Tuberculosis of the female genital tract in patients attending an infertility clinic

Mycobacterium tuberculosis plays a major role in infertility, which is the commonest symptom of genital tuberculosis in women. From August 1987 to July 1988, 109 women presenting with infertility were investigated for tuberculosis. None had any other symptoms or signs of the disease. In all cases it was diagnosed by culture of M. tuberculosis in one or more of the 5 specimens (3 menstrual fluid specimens, endometrial tissue and peritoneal fluid) obtained from each woman. In addition Ziehl-Neelsen staining and histological examination were performed on all the specimens. Twenty-three patients (21%) had positive cultures for M. tuberculosis. Of the 26 positive specimens, 16 (69.6%) were menstrual fluid, 4 (17%) endometrial tissue and 6 (26%) peritoneal fluid (3 patients had more than one positive culture). Chest radiographs were normal in all cases. M. tuberculosis cultured in human tissue must be recognized as a pathogen and necessitates treatment. Selective screening procedures should be done to exclude genital tuberculosis as a cause of infertility.     

In vitro modulation of cisplatin cytotoxicity by sparsomycin inhibition of protein synthesis

Inhibition of protein synthesis can alter cellular responsiveness to the classical anticancer drugs. The in vitro response of Chinese hamster ovary (CHO) cells to cisplatin with or without sparsomycin (Sm) was studied with the use of [3H]leucine and [methyl-3H]thymidine incorporation and clonogenic assay. Pretreatment of exponentially growing CHO cells with 1 microgram Sm/ml for 3 or 5 hours decreased [3H]leucine incorporation by 20% and resulted in significant resistance to cisplatin (P = .005). Sm in a concentration of 10 micrograms/ml reduced [3H]leucine and [methyl-3H]thymidine incorporation after 3 hours by 92 and 84%, respectively, and resulted in potentiation of the cisplatin cytotoxicity (P = .004). This effect was the same in the case of nonproliferating cells (P = .005), while protection due to Sm (1 microgram/ml) was seen only during cell proliferation. Simultaneous incubation and postincubation with Sm proved to have much less or no potentiating effect on cisplatin. The mechanisms of both protection and potentiation are still not clear, but our data indicate that Sm is a promising drug for further studies on the modulation of the cancer cell response to classical anticancer drugs.     

Subacute and chronic extradural haematomas

Over an 8-year period (1982-1989) 43 patients with subacute and chronic extradural haematomas were treated. The clinical picture of the patients, computed tomography (CT) as well as operative findings and prognosis were evaluated. The radiological picture as seen on CT was correlated with the time interval elapsing between initial trauma and surgery. Operative findings are discussed and the terms 'subacute' and 'chronic' are defined.     

Effect of doxorubicin exposure on cell-cycle kinetics of human leukemia cells studied by bivariate flow cytometric measurement of 5-iodo-2-deoxyuridine incorporation and DNA content

Cell kinetics of two human leukemic cell lines, Molt-4 and K562, following a 2-h exposure to doxorubicin, were studied. DNA flow cytometry provided static information that for both cell lines a dose-dependent accumulation occurred at the G2 + M compartment that disappeared in time. Kinetic information was provided by time-monitoring cells labeled with 5-iodo-2-deoxyuridine (IdUrd) by two-parameter flow cytometry, analyzing the IdUrd label and the DNA content. The cell-cycle time (Tc) of exponentially growing Molt-4 cells was determined to be 20 h. Twenty-four hours after a 2-h exposure to 0.25 micrograms/ml doxorubicin, the Tc had increased to 23 h; following exposure to 1.0 micrograms/ml, it increased to 33 h. Cell kinetics of K562 cells following doxorubicin exposure were monitored in time up to 4 days. The average Tc of exponentially growing K562 cells was determined to be 24.7 h. Twenty-four hours following 2-h exposure to 0.25 or 0.5 micrograms/ml doxorubicin, the Tc were determined to be 28 and 32 h, respectively. After an additional 2 days, the Tc were both determined to be 24 h. The dose-dependent, reversible cell-cycle delay that persisted at least 48 h should be taken into account as an additional mode for decrease of a (tumor) cell population doubling time after exposure to doxorubicin.     

The prevalence of Chlamydia trachomatis infections in new patients at the Infertility Clinic, UOFS, Bloemfontein

Chlamydia trachomatis is a common sexually transmitted agent causing infertility. Routine screening tests or empirical antibiotic treatment of infertile couples may be justified by the prevalence of this organism. In this study the female partner of 40 consecutive infertile couples was investigated. As a screening test direct immunofluorescence (DIF) was performed on fixed smears from endocervical swabs. Of a total of 40 specimens, 11 (27.5%) were positive, 25 (62.5%) were negative and 4 (10.0%) were equivocal. DIF was repeated on smears from 3 of the last 4 patients and all 3 specimens were positive for C. trachomatis. One patient was lost to follow-up and excluded from the study. Of a total of 39 specimens the final results yielded 14 (35.9%) positive and 25 (64.1%) negative. Statistical analysis showed no correlation between the clinical history and the presence of C. trachomatis infection.     

