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The Low-Energy Beam and Ion Trap facility LEBIT at the NSCL at MSU has demonstrated that rare isotopes produced by fast-beam fragmentation can be slowed down and prepared for precision experiments with low-energy beams. High-pressure gas-stopping was combined with advanced ion manipulation techniques to carry out these studies with a high-precision 9.4-Tesla Penning trap mass spectrometer. The spectrometer has been used for a series of high precision mass measurements of short-lived neutron- and proton-rich isotopes during the past year. This paper presents an overview of the LEBIT facility and summarizes the first mass measurement results. The mass measurements of 81Se, where ground and isomeric states have been resolved, and of 80As will be discussed in detail.

Background:Nutrition in early life plays a critical role in the growth and neurodevelopment of preterm neonates. However, whether early nutrition modified the association of white matter injury (WMI) with brain maturation and neurodevelopmental outcomes remains unclear. Methods:In this prospective cohort study, very preterm neonates were recruited from the NICU at BC Women’s Hospital. MRI and measures of NAA/choline were obtained. Energy intake was recorded over the first two weeks of life and the cohort was dichotomized. Neurodevelopmental outcomes were assessed at 4.5 years of age using WPPSI-III. Results:Neonates in the high lipid group had higher levels of NAA/choline in the basal ganglia. When accounting for confounders, this relationship was only significant in neonates without WMI (p=0.04).Overall, neonates with larger WMI volumes had lower IQ scores at 4.5 years (p<0.001). However, this relationship was attenuated in the high lipid group (p=0.002) relative to the lower lipid intake group. Conclusions:In this cohort, higher energy intake is associated with increased brain maturation. Similarly, neonates with large WMI had higher full-scale IQ if they received greater lipid intake in the neonatal period, suggesting that greater early lipid intake may contribute to blunting the deleterious effects of WMI on neurodevelopmental outcomes.

Abstract.: The Low-Energy Beam and Ion Trap facility LEBIT at the NSCL at MSU has demonstrated that rare isotopes produced by fast-beam fragmentation can be slowed down and prepared for precision experiments with low-energy beams. High-pressure gas-stopping was combined with advanced ion manipulation techniques to carry out these studies with a high-precision 9.4-Tesla Penning trap mass spectrometer. The spectrometer has been used for a series of high precision mass measurements of short-lived neutron- and proton-rich isotopes during the past year. This paper presents an overview of the LEBIT facility and summarizes the first mass measurement results. The mass measurements of 81Se, where ground and isomeric states have been resolved, and of 80As will be discussed in detail.

The Low-Energy Beam and Ion Trap facility LEBIT at the NSCL at MSU has demonstrated that rare isotopes produced by fast-beam fragmentation can be slowed down and prepared for precision experiments with low-energy beams. High-pressure gas-stopping was combined with advanced ion manipulation techniques to carry out these studies with a high-precision 9.4-Tesla Penning trap mass spectrometer. The spectrometer has been used for a series of high precision mass measurements of short-lived neutron- and proton-rich isotopes during the past year. This paper presents an overview of the LEBIT facility and summarizes the first mass measurement results. The mass measurements of 81Se, where ground and isomeric states have been resolved, and of 80As will be discussed in detail.

