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The detection of coronary artery disease is difficult if a patient has electrocardiographic evidence of left bundle branch block (BBB). Septal blood flow may be reduced in patients with left BBB, despite no angiographic evidence of left anterior descending (LAD) coronary artery disease. We have developed a new method of quantification of Thallium-201 single-photon emission computed tomographic (SPECT) images with the aim of better separating patients with left BBB and LAD disease from these with left BBB alone. The study cohort comprised 8 normal subjects (group I) and 20 patients with left BBB and chest pain who underwent thallium-201 SPECT imaging and coronary angiography. Eight patients (group II) had [less than or equal to]50% LAD stenosis, and 12 (group III) had [greater than or equal to]70% LAD stenosis. Septal abnormality scores on the second short-axis Slice from the base were computed, based on comparison of each subject's short-axis circumferential profile with a normal reference curve. This followed a procedure in which each profile was scaled to minimize differences in its absolute level in relation to the reference curve. Septal abnormality scores on stress images were 0.8 [+ or -] 22 for group I, 27 [+ or -] 43 for group II, and 165 [+ or -] 67 for group III (p= 0.15 for group I vs II, and p (Am J Cardiol 1992;70:1565-1570)

In transcortical aphasia, the patient is capable of repeating sentences, but has severe difficulties in interpreting them or in forming his own sentences. Speech is apparently carried out by the left perisylvian area, that is, the area in the brain near the left Sylvian sulcus, the largest invagination of cerebral cortex on the side of the brain. It has been assumed that transcortical aphasia results when regions surrounding the perisylvian area are damaged by a stroke while the perisylvian area itself remains intact. Therefore, the speech mechanisms remain intact but cut off from surrounding areas which may be critical to connecting speech with meaning. Observations on a series of 21 patients with transcortical aphasia now suggest that this view may be overly simplistic, and that a significant portion of the ability to repeat speech in these patients comes not from the left hemisphere at all, but from the hemisphere nondominant for speech, the right hemisphere. Contrary to expectation, it was found that lesions in the perisylvian area were just as common as lesions surrounding the perisylvian area in these patients. In two patients, both with perisylvian lesions, the injection of amytal into the right internal carotid artery resulted in the abolition of the ability to repeat sentences. This injection technique anesthetizes half the brain, in this case the right half. The abolition of speech repetition indicates that the right hemisphere was necessary for the repetition in these two individuals. The suspicion that the right hemisphere may play a role in speech repetition was strengthened when another patient developed a second stroke, this time in the right hemisphere. This patient lost his ability to repeat sentences. The results suggest that the right hemisphere, normally nondominant for language, might manage language repetition in cases where the normal language centers on the left side of the brain have been damaged. (Consumer Summary produced by Reliance Medical Information, Inc.)

It seems that medical imaging technology will continue to advance as long as there is more to be seen and more information to be extracted. Computed tomography (CT) uses X-rays to reconstruct the three-dimensional relationships of structures, and is a vast improvement over the shadow-casting of conventional radiographic plates. The fact that CT scanning uses X-rays means that radiologists can rely upon a vast storehouse of experience in the interpretation of what CT images actually reflect. This is not true of magnetic resonance imaging (MRI), which is already replacing CT for many applications. The resolution of MRI results in images far sharper than can be achieved with CT. The images reflect variations in the magnetic environment of hydrogen atoms in water, and thus the appearance of lesions on MRI is different from imaging systems based upon X-rays. Lesions may fail to appear on MRI, and lesions of disparate pathology may appear similar on MRI. Furthermore, the sum total of experience on the interpretation of MR images is, at present, still relatively small. The superior image quality, however, ensures that the experience will be sought and that MRI will find increasing use. Attempts have been made to use magnetic resonance for other atoms besides hydrogen. Unfortunately, only water is present in large enough amounts to render a good image in a reasonable time. Therefore, the magnetic resonance of atoms such as phosphorus serves only as a tool for spectroscopy. Nuclear magnetic resonance spectroscopy can observe the ratio of phosphates in different stages of cellular energy metabolism, and thus provide information on the chemical functioning of the brain. More precise data in the biochemical function of the brain can be provided by positron emission tomography (PET) and single photon emission tomography (SPECT), which use emissions from radioactive tracers to construct an image of where the tracers are concentrated in living tissue. Through the appropriate tracer, detailed information about the location of key biochemical processes may be obtained. These imaging technologies, used to complement one another, will yield information about cancer in its living, dynamic state, and complement the pathological analysis of processed tissue specimens. (Consumer Summary produced by Reliance Medical Information, Inc.)

