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Effects of 1-desamo-8-D-arginine vasopressin on behaviour and cognition in primary affective disorder.

DDAVP (1-desamino-8-d-arginine vasopressin), a synthetic analogue of vasopressin with prolonged half-life and high antidiuretic and low pressor activity, was given in a double-blind placebo-controlled trial to four patients with major affective illness. Three of four patients showed highly significant and consistent improvements in tests designed to measure the formation, encoding, and organisation of long-term trace events in memory. Two patients also showed a significant but less consistent amelioration of other depressive symptoms during DDAVP treatment. These findings implicate central vasopressin function in the processing of information and possibly other aspects of affective illness.

Affective Symptoms↗

In vivo depletion of CD8+ cells does not affect primary maedi visna virus infection in sheep.

T-cells have been implicated both, in promoting and reducing viral replication during lentivirus infection. CD8+ lymphocytes are believed to be important in controlling viral load through direct killing of virus-infected cells and by secretion of inhibitory chemokines and cytokines. To evaluate the role of CD8+ T-cells in the induction and control of the primary phase of a lentivirus infection, we have used a non-T-cell tropic lentivirus, maedi-visna virus (MVV), to study the initial pathogenesis and subsequent immune responses in sheep depleted in vivo of CD8+ cells. Sheep were depleted of CD8+ cells in both blood and efferent lymph for up to 14 days. No difference in MVV replication was observed in either the draining efferent lymph or lymph node of these sheep. Surprisingly, these animals displayed a normal induction of pCTL whereas the virus-specific proliferative responses were reduced. This could reflect either that a proportion of functional CD8+ lymphocytes remained in these animals, as suggested by the appearance of pCTLs, or that CD8+ cells are not required for control of primary MVV infection.

Animals↗

Warfarin inhibits metastasis of Mtln3 rat mammary carcinoma without affecting primary tumour growth.

Coumarin anticoagulants inhibit metastasis in several animal models, but the mechanism of this effect is uncertain. In order to determine the role of cytotoxic and/or cytostatic actions of coumarins on the tumour cells, we have studied the effects of warfarin on tumour cell growth in a model in which tumour metastasis is inhibited by this drug. Clonogenic assay, growth curve analysis and thymidine labelling index revealed that warfarin had no effects on Mtln3 mammary carcinoma cell growth in vitro at concentrations below 1 mM. The growth rate of subcutaneously implanted Mtln3 tumour deposits in female F344 rats, assessed by weight and by stathmokinetic analysis of the tumour tissue, was identical in warfarin-treated and control animals. Spontaneous metastasis from such tumours to the lungs was, however, significantly reduced in warfarin-treated animals (median 0 pulmonary tumours per animal in warfarin treated, eight tumours per animal in control animals; P less than 0.05, Mann-Whitney). The mean plasma warfarin concentration in warfarin treated rats was 1.63 microM. These results suggest that warfarin treatment of the host animal can inhibit tumour metastasis without having any direct or indirect effect on the growth rate of the tumour cells.

Adenocarcinoma↗

Oncolytic parvovirus H1 induces release of heat-shock protein HSP72 in susceptible human tumor cells but may not affect primary immune cells.

Certain autonomous parvoviruses preferentially replicate in and kill in vitro-transformed cells and may reduce the incidence of spontaneous and implanted tumors in animals. Hence, these viruses and their derivatives are currently under evaluation as antitumor vectors. However, the mechanisms underlying their tumor-suppressing properties are not yet understood. We asked whether the lytic parvovirus H1 may enhance the immunogenicity of infected tumor cells. Out of human melanoma and gastrointestinal tumor cells, we selected the cell line SK29-Mel-1 being very susceptible to H1-induced apoptotic killing. Here, no upregulation of HLA class I and costimulatory molecules could be observed following H1 infection. However, a strong release of the immunogenic signal-the inducible heat-shock protein HSP72, but not constitutive HSP73-was observed after H1 infection. The HSP72 release was higher and of longer duration than a conventional heat-shock treatment. We also explored H1 replication and cytotoxicity in human immune cells, as such cells may constitute targets for H1 virus replication. Long-term cultured lymphocytes, monocytes, immature and mature dendritic cells were not susceptible to H1 virus. Altogether, parvovirus-mediated cell killing may in vivo enhance tumor immunogenicity by HSP72 release and thus contribute to the antitumor effect of parvoviruses.

Apoptosis↗

Lithium carbonate prophylaxis of depression in three subtypes in primary affective disorder.