Forty-eight normal full-term Chinese babies (25 boys and 23 girls) were followed up every 2 mo in the first year and every 3 mo during the second year of life for anthropometric measurements. Blood samples were taken at birth and at 6, 10, 12, and 18 mo after birth for serum GH-binding protein, IGF-I, and IGF-binding protein 3 analysis. Onset of the childhood phase of growth in the infants was determined from the growth data plotted on Infancy-Childhood-Puberty growth charts. The serum GH-binding protein concentrations were low in cord blood but rose significantly at 6 mo, with slower rises in late infancy and early childhood. However, a significant rise in serum IGF-I and IGF-binding protein 3 levels was only observed from 10 mo of life onward. The change in IGF-I between birth and 6 mo was significantly correlated with length gain (r2= 0.35, p < 0.05) and body mass index gain (r2= 0.41, p < 0.01) during the same period. The 34 infants with onset of childhood phase of growth between 6 and 10 mo had a higher mean serum IGF-I value at 10 mo (8.8 ± 5.8 nM versus 4.9 ± 3.1 nM;p < 0.05) and higher length velocity between 10 and 12 mo (16.3 ± 4.7 cm/y versus 8.8 ± 4.3 cm/y;p < 0.001) compared with the 14 infants with a later onset after 10 mo of age. A significant correlation between a change in serum IGF-I and IGF-binding protein 3 levels was observed during the three 6-mo periods between birth and 18 mo, but a significant correlation between a change in serum GH-binding protein and a change in serum IGF-I or IGF-binding protein 3 levels was only seen between 12 and 18 mo of age. The multiple regression analysis (r2= 0.43, p = 0.0002) revealed that the change in serum GH-binding protein and IGF-I concentrations between 6 and 12 mo of age and the age of onset of childhood phase of growth could explain 43% of the length gain between 6 and 12 mo of age in our babies. The results of our study support the hypothesis that the onset of the childhood phase of growth is associated with the onset of significant GH action on growth.

Submicroscopic evidence of persistent minimal residual disease (MRD) in first remission bone marrow samples from children with acute lymphoblastic leukaemia (ALL) indicates a high risk of clinical relapse. Since microscopic evidence of leukaemic lymphoblasts is often present in the peripheral blood in the weeks before clinical presentation at diagnosis or relapse, peripheral blood may be used instead of bone marrow to detect MRD in ALL patients. We examined a median of 0·165 μg (from 1·0–2·0×104cells) genomic DNA from archived peripheral blood smears collected 8–16 months prior to clinical relapse in eight children with ALL for evidence of MRD. We used the polymerase chain reaction and primers designed to identify clonal antigen receptor gene rearrangements. Among the seven patients with bone marrow relapse, MRD was detected at a median of 1·2 months (0–8 months) prior to clinical relapse, indicating that MRD in the peripheral blood may be a late event in the course of leukaemic relapse. A prospective MRD study in ALL patients analysing larger numbers of peripheral blood cells will be needed to evaluate the utility of peripheral blood over bone marrow for MRD testing in childhood ALL.

Wernicke encephalopathy (WE) is a neurological disorder attributable to thiamin deficiency (TD). Severe TD, in humans and animals, results in highly selective lesions with a symmetrical distribution in brain regions including the mammillary bodies, thalamus, inferior colliculi, periaqueductal and periventricular regions, and inferior olivary nuclei. Experimental TD in the rat provides a robust and reproducible model that allows investigations of mechanisms underlying both apoptotic and necrotic neuronal death. (‐)‐Deprenyl (DEP), a selective monoamine oxidase B (MAO‐B) inhibitor, has been reported to be clinically effective in the treatment of neurodegenerative disorders and to have neuroprotective and/or neurorescue properties in a variety of ex vivo and in vitro paradigms, including experimental TD. Because the metabolites of DEP, amphetamine, and methamphetamine may have adverse behavioral effects, a DEP analog, N‐methyl,N‐propargyl‐2‐phenylethylamine (MPPE) that is not metabolized to amphetamine or methamphetamine was examined in the present studies. Results showed that TD rats treated with MPPE had significantly increased neuronal cell counts compared to vehicle‐treated TD rats. MPPE, like DEP, also significantly decreased the density of reactive astrocytes and the infiltration of microglia/macrophages. Chronic treatment with DEP or MPPE resulted in significant inhibition of MAO‐A and MAO‐B activity compared to VEH‐treated animals. Thus, MPPE, an inhibitor of MAO activity, was shown to be neuroprotective in the TD model of neuronal cell death. Drug Dev. Res. 51:244–252, 2000. © 2001 Wiley‐Liss, Inc.

