Antiviral properties of 3-quinolinecarboxamides: a series of novel non-nucleoside antiherpetic agents

Despite the long history in medicine, the pathophysiological mechanism(s) of seasonal affective disorder (SAD) remain largely unknown. By employing a meta-analytic methodology, the authors of this study attempted to verify the validity of different pathophysiological mechanism(s) proposed for SAD. The findings showed that for phototherapy of medium light intensity, a combination of morning-evening therapy regime yielded the best therapeutic effect, and the antidepressant effect of the morning-evening light regime was superior to a single pulse of light administered at other times of day. Furthermore, the data showed that the antidepressant effect of a single pulse of light was similar for morning, midday, and evening light. These findings supported the photon-count hypothesis and refuted the proposed photoperiod, melatonin, and phase-shifting models of SAD.     

The effect of inhaling a dry powder of sodium chloride on the airways of asthmatic subjects

Wet aerosols of 4.5% sodium chloride (NaCl) are often used to assess the bronchial responsiveness associated with asthma. We questioned whether dry NaCl could be used as an alternative. Dry powder NaCl was inhaled from capsules containing either 5, 10, 20 or 40 mg to a cumulative dose of 635 mg. The powder was delivered via an Inhalator or Halermatic. The airway sensitivity to the dry and wet NaCl was compared in 24 patients with asthma aged 19-39 yrs. All subjects responded to both preparations and the geometric mean (95% confidence intervals) for the provocative dose of NaCl causing forced expiratory volume in one second (FEV1) to fall 20% from baseline (PD[20,NaCl]) for dry NaCl was 103 mg (68-157) versus 172 mg (102-292), p<0.03 for the wet NaCl. The response to dry NaCl was reproducible and on repeat challenge the PD20 was 108 mg (75-153). The mean maximum fall in FEV1 was approximately 25% on each of the two test days. Spontaneous recovery occurred within 60 min after challenge with dry NaCl and within 5 min after bronchodilator. There were no serious side-effects requiring medical attention, however some patients coughed on inhalation of the 40 mg dose and three gagged. Arterial oxygen saturation remained within normal limits. We conclude that a suitably prepared dry powder of sodium chloride could potentially replace wet sodium chloride to assess bronchial responsiveness in patients with asthma, but further studies are required to establish the long-term stability of the dry powder preparation.     

Factors responsible for computed electrogastrographic parameters in humans

OBJECTIVES: Clinical knowledge about myoelectrical frequency is well known, but the factors responsible for recorded myoelectrical amplitude remain less clear. METHODS: We assembled an electrogastrographic system that could automatically compute the dominant myoelectrical frequency and power and power ratio. We enrolled 50 healthy volunteers (25 men and 25 women) to study their myoelectrical characteristics. Three surface electrodes were placed in the fundic, stomach body, and antral positions for two 30-min recordings in the fasting and postprandial states. RESULTS: The three different electrodes recorded similar dominant frequencies of about 3 cpm before and after a meal. The fasting dominant powers from these electrodes were 52.9 +/- 14.7, 44.6 +/- 11.5, and 50.1 +/- 15.1 dB, respectively (p < 0.01), whereas the postprandial dominant powers were 61.6 +/- 28.8, 54.3 +/- 26.6, and 61.9 +/- 27.8 dB, respectively (p < 0.01). Meal ingestion did increase the power (p < 0.05). Women had a lower dominant power than men (p < 0.001). Moreover, the dominant powers of each electrode were significantly correlated with body mass index (r = 0.3-0.36, p < 0.05) regardless of meal ingestion. The postprandial power ratio was not influenced by electrode position, gender, or body mass index. CONCLUSIONS: Myoelectrical dominant frequencies and power ratios are similar throughout the whole stomach area, whereas a lower power area exists on the stomach body. Gender-related variation in dominant power seems to be an effect of body size. The power ratio is the only reliable parameter for expressing myoelectrical amplitude.     

