The chronic non-healing wound: how to make it better

Chronic wounds are a commonly encountered problem. An understanding of their aetiology, combined with a systematic approach to their management, is fundamental to achieving an optimal environment for healing to take place.     

Periurethral fat injection in the treatment of recurrent genuine stress incontinence

A benign, transient proliferation of atypical lymphocytes and a monoclonal rearrangement of the T-cell receptor beta (TRB) locus was found in a 60-year-old woman who presented with low-grade fever, anorexia and fatigue. A marked and transient atypical lymphocytosis (white blood cell count 90.5 x 10(9)/l) with CD8 surface antigen improved without specific treatment. Although tests for IgM antibodies to hepatitis A, varicella zoster, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) were all negative, a monoclonal gene rearrangement of TRB locus was observed in the DNA of the proliferated atypical lymphocytes by Southern blotting. The clonal rearrangement and the atypical lymphocytes disappeared after 14 d, and the patient has remained well for 7 years. These results suggest that monoclonal proliferation of CD8 lymphocytes can occur based on a non-neoplastic aetiology.     

Dissolution kinetics of phenylbutazone

This study investigated the possible effects of simultaneous, noninstantaneous, reversible chemical ionization of carbon acids on the dissolution of a typical pharmaceutical carbon acid, phenylbutazone, and its deutero analog. The dissolution rate versus pH profile for phenylbutazone was consistent with phenylbutazone acting as if it were an acid where the ionization can be considered instantaneous. In view of the dissolution behavior of phenylbutazone under various conditions, it is unlikely that the noninstantaneous ionization kinetics demonstrated for this compound play a major role in determining the dissolution rate, either in vitro or in vivo, since the average residence time in a typical aqueous diffusion layer for phenylbutazone dissolution is longer than the reaction time for its ionization. Slowing the reaction time with a primary isotope effect by deuterium substitution for the ionizable proton caused significant deviation from classical behavior for d-phenylbutazone.     

FATIGUE LIFE UNDER RANDOM LOAD HISTORY DERIVED FROM EXCEEDANCE CURVES USING DIFFERENT ALGORITHMS

Low cycle fatigue life and crack growth rates were analytically estimated for random load sequences, generated from three combat aircraft load exceedance curves using different algorithms, including simulated rainflow cycle count, extreme-to-extreme excursions, upper to lower bound excursions and unrestricted peak-trough excursions. Also, the response of a fatigue meter to a random load sequence was simulated. Fatigue damage for the different load histories was computed using material constants for an Al-Cu alloy. Computed fatigue damage was relatively insensitive to the algorithm used for load sequence generation from combat aircraft load exceedance curves. Fatigue meter data based damage estimates were, however, sometimes unconservative.     

Usefulness of transesophageal echocardiography in the treatment of critically ill patients

To evaluate the usefulness of transesophageal echocardiography (TEE) in the treatment of critically ill patients, 80 patients (51 male and 29 female; mean age, 53 years) undergoing both transthoracic echocardiography (TTE) and TEE were studied in a 2-year period. Of these, 48 patients were studied in the ICU, while the other 32 patients were directly referred from the emergency departments. Indications for the study included suspected aortic dissection (34 patients), hemodynamic instability (22 patients), suspected cardiac source of embolism (11 patients), evaluation of the severity of mitral regurgitation (7 patients), and suspected infective endocarditis (6 patients). The probe was passed successfully in 78 of 80 attempts (98 percent). No significant complications were recorded during the transesophageal echocardiographic study. Transesophageal echocardiography provided critical information that was not obtained by TTE in 39 of 78 studies (50 percent, p < 0.005). Cardiac surgery was prompted by TEE findings in 14 patients (18 percent) and these findings were all confirmed at operation. Transesophageal echocardiography was a safe, well-tolerated, and valuable diagnostic approach for the rapid detection of specific cardiac abnormalities in patients with critical illness; TEE should be considered in the treatment of critically ill patients especially when TTE provided inadequate information.     

