However, the clinical preparations prepared from such insulins differ from endogenous human insulin in several important respects; an example is the absence of C-peptide which has in recent years been shown to have systemic effects itself. Novo Nordisk has also developed a genetically engineered insulin independently using a yeast process.According to a survey that the International Diabetes Federation conducted in 2002 on the access to and availability of insulin in its member countries, approximately 70% of the insulin that is currently sold in the world is recombinant, biosynthetic human insulin. A majority of insulin used clinically today is produced this way, although clinical experience has provided conflicting evidence on whether these insulins are any less likely to produce an allergic reaction. Adverse reactions have been reported; these include loss of warning signs that patients may slip into a coma through hypoglycemia, convulsions, memory lapse and loss of concentration. However, the International Diabetes Federations position statement from 2005 is very clear in stating that "there is NO overwhelming evidence to prefer one species of insulin over another" and "[modern, highly purified] animal insulins remain a perfectly acceptable alternative. "Since January 2006, all insulins distributed in the U.S. and some other countries are synthetic "human" insulins or their analogues.
Persistent polyclonal B-cell lymphocytosis (PPBL) is an anomaly of the human immune system characterized by mildly elevated levels of white blood cells (called leukocytosis), chronic, stable absolute polyclonal B-cell lymphocytosis, elevated polyclonal IgM and binucleated cells. Although cases of non-smoking women or men have been reported, patients are predominantly young smoking women. Signs and symptoms
Ten percent of patients present with splenomegaly and lymphadenopathy. Some patients report a varying degree of fatigue, consistent with a chronic fatigue syndrome, or postviral fatigue as seen in EBV infections while others remain asymptomatic. Genetics
Genetically, PPBL has been associated with a few unusual genetic characteristics. Among them, it is associated with a particular genetic variant of the human leukocyte antigen called HLA-DR7. This variant is normally present in 26% in the Caucasian population. Chromosome analysis has detected an isochromosome +i(3q), with or without premature chromosome condensation. Also, a t(14;18)(q22;21) bcl-2/IgH rearrangement has been described, as usually seen in follicular lymphoma. Immunologically, peripheral B-cells show more functional IgD+ positive CD27 cells than usual. Prognosis
In the followup of 111 patients, most remained stable and event free. However, two patients developed IgM gammopathy 2 lung cancer; one developed cervical cancer and three developed non-Hodgkins lymphoma. The possibility of developing  a clonal proliferation, malignant lymphoma or secondary solid cancer led the authors to conclude not to classify  PPBL as a benign pathology, as has been previously postulated but rather to recommend a careful and continued clinical and biological longterm follow-up. == References ==