The effect of metoclopramide on gastric emptying in traumatic brain injury.

OBJECTIVE: Gastric paresis in traumatic brain injury (TBI) hinders the effectiveness of enteral support in this patient group. In this study we have investigated the effect of metoclopramide on gastric emptying in TBI patients. METHOD: In this prospective, randomized, controlled, double-blind study, 19 TBI patients with Glasgow Coma Scale scores of 3-11 were included. In all patients, enteral nutrition was commenced with a nasogastric feeding tube within 48 hours of trauma. Patients were randomized into two groups. In the metoclopramide (M) group, 10 mg metoclopramide was delivered intravenously three times daily for 5 days. In the control (C) group, an equal volume of saline was administered. Besides demographics, gastric emptying according to a paracetamol absorption test at days 0 and 5, time to reach target nutritional requirements, gastric residues, intolerance to feeding, nutritional complications, and clinical outcomes were recorded for each patient. RESULTS: The gastric residue rates were 2.7+/-7.4 mL and 8.1+/-17.7 mL per 100 patient days for groups C and M respectively (p=0.408). Similarly, feeding intolerance and complication rates did not significantly differ between groups C and M, (respectively p=0.543 and 0.930). Gastric emptying parameters also were similar between the study groups. CONCLUSION: We were unable to document any advantage to using metoclopramide in TBI patients. Simple intragastric enteral feeding with close monitoring of the possible complications seems to be sufficient with acceptable morbidity rates.     

The lack of effects of zinc and nitric oxide in initial state of pilocarpine-induced seizures.

In this study we investigated whether intracerebroventricular (i.c.v.) injection of L-NAME (a nitric oxide synthase inhibitor) or CaEDTA (an extracellular zinc chelator) or the combination of the two could affect the initial phase of pilocarpine induced (2 h) seizures. Two groups of rats were used. Animals from both groups were given with i.c.v. injections of either saline (10 microl), L-NAME (150 microg/10 microl), CaEDTA (100 mM/10 microl) or L-NAME and CaEDTA. One group received pilocarpine HCl (380 mg/kg i.p.) the other served as control. Pilocarpine HCl was injected intraperitoneally 10 min later. The behavior of the animals was observed for 2h and the intensity of their seizures was scored. The rats were then sacrificed and their brains were removed and analyzed for zinc ions by using the immersion autometallography and the TSQ fluorescence staining. All the animals which received pilocarpine HCl developed seizures. Despite treatment with L-NAME and/or CaEDTA we found that the latency and the intensity of seizures were similar in both groups investigated. The distribution of stainable zinc ions and the intensity of staining in hippocampus were not affected by pilocarpine and found unchanged after L-NAME and/or CaEDTA injections in both the control animals and the pilocarpine treated animals. The data suggest that the nitric oxide system and zinc ions do not affect pilocarpine-induced seizures in their initial state.     

The determinants of bronchial hyperresponsiveness in patients with allergic rhinitis.

BACKGROUND: Patients with allergic rhinitis and bronchial hyperresponsiveness (BHR) may be at higher risk of developing asthma. OBJECTIVE: To investigate whether reactivity to aeroallergens in skin prick testing (SPT) and serum eosinophil cationic protein levels can be used to predict BHR in allergic rhinitis patients. METHODS: Fifty-nine consecutive patients with allergic rhinitis underwent SPTs using grass, tree, weed, parietaria, Alternaria, Aspergillus, mites, and cat and dog dander extracts. Methacholine challenge tests were performed using spirometry. RESULTS: Methacholine-induced BHR was detected in 23 patients (39%). Of 59 patients, 14 had 1 positive SPT response, 35 had 2 to 4 positive responses, and 10 had more than 4 positive responses. There was a significant inverse correlation between methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20) and the number of positive SPT responses (r = -0.28; P = .03). The BHR-positive patients had a mean of 4 positive SPT responses, whereas BHR-negative patients had a mean of 2.6 (P = .04). Nine BHR-positive patients (39%) and only 1 BHR-negative patient (3%) had more than 4 positive SPT responses (P < .001). There was no correlation between serum eosinophil cationic protein levels and methacholine PC20 doses. There was a strong association between hyperresponsiveness to methacholine and both cat and dog dander sensitivity (P < .001 and P = .001, respectively). CONCLUSIONS: Allergic rhinitis patients with SPT responses to a higher number of allergens are more likely to have BHR. Whether the number of positive SPT responses correlates with the risk of developing asthma in allergic rhinitis patients remains to be determined.     

