Regional differences in neurovascular coupling in rat brain as determined by fMRI and electrophysiology.

Increases in neuronal activity induce local increases in cerebral perfusion. However, our understanding of the processes underlying this neurovascular coupling remains incomplete and, particularly, how these vary across the brain. Recent work supports an important role for astrocytes in neurovascular coupling, in large part via activation of their metabotropic glutamate receptors (mGluR). Here, using a combination of functional magnetic resonance imaging (fMRI) and electrophysiology we demonstrate regional heterogeneity in the mechanisms underlying neurovascular coupling. Direct electrical stimulation of the rat hindpaw sensorimotor cortex induces blood oxygenation level dependent (BOLD) and cerebral blood volume (CBV) fMRI responses in several anatomically distinct cortical and subcortical structures. Following intraperitoneal administration of the type 5 mGluR antagonist, MPEP, both BOLD and CBV responses to cortical stimulation were significantly reduced, whilst the local field potential (LFP) responses remained largely constant. Spatially, the degree of reduction in fMRI responses varied between cortical and subcortical regions (primary cortex approximately 18% vs. striatum approximately 66%), and also between primary and secondary cortical areas ( approximately 18% vs. approximately 55%). Similarly, greater decreases in response amplitude were seen in the contralateral secondary cortex ( approximately 91%) and ipsilateral striatum (approximately 70%), compared to the primary cortex (approximately 44%). Following MPEP, a negative component of the BOLD and CBV responses became more apparent, suggesting that different mechanisms mediate vasodilatory and vasoconstrictory responses. Interestingly, under baseline conditions the quantitative relationship between fMRI and LFP responses in cortical and subcortical regions was markedly different. Our data indicate that coupling between neuronal and fMRI responses is neither empirically nor mechanistically consistent across the brain.

Nitrous oxide and isoflurane are synergistic with respect to amplitude and latency effects on sensory evoked potentials.

OBJECTIVE: Combinations of anesthetic agents are frequently employed to produce the desired clinical effect. No systematic study has been conducted on the effect of the combination of nitrous oxide with a potent inhalational agent such as isoflurane on sensory evoked responses. METHODS: Median nerve somatosensory evoked responses from the cervical and cortical regions (SSEP), auditory brainstem responses (ABR) and flash visual evoked responses (VEP) were tested in baboons. The latency and amplitude of the major response peaks were recorded at five proportionate mixtures of isoflurane (I) and nitrous oxide (N(2)O) (0.8% I only, 0.6% I/20% N(2)O, 0.4% I/40% N(2)O, 0.2% I/60% N(2)O, and 79% N(2)O only). A similar set of experiments were also conducted with 0.8% isoflurane and 0.6% halothane. All data were normalized to 0.8% isoflurane only and Dunnett's method of analysis used to determine which mixtures deviated from the reference values with 0.8% isoflurane. RESULTS: Several combinations of isoflurane with nitrous oxide produced increases in latency (ABR: wave V, VEP, SSEP cervical and cortical) and decreases in amplitude (ABR: amplitude ratio V/I, VEP, cortical SSEP) from that expected if the effects were additive. No deviations were observed with combinations of isoflurane and halothane. CONCLUSIONS: These studies are consistent with drug synergy when isoflurane is mixed with nitrous oxide. This suggests that if these agents are considered for anesthesia when sensory evoked responses are to be monitored that the combination of these agents may produce more amplitude and latency changes than expected from a proportionate mixture of the individual agents.

Enzyme deficiency in cholesteryl ester storage idisease.

Cholesteryl ester storage disease has been shown to involve severe deficiency of acid cholesteryl ester hydrolase and triglyceride lipase activity in liver, spleen, and lymph node. The cholesteryl ester hydrolase was also deficient in aorta. Tissue storage of both cholesteryl esters and triglycerides is generalized. Both the lipid and enzymatic changes are very similar to those in Wolman's disease.

Measurements of common iliac arterial blood flow in anurans using Doppler ultrasound.

