Conventional drug therapy in inflammatory bowel disease

The conventional treatment of inflammatory bowel disease should center around the liberal use of one of the many available forms of 5-ASA. Sulfasalazine should be used initially with the newer mesalamine-only containing drugs being reserved for sulfasalazine-intolerant patients or for those patients who require larger doses of medication. The choice of the delivery method should be made with the knowledge of the extent of disease and the potential coverage areas of the individual delivery methods. Systemic and topical glucocorticoids are an invaluable adjunct to 5-ASA therapy, but their use must be directed with the goal of remission induction. The tapering of glucocorticoids should be as prompt as the maintenance of remission allows, with a useful general guideline of decreasing the dose by 1 mg per day. Immunosuppressive therapy, including azathioprine and 6-mercaptopurine, holds promise for refractory cases of inflammatory bowel disease and for their potential steroid sparing properties; antibiotic therapy with metronidazole and ciprofloxacin in the absence of documented infectious disease offers additional routes to control disease. The majority of patients require a combination of drugs to attain remission. Only further study will reveal the ideal regimen for each of the different subsets of inflammatory bowel disease.     

In vitro short-term response of human erythrocytes to implant materials used in maxillo-facial rigid internal fixation

A number of retinal proteins are phosphorylated by a variety of kinases, resulting in well-known regulatory effects. The identity and role of corresponding phosphatases is less clear. We simultaneously measured the activity of serine/ threonine protein phosphatases type 1, 2A and 2C in bovine retinae. The enzymes were classified according to substrate specificity, divalent cation requirement and the effect of phosphatase subtype-specific inhibitors. The total- and specific activity of phosphatase type 2A was prevalent. Type 2C was 10-fold less abundant. 80% of type 1 and 50% of type 2A and type 2C, respectively, were soluble. An economic purification scheme was developed. We demonstrated the presence of phosphatase isozymes 2Calpha and 2Cbeta in bovine rod outer segments by enzymatic analysis as well as immunological techniques. The results suggest a yet unknown role of phosphatase type 2C in phototransduction. On the other hand, the immense amount of protein phosphatases found to be soluble - therefore not associated with rod outer segment membranes - points towards participation of these enzymes in the process of visual transduction not considered thus far.     

Phospholipase A2 activity and calpactin I levels in rat lymphokine-activated killer cells: correlation with the cytotoxic activity

The interaction of carnitine with human placental brush-border membrane vesicles was investigated. Carnitine was found to associate with the membrane vesicles in a Na(+)-dependent manner. The time course of this association did not exhibit an overshoot, which is typical of a Na+ gradient-driven transport process. The absolute requirement for Na+ was noticeable whether the association of carnitine with the vesicles was measured with a short time incubation or under equilibrium conditions, indicating Na(+)-dependent binding of carnitine to the human placental brush-border membranes. The binding was saturable and was of a high-affinity type with a dissociation constant of 1.37 +/- 0.03 microM. Anions had little or no influence on the binding process. The binding process was specific for carnitine and its acyl derivatives. Betaine also competed for the binding process, but other structurally related compounds did not. Kinetic analyses revealed that Na+ increased the affinity of the binding process for carnitine and the Na+/carnitine coupling ratio for the binding process was 1. The dissociation constant for the interaction of Na+ with the binding of carnitine was 24 +/- 4 mM. This constitutes the first report on the identification of Na(+)-dependent high-affinity carnitine binding in the plasma membrane of a mammalian cell. Studies with purified rat renal brush-border membrane vesicles demonstrated the presence of Na+ gradient-driven carnitine transport but no Na(+)-dependent carnitine binding in these membrane vesicles. In contrast, purified intestinal brush-border membrane vesicles posses neither Na+ gradient-driven carnitine transport nor Na(+)-dependent carnitine binding.     

Occipitocervical fusion with a five-millimeter malleable rod and segmental fixation

Although occipitocervical fusion is frequently used for instability of the upper cervical spine and the occipitocervical articulation, most currently used techniques have one or more of the following disadvantages: the necessity for sublaminar wires, the use of occipital screws, a fixed angle of instrumentation, or the necessity for routine postoperative halo immobilization. Moreover, many reported techniques are associated with a high rate of nonunion or instrumentation failure. We present our experience with a technically simple method of obtaining rigid occipitocervical arthrodesis using a 5-mm malleable rod that is fixed to the skull by a pair of wires passed through four suboccipital burr holes. Segmental spinal fixation is achieved with Wisconsin interspinous wires and is occasionally supplemented with sublaminar wires. Supplemental autogenous bone graft is used in all cases. A cervical collar is routinely used for postoperative immobilization. The results of treatment were retrospectively reviewed in 16 patients with an average age of 49.4 years (range, 9-69). Mean follow-up was 24 months (range, 12-36 mo). The indication for fusion was instability of the occiput-C1-C2 complex as a result of Chiari malformation, rheumatoid disease, skull base tumor resection, basilar invagination, ankylosing spondylitis, Down's syndrome, cervical laminectomy, and trauma. The average number of levels fused was 5.4 (range, O-C3 to O-T3). Successful occipitocervical arthrodesis was achieved in all but one of the surviving patients. The single patient with a pseudarthrosis was successfully managed with supplemental bone grafting and halo immobilization. There were two deaths from medical complications in chronically ill patients. Other complications included one postoperative instrumentation loosening, one myocardial infarction, and one superficial occipital decubitus. In conclusion, rodding and segmental interspinous wiring is an effective, technically simple method of obtaining rigid occipitocervical fixation, which obviates the need for bulky orthoses.     

