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Biomedical subjects

J H Hammer

Publications and source records attributed to J H Hammer.

At least 19 recordsLinked to original sources

Impact of elective resection on plasma TIMP-1 levels in patients with colon cancer.

OBJECTIVE: Pre- and post-operative plasma tissue inhibitor of metalloproteinases-1 (TIMP-1) levels have a prognostic impact on patients with colorectal cancer. However, the surgical trauma may play an essential role in regulation of plasma TIMP-1 levels, which in turn may influence subsequent TIMP-1 measurements. PATIENTS AND METHODS: Consecutively, 48 patients with colon cancer (CC) and 12 patients with nonmalignant colonic disease were randomised to undergo elective laparoscopically assisted or open resection followed by fast track recovery. Plasma samples were collected just before and 1, 2 and 6 h after skin incision, and 1, 2, 8 and 30 days after surgery. TIMP-1 was determined concurrently in all samples by a validated ELISA method. RESULTS: Geometric mean preoperative TIMP-1 level was 142 ng/ml (range 54-559 ng/ml) among CC patients compared with 106 ng/ml (range 64-167 ng/ml) among patients with nonmalignant diseases (P<0.0001). TIMP-1 levels were decreased significantly 2 h after skin incision compared to the preoperative levels returning to preoperative levels at 6 h. A highly significant (P<0.0001) maximum level was observed 1 day after surgery and was decreasing to preoperative levels 30 days after surgery. Patients undergoing laparoscopically assisted or open resection had similar TIMP-1 levels at each time point. CONCLUSIONS: Major surgery has considerable impact on plasma TIMP-1 levels. Intra- and post-operative changes of plasma TIMP-1 levels are independent of the surgical approach, and resection for CC does not lead to a significant decrease of plasma TIMP-1 levels within 30 days postoperatively.

Aged↗

Measurement of the absolute hohlraum-wall albedo under ignition foot drive conditions.

We present measurements of the absolute albedos of hohlraums made from gold or from high-Z mixtures. The measurements are performed over the range of radiation temperatures (70-100 eV) expected during the foot of an indirect-drive temporally shaped ignition laser pulse, where accurate knowledge of the wall albedo (i.e., soft x-ray wall reemission) is most critical for determining capsule radiation symmetry. We find that the gold albedo agrees well with calculations using the supertransition array opacity model, potentially providing additional margin for inertial confinement fusion ignition.

Journal Article↗

Double Z-pinch hohlraum drive with excellent temperature balance for symmetric inertial confinement fusion capsule implosions.

A double Z pinch driving a cylindrical secondary hohlraum from each end has been developed which can indirectly drive intertial confinement fusion capsule implosions with time-averaged radiation fields uniform to 2%-4%. 2D time-dependent view factor and 2D radiation hydrodynamic simulations using the measured primary hohlraum temperatures show that capsule convergence ratios of at least 10 with average distortions from sphericity of /r 200 MJ.

Journal Article↗

A survey of police officers' experience with Tarasoff warnings in two states.

A desk sergeant at each of 48 Michigan police stations and 52 South Carolina police stations was surveyed about knowledge and experience of Tarasoff warnings. Respondents at 45 stations reported receiving warnings from mental health professionals, with a mean+/-SD of 3. 7+/-8.4 warnings a year. Only three respondents were familiar with the Tarasoff ruling. Twenty-four stations had a specific policy on such warnings. Twenty-seven stations would not warn a potential victim. Michigan stations were much more likely than South Carolina stations to have experience with or policies on Tarasoff warnings. Because police apparently have limited experience with Tarasoff warnings, calling them may not be the best way to protect potential victims from patients making threats.

Duty to Warn↗

Prestorage leukocyte filtration may reduce leukocyte-derived bioactive substance accumulation in patients operated for burn trauma.

