Effects of the helium-neon laser on rat kidney epithelial cells in culture

The cellular mechanisms of action of low power lasers are only partially understood. Therefore, we have studied effects of helium-neon (He−Ne) laser irradiation in a cell culture model. The studies were performed with the permanent rat kidney cell line RK-L. By electron microscopy, significant ultrastructural changes of the cells were seen after He−Ne irradiation at 40 mW/cm² for 4h (569 J/cm²), including detritus-like formations of the cell organelles close to the nucleus. While such changes were not observed after 1 h irradiation (142 J/cm²), the number of cells in mitosis increased under this condition. In addition, the rate of incorporation of³H-thymidine into DNA decreased transiently 6–9 h after 1 h He−Ne irradiation of the cells. The consumption of glucose was also lowered for 10 h after irradiation, while the production of lactate increased. Finally, the synthesis of prostaglandin E₂ was reduced following irradiation. These results show that the He−Ne laser induces significant effects at the cellular level. In addition, our findings support the concept that the biological effects of low power laser treatment involve changes in the cell cycle.     

Infraorbital eyelid edema as the presenting sign of bronchogenic carcinoma

A 59‐year‐old man presented at our department with a 4‐week history of persisting and therapy‐refractory infraorbital edema ( Fig. 1 ). There was no previous history of eyelid edema, allergic reactions, autoimmune diseases, or new medications. Earlier therapy with corticosteroids and antihistamines was ineffective.

Figure 1 Open in figure viewer PowerPoint Persistent swelling of both infraorbital folds     

Lymphocytes proliferate in blood and lymph nodes following interleukin-2 therapy in addition to highly active antiretroviral therapy.

BACKGROUND: Substantial redistribution of lymphocytes occurs upon the initiation of highly active antiretroviral therapy (HAART) and immune-based HIV therapies. OBJECTIVE: To evaluate the relative contribution of apoptosis and proliferation to changes in lymphocyte populations in peripheral blood and lymph node resulting from interleukin-2 (IL-2) therapy in patients receiving stable HAART. METHODS: Lymphocyte apoptosis was analyzed on various subtypes using fluorescence activated cell sorting with an annexin-V antibody in peripheral blood and by the TUNEL (terminal uridine nucleotide end labelling) method in corresponding lymph node sections. Lymphocyte proliferation was evaluated using an antibody against the cell cycle-associated marker Ki-67 (MIB-1) in peripheral blood and lymph nodes. RESULTS: A transient increase in apoptosis was seen in peripheral blood and lymph nodes during a cycle of subcutaneous IL-2. A pronounced proliferative effect of IL-2 (from 6.4% of total lymphocytes in patients only treated with HAART to 23.4% in those treated with HAART + IL-2) was detected in peripheral blood, affecting the CD4, CD8 and CD16/56 subsets to a similar extent. Remarkably, the proliferative effect also occurred in lymphoid tissues. While the lymph node structure gradually disintegrated over 24 months in some individuals, the amount of proliferating lymphocytes, including CD4 cells, B cells and follicular dendritic cells, greatly increased upon IL-2, while HIV RNA load in lymph nodes remained unaffected. CONCLUSION: These results show that IL-2 leads to lymphocyte proliferation in peripheral blood and lymph nodes without an impact on viral load in lymphoid tissue. These results have important implications for attempts to reconstitute the immune system in HIV disease.     

Deconstructing the Pharmacovigilance Hype Cycle

Data science is making increasing contributions to pharmacovigilance. Although the technical innovation of these works are indisputable, efficient progress in real-world pharmacovigilance signal detection may be hampered by corresponding technology life cycle effects, with a resulting tendency to conclude that, with large enough datasets and intricate algorithms, “the numbers speak for themselves,” discounting the importance of clinical and scientific judgment. A practical consequence is overzealous declarations regarding the safety or lack of safety of drugs. We describe these concerns through a critical discussion of key results and conclusions from case studies selected to illustrate these points.     

Is serial determination of inspiratory muscle strength a useful prognostic marker in chronic heart failure?

