Submicroscopic deletions in the Y chromosome of infertile men

Recent investigations have suggested a high prevalence of Y chromosome submicroscopic deletions in men with severely impaired spermatogenesis. We evaluated the frequency of Y chromosome deletions in 160 infertile men using a series of 36 sequence-tagged-sites, emphasizing intervals 5 and 6 of the long arm of the Y chromosome. Peripheral leukocyte DNA was extracted and amplified with two parallel techniques to minimize potential overestimation of the frequency of deletions. The presence of deletions was evaluated relative to patient's sperm concentration, testis volume, and hormonal parameters. Men with sperm concentration <5 x 10(6)/ml had a 7% prevalence of submicroscopic Y chromosome deletions. Deletions were detected in 7% of azoospermic men, 10% of men with <1 x 10(6) spermatozoa/ml, and 8% of men with >1 x 10(6) but <5 x 10(6) spermatozoa/ml. Other clinical parameters did not identify men with Y chromosome deletions prior to polymerase chain reaction (PCR)- based testing for the presence of sequence-tagged-sites. Two distinct regions of Y chromosome deletions were detected, approximately 3.6 Mb and 1.4 Mb in length respectively. These deleted regions are present in AZFb and AZFc respectively. No deletions were detected in AZFa. The loss of these two distinct areas is supported by the finding of highly repetitive sequences along the Y chromosome, predisposing to deletion of specific intervals on the Y chromosome during meiosis. Men with severe male infertility are at high risk for Y chromosome deletions. Testing of men for these genetic abnormalities is indicated prior to treatment with assisted reproduction.      

Disaggregation and invasion of ovarian carcinoma ascites spheroids

Background  

Malignant ascites often develops in advanced stages of ovarian carcinoma, consisting of single and aggregated tumor cells, or spheroids. Spheroids have commonly been used as tumor models to study drug efficacy, and have shown resistance to some chemotherapies and radiation. However, little is known about the adhesive or invasive capabilities of spheroids, and whether this particular cellular component of the ascites can contribute to dissemination of ovarian cancer. Here, we examined the invasive ability of ascites spheroids recovered from seven ovarian carcinoma patients and one primary peritoneal carcinoma (PPC) patient.     

Rheumatoid arthritis: MR imaging manifestations

Radiologic assessment of the stage and treatment response of rheumatoid arthritis (RA) is based on the presence of bone erosions, joint-space narrowing, and osteoporosis. Most radiologic methods for staging RA lack interobserver correlation and are time consuming. Magnetic resonance (MR) imaging provides excellent depiction of soft-tissue abnormalities of the joints affected by RA, which allows detection of early changes. Nineteen joints of 17 patients with RA were studied with surface-coil MR imaging. Measurable abnormalities demonstrated by MR imaging but not clearly seen on plain radiographs included bone erosions, joint effusion, synovial sheath effusion, and cartilage irregularity and thinning. Seven patients of this group underwent MR imaging before and after 6 months of gold therapy. Four patients had significant interval changes on MR images that were not seen on plain radiographs. MR imaging may become a sensitive and objective method for quantitative assessment of the joint changes of RA.     

Osteochondral allograft transplantation

Experience with fresh osteochondral allografting for cartilage defects in the knee now extends two decades. Clinical outcomes and basic scientific investigations have supported the theoretic basis for this procedure. At the University of California, San Diego, our experience has encouraged us to continue to offer this procedure as a primary treatment for both large and small articular cartilage defects in the young knee. The success rate of fresh osteochondral allografting, particularly in isolated femoral condylar defects, compares favorably with other presently available cartilage repair and resurfacing techniques. In our second hundred cases, which we are currently evaluating, failure of monopolar allografts has been exceedingly rare in short-term follow-up. Fresh osteochondral allografting also appears to be effective in treating larger osteochondral lesions, where there are few other attractive alternatives. Fresh osteochondral allografts can thus be used to treat a wide spectrum of articular pathology. Technical refinements, and improvement in our understanding of graft-host interaction, as well as chondrocyte biology, should continue to improve clinical results. Disadvantages of fresh osteochondral allografting include the relative paucity of donor tissue, complexities in procurement and handling, and the possibility of disease transmission through the transplantation of fresh tissue. At present, only institutions that have overcome these obstacles seem capable of routinely performing this type of articular cartilage transplantation. In the future, as tissue banking and cartilage storage technology advance, fresh allograft tissue may become more available, allowing more widespread use of fresh osteochondral allografting in the treatment of articular cartilage lesions.     

