Heat and shear stability of particle stabilised foams for application in gluten-free bread.

Bread forms an integral part of the daily diet in many cultures worldwide. At the same time, a significant number of people try to avoid wheat-based products for either health reasons or due to personal preferences. The absence of a protein network in gluten free bread affects its structure, taste, texture and shelf-life. This paper suggests a technological solution to this issue that uses a pre-foamed mass of gluten free raw materials which is mixed with the bread's ingredients, then kneaded and baked to form a high quality gluten free bread. To survive the high shear stresses during kneading and temperature increase during baking, the foam requires exceptional stability. This stability was achieved through particle stabilisation of the bubble interfaces. Both of the tested foams (with and without particles) exhibited thermal stability up to 80 °C. However, resistance to shear stresses was higher in the particle stabilised foams. Of all the tested particles, linseed press cake and banana powder led to the best results. In conclusion, particle stabilised foams seem very well suited to applications in gluten free baked goods. Further application potential is seen for vegan foamed desserts.

Familial persistent polyclonal B-cell lymphocytosis.

We report the occurrence of the syndrome of persistent polyclonal B-cell lymphocytosis in a brother and a sister. Both showed the morphological and immunophenotypic features of this rare disorder. In addition both had mild splenomegaly, increase of serum IgM and serological evidence of previous EBV infection. Of interest, two additional brothers had no evidence of PPBL but were indistinguishable in terms of HLA haplotype (HLA-DR7), smoking habits or evidence of EBV infection. These observations provide additional support for a genetic basis of the syndrome but suggest that pathogenic factors other than those known so far may be required for its full expression.

Bone marrow involvement in Whipple's disease: rarely reported, but really rare?

Infection with Tropheryma whippelii, the causative agent of Whipple's disease, involves nearly every organ. Involvement of bone marrow may be an overlooked area of Whipple's disease. We report a case of lymphoma-like Whipple's disease with bone marrow involvement together with a brief review of the literature on this topic. Despite minimal documentation, bone marrow may be commonly involved in Whipple's disease and, although not specific, diastase-resistant periodic acid-Schiff (PAS)-positive macrophages in bone marrow may offer an important clue to diagnosis using PAS histology of upper endoscopic biopsies, polymerase chain reaction or electron microscopy.

The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease.

The use of neutrophil left-shift parameters in the diagnosis of inflammatory and infective disease (ID) was evaluated. The level of C-reactive protein (CRP), currently the best quantitative parameter of inflammation, was used as the gold standard. Of 292 patients, 230 (79%) had a level of CRP of 1.0 mg/dL or greater and were classified as having inflammation, whereas 62 (21%) had normal levels. The neutrophil band count in each patient was determined by microscopic examination of 200 WBCs. The diagnostic value of the band count as an indicator for ID was evaluated in comparison to the WBC count, the neutrophil count, and the left-shift indicators of two automated hematologic analyzers, H*1 Technicon (Bayer Technicon Instruments, Tarrytown, NY) and Coulter MAX M (Coulter Electronics, Hialeah, Fla). When receiver operating characteristics were used, the band count was superior to the immature to total neutrophil count (I/T) ratio, the total WBC count, and the neutrophil count. The sensitivity and specificity in identifying ID at designated cutoff points were as follows: band count of 20% or greater of total WBC count (53% and 79%, respectively), I/T ratio of 0.25 or greater (59% and 63%), total WBC count of 9.6 x 10(6)/mL or greater (68% and 56%), and neutrophil count of 8.0 x 10(6)/mL or greater (60% and 58%). The performance of the H*1 Technicon left-shift flag was similar but slightly inferior to the band count (sensitivity, 44%; specificity, 79%), whereas the Coulter MAX M flags had a clearly higher sensitivity (79%) and lower specificity (53%). In addition, microscopic evaluation to determine the presence of reactive morphologic changes in neutrophils, such as toxic granules, Döhle bodies, and cytoplasmic vacuoles, had a high sensitivity (80%) but a low specificity (58%) in predicting ID. The diagnostic value of both microscopic and automated neutrophil left-shift parameters as indicators for ID is limited. Morphologic changes in neutrophils, however, either have a high specificity (band count) or a high sensitivity (toxic signs) in predicting ID and therefore may be a clinically useful tool.

Clomipramine challenge responses covary with Tridimensional Personality Questionnaire scores in healthy subjects.