In vivo and in vitro pharmacokinetic differences between four structurally closely related anthracyclines in hematopoietic cell subtypes in humans

Minor differences in chemical structure of adriamycin (ADM), 4'-epiadriamycin (E-ADM), daunomycin (DNM), and 4-demethoxydaunomycin (D-DNM) lead to large differences between cellular and plasma pharmacokinetic parameters in vivo, as well as in cellular drug handling. Anthracyclines accumulated in cells to several hundred-fold the plasma concentration. Half-lives, as well as the ratio of parent drug/metabolite, differed markedly. The slopes of the in vivo cellular concentration-time curves after the end of the bolus injection resembled the efflux curves observed after a 5-min exposure in vitro. In vivo, the area under the cellular concentration-time curve (AUCc) for equimolar dosages was largest for ADM and smallest for D-DNM. In vitro however, cellular drug levels and AUCc were highest for D-DNM, followed by DNM, E-ADM, and ADM. Final cellular drug concentrations were 300-2500 times the medium concentration, with clearly higher values observed after the 360-min exposure. Minor structural differences were related to considerable variations in cellular drug handling, with different patterns in vivo and in vitro. These studies point to difficulties occurring in the in vitro experimental studies of in vivo pharmacokinetic properties of anthracyclines and stress the need for direct determination of target cell drug concentrations in vivo, in the search for the understanding of cell drug handling-related mechanisms of action of the anthracyclines.     

Positive anatomic orientation of corneal transplant tissue

Anatomic orientation of corneal donor tissue is consistently possible by cutting a "V"-shaped notch in the scleral rim at 12 o'clock. An obvious marker improves the evaluation of suspicious lesions by other observers, facilitates accurate communication of findings to corneal surgeons, and aids in instructing new eye bank technicians. A further possible benefit is that the marker permits anatomically correct orientation of corneal tissue.     

The alpha-L-(1----2)-trirhamnopyranoside epitope on the group-specific polysaccharide of group B streptococci.

A number of epitope specificities associated with the group antigen (group B polysaccharide) of group B streptococci have been identified in a polyclonal antiserum induced in rabbits by a nonencapsulated variant strain of group B streptococci. This was achieved by using a series of oligosaccharide inhibitors, obtained by both synthetic and degradative procedures, to inhibit the binding of the group B polysaccharide to the polyclonal antiserum. While the dominant epitope expressed in the antiserum was alpha-L-Rhap(1----2)alpha-L-Rhap(1----2)alpha-L-Rhap, specificities associated with alpha-L-Rhap and alpha-L-Rhap(1----3)alpha-D-Galp(1----3)beta-D-Glcp-NAc(1----4)alp ha-L-Rhap were also identified. The dominant expression of the former epitope is consistent with its terminal location on the group antigen and also with highly branched multiantennary structure of this antigen. Antibodies specific for the alpha-L-trirhamnopyranoside epitope were purified by affinity chromatography, using the synthetic trisaccharide glucitol as the hapten. Oligosaccharide inhibition studies indicate that the specificity of these antibodies is identical to that of a murine monoclonal antibody induced by the same nonencapsulated strain of group B streptococci.     

VEGF-PLCgamma1 pathway controls cardiac contractility in the embryonic heart

The strength of the heart beat can accommodate in seconds to changes in blood pressure or flow. The mechanism for such homeostatic adaptation is unknown. We sought the cause of poor contractility in the heart of the embryonic zebrafish with the mutation dead beat. We find through cloning that this is due to a mutation in the phospholipase C gamma1 (plcgamma1) gene. In mutant embryos, contractile function can be restored by PLCgamma1 expression directed selectively to cardiac myocytes. In other situations, PLCgamma1 is known to transduce the signal from vascular endothelial growth factor (VEGF), and we show here that abrogation of VEGF also interferes with cardiac contractility. Somewhat unexpectedly, FLT-1 is the responsible VEGF receptor. We show that the same system functions in the rat. Blockage of VEGF-PLCgamma1 signaling decreases calcium transients in rat ventricular cardiomyocytes, whereas VEGF imposes a positive inotropic effect on cardiomyocytes by increasing calcium transients. Thus, the muscle of the heart uses the VEGF-PLCgamma1 cascade to control the strength of the heart beat. We speculate that this paracrine system may contribute to normal and pathological regulation of cardiac contractility.