Incidence of BK with Tacrolimus Versus Cyclosporine and Impact of Preemptive Immunosuppression Reduction

Our purposes were to determine the incidence of BK viruria, viremia or nephropathy with tacrolimus (FK506) versus cyclosporine (CyA) and whether intensive monitoring and discontinuation of mycophenolate (MMF) or azathioprine (AZA), upon detection of BK viremia, could prevent BK nephropathy. We randomized 200 adult renal transplant recipients to FK506 (n = 134) or CyA (n = 66). Urine and blood were collected weekly for 16 weeks and at months 5, 6, 9 and 12 and analyzed for BK by polymerase chain reaction (PCR). By 1 year, 70 patients (35%) developed viruria and 23 (11.5%) viremia; neither were affected independently by FK506, CyA, MMF or AZA. Viruria was highest with FK506-MMF (46%) and lowest with CyA-MMF (13%), p = 0.005. Viruria >/= 9.5 log(10) copies/mL was associated with a 3-fold increased risk of viremia and a 13-fold increased risk of sustained viremia. After reduction of immunosuppression, viremia resolved in 95%, without increased acute rejection, allograft dysfunction or graft loss. No BK nephropathy was observed. Choice of calcineurin inhibitor or adjuvant immunosuppression, independently, did not affect BK viruria or viremia. Viruria was highest with FK506-MMF and lowest with CyA-MMF. Monitoring and preemptive withdrawal of immunosuppression were associated with resolution of viremia and absence of BK nephropathy without acute rejection or graft loss.     

Delayed Reduction of Irreducible Chronic Posterolateral Dislocation of the Knee with Buttonholing of the Medial Femoral Condyle

Abstract Traumatic knee dislocations are relatively rare and almost always respond to closed reduction; however, a small percentage of knee dislocations are irreducible and in these cases open reduction is frequently required. A 65-year-old man with an unreduced posterolateral knee dislocation with laterally dislocated patella was seen 3 weeks after a motor vehicle accident. Medial femoral condyle was found buttonholed through the medial capsule together with the medial collateral ligament and lying in the medial joint space that allowed posterior rotary dislocation of the joint. Both cruciate ligaments and medial meniscus were torn. There was no evidence of any vascular or nerve injury. Reduction was accomplished by removal of the capsuloligamentous structures which were incarcerated in the trochlea and intercondylar notch and by excision of meniscal tear. Following posterior cruciate ligament reconstruction with patellar tendon autograft, lateral patellar release, vastus medialis advancement, and gracilis transfer were done.     

Ofloxacin plus Rifampicin versus Doxycycline plus Rifampicin in the treatment of brucellosis: a randomized clinical trial [ISRCTN11871179]

Background  

The combination therapies recommended by the World Health Organization for treatment of brucellosis are doxycycline plus rifampicin or doxycycline plus streptomycin. Although highly successful results have been obtained with these two regimens, relapse rates as high as 14.4%. The most effective and the least toxic chemotherapy for human brucellosis is still undetermined. The aim of the present study was to investigate the efficacy, adverse effects and cost of ofloxacin plus rifampicin therapy, and doxycycline plus rifampicin therapy and evaluate in the treatment of brucellosis.     

Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with parkinson's disease

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0–3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 ± 6.4% retention of isotope 2 h after the meal compared with 37.0 ± 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.     

Effect of tissue inhomogeneity on beta dose distribution of 32P

In a homogeneous medium of soft tissue the radiation dose distribution due to a nonuniformly distributed beta source can be calculated by convolution of the beta dose point kernel of the nuclide with the source distribution. A possible extension of the technique to the calculation of the dose distribution in heterogeneous media involving relatively simple geometric interfaces requires the knowledge of the resulting perturbation to the beta point kernels in individual media. We simulated a soft-tissue-bone planar interface by a polystyrene (PST)-aluminum junction and measured the change in beta dose from the dose value in homogeneous PST due to a point source of 32P using 7LiF thermoluminescent dosimeters. With the point source at the interface, the dose rates at 0-31, 125-156, and 283-314 mg/cm2 separations from the interface were increased by (12 +/- 3)%, (8 +/- 2)%, and (3 +/- 2)%, respectively, compared with homogeneous PST. With the point source at a PST-air planar interface to simulate a soft-tissue-air junction, the dose rates at 0-31, 139-170, and 283-314 mg/cm2 from the interface were decreased by (25 +/- 4)%, (11 +/- 7)%, and (5 +/- 2)%, respectively. The changes in dose rates for these two interfaces have also been measured with degraded spectra of 32P. Comparison of the experimental data with Monte Carlo calculation for a point source and the two-group method of calculation for a plane source is also presented.     

Behavioural strategies used by the hookworms Necator americanus and Ancylostoma duodenale to find, recognize and invade the human host

The infective third-stage larvae of the hookworms Necator americanus and Ancylostoma duodenale infect their human hosts by active skin invasion, but A. duodenale is in addition capable of oral infection. The behaviour of the larvae when crawling on surfaces has already been described. Here we analyse in various in vitro systems the other behavioural invasion phases: activation, penetration, and orientation within the host. The larvae normally remained in a motionless, energy-saving, resting posture. An activation to sinusoidal locomotion was stimulated in both species by similar cues such as touch, vibration, water currents, heat, light, and chemicals. Human breath in addition stimulated searching and waving (nictating) behaviour, which facilitates a change-over to the host. Activating cues in air streams were warmth and moisture; CO₂ activated only in combination with warmth and/or moisture. Penetration behaviour in both species was stimulated by warmth and skin extracts. The stimulating components of skin extracts were fatty acids, but their stimulating characteristics differed from those inducing schistosome cercarial skin penetration. After penetration into agar substrates, both species showed thermo-orientation, but only A. duodenale followed gradients of serum. The directing serum cues were not amino acids and glucose (the supposed cues for schistosome blood vessel localization), but Ringers solution attracted the larvae. The host-finding and host-invasion behaviour of both hookworm species is well adapted to the invasion of the human skin, and there seems to be no particular adaptation of A. duodenale behaviour to the oral infection mode. Hookworm host-finding behaviour is not as complex as that of schistosome cercariae but seems well adapted to the ecological conditions in the transmission sites.     

