Short-term outcome following elective laparoscopic colorectal cancer resection in octogenarians and nonagenarians.

AIM: The 30-day outcome after laparoscopic resection for cancer in patients over the age of 80 years was studied. METHOD: An electronic database was used to identify patients over 80 years who underwent laparoscopic bowel resection between December 2000 and October 2009 at three UK laparoscopic colorectal training units. Patients who required abdominoperineal excision of the rectum were excluded. RESULTS: In all, 173 patients (80 men) of median age 84 (80-93) years were identified. American Society of Anesthesiologists (ASA) grades were ASA 1, 14; ASA 2, 87; ASA 3, 68; and ASA 4, 4. Median body mass index was 26 (14-45) kg/m(2). Thirteen (7.5%) patients were converted to open surgery. The major causes for conversion were bleeding and adhesions. Thirty-three major complications occurred in 21 (12%) patients. Ten (5.8%) required readmission after discharge for complications giving a total of 17.8% of patients with complications. The median hospital stay was 5 (1-37) days. Three (1.7%) patients died within 30 days of surgery. CONCLUSION: This study confirms that laparoscopic large bowel resection is safe and beneficial in a population over 80 years. It has low morbidity and mortality and a shortened hospital stay. Octogenarians should not be denied major laparoscopic bowel surgery based on age alone.

Obsessive-compulsive disorder following closed head injury.

Obsessive-compulsive disorder (OCD) is a rare sequelae of closed head injury. Frontal, occipital and fronto-temporal injuries are frequent among reported cases. Response to treatment is often poor. This article describes a patient with OCD and reviews relevant anatomic, neurochemical and psychologic aspects of patients with this condition.

Hepatitis C virus NS3 RNA helicase domain with a bound oligonucleotide: the crystal structure provides insights into the mode of unwinding.

BACKGROUND: Hepatitis C virus (HCV) represents a major health concern as it is responsible for a significant number of hepatitis cases worldwide. Much research has focused on the replicative enzymes of HCV as possible targets for more effective therapeutic agents. HCV NS3 helicase may provide one such suitable target. Helicases are enzymes which can unwind double-stranded regions of DNA or RNA in an ATP-dependent reaction. The structures of several helicases have been published but the structural details as to how ATP binding and hydrolysis are coupled to RNA unwinding are unknown. RESULTS: The structure of the HCV NS3 RNA helicase domain complexed with a single-stranded DNA oligonucleotide has been solved to 2.2 A resolution. The protein consists of three structural domains with the oligonucleotide lying in a groove between the first two domains and the third. The first two domains have an adenylate kinase like fold, including a phosphate-binding loop in the first domain. CONCLUSIONS: HCV NS3 helicase is a member of a superfamily of helicases, termed superfamily II. Residues of NS3 helicase which are conserved among superfamily II helicases line an interdomain cleft between the first two domains. The oligonucleotide binds in an orthogonal binding site and contacts relatively few conserved residues. There are no strong sequence-specific interactions with the oligonucleotide bases.

Prospective randomized study of a new method of providing postoperative pain relief following femoropopliteal bypass.

The extensive incision required for femoropopliteal bypass using saphenous vein causes significant postoperative pain, principally within the distribution of the cutaneous branches of the femoral nerve. This prospective randomized study investigated the efficacy of continuous postoperative femoral nerve block in reducing both pain (visual analogue pain score) and the requirement for opiate analgesia. Ten patients received a femoral nerve block by infusion of 0.5 per cent bupivacaine (5 ml/h for 48 h) via an epidural catheter together with a patient-controlled analgesia (PCA) device containing morphine; a further ten patients used a PCA device alone. The median postoperative intravenous morphine requirement was significantly reduced in patients with a nerve block at 24 h (4 versus 33 mg, P < 0.01) and at 48 h (5 versus 37 mg, P < 0.01) compared with controls. Postoperative pain was effectively abolished in the former group. The addition of a nerve block to PCA provides superior pain control after femoropopliteal bypass.

Activation of coagulation and fibrinolysis in open and laparoscopic cholecystectomy.

