Comparative genomic hybridisation of ductal carcinoma in situ of the breast: identification of regions of DNA amplification and deletion in common with invasive breast carcinoma

Comparative genomic hybridisation has been used to map copy number changes in nine cases of ductal carcinoma in situ of the breast obtained from wax-embedded archive material. A wide variety of abnormalities were detected including gain of regions of 1q, 17q, 19q, 20p and 20q and loss on 13q, 14q, 17p, 16q and 22q. Amplification of areas on 10p, 8q and 20q were also observed. Chromosomal alterations were more frequent in higher grade DCIS and closely resemble those previously detected in invasive breast cancer using the same technique. These data provide strong molecular support for the view that DCIS is a precursor lesion of invasive breast carcinoma.     

The relationship between body dysmorphic disorder and depression, self-esteem, somatization, and obsessive-compulsive disorder

Voice disorders are thought to be one of the major occupational hazards of school teaching. The resulting symptoms can affect teachers' ability to function in the classroom and prevent them from developing effective working relationships with other staff and students. Sick leave, speech pathology management, and surgical intervention can be costly. Severe voice problems can also result in a teacher permanently leaving the classroom. Despite the significant implications of voice disorders for teachers, this review of published research demonstrates that findings concerning the prevalence of voice problems in teachers and the causes and contributing factors of those voice problems are inconclusive. Similarly, previous research on the efficacy of prevention programs and treatment of voice problems in teachers provide few firm conclusions. Further research based on sound empirical data is needed, as many past studies have relied on anecdotal or self-report data. More operational definitions of what constitutes a voice disorder and the associated contributing factors should be adopted, along with the use of more instrumental measures and careful attention to methodology and appropriate statistical analyses. Only then will we have a sound basis for the development of effective prevention and education programs for teachers.     

Incidence and clinical consequence of the purple glove syndrome in patients receiving intravenous phenytoin

OBJECTIVE: To determine the incidence, risk factors, and long-term sequelae of the purple glove syndrome (PGS) in hospital patients receiving IV phenytoin. BACKGROUND: PGS is a poorly understood, potentially serious local complication of IV phenytoin administration characterized by progressive distal limb edema, discoloration, and pain. METHODS: The pharmacologic records of the Mayo Foundation hospitals were reviewed to identify 179 consecutive patients who had IV phenytoin ordered during a 3-month period. Their hospital records were then reviewed to confirm IV phenytoin treatment, the frequency of PGS (defined as the progressive development of edema, discoloration, and pain in the limb after administration of IV phenytoin), and the outcome of PGS. RESULTS: A total of 152 patients received IV phenytoin, and nine (5.9%) developed PGS. PGS patients received a greater median initial dose of phenytoin, total 24-hour dose, and total number of doses (all p < 0.05). In addition, the median age of the PGS patients was older, their infusion was more often given for acute seizures, it was less likely to be administered in the operating room, and the length of their hospital stay was longer (all p < 0.05). One patient required surgical therapy, and all other patients resolved within 3 weeks with conservative management. CONCLUSIONS: PGS is not rare and elderly patients and individuals receiving large, multiple doses are particularly at risk. This iatrogenic complication may be preventable by substituting fosphenytoin for IV phenytoin.     

T cell receptor peptide vaccination in rheumatoid arthritis: a placebo-controlled trial using a combination of Vbeta3, Vbeta14, and Vbeta17 peptides

OBJECTIVE: Restricted T cell receptor (TCR) gene usage has been demonstrated in animal models of autoimmune disease and has resulted in the successful use of TCR peptide therapy in animal studies. This clinical trial was undertaken to determine the safety and efficacy of a combination of Vbeta3, Vbeta14, and Vbeta17 TCR peptides in Freund's incomplete adjuvant (IFA) in patients with rheumatoid arthritis (RA). METHODS: A double-blind, placebo-controlled, multicenter, phase II clinical trial was undertaken using IR501 therapeutic vaccine, which consists of a combination of 3 peptides derived from TCRs (Vbeta3, Vbeta14, and Vbeta17) in IFA. A total of 99 patients with active RA received either 90 microg (n = 31) or 300 microg (n = 35) of IR501 or IFA alone (n = 33) as a control. The study medication and placebo were administered as a single intramuscular injection (1 ml) at weeks 0, 4, 8, and 20. RESULTS: Treatment with IR501 was safe and well tolerated. None of the patients discontinued the trial because of treatment-related adverse events. Efficacy was measured according to the American College of Rheumatology 20% improvement criteria. Using these criteria, patients in both IR501 dosage groups showed improvement in disease activity. In the most conservative analysis used to evaluate efficacy, an intent-to-treat analysis including all patients who enrolled, the 90-microg dosage group showed a statistically significant improvement compared with control patients at the 20-week time point after the third injection. Trends toward improvement were shown in both the 90-microg and the 300-microg dosage groups at week 24 after the fourth injection. CONCLUSION: IR501 therapeutic vaccine therapy was safe and well tolerated, immunogenic, and demonstrated clinical improvement in RA patients. Additional clinical trials are planned to confirm and extend these observations.     

Murine strain differences in the volume effect and incidence of radiation-induced colorectal obstruction

We have previously reported high levels of the coagulation inhibitor TFPI in the blood of patients with gastrointestinal cancer. TFPI is not an acute-phase reactant, but high levels have also been reported in patients with septicaemia and disseminated intravascular coagulation (DIC). To study its relationship with other types of malignancy, TFPI activity was first determined in plasma samples from 214 patients with various malignancies. In a second cohort of 83 patients, total and free TFPI antigen, protein C, antithrombin, fibrin monomer and D-dimer were also measured. Elevated TFPI activity and antigens were found in about half of the patients with solid tumours. In contrast, elevated TFPI was rare in haematological malignancies (12%). In the 18 patients with acute nonlymphocytic leukaemia (ANLL), elevated free TFPI was found only in patients who also had DIC. No correlation was found between TFPI levels and fibrin monomer or D-dimer levels. Only four out of 20 patients with solid tumours had normal levels of fibrin monomer and D-dimer, yet three out of these four had elevated TFPI. In conclusion, elevated TFPI in ANLL is related to the coexistence of DIC. In solid tumour disease increased TFPI may reduce protective fibrin formation, but the pathogenic mechanism is as yet unknown.     

Don''t McMuff it

A syndrome of deep pain in the breast during and immediately after lactation has been ascribed to an infection with Candida albicans. A series of 20 patients with deep pain, another 20 with superficial infection and 20 healthy women were compared with respect to the growth of bacteria and fungi. C. albicans was found twice as often in the milk of women with superficial lesions compared to those with deep pain. Bacteria were often found on the nipple and in the milk of those complaining of deep pain. Thus, if the deep pain syndrome is caused by microbes, this study points to a pathogenic role of bacteria rather than fungi.     

Refractive index matching and clear emulsions

Refractive index (RI) matching is a unique way of making clear emulsions to meet market trends. However, RI matching has not been sufficiently investigated in terms of physical principles and methodologies. Snell's law ( n 2 sin r 2 =  n 1 sin r 1) is applicable to cosmetic emulsions. When oil phase and water phase have equal RI ( n 2 =  n 1) values, light will not bend as it strikes obliquely at the emulsion interface. Instead, light is transmitted through the emulsion without refraction, which produces clarity. Theoretical RI values in solution can be calculated with summation of the product of the weight percentage and refractive index of each ingredient ( RImix  = [ W 1 ×  n 1 +  W 2 ×  n 2 + W 3 ×  n 3 + +  Wn  ×  nn ]/ WT ). Oil-phase RI values are normally at 1.4 or higher. Glycols are used to adjust the water phase RI, since they typically have larger RI values than water. Noticeable deviations from calculated RI values are seen in experimentally prepared solutions. Three basic deviation types are observed: negative, positive, and slightly negative or positive, which can occur in glycol aqueous solutions at different concentrations. The deviations are attributed to changes in molecular interaction between molecules in solution, which can lead to changes in specific gravity. Negative RI deviation corresponds to a decrease in specific gravity, and positive RI deviation corresponds to an increase in specific gravity. RI values will deviate from calculated values since an increase or decrease in specific gravity leads to a change in optical density.     

Hydrophobic effects on antibacterial and channel-forming properties of cecropin A-melittin hybrids

The efficacy and tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle, rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post- and menstrual periods; possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptoms. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24, 24/24 and only 2 out of the 24 patients, respectively. Concomitant symptoms consisted in headache (12), mastalgia (14) and discomfort (12). Results were obtained by averaging the data from the treatment periods with each drug. Menstrual pain was reduced from 2.9 +/- 0.7 to 1.9 +/- 0.7 with P administration and to 0.66 +/- 0.4 with the administration of LC, a highly significant difference between treatments (p < 0.0001). Premenstrual pain was reduced nonsignificantly from 0.79% to 0.58% with P administration and significantly to 0.29% with administration of LC (p < 0.001). Intramenstrual pain affecting all patients at baseline was reduced significantly by 9% with P and also significantly by 50% with LC (p < 0.001). No differences were encountered in concomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p < 0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported.