The updated guideline 'Gastric complaints' of the Dutch College of General Practitioners; a reaction from a general practitioner]

Three working diagnoses in gastric complaints are presented: aspecific gastric complaints, ulcer complaints, reflux complaints; these assist the general practitioner in formulating the initial diagnostic and pharmacological interventions and in evaluating the effects of therapy. The guidelines state that eradication treatment of Helicobacter pylori is indicated only in gastritis caused by H. pylori, grade IV bulbitis, a duodenal bulb malformation or peptic ulcers.     

Mutagenic consequences of the incorporation of 6-thioguanine into DNA

The stimulatory effect of phytin added to skim milk on acid production of Lactobacillus casei was examined. Phytin stimulated acid production of L. casei fairly well. The stimulatory effect of phytin on acid production was not shown when phytin was treated with Dowex 50 (H+) and neutralized by NaOH solution. The incinerated product of phytin maintained almost equal stimulatory effect on acid production as that before processing. The addition of Mn2+ in the amount contained in a reagent phytin augmented the stimulatory effect on acid production markedly. The further addition of Fe3+, Ca2+, Mg2+ and PO4(3-) in amounts corresponding to their contents in the preparation of phytin as well as Mn2+ increased the effect slightly. The four preparations of phytin contained 0.045-0.20% of Mn, and the greater the Mn content was, the greater the potentiation of acid production.     

Ornithine decarboxylase transformation of NIH/3T3 cells is mediated by altered epidermal growth factor receptor activity

Ornithine decarboxylase (ODC) has been shown to be oncogenic in transfected NIH/3T3 cells overexpressing the enzyme from a heterologous promoter. These cells, designated as NODC-2 cells, acquire proliferative properties associated with tumorigenic transformation such as loss of contact inhibition, decreased population doubling time, anchorage-independent growth, and tumor production in nude mice. At least one of these parameters, loss of contact inhibition, remains dependent on elevated ODC levels. We have used these cells to investigate the molecular mechanisms by which ODC overexpression drives cell transformation and to examine the involvement of other proto-oncogene products in this process. An interaction between ODC overexpression and the epidermal growth factor receptor (EGF-R) was suggested initially by the elevation of both basal (300%) and ligand-induced (457%) EGF-R tyrosine kinase activities in NODC-2 cells compared to similarly treated control NLK cells. Disruption of EGF-R mediated signal transduction in NODC-2 cells both by treatment with tyrphostin-25 or by transfection with a vector expressing a dominant negative EGF-R mutant resulted in reacquisition of contact-inhibited growth and suppression of anchorage-independent, clonogenic growth in soft agar. We conclude that ODC-induced transformation of NIH/3T3 cells is mediated, at least partly, by alterations in EGF-R signal transduction activity.     

Outcome of rheumatoid arthritis and psoriasis following autologous stem cell transplantation for hematologic malignancy

Based on successful results in animal models, it has been proposed that high-dose myeloablative therapy followed by autologous bone marrow or stem cell transplantation (ABMT/ASCT) may cure autoimmune disease. The coexistence of autoimmune disease and hematologic malignancy provides an opportunity to examine the response of autoimmune disease to ABMT or ASCT. We describe 4 patients with autoimmune disease (3 with psoriasis and 1 with rheumatoid arthritis) and hematologic malignancy. In each patient, the autoimmune disease remitted posttransplantation, but, in 4 patients with long-term followup, it recurred at 8-24 months. The earliest relapse occurred in a patient treated with interferon-alpha. Our experience suggests that a single autograft with unpurged stem cells is unlikely to cure autoimmune disease, but that other strategies building on this approach are worthy of investigation.     

HIV, health care workers and patients: how to ensure safety in the dental office

What can be done to preserve the high standards of patient care, give reasonable assurances to patients and acknowledge the rights of health care workers? Conscientious adherence to infection control is the most responsible option available.     

