Dietary conjugated linoleic acid affects blood parameters, liver morphology and expression of selected hepatic genes in laying hens.

The objective of this research were to investigate the effect of a conjugated linoleic acid (CLA)-enriched diet on Isa Brown laying hen health status and to provide a comprehensive analysis of changes in blood parameters, liver morphology and selected hepatic gene expression. Hens were allocated to the control and experimental group (diet enriched with 0.75% CLA) for a total period of 4 m. At the end of the experiment half of the hens from each group were slaughtered for analyses. The remaining hens were transferred to an organic farm for the next 5 m and fed on the diet without CLA supplementation. The CLA-enriched diet resulted in significant changes in blood and serum parameters; specifically, haematocrit (HCT), mean corpuscular volume (MCV) and white blood cells (WBC) count were decreased compared to the control. The total cholesterol (TC) was not significantly affected while the triacylglycerol's (TG) concentration was elevated. The activity of alanine aminotransferase (ALT) was significantly increased in the CLA-supplemented group, while aspartate aminotransferase (AST) showed an increasing tendency. Liver biopsies showed pathological changes classified as non-alcoholic fatty liver disease (NAFLD). Additionally, the expression of hepatic genes involved in fatty acids synthesis (ME1, ACLY, ACC, FASN, SCD1), oxidation (CPT1α, PPARA), detoxification processes (Cytochrome P450, CYP, Flavin-containing monooxygenase, FMO3), oxidative stress (NOX4, XbP1) and inflammation (IL6, TNFα) were elevated. Cessation of CLA supplementation for 5 m of organic farming resulted in normalisation of blood and hepatic parameters to the levels observed in control hens. The results of this study indicate that dietary CLA triggers an integrated stress response in laying hens and activates mechanisms involved in liver detoxification.

Recognition memory and synaptic plasticity in the perirhinal and prefrontal cortices.

Work is reviewed that relates recognition memory to studies of synaptic plasticity mechanisms in perirhinal and prefrontal cortices. The aim is to consider evidence that perirhinal cortex and medial prefrontal cortex store rather than merely transmit information necessary for recognition memory and, if so, to consider what mechanisms are potentially available within these cortices for producing such storage through synaptic change. Interventions with known actions on plasticity mechanisms are reviewed in relation to their effects on recognition memory processes. These interventions importantly include those involving antagonism of glutamatergic and cholinergic receptors but also inhibition of plasticity consolidation and expression mechanisms. It is concluded that there is strong evidence that perirhinal cortex is involved in information storage necessary for object recognition memory and, moreover, that such storage involves synaptic weakening mechanisms including the removal of AMPA glutamate receptors from synapses. There is good evidence that medial prefrontal cortex is necessary for associative and temporal order recognition memory and that this cortex expresses plasticity mechanisms that potentially allow the storage of information. However, the case for medial prefrontal cortex acting as a store requires further support.

Guatemela: preliminary zircon ages from central cordillera.

Concordia resolution of uranium-lead analyses of zircons from rocks of the Guatemalan Cordillera indicates a period of plutonism, and perhaps metamorphism, in late Paleozoic times (345 +/- 20 million years). Gneisses of the Chuacus Series yield an age of 1075 +/- 25 million years which may be either the age of a source terrain for the original sediments, or the age of principal metamorphism. Zircons from a Paleozoic granite intruding the gneisses appear to contain inherited or contaminating material acquired during the process of magma generation or emplacement, or both.

Space plasma physics: space experiments with particle accelerators.

Electron and plasma beams and neutral gas plumes were injected into the space environment by instruments on Spacelab 1, and various diagnostic measurements including television camera observations were performed. The results yield information on vehicle charging and neutralization, beam-plasma interactions, and ionization enhancement by neutral beam injection.

The early prediction of mortality in acute pancreatitis: a large population-based study.

