Neonatal experience interacts with adult social stress to alter acute and chronic Theiler's virus infection.

Previous research has shown that neonatal handling has prolonged protective effects associated with stress resilience and aging, yet little is known about its effect on stress-induced modulation of infectious disease. We have previously demonstrated that social disruption stress exacerbates the acute and chronic phases of the disease when applied prior to Theiler's virus infection (PRE-SDR) whereas it attenuates disease severity when applied concurrently with infection (CON-SDR). Here, we asked whether neonatal handling would protect adult mice from the detrimental effects of PRE-SDR and attenuate the protective effects of CON-SDR on Theiler's virus infection. As expected, handling alone decreased IL-6 and corticosterone levels, protected the non-stressed adult mice from motor impairment throughout infection and reduced antibodies to myelin components (PLP, MBP) during the autoimmune phase of disease. In contrast, neonatal handling X PRE/CON-SDR elevated IL-6 and reduced corticosterone as well as increased motor impairment during the acute phase of the infection. Neonatal handling X PRE/CON-SDR continued to exacerbate motor impairment during the chronic phase, whereas only neonatal handling X PRE-SDR increased in antibodies to PLP, MOG, MBP and TMEV. Together, these results imply that while handling reduced the severity of later Theiler's virus infection in non-stressed mice, brief handling may not be protective when paired with later social stress.

Margin width is not predictive of residual disease on re-excision in breast conserving therapy.

BACKGROUND: There is lack of consensus regarding re-excision in breast-conserving therapy (BCT) and close margins. We hypothesize that margin width does not predict residual disease. METHODS: The cancer registry was queried from 2003 to 2008 for patients with BCT who underwent re-excision for <2-mm margins. Factors associated with additional disease were evaluated. RESULTS: One thousand eight hundred forty-three patients underwent BCT. Our re-excision rate was 42%. Clinicopathologic factors from 228 patients were analyzed. One hundred five patients (46%) had additional disease; of those, 58% had BCT and 42% mastectomy. One hundred twenty-three (54%) had no additional disease; of those 82% had BCT and 18% mastectomy. Of the 66 patients who underwent mastectomy, 44 (67%) had residual disease; of the 161 who had BCT, 61 (38%) had residual disease (P < 0.01). On univariate analysis, margin width did not correlate with residual disease. Multifocality, non-invasive histology, increasing number of close margins, and higher grade predicted additional disease (P < 0.05). On multivariate analysis, only number of close margins remained significant. CONCLUSIONS: Margin width does not predict additional disease. This challenges the practice of using this to select re-excision candidates. Our data suggest that tumor behavior and extent of disease, defined by volume of residual disease and invasiveness of histology, play a more significant role.

Neonatal maternal separation alters immune, endocrine, and behavioral responses to acute Theiler's virus infection in adult mice.

Previous studies have established a link between adverse early life events and subsequent disease vulnerability. The present study assessed the long-term effects of neonatal maternal separation on the response to Theiler's murine encephalomyelitis virus infection, a model of multiple sclerosis. Balb/cJ mouse pups were separated from their dam for 180-min/day (180-min MS), 15-min/day (15-min MS), or left undisturbed from postnatal days 2-14. During adolescence, mice were infected with Theiler's virus and sacrificed at days 14, 21, or 35 post-infection. Prolonged 180-min MS increased viral load and delayed viral clearance in the spinal cords of males and females, whereas brief 15-min MS increased the rate of viral clearance in females. The 15-min and 180-min MS mice exhibited blunted corticosterone responses during infection, suggesting that reduced HPA sensitivity may have altered the immune response to infection. These findings demonstrate that early life events alter vulnerability to CNS infection later in life. Therefore, this model could be used to study gene-environment interactions that contribute to individual differences in susceptibility to infectious and autoimmune diseases of the CNS.

Niobium sputtered Havar foils for the high-power production of reactive [18F]fluoride by proton irradiation of [18O]H2O targets.

Niobium sputtered Havar entrance foils were used for the production of reactive [(18)F]fluoride by proton irradiation of [(18)O]H(2)O targets under pressurized conditions. The synthesis yield in the routine production of 2-[(18)F]fluoro-2-deoxy-glucose (FDG) was used as an indicative parameter of the reactivity of (18)F. The yield of FDG obtained with (18)F produced in a target with Havar foil was used as a baseline. No statistically significant difference was found in the saturated yields of (18)F when using Havar or Havar-Nb sputtered entrance foils. However, the amount of long-lived radionuclidic impurities decreased more than 10-fold using the Havar-Nb entrance foil. The average decay corrected synthesis yield of FDG, evaluated over a period of more than 2 years, was found to be approximately 5% higher when using a Havar-Nb entrance foil and a marked improvement on the FDG yield consistency was noted. In addition, the frequency of target rebuilding was greatly diminished when using the Nb sputtered entrance foil.