ONE OF THE promises I made upon becoming superintendent in Dorchester County, Md., about five years ago was that our business, local government and faith-based leaders would become a part [...]

AS THE PARADIGMS of public education evolve and sometimes conflict, I have found that a periodic self-assessment of basic leadership principles can keep me grounded and moving forward. In that [...]

Most school district leaders deal with the unpleasant reality of appointment recommendations for posted positions at all levels being questioned and second-guessed. Often, these appointment recommendations are the fodder of [...]

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There is a growing body of evidence that combining radiotherapy with ipilimumab might improve the survival and response rates in patients with metastatic melanoma. However, the patient and treatment variables that predict for improved outcomes have not been well defined. We conducted a retrospective analysis of 69 patients treated with ipilimumab and radiotherapy for metastatic melanoma at a single institution from May 2011 to June 2015. Demographic, clinical, and treatment factors were recorded, and end points of interest included infield and global complete response (CR) after the completion of radiation and ipilimumab based on the RECIST criteria (v1.1), and overall survival (OS). A bivariate and multivariate analysis was then performed to assess the relationship between outcomes and patient variables. In the multivariate analysis, infield CR was significantly associated with completing a full course of ipilimumab, a higher BED, and a smaller size of metastatic area treated. Global CR was significantly associated with increased age and giving radiotherapy to all areas of disease. OS was significantly associated with completing a full course of ipilimumab and a higher BED. Interestingly, after a multivariate analysis, higher BED was associated with an improved infield CR (p= 0.0281) and was not associated with an improved global CR (p= 0.5284) but was marginally associated with improved OS (p= 0.0545). Our findings suggest that the rate of a global CR is independent of the dose of radiation given, but the rate of infield CR and OS might improve with higher doses.

ABSTRACTThere is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

Many individuals with post-traumatic stress disorder (PTSD) experience persistent symptoms despite pharmacological treatment with antidepressants. Several open-label monotherapy and adjunctive studies have suggested that aripiprazole (a second-generation antipsychotic) may have clinical utility in PTSD. However, there have been no randomized placebo-controlled trials of aripiprazole use for PTSD. We thus conducted a pilot randomized controlled trial of adjunctive aripiprazole versus placebo among Veterans with chronic PTSD serving in the US military since 11 September 2001 to assess the feasibility, safety, tolerability, and therapeutic potential of aripiprazole. Sixteen Veterans were randomized, and 14 completed at least 4 weeks of the study; 12 completed the entire 8-week trial. Outcome measures included the Clinician-Administered PTSD Scale (CAPS), PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores. Aripiprazole was well-tolerated in this cohort, and improvements in CAPS, PTSD Checklist, Beck Depression Inventory, Second Edition, and Positive and Negative Syndrome Scale scores were as hypothesized. Although CAPS change scores did not reach statistical significance, aripiprazole outperformed placebo by 9 points on the CAPS in the last observation carried forward analysis compared with the placebo group (n=7 per group), and by 20 points in the group randomized to aripiprazole that completed the entire study (n=5) compared with the placebo group (n=7). Results suggest promise for aripiprazole as an adjunctive strategy for the treatment of PTSD.

Positron emission tomography (PET) can probe biochemical pathways in vivo and can provide quantitative data; for that purpose, tracers labeled with positron-emitting radioisotopes are essential. This report describes the tracers that are being used or that may have future use, their production by cyclotrons, and other needed resources for PET imaging. Current routine and automated methods for convenient production of labeled compounds, coupled with simple computer-controlled accelerators, can support the creation of clinical PET centers in any large medical institution, obviating the need for in-depth research teams. An alternate approach involves the development of regional centers that provide in-house service and that supply fluorine 18— and carbon 11—labeled compounds to nearby hospitals with PET machines.(JAMA 1988;259:1854-1860)

This report describes the current and potential uses of positron emission tomography in clinical medicine and research related to oncology. Assessment will be possible of metabolism and physiology of tumors and their effects on adjacent tissues. Specific probes are likely to be developed for target sites on tumors, including monoclonal antibodies and specific growth factors that recognize tumors. To date, most oncological applications of positron emission tomography tracers have been qualitative; in the future, quantitative metabolic measurements should aid in the evaluation of tumor biology and response to treatment.(JAMA 1988;259:2126-2131)

This report discusses experimental and clinical applications of positron emission tomography to the heart, including measurements of blood flow to the myocardium and studies of metabolism and experimental injury. Most initial clinical studies have concentrated on ischemic heart disease, but the technique also has potential for investigation of cardiomyopathies, studying the neural control of the heart, and evaluating the effects of drugs on cardiac tissues.(JAMA 1988;259:2438-2445)

