Expression of Human Recombination Activating Genes (RAG-1 and RAG-2) in Lymphoma

Two recently discovered genes, the recombination activating genes 1 and 2 (RAG-1 and RAG-2), are necessary to perform variable (V), diversity (D), and joining (J) recombination. They synergistically activate VDJ recombination to generate immunocompetent lymphocytes. Disruption of either gene results in a maturation arrest at a very early B and T cell progenitor stage. Expression and downregulation of RAG's are closely associated with interleukin 7, sIgM and TCR-CD3 complex, respectively. Assessment of RAG mRNA expression is a valuable marker in identifying the genotypic maturation status of leukemias and lymphomas. Persistent RAG expression in otherwise mature lymphoid proliferations may explain puzzling biological and clinical observations such as multiple rearrangements in lymphomas with a mature phenotype. Lack of RAG expression in Hodgkin's disease with abundant Reed-Stern-berg cells is consistent with a mature phenotype of the latter. Availability of a anti-RAG-1 monoclonal antibody in the near future will facilitate RAG analysis of lymphomas.     

Down-Regulation of Estrogen Receptor Immunoreactivity by 17β-estradiol in the Guinea Pig Forebrain

Low amplitude pulses of estradiol-17β (E₂-17β) are more effective than large single bolus injections or constant exposure to E₂-17β in inducing progesterone-facilitated sex behavior in female rats and guinea pigs. The present study examined whether the increased responsiveness to E₂-17β is due to an increase in the number of estrogen receptors in the estrogen receptor rich areas of the hypothalamus and amygdala. Initial studies examined the rapid effects (20 min) of a high dose of E₂-17β (50 μg) on estrogen receptor immunostaining using either the H222 antibody or the ER 21 antiserum. ER 21 immunostaining was not affected by the E₂-17β treatment suggesting that it binds to both occupied and unoccupied estrogen receptors. Therefore the ER 21 antiserum was used to characterize the regulation of estrogen receptor immunoreactivity (ER-IR) by E₂-17β. ER-IR was examined for 48 h and serum E₂-17β for 24 h following a 2 μg s.c. injection of E₂-17β (a dose similar to that used in multiple pulse paradigms). Serum E₂-17β peaked 15 to 30 min following the injection and returned to baseline values by 1 h. In all but one area maximal suppression of ER-IR occurred at 12 h. In summary, 1) decreases in estrogen receptor immunoreactivity following E₂-17β are consistent with studies in which estrogen receptors were assayed by binding assays and estrogen receptor mRNA was determined by in situ hybridization; 2) the ER 21 antiserum is able to detect both occupied and unoccupied estrogen receptors and 3) H222 immunoreactivity is influenced by the presence of E₂-17β, so that the level of H222-IR is a reflection of ligand/receptor binding dynamics. The data suggest that up-regulation of estrogen receptors does not account for the increase in behavioral sensitivity which is observed following multiple pulses of E₂-17β.     

Respiratory failure with diffuse patchy lung infiltrates: an unusual presentation of squamous cell carcinoma

The case history is presented of a patient with squamous cell carcinoma of the lung with diffuse bilateral pulmonary shadowing mimicking bronchioloalveolar cell carcinoma which led to type I respiratory failure.     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine

Background: Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia.

Methods: Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 [mu]g [middle dot]kg-1 [middle dot]min-1 (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 [mu]g [middle dot]kg-1 [middle dot]min-1 and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 [mu]g [middle dot] kg-1 [middle dot] min-1 until skin closure and then 2 [mu]g [middle dot]kg-1 [middle dot]min-1 for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h.

Results: Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects.     

Fluorine-18-fluorodeoxyglucose positron emission tomography for preoperative parathyroid imaging in primary hyperparathyroidism

Fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging was performed in seven consecutive patients with primary hyperparathyroidism to preoperatively locate parathyroid adenomas. Foci of FDG accumulation corresponding to abnormal parathyroid tissue were observed in two out of nine surgically excised parathyroid adenomas. It was concluded that FDG PET imaging demonstrated a too low sensitivity for systematic preoperative detection and localization of parathyroid glands causing primary hyperparathyroidism.     

Guided bone regeneration for immediate non‐submerged implant placement using bioabsorbable materials in Beagle dogs

The aim of the present study was to evaluate the combined application of different bioabsorbable materials for healing of residual peri‐implant defects after placement of non‐submerged implants into fresh extraction sockets. Second and third mandibular premolars were extracted from 10 Beagle dogs, the coronal part of the distal sockets were surgically enlarged and this was followed by immediate placement of specially designed hollow‐screw non‐submerged dental implants. For each animal, the coronal peri‐implant defects were further treated with one of the 4 following procedures: 1) no treatment, control site: 2) grafting with porous hydroxyapatite (HA); 3) collagen membrane tightly secured around the implant and over the defect and 4) grafting with HA covered with a collagen membrane. After 16 weeks of healing, specimens were removed from the mandibule and prepared for a histomorphometric evaluation. The bone-to-implant contact length (BIC) was measured and compared amongst the different treatment modalities. In the defect area, the irregular bone regeneration was similar between all the treatment procedures ( P >0.10). In the sites covered with a collagen membrane alone, the total BIC (47%) was greater than in control sites (28.7%. P <0.05) or sites grafted with HA (22.2%, P <0.02). Total BIC in sites treated with the HA‐membrane combination (43%) was only significantly different from sites treated with HA ( P <0.10). It is concluded that the use of bioabsorbable materials results in a limited increase of osseointegration when used in conjunction with immediate placement of non-submerged implants, although the principle of the one stage surgical approach can be maintained.     

Pre-adaptation, adaptation and de-adaptation to high altitude in humans: hormonal and biochemical changes at sea level

High altitude residence is known to modify body biochemistry and hormone status. However, the effects of such a sojourn on these status observed at sea level both immediately and later after return are not as well established as are the effects of an intermittent acclimation. The aim of this study was therefore to investigate these changes. To achieve our objectives, nine subjects received intermittent acclimation at low pressure in a barometric chamber (8?h daily for 5 days, day 1 at 4500 m, day 5 at 8500 m) before an expedition to the Himalayas. Hormonal and biochemical changes were studied using samples of venous blood taken at sea level before and after acclimation, after return from the expedition and 1 and 2 months after descent. Concentrations of thyroid hormones, adrenaline, noradrenaline (NA), hormones of hydromineral metabolism (aldosterone, renin, arginine vasopressin, atrial natriuretic peptide) as well as prolactin, cortisol, insulin and endothelin 1 were measured. Biochemical measurements made were plasma osmolality, and concentrations of glucose, total cholesterol, total proteins, pre-albumin, transferrin, complement 3C, apolipoproteins A₁ and B and serum iron. Acclimation induced no alteration in hormone (except for NA with increases of about 1.5, fold P<0.05) and biochemistry data. After the expedition, hormone responses were characterized by a higher total triidothyronine concentration (+18%, P<0.05) while other hormones did not vary. A linear relationship was found between thyroid-stimulating-hormone and body mass changes after the expedition (r=0.67, P<0.05). The observed increased concentrations of plasma proteins and total cholesterol (P<0.05) could be related to the restoration of lean body mass. At 1 and 2 months after return, no changes in hormones were observed but a significant decrease in transferrin concentration was noticed. The higher serum iron concentration reported after 1 month (P<0.05) could have been the result of a physiological haemolysis. It was concluded that both acclimation and the expedition in the Himalayas affected hormone status and body biochemistry status even though the observed changes were slight and rapidly reversed.