Color Doppler ultrasonography was used to determine time-average mean velocity and cross-sectional area of the common iliac artery in bullfrogs (Rana catesbeiana) and marine toads (Bufo marinus). Volumetric blood flow and weight-adjusted blood flow measurements were calculated from this data. Volumetric flow rates of frogs (31.8 ml/min) and toads (23.6 ml/min) did not differ statistically. However, when flow rates were adjusted for body mass, toads displayed a significantly greater flow rate of 238.1 ml/min/kg compared to 114.4 ml/min/kg for frogs.

Mating and Memory : Can Mating Cues Enhance Cognitive Performance?

The literature on sexual selection and the social brain hypothesis suggest that human cognition and communication evolved, in part, for the purpose of displaying desirable cognitive abilities to potential mates. An evolutionary approach to social cognition implies that proximate mating motives may lead people to display desirable mental traits. In signaling such traits, one can increase the likelihood of attracting a potential mate. Two experiments demonstrated that exposure to mating cues-highly attractive opposite-sex faces-led people to display enhancements in declarative memory-a process underlying a variety of abilities such as resource acquisition, intelligence, and creativity. Experiment 1 showed that men (but not women) displayed enhanced memory for details of a story that was presented during exposure to highly attractive opposite-sex faces. Experiment 2 demonstrated that heightened displays of declarative memory reflect an enhancement in retrieval rather than in encoding. Findings contribute to the literatures on human mating and cognitive performance and provide novel insight into links between social processes and basic cognition.

Influence of saccharide length on polysaccharide appetite in the rat.

The appetite of female rats for saccharides of different chain lengths was assessed in brief (5-min) one-bottle acceptance and two-bottle preference tests. The saccharides (and their lengths in glucose units) included glucose (1), maltose (2), maltotriose (3), maltooligosaccharide (4-8), maltopolysaccharide (average length 43), and Polycose (1 to 30+); 0.0125 and 0.025 molar solutions of these saccharides were tested. The results revealed that the rats' order of preference for these saccharides was as follows: maltooligosaccharide greater than maltotriose = maltose greater than glucose; and maltooligosaccharide greater than Polycose = maltopolysaccharide greater than maltose. Thus, as saccharide chain length increased from 1 to 4-8 glucose units palatability increased, but with further increases in chain length palatability declined somewhat. Previous findings have suggested that rats have a "polysaccharide" taste receptor and the present results indicate that the receptor is maximally (or near-maximally) stimulated by saccharides of 4-8 glucose units in length.

Long-term prognosis after repair of double-chamber right ventricle with ventricular septal defect.

To determine long-term postoperative results in patients with double-chamber right ventricle and ventricular septal defect, 20 patients who had survived complete repair between 1959 and 1966 were recalled and studied. An interview, physical examination, electrocardiogram and chest x-ray were performed in all 20 patients, a treadmill exercise test in 16, 24-hour Holter monitor recording in 7 and postoperative cardiac catheterization in 8. Mean age at repair was 14 years and at follow-up evaluation 33 years. There were no late deaths. At a mean follow-up of 19 years, 17 patients were in New York Heart Association functional class I, 1 patient was in class II and 2 patients were in class III. Reoperation was performed in 2 patients (10%), and at present only 1 patient (5%) is considered to have hemodynamically significant cardiac compromise. Aortic regurgitation, not present in any patient preoperatively, developed in 5 patients (25%). Mild residual right ventricular outflow obstruction was present in 2 (10%) and the murmur of a hemodynamically insignificant residual ventricular septal defect or tricuspid regurgitation was present in 5 patients (25%). One patient (5%) had cardiomegaly (cardiothoracic ratio greater than 0.55). The frequency of infective endocarditis in the postoperative follow-up period was 1 per 388 patient-years. Thus, 20 years after repair of double-chamber right ventricle, mild residua and sequelae are common, but serious cardiac compromise is infrequent.

Ventricular septal defect: results after repair in infancy.