State-of-the-art magnetic resonance imaging (MRI) generates high-resolution images of the cardiovascular system. Conventional MRI techniques provide images in six to ten minutes per tomographic slice. New strategies have substantially improved the speed of imaging. The technology is relatively expensive, and its cost-effectiveness remains to be defined in relation to other effective, less expensive, and noninvasive technologies, such as echocardiography and nuclear medicine. The ultimate role of MRI will depend on several factors, including the development of specific applications such as (1) noninvasive angiography, especially of the coronary arteries; (2) noninvasive, highresolution assessment of regional myocardial blood flow distribution (eg, using paramagnetic contrast agents); (3) characterization of myocardial diseases using proton-relaxation property changes; and (4) evaluation of in vivo myocardial biochemistry. The three-dimensional imaging capability and the ability to image cardiovascular structures without contrast material give MRI a potential advantage over existing noninvasive diagnostic imaging techniques. This report analyzes current applications of MRI to the cardiovascular system and speculates on their future.(JAMA 1988;259:253-259)

This report reviews the current applications of magnetic resonance imaging of the central nervous system. Since its introduction into the clinical environment in the early 1980s, this technology has had a major impact on the practice of neurology. It has proved to be superior to computed tomography for imaging many diseases of the brain and spine. In some instances it has clearly replaced computed tomography. It is likely that it will replace myelography for the assessment of cervicomedullary junction and spinal regions. The magnetic field strengths currently used appear to be entirely safe for clinical application in neurology, except in patients with cardiac pacemakers or vascular metallic clips. Some shortcomings of magnetic resonance imaging include its expense, the time required for scanning, and poor visualization of cortical bone. JAMA 1988;259:1211-1222)

Positron emission tomography (PET) is a three-dimensional medical imaging technique that noninvasively measures the concentration of radiopharmaceuticals in the body that are labeled with positron emitters. With the proper compounds, PET can be used to measure metabolism, blood flow, or other physiological values in vivo. The technique is based on the physics of positron annihilation and detection and the mathematical formulations developed for x-ray computed tomography. Modern PET systems can provide three-dimensional images of the brain, the heart, and other internal organs with resolutions on the order of 4 to 6 mm. With the selectivity provided by a choice of injected compounds, PET has the power to provide unique diagnostic information that is not available with any other imaging modality. This is the first of five reports on the nature and uses of PET that have been prepared for the American Medical Association's Council on Scientific Affairs by an authoritative panel.(JAMA 1988;259:1531-1536)

When ABC's 'Prime Time Live' news program recently contacted Jewish Hospital in Louisville, Ky., to do a story on a double lung transplant operation, we realized we had a rare [...]

ABSTRACTBackgroundHistorically, resilience has often been conceptualized as the sustained lack of symptoms following trauma exposure. In line with a novel conceptualization of resilience as being dynamic over lifespan, determined by interacting biological and environmental factors, we examined the VA Mid-Atlantic Post Deployment Mental Health Repository (PDMH) comprised of 3876 US Military Veterans with and without PTSD diagnoses.MethodsWe performed regression modelling to study the relationship between resilience (measured with Connor Davidson Resilience Scale; CD-RISC), posttraumatic stress disorder (PTSD) severity (Davidson Trauma Scale; DTS), social support (Medical Outcome Study Social Support Survey; MOSSS), combat exposure (Combat Exposure Scale; CES), childhood trauma (Trauma Life Events Questionnaire; TLEQ), and demographic factors. CD-RISC was positively correlated with years of education and negatively correlated with DTS, CES and TLEQ scores.ResultsWe found an interaction between CD-RISC and CES in predicting PTSD severity (Davidson Trauma Scale). Specifically, high resilience predicted lower PTSD symptom severity than low resilience, this relationship was amplified with increasing levels of combat exposure. Structural equation modelling (SEM) identified an optimal latent variable that represents resilience and relationships between latent variables for resilience, trauma, and illness. We derived a resilience latent variable composed of age, education level, MOSSS and race.ConclusionsOur results support a conceptualization of resilience as a multifactorial determinant that coexists with PTSD, a state rather than trait variable, and can be quantified by biological and behavioural metrics.HIGHLIGHTS• Historically, resilience has often been conceptualized as the sustained lack of symptoms following trauma exposure.• We examined the VA Mid-Atlantic Post Deployment Mental Health Repository (PDMH) comprised of 3876 US Military Veterans.• We found an interaction effect between CD-RISC and CES in predicting PTSD severity (Davidson Trauma Scale)