Psychiatric sequelae of low birth weight at 6 years of age

The study examined the association between low birth weight (LBW) (< or = 2,500 g) and attention deficit hyperactivity disorder (ADHD) in two socioeconomically disparate populations. LBW and normal birth weight (NBW) children from the 1983 to 1985 newborn lists of an urban and a suburban hospital in Southeast Michigan were randomly selected. A total of 823 children, 473 LBW and 350 NBW, participated. Data were gathered in 1990 to 1992, when the children were 6 to 7 years of age. The National Institute of Mental Health Diagnostic Interview Schedule for children-Parent version (DISC-P) was used to elicit information on DSM-III-R diagnoses of simple phobia, overanxious, separation anxiety, oppositional defiant, and ADHD. Teachers' ratings of behavior problems were obtained. LBW was associated with ADHD but not with childhood anxiety disorders or oppositional defiant disorder. The association was stronger in the urban than in the suburban population. Data from teachers' ratings revealed an association between LBW and attention problems. The prognostic significance of the observed psychopathology at 6 years of age requires follow-up assessment as the children mature.     

Poly(A) polymerase contains multiple functional domains

Poly(A) polymerase (PAP) contains regions of similarity with several known protein domains. Through site-directed mutagenesis, we provide evidence that PAP contains a functional ribonucleoprotein-type RNA binding domain (RBD) that is responsible for primer binding, making it the only known polymerase to contain such a domain. The RBD is adjacent to, and probably overlaps with, an apparent catalytic region responsible for polymerization. Despite the presence of sequence similarities, this catalytic domain appears to be distinct from the conserved polymerase module found in a large number of RNA-dependent polymerases. PAP contains two nuclear localization signals (NLSs) in its C terminus, each by itself similar to the consensus bipartite NLS found in many nuclear proteins. Mutagenesis experiments indicate that both signals, which are separated by nearly 140 residues, play important roles in directing PAP exclusively to the nucleus. Surprisingly, basic amino acids in the N-terminal-most NLS are also essential for AAUAAA-dependent polyadenylation but not for nonspecific poly(A) synthesis, suggesting that this region of PAP is involved in interactions both with nuclear targeting proteins and with nuclear polyadenylation factors. The serine/threonine-rich C terminus is multiply phosphorylated, including at sites affected by mutations in either NLS.     

Long-term treatment with abecarnil does not induce diazepam-like dependence in mice

Abecarnil (isopropyl-6-benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate) is a metabolically stable anxiolytic and anticonvulsant beta-carboline derivative with few sedative and muscle relaxant effects in rodents. Abecamil binds with high affinity to benzodiazepine receptors. Because long-term treatment with benzodiazepines leads to development of dependence, we evaluated in mice whether abecarnil also possesses a potential for producing dependence, using electroencephalographic and electromyographic monitoring, and behavioral assessment of anxiety to detect withdrawal responses after chronic treatment. Diazepam was used as a reference. Mice withdrawn from chronic treatment with diazepam (15 mg/kg/day for 12 days) showed a time-related evolution of anxiety, muscle rigidity and seizures between days 4 and 21 after discontinuation of the treatment. A period between withdrawal days 1 and 3 was symptom free. Mice withdrawn from chronic administration of abecarnil (6 mg/kg/day for 12 days) showed no anxiety and no changes in seizure susceptibility and muscle tone. The doses of diazepam and abecarnil used for chronic treatment were equivalent in terms of kinetics and binding to benzodiazepine receptors. These data indicate that long-term treatment with abecarnil does not induce benzodiazepine-like dependence in mice. Thus, it may be predicted that chronic treatment with abecarnil in humans may offer an important alternative to benzodiazepines in the treatment of anxiety.     

Structural and functional characterization of proteolytic fragments derived from the C-terminal regions of bovine fibrinogen

A number of new as well as previously described fragments derived from the D region of bovine fibrinogen by limited proteolysis have been characterized by sequence analysis, differential scanning calorimetry and circular dichroism. Determination of the extremities of the polypeptide chains forming individual fragments allowed the scheme of proteolysis and the borders between domains in the D region of fibrinogen to be established. It was also found that the most thermostable region of the D fragment (TSD) can be substantially reduced in size without loss of its compact structure. The alpha-helical content of the newly prepared 21-kDa TSD2 and 16-kDa TSD3 fragments were 82% and 75%, respectively, strongly supporting a coiled-coil structure for this region of the fibrinogen molecule. The DX and DZ fragments, prepared from a chymotryptic digest of the DLA fragment, were found to be similar to the DL and DY fragments, respectively, except for an internal cleavage at K393-T394 in their beta chains. This cleavage leads to destabilization of all thermolabile domains, indicating interaction between them. The DL and DY fragments, containing only one polymerization site in their beta chains, were able to inhibit fibrin polymerization at high concentration. However, these same fragments failed to bind to fibrin-Sepharose under conditions where their structural analogues, DX and DZ, were tightly bound, indicating that cleavage after K393 substantially increases the affinity of this site.