Cloninger's Unified Biosocial Theory of Personality postulates a relationship between the relative functional activity of central serotonergic, dopaminergic, and noradrenergic neurotransmitter systems, and the strength of three elemental dimensions of personality. These dimensions are Harm Avoidance, Novelty Seeking, and Reward Dependence, respectively. Accordingly, we predicted that neuroendocrine responses to serotonergic challenge would correlate with Harm Avoidance scores, but not with Novelty Seeking or Reward Dependence scores. We examined the relationship between the prolactin and cortisol responses to a 12.5-mg intravenous clomipramine challenge and these personality dimensions as measured by Cloninger's Tridimensional Personality Questionnaire in 32 healthy subjects. The cortisol response correlated only with Harm Avoidance scores, as predicted; however, prolactin response did not correlate with Harm Avoidance scores. Instead, it demonstrated an inverse relationship with Novelty Seeking scores. There was a positive relationship of baseline prolactin with Harm Avoidance in a post hoc analysis. Cortisol response to serotonergic challenge may be a better indicator for responsivity of serotonergic systems as they relate to the personality dimension of Harm Avoidance than is prolactin. Prolactin responses may be overly affected by dopaminergic influences; however, baseline prolactin may still be a valid indicator of serotonergic tone.

Early diagnosis of low grade malignant lymphoma and chronic lymphocytic leukaemia. Verification of morphologically suspected malignancy in blood lymphocytes by flow cytometry.

According to international recommendations, the diagnosis of chronic lymphocytic leukaemia (CLL) is made on the grounds of persistent peripheral lymphocytosis or lymphocytic infiltration of the bone marrow. The appearance of morphologically atypical lymphocytes in low-grade malignant lymphoma (NHL) or CLL is easily overlooked, and is generally not regarded as a diagnostic criterion. We report 12 cases of CLL/NHL who were detected only by morphological screening of routine peripheral blood smears (83,400 blood smears). The diagnosis of CLL/NHL was not suggested by the patients' history, physical or other laboratory findings, and had not been contemplated by the physician in charge. Monoclonality of peripheral lymphocytes was confirmed by immunophenotyping and Southern blotting. The lymphoma was classified histologically according to the International Working Formulation (bone marrow biopsy). A monoclonal lymphatic population was not found by immunophenotyping in the blood of 11 patients whose lymphocytes were morphologically classified as activated-abnormal. However, 3 patients suspected to have NHL/CLL on morphological screening of blood smears had to be classified as benign after immunophenotyping. We conclude that morphological screening of routine blood smears is an inexpensive and easy additional screening method for CLL and low grade malignant NHL.

The effects of age, gender, and season on serotonergic function in healthy subjects.

1. Several factors, including age, gender, and season of the year, have been reported to affect physiologic indices of central serotonergic function, although some of these findings have not been consistent across groups of subjects and types of serotonergic measures. 2. The authors investigated the role that each of these variables might play in the neuroendocrine response to acute intravenous challenge with the serotonin reuptake inhibitor clomipramine (CMI) in healthy volunteers. 3. Thirty seven healthy subjects (17 women and 20 men), with an age range of 19 to 50 years, received 12.5 mg of CMI intravenously under standardized conditions. 4. The maximum change from baseline in plasma prolactin concentrations ("delta-max") was significantly related to age, after controlling for gender and season. 5. In contrast, neither gender nor season was significantly related to prolactin delta-max, after controlling for the other two variables. 6. Although the age range and sample size are relatively limited, the results from this study suggest that age, but not gender or season, may influence serotonergic function, as measured by the prolactin response to CMI challenge.

Prediction of iron deficiency in chronic inflammatory rheumatic disease anaemia.

We prospectively studied 45 anaemic patients (37 women, 8 men) with chronic inflammatory rheumatic diseases. The combination of serum ferritin and CRP (as well as ESR) in its predictive capacity for bone marrow iron stores was examined. The relationship between other iron-related measurements (transferrin, transferrin saturation, soluble transferrin receptor, erythrocyte porphyrins and percentage of hypochromic/microcytic erythrocytes) and bone marrow iron stores was also investigated. Stainable bone marrow iron was taken as the most suitable standard to separate iron-deficient from iron-replete patients. 14 patients (31%) were lacking bone marrow iron. Regression analysis showed a good correlation between ferritin and bone marrow iron (adjusted R2 = 0.721, P < 0.0001). The combination of ferritin and CRP (ESR) did not improve the predictive power for bone marrow iron (adjusted R2 = 0.715) in this cohort of patients with low systemic inflammatory activity. With respect to the bone marrow iron content the best predictive cut-off value of ferritin was 30 micrograms/l (86% sensitivity, 90% specificity). The other iron-related parameters both individually and when combined were less powerful in predicting bone marrow iron than ferritin alone. Only zinc bound erythrocyte protoporphyrin in combination with ferritin slightly improved prediction (adjusted R2 = 0.731). A cut-off point of 11% hypochromic erythrocytes reached a high specificity (90%), but was less sensitive (77%).