BACKGROUND: Activation of coagulation and fibrinolysis occurs as a stress response to surgery and may predispose the patient to thromboembolic complications. Other components of the surgical stress response (cytokine release, neurohumoral response, etc.) have been shown to differ between laparoscopic and open cholecystectomy, and the aim of this study was to investigate the effects of laparoscopic and open surgery on the coagulation and fibrinolytic pathways. METHODS: Fourteen patients undergoing laparoscopic cholecystectomy and 12 patients undergoing open cholecystectomy had blood taken in the perioperative period for fibrinopeptide A (FPA) prothrombin fragment F1.2, antithrombin 3, tissue plasminogen activator (tPA) and its fast-acting inhibitor plasminogen activator inhibitor-1 (PAI-1 antigen and activity), and the euglobulin clot lysis time (ECLT). RESULTS: The only significant differences between the two groups occurred 6 h after surgery when the ECLT was longer (p < 0.005; Mann Whitney), and PAI-1 antigen and activity were higher (p < 0.01 and p < 0.001, respectively; Mann Whitney) after open cholecystectomy than laparoscopic cholecystectomy. CONCLUSIONS: Other changes in fibrinolysis and coagulation were similar for open and laparoscopic cholecystectomy. With respect to hemostasis, laparoscopic cholecystectomy does not increase the risk of thromboembolic complications compared to the conventional procedure.

Crystal structure of p38 mitogen-activated protein kinase.

p38 mitogen-activated protein kinase is activated by environmental stress and cytokines and plays a role in transcriptional regulation and inflammatory responses. The crystal structure of the apo, unphosphorylated form of p38 kinase has been solved at 2.3 A resolution. The fold and topology of p38 is similar to ERK2 (Zhang, F., Strand, A., Robbins, D., Cobb, M. H., and Goldsmith, E. J. (1994) Nature 367, 704-711). The relative orientation of the two domains of p38 kinase is different from that observed in the active form of cAMP-dependent protein kinase. The twist results in a misalignment of the active site of p38, suggesting that the orientation of the domains would have to change before catalysis could proceed. The residues that are phosphorylated upon activation of p38 are located on a surface loop that occupies the peptide binding channel. Occlusion of the active site by the loop, and misalignment of catalytic residues, may account for the low enzymatic activity of unphosphorylated p38 kinase.

X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex.

The X-ray structure of the ternary complex of a calcineurin A fragment, calcineurin B, FKBP12, and the immunosuppressant drug FK506 (also known as tacrolimus) has been determined at 2.5 A resolution, providing a description of how FK506 functions at the atomic level. In the structure, the FKBP12-FK506 binary complex does not contact the phosphatase active site on calcineurin A that is more than 10 A removed. Instead, FKBP12-FK506 is so positioned that it can inhibit the dephosphorylation of its macromolecular substrates by physically hindering their approach to the active site. The ternary complex described here represents the three-dimensional structure of a Ser/Thr protein phosphatase and provides a structural basis for understanding calcineurin inhibition by FKBP12-FK506.

Influence of laparoscopic and conventional cholecystectomy upon cell-mediated immunity.

Surgery, trauma and anaesthesia induce a state of transient immunosuppression. Laparoscopic cholecystectomy has several well documented clinical advantages over traditional cholecystectomy and provokes a lower acute phase response, thought to be a result of the smaller wound size. The influence of laparoscopic cholecystectomy (21 patients) and conventional open cholecystectomy (13 patients) upon components of the cell-mediated immune system was investigated. Cell-mediated immunity was studied by in vitro assays of T lymphocyte proliferation to different mitogens, and by natural killer cell cytotoxicity using a standard 51Cr release assay. Blood samples were taken before and 24 h after the start of the operation. In the sample taken after operation there was significant depression of T lymphocyte proliferation to phytohaemagglutinin (stimulation index 149.4 versus 33.3, P < 0.002), staphylococcal enterotoxin B (85.2 versus 52.6, P = 0.01) and toxic shock syndrome toxin (48.4 versus 14.8, P = 0.08) in the group of patients who underwent open surgery, but not in the group treated by laparoscopic surgery. There was a small but statistically insignificant decrease of natural killer cell cytotoxicity in both groups of patients. These findings suggest that laparoscopic cholecystectomy causes less depression of cell-mediated immunity than open cholecystectomy.