Wernicke encephalopathy (WE) is a neurological disorder attributable to thiamin deficiency (TD). Severe TD, in humans and animals, results in highly selective lesions with a symmetrical distribution in brain regions including the mammillary bodies, thalamus, inferior colliculi, periaqueductal and periventricular regions, and inferior olivary nuclei. Experimental TD in the rat provides a robust and reproducible model that allows investigations of mechanisms underlying both apoptotic and necrotic neuronal death. (-)-Deprenyl (DEP), a selective monoamine oxidase B (MAO-B) inhibitor, has been reported to be clinically effective in the treatment of neurodegenerative disorders and to have neuroprotective and/or neurorescue properties in a variety of ex vivo and in vitro paradigms, including experimental TD. Because the metabolites of DEP, amphetamine, and methamphetamine may have adverse behavioral effects, a DEP analog, N-methyl,N-propargyl-2-phenylethylamine (MPPE) that is not metabolized to amphetamine or methamphetamine was examined in the present studies. Results showed that TD rats treated with MPPE had significantly increased neuronal cell counts compared to vehicle-treated TD rats. MPPE, like DEP, also significantly decreased the density of reactive astrocytes and the infiltration of microglia/macrophages. Chronic treatment with DEP or MPPE resulted in significant inhibition of MAO-A and MAO-B activity compared to VEH-treated animals. Thus, MPPE, an inhibitor of MAO activity, was shown to be neuroprotective in the TD model of neuronal cell death. Drug Dev. Res. 51:244–252, 2000. © 2001 Wiley-Liss, Inc.

Burkholderia cepacia is an opportunistic pathogen that causes severe systemic infections in patients with chronic granulomatous disease (CGD) or with cystic fibrosis (CF), but its mechanisms of virulence are poorly understood. We developed a murine model of systemic infection in wild-type (WT) and gamma interferon knockout (GKO) BALB/c mice to facilitate dissection of components of pathogenicity and host defense. Both WT and GKO mice were susceptible to chronic splenic infection with B. cepacia, but not with Pseudomonas aeruginosa. B. cepacia strains from patients with CGD persisted longer than those from CF patients. C57BL/6 mice were the most susceptible murine strain; bacteria persisted in the spleen for 2 months. DBA/2, BALB/c, and A/J strains of mice were relatively resistant to infection. Certain strains of B. cepacia complex can persist in the murine spleen after systemic infection; this may provide clues to its virulence in compromised hosts, such as those with CGD and CF.

In this study, two factors that could affect fetal drug exposure were examined: 1) the extent of elimination of drug delivered to the fetal liver from the placenta via the umbilical vein; and 2) the degree to which there is preferential distribution of drug in umbilical venous blood to the fetal upper body, as is the case with oxygen and other endogenous substances. Studies were conducted with the histamine H1 antagonist, diphenhydramine (DPHM), in chronically instrumented nonpregnant and pregnant sheep (115-138 days gestation). Hepatic presystemic DPHM elimination was assessed using simultaneous and separate administration of DPHM and stable isotope labeled DPHM ([2H10]DPHM) via the umbilical vein (test route) and abdominal inferior vena cava (control route) in fetal lambs by either bolus injection (N = 6) or 90-min infusion (N = 5), and in nonpregnant sheep (N = 5), by simultaneous and separate bolus injections of the two forms of the drug via the mesenteric vein (test route) and abdominal inferior vena cava (control route). With the bolus injection protocol, hepatic presystemic elimination was estimated by the ratio of the area under the arterial drug concentration vs. time curve for the test and control routes of drug administration, whereas with the fetal infusion study it was calculated as the difference in fetal DPHM clearance values for the test and control routes of administration. To test for isotope effects in the disposition of [2H10]DPHM in the ewe or fetus, both DPHM and [2H10]DPHM were simultaneously injected via the inferior vena cava; however, no isotope effects were noted. In the ewe, there was extensive (93.2 +/- 1.4%) presystemic elimination of DPHM (F 0.068 +/- 0.014). However, in the fetus, this did not occur with bolus drug injection (F = 1.10 +/- 0.07), nor were there differences in the fetal DPHM clearance values estimated from the tarsal and umbilical venous infusions. During the latter experiments, DPHM levels were higher in the femoral artery than in carotid artery, with both umbilical venous and inferior vena caval drug infusion, and this was opposite of the differences in the concentrations of glucose, lactate, and oxygen between these two vessels. Thus, there is extensive hepatic presystemic elimination of DPHM in adult sheep, but no evidence for this phenomenon in the fetus. Furthermore, the preferential distribution of umbilical venous blood to the upper body of the fetal lamb does not result in higher drug levels in ascending aortic blood.

