Effect of plasma exchange in combination with deoxyspergualin on the survival of guinea-pig hearts in macrophage-depleted C6-deficient rats

The present study aimed to evaluate the effect of plasma exchange (PE) in combination with certain immunosuppressive agents on the survival of guinea-pig hearts in C6-deficient (C6-) rats. To deplete macrophages, we gave liposome-encapsulated dichloromethylene diphosphonate (Lip-Cl2MDP) intravenously (i.v.) in a dose of 10 mg/kg on day 2 before transplantation and every 5 days until rejection. Deoxyspergualin (DSG) was also given i.v. in a dose of 10 mg/kg/day from day -2 until rejection. Plasma exchange was performed 1 day before xenografting. All animals were splenectomized just before heart transplantation. Heart xenografts were evaluated twice daily and harvested at the time of rejection. The serum levels of anti-guinea-pig xenoreactive antibody (IgM, IgG) were measured using enzyme-linked immunosorbent assay (ELISA). Graft survival was 2.8 +/- 0.5 days in control rats, and 4.0 +/- 0.3 days with PE alone. A combination of PE with Lip-Cl2MDP or DSG did not improve the results (4.2 +/- 0.6 days vs. 4.8 +/- 0.6 days, respectively). While in rats treated with PE and the combination of Lip-Cl2MDP and DSG, graft survival was significantly prolonged (6.9 +/- 1.1 days, P < 0.01 vs. controls). In untreated control rats, xenoreactive antibody (IgM, IgG) levels decreased immediately after PE, but their levels rapidly returned to normal. In rats treated with DSG or DSG + Lip-Cl2MDP, the IgM levels remained low during the observation period. Immunohistochemistry showed that macrophage infiltration into the graft was suppressed in Lip-Cl2MDP-treated groups at the time of rejection. Our results demonstrate that sustained suppression of antibody levels can be achieved by PE in combination with DSG and xenograft survival is further prolonged in macrophage-depleted C6- rats. These findings suggest that strategies targeting antibody and macrophages may be useful in prolonging xenograft survival.     

Modern cleanroom clothing systems: people as a contamination source

Today, clothing and clothing systems for cleanrooms are mainly tested with regard to material properties such as particle generation, particle filtration, and resistance to wear. The dispersal chamber or "body-box" has been used for studying the protective efficacy of clothing systems in use, for example by Hoborn in 1981 (1) and Whyte and Bailey in 1985. A modified dispersal chamber has recently been installed at KTH. Tests and comparative studies have been performed in the dispersal chamber on selected clothing systems. The latest tests have been performed in two parts. In Part 1, each person performed 12 sequences dressed in new, modern cleanroom clothing systems with small variations, such as with and without goggles, different face masks, and different sizes of hoods. In Part 2, each person performed six test sequences with new, modern cleanroom clothing systems with variations in fabrics, and as a comparison, two sequences with pharmaceutical clothing system and surgical clothing system, respectively. The results are given in total number of airborne particles (> or = 0.5 microm per cubic meter) and airborne aerobic CFU per cubic meter. Statistical evaluations of the results have been performed. The source strengths of the contamination source people wearing modern cleanroom clothing systems have been estimated.     

The Swedish coeliac disease epidemic with a prevailing twofold higher risk in girls compared to boys may reflect gender specific risk factors

In the mid 1980s the incidence of coeliac disease in Swedish children below 2 years of age increased threefold within a few years, and after a 10-year high incidence period returned equally rapidly to the previous level. Analysing the epidemic with respect to any change in female to male ratio over time, or shift in age at diagnosis, may increase the understanding of coeliac disease aetiology. In a population-based incidence study of childhood coeliac disease, 2151 cases (811 boys/1340 girls) were diagnosed from 1973 to 1997. Incidence rates and relative risks (RRs) were calculated by gender, age at diagnosis and calendar time. Cumulative incidences by age and gender were calculated for different birth cohorts. A twofold higher risk (RR: 1.9, 95% confidence interval (CI) 1.7–2.1) for coeliac disease in girls as compared to boys prevailed throughout the epidemic. Further, during the post-epidemic period there was an upward shift in age at diagnosis. So far, however, a majority of the cases diagnosed at older ages belong to birth cohorts of the epidemic period, i.e. cohorts that already had a high coeliac disease risk before 2 years of age. Our results suggest that girls as compared to boys may be genetically more vulnerable to environmental exposures influencing the immunological processes towards coeliac disease. Further, an increased risk for coeliac disease during the first years of life due to, for example, unfavourable infant dietary habits, may result in an increased total childhood risk for coeliac disease. A longer follow-up, even into adulthood, is needed to determine whether or not the lifetime risk has changed.     

Energy-dense meals improve energy intake in elderly residents in a nursing home

BACKGROUND: Several studies have shown that malnutrition is common among nursing home residents. AIM: We hypothesized that addition of natural energy-dense ingredients to a standard diet would improve voluntary energy intake and ability to perform activities of daily living (ADL) and decrease infections in elderly residents under nursing home care. METHODS: Thirty-five residents in a municipality nursing home (median age 83 years) were served either a standard diet (1600 kcal/day) (control group, n=18) or the same meals fortified with natural energy-dense ingredients (2100 kcal/day) (experimental group, n=17). Energy intake and ADL function were measured before and after the intervention. All episodes of infection were registered. Non-parametric statistics were used. RESULTS: Energy intake increased in the experimental group from 23.5 (21.3-28.5) kcal/kg/body weight before, to 31.9 (29.7-33.7) kcal/kg/body weight during the intervention (P<0.001). There was no change in energy intake in the control group. ADL function in the experimental group was unchanged, while it decreased significantly in the control group (P<0.001). The number of infections tended to be lower in the experimental group than in the control group (5 vs 13). The cost for the energy-dense ingredients was approx. 0.11 EUR per resident and day. CONCLUSIONS:Addition of natural energy-dense ingredients to regular meals is an inexpensive way to improve voluntary energy intake in elderly nursing home residents, a treatment that was accompanied by maintained ADL function.     

