Prediction of reparability of meniscal tears in athletes using magnetic resonance.

Meniscal tears account for approximately 15% of all knee injuries and almost 25% of them require surgical procedures. Magnetic Resonance Imaging (MRI) is widely used for noninvasive assessment of the knee joint and is considered reliable and a powerful tool for the detection of soft tissue injuries of the knee. The aim of the study was to evaluate the sensitivity, specificity, and accuracy of magnetic resonance imaging (MRI) to predict the meniscal tears repair in sports practitioners. 104 incoming consecutive patients who underwent knee joint ligament reconstruction and/or arthroscopy for the treatment of meniscal injury at knee joint were imaged using a 1.5-T MRI scanner prior to arthroscopy. MRI images were evaluated for anterior cruciate ligament (ACL), articular cartilage, and meniscal injury. Images were correlated with arthroscopic findings, used as the gold standard. The sensitivity, specificity, and accuracy of MRI in predicting meniscal repair were 61.1%, 65.94%, and 64.58%, respectively. The agreement between MRI and arthroscopy yielded a kappa index of 0.236, indicating fair agreement. When the menisci were evaluated separately, 65.85% sensitivity, 45.45% specificity, and 54.16% accuracy were found for the medial meniscus, while 46.15%, 79.51%, and 75.0% for the lateral meniscus, respectively. The accuracy was 62.09% in whose patients that arthroscopy was performed up to 3 months after MRI and 67.18% in those that this time frame was more than 3 months before surgery. The 54 meniscal injuries occurred more frequently in the posterior horn; most injuries had a longitudinal pattern and were located in the red-red (vascular) zone. We suggest that magnetic resonance imaging is only moderately accurate for the prediction of meniscus reparability.

Early functional rehabilitation or cast immobilisation for the postoperative management of acute Achilles tendon rupture? A systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To determine which postoperative rehabilitation regime is superior following surgical repair of acute Achilles tendon rupture. The primary outcomes were patient safety and satisfaction. DESIGN: Intervention meta-analysis. DATA SOURCES: The MEDLINE and CINAHL electronic databases were searched from their date of inception until June 2015 using keywords related to acute Achilles tendon rupture, surgical repair and rehabilitation. The electronic database search was supplemented with forward citation tracking using the Web of Science. ELIGIBILITY CRITERIA: Randomised controlled trials comparing clinical and/or patient-reported outcomes between patients receiving early functional postoperative ankle motion and weight bearing (bracing group), and traditional ankle immobilisation with a non-weight bearing rigid cast (cast group) were eligible for inclusion. Fourteen articles were identified as potentially eligible; 10 sufficient-quality randomised controlled trials involving 570 patients were included for meta-analysis. MAIN RESULTS: A high proportion of patients were able to return to prior employment and sporting activity in both groups. Five of the six trials measuring the time interval showed a faster return to prior sporting level in the bracing group. Subjective patient outcomes were significantly better in the bracing group (for good and excellent results, p=0.01; OR, 3.13; 95% CI 1.30 to 7.53). There was no difference in major complications between the two groups (p=0.21; RD, -0.03; 95% CI -0.06 to 0.01). Dynamometry and anthropometry measurements favoured functional rehabilitation at 6-12 weeks postoperation; however, by 6 months postoperative, the differences were negligible. CONCLUSIONS: Compared to traditional ankle immobilisation, with a non-weight bearing cast following surgical repair of acute Achilles tendon rupture, early dynamic functional rehabilitation is as safe with higher patient satisfaction.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

BACKGROUND: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). TREATMENT: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.

Prevalence of anti-N-methyl-D-aspartate (NMDA) receptor [corrected] antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune condition caused by immunoglobulin (Ig)G antibodies directed against the NR1 subunit of the NMDA glutamate receptor. Approximately 65% of cases present with psychiatric symptoms, particularly psychosis. It remains to be established whether anti-NMDA receptor antibodies can cause a 'purely' psychotic illness without overt neurological symptoms. METHOD: We conducted a systematic literature search to establish what proportion of patients with schizophrenia and related psychoses have antibodies directed against the NMDA receptor. Studies were included if (a) subjects had a diagnosis of schizophrenia, schizophrenia spectrum disorder or first-episode psychosis (FEP) using standard criteria, (b) serum was analysed for the presence of anti-NMDA receptor antibodies; and (c) the purpose of the study was to look for the presence of anti-NMDA receptor antibodies in patients with a primary psychiatric diagnosis without clinical signs of encephalitis. RESULTS: Seven studies were included, comprising 1441 patients, of whom 115 [7.98%, 95% confidence interval (CI) 6.69-9.50] were anti-NMDA receptor antibody positive. Of these, 21 (1.46%, 95% CI 0.94-2.23) patients were positive for antibodies of the IgG subclass. Prevalence rates were greater in cases than controls only for IgG antibodies; other subclasses are of less certain aetiological relevance. There was significant heterogeneity in terms of patient characteristics and the antibody assay used. CONCLUSIONS: A minority of patients with psychosis are anti-NMDA receptor antibody positive. It remains to be established whether this subset of patients differs from antibody-negative patients in terms of underlying pathology and response to antipsychotic treatment, and whether immunomodulatory treatments are effective in alleviating psychotic symptoms in this group.

