrogen peroxide-mediated peroxidation. This study provides evidence that the ascorbate-glutathione antioxidant system is essential in attenuation of the pro-oxidant potential of redox active acellular Hbs, and superior to either ascorbate or glutathione alone.

Imaging of brain tumors in AIDS patients by means of dual-isotope thallium-201 and technetium-99m sestamibi single-photon emission tomography

Abstract. Our aim was to evaluate the use of dual-isotope thallium-201 (Tl) and technetium-99m sestamibi (sestamibi) simultaneous acquisition in brain single-photon emission tomography (SPET) for the differentiation between brain lymphoma and benign central nervous system (CNS) lesions in AIDS patients. Thirty-six consecutive patients with enhancing mass lesions on magnetic resonance (MR) imaging were included in the study. SPET of the brain was performed to obtain simultaneous Tl and sestamibi images. Regions-of-interest were drawn around the lesion and on the contralateral side to calculate uptake ratios. The final diagnosis was reached by pathologic findings in 17 patients and clinical and/or MR follow-up in 19 patients. Of the 36 patients, 11 had brain lymphoma, 1 glioblastoma multiforme, 15 toxoplasmosis and 9 other benign CNS lesions. Correlation between SPET and the final diagnosis revealed in 10 true-positive, 23 true-negative, 1 false-positive and 2 false-negative studies. All patients with toxoplasmosis had negative scans. A patient with a purulent infection had positive scans. Tl and sestamibi scans were concordant in every lesion. The same lesions that took up Tl were also visualized with sestamibi. However, sestamibi scans showed higher lesion-to-normal tissue uptake ratios (3.7±1.8) compared with those of Tl (2.3±0.8, P<0.002). Simultaneous acquisition of Tl and sestamibi can help differentiate CNS lymphoma from benign brain lesions in AIDS patients.

Long-term effects of prepubertal testicular vessel ligation on testicular function in the rat.

To determine the effects of unilateral testicular vein and artery ligation in the immature rat on the function and final location of the testis at adulthood, 10-day-old male rats underwent either a sham operation or unilateral ligation of these vessels of the still undescended testis. Testicular location, blood flow, size and histology as well as ventral prostate weights were measured 50 days later at adulthood. At age 60 days, it was determined that all testes were descended into the scrotum, and there were no differences in testis and ventral prostate weights, intratesticular sperm counts and mean seminiferous tubular area between the control and sham operated animals. However, there was an 18% reduction in testicular blood flow (ml. per 100 gm. per minute +/- standard error of mean) in the operated animals when compared to the sham (20.43 +/- 1.10 versus 16.69 +/- 0.74, p less than 0.02). These data indicate that although there is a slight but significant reduction in testicular blood flow at adulthood when the testicular artery and vein are ligated early in life, this diminution is not sufficient to alter the ultimate location, testicular weight and spermatogenic function of the testis. This would suggest that after ligation of the main testicular vessels to the immature testis, the collateral blood supply is able to compensate with time to allow normal growth and development of the testis. These experimental observations provide additional support for the 2-staged approach to the high undescended testis whereby the testicular vessels are initially ligated and a subsequent procedure is performed to place the undescended testis into the scrotum.