Assessment of quantitative artificial neural network analysis in a metabolically dynamic ex vivo 31P NMR pig liver study

Quantitative artificial neural network analysis for 1550 ex vivo 31P nuclear magnetic resonance spectra from hypothermically reperfused pig livers was assessed. These spectra show wide ranges of metabolite concentrations and have been analyzed using metabolite prior knowledge based lineshape fitting analysis which had proved robust in its biochemical interpretation. This finding provided a good opportunity to assess the performance of artificial neural network analysis in a biochemically complex situation. The results showed high correlations (0.865 < or = R < or = 0.992) between the lineshape fitting and artificial neural network analysis for the metabolite values, and the artificial neural network analysis was able to fully represent the trends in the metabolic fluctuations during the experiments.     

Patient treatment choice and compliance. Data from a substance abuse treatment program

Conservative surgery (CS) is widely accepted today as the treatment of choice for 60 to 80% of the primary breast cancer. Esthetic results of CS are not good in all the cases and improvement can be obtained thanks to the remodelling of the breast after tumorectomy. The scar should be selected according to the location of the tumor; the glandular tissue should be reshaped using local glandular flaps or following the principles of the reduction mammaplasties. Tumorectomy located in the upper part of the gland can be reshaped with an inferior pedicle type of mammoplasty. Defect located in the inferior part of the gland can be reconstructed with a superior pedicle mammoplasty. These sophisticated tumorectomies are providing good esthetic results on the reconstructed breast but require commonly a symmetry procedure on the contralateral breast. Such contralateral reduction allows a better exploration of the opposite breast and histological examination of the reduction specimen. In a series of 76 CS performed at the European Institute of Oncology (IEO), which were associated with some kind of plastic procedure to lower the risk of bad cosmetic results (representing 25% of the CS associated with plastic surgery), we confirmed the value of the mixed oncologic and plastic approach. The esthetic results observed in this series are better than those observed in another series previously published at the Gustave-Roussy Institute (IGR)--good results: 72% (IEO) vs 50% (IGR), and bad results: 6% (IEO) vs 20% (IGR). Statistically such comparison can be criticised, specially because of the short follow-up of the Milan series. However, the difference is rather important if we consider that the series of Milan was a selection of cases with poor esthetic expectation (25% of all the CS performed during the same period), while the series of Paris did not select the patients in what concerns the risk of poor esthetic result.     

Primary biliary cirrhosis associated with mixed type autoimmune hemolytic anemia and sicca syndrome: a case report and review of literature

A case presenting with an unusual association of primary biliary cirrhosis and mixed type autoimmune hemolytic anemia plus sicca syndrome is described. The 49-yr-old female primary biliary cirrhosis patient had a confirmed sicca syndrome and presented with jaundice and life-threatening anemia. Laboratory tests revealed positive Coombs' test with coexisting cold and warm autoantibodies. She was successfully treated by blood transfusion with packed red cells lacking any red cell antigens corresponding to serum alloantibodies and pulse methylprednisolone therapy. The patient remained stable under maintenance treatment using oral steroids and ursodeoxycholic acid. This case is probably the first reported showing an association between primary biliary cirrhosis and mixed type autoimmune hemolytic anemia plus sicca syndrome and was probably induced by heterogenous and complicated autoimmune reactions.     

In vitro expansion of hematopoietic progenitors and maintenance of stem cells: comparison between FLT3/FLK-2 ligand and KIT ligand

The effects of FLT3/FLK-2 ligand (FL) and KIT ligand (KL) on in vitro expansion of hematopoietic stem cells were studied using lineage-negative (Lin-)Sca-1-positive (Sca-1+) c-kit-positive (c-kit+) marrow cells from 5-fluorouracil (5-FU)-treated mice. As single agents, neither FL nor KL could effectively support the proliferation of enriched cells in suspension culture. However, in combination with interleukin-11 (IL-11), both FL and KL enhanced the production of nucleated cells and progenitors. The kinetics of stimulation by FL was different from that by KL in that the maximal expansion by FL of the nucleated cell and progenitor pools required a longer incubation than with KL. We then tested the reconstituting abilities of cells cultured for 1, 2, and 3 weeks by transplanting the expanded Ly5.1 cells together with "compromised" marrow cells into lethally irradiated Ly5.2 mice. Cells that had been expanded with either cytokine combination were able to maintain the reconstituting ability of the original cells. Only cells that had been incubated with KL and IL-11 for 21 days had less reconstituting ability than fresh marrow cells. These results indicate that there can be significant expansion of progenitors in vitro without compromising the reconstituting ability of stem cells. Addition of IL-3 to permissive cytokine combinations significantly reduced the ability of cultured cells to reconstitute the hematopoiesis of irradiated hosts. These observations should provide a basis for a rational approach to designing cytokine combinations for in vitro expansion of hematopoietic stem cells.     