During the 19 years from 1957 through 1975, there have been 106 patients under age 2 years who have undergone surgery for repair of a large ventricular septal defect at the University of Michigan Medical Center. The majority of the patients had either severe pulmonary hypertension or intractable congestive heart failure. Eighty-three infants survived operation; there has been one late death. The greatest mortality occurred in patients under age 6 months and in those with severe pulmonary hypertension. Surviving infants showed marked symptomatic improvement and change in growth patterns. Complications included the development of complete right bundle branch blodk or left anterior hemiblock in approximately 50 percent of patients and, in one instance, complete atrioventricular block. Forty-five patients have undergone cardiac catheterization 1 to 8 years postoperatively. Although 17 were found to have residual septal defects only 3 of these had a pulmonary to systemic flow ratio of 1.5:1 or more, and reoperation was accomplished without incident in these 3 patients and in 3 others with smaller shunts. With one exception, postoperative pulmonary arterial pressures and pulmonary to systemic vascular resistance ratios were normal or near normal, thus representing a significant contrast with findings in patients operated on after age 2 years. Whereas the complications of surgery appear no greater in the infant than in the older patient, many of the benefits can be realized only with operation at the earlier age.

Fine mapping of glycerol kinase deficiency and congenital adrenal hypoplasia within Xp21 on the short arm of the human X chromosome.

We have studied patients with Duchenne muscular dystrophy (DMD), DMD together with glycerol kinase (GK) deficiency, or DMD together with both GK deficiency and congenital adrenal hypoplasia (AHC). Analysis of deletions in these patients allows the mapping of these mutations in Xp21. The following order is proposed: Xpter - L1 - AHC - GK - DMD - Xcen. One of the boys with DMD, GK, and AHC is shown by pulsed-field-gel electrophoresis to have a deletion which has a proximal endpoint at least 500 kb distal from the pERT87 (DXS164) locus.

Collis-Belsey reconstruction of the esophagogastric junction. Indications, physiology, and technical considerations.

Twenty-four patients underwent combined Collis-Belsey reconstruction of the esophagogastric junction. The primary indication for operation in 19 patients was gastroesophageal reflux. Three patients had achalasia, one diffuse spasm, and one an incarcerated combined sliding and paraesophageal hernia. Postoperatively, symptoms were relieved in all 19 patiients undergoing repair for gastroesophgeal reflux with or without peptic strictures of the esophagus, and barium swallows showed no gastroesophageal reflux. Preoperative average mean and peak pressures in the distal esophageal high pressure zone (HPZ) were 1.38 and 2.72 mm. Hg, respectively; two thirds had no measurable HPZ. Postoperative mean and peak pressures were 6 and 12.36 mm. Hg, respectively; average HPZ length was 2.81 cm. Of 19 patients with massive reflux preoperatively, postoperative acid reflux testing demonstrated no reflux in 14 and minimal to moderate reflux in five. Collis-Belsey reconstruction ot the esophagogastric junction effectively relieves symptoms and controls the complications of gastroesophageal reflux.

Complications and failings of the combined Collis-Belsey operation.

Eighty-three patients with risk factors predisposing to recurrent reflux after standard hiatal hernia repairs have undergone the Collis-Belsey operation. There were two postoperative deaths. Complications related to multiple operations on the lower esophagus included injury to the spleen (three patients); gastrocutaneous fistula (two patients), and localized ischemic necrosis of esophagus two patients). There were two esophageal perforations. In four of 15 patients, the combination of esophagomyotomy and the Collis-Belsey operation produced functional esophageal obstruction. Three patients have experienced late major lower esophageal bleeding from ulceration of mucosa adjacent to the gastroplasty tube; two the these patients have no demonstrable gastroesophageal reflux. In addition to postoperative interviews and barium swallows, 77 patients have been evaluated with esophageal manometry and acid reflux testing. After an average follow-up of 12 montsh, 19 percent have symptomatic reflux, but 30 percent have moderate-to-severe reflux with pH reflux testing. The recent enthusiasm for the combined Collis-Belsey operation should be tempered by continued, cautious, objective assessment of its long-term results.