Restraint stress decreases virus-induced pro-inflammatory cytokine mRNA expression during acute Theiler's virus infection.

Stressful life events have been associated with the onset and/or exacerbation of multiple sclerosis (MS). Our previous studies have indicated that restraint stress (RS) reduces inflammation and virus-induced chemokine expression in the Theiler's virus-induced demyelination (TVID) model of MS. Here we report that RS significantly reduced the virus-induced interferon-gamma mRNA levels in the brain. Additionally, mRNA levels of lymphotoxin-beta, tumor necrosis factor-alpha, and interferon-gamma in the brain were negatively correlated with viral titers in the brain. These results indicated an immunosuppressive effect of stress during early TVID causing impaired viral clearance, which may be a potential exacerbating factor for later demyelination.

Alterations in chemokine expression following Theiler's virus infection and restraint stress.

Restraint stress (RS) applied to mice during acute infection with Theiler's virus causes corticosterone-induced immunosuppression. This effect was further investigated by measuring chemokine changes in the spleen and central nervous system (CNS) using an RNase Protection Assay. mRNAs for lymphotactin (Ltn), interferon-induced protein-10 (IP-10), MIP-1 beta, monocyte chemoattractant protein-1 (MCP-1) and TCA-3 were detected in the spleen at day 2 pi, but not in the brain of CBA mice infected with Theiler's virus. Ltn, IP-10 and RANTES were elevated in both the spleen and the brain at day 7 pi, and were significantly decreased by RS in the brain. RS also resulted in decreased inflammation within the CNS.

Social stress alters the severity of acute Theiler's virus infection.

Our laboratory has previously shown that restraint stress resulted in decreased Theiler's virus-induced CNS inflammation, while exacerbating illness behaviors during the acute phase of disease. In contrast, social disruption stress (SDR) applied prior to infection led to the development of glucocorticoid (GC) resistance, and these animals developed more severe disease course, with increased inflammation. However, when SDR was applied concurrent with infection, GC resistance fails to develop, disease course is less severe and inflammation was moderate. These results suggest that the effects of SDR on Theiler's virus infection are dependent upon the timing of SDR application in relation to infection.

Psychosocial issues near the end of life.

End-of-life care has received increasing attention in the last decade; however, the focus continues to be on the physical aspects of suffering and care to the virtual exclusion of psychosocial areas. This paper provides an overview of the literature on the intra- and interpersonal aspects of dying, including the effects that psychosocial variables have on end-of-life decision-making; common diagnosable mental disorders (e.g., clinical depression, delirium); other types of personal considerations (e.g., autonomy/control, grief); and interpersonal/environmental issues (e.g., cultural factors, financial variables). Six roles that qualified mental health professionals can play (i.e., advocate, counselor, educator, evaluator, multidisciplinary team member, and researcher) are also outlined. Because psychosocial issues are ubiquitous and can have enormous impact near the end of life, properly trained mental health professionals can play vital roles in alleviating suffering and improving the quality of life of people who are dying.

A non-hypersensitive resistance in pepper to the bacterial spot pathogen is associated with two recessive genes.

ABSTRACT The pepper genotype, ECW-12346, was developed with bacterial spot resistance derived from Pep13, PI 271322, and ECW123 (Early Calwonder containing Bs1, Bs2, and Bs3 genes). For genetic analysis of this resistance, ECW12346, ECW123, F(1), F(2), and backcrosses were inoculated with a pepper race 6 (P6) strain. Two recessive genes were identified that determined resistance. The genes are designated bs5 and bs6 for the resistance derived from PI 271322 and Pep13, respectively. In greenhouse and field studies, ECW12346 was highly resistant, whereas ECW123 had significant defoliation. In growth-room studies, electrolyte leakage and population dynamics were determined. Following infiltration of both genotypes with 10(8) CFU/ml of a P6 strain, there was no rapid increase in electrolyte leakage within 72 h, whereas a rapid increase in electrolyte leakage occurred within 24 h when a similar concentration of a P3 strain (containing the avrBs2 gene) was infiltrated into the intercellular spaces of the leaf. When 10(5) CFU/ml of a P6 strain was infiltrated into leaves, complete tissue collapse was evident in ECW123 10 days later as determined by visual assessment and electrolyte leakage data, but no confluent necrosis was detected in ECW12346. Internal populations were at least two logarithmic units higher in ECW123 than in ECW12346. Therefore, ECW12346 inhibits population build-up without inducing the typical hypersensitive reaction characterized by an increase in electrolyte leakage.