Radiologic investigation after laparoscopic inguinal hernia repair

Laparoscopic instead of open surgical repair of inguinal hernias is becoming more frequent. Radiologists may expect different postoperative findings depending on the technique used. We studied how radiology had been used postoperatively and what findings were encountered after laparoscopic herniorraphy. Postoperative radiologic examinations related to hernia repair of all consecutive patients that had had laparoscopic herniorraphy in Malmö University hospital between 1992 and 1998 were retrospectively evaluated. A total of 538 groins were included, 3.9% (n=21) of these were postoperatively examined with ultrasound (n=10), herniography (n=7), plain abdominal films (n=2), CT (n=1), or fistulography (n=1). Significant findings were found in five groins, namely, one sinus tract, two hematomas, one small bowel obstruction, and one recurrence of hernia. Four insignificant seromas were found. The characteristics of the findings and pitfalls are described. Symptoms resulting in radiologic examination are rare after laparoscopic herniorraphy. The radiologist must be familiar with the spectrum of such findings.     

Rapid bone and blood flow formation in impacted morselized allografts: positron emission tomography (PET) studies on allografts in 5 femoral component revisions of total hip arthroplasty

5 patients were revised with impaction of morselized frozen allograft and a cemented total hip arthroplasty (THA) because of loosening and osteolysis of a primary hip arthroplasty. Plain film radiographs of the stems showed stable implants in all patients 15-24 months after surgery. The clinical results were good. We used: 1) Positron Emission Tomography (PET) to evaluate vascularization and new bone formation in the allograft, 2) kinetic [18F]-fluoride PET to produce quantitative images, interpreted as new bone formation in the allograft surrounding the femur stem, 3) [15O]-water PET to quantify bone blood flow, and 4) [15O]-carbon monoxide to determine blood volume. After surgery, all patients were evaluated twice: at 1-8 days and 12 months and 3 patients were also studied at 4 months. As early as at 8 days after surgery, blood flow and bone formation had increased greatly adjacent to the allograft. At 4 months blood flow and bone formation were about the same, but activity was highest in the graft material. At 1 year after surgery, blood flow had declined to the levels of the contralateral femur diaphysis in most of the graft bed. These findings using the PET technique showed that angiogenesis and new bone formation occurred early after impaction of morselized bone allografts around the femoral component in revision THA. We found that PET is a sensitive method for evaluating neovascularization and bone formation in the graft beds.     

Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke

To explore the role of brain-derived neurotrophic factor for survival and generation of striatal neurons after stroke, recombinant adeno-associated viral vectors carrying brain-derived neurotrophic factor or green fluorescent protein genes were injected into right rat substantia nigra 4-5 weeks prior to 30 min ipsilateral of middle cerebral artery occlusion. The brain-derived neurotrophic factor-recombinant adeno-associated viral transduction markedly increased the production of brain-derived neurotrophic factor protein by nigral cells. Brain-derived neurotrophic factor was transported anterogradely to the striatum and released in biologically active form, as revealed by the hypertrophic response of striatal neuropeptide Y-positive interneurons. Animals transduced with brain-derived neurotrophic factor-recombinant adeno-associated virus also exhibited abnormalities in body posture and movements, including tilted body to the right, choreiform movements of left forelimb and head, and spontaneous, so-called 'barrel' rotation along their long axis. The continuous delivery of brain-derived neurotrophic factor had no effect on the survival of striatal projection neurons after stroke, but exaggerated the loss of cholinergic, and parvalbumin- and neuropeptide Y-positive, gamma-aminobutyric acid-ergic interneurons. The high brain-derived neurotrophic factor levels in the animals subjected to stroke also gave rise to an increased number of striatal cells expressing doublecortin, a marker for migrating neuroblasts, and cells double-labelled with the mitotic marker, 5-bromo-2'-deoxyuridine-5'monophosphate, and early neuronal (Hu) or striatal neuronal (Meis2) markers. Our findings indicate that long-term anterograde delivery of high levels of brain-derived neurotrophic factor increases the vulnerability of striatal interneurons to stroke-induced damage. Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages.     

A test method for assessment of spill and leakage from drug preparation systems

Anti-cancer drugs are reactive compounds with known adverse health effects. To prevent occupational exposure to these drugs, there are, in most countries, regulations for handling anti-cancer drugs. Many preparation systems are available, e.g. isolators, biological safety cabinets (BSCs), filter spikes (venting spikes with micro-pore filter) and closed systems (e.g. PhaSeal). Although these systems are used, there are reports of exposure. This causes concern over how efficient these systems are to prevent spill and leakage that may cause undesired exposure when handling cytotoxic drugs. Today, this knowledge is lacking. This paper presents a method (Tc-method) for testing drug preparation systems for spill and leakage. The Tc-method is based on 99Tc(m) as a tracer, with which drug vials used for test preparations are spiked. Wipe samples are then collected around the working area to measure spill and leakage. The Tc-method has been validated using an independent method, showing good agreement between the methods. Spills down to 1 nl cm(-2) can be determined. In an appendix, the Tc-method is described in a detailed step-by-step procedure.