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D Holtzman

Publications and source records attributed to D Holtzman.

At least 37 records · Page 2Linked to original sources
PubMed1997

Multiecho approaches to spectroscopic imaging of the brain.

Spectroscopic imaging (SI) with nuclear magnetic resonance (NMR) is one of the most powerful tools available for studying brain chemistry in vivo. Both proton (1H) and phosphorus (31P) NMR offer valuable biochemical information that can in principle be mapped throughout the entire brain, thereby enhancing our understanding of brain function. With the exception of protons from tissue water and the triglycerides of adipose tissue, however, nuclei contributing to the NMR signals of living tissue are in relatively small (millimolar) concentrations. The low concentration of metabolite nuclei reduces the overall sensitivity of conventional SI techniques, making high-quality metabolite mapping a lengthy procedure. This problem has led to the development and testing of nonconventional methods for reducing SI scan times, including techniques based on the collection of multiple spin-echoes. The extent to which multiecho methods can be used to decrease SI scan times and maintain high-quality metabolite mapping depends on several factors. These include the spectral transverse relaxation times, the spectral resolution required, and J-coupling interactions. We have discussed these various technical aspects of multiecho SI methods as applied to 1H and 31P spectroscopic imaging of the living brain.

Animals↗
PubMed1997

Brain creatine kinase reaction rates and reactant concentrations during seizures in developing rats.

Brain creatine kinase (CK) catalyzed phosphorus fluxes between phosphocreatine (PCr) and ATP and changes in reactant concentrations were measured using [31P] nuclear magnetic resonance spectroscopy ([31P]NMR) before and during pentylenetetrazole-induced seizures in 7 and 21 day old rats. The CK rate constants measured before seizures were three times higher in the older than in the younger rats. The rate constants increased 60% during seizures in the older rats but did not change or decreased in the younger. Small decreases in PCr were seen during seizures at both ages. A small decrease in ATP was seen at 7 days but not at 21 days.

Adenosine Triphosphate↗
PubMed1997

Patterns of health risk behaviors for chronic disease: a comparison between adolescent and adult American Indians living on or near reservations in Montana.

PURPOSE: To compare the chronic disease health risk behavior patterns of adolescents and adults among American Indians living on or near reservations in Montana. METHODS: We analyzed data from the 1993 Youth Risk Behavior Survey of American Indians in Grades 9-12 living on or near Montana reservations. Risk factors included tobacco use, low physical activity, attempted weight loss, and low consumption of fruits, vegetables, and green salad. Similar data were analyzed from a 1994 Behavioral Risk Factor Survey of American Indian adults living on or near reservations in Montana. RESULTS: The prevalence of most adolescent health risk behaviors was high, especially cigarette smoking (45% for males, 57% for females), smokeless tobacco use (44% for males, 30% for females), and infrequent consumption of salad or vegetables (59-76%). With the exception of daily cigarette smoking and inadequate fruit consumption among adolescents of both genders and physical inactivity among adolescent males, the prevalence of chronic disease health risk behaviors among adolescents was similar to or higher than the prevalence of the same risk behaviors among adults. CONCLUSIONS: Many health risk behaviors for chronic diseases are common by the time this group of American Indians in Montana has reached adolescence. Possible reasons may include modeling of familial behaviors, peer pressure, advertising, or age cohort effects. If these risk behavior patterns continue into adulthood, morbidity and mortality from chronic diseases are likely to remain high. Substantial efforts are needed to prevent or reduce health risk behaviors among adolescents and adults in this population.

Adolescent↗
PubMed1997

In vivo brain phosphocreatine and ATP regulation in mice fed a creatine analog.

