[The role of the response to DNA damage in granulomatous diseases]. / Der Rolle der DNA-Schadensantwort bei granulomatösen Erkrankungen.

Granulomas are organized aggregates of immune cells, which are formed in response to a persistent stimulus and are found in various rheumatic diseases, including sarcoidosis, rheumatoid arthritis and granulomatosis with polyangiitis. The core of granulomas contains a multitude of different macrophage subtypes, including multinucleated macrophages and foam cells. The mechanisms which induce the formation of granulomas are not well understood; however, recent data show that the DNA damage response regulates granuloma macrophage differentiation.

The cochlear implant. A technology for the profoundly deaf.

The cochlear implant is a device that enables the profoundly deaf to hear. This article considers the nature of the technology, the need for rehabilitation programs for those who are implanted and the evidence of benefits from this approach. A preliminary economic assessment suggests that costs per QALY for this technology would be of the order of $ 14,000 for children and $ 22,000 for adults. Cochlear implantation appears to be superior to vibrotactile devices, and is an effective technology for appropriately selected persons.

Assessment of physicians' office pathology testing: organisational considerations.

In this paper we consider organizational and design aspects of an assessment of physicians' office pathology testing, and discuss difficulties in measuring the level of performance and effectiveness of such diagnostic services. A major consideration is the trade-off between compliance with a well-defined protocol, and use of the technology in a way which resembles normal operating practice.

Developments in near-patient testing.

Important technologies for near-patient testing include 'desk-top' analysers, kits and systems for continuous monitoring, with the possibility of advances through approaches to genetic testing. Near-patient testing is now used in physicians' office, hospital ward, home care and population screening applications. Analytical performance achieved by operators in these settings may frequently cause concern and has led to increased support for accreditation and educational measures. While near-patient testing has much potential to contribute to health care, hard evidence of benefit is sparse, and the costs of such testing to health care systems may be substantial. The place of this technology still requires critical evaluation, in the context of system performance and relevance to health care.

A comparative study of BP and USP rotating basket dissolution apparatus.

The difference between BP and USP rotating basket dissolution apparatus was investigated by applying both methods to a range of commercial formulations and the NCDA Performance Standard II. No significant differences were obtained between the two sets of apparatus for the commercial tablets. However appreciable difference was observed with the NCDA calibrator.

The determination of leachable chromium from chromicized catgut sutures.

Application of the British Pharmacopoeia (BP) Analytical procedure for the determination of leachable chromium to samples of catgut sutures yielded fading coloured solutions and was considered to constitute a poor basis for an analytical method. The United States Pharmacopeia (USP) method and an adaptation of the American Public Health Association (APHA) method were explored and found to give linear responses over the concentration range of interest. Both these methods were applied to a series of samples and the results obtained were different as the APHA method measures total chromium while the USP procedure determines only chromium (VI).

Identification of a propantheline analog in propantheline bromide tablets.

A major impurity in a sample of propantheline bromide tablets has been identified as 9-hydroxypropantheline on the basis of the proton magnetic resonance (PMR) and mass spectra (MS). This identification was confirmed by methanolysis of the tablet extract, which yielded a mixture of methyl xanthanoate and methyl 9-hydroxyxanthanoate. A liquid chromatographic (LC) procedure is described which will permit quantitation of 9-hydroxypropantheline bromide in the presence of propantheline bromide, xanthone, and xanthanoic acid.

Tensile strength requirements for sutures.

The official requirements for sutures in Australia are those of British Pharmacopoeia (B.P.). The results of a survey conducted by this Laboratory indicate that the B.P. test and specifications for knot pull strength are no longer appropriate for sutures currently available in this country. It is suggested that tensile strength measurements on sutures should be carried out, without prior soaking, using the load cell type of constant rate of extension apparatus rather than the pendulum type tester specified in the B.P. Use of a simple knot is suitable for testing synthetic sutures, but the surgeon's knot is preferred for catgut. All products tested easily met both the B.P. and the United States Pharmacopeia (U.S.P.) requirements for tensile strength.