The pharmacokinetics and disposition of valproic acid (VPA) have been assessed in pregnant sheep after both maternal and fetal iv bolus administration. The time course of VPA and 16 of its metabolites was followed in maternal and fetal arterial blood, amniotic fluid, and fetal tracheal fluid for 48 hr after administration. Fetal blood gas, acid-base, metabolic, cardiovascular, and fetal breathing activity parameters were also monitored. The disposition of VPA in maternal serum is best described by a biexponential function with a terminal elimination half-life of 2.13 +/- 0.49 hr and volume of distribution of 0.242 +/- 0.036 liter/kg. VPA transfer to fetal serum and other fetal fluids was rapid after drug administration. There was significant fetal exposure to VPA after maternal dosing (mean AUCinfinityFA/AUCinfinityMA = 0.410 +/- 0.118). Similarly, the disposition of VPA in fetal serum after fetal dosing is best described by a biexponential decay with a terminal elimination half-life of 3.37 +/- 1.37 hr. Once again, VPA transfer to other fluids was rapid. However, unlike basic compounds studied previously, VPA did not accumulate extensively in either amniotic or fetal tracheal fluid. The following metabolites were detected after drug administration in these experiments: (E)- and (Z)-2-ene VPA, (E)- and (Z)-3-ene VPA, 4-ene VPA, 3-keto VPA, 4-keto VPA, 3-OH VPA, 4-OH VPA, 5-OH VPA, and 2-PGA. Both maternal and fetal bolus administration of VPA elicited a significant reduction in fetal breathing movements, which may be attributed to the drug's action on gamma-aminobutyric acid dynamics in the central nervous system (CNS). This suggests that the significant fetal exposure to VPA may produce further CNS-related effects in utero.

We studied seven patients with brainstem infarction and large fusiform vertebrobasilar (VB) aneurysms to clarify the clinical, radiologic, and pathologic features. All presented with pontine infarcts; one also had a cerebellar infarct. VB TIAs preceded brainstem infarction in four patients. Angiography and CT documented VB fusiform aneurysmal dilatation. Four had intraluminal thrombi and one had severe basilar artery stenosis. Two distinct clinical pictures emerged: unilateral pontine infarcts with favorable outcome, presumably related to obstruction of a pontine penetrating artery at its origin from the posterior wall of the aneurysmal basilar artery, and major fatal bilateral pontine infarcts from basilar artery occlusion. Two patients came to autopsy. One had thrombus in the dilated basilar artery and a posterior cerebral artery branch embolus with hemorrhagic occipital infarction; the other had basilar artery thrombus with aneurysmal rupture and subarachnoid hemorrhage. Fusiform VB aneurysms caused brainstem stroke by intraluminal thrombus, local embolism, atherostenosis, and obstruction of paramedian penetrating arteries. Subarachnoid hemorrhage is an uncommon complication.

