Cytometric analysis and maturation characteristics of reticulocytes from myelodysplastic patients

Myelodysplasia is characterized by a hypoproliferative anaemia with ineffective intramedullary erythropoiesis. We have used the novel technology of the Bayer H3 analyser to characterize reticulocytes (RNA containing red cells) from 32 MDS patients and 10 elderly normal subjects. In comparison with reticulocytes from normal subjects, those from MDS patients were larger with a lower haemoglobin concentration. Reticulocytes from sidero blastic patients had a lower haemoglobin content and concentration than for refractory anaemia patients but no other differences between FAB subtypes were found. H3 reticulocyte RNA content parameters correlated poorly with those derived by the Sysmex R-1000, particularly in the MDS group. On reticulocyte maturation to red cells MDS patients concentrated haemoglobin more than normal subjects and this was most evident in the sidero blastic group. Platelet depletion of whole blood suggested that large platelets in the sidero blastic group may have partly contributed to this observation. Prospective evaluation of changes towards normal reticulocyte cytometric parameters may assist in assessment of early erythroid response to therapy in MDS patients.     

Role of protein and carbohydrate sources on acute appetite responses in lean and overweight men

Dietary protein induces greater satiety compared with carbohydrate in lean subjects, which may involve appetite-regulatory gut hormones. Little is known about the duration of effect, influence of protein and carbohydrate source and relevance to non-lean individuals. We compared the effect of various dietary proteins and carbohydrates on post-prandial appetite ratings, ad libitum energy intake (EI) and appetite hormones in lean and overweight men. Three randomised double-blinded cross-over studies examined appetite response (appetite ratings, ghrelin, glucagon-like peptide-1 (GLP-1) and cholecystokinin) to liquid preloads over three to four hours followed by a buffet meal to assess ad libitum EI. The 1-MJ preloads contained ∼55 g of protein (whey, casein, soy and gluten), carbohydrate (glucose, lactose and fructose) or combined whey/fructose. EI was 10% higher following glucose preloads compared with protein preloads, observed at three hours but not four hours. Protein ingestion was followed by prolonged elevation of cholecystokinin and GLP-1 (two hours) and suppression of ghrelin (three to four hours) compared with glucose and independent of protein type. Replacing some whey with fructose attenuated the effect of protein on these hormones. Treatment effects on EI and appetite hormones were independent of bodyweight status, despite higher GLP-1 and lower ghrelin in overweight subjects. Protein-rich liquid preloads reduce EI over three hours in overweight men compared with glucose. These findings suggest a potential application for protein-rich drinks and/or foods to facilitate reduced EI. Future studies should explore additional dietary manipulations that may enhance this relationship, and confirm these effects within the context of energy-restricted dietary patterns.     

Lentigo Maligna/Lentigo Maligna Melanoma: Current State of Diagnosis and Treatment

BACKGROUND: Lentigo maligna (LM) is a subtype of melanoma in situ that typically develops on sun-damaged skin. Presentation may be quite subtle and delayed diagnosis is common. Clinical margins are often ill defined. Histologic evaluation can be difficult due to the widespread atypical melanocytes that are present in the background of long-standing sun damage. Recurrence following standard therapies is common. OBJECTIVE: To review the clinical features, histopathology, and treatment options for LM. Emphasis is placed on recent advances in the treatment of LM. METHODS AND MATERIALS: Literature review. RESULTS: The estimated lifetime risk of LM progressing to LM melanoma is 5%. Standard excision of LM with 5 mm margins is insufficient in 50% of cases. The recurrence rate with standard excision ranges from 8 to 20%. Mohs surgery and staged excision may offer better margin control and lower recurrence rates (4-5%). Estimates of recurrence rates following nonsurgical therapies such as cryosurgery, radiotherapy, electrodessication and curettage, laser surgery, and topical medications range from 20 to 100% at 5 years. CONCLUSIONS: Adequate treatment of LM requires a comprehensive knowledge of the diagnostic features, histopathology, and treatment options. Surgical modalities with meticulous evaluation of tissue margins appears to offer the lowest rates of disease recurrence.     

