Ovarian cancer and gangrene of the digits: case report and review of the literature.

Digital ischemia has been reported with various types of cancer, especially gastrointestinal. It is more common in elderly women than in any other group, and the most common symptom is a gangrenous finger (or fingers). More than half of the patients have metastatic involvement. Once the primary disease has been treated, when feasible, the digital symptoms usually regress or disappear. The presence of digital ischemia without other rheumatologic stigmata or vascular predisposition in an elderly patient should raise clinical suspicion of a paraneoplastic phenomenon. Herein we describe a 65-year old woman with digital ischemia associated with ovarian cancer. The diagnosis was established by biopsy after extremely high levels of cancer antigen 125 were detected.

Speech performance of adult cantonese-speaking laryngectomees using different types of alaryngeal phonation.

The purpose of the present study was to compare the speech performance of four types of alaryngeal phonation-electrolaryngeal (EL), pneumatic artificial laryngeal (PA), tracheoesophageal (TE), and standard esophageal (SE) speech-by adult Cantonese-speaking laryngectomees. Subjective ratings of (1) voice quality, (2) articulation proficiency, (3) quietness of speech, (4) pitch variability, and (5) overall speech intelligibility were given by eight naive individuals who had no prior experience with any form of alaryngeal speech. Results indicated that SE and TE speech was perceived to be more hoarse than PA and EL speech. EL speech was associated with significantly less pitch variability, and PA speakers produced speech with the least amount of perceived noise. However, articulation proficiency and overall speech intelligibility were found to be comparable in all four types of alaryngeal speakers.

Delivery of poorly soluble compounds by amorphous solid dispersions.

Solid state manipulation by amorphous solid dispersion has been the subject of intensive research for decades due to their excellent potential for dissolution and bioavailability enhancement. The present review aims to highlight the latest advancement in this area, with focus on the fundamentals, characterization, formulation development and manufacturing of amorphous solid dispersions as well as the new generation amorphization technologies. Additionally, specific applications of amorphous solid dispersion in the formulation of herbal drugs or bioactive natural products are reviewed to reflect the growing interest in this relatively neglected area.

[Urinary tract infections and microbiological characteristics of Proteus penneri isolated in Taiwan].

Proteus penneri has been reported to be involved in urinary tract infections and calculi formation. We analyzed 2,265 positive urine cultures from patients hospitalized in Taipei Veterans General Hospital, Taiwan and found that 47 patients (2.1%) were infected by P. penneri. Most of the patients were male with age over sixty and had been treated with various kinds of antibiotics. Most of the patient's urine were collected by catheter. They were alkaline (pH 8.0) and contained amorphous phosphate, triple phosphate and protein. All the isolates of P. penneri in Taiwan showed beta-hemolysis and slight swarming on sheep blood agar plate, and exhibited a green color on upper layer of sulfide-indole-motility medium after addition of Kovacs indole reagent. Except for nitrate reduction and N2 production, the biochemical characteristics of the P. penneri isolated in Taiwan were similar to those of P. penneri isolated otherwise. The Taiwan isolates of this organism were highly susceptible to cefotaxime, cefotazidime, cefotizoxime, moxalactam, nalidixic acid; but were resistant to ampicillin, carbenicillin, cefonicid, cefoperazone, ceftriaxone, cephalexin, cephapirin, chloramphenicol, clindamycin, gentamicin, nitrofurantoin, oxacillin, piperacillin, tetracycline, tobramycin, trimethoprim-sulfamethoxazole, vancomycin, and cephalothin.

Spectral differences between rhodanese catalytic intermediates unrelated to enzyme conformation.

Circular dichroism (CD) spectra and UV absorption spectra of two obligatory intermediates in rhodanese catalysis were compared. A broad CD band between 250 and 287 nm increased in a manner stoichiometrically related to the content of enzyme-bound persulfide. Titration of a sample of sulfur-substituted rhodanese (ES) with either cyanide or sulfite gave a stoichiometry that is consistent with one persulfide/molecule of rhodanese (Mr = 33,000). This result agrees with that determined by x-ray crystallography and a method based on quenching of intrinsic fluorescence. Cyanolysis of the persulfide in ES is accompanied by a decrease of UV absorption in the region between 250 and 300 nm. Cyanide titrations followed by the change in absorbance at 263, 272, and 292 nm gave the expected stoichiometry. The magnitude of the difference between the far UV-CD spectra of E and ES found here is smaller than reported previously. This variability suggests that the differences in the secondary structure of these intermediates may not be obligatorily related to the cyanolysis of the persulfide. This view is compatible with recent evidence which suggested that E and ES may be made different by structural relaxation events that occur outside of the catalytic cycle. Furthermore, the methods developed here will be useful in studies on the stability of the catalytic persulfide that has been suggested to be central in the mechanism of several enzymes important in sulfur metabolism.

Tetracyanonickelate probes the active site of sulfur-free rhodanese.