Modification of hypoxia-induced injury in cultured rat astrocytes by high levels of glucose

BACKGROUND AND PURPOSE: Preexisting hyperglycemia exacerbates central nervous system injury after transient global and focal cerebral ischemia. Increased anaerobic metabolism with resultant lactic acidosis has been shown to cause the hyperglycemic, neuronal injury. The contribution of astrocytes in producing lactic acidosis under hyperglycemic/ischemic conditions is unclear, whereas the protective role of astrocytes in ischemic-induced neuronal injury has been documented. The ability of astrocytes to maintain energy status and ion homeostasis under hyperglycemic conditions could ultimately reduce neuronal injury. Therefore, we determined the effects of increased glucose concentrations on glucose utilization, lactate production, extracellular pH, and adenosine triphosphate concentrations in hypoxia-treated astrocyte cultures. METHODS: Primary astrocytes were prepared from neonatal rat cerebral cortices. After 35 days in vitro, cultures were incubated with 0-60 mmol/L glucose and subjected to hypoxic conditions at 95% N2/5% CO2 for 24 hours. In addition, under high-glucose conditions (30 mmol/L), astrocytes were exposed to up to 72 hours of hypoxia. Determination of lactate dehydrogenase efflux, adenosine triphosphate concentrations, and extracellular lactate concentrations defined astrocyte status. Equiosmolar levels of mannitol were added in place of high glucose concentrations to distinguish hyperosmotic effect. RESULTS: When physiological concentrations of glucose (7.5 mmol/L) or lower concentrations were used, significant cell damage occurred with 24 hours of hypoxia, as determined by increased efflux of lactate dehydrogenase and loss of cell protein. When higher glucose concentrations (15-60 mmol/L) were used, efflux of lactate dehydrogenase was similar to that observed in normoxic cultures, despite an increased utilization of glucose. Lactate concentrations in the media at low or normal glucose concentrations exceeded normoxic levels, but higher glucose concentrations (15-30 mmol/L) failed to increase lactate levels further. Values of adenosine triphosphate for hypoxic astrocytes treated with high glucose concentrations were significantly higher than those of astrocytes with zero or low glucose levels. In cultures exposed to hypoxia and high glucose levels (30 mmol/L), no cellular injury was observed before 48 hours of hypoxia. Lactate concentrations in the media increased during the first 24 hours of hypoxia and reached steady state. The pH of the media decreased to 6.4 after 24 hours and 5.5 at 48 hours. The latter pH was concomitant with a marked increase in extracellular lactate dehydrogenase activity. Hyperosmotic mannitol failed to protect cultured astrocytes against hypoxia. CONCLUSIONS: Hypoxic injury to mature astrocytes was reduced by the presence of 15-60 mmol/L glucose in the medium during 24-30 hours of hypoxia. Injury occurred when the pH of the medium was < 5.5. This protection was not afforded by the hyperosmotic effect of high glucose concentrations, nor was the hypoxic injury at later time periods with 30 mmol/L glucose mediated solely by lactate accumulation.     

Testing an implantable intraspinal drug delivery device in the ewe

OBJECTIVE: The authors report the use of multiple implanted intraspinal port and catheter systems per test animal to study the in vivo functional characteristics and reliability of a new implantable spinal drug delivery port system. METHODS: Four ewes were each implanted with two epidural and one subarachnoid silicone elastomer catheters at the lumbar level. Each catheter was connected in series to one of three Therex filtered spinal delivery ports implanted subcutaneously in a similar grid pattern in each ewe to facilitate percutaneous identification. Saline (2 ml) was injected 3 times weekly in each port. The ease of injection and behavioral responses were recorded for 207-213 days of implantation until sacrifice/necropsy. RESULTS: All ports functioned reliably during the study. However, injection through two of the four subarachnoid catheters resulted in behavioral withdrawal responses intermittently. This behavioral pattern was much less common after epidural port injections. All four subarachnoid and four of eight epidural port and catheter systems were tested with local anesthetic just before sacrifice. Motor block was observed in three of four subarachnoid and three of four epidural port and catheter systems tested. Integrity of the other four epidural ports was tested by injection of methylene blue at sacrifice. This dye did not distribute in the epidural space in one of the latter four epidural ports (not local anesthetic tested) because of a concentric fibrotic reaction about the catheter. Similar fibrotic reactions surrounded the catheters that failed a functional test with local anesthetic. CONCLUSIONS: The implantable intraspinal port system tested functions reliably under repetitive percutaneous access. However, filtering such ports, though desirable to prevent entry of debris into the spinal canal, did not eliminate pericatheter chronic subarachnoid and epidural reaction. The number of test animals required to test 12 ports chronically was reduced by two-thirds without undue trauma to the individual test subject. Chronic percutaneous injection of an implanted subarachnoid system is feasible but may be associated with behavioral effects similar to that seen with chronic epidural systems. Fibrosis around chronic silicone catheters limited functional utility in one-fourth of the implanted test systems. Further study of the potential reactivity of chronic epidural and subarachnoid catheters is indicated.