Objectives:Oral squamous cell carcinoma generally occurs in older men and is associated mostly with tobacco and alcohol as the primary risk factors. The incidence of oral squamous cell carcinoma in younger patients has increased. We report a case of a young woman, 25 weeks pregnant, who presented with stage IV carcinoma of the oral tongue.Methods:The following is a case presentation and literature review.Results:The patient presented with T4 N3 M0 oral tongue cancer. A team consisting of a head and neck surgeon, a radiation oncologist, a medical oncologist, and a maternal-fetal medicine specialist was assembled. The patient initially refused surgery. Chemotherapy was initiated until 32 weeks' gestation. After an infant boy was delivered via cesarean section, the patient began concurrent irradiation and chemotherapy, which induced complete regression of the primary tongue neoplasm with a partial response of the neck nodes. The patient underwent bilateral neck dissection followed by hemiglossectomy for recurrence.Conclusions:Management of advanced oral carcinoma in pregnancy presents a unique set of challenges. Few studies have described chemotherapy and radiotherapy during pregnancy, and long-term results are needed. Care must be taken to balance appropriate and adequate treatment of disease and to ensure the safety of the patient and the fetus.

To test the hypothesis that patients with non–small cell lung cancer and single-level N2 metastases constitute a favorable subgroup of patients with mediastinal metastases, we analyzed the results of the Eastern Cooperative Oncology Group 3590 (a randomized prospective trial of adjuvant therapy in patients with resected stages II and IIIa non–small cell lung cancer) by site of primary tumor and pattern of lymph node metastases.

Liposarcomas are a heterogeneous group of tumors with variable histopathology and clinical behavior. Accurate diagnosis, subtyping, and grading are essential to select appropriate treatment. Well-differentiated tumors are slow-growing and may reach large sizes without symptoms. They are considered local diseases with low metastatic potential but with a tendency to recur and transform into aggressive sarcomas. To prevent excessive treatment of these indolent tumors, terms such “atypical lipomatous tumor” or “atypical lipoma” have been proposed, and although a consensus has not yet been reached, conservative surgical resection with attention to margins is favored. When negative margins are not obtained, radiotherapy may decrease local recurrence. Myxoid variants often metastasize and should be treated aggressively with surgery and judicious use of preoperative or postoperative radiotherapy. Resection of pulmonary metastases prolongs survival in selected patients. Chemotherapy benefits 25 of patients with metastatic or unresectable disease. Its optimal integration with local treatments in adjuvant or neoadjuvant settings is the focus of ongoing clinical trials.

Brain metastases are common in patients with small-cell lung cancer (SCLC) and are usually fatal. About half of all patients who develop brain metastases will remain symptomatic at their time of death, even if the immediate cause of death is not neurologic. While it has been argued that the obtundation that sometimes comes with brain metastases may be a relatively easy way to die, studies which have examined the quality of life of individuals developing brain metastases dispute this. For most patients and their families, the impairment of physical, cognitive, and affective function which accompanies most brain metastases is highly distressing and can be seen as a “loss” of the patient even before his/her death. Thus, improved treatment of overt brain metastases will be of palliative value, and eradication of microscopic disease in the brain may cure patients whose disease in other sites has been eradicated. Prophylactic cranial irradiation (PCI) for patients who have achieved a complete response to induction therapy markedly reduces the risk of central nervous system relapse and modestly but significantly improves survival. Despite the use of PCI, many patients with SCLC will develop brain metastases, and there is increasing interest in surgical treatment of patients with solitary lesions and the use of systemic chemotherapy in treating patients, with both SCLC and non–small-cell lung cancer, who have multifocal brain metastases which are minimally symptomatic, particularly when these patients also have extracranial metastatic disease.

The evidence that true structural congenital heart lesions may be caused by prenatal infections still remains controversial. However, evidence does exist that congenital infections produce endothelial lesions of varying locales and degrees in the fetal circulation without deranging its basic design: pulmonary artery stenosis, endarterial lesions leading to patent ductus, and stenosis of pulmonary and aortic valves, the aortic isthmus, and peripheral arteries. Nonstructural heart lesions caused by infections but leading to profound functional alterations are also well documented and are discussed here.