In the commonly accepted mechanism for enzymatic hydrolysis of cellulose, endo-beta-1,4-glucanases randomly cleave glucosidic bonds within glucan polymers, providing sites for attack by exo-cellobiohydrolases (EC 3.2.1.91). It has been proposed that hydrolysis by Trichoderma reesei cellobiohydrolase II is restricted to the ends of cellulose polymers because two surface loops cover its active site to form a tunnel. In a closely related endoglucanase, E2 from Thermomonospora fusca, access to the substrate appears to be relatively unhindered because the carboxyl-proximal loop is shortened, and the amino-proximal loop is displaced. The hypothesis was examined by deletion of a region in Cellulomonas fimi cellobiohydrolase A corresponding to part of the carboxyl-proximal loop of T. reesei cellobiohydrolase II. The mutation enhanced the endoglucanase activity of the enzyme on soluble O-(carboxymethyl)cellulose and altered its activities on 2',4'-dinitrophenyl-beta-D-cellobioside, insoluble cellulose, and cellotetraose.

We reviewed CTs from 47 patients with 48 spontaneous, supratentorial brain hemorrhages to determine the effect of ventricular blood on outcome. We correlated volumetric analysis of the parenchymal (P) and ventricular (V) blood, as well as other clinical and CT features, with clinical outcome in a statistical analysis. Hemorrhages were located in putamen 20/48 (42), thalamus 13/48 (27), lobar 9/48 (19), caudate 3/48 (6), and miscellaneous locations 3/48 (6). Outcome in putaminal hemorrhages was highly correlated with the total (PV) and P blood volumes, whereas the V blood was less important. For thalamic hemorrhages, outcome correlated more highly with the V and PV volumes than with the P portion. Outcome for ail hemorrhages was significantly correlated, in descending order of importance, with the severity of the initial neurologic deficit, PV blood, hydrocephalus, the number of ventricles containing blood, P, V, and blood in the 4th ventricle. In general patients with more than 20 cc of V blood did poorly. Although hydrocephalus was associated with poor outcome, ventricular drainage did not benefit 8 of 9 patients.

Continuing improvements in intravenous DSA techniques have now shown it to be useful in the angiographic evaluation of STA-MCA bypass function. Both patent and non-patent bypasses were observed in this study. Diagnostically adequate spatial resolution and signal to noise ratio were achieved by electronic magnification and integration techniques. Patient positioning was important and the projection which gave optimal visualization of the STA-MCA bypass, free of vessel overlap, was a 40° oblique, 20° craniocaudal view on the side of interest. Intravenous DSA can complement, and in some cases may supplant, conventional arteriography in the radiologic evaluation of STA-MCA bypass surgery.

AimsTo determine the role of polymerase chain reaction (PCR) based minimal residual disease (MRD) detection of leukaemia specific DNA in testicular relapse in childhood acute lymphoblastic leukaemia.MethodsDNA was obtained from archival testicular and bone marrow samples from boys with acute lymphoblastic leukaemia who relapsed in the testes. Overlapping DJ_H clone specific primers derived from clonal immunoglobulin heavy chain (IgH) gene rearrangement in each case were used to analyse testicular or bone marrow DNA.ResultsHistologically normal end of treatment testicular biopsies in the five patients in longterm remission were all MRD negative, but MRD positive in three of six boys with subsequent testicular relapse. Histologically normal bone marrow samples taken at the end of treatment were MRD negative in five of seven cases, but MRD positive in all cases at the time of isolated testicular relapse. Three boys with unilateral testicular relapse underwent unilateral orchidectomy, rather than bilateral testicular irradiation, as part of their treatment. Two of these boys were MRD positive in the histologically uninvolved testes, and both had subsequent relapses either in the testes or the bone marrow, while the MRD negative patient has not had a testicular relapse.ConclusionsThe presence of MRD in testicular tissue can be assayed with a PCR based method to detect clone specific antigen receptor gene rearrangements. In this setting, PCR is more sensitive than conventional testicular histology for predicting clinical outcomes. MRD assays might be useful in the management of boys at the time of isolated testicular relapse, to confirm the presence of unilateral testicular disease.

