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Biomedical subjects

P Frank

Publications and source records attributed to P Frank.

At least 19 recordsLinked to original sources

Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. I: Derivation of equation.

An equation of the quality of binary random mixtures that applies to powder samples of constant bulk volume was derived from the binomial distribution. In contrast to the Stange-Poole equation for samples of constant mass, this approach can also be used for constituents with large differences in particle size and in bulk density. The validity of this equation was verified with tablets directly compressed from mixtures composed of equal mass proportions of sucrose [volume-weighted/volume-number mean diameter (dv), 504 microns] as the coarse ingredient (A) and of a microcrystalline cellulose (Avicel PH 101)-talc mixture (dv, 60 microns) as the fine constituent (B). Because of the difference in the bulk densities of A and B, the equation estimated a coefficient of the random content variation, which for A was double that for B. The content variations found with the tablets were in excellent agreement with the calculated values and reflected the differences predicted from theory. The Stange-Poole equation yielded identical values of the content variations of A and B, which is in contrast to the experimental results.

Chemistry, Pharmaceutical

Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. II: Applications of equation to optimize tableting conditions.

In a companion communication, an equation (eq 1) of the homogeneity of binary random mixtures, which applies to constituents differing in particle size and in bulk density, was derived. The present paper demonstrates the practical applications of this equation in optimizing tableting conditions with respect to a high dose uniformity. Tablets of 50:50 (w/w) mixtures of coarse sucrose and of fine microcrystalline cellulose (Avicel PH 101)-talc vehicle were produced on a single-punch machine. Without a spin feeder, the tablets showed variations in content uniformity that were significantly higher than those estimated from eq 1. Correlation analysis between the individual mass and the content of the constituents of the tablets revealed this difference to be due to nonuniformity of the die filling and not due to incomplete mixing. Accordingly, the use of a spin feeder allowed production of tablets with higher dose uniformity, which conformed well with the theoretical optimum predicted with eq 1. Further variation of the processing conditions cannot improve the quality (i.e., varying the tableting speed resulted in equal or in poorer uniformity of dose content).

Algorithms

Novel approach to estimate quality of binary random powder mixtures: samples of constant volume. III: Range of validity of equation.

The validity of an equation developed to determine the quality of binary random mixtures (eq 1) was evaluated with tablets prepared from random mixtures of a coarse constituent A (sucrose) and fine constituent B [microcrystalline cellulose (Avicel PH 101)-talc] with the A:B ratios (w/w) varying from 10:90 to 80:20. With all A:B ratios, superior agreement was established between the random content variations determined with eq 1 and the content variations found in the tablets. The 80:20 ratio, however, was just at the boundary, and random quality was achieved with the 50-mg tablets but not with the 200-mg tablets because of segregation. From percolation theory, this result is a consequence of the small proportion by volume (bv) of B that is almost equal to the precolation threshold (Pcb) of B of 0.3. With bv less than Pcb, the fine constituent B does not form a coherent lattice, and eq 1 is no longer valid. To estimate the volume proportions av and bv from the mass proportions a and b, two methods were established. Method 1 assumed the bulk densities of A and B to be representative and was used when av was higher than the percolation threshold (Pca) of A of 0.3 (a, 0.5). Method 2 used the true particle density of A and was valid with av values of less than 0.1 (a, 0.3), in which case the particles of A were dispersed as individuals in the matrix of B.

Chemistry, Pharmaceutical

Evaluation of the Poisson distribution for estimating the quality of drug/diluent random powder mixtures. I. High particle size of the drug constituent.

Use of the Poisson distribution to estimate the quality of random mixtures was evaluated as a measure of the highest attainable degree of dose uniformity of tablets. Ingredient A was assumed to have a large particle size as compared to diluent B. In contrast to the more precise binomial distribution, for the simple Poisson approach no experiments are necessary to investigate the mean proportions of the apparent volume, av and bv, which A and B assume within the powder samples in the die. The range of volume ratios was defined where the Poisson distribution is valid. Accepting an error of 5% of the random content variation of A per sample, av may amount to up to 0.1 (10%). In terms of the proportion by mass of A, a, this range is wider, and commonly of the order of 0.2 or higher. This approach was tested with tablets prepared from mixtures of coarse sucrose A and a fine Avicel/talc diluent B at A:B (m:m) ratios from 10:90 to 50:50. Even with the 30:70 tablets, the variations of the sucrose content were still in good agreement with the content variations of the random mixtures as estimated from the Poisson distribution. Estimates of the 50:50 ratio, however, deviated from the Poisson distribution.

Algorithms

Time-interval analysis of interjudge and intrajudge agreement for stuttering event judgments.