Tetracyanonickelate (Ni(CN)4(2-)) was used as a probe for the active site of sulfur-free rhodanese (E) in physical and kinetic studies. Ni(CN)4(2-) quenches the intrinsic fluorescence as well as the fluorescence of enzyme-bound 2-anilinonaphthalene-8-sulfonic acid (2,8-ANS), an inhibitor that is competitive with respect to thiosulfate. A facile binding method based on centrifugation was developed to study Ni(CN)4(2-) binding to E. Binding studies performed using either of the electrophoretic variants A and B, fractionated by DE52 column chromatography, showed one high affinity Ni(CN)4(2-)-binding site in each species and additional weak sites on the more electropositive form A. The high affinity Ni(CN)4(2-) binding was corroborated by ultrafiltration binding (Kd = 3.95 +/- 0.35 microM), titration of intrinsic fluorescence (Kd = 1.8 +/- 0.11 microM), and displacement of enzyme-bound 2,8-ANS (Kd = 1.9 +/- 1.1 microM). A nonlinear least squares analysis of kinetic data collected under conditions used for the binding studies gave a Ni(CN)4(2-) inhibition constant of 21 microM. It is concluded that Ni(CN)4(2-) binds to sulfur-free rhodanese in solution near the active site as has been shown in x-ray crystal studies (Lijk, L. J., Kalk, K. H., Brandenburger, N. P., and Hol, W. G. J. (1983) Biochemistry 22, 2952-2957). In keeping with recent suggestions that the conformational state of the enzyme is dynamically determined, the discrepancy between Ni(CN)4(2-) affinity as determined by physical methods and that by kinetic methods suggests that Ni(CN)4(2-) may be able to distinguish the conformation of the working enzyme from those of the idle forms.

Characterization of rhodanese-tetracyanonickelate. An active site complex that slows sulfur-free rhodanese conversion to inert conformers.

The structure of the rhodanese-tetracyanonickelate (E X Ni(CN)2-4) complex has been characterized here in spectral and physical studies using urea as a structural perturbant. UV difference absorption, sedimentation velocity ultracentrifugation, fluorescence, and circular dichroism data show no significant conformational differences between sulfur-free rhodanese (E) and the E X Ni(CN)2-4 complex. The urea-induced enzyme structural transition curves were noncoincident when different structural parameters were monitored. For E, the urea concentrations giving half-maximal change (Cm) were: Cm = 3.0 M for activity measurement; Cm = 2.8 M for protein intrinsic fluorescence intensity; Cm = 4.3 M for ellipticity at 220 nm; and Cm = 3.3 M for wavelength of fluorescence emission maximum. For the E X Ni(CN)2-4 complex, Cm was shifted to a higher urea concentration relative to that found for E when activity (Cm = 3.6 M) and native protein fluorescence (Cm = 3.6 M) were the measured parameters but not when the wavelength of the emission maximum and ellipticity were monitored. Furthermore, urea-induced rhodanese structural changes were time-dependent and Ni(CN)2-4 binding on E slowed enzyme inactivation that is associated with structural relaxations. These findings, that Ni(CN)2-4 affects structural relaxations in rhodanese, are of particular interest in light of the recent suggestion that the E X Ni(CN)2-4 complex mimics a normally inaccessible intermediate in catalysis.

Evidence for dynamically determined conformational states in rhodanese catalysis.

Physical and kinetic studies have been used to explore hysteretic effects that are observed in rhodanese catalysis at pH 5 and also at neutral pH when the ionic strength of the medium is high. Experiments that involve observation of changes in intrinsic protein fluorescence of the enzyme and kinetic investigation of its interactions with product thiocyanate anion at pH 5 have implicated enzyme isomerization as the cause of hysteresis. Taken all together, the data indicate that the conformations of enzyme forms in the catalytic cycle are dynamically determined, depending on the relative rates of conformational relaxation and catalysis as influenced by the concentrations of substrates and products.

[A modified medium, bile esculin-pyrrolidonyl-beta-naphthylamide, for rapid differentiation between enterococci and nonenterococci].

A new medium was developed by adding 40 mg pyrrolidonyl-beta-naphthylamide (PYR) to 1 l bile esculin (BE) agar, and was named as BE-PYR agar. To evaluate the efficacy of BE-PYR agar in differentiating enterococci from nonenterococci, we inoculated 207 strains of group D streptococci (including 157 enterococci and 50 nonenterococci) to BE-PYR agar. After incubating overnight at 35 degrees C incubator, following by applying the PYR reagent to test the color change of colonies, results indicate that the accuracy of BE-PYR agar in the differentiation of enterococci from nonenterococci reaches to 100%. Therefore, BE-PYR agar was considered to be an effective laboratory tool in further differentiation of group D streptococci.

Haemodynamic responses to intravenous cimetidine in subjects with normal lung function and in subjects with chronic airway obstruction.

1 The haemodynamic responses to a bolus intravenous injection of 400 mg cimetidine were studied in eight subjects with normal lung function and sixteen with chronic obstructive airway disease (COAD), under continuous systemic and pulmonary arterial monitoring. In all subjects there were significant immediate but transient (less than 10 min) drops in the systemic and pulmonary arterial pressures (both systolic and diastolic), the systemic vascular resistance and total pulmonary resistance. The percentage drops were significant more marked in the COAD group in the following: systemic arterial pressures (systolic and diastolic), systemic vascular resistance and total pulmonary resistance. The cardiac output showed no significant change in the group with normal lung function but rose significantly in the COAD group. None of the subjects had any symptoms associated with the haemodynamic changes. 2 These results can be explained by a generalized vasodilatory effect of cimetidine, but the relationship to its H2-receptor blocking effect is undetermined. Hypoxia and/or hypercapnia may sensitize an individual to the vasodilatory effect of cimetidine.