Labetalol has been previously shown to cause significant maternal and fetal metabolic effects in pregnant sheep after maternal administration. To investigate these observations further, the present study describes the pharmacokinetics, metabolism and pharmacodynamics of labetalol in the fetal lamb after direct fetal i.v. bolus (4 mg) administration. The fetal total body clearance of labetalol (50.45 +/- 1.37 ml m-1 kg-1), which was significantly higher than that previously determined in the ewe, was composed of transplacental and nonplacental CLs of 23.4 +/- 8.99 ml m-1 kg-1 and 27.05 +/- 10.36 ml m-1 kg-1, respectively. The maternal to fetal plasma labetalol area under the curve ratio was 0.031 +/- 0.002 and the CLmp and CLmn were 7.27 +/- 2.11 ml m-1 kg-1 and 30.5 +/- 5.94 ml m-1 kg-1, respectively. Labetalol concentrations in fetal tracheal fluid were consistently higher than that in fetal plasma. The glucuronide conjugate of labetalol was found in the amniotic fluid at up to 20 times the free drug concentration but the oxidative metabolite, 3-amino-1-phenyl-butane, was not detected in plasma or amniotic fluid samples. The fetal effect of labetalol was characterized by an acute lactic acidosis. The calculated hind limb arteriovenous lactate flux showed a net output of lactic acid equal to 3.85 +/- 2.05 g from the hind limb over 24 h after labetalol administration. Although the fetal exposure to labetalol in this study was roughly 4 times that after a 100-mg maternal bolus administration, the magnitude of fetal lactic acidosis was not significantly different in these studies. The clinical implications of the observations made in this study remain to be investigated.

We describe four patients and review prior reports to clarify the clinical, radiographic, and pathologic findings of intracranial vertebral artery (VA) dissection. A 43-year-old man and a 33-year-old woman had chronic bilateral VA dissecting aneurysms. The man had multiple episodes of subarachnoid hemorrhage (SAH) and necropsy showed multiple dissections and defects in the internal elastica. The woman had many brainstem TIAs and strokes during 3 years. Two other patients had SAH and unilateral dissections. Intracranial VA dissection causes four overlapping syndromes: (1) brainstem infarcts are usually due to subintimal dissection extending into the basilar artery, affect younger patients, and often are single fatal events; (2) SAH is due to subadventitial or transmural dissection; (3) aneurysms cause mass effect on the brainstem and lower cranial nerves; and (4) chronic dissections due to connective tissue defects cause extensive bilateral aneurysms and repeated TIAs, small strokes, and SAH.

We used the posterior cerebral artery amobarbital test to examine how each temporal lobe mediates memory for objects. Temporal lobectomy candidates were presented with four objects while one hemisphere was anesthetized. We assessed recall and recognition following recovery from the drug. Verbal recall was significantly better following object presentation to the left hemisphere when the left hemisphere was not the seizure focus. Recognition memory, tested with two identical objects, two objects that shared the same name but had different physical characteristics, and two foils, was superior following object presentation to the right hemisphere. Only the right hemisphere could discriminate identical objects from same-name foils. These data confirm that the left temporal lobe has an advantage in encoding the verbal representation of an object and suggest that the right temporal lobe is critical for memory of specific visual attributes of objects.

This paper presents a low cost open structure motion controller for the industrial robot PUMA 560. Due to the “black box” fashion of most commercial robot controllers which can be neither accessed nor modified, a PC based “home made” motion control system has been developed to replace the original commercial controller of the Unimation PUMA 560 robot manipulator. Rather than adopting the traditional SUN-VME and UNIXVxWorks based set up, which is quite expensive, our control system is simply based on a novel low-cost PC-QNX-Windows95 (NT) configuration. The system developed consists of a 6 DOFs robot arm, a personal computer based controller running QNX multi-tasking realtime operating system and Photon GUI, a real time 3D graphical animation of the robot arm and remote control of the robot arm through QNX network.