BACKGROUND: Identification of patients at risk for mortality early in the course of acute pancreatitis (AP) is an important step in improving outcome. METHODS: Using Classification and Regression Tree (CART) analysis, a clinical scoring system was developed for prediction of in-hospital mortality in AP. The scoring system was derived on data collected from 17,992 cases of AP from 212 hospitals in 2000-2001. The new scoring system was validated on data collected from 18,256 AP cases from 177 hospitals in 2004-2005. The accuracy of the scoring system for prediction of mortality was measured by the area under the receiver operating characteristic curve (AUC). The performance of the new scoring system was further validated by comparing its predictive accuracy with that of Acute Physiology and Chronic Health Examination (APACHE) II. RESULTS: CART analysis identified five variables for prediction of in-hospital mortality. One point is assigned for the presence of each of the following during the first 24 h: blood urea nitrogen (BUN) >25 mg/dl; impaired mental status; systemic inflammatory response syndrome (SIRS); age >60 years; or the presence of a pleural effusion (BISAP). Mortality ranged from >20% in the highest risk group to <1% in the lowest risk group. In the validation cohort, the BISAP AUC was 0.82 (95% CI 0.79 to 0.84) versus APACHE II AUC of 0.83 (95% CI 0.80 to 0.85). CONCLUSIONS: A new mortality-based prognostic scoring system for use in AP has been derived and validated. The BISAP is a simple and accurate method for the early identification of patients at increased risk for in-hospital mortality.

The psychometric properties of the Hospital Anxiety and Depressions Scale adapted for use with people with intellectual disabilities.

BACKGROUND: There is increasing recognition of depression in people with intellectual disabilities (ID). There is a need to develop well-standardised self-report measures for both clinical and research purposes. This paper presents some psychometric properties of the Hospital Anxiety and Depression Scale (HADS) adapted for use with people with ID. The anhedonic emphasis in the depression scale of the HADS may be particularly useful for people with ID who present with high rates of physical co-morbidity. METHOD: A total of 197 people with ID completed an adapted HADS; 32 participants also completed the Zung Depression Scale and 42 also completed the Glasgow Depression Scale. RESULTS: The obtained factor structure is similar to the original form of the scale used with people without ID. However, the underlying question wording of the HADS, where most depression items are phrased positively and most anxiety items are phrased negatively, makes clear interpretation of the factor structure difficult. The HADS has an adequate internal reliability and correlates well with other self-report measures of depression. CONCLUSIONS: The HADS may need further adaptation; however, the measurement of anhedonia is a useful addition to the self-report measures of depression available for people with ID.

Exercise for improving balance in older people.

BACKGROUND: Diminished ability to maintain balance may be associated with an increased risk of falling. In older adults, falls commonly lead to injury, loss of independence, associated illness and early death. Although some exercise interventions with balance and muscle strengthening components have been shown to reduce falls it is not known which elements, or combination of elements, of exercise interventions are most effective for improving balance in older people. OBJECTIVES: To present the best evidence for effectiveness of exercise interventions designed to improve balance in older people living in the community or in institutional care. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (Feb 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to February 2006), EMBASE (1980 to February 2006), other databases and reference lists of articles. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials testing exercise interventions designed to improve balance in older people were included. We excluded trials of interventions targeting individuals with specific conditions in order not to broaden the scope of this review too widely. Trials were included where participants were randomised to receive the following: a single exercise intervention or a multiple exercise intervention and a control group (usual activities or attention or recreational activity). Trials comparing two or more exercise interventions and a control group were also included. DATA COLLECTION AND ANALYSIS: Three pairs of members of the review team independently assessed trial quality and extracted data. For each trial, relative risk and 95% confidence intervals were calculated for dichotomous outcomes, and mean differences and 95% confidence intervals calculated for continuous outcomes. Where appropriate, results of comparable groups of trials were pooled and 95% confidence intervals calculated. MAIN RESULTS: For the 34 included studies there were 2883 participants at entry. Statistically significant improvements in balance ability were observed for exercise interventions compared to usual activity. Interventions involving gait; balance; co-ordination and functional exercises; muscle strengthening; and multiple exercise types appear to have the greatest impact on indirect measures of balance. There was trend towards an improvement in balance with cycling on a static cycle. However, there was limited evidence that effects were long-lasting. AUTHORS' CONCLUSIONS: Exercise appears to have statistically significant beneficial effects on balance ability in the short term but the strength of evidence contained within these trials is limited. Many of these mainly small studies demonstrated a range of methodological weaknesses. The failure across the included studies to apply a core set of standardised outcome measures to determine balance ability restricts the capacity to compare or pool different trials from which firm conclusions regarding efficacy can be made. Further standardisation in timing of outcome assessment is also required as is longer term follow-up of outcomes to determine any lasting effects.

Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma.

