Jeffrey K. Lu

Diffusion tensor imaging of the corpus callosum in Autism.

The corpus callosum is the largest commissural white matter pathway that connects the hemispheres of the human brain. In this study, diffusion tensor imaging (DTI) was performed on subject groups with high-functioning autism and controls matched for age, handedness, IQ, and head size. DTI and volumetric measurements of the total corpus callosum and subregions (genu, body and splenium) were made and compared between groups. The results showed that there were significant differences in volume, fractional anisotropy, mean diffusivity, and radial diffusivity between groups. These group differences appeared to be driven by a subgroup of the autism group that had small corpus callosum volumes, high mean diffusivity, low anisotropy, and increased radial diffusivity. This subgroup had significantly lower performance IQ measures than either the other individuals with autism or the control subjects. Measurements of radial diffusivity also appeared to be correlated with processing speed measured during the performance IQ tests. The subgroup of autism subjects with high mean diffusivity and low fractional anisotropy appeared to cluster with the highest radial diffusivities and slowest processing speeds. These results suggest that the microstructure of the corpus callosum is affected in autism, which may be related to nonverbal cognitive performance.

Diffusion tensor imaging of white matter in the superior temporal gyrus and temporal stem in autism.

Recent MRI studies have indicated that regions of the temporal lobe including the superior temporal gyrus (STG) and the temporal stem (TS) appear to be abnormal in autism. In this study, diffusion tensor imaging (DTI) measurements of white matter in the STG and the TS were compared in 43 autism and 34 control subjects. DTI measures of mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were compared between groups. In all regions, fractional anisotropy was significantly decreased and both mean diffusivity and radial diffusivity were significantly increased in the autism group. These results suggest that white matter microstructure in autism is abnormal in these temporal lobe regions, which is consistent with theories of aberrant brain connectivity in autism.

Superior Temporal Gyrus, Language Function, and Autism

Deficits in language are a core feature of autism. The superior temporal gyrus (STG) is involved in auditory processing, including language, but also has been implicated as a critical structure in social cognition. It was hypothesized that subjects with autism would display different size-function relationships between the STG and intellectual-language-based abilities when compared to controls. Intellectual ability was assessed by either the Wechsler Intelligence Scale for Children–Third Edition (WISC–III) or Wechsler Adult Intelligence Scale–Third Edition (WAIS–III), where three intellectual quotients (IQ) were computed: verbal (VIQ), performance (PIQ), and full-scale (FSIQ). Language ability was assessed by the Clinical Evaluation of Language Fundamentals–Third Edition (CELF–3), also divided into three index scores: receptive, expressive, and total. Seven to 19-year-old rigorously diagnosed subjects with autism (n = 30) were compared to controls (n = 39; 13 of whom had a deficit in reading) of similar age who were matched on education, PIQ, and head circumference. STG volumes were computed based on 1.5 Tesla magnetic resonance imaging (MRI). IQ and CELF–3 performance were highly interrelated regardless of whether subjects had autism or were controls. Both IQ and CELF–3 ability were positively correlated with STG in controls, but a different pattern was observed in subjects with autism. In controls, left STG gray matter was significantly (r = .42, p ≤ .05) related to receptive language on the CELF–3; in contrast, a zero order correlation was found with autism. When plotted by age, potential differences in growth trajectories related to language development associated with STG were observed between controls and those subjects with autism. Taken together, these findings suggest a possible failure in left hemisphere lateralization of language function involving the STG in autism. Superior Temporal Gyrus, Language Function, and Autism

Effects of intrathecal morphine on the ventilatory response to hypoxia.

