CD14 and TNfa promoter polymorphisms in patients with acute arthritis. Special reference to development of chronic spondyloarthropathy

OBJECTIVE: To examine CD14 and TNFalpha gene polymorphisms in early arthritis in relation to clinical outcome. METHODS: We studied 141 Caucasians who had had early arthritis 10 to 38 years earlier. We analysed CD14 (-159) and TNFalpha (-238, -308, -376) polymorphisms using a novel cycle minisequencing method. DNA pools from 370 Caucasian blood donors served as controls. RESULTS: CD14 (-159)C-->T allele frequencies were comparable among patients and controls (39% vs 40%). Fifty men and 42 women had recovered while 24 men and six women had chronic spondyloarthropathy (SpA). Mutant T allele frequency was higher in the chronic SpA group than in the recovered group in women (75% vs 32%, relative risk 1.3, 95% confidence limit 1.1 to 1.6, P = 0.011), but not in men (38% vs 44%). All female patients with chronic SpA had CD14 (-159)T allele and none had a possibly protective TNFalpha (-308)G-->A allele. CONCLUSIONS: Possession of CD14 (-159)T allele does not increase risk of ReA but may increase susceptibility of female patients to development of chronic SpA.     

Acute anemia in high digestive hemorrhage. Margins of security for their handling without transfusion of red globules

Red cells transfusion in the patient with acute hemorrhage, must be evaluated in a risk/benefit rate context. The present tendencies appoint that the use of the hematocrit "magic" number is unsafe and uncertain to decide a red cell transfusion. We have conducted a prospective randomized and controlled trial in 60 patients with acute digestive hemorrhage without haemodynamic failure. We realized two groups: 1) control group: the target of transfusion in these patients was the hematocrit value of > or = 28%. 2) treatment group: these patients were supported with normovolemic haemodilution with crystalloid solutions until a hematocrit value of 21%. All patients have endoscopic diagnosis and they went evaluated across the study with clinic and laboratory controls. Both groups were significative differences in the hematocrit value. We did not see differences between the groups in the hospital stay neither the rate of organs failure. We find difference between the groups in the amount of red cell units (0.61 +/- 0.87 vs. 2.14 +/- 1.10; treatment and control respectively, P < 0.001). The APACHE score was greater in the treatment group. This supports that the oldest patients, who probably have least physiologic reserve, could be treated without complications. Acute hemorrhage-normovolemic haemodilution-digestive hemorrhage transfusion.     

Respiratory sinus arrhythmia as a predictor of sudden cardiac death after myocardial infarction

Background. Measurement of high-frequency (HF) spectral power of heart rate (HR) variability has not been able to identify the patients at risk of sudden cardiac death (SCD) despite the experimental evidence of protective role of vagal activity for fatal arrhythmias.

Aim. We developed a novel respiratory sinus arrhythmia (RSA) analysis method and tested its ability to predict SCD after an acute myocardial infarction.

Method. The RSA analysis method was developed in 13 subjects from simultaneous recordings of respiration and R-R intervals. An adaptive threshold was computed based on the zero-phase forward and reverse digital filtering in the analysis of RSA. With this method, only respiration-related R-R interval fluctuations are included. The prognostic power of RSA, analyzed from 24-hour electrocardiographic recordings, was subsequently assessed in a large postinfarction population including 1631 patients with mean follow-up of 40±17 months.

Results. Depressed RSA was a strong predictor of SCD (hazard ratio 7.4; 95% CI 3.6–15.1; P <0.0001) but only a weak predictor of non-SCD. The RSA index remained an independent predictor of SCD after adjustments for ejection fraction and other clinical risk variables (RR 4.7; 95% CI 2.28–9.85).

Conclusions. Reduced respiratory-related HR dynamics, detected by RSA index, are a specific marker of an increased risk of SCD among postinfarction patients.     

Cosmetic results after wire-guided biopsy of benign breast lesions

Background: There are surprisingly few reports about the cosmetic results of wire-guided biopsy of benign breast lesions as opposed to breast-conserving surgery and irradiation of early breast cancer (BCT).

Study Design: Twenty potential perioperative risk factors for adverse cosmetic results after wire-guided breast biopsy were prospectively evaluated in 101 patients undergoing the first single biopsy after suspicion of a malignant lesion that subsequently proved to be benign. The overall cosmetic result was evaluated by using 6 specific cosmetic indices individually scored 6 months after the breast biopsy.

Results: The overall cosmesis was excellent, good, fair, or poor in 48.5%, 26.7%, 12.9%, and 11.9% of cases, respectively. The corresponding figures according to appraisal by the patients were 22.8%, 58.4%, 17.8%, and 1.0%, respectively. Unsatisfactory (fair or poor) overall cosmetic results were related to excisions extending down to the fascia (p = 0.001) and postoperative complications (p = 0.018) in multivariate analysis. Notably, specimen volume had no significant impact on overall cosmesis, as opposed to cosmesis after BCT.

Conclusions: Cosmetic outcomes after wire-guided biopsy of benign breast lesions were excellent or good in at least 75% of cases. Excisions extending down to the pectoralis fascia and complications were associated with poor aesthetic outcomes.     

Minimizing systemic absorption of topically administered ophthalmic drugs

Due to absorption several ocularly applied medications give rise to systemic side-effects. The problem of systemic drug absorption should be taken into account in designing ocular drug and dosage forms so that oculospecificity of the medications is optimized. In this review we summarize the current knowledge about the systemic absorption of ocularly applied topical drugs. Special emphasis is directed to the methods that can be used to minimize systemic absorption and increase the oculospecificity of drugs, e.g., reducing volume and increasing viscosity of eyedrops, controlling drug release from depot preparations, prodrug-derivatization, and addition of vasoconstrictive agents.     

Mothers' perceptions of and feelings towards their babies' crying

The frequency and type of crying and the parents' perceptions of it were evaluated in 281 Finnish infants underthe age of 1 year. Not many mothers [14#pc] claimed that their babies cried often or very often. The infants less than three months old cried significantly more in the evening than the older ones. Most mothers [94#pc] reported that the crying aroused feelings of tenderness, but 4#pc found it irritating. The most common response to the cry [97#pc] was to pick the baby up. Additional help was wanted by 49 mothers because of their babies' disturbing crying spells. These mothers reorted that their infants cried more and they stated that the cry made them feel more irritated and more often gave them a feeling of failure than the mothers not in need of help. The majority of these mothers would have been glad to help, including advice, whent the infants were under 3 months of age.     

Traumatic fistula between the left anterior descending coronary artery and a left ventricular pseudoaneurysm

A 44-year-old man presented with a fistula of the left anterior descending (LAD) coronary artery to a left ventricular pseudoaneurysm 6 months after a stab injury in the left anterior chest. The color Doppler echocardiography suggested, and angiography confirmed, the diagnosis and the lesion was treated successfully. Traumatic coronary artery fistulas are rare complications, and color Doppler echocardiography proved useful for the diagnosis. Received: 0/00/00/Accepted: 0/00/00     

Pilocarpine release from hydroxypropyl-cellulose-polyvinylpyrrolidone matrices

Characteristics of pilocarpine release from cast plasticized hydroxypropylcellulose (HPC) and HPC-polyvinylpyrrolidone (PVP) matrices were studied using tritiated pilocarpine. Increased concentration of PVP and decreased molecular weight of HPC accelerated release of pilocarpine from the matrices. The aqueous solution penetrated rapidly into the matrices, which swelled rapidly to their equilibrium volumes. With increased molecular weight and concentration of HPC in the matrices, the rate of solvent penetration decreased and swollen volume of the matrix increased. Pilocarpine concentration also decreased in the ungelled cores of the matrices, indicating that the solvent had penetrated these cores. Solvent penetration alone did not control the rate of drug release, because penetration was at least twice as rapid as pilocarpine release. In the matrices without polymer dissolution, the best fits of the release data were obtained with diffusional square-root of time dependence, although relaxation of the polymers caused slight deviations from the Fickian diffusion. Thus the rate-limiting step of pilocarpine release was the diffusion of the drug from the matrix. The decreased rate of pilocarpine release with increased molecular weight and concentration of HPC was due to the decreased rate of drug diffusion from the matrix. Retardation of this diffusion was caused by the increased swelling of the matrix and decreased diffusivity of the drug. High initial concentration of PVP resulted in substantial deformation and attrition of the matrices.     

Nandrolone decanoate added to tamoxifen in the treatment of advanced breast cancer

Summary Since 1980 we have been carrying out a prospective randomized trial comparing tamoxifen with the combination of tamoxifen plus nandrolone decanoate in advanced breast cancer. The tamoxifen dose is 30 mg daily and the nandrolone decanoate dose 100 mg i.m. once a week for four weeks and thereafter every other week. 98 post-menopausal patients have been evaluated for the response. The number of patients is 49 in both groups.The overall response rates (CR +PR) to tamoxifen and tamoxifen plus nandrolone decanoate were not significantly different; in the tamoxifen group the response rate was 49% and in the combination group 45%. The mean time to progression in tamoxifen group is over 13 months and in tamoxifen plus nandrolone decanoate group over 12 months. Our results do not suggest a synergistic effect from combining tamoxifen and nandrolone decanoate treatments. The response rates to tamoxifen at different sites of metastases were as follows: bones 47%, soft tissues 56%, and viscera 48%. The respective figures with the combination therapy were 36%, 64%, and 40%.Both treatments were well tolerated and in no patient was withdrawal of the therapy necessary. Mild virilization and hoarseness were experienced by all patients treated with nandrolone decanoate. Side-effects associated with tamoxifen were rare, although five patients experienced nausea and two had hot flushes.