BACKGROUND: Cyclophosphamide is an established bladder carcinogen, but few studies have examined the relationship between dose and effect. The largest analysis to date included only seven cases of bladder cancer. No investigation has estimated the risk of kidney cancer. PURPOSE: The purpose of this study was to quantify the risk of bladder and kidney cancer following cyclophosphamide therapy. METHODS: Within a cohort of 6171 two-year survivors of non-Hodgkin's lymphoma (NHL), 48 patients with secondary cancer of the urinary tract were identified and matched to 136 control subjects with NHL who did not develop a second malignancy. Detailed information on chemotherapeutic drugs and cumulative dose received was collected for all subjects. Radiation dose to the target organ was estimated from individual radiotherapy records. Evaluations of the risk of second cancer as a result of treatment with cyclophosphamide alone, radiation alone, or both therapies were made relative to those patients who were exposed to neither treatment modality. RESULTS: A significant 4.5-fold risk of bladder cancer (95% confidence interval [CI] = 1.5-13.6) followed therapy with cyclophosphamide, and risk was dependent upon cumulative dose. Among patients who received a total amount of cyclophosphamide of less than 20 g, a nonsignificant 2.4-fold risk of bladder cancer was apparent. Significantly elevated sixfold (95% CI = 1.3-29) and 14.5-fold (95% CI = 2.3-94) risks of bladder malignancy followed cumulative doses of 20-49 g and 50 g or more, respectively (P value for trend = .004). Radiotherapy given without cyclophosphamide was associated with a nonsignificant increased risk of bladder malignancy. Excess bladder cancer risk following treatment with both radiotherapy and cyclophosphamide was as expected if individual risks were summed. Neither radiotherapy nor cyclophosphamide was associated with excesses of kidney cancer. CONCLUSIONS: Cyclophosphamide-related bladder cancer is dose dependent. For patients given cumulative doses between 20 and 49 g, the absolute risk of bladder cancer is on the order of three excess cancers per 100 NHL patients after 15 years of follow-up. At cumulative doses of 50 g or more, the excess risk increases to approximately seven excess bladder cancers per 100 NHL patients. IMPLICATIONS: The strong dose-response relationship and high absolute risk of bladder cancer underscore the importance of limiting the cumulative dose of cyclophosphamide to what is required to achieve therapeutic end points. The risk of secondary bladder malignancy and other late sequelae of therapy must be carefully weighted against the curative gains provided by cyclophosphamide. Moreover, long-term side effects of therapy that might be acceptable in cancer treatment may need to be re-evaluated for patients with non-neoplastic disorders.

Use of the working formulation for non-Hodgkin's lymphoma in epidemiologic studies: agreement between reported diagnoses and a panel of experienced pathologists.

Independent review of slides of 668 cases of non-Hodgkin's lymphoma (NHL) by a panel of 4 experienced pathologists using the Working Formulation (WF) allowed determination of the agreement between reported diagnoses and panel review of slides. The panel agreed with the reported diagnosis of NHL in 93% of cases, but with the NHL subtype in only 55% of cases overall. The ability of the panelists to agree among themselves, however, was only slightly better than the panelists' agreement with the reported diagnosis (60% vs. 54%, respectively). Agreement of the panel with the reported subtype diagnosis varied from 14% to over 90%. The best agreement was with small lymphocytic lymphoma and follicular subtypes. Conclusions from this study are: 1) The WF functions well as common language for translation and comparison of diagnoses of subtypes of NHL. 2) Relative to time and cost involved, panel review using only light microscopy may not be useful in epidemiologic studies of NHL. 3) Small lymphocytic and follicular subtypes of NHL can be used more confidently in epidemiologic studies than can other subtypes whether the subtyping is done from abstracted reports or by panel review.

Risk of leukemia following treatment for non-Hodgkin's lymphoma.