The relationship of blunt head trauma, subarachnoid hemorrhage, and rupture of pre-existing intracranial saccular aneurysms.

Patients with a history of closed head trauma and subarachnoid hemorrhage are uncommonly diagnosed with an intracranial saccular aneurysm. This study presents a group of patients in whom a pre-existing aneurysm was discovered during work-up for traumatic subarachnoid hemorrhage. Without an accurate pre-trauma clinical history, it is difficult to define the relationship between trauma and the rupture of a pre-existing intracranial saccular aneurysm. We retrospectively reviewed 130 patients who presented to Detroit Receiving Hospital between 1993 and 1997 with a diagnosis of subarachnoid hemorrhage (SAH). Of these 130 patients, 70 were spontaneous, and 60 had a history of trauma. Mechanisms of trauma include motor vehicle accident, assault, or fall from a height. Of the 60 patients with subarachnoid hemorrhage and a history of trauma, 51 (86%) did not undergo conventional four-vessel angiography, and had no further neurological sequelae. Nine patients (14%) had a suspicious quantity of blood within the basal cisterns or Sylvian fissure and had a four-vessel angiogram. Five patients (8%) were diagnosed with a saccular intracranial aneurysm, and all underwent surgical clipping of the aneurysm. We conclude that the majority of patients (92%), with post-traumatic SAH do not harbor intracranial aneurysms. However, during initial evaluation, a high level of suspicion must be entertained when post-traumatic subarachnoid hemorrhage is encountered in the basal cisterns or Sylvian fissure, as 8% of our population were diagnosed with aneurysms.

The separation of anatomic components technique for the reconstruction of massive midline abdominal wall defects: anatomy, surgical technique, applications, and limitations revisited.

Reconstruction of massive abdominal wall defects has long been a vexing clinical problem. A landmark development for the autogenous tissue reconstruction of these difficult wounds was the introduction of "components of anatomic separation" technique by Ramirez et al. This method uses bilateral, innervated, bipedicle, rectus abdominis-transversus abdominis-internal oblique muscle flap complexes transposed medially to reconstruct the central abdominal wall. Enamored with this concept, this institution sought to define the limitations and complications and to quantify functional outcome with the use of this technique. During a 4-year period (July of 1991 to 1995), 22 patients underwent reconstruction of massive midline abdominal wounds. The defects varied in size from 6 to 14 cm in width and from 10 to 24 cm in height. Causes included removal of infected synthetic mesh material (n = 7), recurrent hernia (n = 4), removal of split-thickness skin graft and dense abdominal wall cicatrix (n = 4), parastomal hernia (n = 2), primary incisional hernia (n = 2), trauma/enteric sepsis (n = 2), and tumor resection (abdominal wall desmoid tumor involving the right rectus abdominis muscle) (n = 1). Twenty patients were treated with mobilization of both rectus abdominis muscles, and in two patients one muscle complex was used. The plane of "separation" was the interface between the external and internal oblique muscles. A quantitative dynamic assessment of the abdominal wall was performed in two patients by using a Cybex TEF machine, with analysis of truncal flexion strength being undertaken preoperatively and at 6 months after surgery. Patients achieved wound healing in all cases with one operation. Minor complications included superficial infection in two patients and a wound seroma in one. One patient developed a recurrent incisional hernia 8 months postoperatively. There was one postoperative death caused by multisystem organ failure. One patient required the addition of synthetic mesh to achieve abdominal closure. This case involved a thin patient whose defect exceeded 16 cm in width. There has been no clinically apparent muscle weakness in the abdomen over that present preoperatively. Analysis of preoperative and postoperative truncal force generation revealed a 40 percent increase in strength in the two patients tested on a Cybex machine. Reoperation was possible through the reconstructed abdominal wall in two patients without untoward sequela. This operation is an effective method for autogenous reconstruction of massive midline abdominal wall defects. It can be used either as a primary mode of defect closure or to treat the complications of trauma, surgery, or various diseases.

