Assessment of Sertoli cell functional reserve and its relationship to sperm parameters

Sertoli cell functional reserve was assessed in normozoospermic men and oligozoospermic patients and its prognostic potential was evaluated for patient selection and treatment. For the first objective, three groups of normo-follicle-stimulating hormone (FSH)/normozoospermic fertile men (n:12), normo-FSH/oligozoospermic (n:21) and hyper-FSH/oligozoospermic subfertile men participated in the study whereas for the second objective 24 normo-FSH oligozoospermic patients volunteered for a pilot therapeutic trial. For the first part, high purity (hp) FSH (225 i.u., i.m.), human chorionic gonadotropin (hCG) (1500 i.u., i.m.) or their combination was given separately at weekly intervals, with samplings at 0, 3, 24 and 48 h. For the pilot trial, rec-FSH (150 i.u./48 h, i.m.) or placebo were prescribed for 6 months. The main outcome measures for the study were inhibin-B (inh-B), insulin-like growth factor (IGF)-I, testosterone and oestradiol concentrations and the main sperm parameters. Bolus administration of hp-FSH or hp-FSH/hCG combination in normozoospermic men resulted in a significant rise of inh-B in normozoospermic men (mean +/- SD, basal: 183.8+/-24.2 pg/mL in hp-FSH and 175.2+/-23.5 in hp-FSH/hCG treatment; 48 h: 256.1+/-34.2 and 246.3+/-19.0, respectively, p<0.001 for both). In oligozoospermic groups basal inh-B concentration was lower than in normozoospermic men (normo-FSH: 117.4+/-16.5, hyper-FSH: 81.2+/-19.8, p<0.001 for both) with a post-stimulation increase noted only in normo-FSH patients (hp-FSH 24-h: 132.8+/-19.7, p<0.01; hp-FSH/hCG 0 min: 105.7+/-20.1, 24-h: 119.5+/-20.6, p<0.05). Total sperm number and progressive motility showed significant improvements (p<0.05 for both) after 6 months of rec-FSH treatment in the group of patients with a satisfactory response to hp-FSH stimulation. In conclusion, the basal and reserve activity of Sertoli cells, as judged by inh-B secretion, was higher in normozoospermic than in dyspermic men, with a better therapeutic outcome noted in those patients with an adequate response to hp-FSH stimulation.     

Cost-utility analysis comparing free and pedicled TRAM flap for breast reconstruction

The purpose of this study was to compare the free TRAM to the unipedicled TRAM flap in postmastectomy reconstruction, using a cost-utility analysis. A decision analytic model was used for this study. Medical costs associated with the two techniques were estimated from the Ontario Ministry of Health Schedule of Benefits (1998). Hospital costs were obtained from St. Joseph's Healthcare, a university hospital in Hamilton, Ontario. Utilities were obtained from 33 "experts" across Canada and then converted into quality-adjusted life-years (QALYs). The probabilities of various health states associated with unipedicled and free TRAM flaps were obtained by reviewing several key articles. The free TRAM flap was more costly than the unipedicled TRAM flap, but it provided more QALYs. The baseline incremental cost-utility ratio (ICUR) was $5,113.73/QALY, favoring adoption of the free TRAM flap. This study showed that the free TRAM flap is a cost-effective procedure for postmastectomy reconstruction in the Canadian healthcare system.     

Large matrix proteoglycans,versican and perlecan,are expressed and secreted by human leukemic monocytes

THP-1 is a monocytic cell line originally derived from a patient with acute monocytic leukemia. Interactions of THP-1 cells with other cells and their microenvironment are largely determined by proteoglycans (PGs), the identity of which has not been determined. Previous studies on glycosaminoglycan expression by THP-1 cells and peripheral blood mononuclear cells from healthy individuals showed that both cell types secrete mainly chondroitin sulfate PGs to the culture medium, whereas heparan sulfate PGs are mainly retarded at the cell membrane. However, limited data on the type of PGs synthesized by THP-1 is available. In this study, the identification of PG types synthesised by THP-1 cells, which are not differentiated to macrophages, was examined. Analysis at the mRNA level by RT-PCR showed the expression of six cell membrane-associated PGs: syndecan-1, -2 and -4, glypican-1, thrombomodulin and CD44. Cell extraction, ion-exchange chromatography and dot blot analysis of the isolated PG populations with monoclonal antibodies showed the presence of syndecan-1 and thrombomodulin; the other two syndecans were not detected in any of the isolated populations. The synthesis of matrix PGs was also studied. THP-1 monocytes were positive for the mRNA encoding for versican and perlecan, but not for those encoding for decorin, biglycan, betaglycan and fibromodulin. The mRNA encoding for two versican splice variants V0 (351 bp) and V1 (386 bp), but not for V2, were identified. Biochemical analysis showed the presence of perlecan and of two populations of versican in culture medium with protein cores of average molecular sizes similar to those of V0 and V1. The production of these large matrix PGs by THP-1 monocytes is reported for the first time and may be of importance in monocyte malignant transformation and differentiation.     

