Bioreconstructive joint scaffold implant arthroplasty in metacarpophalangeal joints: short-term results of a new treatment concept in rheumatoid arthritis patients

Swanson silicone implant is the "gold standard" of metacarpophalangeal joint reconstruction in rheumatoid arthritis (RA) patients. However, durability problems of silicone implants have led us to develop a new technique based on bioreconstructive implants. PLA96 (poly-L,D-lactide copolymer, L:D ratio of 96:4) scaffolds were engineered. Bioabsorption and substitution of porous PLA96 scaffold with living tissue eventually produce a neojoint. In the current prospective study, 23 RA patients (80 joints) were operated on, using PLA96 implants. Fifteen patients (54 joints) have been monitored for at least 1 year. Pain alleviation was well achieved. Range of motion improvement was emphasized to extension direction of functional arc. The average ulnar deviation was preoperatively 26 degrees, and at follow-up it was 6 degrees. Volar subluxation was noticeable in 56% of joints preoperatively and in 6% at 1-year follow-up. This is the first report of the formation of a living, functional joint in situ by means of a synthetic bioreconstructive joint scaffold. Results of this preliminary short-term study are comparable with previously published data on silicone arthroplasty. However, bioreconstructive prostheses can aid in preventing problems that occur with biostable prostheses. Tissue engineering has created a new era in the reconstruction of damaged joints.     

Effects of carriers and storage of formulation on the lung deposition of a hydrophobic and hydrophilic drug from a DPI

The effects of carriers, the drug:carrier ratio and a 1 month storage period of a formulation in permeable polystyrene tube at 40 degrees C/75% RH on the in vitro pulmonary deposition of model drugs from dry powder inhaler (DPI) were evaluated. Budesonide (hydrophobic) and salbutamol sulphate (hydrophilic) were used as model drugs. Mannitol and glucose were used as the carriers. In addition, lactose 110M was used as the carrier for budesonide. The novel multiple dose Taifun was used as a DPI; Taifun is a breath-actuated inhaler that contains the powder formulation in a reservoir chamber. The respirable fractions (RF%) values of the drugs were determined by the "Andersen" sampler. The RF% values of salbutamol sulphate increased with an increase in the drug:carrier ratio before storage, whereas the drug:carrier ratio did not affect the RF% values after storage. In the case of budesonide, the drug:carrier ratio did not affect the RF% values before storage, instead the RF% values of budesonide increased with an increase in the drug:carrier ratio after storage. The RF% values of salbutamol sulphate decreased after storage of the formulation, this was not dependent on the carrier and the drug:carrier ratio. However, with budesonide the effect of the storage on its RF% values was dependent on which carrier was used and also the drug:carrier ratio. Overall, storage had less effect on the RF% values of budesonide than those of salbutamol sulphate. The highest RF% values of budesonide were obtained when mannitol was used as the carrier. Furthermore, the RF% values of salbutamol sulphate tended to be higher when mannitol was used as the carrier instead of glucose.     

n-3 Fatty acids and 5-y risks of death and cardiovascular disease events in patients with coronary artery disease

BACKGROUND: Data on the association of n-3 fatty acid content in serum lipids with mortality in patients with coronary artery disease (CAD) are limited. OBJECTIVE: We hypothesized that a high proportion of n-3 fatty acids in serum lipids would be associated with reduced risks of death and coronary events in patients with established CAD. DESIGN: We measured dietary intakes via food records and the fatty acid composition of serum cholesteryl esters (CEs) in 285 men and 130 women with CAD (x age: 61 y; range: 33-74 y). The patients participating in the EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) study were followed up for 5 y. RESULTS: During the follow-up, 36 patients died, 21 had myocardial infarctions, and 12 had strokes. The relative risks (RRs) of death adjusted for cardiovascular disease risk factors for subjects in the highest tertile of fatty acids in CEs compared with those in the lowest tertile were 0.33 (95% CI: 0.11, 0.96) for alpha-linolenic acid, 0.33 (0.12, 0.93) for eicosapentaenoic acid, and 0.31 (0.11, 0.87) for docosahexaenoic acid (P for trend = 0.063, 0.056, and 0.026, respectively). A high proportion of eicosapentaenoic acid in CEs was associated with a low risk of CAD death. Compared with no consumption, consumption of fish tended to be associated with a lower risk of death [1-57 g/d, RR = 0.50 (0.20, 1.28); > 57 g/d, RR = 0.37 (0.14, 1.00); P for trend = 0.059]. CONCLUSION: High proportions of n-3 fatty acids in serum lipids are associated with a substantially reduced risk of death.     