Comparison of muscle mass preservation in denervated muscle and transplanted muscle flaps after motor and sensory reinnervation and neurotization

The gracilis muscle model was used either as a denervated muscle in situ or as a transplanted flap in 273 rats to compare the trophic effects of muscle reinnervation and neurotization using sensory and motor nerves. The average gracilis muscle flap weighed 626 +/- 94 mg at the time of the initial procedure. Experimental muscles were examined 6 months following the procedure. In denervated, nontransplanted muscles, both motor nerve reinnervation and neurotization resulted in significantly preserved muscle mass, averaging 570 +/- 69 and 521 +/- 116 mg, respectively, compared with the denervated control average of 178 +/- 22 mg (p < 0.05). Sensory nerve reinnervation and neurotization produced much smaller trophic effects (p > 0.05). In transplanted gracilis free flaps, however, only direct reinnervation with motor or sensory nerves resulted in improved bulk preservation, with average weights of 313 +/- 83 and 327 +/- 91 mg compared with the control average of 201 +/- 76 mg (p < 0.05). Neither sensory nor motor neurotization was significantly effective in the free-flap model (p > 0.05). These data suggest that transplantation may alter the response of muscle to reinnervation.     

Can energy transfer be an indicator for DNA intercalation?

Contact energy transfer from DNA bases to various ligands, which can be represented by the ratio of the fluorescence intensity Q(lambda)/Q310nm, is measured by conventional fluorometer. 4',6-Diamidino-2-phenylindole and 2'-(4-hydroxyphenyl)-5-(4-methyl-1-piperazinyl)-2,5'-bi-1H-benzimidazole can accept energy from DNA bases and exhibit the ratio Q(lambda)/Q310nm, similar to that of intercalators, although these molecules are known to bind preferentially to the minor groove of the adenine-thymine rich region of DNA. When porphyrin is intercalated in DNA or poly[d(G-C)2], the shape of the ratio Q(lambda)/Q310nm is distinct from that of the ethidium-DNA complex with two maxima at 250 nm and 280 nm. The ratio Q(lambda)/Q310nm of the porphyrin-poly[d(A-T)2] complex, in which porphyrin is known to bind 'outside' of the DNA stem, is similar to that of intercalators. Therefore, energy from excited DNA bases can be transferred not only to an intercalated ligand through direct contact but also to that bound in the minor groove. It follows from this observation that using energy transfer as a criterion for DNA intercalation requires extreme caution.     

Residual masses after chemotherapy for metastatic testicular cancer: the clinical implications of the association between retroperitoneal and pulmonary histology. Re-analysis of Histology in Testicular Cancer (ReHiT) Study Group

PURPOSE: We determined the need and sequence of retroperitoneal lymph node dissection and thoracotomy in patients with nonseminomatous testicular cancer, and with residual retroperitoneal and pulmonary masses after chemotherapy. MATERIALS AND METHODS: We studied 159 patients undergoing retroperitoneal lymph node dissection and a thoracotomy following cisplatin based induction chemotherapy for metastatic testicular nonseminomatous germ cell tumor. Several well-known predictors for residual histology (necrosis, mature teratoma and cancer) were evaluated. RESULTS: As expected, necrosis was found more often at retroperitoneal lymph node dissection if the primary tumor was negative for teratoma, the residual mass was small or the decrease in size was great. Contrary, neither residual mass size nor the decrease in size was predictive of the histological status of the residual lung lesion. Histological findings in the retroperitoneum and lung were strongly correlated, such that necrosis at retroperitoneal lymph node dissection was associated with an 89% probability of necrosis in the lung. CONCLUSIONS: Retroperitoneal lymph node dissection should be performed before thoracotomy is considered, since the histological status at dissection is a strong predictor of that at thoracotomy.