Multiple indices of depression were used to evaluate the prophylactic efficacy of lithium carbonate versus placebo in a 4-year, double-blind study of unipolar, bipolar I, and bipolar II patients diagnosed according to strict criteria. Our data indicate lithium prophylaxis of depression on several indices in all three subtypes of affective illness. Additional studies are needed, comparing tricyclic antidepressants alone, monoamine oxidase inhibitors alone, or either drug combination with lithium carbonate for prophylaxis in clearly defined depressive subtypes.

Adult↗

The expression of primary affects in portraits drawn by schizophrenics.

In a psychiatric hospital setting, 15 patients under treatment for schizophrenia and 15 healthy persons were asked to draw (1) a human face, (2) another face that expressed their own feelings at that moment, and (3) afterward the facial expressions of rage, fear, disgust, joy, sadness and shame within a standardized egg-shaped face matrix. Both groups were matched for age, sex and education, and all drawings were coded independently. The schizophrenics drew fewer facial action units, and their facial drawings were more stereotyped than the control group's. Neutral faces without any affective expression were twice as frequent within the experimental group. According to Ekman and Friesen's table of emotion prediction, the accuracy was the same for both groups with the exception of sadness. Only 20% of the action units in the schizophrenics' sadness drawings were accurate compared to 51% in the control group. Based on observations during the drawing process, findings are discussed within the theoretical framework of cathexis defense as an attempt to reduce the impact of the affective stimuli the schizophrenics created themselves.

Adolescent↗

How rapidly can maternal behavior affecting primary sex ratio evolve in a reptile with environmental sex determination?

Theoretical models identify maternal behavior as critical for the maintenance and evolution of sex ratios in organisms with environmental sex determination (ESD). Maternal choice of nest site is generally thought to respond more rapidly to sex ratio selection than environmental sensitivity of offspring sex (threshold temperatures) in reptiles with temperature-dependent sex determination (TSD, a form of ESD). However, knowledge of the evolutionary potential for either of these traits in a field setting is limited. I developed a simulation model using local climate data and observed levels of phenotypic variation for nest-site choice and threshold temperatures in painted turtles (Chrysemys picta) with TSD. Both nest-site choice and threshold temperatures, and hence sex ratios, evolved slowly to simulated climate change scenarios. In contrast to expectations from previous models, nest-site choice evolved more slowly than threshold temperatures because of large climatic effects on nest temperatures and indirect selection on maternally expressed traits. A variant of the model, assuming inheritance of nest-site choice through natal imprinting, demonstrated that natal imprinting inhibited adaptive responses in female nest-site choice to climate change. These results predict that females have relatively low potential to adaptively adjust sex ratios through nest-site choice.

Animals↗

The open abdomen in trauma: do infectious complications affect primary abdominal closure?

OBJECTIVE: One of the primary goals of damage control surgery in the trauma patient is primary closure of the abdomen. We hypothesized that extra-abdominal infections, such as those complicating injuries to the thorax, diaphragm, long bones, or musculoskeletal system, would decrease the likelihood of primary abdominal closure and increase hospital resource utilization in patients requiring open abdominal management. METHODS: The trauma registry of the American College of Surgeons (TRACS) was reviewed retrospectively from 1995-2002 for open abdomen technique and damage control surgery. The outcome was primary fascial closure or delayed closure. Patients who died prior to closure were excluded. We evaluated infectious complications, including ventilator-associated pneumonia (VAP), blood stream infection (BSI), and surgical site infection (SSI). Other parameters studied were multiple rib fractures, long bone fractures, chest injuries, diaphragm injuries, empyema, and transfusion requirements. Hospital charges were obtained from the hospital administrative database. Univariate, multivariate, and regression analyses were performed to identify the effects of infectious complications on primary abdominal closure, length of stay, total hospital charges, and disposition. RESULTS: Three hundred forty-four patients required the open abdomen technique: 67% received damage control laparotomy and 33% decompression of abdominal compartment syndrome. Two hundred seventy-six patients (80%) went on to abdominal closure of some form and constituted the primary study group. Primary abdominal closure was achieved in 180 (65%) with a mean time to closure of 3.5 days. Ventilator-associated pneumonia, BSI, and SSI were associated with lack of primary closure (p < 0.05). Increased blood transfusions also were associated with failure of primary closure (p < 0.05). Ventilator-associated pneumonia and BSI were associated with significantly greater lengths of stay in the intensive care unit (ICU) (24.2 days vs. 12.6 days and 30.5 days vs. 17.9 days; both p < 0.0001) and significantly greater total hospital charges (232,080 US dollar vs. 142,893 US dollar; 247,440 US dollar vs. 160,940 US dollar; and 264,778 US dollar vs. 170,447 US dollar; all p < 0.001). CONCLUSION: Inability to achieve primary abdominal closure was associated with infectious complications (VAP, BSI, and SSI) and large transfusion requirements. Infectious complications also significantly increased ICU utilization and hospital charges. Death was associated with BSI, femur fractures, and large transfusion requirements, whereas infectious complications did not have a significant impact on discharge disposition.

