Carbohydrate sulfotransferases: mediators of extracellular communication

Sulfated carbohydrates mediate diverse extracellular recognition events in both normal and pathological processes. The sulfotransferases that generate specific carbohydrate 'sulfoforms' have recently been recognized as key modulators of these processes and therefore represent potential therapeutic targets.     

Synthesis and applications for unnatural sugar nucleotides

The synthesis and biological evaluation of carbohydrate mimetics has begun to more clearly define the diverse roles of carbohydrates in nature. Often the strategy invoves the design and synthesis of glycosyltransferase and glycosidase inhibitors both as tools to elucidate the mechanism of action of these enzymes and as potential therapeutic agents. An array of unnatural sugar nucleotides have found utility in chemo-enzymatic synthesis. The regio- and stereoselective transfer of sugars by glycosyltransferases such as b1,4-galactosyltransferase, a1,3-fucosyltransferase, a2,3- and a2, 6-sialyltransferases and N-acethylglucosaminyltransferase V has demonstrated the broad application of this approach. This review summarizes the specificity of these well-studied glycosyltransferases for both unnatural sugar donors and acceptors. This information combined with the knowledge of the mechanism of action of those enzymes is valuable in the design of potent selective glycosyltransferase inhibitors and the chemo-enzymatic synthesis of novel carbohydrate mimetics.     

Prognostic value of blood lactate, base deficit, and oxygen-derived variables in an LD50 model of penetrating trauma

OBJECTIVE: To determine whether blood lactate, base deficit, or oxygen-derived hemodynamic variables correlate with morbidity and mortality rates in a clinically-relevant LD50 model of penetrating trauma. DESIGN: Prospective, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized, mechanically-ventilated mongrel pigs (30+/-2 kg, n = 29). INTERVENTIONS: A captive bolt gun delivered a penetrating injury to the thigh, followed immediately by a 40% to 60% hemorrhage. After 1 hr, shed blood and supplemental crystalloid were administered for resuscitation. MEASUREMENTS AND MAIN RESULTS: After penetrating injury, 50.7+/-0.3% hemorrhage (range 50% to 52.5%), and a 1-hr shock period, seven of 14 animals died, compared with six of six animals after 55% to 60% hemorrhage, and 0 of nine animals after < or =47.5% hemorrhage. Only two of 13 deaths occurred during fluid resuscitation. At the LD50 hemorrhage, peak lactate concentration and base deficit were 11.2+/-0.8 mM and 9.3+/-1.5 mmol/L, respectively, and minimum mixed venous oxygen saturation, systemic oxygen delivery, and systemic oxygen consumption were 33+/-5%, 380+/-83 mL/min/kg, and 177+/-35 mL/min/kg, respectively. For comparison, baseline preinjury values were 1.6+/-0.1 mM, -6.7+/-0.6 mmol/L, 71+/-3%, 2189+/-198 mL/min/kg, and 628+/-102 mL/min/kg, respectively. Of all the variables, only lactate was significantly related to blood loss before and after fluid resuscitation in the 16 survivors. However, r2 values were relatively low (.20 to .50), which indicates that only a small fraction of the hyperiactacidemia was directly related to tissue hypoperfusion. In the whole population of survivors and nonsurvivors, both lactate and base deficit (but none of the oxygen-derived variables) correlated with blood loss. CONCLUSIONS: Arterial lactate is a stronger index of blood loss after penetrating trauma than base deficit or oxygen-derived hemodynamic variables. The reliability of arterial lactate depends on several factors, such as the time after injury, the proportion of survivors and nonsurvivors in the study population, and on factors other than tissue hypoxia.     

Riding injuries

The aim of this study was to investigate accidents which occur in connection with horse-riding. The material was found in a data base covering 14% of all case registered in Casualty Departments in Denmark. The number of horse-riding accidents has increased by 150% from 1986 to 1996. The majority of these were girls. The age group 10-19 years accounted for 61% of the accidents. The majority of injuries occurred on falling from the horse and particularly involved the upper part of the body. Out of 1250 injuries, 24% sustained a fracture: 64% were located to the upper extremities, and 19% lower extremities. One hundred patients required hospitalization: 29 for observation for concussion; 51 for reduction of fractures and osteosynthesis; 13 for contusion. Forty-five percent of the accidents happened in a riding arena and 25% in a stable. It is concluded that the proportion of horse-riding accidents is strongly on the increase in Ribe County.     