Mitochondrial and cytosolic creatine kinase (CK) isozymes are active in cells with high and variable ATP metabolic rates. beta-Guanidinopropionic acid (GPA), a competitive inhibitor of creatine transport, was used to study the hypothesis that the creatine-CK-phosphocreatine (PCr) system is important in regulating brain ATP metabolism. The CK-catalyzed reaction rate and reactant concentrations were measured in vivo with 31P nuclear magnetic resonance spectroscopy during energy deficit (hypoxia) or high-energy turnover (seizures) states in urethane-anesthetized mice fed GPA, creatine, or standard chow (controls). Brain phosphagen (i.e., cellular energy reserves) or PCr plus phosphorylated GPA (GPAP) concentrations were equal. The phosphagen-to-NTP ratio was lower than in controls. In vivo CK reaction rate decreased fourfold, whereas ex vivo CK activity that was biochemically measured was doubled. During seizures, CK-catalyzed fluxes increased only in GPA-fed mice. Phosphagen increased in GPA-fed mice, whereas PCr decreased in controls. Survival was higher and brain phosphagen and ATP losses were less for hypoxic GPA-fed mice than for controls. In contrast to mice fed GPA, hypoxic survival and CK reactant concentrations during hypoxia and seizures were the same in creatine-fed mice and controls. Thus GPA, GPAP, or adaptive changes in ATP metabolism stabilize brain ATP and enhance survival during hypoxia in mice.

Adenosine Triphosphate↗
PubMed1996

Population estimates of household firearm storage practices and firearm carrying in Oregon.

OBJECTIVES: To examine statewide data on exposure of adults and children to loaded and unlocked household firearms, and to estimate the prevalence of firearm carrying among adults in Oregon. DESIGN: Analyses of 1992 and 1993 telephone survey data from 6202 adults aged 18 years and older using the Oregon Behavioral Risk Factor Surveillance System. MAIN OUTCOME MEASURES: Number of adults and children exposed to household firearms always or sometimes stored loaded and unlocked. Adjusted odds ratios (ORs) for exposure to loaded and unlocked firearms and firearm carrying among adults by demographic and alcohol use patterns. RESULTS: Ten percent of adults (197 400 persons) lived in households with firearms that were always or sometimes stored loaded and unlocked. An estimated 6.2% of households with children had firearms that were loaded and unlocked, and about 40 000 children lived in these households. Overall, 4.4% of adults carried loaded firearms in the past month. Rural residence, male sex, and less than a college education were associated with living in a household with loaded and unlocked firearms and with firearm carrying. Drinking 5 or more alcoholic beverages on 1 or more occasions in the past month (OR, 1.7; 95% confidence interval, 1.3-2.3) or drinking 60 or more alcoholic beverages in the past month (OR, 1.8; 95% confidence interval, 1.2-2.7) were independently associated with living in households with loaded and unlocked firearms. CONCLUSIONS: Many adults and children are exposed to unsafely stored firearms in Oregon, and many adults carry loaded firearms. Improved public health surveillance of firearm storage and firearm carrying using standardized questions and definitions is needed at the national, state, and local levels.

Adolescent↗
PubMed1996

Relative phosphocreatine and nucleoside triphosphate concentrations in cerebral gray and white matter measured in vivo by 31P nuclear magnetic resonance.

Rates of ATP metabolism generally are higher in cerebral gray matter compared to white matter. In order to study the physiology of this regional difference in vivo, the 1-dimensional chemical shift imaging technique (1D-CSI) was used to acquire 31P nuclear magnetic resonance spectra from 2.5 mm slices of 4-week old piglet brains. Spectra from predominantly gray matter slices (estimated 76% gray matter, 7 mm below the scalp) were compared to predominantly white matter slices (56% estimated white matter, 13 mm below the scalp) as assessed by magnetic resonance images. The 1D-CSI technique introduced no systematic changes in the ratio of signals from a single chamber phantom containing a phosphocreatine (PCr) and ATP solution. Gray matter slices showed a PCr/NTP ratio of 0.93 +/- 0.11 (mean +/- S.D.) using a 2 s interpulse interval, a value very close to the ratio in surface coil localized spectra. The predominantly white matter slices showed a PCr/NTP ratio of 1.32 +/- 0.18 (P < 0.02 for gray versus white matter). Using the estimated percentages of gray and white matter in the two slices and calculated concentrations from fully relaxed spectra, the gray matter PCr/NTP ratio is approximately 0.77, while the ratio in white matter is approximately 2.18. The difference in PCr/NTP measured in vivo suggests that either the total NTP concentration is higher or the steady state PCr concentration is lower in gray matter than in white matter in the piglet brain.

