Routine blood monitoring in maintenance immunoglobulin treatment of inflammatory neuropathy: Is it clinically relevant?

BACKGROUND: Pre-treatment screening for IgA deficiency and close monitoring of full blood count(FBC) and renal function is recommended with intravenous immunoglobulin(IVIg) therapy in neurological diseases. AIMS: To examine the frequency of biochemically defined and clinically significant episodes of treatment associated haemolysis, neutropenia, thrombocytopenia and acute kidney injury(AKI) in a cohort of patients on maintenance Immunoglobulin(Ig) therapy for inflammatory neuropathy. METHODS: A retrospective review of routine blood monitoring in patients from two UK specialist peripheral nerve centres. Accepted definitions for clinically and biochemically significant haemolysis, neutropenia, thrombocytopenia and AKI were used. RESULTS: 1919 infusion episodes in 90 patients were analysed. Age(mean(S.D)) = 58.09(14.4)years, 63% male, 72% CIDP(28% MMN), 97% IVIg(3% SCIg). Dose = 1.57(0.79)g/kg/month or 97.1(37.3)g/infusion, frequency:3.9(1.4) weeks. Relative IgA deficiency was noted in 2 individuals (prevalence:2.2%, 95%C.I.:0-5.2) who received a combined total of 38 infusions(3800 g IVIg) without adverse event. No clinically significant episodes of haemolysis, neutropenia, thrombocytopenia or AKI occurred in relation to treatment. An asymptomatic drop>10 g/L haemoglobin(Hb) occurred in 3.5%(95%CI:2.7-4.3) of treatment episodes in 38 individuals, mean reduction:17.7(7.4)g/L; lowest Hb:86 g/L. Lower pre-treatment haemoglobin correlated with risk of recurrent Ig-related drop(p:0.007). Two patients with chronic renal failure(stage 1 and 3) received 28(IV) and 104(SC) infusions respectively(6416 g) without impact on estimated glomerular filtration rate(eGFR). CONCLUSIONS: No clinically significant Ig-related episodes of haemolysis or AKI were identified in this representative cohort. This suggests that routine monitoring is not essential in long-term Ig use but should be considered when clinically indicated.

Long-term follow-up of Morton's neuroma.

The long-term results of neurectomy are evaluated in 70 symptomatic Morton's neuromas in 53 patients with an average postoperative follow-up of 4.8 years, and a maximum of 8.6 years. The presentation, number, and location of neuromas in this series, in some instances, coincides with previous publications. Neurectomy, by means of a dorsal approach, provided 93% patient satisfaction at long-term follow-up.

Freiberg's disease in diabetes mellitus.

We evaluated a total of 13 cases of Freiberg's disease in patients aged 47-77 years collected over an 8-year period. Seven were associated with diabetes mellitus and one with chronic renal failure; the remainder had no underlying disease. Atrophy of intrinsic small foot muscles secondary to neuropathy, which is prevalent in diabetes mellitus, may play a part in the development of Freiberg's infraction.

The proto-oncogene c-fos is over-expressed in the majority of human osteosarcomas.

The expression of fos protein was examined in 30 cases of human osteosarcoma as formalin-fixed and paraffin-embedded tissue sections using two monoclonal antibodies and, for five cases, as frozen sections using 3 polyclonal antibodies. Nuclear antibody labeling intensities were determined either by visual scoring (3 pathologists) or by microdensitometry and included over 700 tumor, 350 normal and 150 benign tissue observations. Visual scores were shown to be linear with optical density with a correlation coefficient of 0.97. Analysis of the osteosarcoma cases at one antibody concentration revealed two groups: a minority (39%) with a low average visual score of 2 +/- 0.2 which was very similar to benign and normal tissues, and a majority (61%) with an average score of 3.1 +/- 0.3. The difference is highly significant (t-test), P less than or equal to 0.01. The results were supported by an analysis of partial immunotitration curves using a curve-fitting procedure which yielded estimates of FOSo (maximum relative fos protein concentration) which were ca. 150% increased for the majority tumor group compared to the minority group or benign or normal tissues. In previous studies of v-sis transformed cells, which exhibit ca. 300% over-expression of c-fos protein as observed here, antisense techniques were used to show that over-expression leads to increased growth and loss of contact inhibition. Thus the combined results suggest that steady state c-fos protein is significantly elevated in, and may contribute to, the aggressive growth properties of a majority of human osteosarcomas.