BACKGROUND: There have been few evaluations of the risk of acute nonlymphocytic leukemia (ANLL) following therapy for non-Hodgkin's lymphoma (NHL). Further, the relationship between cumulative dose of cytotoxic drug, radiation dose to active bone marrow, and the risk of ANLL following NHL have not been well described. PURPOSE: Our purpose was to examine the risk of ANLL in relationship to all prior treatment for NHL. METHODS: Within a cohort study of 11,386 2-year survivors of NHL, 35 case patients with secondary ANLL were identified and matched to 140 controls with NHL who did not develop ANLL. The primary eligibility criteria for the cohort included a diagnosis of NHL as a first primary cancer from January 1, 1965, through December 31, 1989; age 18 through 70 years at the time of initial diagnosis; and survival for 2 or more years without the development of a second invasive primary malignancy. Detailed information on chemotherapeutic drugs and radiotherapy was collected for all patients. Standard conditional logistic regression programs were used to estimate the relative risk (RR) of ANLL associated with specific therapies by comparing the exposure histories of case patients with individually matched controls. RESULTS: Significant excesses of ANLL followed therapy with either prednimustine (RR = 13.4; 95% confidence interval [CI] = 1.1-156; P trend for dose < .05) or regimens containing mechlorethamine and procarbazine (RR = 12.6; 95% CI = 2.0-79; P < .05). Elevated risks of leukemia following therapy with chlorambucil were restricted to patients given cumulative doses of 1300 mg or more (RR = 6.5; 95% CI = 1.6-26; P < .05). Cyclophosphamide regimens were associated with a small, nonsignificant increased risk of ANLL (RR = 1.8;95% CI = 0.7-4.9), with most patients receiving relatively low cumulative doses (< 20,000 mg). Radiotherapy given at higher doses without alkylating agents was linked to a nonsignificant threefold risk of ANLL compared with lower dose radiation or no radiotherapy. CONCLUSIONS: Our results suggest that prednimustine may be a human carcinogen, with a positive dose-response gradient evident for ANLL risk. The low, nonsignificant risk of leukemia associated with cyclophosphamide was reassuring because this drug is commonly used today. Despite the excesses of ANLL associated with specific therapies, secondary leukemia remains a rare occurrence following NHL. Of 10,000 NHL patients treated for 6 months with selected regimens including low cumulative doses of cyclophosphamide and followed for 10 years, an excess of four leukemias might be expected.

Changes in diagnosis of non-Hodgkin's lymphomas over time.

The question is raised as to whether changes in criteria for the diagnosis of non-Hodgkin's lymphomas, both clinical and pathological, have changed over the past four decades in sufficient scale to create a spurious increase in the apparent incidence of this grouping of disease. In the decade of the 1970s refinement in histomorphological criteria for the diagnosis of Hodgkin's disease resulted in as many as 10-15% of cases which previously would have been diagnosed as Hodgkin's disease being diagnosed instead as non-Hodgkin's lymphoma. Other considerations, including distinction of non-Hodgkin's lymphomas from leukemias and plasma cell myelomas, and recent recognition of angioimmunoblastic lymphadenopathy and extranodal "pseudolymphomas" as variant forms of non-Hodgkin's lymphoma, appear to have added only marginally to the total of reported cases. It is concluded that the increase in reported incidence of non-Hodgkin's lymphoma cannot be explained on the basis of changes in diagnostic criteria.

The role of protein kinase C activation and inositol phosphate production in the regulation of cell-surface expression of Mac-1 by complement fragment C5a.

The adhesion of leukocytes to endothelial and other cell types is an essential part of the acute inflammatory response. One means by which adherence can be increased is by activation of the CD11/CD18 family of leukocyte glycoproteins. Chemotactic peptides, lipid mediators, phorbol esters and tumour necrosis factor are all able to increase the cell surface expression of one member of this family, CD11b/CD18 or Mac-1, by an unknown signal transduction mechanism. In this report, regulation of Mac-1 expression by C5a is shown to be independent of protein kinase C (PK-C) activation. The inhibitor of PK-C, H-7, has no effect on the action of C5a and only a slight effect on phorbol ester-induced up- and down-regulation of Mac-1, at a concentration that inhibits superoxide production in response to both factors by 40%. Inositol phospholipid hydrolysis, an important pathway leading to PK-C activation, and the transient increases in cytosolic Ca2+ associated with inositol phosphate production, are also shown to be not essential processes in C5a-stimulation of Mac-1 expression.

Clinical correlates of distinct immunophenotypic and histologic subcategories of lymphocyte-predominance Hodgkin's disease.

Histologic and paraffin immunohistologic studies were carried out on 32 patients with lymphocyte-predominance Hodgkin's disease (LPHD) seen from 1970 through 1982. While nodular histology was accurately predictive of B-cell phenotype (Leu M1 -/L26+), diffuse histology corresponded to either B-cell or Hodgkin's (Leu M1 +/L26-) phenotype, not invariably predictable even when attention was paid to subtle paragranuloma cytology. Clinical characteristics were compared between histologic (diffuse v nodular) and immunophenotypic (Leu M1 +/L26-, Hodgkin's phenotype, v Leu M1 -/L26+, B-cell phenotype) subgroups. Ten patients have since died, and the median follow-up of the living patients was 14 years (range, 6 to 31). Of the several clinical parameters compared, only axillary nodal presentation was strongly associated with both B-cell phenotype and nodular histology, while male predominance related more to B-cell phenotype than nodular histology. No significant difference in overall survival or relapse rate was apparent among either the histologic or the immunophenotypic subgroups. However, very late but salvageable relapses were associated with nodular histology. The incidences of secondary malignancies and death from Hodgkin's disease (HD) were also comparable between the subgroups. Although difference in clinical presentation may exist, neither the histologic nor the immunophenotypic subcategories of LPHD could be demonstrated to correlate with differences in clinical outcome.