Analysis of haloperidol tablets by high-performance liquid chromatography--an inter-laboratory study.

A high-performance liquid-chromatographic (HPLC) method for the determination of haloperidol in tablets was developed and evaluated by an inter-laboratory study. The spectrophotometric method of the British Pharmacopoeia 1973 was evaluated concurrently, and the accuracy and precision of the methods were compared. Two samples of a commercially available haloperidol tablet formulation were analysed by thirteen laboratories with satisfactory results for column performance and precision of assay. The total error standard deviations, SD, for the HPLC method and the spectrophotometric method were 3.92 and 2.58%, respectively. The HPLC method is considered suitable for official testing purposes.

Specification of limits for particulate contamination in pharmaceutical dosage forms.

Limits for the control of particulate contamination in large volume parenteral solutions and metered-dose aerosols are discussed. It is suggested that is would be desirable to use limits based on measurement of both mean and the standard deviation of the particle counts obtained for each of the containers tested. Use of the statistic ST, assuming a target value of zero, is considered to be an appropriate means of measuring the container to container variation in particulate contamination.

Tests for foreign particles in metered-dose aerosols.

A simple method for the determination of foreign particular matter in metered-dose aerosols (MDA's) has been developed. The method compares favourably with a procedure currently used in pharmaceutical industry and has the advantage of providing information on container to container variation. A linear relationship between log particle count and particle size was found for a number of MDA's, although there was considerable product-to-product variation. On the basis of the results obtained in this study, commercially available MDS's would in general comply with a limit for foreign particles greater than 100 micrometers of not more than 150 particles per container with the sum of the mean count and twice the standard deviation not more than 200.

High performance liquid chromatographic analysis of hydrocortisone acetate ointments: interlaboratory study.

An interlaboratory was carried out on a high performance liquid chromatographic method for determining hydrocortisone acetate in ointments. The method represents an alternative to the colorimetric procedure of the British Pharmacopoeia. Two samples of a commercially available hydrocortisone acetate ointment were analyzed by 14 laboratories. Column performance and precision of the assay were satisfactory. The total error standard deviation for the method was 3.69%.

Absorption of quinidine and dihydroquinidine in humans.

Quinidine and dihydroquinidine were administered as the sulphates in an oral solution to seven healthy volunteers. In all subjects, dihydroquinidine was absorbed to a lesser extent than quinidine. On the basis of comparative AUC pu to 6 h after administration, dihydroquinidine was 73% as available as quinidine. Rates of elimination of the compounds were similar. No correlation could be found between saliva and plasma levels for either compound. Limits for content of dihydroquinidine in commercial quinidine preparations seem essential to ensure adequate bioavailability.

Analysis of hydrocortisone acetate ointments and creams by high-performance liquid chromatography.

High-performance liquid chromatographic (HPLC) methods for the analysis of hydrocortisone containing ointments and creams have been investigated. A method which uses a silica column and involves a minimum of sample pre-treatment has been shown to compare favourably with the triphenyltetrazolim chloride method of the British Pharmacopoeia. For hydrocortisone ointments the HPLC procedure provides results of equivalent precision and has advantages with respect to the time taken for each analysis and specificity. Application of the method to the analysis of hydrocortisone creams has been explored and the deviation between the HPLC and colorimetric method requires further investigation.

Analysis of diethylstilbestrol and its impurities in tablets using reversed-phase high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method is described which is capable of resolving cis- and trans-diethylstilbestrol (DES), DES mono- and dimethyl ethers and 4,4'-dihydroxystilbene. The mobile phase and internal standard used stabilise the cis-trans DES isomer ratio, and the method is capable of quantitating both isomers in dosage forms without derivatisation. Recovery of DES from tablets is quantitative. Results of tablet analyses using this method are compared with those obtained with the official spectrophotometric procedure.