Three-dimensional ultrasonographic ovarian measurements and in vitro fertilization outcome are related to age

OBJECTIVE: To evaluate whether the number of ovarian antral follicles, ovarian volume, and ovarian stromal blood flow change with age and to prospectively analyze whether three-dimensional ultrasonographic measurements predict ovarian response and IVF outcome. DESIGN: Prospective analysis. SETTING: Assisted reproductive unit. PATIENT(S): Fifty-six consecutive women 22 to 43 years of age with normal basal serum FSH concentrations who were undergoing their first IVF cycle. MAIN OUTCOME MEASURE(S): Number of ovarian antral follicles, ovarian volume, and ovarian stromal flow index were determined by three-dimensional and power Doppler ultrasonography. Pretreatment measurements were compared with number of recovered oocytes, fertilization rates, and pregnancy rates. RESULT(S): As patient age increased, significant trends in ovarian volume, number of follicles, and stromal vascularity decreased. Three-dimensional ovarian measurements and fertilization rates differed significantly among age groups. For each age group, a higher number of antral follicles, greater ovarian volume, and favorable ovarian stromal vascularity was associated with higher number of retrieved oocytes and increased pregnancy rates. CONCLUSION(S): Increasing patient age is associated with poor ovarian response, as represented by smaller ovarian volume, lower antral follicle count, and poor stromal vascularity. Three-dimensional power Doppler ultrasonography can help to individualize IVF in patients regardless of age.     

Identification of the B-cell epitopes of the early endosome antigen 1 (EEA1)

Early endosome antigen 1 (EEA1) is a target autoantigen in patients diagnosed with neurological and other autoimmune conditions. Eighteen of 65 sera (28%) that displayed a vesicular cytoplasmic staining pattern also immunoprecipitated the recombinant EEA1. These 18 sera were selected for further clinical, serological and epitope mapping studies. Thirty-six percent of the 18 patients had neurological diseases. Seventeen sera (94%) reacted with the partial length EEA1 constructs that included the C-terminal zinc finger (+FYVE) and the methyl accepting domain (LeuMA: amino acids 82-1411) in an addressable laser bead assay suggesting that the assay may be used for rapid laboratory detection of anti-EEA1 antibodies. Three of seven sera selected for epitope mapping studies bound to EEA1 peptides represented by amino acids 1096-1125, and two reacted with peptides represented by amino acids 1296-1320. One serum reacted only with the C-terminal peptide 1096-1125. The remaining serum reacted with other EEA1 epitopes. This data was supported by the observations that all the sera immunoprecipitated the C-terminal +FYVE (EEA1 1064-1411) construct, a peptide that also contained the linear epitopes 1096-1140. The limited epitope mapping studies suggest that the sera from patients with non-neurological diseases recognized epitopes in the central and C-terminal EEA1 domains, whereas the patients with neurological disease recognized a more restricted set of epitopes in the C-terminal.     

Is pregnancy a model how we should control some autoimmune diseases?

Pregnancy and parturition are the physiological conditions that affect the course and severity of numerous autoimmune diseases. If genotype might be primarily considered as a determinant of whether or not autoimmunity develops, clinical heterogeneity of the disease might arise from the interaction of the genotype and the environment. Numerous external factors with extremely important immunoregulatory properties, including hormones, affect an in vivo open complex immune system. The further investigation of the role of neuroendocrine-immunological network, including a pregnancy-associated immunomodulation, as much as the role of "causative" or "trigger" agents, may allow the rational basis of new alternative treatment of numerous autoimmune diseases.     

Loss of heterozygosity of DPC4 tumor suppressor gene in human sporadic colon cancer

We investigated the prevalence of DPC4 loss of heterozygosity in sporadic colorectal cancer. Thirty-six cases of human sporadic colon carcinoma and corresponding normal tissue samples were examined to evaluate loss of heterozygosity at the DPC4 tumor suppressor locus using variable nucleotide tandem repeat (VNTR) analysis and three polymorphic markers. From 36 analyzed samples 35 (97%) were heterozygous or informative. Loss of heterozygosity at the DPC4 locus was detected in 18 (51%) of informative tumor DNAs. The DPC4 LOH was more frequent in smaller tumors (<5 cm) than in larger ones. There was no correlation between DPC4 LOH and age or sex of patients. There was a negative correlation between DPC4 LOH and histological grade or Dukes' stage of tumors, but without statistic significance. Observed results are in agreement with the view that malignant progression is consequence of many genetic changes. It can be concluded that inactivation of the DPC4 gene plays a role in a multistep process of outgrowth and progression of colon cancer.     

Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans

In this study, we have examined the correlation between the histological and histochemical changes of articular cartilage and bone parameters of the underlying subchondral bone. The aim was to elucidate patterns of bone parameter changes within different depths of subchondral bone in the joints with macroscopically normal cartilage and in joints with osteoarthritis (OA). Ten tibial plateaus were taken from patients during total knee replacement surgery due to severe OA. They were compared with 10 sets of tibial condyles obtained from autopsy subjects with no history of bone or joint disease. The cylindrical cartilage-bone samples were taken out from the anterior, posterior, external, and internal areas of the condyles for cartilage assessment (Mankin score) and subchondral bone histomorphometry. Four histomorphometric parameters were measured: bone volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and trabecular separation (Tb.S). Our study showed that subchondral bone from the OA group had significantly higher bone volume (54.1 +/- 10.6%) than control group (37.8 +/- 8.1%) (P < 0.01). In addition, trabecular parameters from the OA subchondral bone showed a smaller number of sparsely distributed and thicker trabecules than in control group (P < 0.05). Medial and lateral condyle from the control group did not differ significantly, while medial condyle from OA group showed a high increase of bone volume (62.8 +/- 13.3) and consecutively different trabecular parameters when compared with the lateral condyle from the same group. Also, it was shown that there are regional differences (anterior, posterior, internal, and external) in bone parameters between both condyles within both, control and OA groups. Comparison of bone parameters from three different stage of articular cartilage degeneration (Mankin score) showed that higher degree of cartilage degeneration is followed by significant changes in subchondral bone architecture. Furthermore, we have found that progression of cartilage degeneration leads to changes in bone parameters which affected deeper levels of subchondral bone. According to these results, it can be suggested that changes in histomorphometric parameters of subchondral bone are secondary to cartilage damage and proceed deeper into subchondral bone with increasing cartilage degeneration.     

Primary MALT lymphoma of the kidney

A primary mucosa associated lymphoid tissue tumor (MALT) of the kidney in a 50-year-old man who suffered from on therapy resistant high blood pressure over 15 years period is presented. A mass in the right kidney (6x5x3 cm) during routine check up was discovered on ultrasonography and confirmed on CT scan and NMR. The patient was submitted to nephrectomy. A mass involving kidney, pyelon and upper part of the ureter was found. Histology showed low grade non-Hodgkin B-cell lymphoma of MALT type. The neoplastic cells were positive for monoclonal antibodies CD20, CD79alpha, surface and cytoplasmic and IgM immunoglobulins and showed light chain restriction (kappa+). After histology was available, a careful staging was performed. The disease was not found anywhere else. It was concluded that the patient belonged to the stage IE of primary kidney MALT lymphoma. Gastroscopy showed signs of chronic superficial gastritis. Urease test was positive and IgG antibodies against Helicobacter pylori in titer 421 were found as well. Except for Helicobacter pylori no additional therapy was given.     

Pulmonary lymphohistiocytic reactions temporally related to etanercept therapy.

This report details the pulmonary pathologic findings in four patients with rheumatoid arthritis, who developed new onset of pulmonary signs and symptoms with alveolar infiltrates temporally related to the institution of etanercept therapy. Biopsy findings showed an interstitial and air space lymphohistiocytic infiltrate with non-necrotizing granulomas, in the setting of negative cultures and special stains for microorganisms. The association with etanercept therapy and granulomatous reactions is discussed along with the differential diagnosis.     

Impaired visuospatial associative memory and attention in obsessive compulsive disorder but no evidence for differential dopaminergic modulation

Rationale  

Patients with obsessive compulsive disorder (OCD) demonstrate impaired cognition in some selected domains. Although serotoninergic dysfunction has been implicated in OCD, recent evidence suggests that dopamine may play a role as well.     

Matrix metalloproteinase-9 and cell kinetics during the collection of peripheral blood stem cells by leukapheresis.

The plasma levels of matrix metalloproteinase-9 (MMP-9) were determined during 41 collections of peripheral blood stem cells (PBSC) by standard volume (two blood volumes) leukaphereses (SVL) in 29 donors (7 allogeneic and 22 autologous) mobilized with the granulocyte-colony stimulating factor (G-CSF). The association between MMP-9 levels and cell counts in donor's blood was explored. During the processing of the first blood volume (BV), MMP-9 levels declined on average by 31% and persisted at the same level during the processing of the second BV. During the collection, a slight decline of white blood cells (WBC), polymorphonuclear neutrophils (PMN) and platelets (PLT) in donor's blood was accompanied by a significant drop of CD34+ cells by 37% after 1 BV and by 44% after 2 BV had been processed (p=0.001). The drop of MMP-9 plasma levels showed a loose correlation with the decrease of WBC (r=0.68, p=0.002) and PMN counts (r=0.67, p=0.001). We conclude that the levels of MMP-9 that have been elevated by the mobilization of donors with G-CSF, decrease during the collection of PBSC by 4h SVL. The observed decrease was indirectly related to the drop of WBC and PMN counts, suggesting that certain other factors have an influence on MMP-9 kinetics during PBSC collection.