Patterns of failure in primary testicular non-Hodgkin's lymphoma.

Patterns of failure were analyzed in 30 patients with testicular non-Hodgkin's lymphoma: 16 had stage IE disease, ten had stage IIE, and four had stage IV. After orchiectomy, two of the 16 patients with stage IE disease received no additional therapy, one received multiagent chemotherapy, and 13 received pelvic and para-aortic radiation. Twelve patients with stage IE disease had progression, and the median time to progression was 12 months. Of the 14 patients with extratesticular involvement (stage IIE or IV), one (stage IV) received no treatment after orchiectomy, three (stage IIE) received para-aortic and pelvic radiation, and ten (seven stage IIE and three stage IV) received multiagent chemotherapy with or without radiation. Eight of the patients with stage IIE or IV disease had progression, and the median time to progression was 11 months. Widespread extranodal progression was observed in 17 of the 20 patients who had progression. The tendency of testicular lymphoma for early systemic progression suggests a need for multiagent chemotherapy in initial management.

Leukemia following low-dose total body irradiation and chemotherapy for non-Hodgkin's lymphoma.

PURPOSE: Low-dose total body irradiation (TBI) is used to treat non-Hodgkin's lymphoma (NHL) and several other malignancies. Large volumes of bone marrow and other tissue receive considerable exposure, but few studies have quantified late carcinogenic sequelae. PATIENTS AND METHODS: A cohort of 61 2-year survivors of NHL treated initially with low-dose TBI was monitored for second cancer occurrence. Data on primary and subsequent therapy were collected, and cumulative dose of radiation to active bone marrow (ABM) (median, 5.2 Gy) was reconstructed. RESULTS: Thirteen second primary cancers occurred. Four patients developed acute nonlymphocytic leukemia (ANLL), which represents a relative risk (RR) of 117 (95% confidence interval [CI], 31.5 to 300) compared with population rates. A fifth patient was diagnosed with myelodysplastic syndrome (MDS). All five patients with secondary hematologic malignancies subsequently received salvage treatment, with either alkylating agents alone (n = 1) or combined modality therapy (CMT) (n = 4). Overall, eight solid tumors were observed (RR = 2.0; 95% CI, 0.9 to 4.0). The 15-year cumulative risks of all second cancers and secondary ANLL were 37% and 17%, respectively. CONCLUSIONS: Despite the small number of subjects, a considerable risk of leukemia was observed among patients treated with low-dose TBI in combination with CMT including alkylating agents. Based on these results, approximately eight to nine excess ANLLs might be expected to occur among 100 NHL patients treated with low-dose TBI and salvage treatment and followed-up for 15 years.

A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study.

PURPOSE: A randomized clinical trial was undertaken to compare the therapeutic effectiveness of idarubicin (IDR) to daunorubicin (DNR), and both were given in combination with cytarabine (CA) in acute myelogenous leukemic (AML) patients. PATIENTS AND METHODS: Newly diagnosed patients were given a daily infusion of CA (100 mg/m2) for 7 days and were assigned randomly to receive DNR (45 mg/m2) or IDR (12 mg/m2) daily for the first 3 days. Those patients who achieved a complete remission (CR) were given three consolidation courses that consisted of CA (100 mg/m2 intravenously [IV]) and thioguanine (TG; 100 mg/m2 orally) every 12 hours for 5 days and either DNR (50 mg/m2) or IDR (15 mg/m2) on the first day of each cycle. After consolidation, patients received late intensification, which consisted of the same drugs used for induction except that the CA was given for 5 days and the anthracycline for 2 days. Four courses were planned at 13-week intervals. RESULTS: The CR rates were 75 of 105 (71%) on the IDR arm and 65 of 113 (58%) on the DNR arm (P = .03). The median survival and median remission durations were 297 and 433 days, respectively, on the IDR arm. The median survival and median remission durations were 277 and 328 days, respectively, on the DNR arm. Six deaths occurred during late intensification, five on IDR and one on DNR; this approach was abandoned after 47 patients were entered. The median survival was significantly longer for patients who received late intensification. CONCLUSION: This trial demonstrated that IDR was more effective than DNR in remission induction in AML.