Usefulness of tissue marker clips in patients undergoing neoadjuvant chemotherapy for breast cancer.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of a tissue marker clip in patients undergoing preoperative chemotherapy for breast carcinoma. MATERIALS AND METHODS: Between June 1996 and July 1998 (26 months), a tissue marker clip was placed in 29 patients with breast carcinoma who showed significant clinical response to preoperative chemotherapy. In these patients, 13 clips were placed stereotactically and 16 clips were placed using sonographic guidance. A retrospective review of these cases was made to evaluate helpfulness of the clip during preoperative needle localization. RESULTS: One patient relocated to another city, so surgical follow-up was available in 28 patients. Twenty-four of these 28 patients required preoperative wire localization and four still had a palpable tumor at the time of surgery. Preoperative wire localization would have been possible without any difficulty in eight patients (28.6%), possible but with some difficulty in six patients (21.4%), and impossible in 10 patients (35.7%) without the clip. Thus, clip placement was valuable in 16 (57.1%) of 28 patients at the time of preoperative needle localization. CONCLUSION: With the newer chemotherapeutic agents, the response of breast carcinoma to preoperative chemotherapy may be dramatic. In some patients, the tumor is no longer visible either on mammography or sonography, thus making the preoperative needle localization difficult or even impossible. By placing a radiopaque marker before the lesion becomes unidentifiable, one can confidently localize the tumor bed at surgery.

Degradation of oat mRNAs during seed development.

The genes AV1, AV10, and Z1 encode proteins that accumulate during oat seed development. In developing endosperm of Avena sativa (cultivated oat), AV1, AV10 and Z1 mRNAs reach maximal levels midway through seed development but fall to very low levels in mature seeds. Similarly, mRNAs for these proteins peak during endosperm development of Avena fatua (wild oat) and are later degraded. However, during late maturation of A. fatua seeds, populations of mRNA fragments shorter than the intact transcripts accumulate as the full-length transcripts decline in abundance. The smaller RNA molecules, which are apparently long-lived decay intermediates, are derived randomly from the entire transcripts and are most likely not generated by cleavage at precisely defined sites. Other A. fatua endosperm mRNAs that are degraded during late seed development, such as those for ADP glucose pyrophosphorylase and starch synthase, do not produce detectable decay intermediates. Decay intermediates of AV1 and Z1 mRNAs persist at high levels during late seed development of two other undomesticated oat species, Avena strigosa and Avena barbata. The persistence of decay intermediates for these endosperm mRNAs in wild grass species may represent a model system for studying RNA decay process in plant tissues.

Breast care consultation center: role of the pathologist in a multidisciplinary center.

The Breast Care Consultation Center (BCCC) is a multidisciplinary center providing, in a single setting, a complete outpatient facility for women who have been diagnosed with or suspected of having breast cancer. A team of specialists are available to provide comprehensive, diagnostic (radiologist, surgeon, and pathologist), therapeutic (surgeon, radiotherapist, and medical oncologist), and support options. The pathologist, as a member of the diagnostic team, evaluates the material obtained or received at the BCCC. These include fine-needle aspirations (FNAs) obtained on-site as well as previously prepared cytohistological specimens. The pathologist renders the diagnosis following examination of the material and consultation with the multidisciplinary team. Thus, this approach is conducive for appropriate and accurate diagnosis where all data are available. In addition, the pathologist discusses the findings of each patient in the multidisciplinary conference. One thousand four hundred eighteen patients were evaluated at Magee-Womens Hospital BCCC from February 1992 through December 1994, during which time 366 FNAs were performed. The accuracy for positive diagnosis was 100%. Six negative cases had cancer on histology; these were due to sampling error (the lesion was missed). A multidisciplinary team is ideal for the evaluation of breast lesions that are suspicious for malignancy as it provides one-stop shopping and same-day diagnosis and therapeutic decisions.

A polysynaptic feedback circuit in rat visual cortex.