Molecular characterization of a satellite RNA associated with blackcurrant reversion nepovirus

Summary.  A satellite RNA (satRNA) associated with blackcurrant reversion nepovirus (BRV) was isolated and its nucleotide sequence was determined from cDNA clones. BRV satRNA was 1432 nucleotides (nt) in length excluding the poly(A)-tail, and contained one open reading frame which encodes a polypeptide of 402 amino acids, with a calculated M_r of 44 220. The coding region was bordered by a 5′ leader sequence of 25 nt and a 3′-nontranslated region of 201 nt. Two in vitro translation products of approximately 45 kDa and 40 kDa were detected, indicating that two in-frame AUG codons at positions 26 and 134 may both be functional. Nucleotide sequence comparisons revealed a stretch of 865 nt that was 63% identical between BRV satRNA and the large satRNA of chicory yellow mottle nepovirus. A 5′-terminal consensus sequence and a 40 nt motif (located at positions 264–303 of BRV satRNA) were conserved between BRV satRNA and other nepoviral large satRNAs. Received March 22, 1999/Accepted August 30, 1999     

Radiographic joint space in rheumatoid elbow joints. A 15-year prospective follow-up study in 74 patients

OBJECTIVE: To evaluate radiographically the humeroulnar (HU) and humeroradial (HR) joint spaces in patients with long-term rheumatoid arthritis (RA). METHODS: An inception cohort of 74 patients with RA were followed for 15 yr. At the end-point, 148 elbows were radiographed by a standard method. The HU and HR joint spaces were examined from the anteroposterior radiographs by measuring the shortest tangential distance in the middle of the joints. Destruction of the elbow joints, assessed with the Larsen method on a scale of 0-5, was studied in relation to the joint-space measurements. RESULTS: Mean (s.d.) HU joint space (n=148) in RA patients was 2.5 (1.1) mm, range 0-4 mm [2.9 (0.8) mm in men and 2.4 (1.1) mm in women]. Mean (s.d.) HR joint space (n=140) was 2.3 (0.9) mm, range 0-4 mm [2.5 (0.8) mm in men and 2.3 (1.0) mm in women]. HU and HR spaces of the affected joints (Larsen grades 2-5) [1.9 (s.d. 1.1) and 1.8 (0.9) mm respectively] were notably narrower than those of the unaffected (Larsen grades 0-1) joints [3.1 (0.7) and 2.9 (0.6) mm]. All the joints graded as Larsen 4 or 5 (n=13) had a value of 0 mm for both joint spaces. Both the HU and the HR joint-space narrowing was associated with increasing destruction (Larsen grading) of the joint. [r= -0.69 (95% CI -0.77 to -0.60) and r= -0.70 (-0.78 to -0.60)]. The monotonic narrowing was significantly increasing from unaffected (Larsen 0, 1), slightly (2), moderately (3) to severely (4, 5) affected joints (P<0.001). A step in this process occurred between Larsen grades 3 and 4, when the mean joint space diminished from 1.4 and 1.5 respectively to 0 mm. CONCLUSIONS: Joint-space narrowing is a frequent consequence of rheumatoid affection of the elbow joint. HR joint space decreases together with HU joint space; however, the HR joint space is already slightly narrower at the start. The narrowing is a rather late phenomenon, occurring only after erosive destruction. This should be borne in mind when using the Larsen method to evaluate changes in the elbow joint.     

Intron 4 polymorphism of the endothelial nitric oxide synthase gene is associated with elevated blood pressure in type 2 diabetic patients with coronary heart disease

The endothelial nitric oxide synthase (eNOS) gene is responsible for constitutive nitric oxide synthesis and arterial vasodilatation. Recently two polymorphisms, the 27-bp repeat sequence in intron 4 and the Glu298Asp substitution in exon 7 of the eNOS gene have been reported to be related to coronary heart disease (CHD). We screened these polymorphisms of the eNOS gene in 308 unrelated nondiabetic subjects with CHD, in 251 unrelated patients with type 2 diabetes with CHD, and in 110 randomly selected healthy subjects without CHD. The 4a and Asp298 allele frequencies of the eNOS gene were 0.19 and 0.36 in nondiabetic patients with CHD, 0.21 and 0.27 in type 2 diabetic patients with CHD, and 0.16 and 0.31 in nondiabetic subjects without CHD (n.s. between the groups). The Asp298 allele in exon 7 of the eNOS gene was not associated with elevated blood pressure in any of the study groups. Among type 2 diabetic patients with CHD the 4a allele in intron 4 of the eNOS gene was associated with elevated levels of systolic (P=0.035) and mean arterial blood pressure (P=0.040). In nondiabetic subjects these associations were not statistically significant. When all study groups were pooled in statistical analysis the 4a allele of the eNOS gene was associated with elevated diastolic (P=0.032) and mean (P=0.030) arterial blood pressure even after adjustment for confounding factors. We conclude that the 4a allele of the eNOS gene is not associated with CHD or type 2 diabetes, but that it is related to elevated blood pressure levels particularly among type 2 diabetic patients with CHD.     