Human malignancy-associated nucleolar antigen as a marker for tumor cells in patients with acute leukemia

Tumor burden in adult patients with acute leukemia is assessed using the percentage of blast cells in the bone marrow or blood. It is clear, however, that not all blast cells are leukemic cells, especially during rapid marrow regeneration. Similarly, some leukemia cell lines have been shown to differentiate in vitro, and the same process also occurs in vivo. Therefore, the leukemic burden may be due to more differentiated cells as well as to blast cells. The purpose of this study was to investigate whether the human malignancy-associated nucleolar antigen (HMNA) could be used as a marker for leukemic cells and to examine its potential as a diagnostic tool. The proportion of HMNA-positive cells in the bone marrow of patients with acute leukemia was determined by indirect immunofluorescence with antibodies to HMNA and was compared with the differential counts routinely made in the clinic laboratory. The percentages of HMNA-positive cells among the nucleated cells in the marrow of 72 patients with clinical evidence of leukemia were significantly higher (range 9%-98%, median 83%) than those observed for nonleukemic individuals (range less than 0.05%-2.5%, median 1%) or for fractions of marrow cells from normal volunteers enriched for normal early progenitor cells (less than or equal to 2%). Patients with leukemia in remission had a lower percentage of HMNA- positive cells (range 0%-83%, median 3%). The percentage of HMNA- positive cells increased as patients approached relapse. Although the percentage of HMNA-positive cells was related to the percentage of blast cells in the bone marrow of the patients with leukemia, some partially differentiated cells were also HMNA-positive in some specimens, and some blastic cells were HMNA-negative in other specimens. These studies indicate the potential usefulness of HMNA as a marker for leukemic cells.     

Epilepsy in very preterm infants: neonatal cranial ultrasound reveals a high-risk subcategory

The aim of this study was to investigate the association between epilepsy and perinatal brain injury in a cohort of 610 infants born preterm at <33 weeks' gestation. The prevalence of epilepsy in this cohort was 4.3% as determined by a postal questionnaire survey. Most children with epilepsy (16 of 24) had high-risk cranial ultrasound lesions including haemorrhagic parenchymal infarction (HPI), posthaemorrhagic hydrocephalus, and cystic periventricular leukomalacia (PVL). Of all the children in our cohort with high-risk brain lesions, those with epilepsy were more likely to have HPI and significantly less likely to have cystic PVL, although it is possible that PVL was not noticed in some cases. Children with epilepsy and high-risk cranial ultrasound lesions also showed more cognitive impairment than children with high-risk lesions but no epilepsy, which suggested more cortical grey-matter damage. We suggest that brain injury has occurred outside the confines of the periventricular white matter in this group of preterm infants with epilepsy.     

Systemic to pulmonary arterial shunts in neonates

Background The major strategy for palliation of cyanotic lesions in neonates is the systemic to pulmonary arterial shunt. Methods Between May 1995, and December 2002, 48 consecutive neonates underwent systemic to pulmonary arterial shunts for cyanosis with reduced pulmonary blood flow. The mean age was 11.6 days (±SD 7.38) and the mean weight, 3.2kg (±SD 0.52). The babies were classified into three groups: Group I-Tetralogy-pulmonary Atresia (n=18), Group II-single Ventricle-Pulmonary atresia without (n=19) and with (n=5) isomerism, Group III-Pulmonary Atresia with Intact ventricular septum (n=6). Diagnosis was made by 2D echocardiography. Indication for cardiac catheterization was delineation of pulmonary anatomy/ductus laterality (n=4) or balloon atrial septostomy (n=4). The surgical procedure was a modified Blalock-Taussig shunt on the side of the situs. Post-operatively, no anti-coagulation or anti-platelet medication was employed. Results There was no mortality. Four cases required revision of the shunt in the immediate post-operative period for shunt thrombosis. The mean follow up was 17.54 months (±SD 8.36). In Group I, nine patients have undergone total correction with or without a conduit, while three required new arterial shunts for shunt/pulmonary artery stenosis. In Group II, nine patients have undergone bi-directional Glenn with atrial septectomy (n=2) and pulmonary artery plasty (n=4) and one patient underwent Fontan completion. In Group III, two patients underwent bi-directional Glenn and two had pulmonary valvotomy with/without right ventricular outflow tract widening. All the remaining babies are waiting for the second/final stage palliation or total correction. Conclusion Systemic to pulmonary arterial shunts in neonates is a gratifying and reasonably safe surgical procedure. Most babies become candidates for eventual univentricular/bi-ventricular repair.