New malignant diseases after allogeneic marrow transplantation for childhood acute leukemia.

PURPOSE: To determine the incidence of and risk factors for second malignancies after allogeneic bone marrow transplantation (BMT) for childhood leukemia. PATIENTS AND METHODS: We studied a cohort of 3, 182 children diagnosed with acute leukemia before the age of 17 years who received allogeneic BMT between 1964 and 1992 at 235 centers. Observed second cancers were compared with expected cancers in an age- and sex-matched general population. Risks factors were evaluated using Poisson regression. RESULTS: Twenty-five solid tumors and 20 posttransplant lymphoproliferative disorders (PTLDs) were observed compared with 1.0 case expected (P <.001). Cumulative risk of solid cancers increased sharply to 11.0% (95% confidence interval, 2.3% to 19.8%) at 15 years and was highest among children at ages younger than 5 years at transplantation. Thyroid and brain cancers (n = 14) accounted for most of the strong age trend; many of these patients received cranial irradiation before BMT. Multivariate analyses showed increased solid tumor risks associated with high-dose total-body irradiation (relative risk [RR] = 3.1) and younger age at transplantation (RR = 3.7), whereas chronic graft-versus-host disease was associated with a decreased risk (RR = 0.2). Risk factors for PTLD included chronic graft-versus-host disease (RR = 6.5), unrelated or HLA-disparate related donor (RR = 7. 5), T-cell-depleted graft (RR = 4.8), and antithymocyte globulin therapy (RR = 3.1). CONCLUSION: Long-term survivors of BMT for childhood leukemia have an increased risk of solid cancers and PTLDs, related to both transplant therapy and treatment given before BMT. Transplant recipients, especially those given radiation, should be monitored closely for second cancers.

Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin 3 fusion protein, on human tumor colony-forming units taken directly from patients.

PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin 3 (GM-CSF/IL-3) genetically engineered hybrid, has shown greater biological activity in stimulating committed myeloid progenitors than either GM-CSF or IL-3 in vitro, in vivo, and in patients treated with high-dose chemotherapy. However, one concern is that PIXY321 may stimulate the proliferation of malignant cells which have functional GM-CSF or IL-3 receptors. Therefore, using a human tumor cloning assay, we have tested the effects of several concentrations of PIXY321 ranging from 0.1 to 100 ng/ml on tumor cells taken directly from 98 patients with solid tumors and Hodgkin's or non-Hodgkin's lymphomas. Of the 34 evaluable specimens, including 15 breast cancers, 5 ovarian cancers, 5 lung cancers, and 9 lymphomas, none showed stimulation of tumor growth. Interestingly, a significant inhibition of the tumor proliferation was seen in one breast cancer and in one large cell immunoblastic non-Hodgkin's lymphoma after continuous exposure of PIXY321. In conclusion, the use of PIXY321 to reduce myelosuppression after high-dose chemotherapy appears unlikely to result in stimulation of the growth of malignant cells in patients with lymphoma or cancers of the breast, lung, and ovary.

Splenectomy for Felty's syndrome. Clinicopathological study of 27 patients.

The major clinical and pathological features and the long-term follow-up of 27 patients with Felty's syndrome who were treated with splenectomy for sever granulocytpenia and for acute, chronic, or recurrent infection were studied. Granulocyte counts rose within days in most patients, although slow responses and transient granulocytopenia did occur; only 12% of the patients had persistent or recurrent granulocytopenia. Infections resolved promptly in 77% of the patients, more slowly in the remainder, and only one patient had new problems of infection after aplenectomy. Splenic enlargement, present in all but one case, was attributable to expansion of the sinusoidal pulp. The most substantial pathological features of immune stimulation included germinal center hyperplasia and prominent clusters of plasma and preplasma cells within sinuses.

In search of a recognition memory engram.

A large body of data from human and animal studies using psychological, recording, imaging, and lesion techniques indicates that recognition memory involves at least two separable processes: familiarity discrimination and recollection. Familiarity discrimination for individual visual stimuli seems to be effected by a system centred on the perirhinal cortex of the temporal lobe. The fundamental change that encodes prior occurrence within the perirhinal cortex is a reduction in the responses of neurones when a stimulus is repeated. Neuronal network modelling indicates that a system based on such a change in responsiveness is potentially highly efficient in information theoretic terms. A review is given of findings indicating that perirhinal cortex acts as a storage site for recognition memory of objects and that such storage depends upon processes producing synaptic weakening.