Adenosine Triphosphate↗
PubMed1996

Cerebral metabolic recovery from deep hypothermic circulatory arrest after treatment with arginine and nitro-arginine methyl ester.

BACKGROUND: Recent studies suggest that nitric oxide is important in the pathogenesis of ischemic brain injury and also has a role in controlling cerebrovascular tone. This study examines the net effects of nitric oxide on cerebral metabolic recovery after deep hypothermic circulatory arrest. METHODS: Two-week-old piglets were supported by cardiopulmonary bypass and cooled to 15 degrees C followed by 1 hour of deep hypothermic circulatory arrest, 45 minutes of reperfusion and rewarming, and then 3 hours of normothermic perfusion. Groups of 10 piglets received one of four treatments before bypass; L-nitro-arginine methyl ester, inhibitor of nitric oxide synthesis, 10 mg/kg intravenously; L-arginine, to enhance nitric oxide synthesis, 30 mg/kg intravenously before bypass and then 10 mg/kg per minute during the first hour of reperfusion; a combination of L-nitro-arginine methyl ester plus L-arginine at these same doses; and no pretreatment (controls). Cerebral high-energy phosphates and pH were measured by magnetic resonance spectroscopy in half the animals. Cerebral blood flow, metabolic rates for oxygen and glucose, and the oxidation/reduction state of cytochrome aa3 and oxygenated and deoxygenated hemoglobin measured by near-infrared spectroscopy were assessed in the other half of the piglets. RESULTS: L-nitro-arginine methyl ester significantly increased cerebral vascular resistance and markedly reduced recovery of high-energy phosphates, pH, and oxidation state of cytochrome aa3, L-arginine increased cerebral blood flow, cerebral glucose and oxygen consumption, and recovery of cytochrome aa3 oxidation and high-energy phosphates. L-Arginine did not reverse completely the effects of L-nitro-arginine methyl ester on cerebral metabolic recovery. CONCLUSION: In a piglet model of deep hypothermic circulatory arrest, L-nitro-arginine methyl ester has a deleterious effect and L-arginine has a beneficial effect on cerebral metabolic recovery. The deleterious metabolic effects of L-nitro-arginine methyl ester are only partially reversed by L-arginine. This fact suggests that there may be mechanisms in addition to inhibition of nitric oxide synthesis contributing to the neurotoxicity of L-nitro-arginine methyl ester in this model.

Animals↗
PubMed1996

Phosphocreatine and creatine kinase in piglet cerebral gray and white matter in situ.

Rates of adenosine triphosphate (ATP) metabolism are higher in cerebral gray matter than in white matter. Like other excitable tissues, brain contains a phosphocreatine (PCr)/creatine kinase (CK)/ATP system including cytosolic (B-CK) and mitochondrial (Mi-CK) isozymes. High B-CK activity is present in white and gray matter while Mi-CK is mostly in gray matter. An in situ localizing 31P-NMR technique, one-dimensional chemical shift imaging (1D-CSI), has been used to study the PCr/CK/ATP system in these regions. In the metabolically mature 4-week-old piglet, the PCr/nucleoside triphosphate (NTP) ratio measured by the 1D-CSI technique is at least 50% higher in white than gray matter. Total creatine (Cr), ATP, and total NTP concentrations are the same in rapidly frozen rat white and gray matter, suggesting that PCr/Cr ratio is much higher in white matter. The PCr increases more in gray than white matter between 4 days and 4 weeks of age in piglet brain. The CK catalyzed reaction rate constant, measured by combining the saturation transfer experiment with the 1D-CSI, is also much higher in white than gray matter at both ages. The postnatal maturational increase in the CK rate constant is greater in gray matter. In summary, these differences in PCr concentration and CK reaction rates and isozymes characterize two physiologically different PCr/CK/ATP systems in gray and white matter.