Adverse effects of perioperative blood transfusion appear to be storage-time-dependent and may be related to extracellular accumulation of bioactive substances in blood products. In this study the clinical effects of leukofiltered and non-filtered blood products in patients undergoing surgery for burn trauma are investigated. 24 consecutive patients were randomly selected to receive transfusion with non-filtered blood components (group A, n = 12) or similar products, which were prestorage leukofiltered (group B, n = 12). The burn injury was scored using the Bull and Fischer index of age and burn surface area. Histamine, interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), eosinophil cationic protein (ECP) and myeloperoxidase (MPO) were analysed in plasma or serum collected from all patients 30 min before skin incision, at skin incision and 5, 10 and 30 min and thereafter every 30 min after skin incision until the grafts were secured by wrapping. Samples were also taken 8 h after skin incision and in the morning of postoperative days 1-5. The amount of blood products transfused from admission until day 5 postoperatively was recorded. All patients were followed until discharge or death. The Bull and Fischer index was comparable in the two groups. Prestorage leukofiltration reduced the amount of blood products required for transfusion significantly (p < 0.05) compared with non-filtered products. The levels of the various bioactive substances changed during and after the operation. In particular, ECP and MPO levels increased significantly (p < 0.05) in group A patients compared with unchanged (ECP) or decreased (MPO) levels in group B patients. IL-6 analyses showed, that the trauma had more severe impact on group B patients than on group A patients. Nevertheless, 4 patients died in group A and 2 in group B; all with a Bull and Fischer index between 1.0 and 2.0. Prestorage leukocyte filtration may reduce transfusion related accumulation of various bioactive substances and the requirement for blood in burn trauma patients.

Adult↗

Prestorage and bedside leucofiltration of whole blood modulates storage-time-dependent suppression of in vitro TNFalpha release.

Immunosuppression after transfusion may be related to the content of leucocytes in the transfused blood. Therefore we studied the effects of prestorage and bedside leucodepletion by filtration on the suppression by whole blood of in vitro stimulated tumour necrosis factor alpha (TNFalpha) release. Nine units of whole blood were leucofiltered prestorage and stored for 35 d. 27 units, 3 x 9, were stored and leucofiltered at the bedside after 7, 21 and 35 d. Supernatants were collected from all units during storage and added to a whole blood assay of E. coli-LPS-stimulated TNFalpha release. The effects of storage were assessed and compared with supernatants collected immediately after donation as reference. TNFalpha release was storage time dependently suppressed to: 81%, 74% and 57% by supernatants from non-filtered blood stored for 7, 21 and 35 d, respectively. Prestorage leucofiltration almost eliminated this effect, but we still observed a storage-time-dependent suppression by bedside-leucofiltered blood to 88%, 78% and 65%, respectively. Prestorage leucofiltration appeared to reduce storage-time-dependent suppression of in vitro stimulated TNFalpha release induced by plasma from whole blood compared with non-filtered and bedside-leucofiltered whole blood.

Blood↗

Reduction of bioactive substances in stored donor blood: prestorage versus bedside leucofiltration.

Leucocyte filtration has been suggested to improve transfusion products. We studied the effect of prestorage versus bedside leucofiltration on reduction of bioactive substances and leucocyte content in donor blood. Forty-five units of whole blood from healthy blood donors were studied. Of these units, 9 were stored under standard conditions for 35 d, 9 were leucofiltered after donation and then stored for 35 d, and 3x9 units were stored for 7, 21 and 35 d, respectively, before leucofiltration. Samples were collected from blood units immediately after donation, and before and after leucofiltration, and analysed by ELISA and RIA methods for extracellular content of myeloperoxidase (MPO), eosinophil cationic protein (ECP), histamine (HIS) and plasminogen activator inhibitor-1 (PAI-1). Leucocyte content was counted in all samples. In non-filtered blood extracellular MPO, ECP, HIS and PAI-1 were accumulated in a storage time-dependent manner, while prestorage leucofiltration prevented this accumulation. Leucofiltration after storage for 7, 21 or 35 d did not significantly reduce the accumulated bioactive substances, which were similar to levels in non-filtered blood stored for the same period of time. Prestorage and bedside leucofiltration on day 7 reduced the leucocyte content to less than 0.5x10(6)/L, whereas the median content in blood stored for 21 or 35 d was only reduced to 32.0 and 52.2x10(6)/L, respectively. Prestorage leucofiltration may thus be advantageous to bedside leucofiltration.