BACKGROUND Intrathecal administration of morphine produces intense analgesia, but it depresses respiration, an effect that can be life-threatening. Whether intrathecal morphine affects the ventilatory response to hypoxia, however, is not known. METHODS We randomly assigned 30 men to receive one of three study treatments in a double-blind fashion: intravenous morphine (0.14 mg per kilogram of body weight) with intrathecal placebo; intrathecal morphine (0.3 mg) with intravenous placebo; or intravenous and intrathecal placebo. The selected doses of intravenous and intrathecal morphine produce similar degrees of analgesia. The ventilatory response to hypercapnia, the subsequent response to acute hypoxia during hypercapnic breathing (targeted end-tidal partial pressures of expired oxygen and carbon dioxide, 45 mm Hg), and the plasma levels of morphine and morphine metabolites were measured at base line (before drug administration) and 1, 2, 4, 6, 8, 10, and 12 hours after drug administration. RESULTS At base line, the mean (+/-SD) values for the ventilatory response to hypoxia (calculated as the difference between the minute ventilation during the second full minute of hypoxia and the fifth minute of hypercapnic ventilation) were similar in the three groups: 38.3+/-23.2 liters per minute in the placebo group, 33.5+/-16.4 liters per minute in the intravenous-morphine group, and 30.2+/-11.6 liters per minute in the intrathecal-morphine group (P=0.61). The overall ventilatory response to hypoxia (the area under the curve) was significantly lower after either intravenous morphine (20.2+/-10.8 liters per minute) or intrathecal morphine (14.5+/-6.4 liters per minute) than after placebo (36.8+/-19.2 liters per minute) (P=O.003). Twelve hours after treatment, the ventilatory response to hypoxia in the intrathecal-morphine group (19.9+/-8.9 liters per minute), but not in the intravenous-morphine group (30+/-15.8 liters per minute), remained significantly depressed as compared with the response in the placebo group (40.9+/-19.0 liters per minute) (P= 0.02 for intrathecal morphine vs. placebo). Plasma concentrations of morphine and morphine metabolites either were not detectable after intrathecal morphine or were much lower after intrathecal morphine than after intravenous morphine. CONCLUSIONS Depression of the ventilatory response to hypoxia after the administration of intrathecal morphine is similar in magnitude to, but longer-lasting than, that after the administration of an equianalgesic dose of intravenous morphine.

The Dose-response Pharmacology of Intrathecal Sufentanil in Female Volunteers

The pharmacologic effects of intrathecal sufentanil (ITS) beyond what is clinically administered (10 micro g) are not known.We observed 18 healthy, young, adult female volunteers who received 12.5, 25, or 50 micro g of ITS in a randomized, double-blind fashion for 11 h. Analgesia was assessed by pressure algometry at the tibia. Respiratory function was assessed by pulse oximetry, respiratory rate, arterial blood gas, the ventilatory response to CO2, and a respiratory intervention score (RIS). The incidence and severity of side effects also were documented. Serum sufentanil levels were measured for 4 h after ITS administration. We found that ITS produced statistically significant changes in algometry, doubling the pressure required to produce moderate pain. However, doses of ITS greater than 12.5 micro g failed to produce proportionate increases in the duration or intensity of analgesia. All doses of ITS produced significant respiratory depression, but only the RIS was significantly related to ITS dose. Neither respiratory rate nor sedation reliably predicted hypoxemia. Supplemental oxygen by nasal cannula consistently prevented pulse oximeter readings below 90%. Serum sufentanil concentrations were related to ITS dose in a statistically significant manner, reached clinically significant concentrations, and followed a time course similar to analgesia and measures of respiratory depression. However, there was no significant increase in measured analgesia associated with the increases in serum sufentanil concentrations. We conclude that in our volunteer model of lower extremity pain, administering ITS in doses larger than 12.5 micro g does not improve the speed of onset, magnitude, or duration of analgesia and only causes dose-related increases in serum sufentanil concentrations, which may augment respiratory depression. (Anesth Analg 1997;85:372-9)

Maternal Respiratory Arrests, Severe Hypotension, and Fetal Distress after Administration of Intrathecal, Sufentanil, and Bupivacaine after Intravenous Fentanyl

THERE have been several reports of respiratory depression occurring in association with combined spinal epidural (CSE) analgesic techniques. 1-3 Intravenous fentanyl has been commonly administered in our institution to laboring women who either do not desire epidural analgesia or request analgesia before placement of an epidural catheter. The use of intrathecal sufentanil (ITS) plus low dose bupivacaine in CSE techniques for labor analgesia has become popular, although the use of CSE analgesia techniques may increase the risk of respiratory depression if administered after intravenous opioids have been previously given. We report one case of maternal respiratory arrest and one case of maternal respiratory arrest and severe hypotension, both accompanied by fetal distress, in two parturients who received ITS and bupivacaine after intravenous fentanyl.