Real Time Detection of Photoreactivity in Pharmaceutical Solids and Solutions with Isothermal Microcalorimetry

Purpose. In this study an irradiation cell made as an accessory for an isothermal microcalorimeter is introduced, and its suitability for detection photoreactivity in pharmaceutical solutions and solids is demonstrated. The pharmaceuticals employed are chosen as sample materials to evaluate the usefulness and stability of the irradiation cell. Methods. An irradiation cell has been constructed and tested in an isothermal microcalorimeter with pharmaceutical solutions and solids known to be sensitive to daylight or UV light. Light is produced with an Xe-arc lamp, split into two parts and introduced into calorimetric vessels with optical light cables. One of the vessels containing the reference sample gives the response to the heat absorbed by the material (radiant power), and the other vessel containing the sample material gives the response also to the photoreaction. The two irradiation cells are positioned in the sample sides of two separate twin microcalorimetric units. Results. Nifedipine and L-ascorbic acid were found to be photosensitive in solutions and solid states, the extent of the degradation depending on the irradiation intensity and wavelength. The threshold values of the wavelength for the photoreactions, as well as the wavelengths for the maximum reaction rates, were estimated via the scanning irradiation measurements. The ability of photons with different energies to produce heat in the photosensitive reaction of nifedipine was calculated using constant measurements. Conclusions. The technique introduced offers a rapid and versatile method to study the photosensitivity of materials in any state. In the measurements, various conditions can be simulated and thus provide information on the real behavior of materials.     

The Experience of Death Anxiety in Iranian War Veterans: A Phenomenology Study

Recognition of death anxiety experienced by patients who have survived violence and threats to life during war is of strong importance in delivery of best care for veterans experiencing health stressors. The aim of the study was to explore the death anxiety experience of veterans from the Iran–Iraq war. Using a phenomenological approach, 11 war veterans were interviewed related to death anxiety experiences. Four major themes included afterlife fears; alienated farewell; ambiguous separation; and physical dissolution. Patients who have been exposed to death trauma in the battlefield may carry added burden from unique cognitions and fears related to personal death.     

The multifidus muscle in patients with lumbar disc herniation. A histochemical and morphometric analysis of intraoperative biopsies

Structural changes in the multifidus muscle were analyzed in 41 patients operated on for herniated intervertebral disc. Twelve cadavers served as controls. The two main findings follow: Both in the patients and in the controls the Type 2 muscle fibers were markedly and selectively smaller than the Type 1 fibers, which were of normal size for striated muscles, and the internal structure of Type 1 fibers showed so-called core-targetoid and/or moth-eaten change. Group atrophy or fiber-type grouping (indicators of denervation and reinnervation) were observed only in a few patients. The selective small size of the Type 2 fibers may indicate atrophy due to relative inactivity of the multifidus muscle both in the patients and in the controls, ie, it does not need to be related to the herniated disc. Definite proof for denervation of the multifidus muscle was not observed, but neither the possibility be excluded. The cause of the core-targetoid and/or moth-eaten changes cannot yet be determined with certainty, because these changes are not specific for any single entity but may be due, for example, to denervation, ischemia, or altered use of the muscles because of pain. In any case, because the changes were significantly more common in the patients than in the controls, they signal for a pathologic condition, the character of which remains to be elucidated.     

Repair of the anterior cruciate ligament. Augmentation versus conventional suture of fresh rupture

A prospective case control study was made by comparing the results of a modified combination parapatellar tendon transposition repair of a fresh anterior cruciate ligament rupture with those of the conventional Palmer technique. The mean follow-up time was 4 (3-7) years. A tendency to better stability was shown by an objective clinical device. Subjective results concerning stability sensations of the knee were also better than those obtained by the conventional method.