Females are at higher risk than males for developing posttraumatic stress disorder symptoms (PTSS) following exposure to trauma, which may stem from gender differences in initial physiological and psychological responses to trauma. The present study aimed to examine a number of peri- and initial post-traumatic reactions to motor vehicle accidents (MVAs) to determine the extent to which they contributed to gender differences in PTSS. 356 adult MVA survivors (211 males and 145 females) reported on peritraumatic dissociation, perception of life threat and initial PTSS. In addition, heart rate and urinary cortisol levels were collected in-hospital. 6 weeks and 6 months later, PTSS were assessed via clinical interviews. Results suggested that initial PTSS and peritraumatic dissociation were marginally significant mediators at 6-week follow-up and significant mediators at 6-month follow-up, providing partial support for the hypothesis that initial responses to trauma may account for observed gender differences in PTSS development.

Objective/Introduction Secondary pharmacological interventions have shown promise at reducing the development of posttraumatic stress disorder symptoms (PTSS) in preclinical studies. The present study examined the preliminary efficacy of a 10-day low-dose (20 mg bid) course of hydrocortisone at preventing PTSS in traumatic injury victims. Methods Sixty-four traumatic injury patients (34% female) were randomly assigned in a double-blind protocol to receive either a 10-day course of hydrocortisone or placebo initiated within 12 hours of the trauma. One-month and 3-months posttrauma participants completed an interview to assess PTSS and self-report measures of depression and health-related quality of life. Results Hydrocortisone recipients reported fewer PTSD and depression symptoms, and had greater improvements in health-related quality of life during the first 3 months posttrauma than did placebo recipients. Hydrocortisone recipients who had never received prior mental health treatment had the lowest PTSD scores. Conclusion Low-dose hydrocortisone may be a promising approach to the prevention of PTSD in acutely injured trauma patients, and may be particularly efficacious in acutely injured trauma victims without a history of significant psychopathology.

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SUMMARYThe microenvironment within solid tumours has often been shown to exhibit an acidic local pH. In recent studies we could demonstrate that an acidic extracellular pH (pH e ) inhibits the non-major histocompatibility complex (MHC) -restricted cytotoxicity of immunocompetent effector cells. However, within tumours the activation of cytotoxic cells may already be impaired by low pH e . Therefore, we investigated the in¯uence of acidic conditions on the generation of active killer cells. The cytotoxic activity of natural killer (NK) as well as lymphokine-activated killer (LAK) cells against K562, Daudi and Raji cells was analysed after an activation period of 3 days at pH e 7 . 2±6 . 5. A minor reduction of pH e from 7 . 2 to 7 . 0 during the culture period resulted in a strong inhibition of the natural cytotoxicity of NK cells. Furthermore, acidic pH e below 7 . 2 prevented the generation of activated LAK cells by interleukin-2 (IL-2). The cytotoxic capacity could not be reconstituted if cells cultured at a pH e of 6 . 5 were returned to physiological pH for another 24 hr. Analysis of the cellular subtypes within the various cultures did not reveal differences regarding the frequencies of NK cells, CD8 + T cells, or CD4 + T cells. However, an acidic pH e clearly inhibited the activationinduced increase of relevant adhesion molecules. The production of cytokines which are involved in the regulation of the cytotoxic process (tumour necrosis factor-a, interferon-c, IL-10, IL-12 and transforming growth factor-b 1 ) was also affected by pH e , as their release was strongly inhibited at pH e 7 . 0. Furthermore, we observed a considerable decrease in the metabolic activity of effector cells at acidic pH e . In summary, our ®ndings suggest that an acidic microenvironment impairs the induction of an anti-tumoral immune response within solid tumours.

Local immunosuppression may explain the failure of an effective immune response against solid tumors. Although it is well known that the interstitial pH is significantly lower in solid tumors than in normal tissue, only a few studies in the mouse system have investigated the influence of this acidic milieu on the anti-tumoral cytotoxic response. Here the authors report the suppression of human non-major histocompatibility complex (MHC)-restricted cytotoxicity against tumor cells by an acidic extracellular pH (pHe). Unstimulated peripheral blood mononuclear cells, lymphokine-activated killer (LAK) cells, and natural killer cell clones were used as effector cells. According to pH measurements in solid tumors, representative pH values of 7.2 to 5.3 were chosen during the cytotoxic assays. Target cell lysis was measured using two nonradioactive fluorometric methods, namely two-color flow cytometry and a modified calcein-release assay, which allowed cell-mediated cytotoxicity to be measured and compared with that in adherent targets. Using K562, Daudi, or Raji as suspended target cell lines, the cytotoxic activity of unstimulated peripheral blood mononuclear cells and of LAK cells was markedly reduced by a decreasing pHe. An extracellular pH of 5.8 to 5.3 resulted in a nearly complete loss of the cytotoxic response. This pHe-dependent impairment of the killing activity could also be shown for killer cells stimulated with interleukins-7 and -12, phytohemagglutinin, or lipopolysaccharide. The lytic potential of homogeneous natural killer cell clones as effectors was also strictly influenced by the surrounding pH. The pHe dependence of the non-MHC-restricted killer cell functions against tumor cells seems to be a general phenomenon, because the cytolytic activity of LAK cells against six human adherent tumor cell lines (HeLa, HepG2, LS174T, LS174Te, MCF-7, and RT112) was also clearly reduced under acidic conditions. To initiate the killing process, adhesion molecules play an important role in recognition and binding of the target cell. However, flow cytometric analysis revealed that the expression pattern of relevant adhesion molecules was unaffected by acidic pHe. In conclusion, these data clearly indicate an inhibition of non-MHC-restricted cytotoxicity against tumor cells by an acidic pHe, which may contribute to the failure of immunosurveillance against solid tumors. Consequently, efforts to enhance the anti-tumoral cytotoxicity by immunotherapies may have limited success.

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Laser hair depilation is a promising therapy in the management of pilonidal disease. However, the literature published to date is heterogeneous and has limited generalizability. Additional research is needed to determine the effectiveness of laser hair depilation to prevent pilonidal disease recurrence.

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