Delays in the detection of hypoxemia due to site of pulse oximetry probe placement

STUDY OBJECTIVES To determine if there were any differences in the time to detect hypoxemia related to the site of peripheral pulse oximetry (ear, hand, and foot) during the rapid induction of hypoxemia in healthy volunteers. DESIGN Repeated-measures, longitudinal, observational study. SETTING Anesthesia clinical research area of the Department of Anesthesiology. PATIENTS 13 healthy volunteers, aged 18 to 44 years. INTERVENTIONS Nellcor N-200 (Nellcor, Inc., Pleasanton, CA) oximeter probes were placed at the ear, hand, and foot. All units were turned on simultaneously with averaging times set for 5 seconds and signals sampled at 2 Hz. A computer-controlled anesthesia circuit was employed to induce mild hypercapnia and hyperoxia (end-tidal gas partial pressures: PETCO2 = 42 +/- 2 mmHg and PETO2 = 130 mmHg) for 5 minutes. PETO2 was then decreased to 45 +/- 2 mmHg over 60 seconds and held at that value for 5 minutes. MEASUREMENTS AND MAIN RESULTS The mean differences in time (sec) for pulse oximeters to detect hypoxemia (read less than 90%) between probe sites were determined and compared. The following mean differences in time (sec) for pulse oximeters to detect hypoxemia (read less than 90%) between probe sites were found: ear-hand = 6; hand-foot = 57; ear-foot = 63. Paired t-tests revealed statistically significant mean time delay differences of 51 seconds (p < 0.005) and 57 seconds (p < 0.005) for ear-hand versus hand-foot and for ear-hand versus ear-foot, respectively. CONCLUSIONS In healthy volunteers, significant delays in the detection of acute hypoxemia by pulse oximetry occur when pulse oximeters are placed at the toe as compared with probes at either the ear or hand.

Regional Callosal Morphology in Autism and Macrocephaly

Previous investigations have reported decreased size of the corpus callosum (CC) in autism. However, little is known of the regional distribution of these callosal abnormalities. Additional uncertainty exists regarding the role of head size with respect to variations in callosal size in individuals with autism. This study investigated the size of the CC in 5 groups of high functioning individuals: (1) normocephalic autistic individuals; (2) autism with macrocephaly; (3) non-autistic normocephalic controls; (4) non-autistic participants with benign macrocephaly; and (5) a reading disordered (RD) group, comprised of non-autistic individuals with a deficit in reading. The CC was traced from midsaggital MRIs and the outlines partitioned into 99 equidistant width measures. Factor analysis of the 99 widths revealed 10 contiguous callosal regions. Individuals with macrocephaly (autistic and non-autistic) had larger total CC size. Regional analysis revealed a significantly larger CC midbody in macrocephaly, regardless of presence or absence of autism. Within normocephalic individuals, those with autism had a smaller CC genu and midbody than either non-autistic controls or RD individuals. These results underscore the importance of considering head size in studies of CC morphology in autism. These findings add to the literature implicating problems of interhemispheric connectivity being present in individuals with autism.

Quantitative magnetic resonance image analysis of the cerebellum in macrocephalic and normocephalic children and adults with autism

A detailed morphometric analysis of the cerebellum in autism with and without macrocephaly. Four subject groups (N = 65; male; IQs > or = 65; age 7 to 26 years) were studied with quantitative MRI; normocephalic and macrocephalic individuals with autism without mental retardation were compared to normocephalic and benign macrocephalic typically developing individuals. Total cerebellum volumes and surface areas of four lobular midsagittal groups were measured. Independent t-tests between autism and control subjects matched for head size revealed no significant differences. Multivariate analyses of variance were also performed, using the diagnostic group as the fixed factor, cerebellar measures as the dependent variables and total intracranial volume, total brain volume, age, verbal IQ, and performance IQ as covariates. No significant differences were found; however, a trend was noted in which macrocephalic individuals with autism consistently exhibited slightly smaller cerebellar volume or surface area when compared to individuals with benign macrocephaly. In autism, with and without macrocephaly, cerebellar structures were found to be proportional to head size and did not differ from typically developing subjects.

Minimally invasive aortic valve replacement with orthotopic liver transplantation: report of a case

Cardiac surgery and liver transplantation (LT) are rarely performed at the same time, because of the potential risks of coupling two such complex surgical procedures [1–3]. This combined surgery is typically reserved for patients with structural heart disease, including multivessel obstructive coronary artery disease and severe valvular disease with heart failure and end-stage liver disease, in whom the untreated organ may decompensate if only one organ is addressed [4]. Combined aortic valve replacement (AVR) and LT is the rarest of such combined surgery, with only ten cases published previously. We present the first reported case of combined minimally invasive AVR and LT and review the literature on similar combined surgery.