Inflammatory insults and mental health consequences: does timing matter when it comes to depression?

It has become widely accepted that the immune system, and specifically increased levels of inflammation, play a role in the development of depression. However, not everyone with increased inflammation develops depression, and as with all other diseases, there are risk factors that may contribute to an increased vulnerability in certain individuals. One such risk factor could be the timing of an inflammatory exposure. Here, using a combination of PubMed, EMBASE, Ovid Medline and PsycINFO, we systematically reviewed whether exposure to medically related inflammation in utero, in childhood, and in adolescence, increases the risk for depression in adulthood. Moreover, we tried to determine whether there was sufficient evidence to identify a particular time point during the developmental trajectory in which an immune insult could be more damaging. While animal research shows that early life exposure to inflammation increases susceptibility to anxiety- and depressive-like behaviour, human studies surprisingly find little evidence to support the notion that medically related inflammation in utero and in adolescence contributes to an increased risk of developing depression in later life. However, we did find an association between childhood inflammation and later life depression, with most studies reporting a significantly increased risk of depression in adults who were exposed to inflammation as children. More robust clinical research, measuring direct markers of inflammation throughout the life course, is greatly needed to expand on, and definitively address, the important research questions raised in this review.

Preliminary studies of photoinactivation of human immunodeficiency virus in blood.

The transmission of human immunodeficiency virus (HIV) by blood or blood components is a major concern in blood banking. A photodynamic flow cell system was designed to inactivate cell-free HIV mixed with blood from a healthy donor. Blood containing 4 x 10(3) infectious units of HIV was treated with 10 and 20 micrograms per mL of commercially available dihematoporphyrin ether (DHE) per mL. Aliquots of this mixture were then held in the dark or irradiated in a flow cell illuminated at a light energy density of 5 J per cm2 provided by a xenon light source equipped with a 630 +/- 5 nm band-pass interference filter; the aliquots were subsequently placed in A.301 cells. All infected cultures were assessed for reverse transcriptase (RT) activity for 17 days. RT activity for either concentration of dye was significantly reduced in irradiated samples as compared to that in samples held in the dark. Blood samples from volunteers also were assessed for the effects of the inactivation process on red cells at concentrations of DHE up to 200 micrograms per mL. No effects were observed on red cell 2,3 DPG or ATP, whole blood potassium concentrations, red cell osmotic fragility, or blood cell antigens.

Photodynamic inactivation of simian immunodeficiency virus.

A photodynamic flow system employing a dihematoporphyrin ether (DHE) was tested for its ability to inactivate the in vitro infectivity of simian immunodeficiency virus (SICMac) at 630 +/- 5 nm with a light fluence of 5 J/cm2. Cell-free SIVMac was inactivated by photoactivated hematoporphyrin derivative in a dose-dependent fashion. Since SIVMac is closely related to human immunodeficiency virus type 2 (HIV-2) and we have previously reported the successful photodynamic inactivation of HIV-1 in cell-free medium as well as in whole human blood, this technology has the potential for the eradication of transfusion-associated acquired immunodeficiency diseases caused by the above-mentioned retroviruses.

Photodynamic therapy of viral contaminants with potential for blood banking applications.

A photodynamic method has been evaluated as a means of eradicating viral contaminants with the potential for rendering blood safe for transfusion. Herpes simplex virus type 1 (HSV-1) was tested under flowing conditions in culture media or in blood supplemented with the virus. Hematoporphyrin derivative was used as the sensitizer and was photoactivated with visible light at 630 nm and 5 J/cm2. HSV-1 in suspension both in culture medium as well as in blood was shown to be killed. The human immunodeficiency virus was also found to be photoinactivated in flowing cell culture medium and, thus, potentially may be inactivated in blood. These findings extend our previous studies which demonstrated that enveloped viruses can be photoinactivated with hematoporphyrin derivative in a static fluid system. Analysis of blood cell number, red cell lysis, plasma proteins, and other standard hematological tests showed no significant change. The possibility that transfusion-associated acquired immunodeficiency syndrome (AIDS) may result from a blood unit infected with human immunodeficiency virus that tested negative makes it imperative that a safe and effective means of viral killing be developed. The system reported here offers promise as an effective approach to this problem.