BACKGROUND: A prior positron emission tomographic study from The Johns Hopkins University, Baltimore, Md, using N-methylspiperone labeled with carbon 11 reported elevated basal ganglia D2 dopamine receptor density (Bmax) values in neuroleptic-naive schizophrenic patients compared with controls. We have now extended these studies to include patients with bipolar disorder. METHODS: Patients with bipolar disorder (n=14) either had never received neuroleptic medication or had been neuroleptic-free for more than 6 months, and they met DSM-III criteria for currently symptomatic affective disorder. Patients with bipolar disorder were compared with matched schizophrenic patients and normal controls. All received two positron emission tomographic scans, the second of which was preceded by oral administration of haloperidol lactate, to permit the calculation of D2 dopamine receptor Bmax. RESULTS: Diagnostic groups differed in Bmax by analysis of variance (P<.0001); post hoc tests showed higher Bmax values for psychotic patients with bipolar disorder and schizophrenic patients compared with normal controls and for schizophrenic patients and psychotic patients with bipolar disorder compared with nonpsychotic patients with bipolar disorder. Among patients with bipolar disorder, Bmax values correlated significantly with the severity of psychotic symptoms (r=.63) on the Present State Examination but not with the severity of nonpsychotic mood symptoms. CONCLUSIONS: We conclude that, like schizoprenic patients, patients with psychotic bipolar disorder have elevations of D2 dopamine receptor Bmax values and that such elevations in affective disorder are more closely associated with the presence of psychosis than with mood abnormality. Elevations in dopamine receptor values thus may occur in psychiatric states that are characterized by psychotic symptoms rather than being specific to schizophrenia.

• We examined the effects of cocaine hydrochloride (40 mg intravenously) on regional cerebral metabolic rates for glucose and on subjective self-reports of eight polydrug abusers in a double-blind, placebo-controlled, crossover study. The regional cerebral metabolic rate for glucose was measured by the [fluorine 18]-fluorodeoxyglucose method, using positron emission tomography. With eyes covered, subjects listened to a tape that presented white noise, "beep" prompts, and questions about subjective effects of cocaine or saline. Cocaine produced euphoria and reduced glucose utilization globally (mean reduction, 14%). Twenty-six of 29 brain regions (all neocortical areas, basal ganglia, portions of the hippocampal formation, thalamus, and midbrain) showed significant decrements (5% to 26%) in the regional cerebral metabolic rate for glucose. No significant effects of cocaine were observed in the pons, the cerebellar cortex, or the vermis. Right-greater-than-left hemispheric asymmetry of regional cerebral metabolic rates for glucose occurred in the lateral thalamus. The findings demonstrate that reduced cerebral metabolism is associated with cocaine-induced euphoria.

• Morphine sulfate effects (30 mg, intramuscularly) on cerebral glucose utilization and subjective self-reports were examined in 12 polydrug abusers by positron emission tomography and [fluorine 18]fluorodeoxyglucose in a double-blind placebocontrolled crossover study. During testing, subjects sat with eyes covered, listening to white noise and "beep" prompts. Morphine significantly reduced glucose utilization by 10% in whole brain and by about 5% to 15% in telencephalic areas and the cerebellar cortex, assuming no contribution of hypercapnia. When the contribution of Paco2 (45 minutes after morphine was administered) was partialled out, significant morphine-induced reductions persisted in whole brain and six cortical areas. Irrespective of morphine, left-greater-than-right asymmetry occurred in the temporal cortex, and an interaction between hemisphere and drug was noted in the postcentral gyrus. In most cases, effects on glucose utilization were not significantly related to measures of euphoria.

Pheochromocytomas are catecholamine-secreting tumors arising from the adrenal medulla or rarely from other structures derived from neurocrest origin. Because biochemical evidence of catecholamine production usually precedes clinical manifestations, patients who have undergone resection of a pheochromocytoma are followed with serial monitoring of catecholamines. If urinary catecholamines are elevated, localization of recurrent and/ or metastatic lesions is obtained by imaging procedures. Computed tomography and magnetic resonance imaging are useful techniques, but they do not provide specific metabolic information. Scintigraphy with metaiodobenzylguanidine (MIBG) labeled with either 123I or 131I is recommended for detection of metabolically active pheochromocytomas [1]. However, a subset of these tumors are MIBG-negative. The 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) method has proven useful in the localization of neoplasms. The use of PET with both FDG and 82Rb (Rubidium) has been described in the localization of MIBG-negative suprarenal and thoracic pheochromocytomas [2, 3]. We report the utility of FDG-PET to detect pelvic recurrence of pheochromocytoma in an MIBG-negative patient.