Selection of rainbow trout resistant to viral haemorrhagic septicaemia virus and transmission of resistance by gynogenesis

In 1984 a programme of selection for resistance to viral haemorrhagic septicaemia virus (VHSV) in rainbow trout was initiated. The progenies of 14 males were submitted to a VHSV waterborne challenge. The mortality ranged from 30 to 95% and the heritability of resistance was estimated to be 0.63 +/- 0.26. One male consistently provided the most resistant offspring, and the second generation was produced from sires and dams selected among these families. The mean resistance improved and several females giving birth to resistant offspring were identified (0-10% mortality while the mortality in the controls was from 70 to 90%). The meiotic gynogenetic progeny of these females also demonstrated high resistance (mortality less than 10%). The role of superficial tissues in the resistance was confirmed and there was a striking difference in the growth of VHSV in fins excised and infected in vitro. The fins from resistant fish replicated the virus poorly as compared with the fins of susceptible fish.     

Ex vivo expansion with stem cell factor and interleukin-11 augments both short-term recovery posttransplant and the ability to serially transplant marrow

The characterization of many cytokines involved in the control of hematopoiesis has led to intense investigation into their potential use in ex vivo culture to expand progenitor numbers. We have established the optimum ex vivo culture conditions that allow substantial amplification of transient engrafting murine stem cells and which, simultaneously, augment the ability to sustain serial bone marrow transplantation (BMT). Short-term incubation of unfractionated BM cells in liquid culture with stem cell factor (SCF) and interleukin-11 (IL-11) produced a 50-fold amplification of clonogenic multipotential progenitors (CFU-A). Following such ex vivo expansion, substantially fewer cells were required to rescue lethally irradiated mice. When transplanted in cell doses above threshold for engraftment, BM cells expanded ex vivo resulted in significantly more rapid hematopoietic recovery. In a serial transplantation model, unmanipulated BM was only able to consistently sustain secondary BMT recipients, but BM expanded ex vivo has sustained quaternary BMT recipients that remain alive and well more than 140 days after 4th degree BMT. These results show augmentation of both short-term recovery posttransplant and the ability to serially transplant marrow by preincubation in culture with SCF and IL-11.     

Feasibility of a long-term low-sodium diet in mild hypertension

The present study set out to assess the feasibility of long-term moderate dietary sodium restriction in patients with mild hypertension in general practice. After screening and a run-in phase of 6-8 weeks, a total of 77 previously undiagnosed mildly hypertensive patients were identified. Half of them were randomized to receive a few simple dietary instructions from their general practitioners in order to reduce salt usage; the others were randomized to receive no advice. The patients were followed up for 12 months with quarterly visits. A total of 56 patients (72.7%) completed the study, 26 on a low-sodium diet (LD) and 30 on their usual diet (UD). At each visit in the diet phase, patients provided 24h urine, which was analysed for volume and sodium concentration in order to assess their sodium intake. Blood pressure, heart the rate and body weight were recorded. The mean urinary sodium excretion for all diet phase visits overlapped in the two groups (177.0 +/- 32.9 vs. 169.3 +/- 49.4 mEq/24h respectively in the LD and UD groups). Nevertheless the mean systolic and diastolic blood pressures for all diet phase visits were significantly lower in the LD than in UD group (144.2 +/- 11.1/91.6 +/- 6.4 and 148.0 +/- 13.7/95.6 +/- 4.7 mmHg respectively, P less than 0.01). Our data suggest that it is not feasible at present to reduce sodium intake in mild hypertensives with simple and inexpensive dietary instructions, the only ones suitable for widespread application in general practice.     

Antimicrobial activity and spectrum of LB20304, a novel fluoronaphthyridone

Compound LB20304 is a fluoronaphthyridone carboxylic acid with a novel pyrrolidine substituent. This drug was compared with ciprofloxacin, levofloxacin, ofloxacin, and trovafloxacin against over 800 pathogens, most from blood stream infections, by National Committee for Clinical Laboratory Standards reference methods. LB20304 was the most active agent against gram-positive species including strains observed to be resistant to other fluoroquinolones and glycopeptides. The potency of LB20304 (MIC50, 0.03 micrograms/ml) against the Enterobacteriaceae was exceeded only by that of ciprofloxacin (0.015 micrograms/ml). It has limited activity against gram-negative anaerobes.