Animals↗
PubMed1996

'Hot spots' of creatine kinase localization in brain: cerebellum, hippocampus and choroid plexus.

Creatine kinase (CK) isoenzymes, with emphasis on the mitochondrial CK isoenzymes, were characterized and localized in chicken cerebellum. Chicken cerebellum extracts analyzed by two-dimensional gels, using antipeptide antibodies specific for sarcomeric muscle-type mitochondrial CK (Mib-CK) and revealed the presence of a Mib-CK variant in avian cerebellum. This CK isoform was localized by immunofluorescence staining exclusively in the Purkinje neurons. The co-expression of this Mib-CK together with cytosolic muscle-type MM-CK, as observed in the same Purkinje neurons, may reflect the specific energy requirements associated with highly fluctuating Ca2+ levels (Ca2+ spiking) in these specialized neurons. Ubiquitous brain-type mitochondrial Mia-CK was found together with cytosolic BB-CK mainly in the glomeruli structures of the cerebellar granular layer. BB-CK, but much less so Mia-CK however, was also very prominent in Bergmann glial cells of the two mitochondrial Mi-CK isoenzymes in the chicken cerebellum is demonstrated. Other hot spots of CK localization were the granule and pyramidal cells of the hippocampus in rat. There, a developmental stage-dependent immunofluorescence staining, especially with antibodies against Mia-CK was noted. Epithelial cells of the choroid plexus were also highly enriched in CK. The possible implications of a CK/PCr circuit at these various cellular locations of the brain are discussed with respect to normal brain physiology and pathology.

Animals↗
PubMed1996

Cerebral oxygenation measured by near infrared spectroscopy during cardiopulmonary bypass and deep hypothermic circulatory arrest in piglets.

Near infrared spectroscopy (NIRS) shows large changes in cerebral oxyhemoglobin (Hbo2), deoxyhemoglobin (Hb), and oxidation state of cytochrome aa3 (Cyto2) in infants undergoing cardiopulmonary bypass and deep hypothermic circulatory arrest (CPB-DHCA). To evaluate the physiologic significance of these clinical NIRS measurements, we applied the technique in a piglet model of CPB-DHCA. After an initial stabilization period on CPB, animals (n = 8) were cooled to 15 degrees C, subjected to DHCA for 1 h, then reperfused with rewarming and monitored for 180 min. NIRS measurements were compared with determinations of cerebral blood flow (CBF). During cooling, Cyto2 decreased markedly, whereas Hbo2 increased. DHCA was associated with a sharp decrease in Hbo2, a corresponding increase in Hb, and a smaller, less consistent further decrease in Cyto2. NIRS measurements recovered toward baseline with reperfusion. CBF decreased during cooling and recovered to baseline levels with reperfusion. These findings are consistent with existing human data and show that 1) cooling is associated with increased oxygenation of cerebral hemoglobin despite a reduction in CBF; 2) Cyto2 becomes more reduced during cooling, consistent with a net cellular oxygen deficit; and 3) DHCA is associated with rapid cerebral hemoglobin deoxygenation and a small further reduction of Cyto2.

Animals↗
PubMed1996

Nevermore: the hymen and the loss of virginity.

A major milestone in a woman's life is the loss of virginity, "defloration," with the breaking of the hymen. Psychoanalysis has paid little attention to the meaning of defloration to either women or men, and virtually none to the hymen as a part of the female genitalia. The reasons for this disregard or avoidance are explored. Utilizing the few psychoanalytic writings, mythology, literature, and anthropological studies in addition to numerous clinical examples, the authors find that the unconscious meanings of the loss of virginity and the hymen emerge clearly. The common theme is that of negation, never, never again, never seen, known or named. Theoretical considerations regarding female sexuality are discussed. Technical implications for analyst-patient are presented.

Adult↗
PubMed1995

Enamel hypoplasia, bilateral cataracts, and aqueductal stenosis: a new syndrome?