High grade malignant lymphoma with clinical characteristics and immunophenotype of natural killer cells.

The malignant proliferation of natural killer (NK) cells which are morphologically characterized as large granular lymphocytes (LGL) is a well known clinical entity which was named after its morphological appearance as LGL-leukemia/lymphoma. Similar to non-malignant NK-cells, these tumors can be divided into those which express the CD3-T-cell receptor complex and those which do not. The CD3-positive type of LGL-leukemia is immunophenotypologically characterized by the expression of CD16, and variably CD 56 and CD 57, and generally follows a more indolent course. In contrast, malignant proliferations of CD3-negative LGL express either CD16 or CD 56, and only occasionally CD 57 on their cell surface. Clinically, CD3-negative NK-lymphomas tend to progress rapidly. We report here the case of a high grade malignant lymphoma which was characterized by an immunophenotype typical for CD3-negative NK-cells (CD2+, CD3-, CD16+, CD56(+), CD57-). The disease proved to be rapidly fatal despite aggressive chemotherapy. Interestingly, the patient suffered from a high turn over pancytopenia, which also characterizes NK-cell leukemias/lymphomas of the LGL-type. However, our patient's lymphatic cells appeared highly immature, and cytoplasmic granules, characteristic for LGL-cells, could not be discerned either microscopically or electronmicroscopically. Furthermore, the malignant lymphatic population had the T-cell receptor beta-chain rearranged. We therefore concluded that our patient might have suffered from a malignant proliferation of a putative precursor cell intermediate between T-cells and NK-cells.

Epinephrine test and plasma elastase as diagnostic tools in a patient with CD3+ large granular lymphocyte proliferation.

Large granular lymphocytes (LGL) proliferation is characterized by expansion of cytotoxic lymphocytes and associated with neutropenia. In a case of CD3+ LGL-proliferation the epinephrine stimulation test (EST) induced a striking elevation of CD3+, CD8+, CD57+ LGL in peripheral blood from 2.7 x 10(9)/l to 20 x 10(9)/l and might be an additional diagnostic tool in patients with normal or low absolute numbers of circulating LGL. After treatment with steroids, plasma elastase--a marker of neutrophil destruction--decreased from 162 to 40 micrograms/l (normal < 47 micrograms/l) which correlated well with a simultaneous increase in peripheral neutrophil counts from 0.14 to 1.0 x 10(9)/l. This finding supports the hypothesis that neutropenia in CD3+ LGL proliferation is due to neutrophil destruction, possibly mediated by LGL.

Altered prolactin response to clomipramine rechallenge in healthy subjects.

The effect of an initial challenge with the serotonin (5-HT) uptake inhibitor clomipramine (CMI) on subsequent rechallenge was studied in healthy men who served as volunteers. Carefully screened volunteers were assigned to one of three conditions: (1) CMI challenge followed 2 weeks later by CMI rechallenge; (2) placebo challenge followed 2 weeks later by CMI challenge; and (3) CMI challenge followed 4 weeks later by CMI rechallenge. We found significant blunting of the prolactin response to CMI rechallenge 2 weeks (Signed Rank = -12, p = 0.05), but not 4 weeks after an initial challenge. Placebo challenge did not effect CMI challenge 2 weeks later. These findings suggest that a single exposure to IV CMI may cause 5-HT receptor changes that are present 2, but not 4 weeks later. The ramifications of this finding with regard to the use of 5-HT challenge paradigms in a test-retest design are discussed.

Neuroendocrine effects of intravenous clomipramine in depressed patients and healthy subjects.

OBJECTIVE: Neuroendocrine challenge paradigms have been used to asses serotonergic systems in depression, but limitations in the specificity of many of these tests have been noted. In this study, the neuroendocrine responses to acute intravenous administration of the serotonin (5-HT) reuptake inhibitor clomipramine were assessed in depressed patients and matched control subjects. METHODS: Thirty hospitalized patients who met DSM-III-R criteria for major depression, and 30 healthy control subjects who were matched for age, sex, and season of year for the time of study, received 12.5 mg of intravenously administered clomipramine. RESULTS: The depressed patients demonstrated significant blunting of prolactin responses to clomipramine, as well as trends toward blunted ACTH and cortisol responses. There was no difference between the patient and control groups in growth hormone responses, plasma clomipramine levels, or self-reports of side effects. CONCLUSIONS: These data support the hypothesis that depressed patients have abnormal neuroendocrine responses to the intravenous administration of the 5-HT reuptake inhibitor clomipramine. Further study is required to delineate the mechanisms responsible for the abnormal response to intravenously administered clomipramine in depression.