Previous studies have reported a therapeutic window of 0.8 to 2.0 ng/ml within which clonidine exerts its antihypertensive effect. This study was designed to investigate whether there was any loss of blood pressure control when plasma clonidine concentrations exceeded this window owing to its accumulation in renal insufficiency. The results indicate that clonidine concentrations of up to 30 ng/ml in patients with end-stage renal disease (ESRD) can be associated with a maintenance of blood pressure control. It remains to be learned whether this phenomenon of high concentrations and control of blood pressure in our ESRD patient population may be related to altered (decreased) peripheral α-receptor sensitivity and inability to develop vasoconstriction. There is precedence for autonomic imbalance and altered tissue sensitivity in ESRD.

Skin conductance orienting response (OR) to a whistle was measured during selective cerebral deactivation associated with posterior cerebral (PCA) and intracarotid (ICA) amobarbital procedures in a seizure disorder patient. Complete suppression of the OR occurred following both right and left ICA procedures, whereas no reduction in the OR occurred following either PCA injection. Memory performance was independent of OR suppression, as adequate memory was evident in the Intact right hemisphere and poor memory in the seizure focus hemisphere with both the ICA and PCA tests. Anosognosia occurred after the right ICA, but not the PCA procedures or the left ICA procedure. Selective unllateral deactivation of the hippocampus, mesial temporal and calcarine cortex, and lateral thalamus does not impair OR elicitation or awareness of deficit, whereas unilateral deactivation of ICA vascularized regions abolishes the OR. Conversely, anosognosia occurs following right ICA, but not with selective suppression of PCA vascularized cortical territories.

Objectives. We explored racial differences in ischemic cerebrovascular disease. Methods. Clinical and magnetic resonance angiographic (MRA) features were compared in 21 white and 21 Asian patients with symptomatic ischemic cerebrovascular disease. Results. When all carotid artery sites were combined and compared, whites had more stenotic lesions of internal carotid artery origin, and Asians had more stenotic lesions of the middle cerebral artery (MCA) stem. In the vertebrobasilar territory, there were no significant differences in the distribution of extracranial and intracranial stenotic lesions between the two races. In symptomatic territories, the distribution of extracranial and intracranial stenosis were not significant differences for white and Asian patients. In asymptomatic territories, whites had a higher tendency for isolated extracranial stenosis, whereas Asians had an increased incidence of isolated intracranial stenosis. In the combined symptomatic and asymptomatic, carotid and vertebrobasilar territories, there was an increased incidence of extracranial carotid stenotic lesions in white patients and intracranial anterior circulation stenotic lesions in Asians. Demographic factors alone seemed to explain the difference. Conclusions. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of different pathophysiologic abnormalities.

The pretreatment mixed cross‐sectional and longitudinal height measurements of 203 patients with Turner's syndrome (TS) were analysed. Only one observation was included per year per child and a total of 858 observations formed the basis of the growth study. The mean and SD values were fitted separately by a second‐degree polynomial function, giving smoothed growth curves. The spontaneous growth pattern of Chinese girls with TS runs parallel to published Caucasian TS growth curves. The mean final height of Chinese patients with TS was 142 cm compared to 147 cm and 139 cm observed in Northern European and Japanese patients, respectively. Patients with the 46, X, i(Xq) karyotype were found to be significantly shorter, whereas children with the 45, X/46, XY and 46, X, del(Xq) karyotypes were significantly taller among this group of patients. Patients with TS who were disomic for Xp are significantly taller than patients who were monosomic for Xp. Our results suggest that karyotype can have a significant effect on the growth of children with TS.