Abdominal Injuries↗

Factors affecting primary health care utilization.

Using a one-stage random probability sample of households, 5806 people in an area of Norway were interviewed about illness, use of medicines, self-treatment and visits to the doctor in the previous two weeks. Several social and demographic variables that might influence primary health care utilization were divided into five categories: need of medical care; self-care; availability of the doctor; sociodemographic factors; social network factors. Multiple classification analysis was used for the statistical analysis. The greatest influence on the percentage of people seeing the doctor was the need for medical care, the second largest influence was self-care. The availability of the doctor had a different effect according to whether the illness was chronic or non-chronic. Difficulties in reaching the doctor reduced the number of consultations for non-chronic diseases while the opposite was the case for chronic diseases. Among the sociodemographic variables neither level of education nor income had any influence on utilization when other variables were taken into account. Increasing age, however, caused a large increase in the percentage seeing the doctor, except after the age of 85 years when there was a large drop in consultation rate despite increasing illness. Social network factors had little effect on health care utilization.

Acute Disease↗

Factors affecting primary care physician participation in Medicare.

OBJECTIVES: This study investigates the levels of participation and the relative association of economic and noneconomic factors on primary care physician participation in the Medicare program. METHODS: Demographic information, participation in Medicare, and attitudes toward both the Medicare program and Medicare patients were collected in a written survey mailed to half the primary care physicians in Iowa. Ordinary least squares and logistic regression analyses were conducted to determine factors associated with the percentage of Medicare patients in a practice and the acceptance of all new Medicare patients, respectively. RESULTS: Two thirds of physicians were accepting all new Medicare patients, whereas 16% were accepting no new Medicare patients. Factors associated with having a higher percentage of Medicare patients in a practice were as follows: (1) a larger proportion of Medicare recipients in the county, (2) practice as a general internal medicine physician, (3) more years in practice at the current location, (4) greater enjoyment treating elderly patients, (5) less concern about having too many Medicare patients, and (6) a stronger belief that the Medicare program respects their professional judgment. Physicians less concerned about having too many Medicare patients in their practice and physicians in counties with a higher percentage of Medicare patients were significantly more likely to accept all new Medicare patients. CONCLUSIONS: These results suggest that as Medicare reforms are discussed, careful consideration of the impact of these reforms on noneconomic issues is important to ensure adequate physician participation and access for elderly patients through the Medicare program.

Adult↗

Adenovirus type 5 and 7 capsid chimera: fiber replacement alters receptor tropism without affecting primary immune neutralization epitopes.

The efficient uptake of adenovirus into a target cell is a function of adenovirus capsid proteins and their interaction with the host cell. The capsid protein fiber mediates high-affinity attachment of adenovirus to the target cell. Although the cellular receptor(s) for adenovirus is unknown, evidence indicates that a single receptor does not function as the attachment site for each of the 49 different serotypes of adenovirus. Sequence variation of the fiber ligand, particularly in the C- terminal knob domain, is associated with serotype-specific binding specificity. Additionally, this domain of fiber functions as a major serotype determinant. Fiber involvement in cell targeting and its function as a target of the host immune response make the fiber gene an attractive target for manipulation, both from the perspective of adenovirus biology and from the perspective of using adenovirus vectors for gene transfer experiments. We have constructed a defective chimeric adenovirus type 5 (Ad5) reporter virus by replacing the Ad5 fiber gene with the fiber gene from Ad7A. Using the chloramphenicol acetyltransferase reporter gene, we have characterized this virus with respect to infectivity both in vitro and in vivo. We have also characterized the role of antifiber antibody in the host neutralizing immune response to adenovirus infection. Our studies demonstrate that exchange of fiber is a strategy that will be useful in characterizing receptor tropism for different serotypes of adenovirus. Additionally, the neutralizing immune response to Ad5 and Ad7 does not differentiate between two viruses that differ only in their fiber proteins. Therefore, following a primary adenovirus inoculation, antibodies generated against fiber do not constitute a significant fraction of the neutralizing antibody population.

Adenoviridae↗