In response to the recognized need for a valid and reliable way to measure stuttering, this study investigates a measurement methodology based on time-interval analyses of stuttering event judgments. Three groups of judges, differing in stuttering judgment experience, identified stuttering events in 12 repeated presentations of five 1-min speech samples. Fixed time intervals ranging from 0.2 sec to 7.0 sec were then superimposed on the event judgments by a data analysis program. Inter- and intrajudge interval-by-interval agreement, and agreement for total numbers of intervals containing stuttering event judgments, were calculated for each judge group. Results showed that agreement was superior among more experienced judges and in longer interval lengths. Agreement varied across speech samples but not across the repeated judgment opportunities. Agreement was maximized at greater than chance levels for an interval of approximately 3.0 sec, but even this best agreement did not exceed a mean of approximately 60% for experienced judges.

Adolescent

A method for rapid and frequent blood collection from the rat tail vein.

A technique is described for the collection of blood samples after dilation of rat tail veins using a controlled temperature device. Frequent blood samples of seven or eight per rat were collected during a 6-hr period. Further samples were taken from the same vein after recannulation during the next 5 days. This technique was also used to administer drugs intravenously through one vein and to collect blood samples from the contralateral vein.

Animals

Class II ribonuclease H comigrates with, but is distinct from, the third largest subunit of calf thymus RNA polymerase I.

It has been reported (Iborra et al. (1979) J. Biol. Chem. 254, 10920-10924) that the third and the fifth largest subunit of yeast RNA polymerase I exhibit ribonuclease H activity. The authors suggested that the third largest subunit is identical with the chromatin-associated ribonuclease H49, the putative yeast equivalent of bovine ribonuclease H IIb. Although the third largest subunit of calf thymus RNA polymerase I and ribonuclease H IIb display nearly identical molecular masses under denaturing conditions, serological analysis reveals that, in contrast to their counterparts in yeast, these mammalian proteins are distinct entities. Interestingly, sera from some patients with mixed connective tissue disease which contain antibodies directed against RNA polymerase I, also react with ribonuclease H IIb epitopes. This observation suggests that a protein displaying ribonuclease H IIb antigenicity could be associated with RNA polymerase I. Additional indications supporting this conclusion are discussed.

Animals

Calf thymus ribonuclease H IIa activity lacks ribonuclease H specificity.

Less purified fractions of ribonuclease H IIa activity of calf thymus display divalent cation-dependent ribonuclease H activity and divalent cation-independent ribonuclease activity. Because the ratio of the two enzyme activities does not change during successive chromatographic procedures, we suggest that ribonuclease H IIa activity is indeed able to degrade both ssRNA and the RNA moiety of RNA.DNA-hybrids. Ribonuclease H IIa activity can therefore be differentiated from calf thymus ribonuclease H I and H IIb by its lack of ribonuclease H specificity. The native molecular mass of ribonuclease H IIa activity is between 23 and 28 kDa. Under denaturing conditions a 23 kDa-protein band copurifies with the enzyme activity suggesting that this enzyme is monomeric.

Animals

[Blind-pouch syndrome after side-to-side intestinal anastomosis].

Side-to-side anastomosis is a bad technique to restore intestinal continuity. In fact, it leads to the progressive distention of the cul-de-sac, which produces definite pockets of stasis and bacterial infection. Although it is well tolerated by a number of patients, it causes a number of gathered complications in others. This array of signs is called the blind pocket syndrome, the characteristics of which are described by the authors on the basis of a 76-case series, including 3 personal cases. They again condemn the side-to-side anastomosis and prefer end-to-end anastomosis, which prevents these disadvantages.

Aged

Purification and spectroscopic characteristics in N-methylformamide of the Azotobacter vinelandii Fe-Mo cofactor.

The iron-molybdenum cofactor from Azotobacter vinelandii can be removed from significant amounts of extraneous iron and other contaminants using anaerobic gel filtration. Electronic absorption spectra of the so-purified FeMoco along with analysis of the so-called 'easily complexed' iron are suggestive that FeMoco occupies at least two different states in N-methylformamide solution. Batch-related differences in spectral characteristics of independently isolated FeMoco samples are demonstrated. Non-cofactor iron, found in unpurified FeMoco, may affect the interpretation of ligand binding and other experiments probing FeMoco structure and reactivity. Oxidized FeMoco is shown to be clearly discernable from the semi-reduced species by means of electronic spectroscopy, and this method now forms a convenient analytical tool for study of the chemistry and electronic structure of FeMoco.

Azotobacter

Serological analysis and characterization of calf thymus ribonuclease H IIb.