The effects of diphenhydramine on fetal behavioral states, breathing activity, blood gas status, arterial pressure and heart rate have been investigated in the fetal lamb after maternal or fetal drug administration to steady state in chronically instrumented pregnant sheep. During maternal drug infusion there were declines in the percentage of low voltage electrocorticographic (ECoG) pattern 55-46%), the percentage of low voltage ECoG activity containing rapid eye movements (80-55%), the overall incidence of fetal breathing (42-21%) and in the amount of breathing during low voltage ECoG activity (67-36%). These sedative like effects occurred at fetal plasma drug concentrations (approximately 36 ng/ml) lower than those resulting in discernable central nervous system effects in adults. Drug infusion to fetus achieved higher fetal plasma drug levels (approximately 448 ng/ml) and resulted in a transient decline in arterial Po2 and pH, associated with transient tachycardia and vigorous breathing movements during the initial portion of the infusion. There was also a significant fall in the amount of low voltage ECoG pattern (51-26%) and marked increases in the amount of intermediate voltage pattern (8-46%), and an increase in the occurrence of rapid eye movements during this intermediate voltage pattern (8-63%). In summary, diphenhydramine elicits significant effects in the fetal lamb, the precise nature of which varies with drug concentration.

After radiotherapy, 20 patients, 18 with documented progression of malignant glioma and 2 with Grade II astrocytoma, received a total of 52 courses of intracarotid 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) at a dose of 150 mg/m2 dissolved in 5% dextrose in water. The patients were treated at 6-week intervals for a maximum of five courses of chemotherapy per patient. Response to treatment was analyzed on computed tomographic scans by measuring the volume of the enhancing tumor and any central low density. From these data, tumor doubling times ranging from 110 to 968 days were obtained. An 11 to 60% reduction in enhancing tumor volume was noted in 8 patients, 2 of whom had a greater than 50% decrease in tumor volume. One patient had no change in tumor volume 110 weeks after the initiation of BCNU chemotherapy. Four patients had tumor in more than one vascular territory; tumor growth was arrested in the perfused territory, but continued in the nonperfused area. In 1 of the 4 patients, tumor also grew along a shunt catheter tract and spread over the surface of the ipsilateral hemisphere. One patient developed clinically asymptomatic leukoencephalopathy after five courses of BCNU. Two patients had postradiation leukoencephalopathy before BCNU treatment. Seventeen patients had peritumoral low density with mass effect after BCNU; thus, the true incidence of BCNU-related leukoencephalopathy could not be determined. All patients experienced transient unilateral orbital pain during the infusion and scleral erythema that lasted for several hours afterward. Loss of vision was noted in 2 patients, although it seemed to be related to the therapy in only 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

ABSTRACTCryptosporidiumisolates from diarrheic foals in New Zealand (n= 9) were identified as C. parvum, subtyped at two polymorphic loci, and compared with human (n= 45) and bovine (n= 8) isolates. Foal C. parvumisolates were genetically diverse, markedly similar to human and bovine isolates, and carried GP60 IIaA18G3R1 alleles, indicating a zoonotic potential.

In our home hemodialysis training program, we have tained family members of ten patients to perform venipunctures in arterialized veins of subcutaneous fistulae. Fistula venipuncture training time has not prolonged the total dialysis training period. No fistula has required surgical revision. Our current fistulae dialysis experience at home totals 56 patient months and 604 dialyses. The fistula venipuncture complication rate at home during this period has involved less than 1.5% of all venipunctures. Both the staff and the patients in our hemodialysis unit prefer the subcutaneous arteriovenous fistula to standard arteriovenous shunts.

To the Editor.—In many parts of the country, naturally occurring concentrations of calcium and magnesium necessitate pretreatment of water before dialysis.1 The following case is presented to describe a serious hypernatremia during home hemodialysis resulting from malfunction of a water softener.Report of a Case.—A 44-year-old man with uremia due to chronic glomerulonephritis had been treated by home hemodialysis since March 1967, performed with disposable twin-coil dialyzers in a single-canister, 100-liter tank. Water for dialysis is processed by an automatically cycled cation exchange resin water softener.On April 3, 1970, after two hours of uneventful dialysis, just after a change of the dialysis bath, the patient suddenly felt flushed, developed severe pain in the neck and a headache, and complained of yellow vision. Following a period of profound thirst, he vomited and became combatitive and disoriented. Dialysis was discontinued approximately 10 to 15 minutes after the onset

The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (≥50 stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic temtories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterol-emia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations.