Recent advances of genetic ancestry testing in biomedical research and direct to consumer testing

In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable.     

Egg sharing and egg donation: attitudes of British egg donors and recipients

The question of payment to egg donors has recently focused the attention of both the Human Fertilisation and Embryology Authority (HFEA) and licensed clinics. An acute shortage of egg donors and the rising costs of assisted conception treatment are matters of grave concern to many patients. To understand the emotional and social effects of egg sharing and egg donation, we conducted a survey of attitudes in a group of women who had some knowledge or experience of egg donation. A total of 750 questionnaires were sent out of which 217 were returned within the specified time limit. From these, 107 respondents had experience of egg donation and 110 had made enquiries about donation. The data from these questionnaires were collated and tabulated by the National Opinion Polls (NOP) Research Group. An analysis of the data produced the following key findings: (i) donating or sharing eggs is a social issue, 94% discuss it with partners/family/friends; (ii) altruistic motives are not the prerogative of non-patient volunteers-egg share donors felt that helping the childless was as important as having a chance of in-vitro fertilization (IVF) for themselves; (iii) the treatment procedure causes the most anxiety for egg donors. The recipients were most concerned about delays, donor characteristics and how the eggs were allocated; (iv) most respondents (65%) with prior experience of egg sharing would do it again - 63% of egg share donors, 72% of egg share recipients; (v) cash rewards to egg donors and outright advertising for donors were rejected by 64 and 62% of the sample respectively; and (vi) counselling was highly valued and there were no instances of 'shattered lives' after treatment. The findings do not support the recently announced intentions of the HFEA to disallow payment to gamete donors on the grounds of devalued consent. There is no precedent in modern medicine for egg sharing. The patients surveyed drew a clear distinction between egg sharing and financial rewards. As long as egg donation is not covered by the National Health Service, it is fairer to offer egg sharing than to refuse treatment to those unable to pay.      

Outcomes of re-excision after unplanned excisions of soft-tissue sarcomas

BACKGROUND AND OBJECTIVES: Unplanned excisions of soft-tissue sarcomas of the extremities occur commonly. Our goal was to evaluate the presence of residual disease, the treatment outcomes as they relate to local and distant recurrence and 5-year survival, and the limb functional outcomes in patients with unplanned sarcoma excision who were treated with re-excision and adjuvant therapy. METHODS: Between 1993 and 1999, 42 patients presented to our institution after unplanned excision of soft-tissue sarcomas. Of those 42 patients, 38 without gross residual disease or metastatic lesions formed the basis of this review. All 38 patients underwent revision wide excision; most (31) also received adjuvant therapy (radiation and/or chemotherapy). Clinical data were obtained from analysis of patient records and radiographic studies. Univariate analysis was performed with logistical regression, and multivariate analysis was performed with Cox modeling. RESULTS: The overall 5-year survival rate was 91.3% and the disease-free 5-year survival rate was 82.2%. Univariate analysis showed that stage-III disease (American Joint Committee on Cancer classification of soft-tissue sarcomas), lesions below the fascia, a histologic high-grade, and the development of organ metastasis were statistically significant factors for mortality. Stage-III disease also was significant for mortality on multivariate analysis. Only stage-III disease was significant for the development of local recurrence. Eighty-four percent of the patients had good to excellent functional outcomes. CONCLUSIONS: Re-excision with adjuvant therapy proved to be a safe and effective method for treating the disease and preserving limb function.     

Inhibitory synaptogenesis in mouse somatosensory cortex

It is widely believed that inhibitory synapses are not present or present in only small numbers in the rodent cerebral cortex during the early postnatal period when the cortex is being innervated by thalamocortical fibers. Quantitative electron microscopy was carried out on the posteromedial barrel subfield of mouse somatosensory cortex from postnatal day 4 (P4) when thalamocortical innervation of the barrels is becoming established, through to sexual maturity (>P32), and in adulthood. Both asymmetrical (putatively excitatory) and symmetrical (putatively inhibitory) synapses were present in all layers from P4. The symmetrical synapses were immunoreactive for GABA at all ages. There was a progressive increase in both asymmetrical and symmetrical synapses up to P32, density in all layers increasing 16-fold, with the production of asymmetrical synapses leading and greatly outstripping that of symmetrical. From P32 to P120, the oldest age studied, synaptic numbers declined by 18% to 13 times the P4 level, but this affected predominantly layers II/III, IV and V, and mainly involved asymmetrical synapses. The relative percentage of asymmetrical to symmetrical synapses from P4 to P8 was 57%/43% but at P32 it was 89.5%/10.5% and in adulthood 85.4%/14.6%. These data indicate that inhibitory synaptogenesis in the rodent cortex begins earlier than previously thought, a basis for inhibition being present from the earliest period. Pruning of all synapses occurs well after thalamocortical innervation is established and inhibitory synapses are less affected by the pruning process.      

