Some pharmacokinetic parameters of doxycycline in east African goats after intramuscular administration of a long-acting formulation

A compartmental and non-compartmental study was carried out on five adult goats following intramuscular administration of doxycycline at 20 mg/kg bodyweight. The concentration of the drug in serum was determined by a microbiological assay employing Bacillus cereus var mycoides (ATCC 11778) as the test organism. The mean serum concentration (Cmax) and the time of maximum concentration (Tmax) were 1.87 micrograms/ml and 0.85 h, respectively. Using compartmental analysis, the plasma concentration-time curve of doxycycline best fitted a three-compartment open model with first-order absorption. A three-phase disposition of doxycycline was found, the terminal elimination half-life being approximately 40 h. The statistical moment theory was mainly used for non-compartmental analysis. The value obtained for the mean residence time (MRT) was 16.4 h. The mean values for the volume of distribution at steady state (Vdss), determined by compartmental and non-compartmental analyses, were 8.73 and 13.19 L/kg, respectively. There were no statistically significant differences when the major pharmacokinetic parameters were compared. It was concluded that the pharmacokinetic behaviour of doxycycline in goats after intramuscular administration is characterized by a three-compartment model with a slow terminal elimination phase. Based on current knowledge, this could be due to enterohepatic recycling and/or flip-flop kinetics. The study indicated that a single intramuscular administration of 20 mg/kg of doxycycline may only provide therapeutic concentrations for up to 24 h owing to slow absorption at the injection site.     

Thymic microenvironment and lymphoid responses to sublethal irradiation

Sublethal irradiation of the murine thymus has been a useful tool for depleting the thymus of dividing immature thymocyte subsets, to sequence thymocyte differentiation events occurring from radiation-resistant precursors. This massive reduction in thymocytes also represents a model in which the bidirectional interplay between the thymic stromal cells and lymphocytes can be investigated. The purpose of this study was thus twofold: to precisely map the initiation of thymopoiesis as a prelude to assessing the effects of injected mAb to novel thymic antigens; and to use a panel of mAbs to determine the alterations in the thymic stroma during the T-cell depletion and reconstitution phases. The striking finding from this study was that following T-cell depletion, there was a marked upregulation of specific stromal antigens, which retracted with the reappearance of T cells. Thus, following sublethal irradiation, there are modifications in the thymic microenvironment that may by necessary to support renewed thymopoiesis and the complete restoration of the thymus involved the synchronous development of both the stromal and lymphocytic components.     

The effect of haemolysis on blood glucose meter measurement

A study was performed to assess the effect of varying degrees of sample haemolysis on the measurement of blood glucose by the Accutrend, Companion 2, ExacTech, Glucometer II, Glucometer 4, One Touch II, and Reflolux II blood glucose meters. Fresh venous blood was sonicated to induce complete haemolysis and then added in increasing proportions to homologous untreated blood to obtain nine samples with free haemoglobin concentrations up to 50 g l-1. The Accutrend meter showed the only significant (p < 0.05) linear relationship to degree of haemolysis (r = 0.988, p < 0.0001). For every 7% of red cells lysed, the Accutrend value increased by 15%. All other meters gave results which were within 15% of the non-haemolysed value. However, extreme (100%) haemolysis not only affected the Accutrend (glucose value 108% greater than reference) but also the ExacTech (+98%), the Glucometer II (-32%), and the Companion 2 (-41%). Thus, unwitting use of a haemolysed sample to measure whole blood glucose may, with the Accutrend in particular, lead to erroneous results.     

A study of the association of Epstein-Barr virus with Burkitt''s lymphoma occurring in a Chinese population

Several (carbamoylalkenyl)- and (carbamoylalkenyl)phenyloxy carboxylic acids (Table 1) and some of their ethyl esters (Table 2) were synthesized and evaluated in vitro as inhibitors of steroid 5 alpha-reductase. Inhibitors of this enzyme may be useful in treating dihydrotestosterone-related diseases such as prostate cancer and benign prostatic hyperplasia. Using an enzyme preparation obtained from human prostate carcinoma tissue, the inhibition values ranged from 0 to 57% at the given dose of 100 microM. In the series of free acids, surprisingly, the compounds showed only modest inhibitory potency (0-26%). By contrast, the ethyl esters displayed inhibition values up to 57%. Structure-activity relationships are discussed.     

Imputation for exposure histories with gaps, under an excess relative risk model

An Onchocerca volvulus expression library was differentially screened to identify a molecular marker distinguishing sowda (lichenified onchodermatitis) from other onchocerciasis forms. One clone, PG3, was recognized by pooled sera from patients with sowda, but not by pooled sera from patients with generalized onchocerciasis; it was not recognized by sera from patients with lymphatic filariasis or other helminth infections. The DNA of PG3 hybridized strongly with O. volvulus Eco RI-digested DNA, but not with DNA from Brugia spp., Trichinella spp., and humans. A weak reaction was observed with DNA from O. gibsoni and Acanthocheilonema viteae. The PG3 DNA sequence showed a high homology with both human and nematode collagens. Confirmation of the collagen-like nature of the sowda-specific PG3 product was obtained by amino terminal sequencing of the PG3 expression product, as well as by demonstrating its susceptibility to collagenase digestion. The characteristic recognition of the O. volvulus collagen specified by clone PG3 was confirmed by measuring antibody levels to the expressed product in individual sowda and generalized onchocerciasis sera, respectively. Identification of a nematode collagen antigen mainly recognized in sowda patients raises the possibility that this extreme form of dermatitis might arise through cross-reactivity between anti-O. volvulus collagen antibodies and human collagen. However, a relationship between the PG3 recognition by antibodies and the sowda pathogenesis could not be demonstrated.     

Evolving role of CNSs in developing risk-anchored preventive interventions

Emerging emphases on systems of care, cost containment, and preventive interventions require the CNS to recognize risk factors and change health behaviors before complications develop. To lower substantially the rate of nontraumatic lower extremity amputation, high-risk populations must be screened and must receive appropriate management, including education and self-care interventions. In this article, two studies that examined foot risk factors in ambulatory elderly with intact feet are compared. American Diabetes Association and Gillis W. Long Hansen's Disease Center risk criteria were applied to both datasets. Recommendations for education, management, and referrals based on the calculated level of risk are presented.     

The Charing Cross Hospital experience with temozolomide in patients with gliomas

Temozolomide, a new oral cytotoxic agent, was given to 75 patients with malignant gliomas. The schedule used was for the first course 150 mg/m2 per day for 5 days (i.e. total dose 750 mg/m2), escalating, if no significant myelosuppression was noted on day 22, to 200 mg/m2 per day for 5 days (i.e. total dose 1000 mg/m2) for subsequent courses at 4-week intervals. There were 27 patients with primary disease treated with two courses of temozolomide prior to their radiotherapy and 8 (30%) fulfilled the criteria for an objective response. There were 48 patients whose disease recurred after their initial surgery and radiotherapy and 12 (25%) fulfilled the criteria for an objective response. This gave an overall objective response rate of 20 (27%) out of 75 patients. Temozolomide was generally well tolerated, with little subjective toxicity and predictable myelosuppression. However, the responses induced with this schedule were of short duration and had relatively little impact on overall survival. In conclusion, temozolomide given in this schedule has activity against high grade glioma. However, studies evaluating chemotherapy in primary brain tumours should include a quality-of-life/performance status evaluation in addition to CT or MRI scanning assessment.     

Small bowel injury in gastroschisis: relation to fetal presentation

The study presented here attempts to assess the cost savings attributable to having an on-site corporate medical clinic. For a period of 4 months, employees using the clinic were surveyed regarding: (1) whether they would have used an outside doctor if the corporate medical department clinic were not available, and (2) how many days per year they estimated that they came to work because there was an on-site medical center when they would otherwise have stayed at home. The results indicated that, on average, employees who used the facility saved 3.3 days of absenteeism. That total cost savings was calculated to be $499,212 per year. In addition, 69% of employees indicated that they would have sought attention elsewhere, suggesting that the presence of an on-site medical center does not induce demand. The findings concerning the hidden savings brought about by an on-site medical center are also discussed.