Anti-s antibody-associated delayed hemolytic transfusion reaction in patients with sickle cell anemia

PURPOSE: Signs and symptoms of delayed hemolytic transfusion reaction (DHTR) may resemble those of vaso-occlusive crises in patients with sickle cell anemia (SCA). The diagnosis of DHTR therefore presents a challenge to the clinician when treating such patients. The current study describes a patient with SCA and DHTR secondary to red cell anti-s antibody, manifesting as painful extremeties, severe hemolytic anemia, and acute oliguric renal failure. PATIENTS AND METHODS: A 17-year-old patient with homozygous hemoglobin S presented 8 days after partial exchange transfusions with severe anemia and signs and symptoms resembling vaso-occlusive crisis. Clinical course was complicated by intravascular hemolysis and acute renal failure. RESULTS: Anti-s antibody was detected in the eluate. Diagnosis of DHTR was made. Treatment included single volume whole blood exchange transfusion and continuous veno-venous hemofiltration with dialysis. CONCLUSIONS: The possibility of DHTR should be considered in a patient with SCA with hemolytic anemia. Acute renal failure is a rare complication of anti-s antibody-associated DHTR. Such reactions can be successfully managed with exchange transfusion and continuous hemofiltration with dialysis.     

Supraacetabular insufficiency fractures

Insufficiency fractures in the supraacetabular region were identified in five women, aged 55-83 years. Factors contributing to the diminished resistance of their bones included postmenopausal osteoporosis, steroid therapy, radiation therapy, and rheumatoid arthritis. The supraacetabular fractures were seen on routine radiographs as hazy bands of sclerosis located immediately above and parallel to the acetabular roof. All five patients had additional fractures in the spine or pelvis. Supraacetabular insufficiency fractures may be an unsuspected cause of hip pain, especially in older women.     

Evaluation of pain-related behavior, bone destruction and effectiveness of fentanyl, sufentanil, and morphine in a murine model of cancer pain

The present study was conducted to evaluate the pain development and bone destruction during bone cancer growth in a murine model of bone cancer pain and to evaluate the analgesic efficacy of fentanyl, sufentanil, and morphine in this model. C3H/HeNCrl mice were inoculated into the intramedullary space of the femur with osteolytic NCTC 2472 fibrosarcoma cells, and followed during a 3-week period to assess pain behaviors (spontaneous lifting and limb-use during forced ambulation on rotarod) and bone destruction (parameters indicative of bone lesions determined by microCT-scans of the tumor-bearing bones) during bone cancer growth. The results showed that in this murine model of cancer-induced bone pain, behavioural manifestations of pain emerge in parallel with the progression of bone destruction. The subcutaneous administration of fentanyl (0.025-0.64 mg/kg), sufentanil (0.005-0.04 mg/kg), and morphine (2.5-40 mg/kg) on the test days 15 and 22 post-inoculation reduced pain-related behaviors in a dose dependent manner. A complete relief from pain-related behaviors was achieved with the following doses: > or =0.16 mg/kg fentanyl, 0.02 mg/kg sufentanil, and 20 mg/kg morphine. In conclusion, the results showed a clear link between tumor growth-induced bone destruction and behavioral pain manifestations, the latter was effectively controlled by the opioids fentanyl, sufentanil, and morphine.     

A preclinical comparison between different opioids: antinociceptive versus adverse effects

Reduced side-effect liability of opioids may enhance the patient's quality of life and decrease the incidence of opioid-insensitive pain. Literature offers few comparative data between different opioids at equianalgesic doses. Therefore morphine, fentanyl, buprenorphine, codeine, hydrocodone and oxycodone were compared for analgesic properties and side-effect profiles in rats. Analgesic efficacy was analysed using a tail withdrawal test for acute thermal nociception, a formalin test for chemically induced inflammatory pain and a von Frey test for mechanical hypersensitivity. For side-effect profiling inhibition of gastrointestinal activity was evaluated in a charcoal and ricinus oil test, arterial PCO(2) was determined for measuring respiratory depression, the discriminative stimulus properties linked to the narcotic cue were assessed using a drug discrimination learning test, and motor coordination was tested through rotarod performance. ED(50)'s for the occurrence of side-effects were compared to ED(50)'s in behavioural pain tests. Fentanyl had a strong analgesic potency and, compared to other opioids, an acceptable side-effect profiling at analgesic ED(50)'s. Also consistent was the ceiling effect of buprenorphine implying an increased safety margin for side-effects, but a decreased analgesic efficacy. Differences between opioids as observed in this study can have important indications for their use in acute as well as in the onset of chronic treatments.     

Herpes simplex virus pneumonia in a patient with ependymoma

The authors report a fatal outcome in a 4-year-old boy with herpes simplex virus (HSV) pneumonia and ependymoma. The patient had respiratory distress that worsened despite antibiotic treatment. Bronchoalveolar lavage showed intranuclear viral inclusions, and culture was positive for HSV type 1. His T-cell count was significantly decreased. Although acyclovir and foscarnet were given, the patient died. Postmortem examination showed HSV pneumonitis with severe alveolar damage and severe involutional changes of the thymus with absence of Hassall's corpuscles. HSV must be considered in the differential diagnosis of patients with interstitial pneumonia and T-cell deficiency, especially after craniospinal irradiation.     

Learning effect of a novel interactive basic life support CD: the JUST system

INTRODUCTION: Electronic interactive learning environments can enhance the learning experience and may prove beneficial in basic life support (BLS) training. As part of the European Union funded project "JUST-in-time health emergency interventions-training of non-professionals by virtual reality and advanced IT tools", an innovative interactive CD-ROM on BLS and other emergency medicine topics was developed. We hypothesised that individuals without previous BLS training could learn CPR techniques from this CD. METHODS: Sixty-two students were randomised into a group studying the JUST CD in a computer class room for up to 60 min, and a control group who did not receive any training (serving as a reference). CD users also completed a satisfaction questionnaire immediately after studying the CD. The BLS skills of both groups were assessed in a mock BLS scenario on a training manikin. BLS performance was video recorded and analysed. RESULTS: After studying the CD for a mean period of 42 min, users of the CD had better assessment skills and were more likely to show a positive helping attitude, but chest compression and breathing techniques were ineffective. Most users rated the CD as very good and a positive learning tool. CONCLUSION: Individuals without prior BLS training showed improved behaviour and assessment skills after exposure to the CD, but motor skill acquisition requires alternative learning strategies.     

Attenuation of the gerbil writhing response by mu-, kappa- and delta-opioids, and NK-1, -2 and -3 receptor antagonists

Mu-, kappa- and delta-opioid receptor agonists are reported to attenuate the acetic-acid-induced abdominal constriction response in mice. NK-1, -2 and -3 receptor antagonists also display activity in several visceral pain models. As the gerbil NK-1 receptor is comparable to the human receptor, we evaluated the efficacy of NK-1, -2 and -3 receptor antagonists and opioids (both alone and in combination) in the writhing test in this species. The effects of a selective L-type calcium (Ca2+) channel antagonist on the writhing response were also assessed to determine the contribution of Ca2+ channel antagonism to the antinociceptive effects of the NK-1 antagonists. Gerbils received subcutaneous injections of either the mu-opioids morphine or fentanyl, the kappa-opioid U50,488-H, the delta-opioid SNC80, NK-1 antagonists R116301, CP-96,345 or GR203040, the NK-2 antagonist SR-48968, the NK-3 antagonist SR-142801 or the Ca2+ channel antagonist nimodipine. Writhing was evoked 1 h after treatment by intraperitoneal injection of 0.2 ml 1% acetic acid solution and the frequency was recorded. Morphine, fentanyl and U50,488-H attenuated the writhing response dose dependently with complete inhibition occurring at the highest doses. SNC80 did not significantly attenuate the writhing response even at a dose of 40 mg/kg. The tachykinin NK-1 antagonists CP-96,345 and GR203040, the NK-2 antagonist SR-48968 and the NK-3 antagonist SR-142801 reduced the writhing frequency although without complete inhibition. The NK-1 antagonist R116301 displayed limited activity at doses up to 40 mg/kg. Nimodipine did not exhibit any antinociceptive efficacy in this assay. Adding the NK-1, -2 or -3 antagonists to the opioids did not improve the efficacy of the opioids. Selective NK antagonists may therefore be effective in a visceral nociception assay in gerbils but do not modulate opioid action.     