Substernal gastric bypass of the excluded thoracic esophagus for palliation of esophageal carcinoma.

Curative resection is impossible in most patients with carcinoma of the esophagus or malignant tracheoesophageal fistulas, because of local tumor invasion or distant metastases. Optimal palliative therapy in these patients should relieve dysphagia and aspiration and restore the ability to swallow comfortably. This report describes a technique for palliation of carcinoma of the esophagus with a substernal gastric bypass after exclusion of the thoracic exophagus with the GIA surgical stapler. The results of this procedure in 10 patients with advanced malignant disease are discussed. Although postoperative morbidity and mortality rates were high, the quality of life achieved with this method of palliation was gratifying. Substernal gastric bypass of the excluded thoracic esophagus is an effective alternative to feeding tubes, prolonged radiation therapy, esophagogastrectomy, or colon bypass in patients with incurable, malignant esophageal disease.

Esophagectomy without thoracotomy.

Blunt esophagectomy without thoracotomy has been performed in 26 patients: four with benign disease and 22 with carcinomas involving various levels of the esophagus (10 cervicothoracic, one upper third, five middle third, and six distal third). Continuity of the alimentary tract was restored by anastomosing the pharynx or cervical esophagus either to stomach (19 patients) or to a colonic graft (seven patients). Esophageal resection and reconstruction were performed in a single stage in 25 patients, and the esophageal substitute was positioned in the posterior mediastinum in the original esophageal bed in 24 patients. There were no deaths directly related to the technique of blunt esophagectomy. Average intraoperative blood loss was 1,350 ml. for the entire group, 1,650 ml. for those requiring concomitant laryngectomy and 1,050 ml. for those undergoing esophagectomy without laryngectomy. Complications in these patients included pneumothorax (eight), transient hoarseness (five), pleural effusion (five), anastomotic leak (four), subphrenic abscess (one), and cerebrovascular accident (one). The five deaths were due to pheumonia (two), innominate artery rupture (two), and pulmonary embolus (one). Blunt esophagectomy without thoracotomy is safe and is far better tolerated physiologically than the combined transthoracic and abdominal operations more traditionally used for exophageal resection and reconstruction.

Correction of truncus arteriosus in the neonate using a nonvalved conduit.

Successful correction of truncus arteriosus in two neonates, both 4 days of age, is described. Nonvalved polytetrafluoroethylene (PTFE) conduits were used because of the small size of the infants. Both recovered from operation with no signs right ventricular failure and remain well. Catheterization data on one patient show satisfactory hemodynamics 1 year after operation with only residual branch pulmonary artery stenosis. These data suggest that a conduit valve is not essential in the correction of truncus arteriosus even in the neonate.

Increased spinal monoamine concentrations after chronic thoracic dorsal rhizotomy in goats.

In goats, bilateral thoracic dorsal rhizotomy (TDR) causes severe ventilatory failure during exercise, followed by progressive functional recovery. We investigated spinal neurochemical changes associated with TDR and/or functional recovery by measuring spinal concentrations of the monoamines serotonin (5-HT), norepinephrine, and dopamine via HPLC. Changes in 5-HT and calcitonin gene-related peptide were visualized with immunohistochemistry. Goat spinal cords were compared 4-15 mo after TDR from T(2) to T(12) (n = 7) with sham-operated (n = 4) or unoperated controls (n = 4). TDR increased the concentration of cervical 5-HT (C(5)-C(6); 122% change), caudal thoracic norepinephrine (T(7)-T(11); 53% change), and rostral thoracic dopamine (T(3)-T(6); 234% change). TDR increased 5-HT-immunoreactive terminal density (dorsal and ventral horns) and nearly eliminated calcitonin gene-related peptide immunoreactivity in the superficial laminae of the dorsal horn in rostral thoracic segments; both effects became less pronounced in caudal thoracic segments. Thus TDR elevates monoamine concentrations in discrete spinal regions, including possible compensatory changes in descending serotonergic inputs to spinal segments not directly affected by TDR (i.e., cervical) but associated with functionally related motor nuclei (i.e., phrenic nucleus).