New and sensitive standard cell culture technique for the detection of cytomegalovirus in clinical specimens

Conventional tube cell culture has been recognised as the most sensitive technique available for human cytomegalovirus (HCMV) detection. Low-speed centrifugation of specimen inocula onto cell culture monolayers has been shown to increase the efficiency of infection with the AD 169 strain of HCMV. Therefore a centrifugal force of 900g for 1 hour at 37 degrees C was used to enhance the detection of HCMV cytopathic effect (CPE) in shell vials that contained circular coverslips with a monolayer of human embryonic lung (HEL) fibroblasts. Of 195 specimens, HCMV CPE was detected in 18 specimens (9.02%) on shell vial culture assay, whereas conventional tube cell culture was positive in only 13 specimens (6.6%). The shell vial culture assay was significantly more sensitive (P less than 0.05). Furthermore the development of the cytopathic effect on shell vial culture assay was significantly earlier (P less than 0.01) and more extensive. Urine samples were sonicated and the results obtained with immunofluorescence using human immune serum demonstrated that sonication increased both the intensity of fluorescence and number of fluorescent foci of HCMV-infected cells and also decreased the non-specific fluorescence of the background.     

Behaviour of guinea pig T cells stimulated by antigen, allo-antigen and mitogen

The expression of major histocompatibility (MHC) antigens on guinea pig T cells was used as a functional marker for lymphocyte activation. Antigen-stimulated lymphocytes were recovered from guinea pigs responding to the contact sensitizer DNFB, and isolated T cells were then phenotyped using a new antiguinea pig monoclonal antibody, MSgp7. The level of expression of MHC class II, as defined by the monclonal antibody, MSgp8, was increased on T cells recovered 4 days after sensitization, as compared with unsensitized controls. The value of this experiment was extended by measuring MHC class II expression on T cells stimulated in vitro by the mitogen concanavalin A, where a clear increase in MSgp8 binding was also observed. Confirmation of the specificity of MSgp8 for guinea pig MHC class II antigens was achieved by studying the inhibitory capacity of this antibody on an MHC class II restricted mixed leucocyte reaction. The combination of antibodies MSgp7 and MSgp8 with flow cytometry could be applied to other guinea pig experimental models to quantitate the expression of MHC class II antigens on T cells to determine their putative value in disease manifestation.     

Cigarette smoke prevents apoptosis through inhibition of caspase activation and induces necrosis

Emphysema is characterized by enlargement of the distal airspaces in the lungs due to destruction of alveolar walls. Alveolar endothelial and epithelial cell apoptosis induced by cigarette smoke is thought to be a possible mechanism for this cell loss. In contrast, our studies show that cigarette smoke condensate (CSC) induces necrosis in alveolar epithelial cells and human umbilical vein endothelial cells. Furthermore, study of the cell death pathway in a model system using Jurkat cells revealed that in addition to inducing necrosis, CSC inhibited apoptosis induced by staurosporine or Fas ligation, with both effects prevented by the antioxidants glutathione and dithiothreitol. Time course experiments revealed that CSC inhibited an early step in the caspase cascade, whereby caspase-3 was not activated. Moreover, cell-free reconstitution of the apoptosome in cytoplasmic extracts from CSC-treated cells, by addition of cytochrome-c and dATP, did not result in activation of caspases-3 or -9. Thus, smoke treatment may alter the levels of pro- and antiapoptogenic factors downstream of the mitochondria to inhibit active apoptosome formation. Therefore, unlike previous studies, cell death in response to cigarette smoke by necrosis and not apoptosis may be responsible for the loss of alveolar walls and inflammation observed in emphysema.     

Salsola pollen as a predominant cause of respiratory allergies in Kuwait.

BACKGROUND: Respiratory allergies are common in Kuwait, and the role of certain allergens has been previously documented. OBJECTIVE: To evaluate the results of skin prick tests to a range of allergens that were considered relevant to the vegetation surveys and aerobiological studies performed in Kuwait. METHOD: New patients attending our center during August 2002 to February 2003 with asthma or allergic rhinitis underwent skin prick tests to a battery of allergens. RESULTS: A total of 451 patients aged 5 to 60 years (mean age, 29.5 years) were tested. Of these patients, 403 (89.4%) had a positive test result to at least one allergen and were considered allergic. A total of 76.7% of the allergic patients had a positive reaction to Salsola pollen, with a mean wheal diameter of 8.25 mm (median, 8 mm). Chenopodium album was positive in 57.6% and Bermuda grass was positive in 38.2% of the allergic cases. Indoor allergens seemed to play a lesser role than pollens: Dermatophagoides pteronyssinus was positive in only 37.5%, and American and German cockroaches were positive in 33.2% and 22.3%, respectively. All the allergens other than Salsola elicited a mean wheal diameter of less than 6.25 mm (median, < or = 6 mm). CONCLUSIONS: Indoor allergens seem to play a lesser role in respiratory allergies in Kuwait. Most allergic patients become sensitized to pollens; the strongest and most frequent reaction is from Salsola pollen. Salsola imbricata is found growing extensively in most areas of the country, flowering mainly in autumn, when the most common pollen is of the Chenopod-Amaranth type and when most patients with seasonal allergic rhinitis become symptomatic.