Pre-ECT cardiology consultation

A case of multiple primary Carcinomas of the gastrointestinal tract is reported in a man presenting with Carcinomas of the rectum and oesophagus.     

Relation between intracarotid amobarbital memory asymmetry scores and hippocampal sclerosis in patients undergoing anterior temporal lobe resections

The intracarotid amobarbital procedure (IAP) is used to evaluate memory function preoperatively in candidates for anterior temporal lobe resections (ATL). We examined IAP memory asymmetry scores in 30 patients undergoing ATL (17 R, 13 L), as a function of the presence (HS+) or absence (HS-) of hippocampal sclerosis. Ictal onset zones were determined by extraoperative recording with subdural strip electrodes in all but 3 patients in whom magnetic resonance imaging (MRI) scan showed HS. MRI scans were otherwise normal. All patients were left hemisphere dominant for language except 1, in whom language was represented bilaterally. IAP memory testing involved presentation of eight subjects during anesthesia of each hemisphere, followed by recognition testing after patients recovered from amobarbital effects. A score of 1 was given for each correctly recognized object, and 0.5 was deducted for each false-positive identification. There were 16 foils. A total asymmetry score was calculated, which was positive if there was agreement between the direction of the symmetry and side of operation and negative if reversed. The mean asymmetry score for HS- (n = 8) was 0.9; that for HS+ (n = 22) was 4.1 (p < 0.01). IAP memory performance provided lateralizing information (asymmetry score > or = + or -2) in 73% of cases; among these, the lateralization was correct in 91%. Our data indicate that IAP memory asymmetry predicts both laterality of ictal onset and the presence of HS.     

Laparoscopic cholecystectomy under epidural anesthesia in patients with chronic respiratory disease

BACKGROUND: Laparoscopic cholecystectomy (LC) has become firmly established as a procedure of choice for gallstone disease. The procedure usually necessitates general anaesthesia and endotracheal intubation to prevent aspiration and respiratory embarrassment secondary to the induction of pneumoperitoneum. There is a paucity of data in the literature on the procedure being performed under regional (epidural) anaesthesia, especially in patients with coexisting pulmonary disease and pregnancy, who are deemed high risk for general anaesthesia. We report our preliminary experience with LC using epidural anaesthesia in patients with chronic obstructive pulmonary disease (COPD). METHODS: We performed LC in six patients (one man and five women), with a median age of 56 years (range, 38-74), under epidural anaesthesia over an 8-month period. All patients were ASA grade III/IV and the mean FEB1/FVC was 0.52 (range, 0.4-0.68), due to chronic asthma (two cases) and COPD (four cases). They were admitted a day prior to surgery for pulmonary function tests, nebulisers, and chest physiotherapy. An epidural catheter was introduced at T10/11 intervertebral space, and a bolus of 0.5% Bupivacaine was administered. Depending on the patient's pain threshold and the segmental level of analgesia achieved, incremental doses of 2 ml of 0.5% Bupivacaine along with boluses of intravenous 100 mcg Alfentanil was given to each patient. The patients were breathing spontaneously. No nasogastric tube was inserted, and a low-pressure (10 mmHg) pneumoperitoneum was created. LC was performed according to the standard technique. RESULTS: All the patients tolerated the procedure well and made an uneventful postoperative recovery. Median operating time was 50 min; average length of hospital stay was 2.5 days (range, 2-4). The epidural catheter was removed the morning after the operation. Only one patient required postoperative opioid analgesia. Two patients complained of persistent shoulder tip pain during surgery and required intraoperative analgesia (Alfentanil). There was no change in the patient's cardiorespiratory status, including PO2 and pCO2, and no complications occurred either intra- or postoperatively. CONCLUSIONS: LC can be performed safely under epidural anaesthesia in patients with severe COPD. Intraoperative shoulder tip or abdominal pain does not seem to be a major deterrent and can be effectively controlled with small doses of opioid analgesia.