Efficient immunocastration of male piglets by immunoneutralization of GnRH using a new GnRH-like peptide

BACKGROUND: DTIC and interleukin-2 (IL-2), as single agents, have a limited anti-tumor activity in patients with metastatic melanoma. Experimentally, thymosin alpha 1 (TA1) may modulate the action of IL-2. We investigated the clinical and immunological effects of a combination with these three agents. PATIENTS AND METHODS: Forty-six patients with measurable metastatic melanoma were treated with DTIC 850 mg IV on day 1, TA1 2 mg s.c. on days 4 to 7, and IL-2 18 MU/m2/d by continuous intravenous infusion on days 8 to 12. Cycles were repeated every 3 weeks. RESULTS: Objective responses were obtained in 15 (36%) of 42 evaluable patients (CI at 95%: 22%-50%). Two patients experienced complete responses, and stable disease was observed in five. The median time to progression was 5.5 months and median survival was 11 months. Side effects were predominantly caused by IL-2. Treatment was tolerated reasonably well, and there was no overlapping toxicity or interference between chemotherapy and biotherapy. Baseline sCD4 levels seem to correlate to tumor burden. Patients benefiting from treatment had lower sCD4 and higher sCD8 than did progressing patients. CONCLUSIONS: The combination of DTIC + TA1 + IL-2 is active in the treatment of advanced melanoma, with acceptable toxicity. However, even more active regimens are needed, and the interactions between thymic hormones and cytokines should be further explored.     

Fluoride uptake and release characteristics of glass ionomer cements

The aims of this study were firstly to investigate the fluoride-releasing characteristics of five commercial glass ionomer materials: Ketac Fil, Chemfil Superior, Fuji II LC, Aquacem and Vitrebond. The second aim was to assess the fluoride uptake and subsequent release from the same range of materials. In both tests, ten discs, 6 mm in diameter with a thickness of 1.5 mm, were made for each material. The initial fluoride release was assessed over a 60-day period for all materials. Each disc was immersed in 2 ml of de-ionised water within a plastic vial. The solutions were changed daily up to day 15, and thereafter every 3 and 4 days until the end of the test. All of the materials released measurable amounts of fluoride throughout the test period, with a considerable range on day 1 (15.3-155.2 ppm F). The concentration of fluoride released on the 2nd day fell sharply for all materials (range 6.3-44.3 ppm F). By day 60 all materials continued to release fluoride, albeit to a lesser extent (range 0.9-3.99 ppm F). With regard to the uptake and release of fluoride, a similar protocol was employed, although all samples were immersed in 1 litre of de-ionised water for 60 days to allow the majority of the fluoride to leach out from the materials. The ten pellets for each material were divided into two groups, five samples as control and five samples as test. Each day over a 20-day period all test samples were exposed to a 1000-ppm F solution for 2 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Magnetic resonance imaging of a mediastinal ependymoma

Ependymomas typically occur in the brain and spinal cord, and represent 5% and 16% of primary intracranial and spinal cord tumors respectively. Ependymomas arising outside the central nervous systems are uncommon and when they do occur are usually seen in the sacrococcygeal region. Other reported sites include the pelvis, spinal nerve roots, and lung. An extraspinal mediastinal ependymoma is a rare occurrence, with only two previously reported cases to our knowledge. In both instances, the lesion arose in the posterior mediastinum, and were imaged with either chest radiographs alone or chest radiographs and computed tomography. In our case, plain radiography was followed by magnetic resonance imaging. This report documents the clinical, pathological, and magnetic resonance imaging findings in a case of a posterior mediastinal ependymoma. Primary mediastinal ependymomas are rare lesions that may be considered in the differential diagnosis of a posterior mediastinal mass.     

Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial

Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems. We conducted a 1-year prospective, randomized, double-blind trial in 143 postmenopausal osteoporotic women (mean +/- SD age, 68.4+/-5.0 years) with at least one prevalent vertebral fractures and low bone mineral density (BMD), comparing groups receiving raloxifene at 60 mg/day (RLX60) or 120 mg/day (RLX120) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding, thrombophlebitis, breast abnormalities, or increased endometrial thickness (assessed by ultrasonography). As compared with controls, the changes in values over 1 year for RLX60 and RLX120, respectively, were significant for serum bone alkaline phosphatase (-14.9%, -8.87%), serum osteocalcin (-20.7%, -17.0%), and urinary C-telopeptide fragment of type I collagen/creatinine (-24.9%, -30.8%), markers of bone turnover; for serum total cholesterol (-7.0% for RLX60) and low density lipoprotein cholesterol (LDL) (-11.4% for RLX60) and for the LDL/HDL cholesterol ratio (-13.2%, -8.3%). BMD increased significantly in the total hip (1.66% for RLX60) and ultradistal radius (2.92%, 2.50%). There were nonsignificant trends toward increases over controls in BMD for lumbar spine, total body, and total hip (for RLX120). Using a >15% cutoff definition, raloxifene had no effect on incident fractures, but using a >30% cutoff, there was a dose-related reduction (p = 0.047). We conclude that raloxifene therapy is well tolerated, reduces serum lipids, and does not stimulate the uterus or breasts. It has beneficial effects on bone, although, under the conditions of this study, these appear to be of a smaller magnitude than have been reported with estrogen therapy.     