Tailored hormonal therapy in secretory adrenocortical cancer

Mitotane is often considered the front-line hormonal therapyof adrenocortical carcinoma (ACC). An illustrative case concerningthis issue and the rationale to ponder other alternatives isreported. A 69 year-old woman, diagnosed with ACC was admittedwith hypertensive crisis, supraventricular tachycardia, congestiveheart-failure, diarrhoea and rabdomyolisis. Two years earlier,she had undergone     

A clinical,randomized study on the influence of dental whitening on Streptococcus mutans population

Background

Dental whitening with peroxides has been popularized through the at‐home technique, which employs low concentrations of peroxide applied in individual trays. However, there are few clinical trials reporting the effects of its continuous use on oral microbiota. Thus, the purpose of the present clinical, randomized study was to evaluate the influence of at‐home whitening treatment on Streptococcus mutans in saliva, buccal mucosa, and subgingival and supragingival plaque.

Methods

Thirty volunteers were randomly divided into two study groups (N = 15) according to the whitening therapy: G CP, whitening using 10% carbamide peroxide 4 h daily for 21 days; and G HP, whitening using 6% hydrogen peroxide 1.5 h daily for 21 days. Samples from the predetermined locations were collected at three evaluation periods: T1, before; T2, immediately after; and T3, 30 days after the beginning of the treatment. The microbiological evaluation was made using conventional and molecular methods.

Results

Student's t‐test demonstrated a statistically significant decrease in S. mutans population in the subgingival and supragingival plaque for HP samples between T1 and T2 no difference was found between T1 and T3 regardless of the location and the whitening product used (α = 0.05).

Conclusions

Although HP reduced S. mutans during treatment, the levels returned to baseline when assessed 30 days after the treatment.     

Airway pressure and transpulmonary pressure during high-frequency oscillation for acute respiratory distress syndrome

High-frequency oscillation is a novel form of ventilation increasingly being used to treat refractory hypoxic respiratory failure resulting from acute lung injury or acute respiratory distress syndrome. Although there is no known relationship between airway pressure and transpulmonary pressure during conventional mechanical ventilation, no study has attempted to determine transpulmonary pressure during high-frequency oscillation.

BACKGROUND:

High-frequency oscillation (HFO) is used for the treatment of refractory hypoxic respiratory failure.

OBJECTIVE:

To demonstrate that the mean transpulmonary pressure (P_L) cannot be inferred from mean airway pressure (mPaw).

METHODS:

In seven patients already undergoing HFO for refractory acute respiratory distress syndrome, esophageal pressure (Pes) was measured using an esophageal balloon catheter. Pleural pressure (Ppl) and P_L were calculated from Pes.

MAIN RESULTS:

In the seven patients (mean [± SD] age 59±9 years) treated with HFO at 5±1 Hz and amplitude 75±10 cmH₂O, the mPaw was 27±6 cmH₂O, Ppl was 9±6 cmH₂O and P_L was 18±11 cmH₂O. Successful catheter placement and measurement of Pes occurred in 100% of subjects. There was no correlation between P_L and mPaw. The majority of subjects required hemodynamic support during the use of HFO; the frequency and degree of support during the study period was no different than that before the study.

CONCLUSION:

The present report is the first to describe measuring Pes and calculating Ppl during HFO for acute respiratory distress syndrome. While both current guidelines and recent trials have titrated treatment based on mPaw and oxygenation, there is wide variability in P_L during HFO and P_L cannot be predicted from mPaw.     

Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients

Initial studies have shown that recombinant human interleukin-6 (rhIL- 6) induces anemia. Until now, the pathophysiologic mechanism of this induced anemia has been unknown. To unravel the underlying mechanism, we examined 15 cancer patients receiving rhIL-6 as an antitumor immunotherapy in a phase II study. rhIL-6 was administered subcutaneously at 150 micrograms once daily for 6 consecutive weeks. Various hematologic and biochemical parameters were measured weekly during rhIL-6 treatment and 4 weeks after rhIL-6 discontinuation. To determine plasma volume and red blood cell (RBC) volume, radioisotope dilution assays with labeled autologous RBCs and with human serum albumin were performed before rhIL-6 administration and on day 8 of rhIL-6 therapy. Hemoglobin levels decreased (mean change +/- SE) 7% +/- 1.5% within 3 days after the start of rhIL-6 therapy (P < .0001) and 19% +/- 2% at week 4. Levels had normalized at follow-up. The plasma volume increased 18% +/- 5% during the first week of rhIL-6 administration (P < .003), whereas RBC volume remained unaffected. The mean RBC corpuscular volume remained unchanged for 2 weeks and then began to decrease slowly, reaching its nadir at week 6 (5% +/- 1%; P < .01). Serum iron levels decreased 65% +/- 12% at week 4 (P < .002) and then returned to initial baseline values. Erythropoietin levels increased rapidly up to 68% at week 3 (P < .0001) and had normalized 4 weeks after rhIL-6 therapy. Levels of serum albumin, prealbumin, and transferrin decreased (P < .0001, P < .003, and P < .0001, respectively), whereas levels of serum amyloid A (P < .003), C-reactive protein, haptoglobin, and alpha-1-antitrypsin (P < .0001) increased during rhIL-6 treatment. All levels returned to pretreatment values after discontinuation of rhIL-6. No alterations in reticulocyte counts, serum lactic dehydrogenase levels, and bilirubin levels were observed. A 6-week regimen of subcutaneous rhIL-6 results in a rapid dilution anemia, caused by an acute and significant increase in plasma volume and followed by hypoferremia. This anemia is reversible after the cessation of rhIL-6 treatment.