Ribonuclease H IIb, which seems to play a physiological role during transcription, was purified from calf thymus tissue. A polyclonal antibody, raised against the most purified ribonuclease H IIb fraction, recognizes in crude extracts almost exclusively a 52-kDa protein band. By immunoaffinity chromatography and immunoprecipitation experiments, we are able to deplete enzyme extracts from the crossreacting 52-kDa protein band and from ribonuclease H IIb activity. Enzyme activity is eluted from the immunoaffinity matrix in association with a 52-kDa protein under denaturing conditions. Immunoaffinity chromatography enables us also to calculate a purification factor of around 20,000 from the crude extract. The native molecular mass for the enzyme of around 45 kDa, as determined by gel filtration, suggests that calf thymus ribonuclease H IIb is most probably monomeric. The enzyme possesses an isoelectric point of 7.0. It requires Mg2+ ions for activity, is inhibited by N-ethylmaleimide, and exhibits a pH optimum of 9.0-9.5. The enzyme releases oligoribonucleotides with 3'-OH and 5'-phosphate ends, probably in an exonucleolytical manner. The third largest subunit of yeast RNA polymerase A (I) displays ribonuclease H activity [Huet et al. (1976) Nature 261, 431-433]. We discuss our findings in the light of a possible association of ribonuclease H IIb and RNA polymerase A (I) in higher eukaryotes.

Animals

[Single support of atrophic edentulous mandible with endosseous implants. Modified method of implantation with Ledermann titanium plasma-coated screw implants (TPS)].

In contrast to the usual technique of Ledermann to implant four TPS-implants in edentulous mandibles a modified method with only two implants is described. The advantages of taking only two implants are the easier implantation technique, the lower costs, and especially a better dynamic of the full denture. In connection with a round bar most of the pressure produced by the masticatory muscles is taken by the mucosae and almost no eccentric forces effect on the implants. This technique should only be applied combined with a denture in the edentulous upper jaw. Strictly regarding the range of indications our rate of failure with two implants is not higher than with the usual method described by Ledermann.

Bone Resorption

[Therapeutic problems of intra-abdominal liposarcoma].

Intra-abdominal liposarcomas are very rare tumors. We present our personal experience with one case of mesenteric liposarcoma which had perforated into the peritoneal cavity, occurring in a seven-month pregnant female patient. Seven years later, the patient is doing well. The authors have carried out a review of the literature. In addition to liposarcomas of the mesentery and the mesocolon, they observed some cases of liposarcoma localized in the omentum and the stomach; other abdominal localizations occurred sporadically. Radical surgical excision was the choice treatment. Both the propensity for locoregional spread and the histological diversity set the conditions for prognosis; the latter seemed minimally influenced by either radio- or chemotherapy.

Abdominal Neoplasms

[Right heart ventriculography using Gelifundol].

Forty patients (14 women, 26 men, mean age 58 years) with suspected anomaly of the right heart and suspected tricuspid insufficiency or atrial septal defect were given four injections of Gelifundol in five-minute intervals via the right cubital vein. Before, during, and after each injection an echocardiogram was obtained (four-chamber-view). One subcostal view was recorded. Contrast echocardiograms were analyzed according to a subjective score scheme by two independent observers and by video-intensitometry. After injection of contrast medium no patient showed ECG changes, nor did any patient report side effects after the injection of Gelifundol. Concerning the subjective parameters there were no significant differences between both observers. Score points varied between 5.2 to 5.5, intensitometric maxima lay between 54.6 and 58.0 relative intensity units, and the half-time of the intensity maximum (T1/2) varied between 7.2 s and 8.1 s. There were no statistical differences between the two observers. In all patients a diagnotic improvement could be achieved. A tricuspid insufficiency which was not diagnosed in the native echocardiogram could be diagnosed in 13 patients with Gelfundol. Thus, Gelifundol seems well suited for the assessment of right ventricular lesions in man.

Adolescent

Heterotopic ossification with total hip endoprostheses in various models of thrombosis prophylaxis.

The influence of thrombosis prophylaxis on the occurrence of heterotopic ossification after implantation of total hip endoprostheses was analyzed in a series of randomized studies. When low-dose heparin or dextran 40 was administered, the rate of ossification was comparatively high (30.1% and 65.1%). When a combination of acetylsalicylic acid and an antirheumatic (oxyphenbutazone) or low-dose heparin with an antirheumatic (indomethacin) was administered, the ossification rate became significantly lower (6.2% and 16.7%). No severe ossification (Arcq degree III) was observed in the groups given an antirheumatic in addition to thrombosis prophylaxis.

Aspirin