Standing on the shoulders of giants: Understanding calcium and vitamin D requirements

The quote by Sir Isaac Newton, ‘If I have seen further it is by standing on ye sholders of Giants’ was the theme of the British Nutrition Foundation (BNF) Annual Lecture 2012. Illustrations of the seminal contributions of six ‘giants’ of nutrition science, chosen because of their links to the BNF and to vitamin and mineral research in Cambridge, were used to give a historical context to recent studies and controversies on calcium and vitamin D requirements, particularly focusing on rickets and maternal and child nutrition.     

Breast feeding increases concentrations of IgA in infants' urine.

To investigate the influence of breast feeding on mucosal immunity the concentrations and daily outputs of IgA and lactoferrin in urine were measured in 10 breast fed and 12 infants fed on formula milk at 6 and 12 weeks of age. The concentrations and outputs of secretory IgA in urine were significantly higher in the breast fed group by a factor of three. The secretion of IgA in urine by the breast fed infants was characteristic of the baby and was not related to the intake of IgA from breast milk. Lactoferrin concentrations were similar in the two groups at both ages. In addition to secretory IgA, two thirds of all samples contained proteins with alpha chain but no secretory component antigenic determinants. Breast feeding seems to increase the local production of secretory IgA into the urinary tract during early childhood, thus providing enhanced protection from infection.     

FLUDAP: salvage chemotherapy for relapsed/refractory aggressive non-Hodgkin's lymphoma

The aim of this study was to investigate the combination of fludarabine phosphate, dexamethasone, cytosine arabinoside and cis-platinum (FLUDAP) in the treatment of patients with relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL). This regimen comprises: dexamethasone 100 mg/d continuous infusion (cont. inf.) d1-3; cytosine arabinoside (ara-C) 1 g/m2/d cont. inf. d 2,3; fludarabine phosphate 30 mg/m2 short inf. 4hr prior to each 24hr ara-C inf.; cis-platinum 50 mg/m2 4hr inf. at the start of each 24hr ara-C inf. G-CSF (lenograstim, Granocyte) is given at 263 microg s.c. daily from day 7 until the neutrophil count reaches 1.0x10(9)/l. The regimen repeats at 21 day intervals. A total of 33 patients were registered (median age 47 years; 24 males, 9 females); the majority (73%) were refractory to their previous treatment and most had advanced disease by Ann Arbor stage. Thirteen (39%) of the 33 enrolled patients (52% of the 25 fully evaluable patients who received at least 2 courses of FLUDAP) responded to treatment. A maximum response of complete remission was achieved in 5 patients, good partial remission in 3, and partial remission in 5. Twelve patients went on to successful stem cell supported intensification therapy. Median survival times were higher in the responding patients, and in those patients transplanted post-FLUDAP. The toxicity associated with the FLUDAP regimen was generally predictable; frequently reported severe events included haematological toxicity and infection. In conclusion, the FLUDAP regimen shows promise as a salvage regimen and increases the available therapeutic options in the treatment of recurrent/refractory aggressive NHL.     

Future possibilities in the prevention of breast cancer: Fat and fiber and breast cancer research

The potential for a reduction in dietary fat or for an increase in dietary fiber to reduce breast cancer risk has been debated for some years. It is argued here that available research data, even though extensive, leave open hypotheses ranging from little or no potential to major public health potential for breast cancer prevention by means of these dietary maneuvers. Some elements of a research strategy for testing these and other dietary breast cancer prevention hypotheses are described.     

The effect of intramuscular stanozolol on fibrinolysis and blood lipids

The effects of a single 50 mg intramuscular injection of the anabolic steroid stanozolol (Stromba) on fibrinolysis, blood coagulation and lipids was evaluated in 12 healthy male volunteers. Significantly increased plasminogen activator levels (p < 0.05) was noted 24 hours following the injection and these remained elevated for one week. Plasminogen levels increased significantly by day two (p < 0.01) and remained elevated for three weeks. HDL cholesterol fell (p < 0.01) and both total and LDL cholesterol increased (p < 0.05) when measured one month post injection. Stanozolol appears to have therapeutic potential as an activator of the fibrinolytic system when given by intramuscular injection.     

The proteolytic action of ancrod on human fibrinogen and its polypeptide chains

The digestion of human fibrinogen and fibrin by the coagulant enzyme ancrod (Arvin) was studied, and by use of polyacrylamide gel electrophoresis in sodium dodecyl sulphate (SDS) the molecular weights of subunit polypeptides and digestion products were estimated. Ancrod attacked only the α (A) chain of human fibrinogen to produce a polypeptide of molecular weight 39,000 which was bound within the clot, and also a free polypeptide of 31,000 which appeared in the supernatant and was further digested to fragments of 27,000, 25,000, 16,000 and about 10,000. Ancrod in higher concentrations also digested the α polymers of crosslinked fibrin producing fragments similar to those from the α (A) monomer but differing in their distribution between clot and supernatant. Digestion of the separated α (A), β (B) and γ chains of S-carboxymethyl fibrinogen by ancrod showed the α (A) chain to be the most susceptible to proteolysis and that the same digestion products were formed as from the intact fibrinogen molecule. Additionally, limited proteolytic digestion of the separated γ chain was observed.