Correlation of different markers (p53, EGF-R, c-erbB-2, Ki-67) expression in the diagnostic biopsies and the corresponding resected tumors in non-small cell lung cancer

Substaging using molecular markers has been proposed to try to identify prognostic factors allowing to define groups of patients with lung cancer for whom specific therapy might be of benefit. The pre-operative assessment of these markers seems to be important specially in case of neoadjuvant chemotherapy. The aim of our study was to compare the expression of two potential prognostic factors (p53 and Ki-67) and two potential therapeutic targets (EGF-R and c-erbB-2) assessed on biopsy samples (B) of non-small cell lung cancer (NSCLC) with that of the corresponding resected tumor (RT). The expression of these biological markers was evaluated by immunohistochemistry on B and on the paired RT in 28 patients. The mean percentage of p53 positive cells was 28% in RT and 38% in B with 81% CR between B and RT and 19% FP on B. Considering RT results as standard, the positive (PPV) and negative predictive value (NPV) of the B were, respectively, 74 and 100%. The mean percentage of EGF-R positive cells was 11% in RT and 28% in B. With a cut-off of 1%, we found 85% concordant results (CR) between B and RT, 4% false negative (FN) and 11% false positive (FP) on B. The PPV and NPV values of the B were, respectively, 80 and 92%. The 8% B and 19% RT were considered as positive for c-erbB-2. We found 15% FN and 4% FP on B with 81% CR between B and RT for c-erbB-2. The NPV of the B was 83%. The mean percentage of Ki-67 positive cells was 32% in RT and 14% in B. We found 82% CR between B and RT, 14% FN and 4% FP on B. The PPV of the B was 96%. In conclusion, biopsies may provide reliable information about p53, EGF-R, c-erbB-2 and Ki-67 in lung carcinoma and could help to elaborate a therapeutic strategy.     

A chronic-constriction injury of the sciatic nerve reduces bilaterally the responsiveness to formalin in rats: a behavioral and hormonal evaluation

Application of four loose ligatures to the sciatic nerve of a rat (chronic constriction injury [CCI]) induces clear hypersensitivity to non-noxious stimulation and chemical irritants. However, in this study, an injection of formalin in the hind paw of a rat with CCI-induced mononeuropathy resulted in an ipsilateral decreased flinching and licking or biting behavior in both phases of the formalin testing. The effect was independent of the formalin concentration used. This altered behavior was accompanied with smaller plasma levels of adrenocorticotrope hormone and corticosterone compared with sham and non-operated animals. Formalin injection in the contralateral nonligated hind paw of CCI rats also reduced the licking or biting behavior as compared with sham-operated and non-operated control animals only in the second phase of the formalin test. Thus, CCI reduces the pain reactivity and hypothalamic-pituitary-adrenal-axis activation to ipsilateral and contralateral formalin injection. Further research should investigate whether the decreased pain reactivity by CCI is situated at the peripheral, spinal, or supraspinal level or is result of changes in the stress reactivity and coping strategies. IMPLICATIONS: We evaluated the changes in the behavioral reactions and the hormonal effects of a noxious chemical stimulus, i.e., formalin injection in animals with previously induced chronic constriction injury to the sciatic nerve. The effect in animals injected at the ipsilateral and contralateral site, sham-operated and controls, were compared.