Respiratory gating for liver tumors: use in dose escalation

PURPOSE: To determine the clinical impact of the Varian Real-Time Position Monitor (RPM) respiratory gating system for treatment of liver tumors. METHODS AND MATERIALS: Ten patients with liver tumors were selected for evaluation of this passive system, which tracks motion of reflective markers mounted on the abdomen with an infrared-sensitive camera. At simulation, a fluoroscopic movie, breathing trace, and CT scans synchronized at end-expiration (E-E) and end-inspiration were acquired in treatment position using the RPM system. Organs and gross tumor volume were contoured on each CT. Each organ's positional change between two scan sets was quantified by calculation of the center of volume shift and an "index coefficient," defined as the volume common to the two versions of the organ to the volume included in at least one (intersection/union). Treatment dose was determined by use of normal tissue complication probability calculations and dose-volume histograms. Gated portal images were obtained to monitor gating reproducibility with treatment. RESULTS: Eight patients received 177 treatments with RPM gating. Average superior-to-inferior (SI) diaphragm motion on initial fluoroscopy was reduced from 22.7 mm without gating to 5.1 mm with gating. Comparing end-inspiration to E-E CT scans, average SI movement of the right diaphragm was 11.5 mm vs. 2.2 mm for two E-E CT scans. For all organs, average E-I SI organ motion was 12.8 mm vs. 2.0 mm for E-E studies. Index coefficients were closer to 1.0 for E-E than end-inspiration scans, indicating gating reproducibility. The average SI displacement of diaphragm apex on gated portal images compared with DRR was 2.3 mm. Treatment was prolonged less than 10 minutes with gating. The reproducible decrease in organ motion with gating enabled reduction in gross tumor volume-to-planning target volume margin from 2 to 1 cm. This allowed for calculated dose increases of 7%-27% (median: 21.3%) in 6 patients and enabled treatment in 2. CONCLUSION: Gating of radiotherapy for liver tumors enables safe margin reduction on tumor volume, which, in turn, may allow for dose escalation.     

Simultaneous quantification of daptomycin and rifampicin in plasma by ultra performance liquid chromatography: Application to a pharmacokinetic study

A rapid and simple method based on ultra performance liquid chromatography (UPLC) with ultra violet detection has been developed for the determination of daptomycin (DPT) and rifampicin (RFM) in rabbit plasma using 4-nitrophenol as internal standard (IS). Sample preparation involved protein precipitation with an acetonitrile:methanol mixture and centrifugation. Chromatographic separation was achieved on an Acquity BEH C18 column (100 mm × 2.1 mm, 1.7 μm) using gradient elution with methanol and 0.1% aqueous TFA. The total analysis time was 4.5 min with DPT and RFM eluting at 1.9 and 2.1 min, respectively. The method was fully validated with a lower limit of quantitation (LLOQ) of 2 μg mL⁻¹ for both DPT and RFM. The intra- and inter-day precision, measured as % relative standard deviation, were less than 12.1 for DPT and 10.7 for RFM, respectively. This validated method was successfully applied to a pharmacokinetic study involving intravenous administration of 14 mg kg⁻¹ DPT and 30 mg kg⁻¹ RFM to rabbits.     

Recurrent massive hemoptysis due to postbronchotomy bronchial artery aneurysm: A case report

Bronchial artery aneurysm (BAA) is a rare clinical entity. A case of intrapulmonary BAA associated with previous bronchotomy at the same site is described. A 22-year-old woman, who had undergone bronchotomy of the intermediate bronchus for the removal of a foreign body four years previously, presented with recurrent hemoptysis. Because of an increased risk for spinal cord ischemia, she immediately underwent lung resection rather than therapeutic embolization. The incidental finding of a BAA of any cause cannot be assumed to be stable, and immediate management should be undertaken regardless of the presence or absence of symptoms.     

Management of gynaecomastia: an update

Gynaecomastia, a benign enlargement of the male breast as a result of proliferation of the glandular component, is common, being present in 30-50% of healthy men. It may be an incidental finding, an acute unilateral or bilateral tender breast enlargement or a progressive painless enlargement of the male breast. A general medical history and careful physical examination, looking for features suggestive of breast cancer, often suffice for evaluation in patients without symptoms or those with incidentally discovered breast enlargement. If the gynaecomastia is of recent onset, a more detailed evaluation, including selected laboratory tests to search for an underlying cause is necessary. Treatment depends on the cause: an offending drug may need to be withdrawn or alternatively radiation, surgery and/or medical therapy may be necessary. The use of a combination of surgical excision and liposuction through a periareolar incision represents the surgical approach of choice.     

Nonbacterial osteitis: a clinical, histopathological, and imaging study with a proposal for protocol-based management of patients with this diagnosis

Background  

Nonbacterial osteitis (NBO), a term referring to sterile bone lesions with nonspecific histopathological features of inflammation, may be either unifocal or multifocal, acute (≤6 months) or chronic, and recurrent. Only when the condition is chronic, recurrent, and multifocal is it appropriate to use the term chronic recurrent multifocal osteomyelitis (CRMO). We present our clinical experience as the largest reported series of children with NBO to date.