Carfentanil is a potent, synthetic opiate that binds to mu opiate receptors with very high affinity (K1= 0.051 n M, 37°). In rat brain, carfentanil is 90 and 250 times more selective for mu opiate receptors compared with delta and kappa opiate receptors, respectively. Carbon-11-carfentanil was synthesized by reacting [11C]methyliodide with the carboxylic acid precursor of carfentanil. Carbon-11-carfentanil was injected intravenously in man and a baboon and the distribution of the radioactivity in the brain was monitored using positron emission tomography. High concentrations of radioactivity were observed in the basal ganglia and thalamus, intermediate concentrations in the frontal and parietal cerebral cortex, and low concentrations in the cerebellum and occipital cortex; this distribution corresponds to the known regional density of opiate receptors measured using in vitro techniques. This heterogeneous distribution could be abolished by pretreatment with naloxone (1 mg/kg), an opiate antagonist. The percent inhibition of binding by naloxone is approximately 90 in the caudate nucleus and medial thalamus for the period 30–60 min after injection; therefore, this method is associated with a high level of specific binding to opiate receptors compared with nonspecific binding sites. The ability to measure opiate receptors in vivo in man makes it possible to study a variety of neurologic and psychiatric disorders in which opiate receptors are thought to be abnormal and to study physiologic role of opiate receptors in the central nervous system.

Surgicaln atlas of positron emission tomographic images of dopamine and serotonin receptor distribution in the normal and abnormal human brain has been generated using 3-N-[11C]methylspiperone as the tracer.

Mild-moderate closed head injury (CHI) can be followed by neuropsychological impairments in recent memory and attention, despite the absence of discernible structural abnormalities in a significant number of patients. To determine whether CHI may result in cerebral glucose metabolic abnormalities, we used fluorodeoxyglucose (FDG) technique with PET imaging to measure local cerebral metabolic rates for glucose (LCMRGlu) in three CHI patients and three matched normal controls. The CHI patients were between 3–12 months post-injury. All had deficits in attention and recent memory shown by neuropsychological testing. CT, MRI, EEG and drug screens were negative at the time of PET scanning. Subjects were engaged in a vigilance task throughout the initial 30 min following FDG administration. Group comparisons were made using t tests. There were no significant group differences found in global glucose metabolic rate. Nevertheless, the CHI group exhibited significantly decreased LCMRGLu in medial temporal, posterior temporal, and posterior frontal cortices, as well as in the left caudate nucleus. LCMRGlu was significantly increased, relative to controls, in anterior temporal and anterior frontal cortices. These results suggest that CHI patients can have regional glucose metabolic abnormalities, indicative of altered neuronal function, despite the absence of discernible anatomic abnormalities.

The kynurenines, endogenous trytophan metabolites with convulsant properties, have been postulated to play a role in the genesis of seizure disorders. We have previously reported that concentrations of 3-hydroxykynurenine (3-HK) higher than 0.2 mM are present in the brains of neonatal rats perinatally deprived of vitamin B-6. At a 1 mM concentration 3-HK significantly decreased the affinity of 3H-flunitrazepam for benzodiazepine receptor sites in rat brain membrane preparations. Furthermore, lower concentrations (Ki=250μM) of 3-HK antagonized the enhancing effect of GABA on 3H-flunitrazepam binding. These results suggest that 3-HK may have a modulatory effect on the GABA/benzodiazepine/barbituate receptor complex.

Summary Antibodies have been obtained that specifically interact with the transport enzyme (Na++K+-activated ATPase. The antigen used was purified (Na++K+)-ATPase from canine renal medulla. Purified γ globulin from immunized animals, but not from control animals or preimmune serum, inhibited (Na++K+)-ATPase from canine renal medulla with reduction of activity to 33±4 (sd) % in a concentration-dependent manner. Maximum inhibition occurred in less than 5 minutes at 37°C. The Mg++-dependent, nonouabain inhibited component of activity (Mg++-ATPase) was unaffected. Fab fragments obtained by papain cleavage of the γ globulin fraction had similar inhibitory activity and specificity. These antibodies also produced varying degrees of concentration-related inhibition of canine myocardial, calf brain, and human red cell ghost (Na++K+)-ATPase, but not Mg++-ATPase activity.

We characterized the bronchopulmonary distribution of a 0.9 percent saline aerosol (1.12 µM) labelled with 99mTc sulfur colloid in nine normal subjects and five patients with CF. Homogeneity of distribution was quantified using indices derived from computerized analysis of Anger camera pulmonary images including skew (a measure of distribution asymmetry) and kurtosis (a measure of distribution range). Aerosol clearance in 97 minutes (a measure of large, central airway deposition) was also assessed. Values of skew and kurtosis were reproducible for the patients with CF and were significantly elevated compared to the normal subjects. Reproducibility of skew and kurtosis were not studied in the normal subjects. Clearance was not significantly different in the two groups. We conclude that the bronchopulmonary distribution of this radioaerosol is nonuniform in patients with CF, compared to normal subjects, and clearance may be impaired in patients with CF who are severely ill.