Feedback connections from extrastriate cortex to primary visual cortex (V1) in the primate may provide "top-down" information that plays a role in visual attention and object recognition. Our work in a rodent model of corticocortical circuitry demonstrates that feedback pathways synapse preferentially with pyramidal cells in V1 () and favor excitation over inhibition in cortical microcircuits (). To investigate the polysynaptic circuits activated by feedback inputs, we studied chains of neurons postsynaptic to feedback connections using a combination of axonal tract tracing and anterograde degeneration. This approach enabled independent labeling of local collaterals of forward-projecting neurons in V1 and feedback connections from extrastriate lateromedial (LM) visual area to V1. Postsynaptic targets were identified in the electron microscope after retrograde transport of biotinylated dextran amine (BDA) to identify dendrites of forward-projecting neurons (i.e., from V1 to LM) and postembedding immunogold labeling to identify GABAergic interneurons. The results show that feedback connections provide strong monosynaptic input to forward-projecting neurons in V1. These neurons in turn make local connections that preferentially form synapses with other pyramidal cells ( approximately 97%), many of which were identified as forward-projecting neurons. This indicates that feedback pathways provide input directly to neurons which make the reciprocal forward connection, and that feedback-recipient forward-projecting neurons are strongly interconnected. The function of these excitatory networks within V1 may be to amplify feedback activity and provide a circuit for modulation of striate cortical activity by top-down influences.

Intestinal absorption of trace amounts of aluminium in rats studied with 26aluminium and accelerator mass spectrometry.

1. Until recently studies of intestinal aluminium absorption used pharmacological amounts of stable 27Al. 2. To examine the intestinal absorption of trace amounts of different chemical compounds of aluminium, in the present study we have employed the long half-life isotope of aluminium, 26Al, and accelerator mass spectrometry. Trace amounts of 26Al (2.7-12.1 ng) as the hydroxide, citrate, citrate plus 1 mmol/kg sodium citrate, or maltolate respectively, were administered to four groups of rats (n = 9 per group) by gavage. Blood and urine samples were collected for 5 h and the 26Al content (as a percentage of the administered dose) determined by accelerator mass spectrometry. 3. The 5 h urinary 26Al excretion amounted to 0.1 +/- 0.02, 0.7 +/- 0.2, 5.1 +/- 1.5 and 0.1 +/- 0.1% of administered dose in the four groups respectively. There was a strong positive correlation between peak plasma 26Al (r = 0.98) and urinary 26Al excretion in individual animals (P < 0.001). 4. We conclude that the fractional intestinal absorption of trace oral doses of aluminium hydroxide is at least 0.1% (compared with the previous estimate of 0.01% using large 27Al oral loads). Absorption of aluminium citrate given alone is significantly greater (0.7%) and is further increased to 5% by the accompanying sodium citrate, consistent with an enhancing effect of added citrate upon mucosal aluminium permeability. Aluminium maltolate absorption approximates that of aluminium hydroxide (0.1%).

The neurovascular complications of cocaine.

BACKGROUND: Cocaine use has been temporally associated with neurovascular complications, including the rupture of intracerebral aneurysms. The purpose of the current study was to determine the type of neurovascular complications associated with cocaine use in our patient population, the temporal relationship between cocaine use and their onset, and whether cocaine users with subarachnoid hemorrhage (SAH) presented with smaller aneurysms at an earlier age than a control group of noncocaine users with SAH. METHODS: Thirty-three patients who presented to the Detroit Medical Center with neurovascular sequelae associated with cocaine use were identified. All patients were chronic cocaine users who related a history of recent use confirmed by a drug screen. Cocaine users with SAH were compared to a control group of 44 patients with SAH who presented without evidence of cocaine use. RESULTS: Sixteen patients presented with SAH. Twelve patients subsequently underwent four-vessel cerebral arteriogram revealing 14 aneurysms; six patients presented with intracerebral hemorrhage (ICH) and seven patients with evidence of ischemic stroke. Eighteen (54.5%) patients noted onset of their symptoms while using cocaine, 87.9% noted onset within 6 hours of use. Delayed presentation occurred predominantly in patients who suffered ischemic strokes. The average age of patients who used cocaine and presented with SAH secondary to a ruptured intracerebral aneurysm was 32.8 years with an average aneurysm diameter of 4.9 mm versus an average age of 52.2 years with an average aneurysm diameter of approximately 11.0 mm in noncocaine users. Population differences were statistically significant at the p < 0.05 level. Mortality was 27.3% for patients who presented with neurovascular sequelae of their cocaine use, with 77.8% of deaths occurring in patients who presented with SAH. CONCLUSIONS: Chronic cocaine use appears to predispose patients who harbor incidental neurovascular anomalies to present at an earlier point in their natural history than similar non-cocaine users.