We report on a 12-year-old girl who presented with generalized enamel hypoplasia, cataracts, and enlargement of the cerebral ventricles secondary to aqueductal stenosis. Previously described syndromes of enamel defects with or without cataracts were excluded on the basis of clinical criteria and appearance of the dentition. Metabolic conditions which could have caused cataracts were excluded clinically and by biochemical tests. The combination of signs in this patient may represent a new syndrome.

Abnormalities, Multiple↗
PubMed1995

Phosphocreatine and ATP regulation in the hypoxic developing rat brain.

Decreased brain ATP and phosphocreatine (PCr) concentrations and intracellular pH were compared in hypoxic 4-, 10-11, and 24-25-day-old rats. Surface coil 31P-nuclear magnetic resonance (NMR) spectra were acquired in vivo every minute before, during, and after 7 min of breathing 4% O2. At all ages PCr decreased rapidly. At the two younger ages, the nucleoside triphosphate signal was still 80-85% of pre-hypoxic values, indicating 20-30% decrease in ATP, when PCr was almost fully depleted. At 24-25 days, PCr initially decreased 40-50% with an ATP loss of about 30%. Then, PCr and ATP decreased simultaneously. The decrease in brain pH was greatest at 24-25 days. More electrocortical seizure activity during hypoxia was seen at 10-11 days than at other ages. Seizure activity was seen only when ATP was less than 20% depleted and was not associated with more rapid decreases in ATP or PCr. At all ages, loss of electrocortical activity occurred when ATP was about 30% depleted. Brain creatine kinase catalyzed flux, measured by the NMR saturation transfer experiment before the hypoxic period, was 4-fold higher at 24-25 days than at 4- or 10-11 days. In conclusion, the temporally coupled depletion of PCr and ATP during hypoxia, which is characteristic of the mature brain, is seen only after the maturational increase in brain CK activity.

Adenosine Triphosphate↗
PubMed1995

Creatine and nucleoside triphosphates in rat cerebral gray and white matter.

In vivo localized nuclear magnetic resonance spectroscopy has shown three-fold higher phosphocreatine/nucleoside triphosphate (PCr/NTP) ratios in cerebral white compared to gray matter. To interpret these results, total creatine (Cr) and ATP concentrations were measured enzymatically in samples taken from rapidly frozen rat cerebral cortex and corpus callosum. Total Cr (PCr plus Cr) and ATP concentrations were the same in the two regions. High performance liquid chromatography showed similar concentrations of total NTP in the two regions. These results suggest that higher in vivo PCr/NTP ratios in white compared to gray matter may be due to a higher PCr/Cr ratio in white matter and/or higher percentages of non-adenine mono- or diphosphate nucleotides in gray matter.

Animals↗
PubMed1995

pH strategies and cerebral energetics before and after circulatory arrest.

The pH-stat strategy compared with the alpha-stat strategy provides more rapid recovery of brain high-energy phosphate stores and intracellular pH after 1 hour of hypothermic circulatory arrest in pigs. Possible mechanisms for this difference are (1) improved oxygen delivery and homogeneity of brain cooling before deep hypothermic circulatory arrest and (2) greater cerebral blood flow and reduced reperfusion injury owing to extracellular acidosis during the rewarming phase. To identify which of these mechanisms is predominant, we studied 49 4-week-old piglets undergoing 1 hour of deep hypothermic circulatory arrest. Four groups were defined according to cooling/rewarming strategy: alpha/alpha, alpha/pH, pH/alpha, and pH/pH. In 24 animals cerebral high-energy phosphate levels and intracellular pH were measured by magnetic resonance spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 5). In 25 animals cerebral blood flow was measured by labeled microspheres, cerebral metabolic rate by oxygen and glucose extraction, and the redox state of cytochrome aa3 and hemoglobin oxygenation by near infrared spectroscopy (alpha/alpha group 7, alpha/pH group 5, pH/alpha group 7, pH/pH group 6). Cerebral blood flow was greater with pH-stat than alpha-stat during cooling (56.3% +/- 3.7% versus 32.9% +/- 2.1% of normothermic baseline values, p < 0.001). Cytochrome aa3 values became more reduced during cooling with alpha-stat than with pH-stat (p = 0.049). Recovery of adenosine triphosphate levels in the initial 45 minutes of reperfusion was more rapid in group pH/pH compared with that in the other groups (p = 0.029). Recovery of cerebral intracellular pH in the initial 30 minutes was faster in group pH/pH compared with that in group alpha/alpha (p = 0.026). Intracellular pH became more acidic during early reperfusion only in group alpha/alpha, whereas it showed continuous recovery in the other groups. This study suggests that there are mechanisms in effect during both the cooling and rewarming phases before and after deep hypothermic circulatory arrest that could contribute to an improved cerebral outcome with pH-stat relative to more alkaline strategies.