Aortopulmonary window with aortic isthmic hypoplasia is an unusual combination of congenital heart lesions that usually causes severe heart failure, poor systemic perfusion, and death shortly after birth. In 21 previously reported cases, survival beyond infancy was uncommon, yet only one neonate survived operation. This report describes three cases of aortopulmonary window and aortic isthmic hypoplasia and a two-stage operative approach that proved successful in both infants in which it was tried. During the first step the isthmic obstruction is relieved, the ductus is ligated, and the aortopulmonary window is plicated via a left thoracotomy. The second stage consists of definitive closure of the aortopulmonary window using the technique of deep perfusion hypothermia.

Over a 2 year period ending in April, 1981, 268 premature infants with birth weight below 1,750 gm underwent operation for a "hemodynamically significant" patent ductus arteriosus. Operations were performed in 13 centers participating in a collaborative study, which was primarily designed to evaluate the role of indomethacin in the management of patent ductus arteriosus. No patient died during the operations, which were done at a median age of 10 days. Eight infants (3%) died within 36 hours after operation. In only one was the death directly attributable to the operative procedure. Hospital mortality (23%) and postoperative morbidity, which included bronchopulmonary dysplasia, pneumothorax, and sepsis, were unrelated to birth weight, age at operation, and degree of preexisting pulmonary disease or preoperative treatment of the infant with indomethacin. Results indicate that surgical ligation is a safe and effective procedure for treating patent ductus arteriosus with large left-to-right shunting in small premature infants.

Previous studies suggest that arteriovenous shunts are present in peripheral arterial disease and account for early venous opacification seen during arteriography. To evaluate this hypothesis, thirty patients were studied by injecting 99mtechnetium-labeled microspheres intra-arterially following translumbar catheterizadon of the abdominal aorta. With this technique, if shunting is present, increased counts will be detectable while counting over the lungs. Repeat shunt determinations were made in 20 patients after injection of radiopaque contrast material, and in 10 patients during the period of reactive hyperemia following 5 minutes of arterial occlusion. Significant arteriovenous shunting was not present in any of the study groups.

Transposition of the great arteries {S,D,D} is a common congenital cardiovascular malformation that is occasionally associated with ventricular septal defect and left ventricular outflow tract obstruction. Recently right ventricular outflow tract obstruction associated with an aortic arch anomaly has been recognized as an infrequent but important variant of transposition of the great arteries, and this constellation presents a unique surgical challenge. Five infants with this constellation whose systemic circulation was dependent on flow through the ductus arteriosus have undergone definitive surgical treatment with four survivors. An anatomical review of 129 specimens with transposition of the great arteries revealed that 17% had right ventricular outflow tract obstruction and 7% had associated aortic arch obstruction as well. All specimens with aortic arch obstruction and ventricular septal defect except one had a malalignment type ventricular septal defect. Although several treatment options may be considered, recent experience with arterial switch repair in the neonate with transposition of the great arteries {S,D,D} prompted repair in these patients by arterial switch, ventricular septal defect closure, repair of aortic arch obstruction, and augmentation of the right ventricular outflow tract.

The hemodynamic and respiratory effects of unilateral pneumothorax were studied during positive-pressure mechanical ventilation in five sheep. The sheep were anesthetized, intubated, and placed on mechanical ventilation with positive end-expiratory pressure (5 cm H2O). After baseline studies, including chest roentgenograms, were taken, increments of air were injected into the right pleural cavity. Measurements were repeated at pneumothoraces of 500, 1,000, and 1,500 ml. There was a steady fall in cardiac output (p < 0.02) at pneumothoraces of 1,000 and 1,500 ml. The decrease in cardiac stroke volume paralleled that of cardiac output. Heart rate rose (p < 0.05) at a pneumothorax of 1,500 ml. There appeared to be a linear relationship between the percent increase in pneumothorax as estimated by roentgenogram and the percent fall in cardiac output (r = 0.991). There was a steady rise in mean pulmonary arterial, pulmonary arterial capillary wedge, superior vena caval, and inferior vena caval pressures, although the changes in inferior vena caval pressure were not statistically different from baseline. Peak airway pressure increased from baseline at pneumothoraces of 1,000 and 1,500 ml. Both right and left end-expiratory intrapleural pressures increased and were statistically different (p < 0.01) from baseline. However, there was a substantially greater rise in right intrapleural pressure than left. Arterial oxygen tension remained physiological throughout the study. This study indicates that cardiac output decreases as the amount of pneumothorax increases in sheep during mechanical ventilation. This study also demonstrates that, during positive-pressure mechanical ventilation, a relatively benign-appearing pneumothorax by chest roentgenogram may be associated with a significantly depressed cardiac output. In addition, arterial oxygen tension may not be useful in predicting the onset of pneumothorax during mechanical ventilation.