Blood Donors↗

Effect of heating on extracellular bioactive substances in stored human blood: in vitro study.

BACKGROUND: We have previously shown extracellular accumulation of various leukocyte and platelet-derived bioactive substances in human blood during storage. Release of bioactive substances may be temperature-dependent, and we studied the effect of heating during in vitro transfusion on bioactive substance accumulation in stored human blood. METHODS: Eight units of whole blood and eight units of prestorage leukofiltered whole blood were stored at 4 degrees C for 7 days. Subsequently, the blood from all 16 units was transfused via a blood-heating device, which increased the blood temperature to 37 degrees C at outlet. Samples for enzyme-linked immunosorbent assay or radioimmunoassay analyses of histamine, myeloperoxidase (MPO), eosinophil cationic protein (ECP), and plasminogen activator inhibitor-1 (PAI-1) were drawn from the units at donation, after 7 days of storage just before transfusion, and during the in vitro transfusion. RESULTS: Extracellular concentrations of histamine, MPO, ECP, and PAI-1 were significantly (p < 0.05) increased in nonfiltered whole blood stored for 7 days compared with concentrations in fresh donated blood and in prestorage leukofiltered whole blood stored for 7 days. Heating reduced histamine, MPO, and ECP concentrations significantly (p < 0.05) in nonfiltered whole blood, whereas PAI-1 concentrations increased significantly (p < 0.05). Finally, there was no difference in concentrations of histamine, MPO, ECP, and PAI-1 in samples collected before and after heating of leukofiltered whole blood. CONCLUSIONS: Heating reduces accumulation of extracellular leukocyte-derived bioactive substances in whole blood, whereas it increases platelet-derived substances. Prestorage leukofiltration, however, reduces the obligatory extracellular accumulation of leukocyte and platelet-derived bioactive substances, which in addition is unchanged by heating.

Blood Preservation↗

Effect of ranitidine and low-dose interleukin-2 in vitro on NK-cell activity in peripheral blood from patients with liver metastases from colorectal cancer.

Peripheral venous blood from 12 patients with colorectal cancer and eight healthy volunteers was used to identify the lowest in vitro dose of human, recombinant interleukin-2 (rIL-2) with immunoactivity on NK-cell lysis of K562 tumour cells. Subsequently, this dosage of 200 units/ml rIL-2, which may respond to 10(6) units in vivo, was used alone or in combination with ranitidine (0.02 mg/ml, which may correspond to 100 mg in vivo) to improve in vitro NK-cell activity in peripheral blood from 25 patients with liver metastases from colorectal cancer. A standard 4-hour Cr51-release assay of K562 tumour cells was used for the analyses. Spontaneous NK-cell activity was 19.0% (6.5-33.2), while ranitidine-induced NK-cell activity was 23.6% (7.8-46.2), and without statistical difference from spontaneous activity. Recombinant IL-2-induced NK-cell activity was 37.1% (11.1-71.7) (P < 0.05 compared to spontaneous activity), and rIL-2 plus ranitidine-induced NK-cell activity was 52.7% (18.9-85.6) (P < 0.05 compared to spontaneous and to rIL-2-induced activity, respectively). These results suggest a synergistic increase of low-dose rIL-2-induced NK-cell activity by ranitidine. Therefore, the combination of low-dose rIL-2 and ranitidine may be beneficial to improve post-operative immune competence, and should be considered in future adjuvant treatment regimens of cancer patients.

Antineoplastic Combined Chemotherapy Protocols↗

Possible role of histamine in pathogenesis of autoimmune diseases: implications for immunotherapy with histamine-2 receptor antagonists.