Treatment of hypertension in the presence of coexisting medical conditions

Treating hypertension reduces morbidity and mortality. Unfortunately, hypertension often exists in patients with other medical conditions. In these patients, the selection of an antihypertensive agent is often influenced by the presence of the coexisting condition. Conversely, the treatment of the coexisting medical condition may be influenced by the presence of hypertension. Given the vast array of antihypertensive medications available today, appropriate treatment of both hypertension and coexisting conditions can be achieved with careful selection of medications. This review discusses factors to consider when treating elderly patients with hypertension with the following coexisting conditions: dyslipidaemia, glucose intolerance, sexual dysfunction, cardiovascular disease, pulmonary disease, renal disease and neuropsychiatric disorders. Hypothyroidism, hyperthyroidism and various states of high cardiac output may cause hypertension. These conditions should be identified, since they are often treatable with subsequent resolution of the hypertension.     

Role of zinc during hamster sperm capacitation

Zinc stabilizes somatic cell membranes and DNA, inhibits respiration, is present in high concentrations in the male reproductive tract, and may stabilize sperm during storage and ejaculation. Zinc removal from sperm may be necessary to prepare sperm for fertilization (capacitation). Incubation with Zn2+ chelators, e.g., D-penicillamine, can capacitate hamster sperm (Andrews and Bavister, Gamete Res 1989; 23:159-70). In the present study, the Zn(2+)-specific fluorochrome N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide (TSQ) and the vital stain propidium iodide were used to assess the zinc content of live hamster sperm with flow cytometry before and after capacitation. Capacitation was monitored with a salt-stored zona pellucida penetration assay or the occurrence of spontaneous or induced (with lysophosphatidylcholine) acrosome reactions. The effect of added zinc on sperm capacitation was also evaluated. Image Analysis was used to determine the subcellular location of zinc (TSQ fluorescence) and atomic absorption to determine whether the total zinc content of sperm changes during capacitation. Sperm incubated under non-capacitating conditions had high TSQ fluorescence and could not penetrate zonae pellucidae. Sperm incubated under capacitating conditions (plus BSA or D-penicillamine) were zinc-depleted (low fluorescence) and penetrated 90% or 78% of zonae, respectively. Image analysis showed a significant reduction in zinc in the acrosomal region during capacitation with BSA, but this did not correlate with the occurrence of spontaneous acrosome reactions. The atomic absorption data showed that the total zinc content of sperm was reduced by 44% or 40% when sperm were incubated under capacitating conditions (BSA or D-penicillamine, respectively). Zona pellucida penetration was completely inhibited when zinc was present throughout the capacitation period but not when it was added at the end of incubation. These data indicate that removal of zinc from hamster sperm is correlated with capacitation and may play a key regulatory role in this process.     

Effects of WB4101 and chloroethylclonidine on the positive and negative inotropic actions of phenylephrine in rat cardiac muscle

This study was designed to determine if the positive and negative inotropic actions of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium are mediated via different alpha-1-adrenergic receptor (AR) subtypes. Inotropic effects of phenylephrine were examined in isolated left atrial and papillary muscle before and after treatment with prazosin, WB4101 (N-[2-(2,6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine), chloroethylclonidine (CEC) and WB4101 plus CEC. Phenylephrine (10 microM) elicited a monophasic positive inotropic response in left atrial muscle and a triphasic inotropic action in papillary muscle (transient positive, then negative inotropic components preceding a sustained positive inotropic response). CEC, WB4101 and prazosin each antagonized the monophasic response in isolated left atria and the sustained positive inotropic response in papillary muscle. CEC and prazosin each antagonized the transient negative inotropic component in papillary muscle. The transient positive inotropic response was not affected by CEC, WB4101 or CEC plus WB4101, but was antagonized by higher concentrations of prazosin. These data suggest that the sustained positive inotropic effect of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of alpha-1A and alpha-1B ARs, whereas the transient negative inotropic component of the triphasic response in ventricular preparations is mediated via alpha-1B ARs. However, present data do not exclude the possibility that the CEC-sensitive inotropic responses elicited by phenylephrine may be mediated in part by other recently described alpha-1 subtypes. The receptors involved in the transient positive inotropic action cannot be identified by current results.     

Uncemented total shoulder arthroplasty. A review

Clinicians have had much experience with uncemented humeral components. A press-fitted humeral component will usually remain stable in the absence of a glenoid component. From the information available, surgeons should not continue to use press-fitted humeral components for total shoulder arthroplasty. Tissue ingrowth humeral components offer promise; however, the reports to date have short or intermediate length followup, and radiographic results do not equal those of cemented components. Early clinical results with tissue ingrowth glenoid components are excellent; radiographically evident changes occur much less frequently than they do following cement fixation. However, their disadvantage is the possibility of accelerated polyethylene wear and subsequent metal-induced synovitis. As such, there are no clear cut indications for cement fixation versus tissue ingrowth fixation for the glenoid component other than those intuitively based on bone quality and quantity in the glenoid fossa. Accruing experience will help to define the indications better, but given the similarity of clinical outcomes to date, distinction between the options may be difficult.     

Antimicrobial strategies in the care of organ transplant recipients

OBJECTIVE: To evaluate amniotic fluid lamellar body counting as a fetal lung maturity test. Lamellar body particles can be rapidly counted using the platelet channel of most blood cell analyzers. METHODS: We conducted a 3-year prospective clinical outcome study. During the interval under study, outcomes of 247 neonates were used to evaluate the test; 28 neonates developed respiratory distress syndrome (RDS). Lecithin-sphingomyelin ratio (L/S) was available for 187 cases. RESULTS: All cases of RDS had lamellar body counts of 55,000/microL or less and L/S of 2.2 or less; 59% of cases with no RDS had counts greater than 55,000/microL and 70% of normal cases had L/S higher than 2.2. CONCLUSION: Use of lamellar body counts is justified as a rapid screening test to predict fetal lung maturity. Immature results should be followed by a more specific test such as L/S.