Basic isoferritin and hypercalcaemia in renal cell carcinoma

A 63-year-old man with iron loss anaemia and hypercalcaemia was found to have a renal cell carcinoma. Despite the iron-deficient blood and bone marrow picture, the serum ferritin concentration was markedly raised. This was mainly due to a “basic isoferritin”. The serum parathormone concentration was normal. The serum ferritin and calcium concentrations returned to normal after the tumour was removed. We propose that the renal cell carcinoma cells in this patient secreted the basic isoferritin as well as humoral factor(s) responsible for hypercalcaemia.     

Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.      

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

Impact of an oncology pharmacy residency training program on quality improvement initiatives in an oncology center

The concept of quality care is something every patient expects, regardless of how they enter the health care system. The specialty-trained oncology pharmacy practitioner possesses many skills to offer the patient and other health care practitioners. Oncology pharmacy residency training involves specific types of learning situations and experiences, which will be critical for future roles the specialty resident may assume. Oncology practice is an area requiring a high level of care for patients, and highly skilled pharmacy practitioners are crucial for the care of these patients.     

Growth monitoring with the British 1990 growth reference

AIM: To provide a simple method for assessing centile change based on the British 1990 growth reference. STATISTICAL METHOD: The change in SD score over a period of time has SD square root of 2(1-r), where r is the correlation between the first and second SD score. This leads to an SD score for centile change. DATA: Annual height measurements from 2 to 9 years for 318 children from the French longitudinal growth study. RESULTS: The correlations between heights at different ages are higher for shorter measurement intervals and at older ages. The chance of a child's height centile falling one centile band width is correspondingly smaller for shorter measurement intervals and at older ages. An increase in height measurement error reduces the correlations and dramatically increases the chances of centile crossing. CONCLUSIONS: Quantitative height monitoring based on centile change is provided for whole year periods between 2 and 9 years of age. Effective monitoring requires the measurement error to be as small as possible.