The immunosuppressive chemical drugs cyclosporine A (CsA) and methotrexate (Mx) have recently been shown to be of benefit in several different diseases of autoimmune origin. Cellular immune responses may play a major role in autoimmunity as autoreactive T lymphocytes appear to recognize autoantigens and major histocompatibility complex (MHC) class II restriction molecules presented by non-immune, aberrant cells, subsequently leading to damage on healthy tissues. Psoriasis is suggested to be an autoimmune disease and in severe, uncontrollable psoriasis CsA and Mx are of value in reducing disease activity. Histamine is suggested to be involved in the pathogenesis of psoriasis and the histamine-2 receptor antagonist ranitidine has been shown to be of value to reduce severe psoriatic disease. The finding that CsA and Mx efficiently reduce histamine formation and release raises the possibility, that histamine is one of the molecules involved in pathogenesis of autoimmune diseases. T cell mediated regulation and suppression of autoreactive T cells seem to be ineffective in controlling the enhanced immune reaction in patients where the discrimination between self and non-self is changed. A consequence of this may be induction of interferon-gamma (IFN-g) production and release by cytotoxic T cells, subsequently leading to expression of MHC II molecules on non-immune tissues. As immunotherapy may be of value in some autoimmune diseases the use of histamine-2 receptor antagonists should be evaluated in patients where conventional therapy is ineffective to reduce disease activity.

Autoimmune Diseases↗

Duration of postoperative immunosuppression assessed by repeated delayed type hypersensitivity skin tests.

The duration of postoperative impairment in cell-mediated immunity was assessed by repeated skin testing with seven delayed type common antigens in 15 patients undergoing major elective abdominal surgery compared to a similar testing regimen in 10 healthy volunteers. All were skin tested four times, with 72-hour intervals, and in the surgical patients the first test was applied 2 days before surgery, followed by tests on postoperative days 1, 4 and 7. The tests were read after 48 h. Postoperatively, the skin test area decreased on day 3 (p less than 0.01) and recurred to preoperative levels on day 9. In contrast, the skin test area in the volunteers increased from test to test (p less than 0.001) during the study, confirming a previous finding of a vaccination effect. These results suggest that the postoperative immunosuppression is maintained for about 6-9 days.

Female↗

Ranitidine improves postoperative suppression of antibody response to preoperative vaccination.

The effect of the histamine-2 receptor antagonist ranitidine (100 mg intravenously every 12 hours for 72 hours) on postoperative serum antibody responses to preoperative immunization with six limit of flocculation tetanus toxoid and six limit of flocculation diphtheria toxoid was assessed in a double-blind, placebo-controlled randomized study in 26 patients undergoing major abdominal surgery. The preoperative antitetanus antibody level was less than 0.1 IU/ml in all patients, and they were inoculated with both antigens 48 hours before surgery. Serum samples for analysis of antitetanus toxoid and antidiphtheria toxoid were drawn before skin incision and on postoperative days 1, 3, 5, 7, 10, 14, 21, and 28. Ranitidine significantly increased the postoperative antibody response to tetanus toxoid, (p less than 0.01) and insignificantly increased that to diphtheria toxoid vaccination (p less than 0.2) compared with placebo.

Adult↗

Comparison of the effects of SAG-M and whole-blood transfusions on postoperative suppression of delayed hypersensitivity.

The influence of perioperative whole-blood transfusion and transfusion with erythrocyte suspension (SAG-M blood) on postoperative depression of cell-mediated immunity (CMI) was investigated in 67 patients who underwent elective resection for colorectal cancer. Cell-mediated immunity was assessed pre- and postoperatively by skin testing with seven common delayed-type hypersensitivity (DTH) antigens. The postoperative skin-test response decreased more in the patients who received whole blood (15 patients) than in those who received SAG-M blood (16 patients) (60% versus 42%, p less than 0.001) and in those who did not receive a blood transfusion (36 patients) (60% versus 40%, p less than 0.001). The enhanced postoperative immunosuppression in patients who received whole-blood transfusions persisted after matching according to age, sex, height, weight, hemoglobin and serum albumin levels, duration of surgery and diagnosis. Thus, perioperative transfusion with SAG-M blood does not enhance surgically induced immunosuppression as effectively as does transfusion with whole blood.