Adenosine Triphosphate↗
PubMed1995

Reduction of cytochrome aa3 measured by near-infrared spectroscopy predicts cerebral energy loss in hypoxic piglets.

Near-infrared spectroscopy is a noninvasive monitoring technique that allows quantitative measurement of changes in cerebral oxygenated Hb (HbO2), deoxygenated Hb (Hb), total Hb, and oxidized cytochrome aa3 (CytO2). Changes in cerebral Hb oxygenation and CytO2 have been measured in human neonates and infants under a variety of conditions. However, the association of these measurements with cerebral high-energy phosphate loss is not known. We studied simultaneous changes in cerebral HbO2, Hb, total Hb, and CytO2 by near-infrared spectroscopy and changes in nucleoside triphosphate (NTP, mostly ATP) and phosphocreatine (PC) concentrations and intracellular pH by in vivo 31P-labeled magnetic resonance spectroscopy. Four-wk-old piglets (n = 8) underwent sequential hypoxic episodes of increasing severity (inspired O2 concentration, 12, 8, 6, 4, and 0%). Animals were anesthetized and mechanically ventilated. At all levels of hypoxia, cerebral HbO2 decreased, and Hb increased. Loss of PC or NTP was not observed until inspired O2 concentration was decreased to less than 12%. With such severe hypoxia, hypotension, intracellular acidosis, and increasingly severe PC and NTP depletions occurred. Decreases in PC and NTP correlated closely with decreased CytO2 and arterial blood pressure (p < 0.0001) but not with changes in HbO2 and Hb. In conclusion, cerebral hypoxemia is readily detected by near-infrared spectroscopy as a decrease in HbO2 and an increase in Hb. However, relative changes in cerebral HbO2 and Hb have low predictive value for cerebral energy failure. Reduction of CytO2 is highly correlated with decreased brain energy state and may indicate impending cellular injury.

Animals↗
PubMed1995

Trends in risk behaviors for HIV infection among U.S. high school students, 1989-1991.

The objective of this study was to examine trends in rates of self-reported HIV-related instruction and behaviors among high school students in the United States. Self-administered questionnaires were completed by three independent, multistage national probability samples of public and private school students in grades 9 through 12 who were surveyed in the spring of 1989, 1990, and 1991, respectively. Controlling for demographic characteristics, we used logistic regression to test for trends from 1989 to 1991. From 1989 to 1991, the proportion of students who had received HIV instruction in school significantly increased from 53.7% in 1989 to 83.3% in 1991. At the same time, the proportion of students engaging in selected sexual behaviors generally decreased. We found significant declines in the proportion of students who had engaged in sexual intercourse (58.5% in 1989 to 54.1% in 1991), had two or more sex partners during their lifetime (40.1% in 1989 to 35.2% in 1991), and had four or more lifetime sex partners (23.6% in 1989 to 18.7% in 1991). School-based HIV instruction, which is reaching greater numbers of U.S. students, may be contributing to the decline in reported risk behavior. However, because the current level of HIV-related behavior is still too high, risk-reduction efforts for adolescents should be maintained and strengthened.

Adolescent↗