Esthesioneuroblastoma: an unusual cause of frontal lobe dysfunction.

Esthesioneuroblastoma (olfactory neuroblastoma) is an unusual tumor of neuroectodermal origin, and initial presentation with symptoms characteristic of frontal lobe dysfunction is quite rare. This article describes the case of a patient who was referred to the Charleston Area Medical Center for "depression" but was found to have a esthesioneuroblastoma.

Preservation of the spleen improves survival after radical surgery for gastric cancer.

One hundred and ninety five consecutive, potentially curative resections for adenocarcinoma of the stomach were performed in one surgical department between 1970 and 1989: 76 patients underwent gastrectomy with splenectomy and 119 gastrectomy without splenectomy. Operative mortality was 12% after gastrectomy with splenectomy, but only 2.5% after gastrectomy without splenectomy (p < 0.05). Postoperative complications were also significantly more common when splenectomy was combined with gastrectomy (41% v 14%, p < 0.01). Cumulative five year survival was 45% after gastrectomy with splenectomy, compared with 71% after gastrectomy alone (p < 0.01). When the results of the two groups of patients were compared, stage for pathological stage, no evidence was found that splenectomy improved survival. Application of Cox's proportional hazards model, which makes allowance for other variables such as the T and N stages, showed that splenectomy had an adverse influence on patients' survival. Splenectomy does not benefit the patient and its routine use in the course of radical resections for carcinoma of the stomach should be abandoned.

A combined internal medicine-psychiatry clinic at a community hospital: initial experiences.

A new internal medicine/psychiatry outpatient clinic was recently established at Charleston Area Medical Center (CAMC). This report describes the clinical profiles of the first 52 patients and also reviews the clinic's staffing, facilities, referral sources and reimbursement. For large community hospitals, a med-psych clinic may be a useful method of providing psychiatric treatment to medically-ill outpatients.

Structure and mechanism of interleukin-1 beta converting enzyme.

Interleukin-1 beta converting enzyme (ICE) processes an inactive precursor to the proinflammatory cytokine, interleukin-1 beta, and may regulate programmed cell death in neuronal cells. The high-resolution structure of human ICE in complex with an inhibitor has been determined by X-ray diffraction. The structure confirms the relationship between human ICE and cell-death proteins in other organisms. The active site spans both the 10 and 20K subunits, which associate to form a tetramer, suggesting a mechanism for ICE autoactivation.

Geophagia in a chronic hemodialysis patient.

Geophagia, the deliberate ingestion of earth, is a serious clinical problem, particularly for dialysis patients. This article presents a geophagic patient with end stage renal disease and reviews the etiology, consequences and treatment of this disorder.

Eating disorders among diabetics: a case report and literature review.

This report describes the challenging clinical problem of the coexistence of an eating disorder and diabetes mellitus in the same patient. Review of prior cases reveals young female, anorexic diabetics are most frequently reported. A review of previously published surveys indicates the prevalence of eating disorders among diabetics is 11 percent. Relevant clinical interactions from the biologic, psychologic and family perspectives are reviewed.

Open versus laparoscopic cholecystectomy: a retrospective comparative study.

Two groups of 40 patients (31 females, 9 males), matched for age and body mass index, who underwent either elective open cholecystectomy (Group I) or elective laparoscopic cholecystectomy (Group II) have been studied retrospectively to detect differences in operating time, morbidity and mortality, hospital length of stay, and use of postoperative analgesics. The two groups of patients had almost identical histories of gallstone disease. The median operating time for the patients in Group I was 45 min (range 35-95) compared with 90 min (range 50-135) in Group II. An intraoperative cholangiogram was performed in 21 of the patients in Group I and 22 patients in Group II. There were no deaths in either group. The overall complication rate was 22.5% in Group I and 10% in Group II. Median postoperative length of stay was 5 days for Group I patients (range 1-19) and 2 days for Group II patients (range 1-5). All Group I patients required postoperative intravenous or intramuscular opiates, while 10% of Group II patients did not require any analgesia at all and pain was controlled with oral analgesics alone in 16%. Median total morphine dose for Group I patients was 46.9 mg (range 9.4-180), as compared with only 15.6 mg (6.2-37.5) for Group II patients. This study concludes that laparoscopic cholecystectomy led to less complications, shorter hospital length of stay, and minimal use of postoperative analgesia.