Hematologic and coagulation studies on cotton rats, Sigmodon hispidus.

1. Blood coagulation factor levels and the normal ranges of commonly used coagulation tests were established for Sigmodon hispidus. 2. The white cell, red cell and platelet counts have been determined together with the red cell parameters as measured by the Coulter model S-plus. 3. The relationship between the results reported here and those published for related species are discussed.

The treatment of postperfusion bleeding using epsilon-aminocaproic acid, cryoprecipitate, fresh-frozen plasma, and protamine sulfate.

The evaluation of excessive hemorrhage was carried out in 774 patients after cardiopulmonary bypass. Excessive hemorrhage was defined in any adult patient as chest tube drainage of more than 600 ml within the first eight hours after operation. Using the prothrombin time, partial thromboplastin time, fibrinogen level, and tri-F titer tests, it was possible to differentiate medical from surgical bleeding. Hyperfibrinolytic bleeding was the most frequently identifiable coagulation disorder and occurred in 159 patients (20%). All these patients were successfully treated with Amicar (epsilon-aminocaproic acid) alone, or with Amicar supplemented with cryoprecipitate or fresh-frozen plasma. Three patients (0.4%) were noted to have residual heparin and required additional protamine sulfate. Five patients (0.6%) had normal coagulation studies and required immediate reexploration. The overall blood consumption per patient was 2.1 units of packed cells. Whole blood and platelets were not used.

The evaluation of hemorrhage in cardiac patients who have undergone extracorporeal circulation.

The present study defines excessive bleeding in patients who undergo cardiopulmonary bypass, and evaluates the use of coagulation testing to predict those patients that bleed excessively. Evaluation of 774 consecutive patients undergoing aortocoronary bypass surgery was carried out. Cardiopulmonary bypass consisted of a bloodless prime and a Harvey bubble oxygenator. In the postoperative period, excessive hemorrhage was defined as that exceeding 600 ml chest tube drainage in the first eight hours. One hundred and sixty-three patients (21%) were noted to be in this category. Excessive bleeding postoperatively was best predicted by a PTT greater than 45 seconds, a PT greater than 19 seconds, a fibrinogen level less than 225 mg/dl and a TFT equal to or less than 1:32. These laboratory findings occur singly or in combination. The assessment of platelet, numbers or function and fibrin(ogen) split products were of no prognostic value. Using these criteria, the re-exploration rate for excessive hemorrhage and/or tamponade was 0.6 per cent (5 out of 774 patients). No preoperative laboratory test of hemostatic function was useful in predicting coagulopathies resulting from cardiopulmonary bypass.

Evaluation of the bleeding patient.

The evaluation of the bleeding patient starts with the integration of data from the history and physical examination. From this results either one probable explanation that can easily be substatniated by laboratory studies or, as more commonly occurs in practice, several possibilities that are reasonable and must be investigated by more extensive laboratory tests. In either event, the initial laboratory evaluation usually includes examination of the peripheral blood and measurement of the platelet count, bleeding time, prothrombin time, partial thromboplastin time, and thrombin time. More specific laboratory tests are then performed if indicated.

Retinal hemorrhage associated with thrombasthenia.

A healthy 20-year-old man presented with a spontaneous unilateral retinal hemorrhage. Because of a history of easy bruisability, we obtained hematologic studies and diagnosed thrombasthenia, a hereditary hemorrhagic disorder. The association of retinal hemorrhage and thrombasthenia is rare. Thrombasthenia and other platelet functional disorders are becoming better defined as tests for these abnormalities become more reliable and available. Patients with apparent spontaneous retinal hemorrhages of unknown origin should be questioned about hemorrhagic tendencies, and the various tests for hemorrhagic disorders should be obtained. The hematologic survey should include the more sophisticated tests of platelet function. Patients with thrombasthenia should avoid aspirin intake.