BACKGROUND: Little data exists on the prognostic role of inspiratory muscle strength (PImax) in chronic heart failure (CHF). Training studies, however, frequently use it as a therapeutic target and surrogate marker for prognosis. The prognostic value of changes of PImax that allow this extrapolation is unknown. DESIGN: Patients with stable CHF were prospectively included and 1-year and all-time event rates recorded for endpoint analysis. METHODS: In 158 patients (85% men; New York Heart Association functional class: 2.4+/-0.6), PImax was measured along with clinical evaluations at two visits, the initial visit and the second visit, 6.4+/-1.4 months apart. The mean follow-up was 59+/-34 months. RESULTS: Overall, 59 patients (37%) reached the primary endpoint of death or hospitalization (endpoint positive), and overall mortality rate (secondary endpoint) was 26% (42 patients). PImax did not differ between endpoint-negative and endpoint-positive patients, both at the initial and at the second visit (8.3+/-5.6 vs. 7.3+/-3.4 kPa and 8.8+/-6.0 vs. 7.9+/-3.6 kPa, respectively; P=NS), and both groups showed increased PImax (0.6+/-2.6 vs. 0.6+/-2.8 kPa; P=NS). Cox analyses found neither the absolute nor the relative change of PImax to be significant predictors for the primary and secondary endpoints (P=NS for both), both for the 1-year and for the all-time event rates. Endpoint rates did not differ between patients showing increasing or decreasing PImax (P=NS; relative risk (RR): 0.77; 95% confidence interval: 0.47-1.27). CONCLUSION: Trials focusing on inspiratory muscle function should use the actual levels of PImax as a surrogate marker to represent prognostic information, rather than relative or absolute changes. This is the first study to investigate the prognostic information of the changes of PImax over time, regarding both short-term and long-term morbidity and mortality in patients with stable CHF.     

Mental stress and gastric acid secretion

In 14 healthy male volunteers, we studied the influence of acute mental (=psychological) stress induced by performing mental arithmetic and solving anagrams against a financial reward on endogenously stimulated gastric acid output. Personality factors were determined by the Personality Research Form. Acute mental stress significantly (P<0.05) increased systolic blood pressure (+8.9±2.0 mm Hg±sem) and heart rate (+5.3±1.6 beatslmin). The mean gastric acid output during the mental stress period (17.9±2.7 mmol/32 min) did not significantly differ from pre- (16.9±2.3 mmol/32 min) and poststress (18.1±2.2 mmol/32 min) values. However, detailed analysis revealed that mental stress induced contrary changes of gastric acid output in different subjects. About half the individuals reacted with a decrease (up to 60%) and the other half with an increase (up to 60%) in acid output. In some individuals the changes of gastric acid output were very small. By multiple correlations, impulsivity was identified as the personality trait with the highest correlation coefficient (r=0.82) with changes of gastric acid output during the acute mental stress period. During the mental stress period, gastric acid output increased in subjects with high scores on the impulsivity scale, but significantly decreased in those with low scores. We conclude that (1) there is a great individual variability in gastric acid response to acute mental stress, and (2) this variability may be partly attributed to differences in personality traits.     

Influence of E. coli Strain Nissle 1917 (EcN) on Intestinal Gas Dynamics and Abdominal Sensation

E. coli strain Nissle 1917 (EcN) is a probiotic clinically used with various indications. However, especially at the beginning of treatment, some patients report abdominal bloating. In a prospective, randomized, double-blind study in 30 healthy individuals we assessed the influences of EcN on intestinal gas dynamics and abdominal sensation. After one week without medication volunteers orally received 2.5–25 × 10⁹ colony-forming units of EcN or placebo per day for 21 days. EcN was well tolerated and did not significantly affect abdominal symptoms, stool frequency or stool consistency. During gas challenge at different days no difference in the perception scores (range from 0 = no perception to 6 = pain) was observed between the two groups: the mean perception score was 1.2 (SD 0.2) in the EcN group and 1.4 (SD 0.2) in the placebo group. EcN had no relevant influence on intestinal gas dynamics.     

Human and Animal Isolates of Yersinia enterocolitica Show Significant Serotype-Specific Colonization and Host-Specific Immune Defense Properties

Yersinia enterocolitica is a human pathogen that is ubiquitous in livestock, especially pigs. The bacteria are able to colonize the intestinal tract of a variety of mammalian hosts, but the severity of induced gut-associated diseases (yersiniosis) differs significantly between hosts. To gain more information about the individual virulence determinants that contribute to colonization and induction of immune responses in different hosts, we analyzed and compared the interactions of different human- and animal-derived isolates of serotypes O:3, O:5,27, O:8, and O:9 with murine, porcine, and human intestinal cells and macrophages. The examined strains exhibited significant serotype-specific cell binding and entry characteristics, but adhesion and uptake into different host cells were not host specific and were independent of the source of the isolate. In contrast, survival and replication within macrophages and the induced proinflammatory response differed between murine, porcine, and human macrophages, suggesting a host-specific immune response. In fact, similar levels of the proinflammatory cytokine macrophage inflammatory protein 2 (MIP-2) were secreted by murine bone marrow-derived macrophages with all tested isolates, but the equivalent interleukin-8 (IL-8) response of porcine bone marrow-derived macrophages was strongly serotype specific and considerably lower in O:3 than in O:8 strains. In addition, all tested Y. enterocolitica strains caused a considerably higher level of secretion of the anti-inflammatory cytokine IL-10 by porcine than by murine macrophages. This could contribute to limiting the severity of the infection (in particular of serotype O:3 strains) in pigs, which are the primary reservoir of Y. enterocolitica strains pathogenic to humans.