Inside polyomavirus at 25-A resolution.

Empty capsids and complete virions of polyomavirus crystallize isomorphously. Here we use difference Fourier analysis of X-ray diffraction data at 25-A resolution from these crystals to obtain an electron-density map of the inside of the virion. The polyomavirus capsid is built from 72 pentamers of VP1 that form three different types of connections in the T = 7d icosahedral surface lattice. Self-assembly of purified recombinant VP1 into capsid-like aggregates has shown that switching of the bonding specificity to form the unanticipated non-equivalent connections is an inherent property of the VP1 pentamers. Our map of the inside of the virion displays 72 prongs of electron density extending from the core into the axial cavities of the VP1 pentamers. We identify these prongs with the VP2 and VP3 molecules, which may function to guide the assembly of the highly ordered capsid on the nucleohistone core. The atomic structure of the closely related simian virus-40 capsid has been determined from the high-resolution diffraction data. Our polyomavirus map, calculated using all the low-resolution diffraction data, shows no indication of regular order inside the spherical core.

Structural analysis of a series of antiviral agents complexed with human rhinovirus 14.

The binding to human rhinovirus 14 of a series of eight antiviral agents that inhibit picornaviral uncoating after entry into host cells has been characterized crystallographically. All of these bind into the same hydrophobic pocket within the viral protein VP1 beta-barrel structure, although the orientation and position of each compound within the pocket was found to differ. The compounds cause the protein shell to be less flexible, thereby inhibiting disassembly. Although the antiviral potency of these compounds varies by 120-fold, they all induce the same conformational changes on the virion. The interactions of these compounds with the viral capsid are consistent with their observed antiviral activities against human rhinovirus 14 drug-resistant mutants and other rhinovirus serotypes. Crystallographic studies of one of these mutants confirm the partial sequencing data and support the finding that this is a single mutation that occurs within the binding pocket.

Refined crystal structure of dogfish M4 apo-lactate dehydrogenase.

The crystal structure of M4 apo-lactate dehydrogenase from the spiny dogfish (Squalus acanthius) was initially refined by a constrained-restrained, and subsequently restrained, least-squares technique. The final structure contained 286 water molecules and two sulfate ions per subunit and gave an R-factor of 0.202 for difraction data between 8.0 and 2.0 A resolution. The upper limit for the co-ordinate accuracy of the atoms was estimated to be 0.25 A. The elements of secondary structure of the refined protein have not changed from those described previously, except for the appearance of a one-and-a-half turn 3(10) helix immediately after beta J. There is also a short segment of 3(10) helix between beta C and beta D in the part of the chain that connects the two beta alpha beta alpha beta units of the six-stranded parallel sheet (residues Tyr83 to Ala87). Examination of the interactions among the different elements of secondary structure by means of a surface accessibility algorithm supports the four structural clusters in the subunit. The first of the two sulfate ions is in the active site and occupies a cavity near the essential His195. Its nearest protein ligands are Arg171, Asp168 and Asn140. The second sulfate ion is located near the P-axis subunit interface. It is liganded by His188 and Arg173. These two residues are conserved in bacterial lactate dehydrogenase and form part of the fructose 1,6-bisphosphate effector binding site. Two other data sets in which one (collected at pH 7.8) or both (collected at pH 6.0) sulfate ions were replaced by citrate ions were also analyzed. Five cycles of refinement with respect to the pH 6.0 data (25 to 2.8 A resolution) resulted in an R value of 0.191. Only water molecules occupy the subunit boundary anion binding site at pH 7.8. The amino acid sequence was found to be in poor agreement with (2Fobs-Fcalc) electron density maps for the peptide between residues 207 and 211. The original sequence WNALKE was replaced by NVASIK. The essential His195 is hydrogen bonded to Asp168 on one side and Asn140 on the other. The latter residue is part of a turn that contains the only cis peptide bond of the structure at Pro141. The "flexible loop" (residues 97 to 123), which folds down over the active center in ternary complexes of the enzyme with substrate and coenzyme, has a well-defined structure. Analysis of the environment of Tyr237 suggests how its chemical modification inhibits the enzyme.