AL amyloidosis patients ineligible for dose‐intensive melphalan (200 mg/m2) were enrolled on a phase II trial to be treated with two cycles of intermediate‐dose melphalan (IDM 100 mg/m2) and ...mobilized blood stem cells (BSC). For mobilization patients were randomized to either GM‐CSF 250 μg/m2 for 3 d followed by G‐CSF 10 μg/kg for 3 d (GM+G), or G‐CSF 10 μg/kg for 6 d (G‐alone), with leukaphereses on days 5, 6 and 7. To minimize morbidity, we planned to support each cycle with 3.5 × 106 CD34+ cells/kg and had a collection target of 7 × 106 CD34+ cells/kg. Those who did not achieve the target were treated with one cycle of IDM. 30 patients, a median of 62 years old and 7 months from diagnosis, were enrolled. Both mobilization regimens were generally well tolerated, and similar in terms of CD34+ cells and CFU‐GM collected, but only 6/28 patients achieved the collection target (GM+G four, G‐alone two). Despite a 19% incidence of grade 4 toxicities, IDM therapy was well tolerated. At a median follow‐up of 24 months (19–36) 57% of patients had survived, 17% with durable complete haematological responses and 40% with improved or stable amyloid organ involvement, including 3/9 patients with predominant cardiac amyloid who are alive 2–3 years after treatment. The 100 d mortality was 20%. In conclusion, no definitive differences were identified between the mobilization regimens and IDM was an active regimen in AL for selected patients.
The primary objective of this study was to determine how yogurt ingredients affect aroma release in the mouth during eating. A model strawberry flavor consisting of ethyl butanoate, ethyl ...3-methylbutanoate, (Z)-hex-3-enol, 2-methylbutanoic acid, 5-hexylhydro-2(3H)-furanone, and 3-methyl-3-phenylglycidic acid ethyl ester was added to unflavored, unsweetened yogurt that had different added sweeteners and hydrocolloids. In all, 12 yogurt formulations were examined to determine the effects of gelatin, modified food starch, pectin, sucrose, high-fructose corn syrup, and aspartame on aroma release. Aroma release was monitored by breath-by-breath analysis (proton-transfer reaction−mass spectrometry) during eating of the test yogurts. Results showed aroma release of the ethyl butanoate, (Z)-hex-3-enol, and ethyl 3-methylbutanoate to be suppressed by sweeteners, with 55 DE high-fructose corn syrup having the greatest effect. Addition of thickening agents had no significant effect on the aroma release profiles of the compounds under study. Keywords: Proton-transfer reaction−mass spectrometry; yogurt; high-fructose corn syrup; aroma release; flavor release; breath-by-breath
OBJECTIVE: Garcinia mangostana Linn., commonly known as mangosteen, is a tropical fruit with a thick pericarp rind containing bioactive compounds that may be beneficial as an adjunctive treatment for ...schizophrenia. The biological underpinnings of schizophrenia are believed to involve altered neurotransmission, inflammation, redox systems, mitochondrial dysfunction, and neurogenesis. Mangosteen pericarp contains xanthones which may target these biological pathways and improve symptoms; this is supported by preclinical evidence. Here we outline the protocol for a double- blind randomized placebo-controlled trial evaluating the efficacy of adjunctive mangosteen pericarp (1,000 mg/day), compared to placebo, in the treatment of schizophrenia. METHODS: We aim to recruit 150 participants across two sites (Geelong and Brisbane). Participants diagnosed with schizophrenia or schizoaffective disorder will be randomized to receive 24 weeks of either adjunctive 1,000 mg/day of mangosteen pericarp or matched placebo, in addition to their usual treatment. The primary outcome measure is mean change in the Positive and Negative Symptom Scale (total score) over the 24 weeks. Secondary outcomes include positive and negative symptoms, general psychopathology, clinical global severity and improvement, depressive symptoms, life satisfaction, functioning, participants reported overall improvement, substance use, cognition, safety and biological data. A 4-week post treatment interview at week 28 will explore post-discontinuations effects. RESULTS: Ethical and governance approvals were gained and the trial commenced. CONCLUSION: A positive finding in this study has the potential to provide a new adjunctive treatment option for people with schizophrenia and schizoaffective disorder. It may also lead to a greater understanding of the pathophysiology of the disorder.
Amylase isoenzyme analysis of serum, urine and other bodily fluids using dextran gel and ion exchange chromatography provides a new dimension in the identification of pancreatic disease. Examples are ...described that illustrate the clinical application of such analysis and the usefulness of the information that may be derived.
Summary
Malignant cells infiltrating the bone marrow (
BM
) interfere with normal cellular behaviour of supporting cells, thereby creating a malignant niche. We found that
CXCR
4‐receptor expression ...was increased in paediatric precursor B‐cell acute lymphoblastic leukaemia (
BCP
‐
ALL
) cells compared with normal mononuclear haematopoietic cells (
P
<
0·0001). Furthermore, high
CXCR
4‐expression correlated with an unfavourable outcome in
BCP
‐
ALL
(5‐year cumulative incidence of relapse ± standard error: 38·4% ± 6·9% in
CXCR
4‐high
versus
12% ± 4·6% in
CXCR
4‐low expressing cases,
P
<
0·0001). Interestingly,
BM
levels of the
CXCR
4‐ligand (
CXCL
12) were 2·7‐fold lower (
P
=
0·005) in diagnostic
BCP
‐
ALL
samples compared with non‐leukaemic controls. Induction chemotherapy restored
CXCL
12 levels to normal. Blocking the
CXCR
4‐receptor with Plerixafor showed that the lower
CXCL
12 serum levels at diagnosis could not be explained by consumption by the leukaemic cells, nor did we observe an altered
CXCL
12‐production capacity of
BM
‐mesenchymal stromal cells (
BM
‐
MSC
) at this time‐point. We rather observed that a very high density of leukaemic cells negatively affected
CXCL
12‐production by the
BM
‐
MSC
while stimulating the secretion levels of granulocyte colony‐stimulating factor (G‐
CSF
). These results suggest that highly proliferative leukaemic cells are able to down‐regulate secretion of cytokines involved in homing (
CXCL
12), while simultaneously up‐regulating those involved in haematopoietic mobilization (G‐
CSF
). Therefore, interference with the
CXCR
4/
CXCL
12 axis may be an effective way to mobilize
BCP
‐
ALL
cells.
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