Regional cerebral blood flow (rCBF) was compared in the gerbil by means of [3H]nicotine, [14C]-iodoantipyrine, and hydrogen clearance techniques. In agreement with other studies, nicotine and iodoantipyrine methods gave virtually identical results. With these methods, it was observed that a reduction in blood flow occurred shortly after insertion of an electrode into the striatum for hydrogen clearance measurement, affecting rCBF throughout the impaled hemisphere. The reduction was moderate (30%) in the striatum and hippocampus, but much greater (70%) in cortical regions. Identical deficits were observed following brief penetrations involving only cortex. Following chronic electrode placement in the striatum, regional blood flow values obtained with [3H]nicotine returned to the control range within 6 h. Blood flow estimates obtained in the striatum with the implanted electrode increased with a similar time course, so that by 6–24 h, hydrogen clearance gave values indistinguishable from control values obtained with [3H]nicotine. These results clearly demonstrate that reduction of CBF subsequent to electrode placement can account for the low values frequently obtained with the hydrogen clearance method in small animals. The distribution of the deficit and the time course of its recovery are similar to blood flow changes associated with spreading depression. While mechanisms responsible for this effect remain to be fully identified, chronic implantation is a practical solution that allows the continued use of hydrogen clearance as a convenient method for repeated measurement of blood flow in the same animal.

This study investigated the influence of biological and technical factors on variations of global and regional cerebral metabolic rate of glucose (CMRglc) measured with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG). Twelve male volunteers (22–40 years) were investigated on three or four occasions for a total of 42 studies. We calculated the variance/covariance of the following parameters: CMRglc, six parameters of the blood clearance of [18F]FDG, hour of injection, peak time of blood radioactivity, and six components of the operational equation (nonradioactive blood glucose concentration, brain radioactivity, two integrals, numerator, and denominator). There was correlation among these six components, except for nonradioactive blood glucose. However, the correlation between the CMRglcand the individual components of the operational equation was poor. The inter- and intrapersonal CMRglccoefficients of variations were 13.8 and 7.1%, respectively. In contrast, coefficients of variations of the numerator and denominator of the operational equation were 34.6 and 32.6%, respectively, and were always in the same direction. No correlation was found between CMRglcand the technical factors in the numerator and denominator of the operational equation. Factor analysis disclosed that a single factor was responsible for 70% of the variance. This factor included caudate, putamen, thalamus, frontal cortex, temporal cortex, and cingulate gyrus. These structures are involved with multiple complex functions, from autonomic motor control to behavior and emotions. The intrinsic metabolic variability of these structures, along with the basal metabolic processes that are continuously going on in the brain, may be the best explanation for the variance encountered in our investigation.

In carbon-11 labeled radiotracer studies of neuroreceptors in the brain, a state of practical equilibrium, monitored with a simple dual-probe detector system, was achieved by injection of a bolus of tracer followed by a continuous infusion of the tracer. After investigating several different bolus-to-infusion activity ratios, we observed that a practical equilibrium state could be achieved with a slope of 0.02±0.001 cpsxkg/µCi/min for [11C]carfentanil studies in normal human beings. The usefulness of this approach to assess neuroreceptor occupancy was demonstrated in two cases.

Cerebral glucose utilization measured with fluorine-18-fluoro-2-deoxy-D-glucose is characterized by considerable variability both among different persons and for the same person examined on different occasions. The goal of this study was to explore whether some regions of the brain were more variable than others with respect to glucose utilization and whether there was a pattern in their covariance. The global and regional cerebral utilization of glucose was measured in 12 healthy young volunteers on 3 or 4 occasions. In all, 24 regions were examined. The interrelation of the glucose utilization rates of the brain regions was investigated by factor analysis of the metabolic rates. Some 70% of the total variance was attributable to only 1 factor, while 80% of the total variance could be attributed to 2 factors. Regions making up the first factor were the frontal and temporal cortex, cingulate gyrus, caudate nucleus, thalamus and putamen. These regions are functionally related to the limbic system. Regions of the second factor were the parietal cortex, occipital cortex and cerebellum, regions more clearly related to sensory and motor functions. The 2-factor pattern was highly reproducible, being found with different algorithms for factor extraction and rotation. Under resting conditions, the variance of cerebral metabolism seems to be primarily related to regions which are closely involved with the limbic system. Cortical regions involved primarily in motor and sensory functions have less influence on the variance.