BB-10010 is a genetically engineered variant of human macrophage inflammatory protein-1 alpha (hMIP-1 alpha) with improved pharmaceutical formulation properties. Although initially described as a pro-inflammatory cytokine, it is now recognised that hMIP-1 alpha has additional effects on haemopoietic stem cell cycling and on human immunodeficiency virus uptake by macrophages. In view of the potential clinical utility of the molecule, we have embarked on a clinical trials programme to evaluate the safety, tolerability and haematological effects of BB-10010. We now report the results of two phase I clinical studies in which 49 subjects (9 patients with advanced breast carcinoma and 40 normal healthy volunteers) received escalating doses of BB-10010, from 0.1 to 300 micrograms/kg using the subcutaneous (s.c.) or intravenous route (i.v.) of administration. Treatment was associated with a dose-related increase in monocyte count which peaked at 200% of steady-state levels and was preceded by an acute, short-lived, monocytopenia, 50-100% of baseline. no measurable effects were noted on other leucocyte subsets or on circulating progenitor cell numbers. In all cases, BB-10010 was extremely well tolerated with no significant toxicity observed at any dose level and a maximum tolerated dose was not defined. Pharmacokinetic analysis revealed that serum concentrations of BB-10010 were detectable using doses of > or = 10 micrograms/kg i.v. or > or = 30 micrograms/kg s.c., and that a single s.c. injection resulted in sustained plasma levels over a 24 h period. These preliminary studies have confirmed the safety and tolerability of BB-10010 using a dose range up to 300 micrograms/kg. Further clinical studies are ongoing to determine the biological effects and to investigate the potential myeloprotective properties using a variable dose range and schedule of BB-10010 in combination with cytotoxic chemotherapy.

Adult↗

PubMed1998

Issues of quality and practicability in task analysis: preliminary results from two surveys.

Surveys of task analysis studies in two different industrial sectors within the UK, defence and nuclear power, have shown that there can be wide variability between them, both in terms of level of reporting and the depth of analysis. Particularly prevalent shortcomings were that data sources and methods were often either not specified or were described in insufficient detail. Thus users of the information could be asked to accept potentially costly design recommendations with little indication of the strength of the evidence, or of the effects of taking no action. Some tentative conclusions are drawn about the use of specific task analysis techniques but, while these are useful pointers, more evidence is required. Therefore, further study of task analysis techniques is needed in order to provide analysts with better guidance regarding the selection and use of task analysis methods and the reporting of task analysis findings.

Data Collection↗

PubMed1998

Is forced dextrality an explanation for the fall in the prevalence of sinistrality with age? A study in northern England.

OBJECTIVES: The fall in the prevalence of left handedness with age has been attributed to either premature mortality or a cohort effect of forced dextrality. Evidence for forced dextrality was sought to differentiate between these competing theories. DESIGN: 6097 Edinburgh handedness inventories were used to calculate laterality quotients (LQ) with and without the questions relating to writing and drawing. These questions might be expected to be most influenced by forced dextrality. SETTING: The study was performed in a small industrial town in Lancashire, UK. PARTICIPANTS: Using the British family practitioner service where over 95% of the population are registered with a general practitioner a response rate of 82.17% was obtained with respect to the Edinburgh Inventory. RESULTS: Questions about writing and drawing on the Edinburgh Inventory contributed to the positivity (right handedness) of the mean LQ, but equally across the ages. When a negative LQ was used to define left handedness the prevalence of left handedness fell from 11.2% at age 15 to 4.4% at age 70. Removal of the questions about writing and drawing caused the prevalence of left handedness to fall from 10.5% at age 15 to 4.95% at age 70. CONCLUSIONS: Less than 20% of the fall in the prevalence of left handedness was accounted for by questions relating to writing and drawing. The fall in the prevalence of sinistrals in older age groups is not adequately explained by cohort effects of forced dextrality on the writing hand.

Adolescent↗

PubMed1997