Adult↗

[Production of slides using a microdatamat].

For production of dias for presentation of scientific data, a personal computer, a dias programme and a camera are necessary. A microdatamat with a 80286 precessor, 20 MB hard disc and an EGA colour screen are the minimum configurations which can be recommended. A hard disc between 40 and 85 MB and a VGA screen provide a better solution. Out of the numerous dias programmes, Harvard Graphics appears to be suitable for production of dias for scientific use. In this programme, it is easy to combine text, graphic and hand drawing. Many other excellent programmes such as 35 mm Express and Mirage are also available. In the choice of camera, a solution of at least 4,000 x 4,000 lines is required and the camera concerned must be capable of working with recognized statistical and graphic parcels as more special graphs cannot be produced in ordinary dias programmes. Among the numerous cameras, the following may be mentioned: Montage which costs of 70,000 Danish crowns (approximately 6,000 pounds), Matrix PCR at 100,000 Danish crowns (approximately 9,000 pounds), Matrix QCR-Z at 200,000 Danish crowns (approximately 18,000 pounds) and Lasergraphic's two models at 60,000 and 120,000 Danish crowns, respectively (approximately 5,000 pounds and 10,000 pounds). In the price class of about 100,000 Danish crowns, Matrix PCR can be recommended particularly as this camera has an excellent optic and advanced self calibrating system. Among the cheaper cameras. Montage is recommended which e.g. functions well with Harvard Graphics.(ABSTRACT TRUNCATED AT 250 WORDS)

Audiovisual Aids↗

[Immunologic consequences of surgery, anesthesia and blood transfusion. Surgical immunosuppression].

On the basis of the literature and the authors own investigations, the present article provides a brief schematic review of the fraction of the physiological immune response which has hitherto been investigated in connection with surgical trauma. Surgery, anaesthesia and blood transfusion induce temporarily acquired immune suppression and thus a potentially increased risk for postoperative infectious complications and recurrence after cancer surgery. The pathological physiological alterations in immune function which develop as a result of anaesthesia, surgery and perioperative blood transfusion are reviewed. The clinical sequelae of preoperative and postoperative immune suppression are increased morbidity and mortality rates. Future research in this field must, therefore, be focussed on detailed investigation of the mechanisms which lead to postoperative immune suppression and development of methods to prevent these.

Anesthesia↗

Ranitidine prevents postoperative transfusion-induced depression of delayed hypersensitivity.

The influence of perioperative blood transfusion on postoperative depression of cell-mediated immunity (CMI) and the effect of ranitidine on transfusion-induced changes in postoperative CMI were investigated. CMI was assessed preoperatively and postoperatively by skin testing with seven common delayed-type antigens in 83 consecutive patients undergoing major elective abdominal surgery. Sixty-six of these patients were randomly divided into ranitidine or no-ranitidine-treatment groups, and the remaining 17 patients were operated on without ranitidine. Thus, 50 patients were operated on without ranitidine therapy, and whole blood transfusion was given to 24 of these patients. Postoperative skin test response was more reduced in transfused vs nontransfused patients (-57% vs -38%, p less than 0.0001). Fourteen of the 24 patients receiving blood transfusion could be exactly matched to 14 patients not receiving transfusion (age, sex, B-hemoglobin, S-albumin, type and duration of surgery, etc.), which confirmed that a more pronounced reduction in postoperative skin test response was found in transfused patients (-55% vs -31%, p less than 0.0001). Seventeen of the 33 patients treated with perioperative ranitidine, 50 mg intravenously every 6 hours for 72 hours, received perioperative blood transfusion. Eleven of these patients could be matched to 11 transfused patients not receiving perioperative ranitidine. Ranitidine prevented postoperative reduction in skin test response (+6% vs -55%, p less than 0.0001). It is concluded that perioperative transfusion with whole blood amplifies the postoperative impairment in delayed hypersensitivity and that transfusion-induced postoperative impairment in delayed hypersensitivity may be prevented by perioperative ranitidine treatment.

Abdomen↗