Spontaneous contractions and stretch-evoked responses of isolated lymph nodes

Summary In this study the spontaneous activities of prescapular lymph nodes, which were isolated from calves, goats and sheep and mesenteric lymph nodes of guinea-pigs were recorded and analysed in the frequency domain. Stretch-evoked contractions of the mesenteric lymph nodes were also recorded and their frequency characteristics analysed.The preparations were placed in a Krebs solution which was kept at 37° C and bubbled continuously with a mixture of 95% O₂ and 5% CO₂. The tension changes occurring in the lymph nodes were recorded. The patterns obtained were initially transformed into numerical values which were then used to obtain autocorrelation functions and power spectra, according to the time series analysis method. A passive stretch of 100 s duration was applied to the mesenteric lymph nodes and the responses were examined using the transient response-frequency characteristics method.It was observed that prescapular and mesenteric lymph nodes had spontaneous activities due to the contractions of the smooth muscles within the nodes. A frequency analysis of these contractions indicated that at least three contractile components were responsible for the contractions; these components contract within the frequency bands of 0.01–0.04 Hz, 0.05–0.07 Hz and 0.09–0.14 Hz respectively. It was also observed that the spontaneous activities could be regulated and synchronized by stretch. It is suggested that these contractions of the lymph nodes play an essential role in lymph propulsion within the nodes.     

A case of cellulitis causing tissue defect during etanercept therapy

Tumor necrosis factor-alpha (TNF-α) antagonists are employed increasingly during recent years in patients with active rheumatoid arthritis who do not respond to disease-modifying anti-rheumatic drugs. Contraindications such as infections, auto-antibody formation and hypersensitive reactions can be observed during the treatment with TNF-α antagonist drugs. Our case was a 52-year-old woman, followed by several centers for a period of 21 years with a seropositive, erosive and nodular RA diagnosis. Anti TNF-α treatment was commenced due to the failure to control the disease. During the treatment, a serious cellulite developed, which required hospitalization and surgical debridement as well as intravenous antibiotics treatment. Through the present case, we aimed to draw attention to the skin infection during the use of etanercept in a patient with RA.     

Antigen‐specific regulatory T cells can induce tolerance to immunogenic grafts without the need for chronic immunosuppression

Regulatory CD4⁺CD25⁺Foxp3⁺ T cells (Tregs) play an important role in the induction of allospecific tolerance. However tolerance in solid organ transplantation by mere transfer of Tregs has been difficult. Besides this the stability of the differentiation phenotype of Tregs has recently been questioned. We therefore aimed in generating large numbers of stable allospecific Tregs from naïve T cells by retroviral transduction with Foxp3. These were tested in an immunogenic skin transplantation model (C57BL/6→BALB/c). We established a system of transduction of mouse T cells with ecotropic retroviruses expressing Foxp3 and Thy1.1 as a surface marker to follow up transduced T cells. Alloantigen‐specific Tregs were generated by stimulating naïve recipient CD4⁺ T cells with irradiated donor splenocytes. CD25⁺ and/or CD69⁺ allospecific recipient CD4⁺ T cells were isolated and transduced with Foxp3. Alloantigen‐specific Foxp3 T cells (iTregs) showed high expression for the Treg markers Foxp3, CTLA4 and GITR. They could suppress a MLR in an alloantigen‐specific manner. Furthermore, they could be expanded up to 18 fold in vitro while maintaining their Treg phenotype and expression of lymph node homing markers like CCR7 and CD62L. iTregs prevented skin graft rejection without the need for chronic immunosuppression and recipients showed systemic allospecific allotolerance. Alloantigen‐specific Tregs were far more potent than polyspecific Tregs. Mechanisms of tolerance were graft specific homing, expansion and long‐term persistence of Tregs within the graft (>100 days, 90% of intragraft Tregs were alloantigen‐specific). In fact, tolerance could be transferred with re‐transplantation of the tolerant graft onto secondary recipients. Third party grafts were readily rejected demonstrating specificity of tolerance. Due to the Foxp3 transduction, iTregs did not lose their Treg phenotype. The results prove that large numbers of stable alloantigen‐specific Tregs can be generated from a polyclonal repertoire of naïve T cells. This is the first time that allotolerance was achieved in a non‐lymphopenic transplant model using skin grafts in an immunogenic strain combination. Therefore, antigen‐specific Tregs might have a huge therapeutic potential after solid organ transplantation.     

Renal function in pediatric patients with β-thalassemia major

In patients with β-thalassemia major, the most important cause of mortality and morbidity is organ failure due to deposits of iron.. In this study, the nature of the kidney injury and possible pathogenetic factors were investigated. Seventy children with β-thalassemia major and 14 age and sex-matched healthy children were involved in the study. Blood and timed urine samples were obtained for hematological and biochemical tests. The mean values of blood urea nitrogen (BUN), serum creatinine, creatinine clearance, serum sodium, urine osmolality, fractional excretion of sodium, potassium, and uric acid were not statistically different between the groups. Serum levels of potassium, phosphorus, and uric acid and the urine volume, high urinary protein to creatinine (U_P/Cr), urinary N-acetyl-β-d-glucosaminidase to creatinine (U_NAG/Cr), and urinary malondialdehyde to creatinine, (U_MDA/Cr) and the tubular phosphate reabsorption (TRP) values were statistically different between two groups (P<0.05). Increased serum levels of potassium, phosphorus, and uric acid in the patient group were attributed to the rapid erythrocyte turnover. The presence of high U_P/Cr, U_NAG/Cr and U_MDA/Cr ratios shows that in these patients with proximal renal tubular damage may be secondary to oxidative lipid peroxidation mediated by the iron overload. Received: 30 September 1999 / Revised: 19 May 2000 / Accepted: 22 May 2000