Effects of interleukins, colony-stimulating factor and tumour necrosis factor on human hair follicle growth in vitro: a possible role for interleukin-1 and tumour necrosis factor-α in alopecia areata

The immune system may be involved in the regulation of normal hair follicle growth as well as in the pathogenesis of some hair diseases. Immunomodulatory cytokines not only act as mediators of immunity and inflammation but also regulate cell proliferation and differentiation and. as such, may play an important part in regulating hair growth. We have investigated the effects of a number of interleukins (IL). colony stimulating factors and tumour necrosis factors (TNF) on hair follicle growth in vitro. Dose-response studies showed that IL-1α. IL-1ß and TNF-o were potent inhibitors of hair follicle growth. The histology of hair follicles maintained with inhibitory doses of IL-1α. IL-1ß and TNF-α showed similar changes in hair follicle morphology, resulting in the formation of dystrophic anagen hair follicles. These changes in histology were characterized by the condensation and distortion of the dermal papilla, marked vacuolation of the hair follicle matrix, abnormal keratinization of the follicle bulb and inner root sheath, disruption of follicular melanocytes and the presence of melanin granules witbin the dermal papilla. Moreover, these changes in hair follicle morphology are similar to those reported in alopecia areata and suggest that IL-1α, IL-1ß and TNF-α may play an important part in the pathophysiology of inflammatory hair disease.     

Influence of Using Different Sources of Carotenoid Data in Epidemiologic Studies

Objective This study compared distributions of carotenoid intake and diet-serum correlations using two sources of carotenoid data: the US Department of Agriculture-National Cancer Institute (USDA-NCI) carotenoid food composition database and values accompanying the Block-NCI Health Habits and History Questionnaire (HHHQ).

Design and subjects A 100-item food frequency questionnaire was used to collect dietary data from 2,152 adults, aged 43 to 85 years, who were participating in the Nutritional Factors in Eye Disease Study, a population-based study designed to evaluate nutritional factors associated with age-related eye disease. Blood samples were collected from a random sample of 400 nonfasting participants in the study.

Results Median carotenoid intakes using HHHQ vs USDA-NCI data were alpha carotene (229 vs 223 μg/day), beta carotene (1,321 vs 1,325 μg/day), beta cryptoxanthin (72 vs 21 μg/day), lutein + zeaxanthin (653 vs 811 μg/day), and lycopene (593 vs 1,615 μg/day). All paired differences in carotenoid intake were significantly different from zero (Wilcoxon signed-rank, P<.0001). Despite these differences, the two databases similarly ranked individuals according to carotenoid intake: Spearman correlations ranged from .71 (lycopene) to .93 (alpha carotene). Differences between diet-serum correlations (adjusted for energy, body mass index, high density lipoprotein, and total cholesterol) using HHHQ vs USDA-NCI data were minor and not significant (P>.05): alpha carotene (r=.33 vs .32), beta carotene (r=.27 vs .32), beta cryptoxanthin (r=48 vs .53), lutein + zeaxanthin (r=.28 vs .24), and lycopene (r=.29 vs .25).

Conclusions Although estimates of carotenoid intake differed significantly, only minor differences in carotenoid rankings and diet-serum correlations were observed using either data source in this population. J Am Diet Assoc. 1996; 96:1271-1275.     

Apoptosis occurs early in the basal layer of the oral mucosa following cancer chemotherapy

Background: Oral mucositis, a debilitating side‐effect of chemotherapy, is difficult to prevent or treat. The aim of this study was to characterize the histological and ultrastructural change in the human oral mucosa following cytotoxic chemotherapy. Methods: Oral buccal mucosa biopsies were taken from four volunteers and 20 cancer patients. Each patient had one biopsy prior to chemotherapy and a second biopsy at varying intervals after chemotherapy. Biopsies were assessed histologically and ultrastructurally. Results: Apoptosis increased in the basal layer in the first 3 days after chemotherapy, began to decline at 6 days, but never returned to levels of volunteers by 11 days after treatment. Ultrastructural changes included increased intercellular fibres in basal layer cells, cytoplasmic vacuolation, loss of membrane contact with neighboring cells, multinucleation of suprabasal cells and loss of cellular cytoplasm. These changes persisted in prechemotherapy biopsies in patients who had prior chemotherapy. Conclusions: Apoptosis occurs early, and persists in the basal layer of the buccal mucosa after chemotherapy. Ultrastructural changes were present and remained up to 11 days after chemotherapy.