Transient pure red cell aplasia caused by antilymphoblast globulin after cadaveric renal transplantation.

Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin developed reticulocytopenia (less than 17,000 reticulocytes/mm3), with complete disappearance of reticulocytes in 65% of patients and increased requirement for red cell transfusion. PRCA, with selective aplasia of erythroblasts was confirmed by bone marrow aspiration in 4 patients volunteering for aspiration, and by the kinetic of the disappearance of blood reticulocytes in relation to the beginning of ATG treatment. The nadir of thrombocytes and lymphocytes, blood cells directly destroyed by ATG in circulation, followed the start of ATG treatment within 1 to 4 days. In contrast the nadir of reticulocyte counts occurred later, between day 7 and 13 after ATG was begun, reflecting the fact that toxicity was directed against red cell precursors rather than mature circulating cells. In agreement with these clinical findings ALG was found to be cytotoxic in vitro for erythroid precursors. Analogously to autoimmune PRCA caused by autoantibodies to erythroblasts, this type of PRCA could be viewed as "heteroimmune disease."

Abnormal neuroendocrine responsivity to clomipramine in depression.

We used a pharmacologic probe that measures the neuroendocrine response to acute, intravenous "challenge" with the serotonin re-uptake inhibitor, clomipramine, in our studies of the biochemical bases of depressive illness. In two studies conducted at different sites, depressed patients consistently demonstrated blunted prolactin responses to clomipramine, compared with healthy control subjects. In order to clarify the mechanisms that might account for this abnormal neuroendocrine response to clomipramine in depression, we administered a thyrotropin-releasing hormone (TRH) stimulation test to 7 depressed patients who had also received a clomipramine challenge test. Although these patients demonstrated blunted prolactin responses to clomipramine, their prolactin responses to TRH were robust. These observations suggest that the blunted prolactin response to clomipramine in depression is not attributable to diminished hormonal secretory capacity in anterior pituitary lactotrophs and may be a reflection of dysregulation in central serotonergic systems.

Gepirone as a 5-HT1A agonist in the treatment of major depression.

Twenty-four patients with major depression were treated in a single-blind design with 25 mg to 75 mg gepirone, a pyrimidinyl piperidinedione analog of buspirone with serotonin1A (5-HT1A) receptor affinity properties. Twenty-four-Item Hamilton Rating Scale for Depression-(HAM-D) scores decreased by 36 percent when mean baseline scores were compared with an endpoint analysis of 6 weeks' gepirone treatment. Several subjects demonstrated marked improvements over baseline. The data are discussed within the context of 5-HT1A receptor desensitization as a potential component of antidepressant treatment.

Introduction of a standardized report form improves the quality of mental status examination reports by psychiatry residents.

The quality of mental status examination (MSE) reports in consecutive admission notes by psychiatric residents was compared before and after the introduction of a structured, pre-printed MSE form that had been designed for teaching and quality of care purposes. We found the use of the form to be associated with a marked improvement in the quality of the reports; however, an important item not on the form was less likely to be recorded than with an unstructured record of the MSE. We conclude that the use of structured MSE forms leads to a significant improvement in the comprehensiveness of MSE records. We therefore recommend that some version of a comprehensive, structured MSE form be adopted for use on adult inpatient psychiatry units where residents are being trained.

Depression in the aged. An overview.

Depression in the aged is common and associated with substantial medical and social morbidity and mortality. It is often missed or misdiagnosed because of masked or somatic symptoms, delusions, and pseudodementia. At any given time, about 2 per cent of the elderly have major depression and a third to a half of older psychiatric inpatients and outpatients have mood disorders. Aged depressives have more somatization, hypochondriasis, anxiety, retardation, and delusionality but less guilt, loss of libido, and family history of depression than young ones. Both the illnesses common in the elderly and the medicines used to treat them may be etiologically connected with depression. After precipitating causes are remedied, remaining symptoms respond to antidepressant treatment. Medication doses are much lower and side effects more troublesome. ECT or concomitant antipsychotic medication are more likely to be indicated.