Molecular breakpoint analysis and relevance of variable mosaicism in a woman with short stature,primary amenorrhea,unilateral gonadoblastoma,and a 46,X,del(Y)(q11)/45,X karyotype

Congenital hydrocephalus associated with aqueductal stenosis and/or agenesis of the corpus callosum has been described in newborn males with mutations in L1CAM, a gene that encodes a neural cell adhesion molecule. These males usually have severe mental retardation and may have spastic paraplegia and adducted thumbs. In contrast, Hirschsprung disease, or absence of ganglion cells in the distal gut, has rarely been described in such individuals. We report a male infant who had severe hydrocephalus identified in the prenatal period with evidence of aqueductal stenosis and adducted thumbs at birth. He developed chronic constipation, and rectal biopsy confirmed the diagnosis of Hirschsprung disease. Molecular testing of the L1CAM gene revealed a G2254A mutation, resulting in a V752M amino acid substitution. A common polymorphism in RET, but no mutation, was identified. Our patient represents the third example of coincident hydrocephalus and Hirschsprung disease in an individual with an identified L1CAM mutation. We hypothesize that L1CAM‐mediated cell adhesion may be important for the ability of ganglion cell precursors to populate the gut, and that L1CAM may modify the effects of a Hirschsprung disease–associated gene to cause intestinal aganglionosis. © 2002 Wiley‐Liss, Inc.     

Psoas abscess: Difficulties encountered

From 1961 to 1989, 67 patients underwent various surgical procedures for psoas abscess. Retrospective analysis was undertaken in an effort to determine optimal surgical therapy. Forty patients were cured with one operation. Twenty-one patients required two operations, four patients required three operations, and two patients required more than three operations. The reason for failure of treatment was failure to resect the diseased bowel or to drain the psoas abscess adequately. A technique to recognize and treat the abscess definitively will be illustrated. The most common etiologies were Crohn's disease in 49 patients, postoperative sepsis in eight patients, and complications of renal disease in four patients. The length of hospital stay ranged from 5 to 392 days (mean, 26 days). There were two deaths. Failure to recognize and treat psoas abscess results in considerable morbidity.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, April 29 to May 4, 1990.     

Factors affecting patency of internal thoracic artery graft: clinical and angiographic study in 1434 symptomatic patients operated between 1982 and 2002.

OBJECTIVE: The purpose is to define factors influencing long-term patency of the internal thoracic artery (ITA) to optimize the operative strategy. METHODS: 1482 left internal thoracic artery (LITA) and 636 right internal thoracic artery (RITA) symptom-directed angiograms were studied in 1434 patients. Data were prospectively collected from patients who had primary coronary artery bypass surgery during the period 1982-2002. The mean age of patients was 59 years; 85% were male. The mean period from operation to re-angiogram was 80 months. LITA was grafted to left anterior descending coronary artery (LAD) in 82% of cases, RITA to right coronary artery (RCA) in 40% and circumflex artery in 35% of cases. Graft failure was defined as > or =80% stenosis. RESULTS: 96.3% of LITA and 88.1% of RITA grafts were patent. No patient variables were significantly associated with graft patency (age, gender, diabetes, hypertension, LVEF, NYHA, AMI). Target coronary artery was associated with patency of both LITA and RITA grafts with maximum patency when grafted to LAD (P = 0.02) RITA had the worst patency to RCA, patency for the left system was identical to LITA. Proximal anastomosis to aorta (free RITA) had significantly better patency when compared with in situ RITA to RCA system (P = 0.005) while similar patency when grafted to left system. ITA diameter and target artery diameter were not associated with graft patency. Recent operations had better RITA patency (P = 0.03). The interval from operation to angiogram was not associated with ITA patency (96% patency for LITA and 88% patency for RITA, remained stable when studied at <1, 1-4, 5-9, 10-14 and >15 years). CONCLUSIONS: Even in a patient cohort that had adverse symptoms, excellent LITA and RITA patency was achieved which almost remained constant through all time intervals studied.     