Esophageal atresia. A 41-year experience.

Since the first attempted repair in 1935, a total of 365 infants have undergone treatment for esophageal atresia with or without tracheoesophageal fistula. To evaluate the improvement in our results, we have divided our patients into four, approximately equal, time periods. The overall late survival has indeed improved during each of the four decades from between 36% and 53% to 68% in the last ten years. During this past decade, the group A risk infants (35 patients) had a 3% mortality, the group B (20 patients) had a 5% mortality, but the group C babies (22 patients) had a 41% mortality due to associated anomalies or severe prematurity. Anastomotic leaks and recurrent fistulas were each encountered in approximately 5% of the cases in all decades. Postoperative stricture has been encountered in 20% of the entire series and no esophageal replacements have been required.

The breeding and feeding of thoracic surgeons.

A brief recapitulation of the history of The American Board of Thoracic Surgery reveals that in its 27-year lifetime it has strived to improve the quality of thoracic surgical training. Most recently the Board has decided that candidates from unapproved programs who begin their training after June 30, 1976, will be ineligible for the Board examination. A population of approximately 2,000 thoracic surgeons should be more than adequate to provide patient care in the United Sates. At the present rate of certification the thoracic surgeon population would number about 4,000 within 25 years. With the birth rate in the United States nearing zero population growth, the number of new thoracic surgeons trained and certified each year must be limited, and it is imperative that the profession rather than the federal government be in control of this. Continuing education and evaluation of clinical competence will soon be required in the specialty of thoracic surgery. Cooperation among the major groups concerned with thoracic surgery is necessary for successful development of continuing education and the necessary evaluation of competence.

Technique of mitral valve replacement.

A technique for mitral valve replacement is described that provides adequate exposure for excision of the valve and secure suturing of the annulus, even in patients with a small left atrium. The technique has been used in more than 100 patients and has resulted in only a minimal amount of perivalvular leak.

Combined Collis-Nissen reconstruction of the esophagogastric junction.

Recent reports have indicated that combined Collis-Belsey reconstruction of the esophagogastric junction fails to control reflux in 30 to 46% of patients undergoing the procedure. The major factor thought to be responsible for this result is the limited Belsey fundoplication possible after construction of the gastroplasty tube. This report describes our technique of combining the Collis gastroplasty with a 360-degree Nissen type fundoplication. The radiographic and manometric characteristics of the distal esophageal high-pressure zone produced by the Collis-Nissen operation are discussed.

Mediastinal metastases in bronchogenic carcinoma: influence of postoperative irradiation, cell type, and location.

A 17-year experience with 136 patients with bronchogenic carcinoma and mediastinal metastases is reported. Six died postoperatively. Postoperative mediastinal irradiation was given to 110 patients surviving curative resection who had evidence of tumor spreading to the mediastinal lymph nodes. The remaining 20 patients did not receive radiation therapy. Of the 136 patients, 29 (21.3%) lived 5 years free from disease and 9 survived 10 or more years. Of the 110 patients who survived operation and underwent irradiation, 29 (26.4%) survived 5 years. None of the 20 patients not receiving radiation therapy lived 5 years. Of the patients who underwent irradiation, 18 of the 50 patients with squamous cell carcinoma survived 5 years, while only 7 of 55 with adenocarcinoma survived 5 years. We do not believe that the discovery of mediastinal lymph node involvement in bronchogenic carcinoma is a contraindication to pulmonary resection. As in our previous reports, histological cell type has proved to be an important indicator of absolute survival. Patients with squamous cell carcinoma had an absolute-5-year survival of 33.9%, while the patients with adenocarcinoma had an absolute survival of 12.3%. The level of lymph node metastasis has an influence on prognosis as well. Patients with subcarinal lymph node metastases had a lower survival than patients with superior mediastinal involvement.