Review article: The role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective

PURPOSE: Anticonvulsant drugs are effective in the treatment of chronic neuropathic pain but were not, until recently, thought to be useful in more acute conditions such as postoperative pain. However, similar to nerve injury, surgical tissue injury is known to produce neuroplastic changes leading to spinal sensitization and the expression of stimulus-evoked hyperalgesia and allodynia. Pharmacological effects of anticonvulsant drugs which may be important in the modulation of these postoperative neural changes include suppression of sodium channel, calcium channel and glutamate receptor activity at peripheral, spinal and supraspinal sites. The purpose of this article is to review preclinical evidence and clinical trial data describing the efficacy and safety of anticonvulsant drugs in the setting of postoperative pain management. SOURCE: A Medline search was performed to retrieve available literature on the basic and clinical pharmacology of anticonvulsant drugs as they pertain to postoperative pain management. PRINCIPAL FINDINGS: Numerous laboratory studies have described analgesic effects of different anticonvulsant drugs in experimental pain models. Furthermore, several recent clinical trials have shown that anticonvulsants may reduce spontaneous and movement-evoked pain, as well as decrease opioid requirements postoperatively. Some early findings suggest further that anticonvulsant drugs may alleviate postoperative anxiety, accelerate postoperative functional recovery and reduce chronic postsurgical pain. CONCLUSION: Given the incomplete efficacy of currently available non-opioid analgesics, and the identified benefits of opioid sparing, anticonvulsant medications may be useful adjuncts for postoperative analgesia. Further research in this field is warranted.     

Supply and demand in cerebral energy metabolism: the role of nutrient transporters.

Glucose is the obligate energetic fuel for the mammalian brain, and most studies of cerebral energy metabolism assume that the majority of cerebral glucose utilization fuels neuronal activity via oxidative metabolism, both in the basal and activated state. Glucose transporter (GLUT) proteins deliver glucose from the circulation to the brain: GLUT1 in the microvascular endothelial cells of the blood-brain barrier (BBB) and glia; GLUT3 in neurons. Lactate, the glycolytic product of glucose metabolism, is transported into and out of neural cells by the monocarboxylate transporters (MCT): MCT1 in the BBB and astrocytes and MCT2 in neurons. The proposal of the astrocyte-neuron lactate shuttle hypothesis suggested that astrocytes play the primary role in cerebral glucose utilization and generate lactate for neuronal energetics, especially during activation. Since the identification of the GLUTs and MCTs in brain, much has been learned about their transport properties, that is capacity and affinity for substrate, which must be considered in any model of cerebral glucose uptake and utilization. Using concentrations and kinetic parameters of GLUT1 and -3 in BBB endothelial cells, astrocytes, and neurons, along with the corresponding kinetic properties of the MCTs, we have successfully modeled brain glucose and lactate levels as well as lactate transients in response to neuronal stimulation. Simulations based on these parameters suggest that glucose readily diffuses through the basal lamina and interstitium to neurons, which are primarily responsible for glucose uptake, metabolism, and the generation of the lactate transients observed on neuronal activation.     

Cognitive rehabilitation in the elderly: overview and future directions.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.     

Signs of ocular disease: A prevalence study in optometric practice

Data on the prevalence of all ocular conditions seen in 1500 consecutive optometric patients were obtained during an investigation into the effectiveness of routine visual field screening. In many instances, these are the first prevalence figures for optometric patient populations. Some of the estimates of prevalence are compared with other optometric and general population surveys. Many disorders were observed, the most frequent being slight to moderate increases in retinal arterial reflex and attenuation, optic cup/disc ratio of 0.4, shallow anterior chambers and family history of glaucoma. The occurrence of some conditions was sporadic, resulting from the relatively small sample. However, this survey may serve as an audit of ocular disease detection for other practitioners.