Perforin-2 restricts growth of Chlamydia trachomatis in macrophages.

Chlamydia trachomatis is a Gram-negative obligate intracellular bacterium that preferentially infects epithelial cells. Professional phagocytes provide C. trachomatis only a limited ability to survive and are proficient killers of chlamydiae. We present evidence herein that identifies a novel host defense protein, perforin-2, that plays a significant role in the eradication of C. trachomatis during the infection of macrophages. Knockdown of perforin-2 in macrophages did not alter the invasion of host cells but did result in chlamydial growth that closely mirrored that detected in HeLa cells. C trachomatis L2, serovar B, and serovar D and C. muridarum were all equally susceptible to perforin-2-mediated killing. Interestingly, induction of perforin-2 expression in epithelial cells is blocked during productive chlamydial growth, thereby protecting chlamydiae from bactericidal attack. Ectopic expression of perforin-2 in HeLa cells, however, does result in killing. Overall, our data implicate a new innate resistance protein in the control of chlamydial infection and may help explain why the macrophage environment is hostile to chlamydial growth.

No increase in adverse events with lateral extra-articular tenodesis augmentation of anterior cruciate ligament reconstruction - Results from the stability randomized trial.

OBJECTIVES: Results from the Stability Study suggest that adding a lateral extra-articular tenodesis (LET) to a hamstring tendon autograft reduces the rate of anterior cruciate ligament reconstruction (ACLR) failure in high-risk patients. The purpose of this study is to report adverse events over the 2-year follow-up period and compare groups (ACLR alone vs. ACLR + LET). METHODS: Stability is a randomized clinical trial comparing hamstring tendon ACLR with and without LET. Patients aged 14-25 years with an ACL deficient knee were included. Patients were followed and adverse events documented (type, actions taken, resolution) with visits at 3, 6, 12, and 24 months postoperatively. Adverse events were categorized as none, minor medical, minor surgical, contralateral ACL rupture, or graft rupture. Patient reported outcome measures (PROMs) collected at each visit included the Knee Injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee Score (IKDC), and ACL Quality of Life Questionnaire (ACL-QOL). RESULTS: In total, 618 patients were randomized (mean age 18.9 years, 302 (49%) male). Forty-five patients (7%) suffered graft rupture; 34 (11%) in the ACLR group compared to 11 (4%) in the ACLR + LET group (RRR = 0.67, 95% CI 0.36 to 0.83, p < 0.001). There were no differences in effusion or infection rates between groups. The ACLR + LET group experienced an increased number of hardware removals (10 vs. 4). Overall, the rate of minor medical events (11%), minor surgical events (7%), and ipsilateral or contralateral ACL tears (10%) were low considering the high-risk patient profile. Increasing severity of adverse events was associated with lower PROMs at 24 months post-operative. Patients in the ACLR + LET group reported greater degree of pain at 3 months only. There were no clinically significant differences in range of motion between groups. CONCLUSIONS: The addition of LET to hamstring tendon autograft ACLR in young patients at high risk of re-injury resulted in a statistically significant reduction in graft rupture. While the addition of LET may increase rates of hardware irritation, there was no significant increase in overall rates of minor medical adverse events, minor surgical events, or overall re-operation rates. The concerns regarding complications associated with a LET did not materialize in this study. LEVEL OF EVIDENCE: Level I.

An evaluation study of EGFR mutation tests utilized for non-small-cell lung cancer in the diagnostic setting.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation is predictive for the efficacy of EGFR tyrosine kinase inhibitors in advanced non-small-cell lung cancer (NSCLC) treatment. We evaluated the performance, sensitivity, and concordance between five EGFR tests. MATERIALS AND METHODS: DNA admixtures (n = 34; 1%-50% mutant plasmid DNA) and samples from NSCLC patients [116 formalin-fixed paraffin-embedded (FFPE) tissue, 29 matched bronchofiberscopic brushing (BB) cytology, and 20 additional pleural effusion (PE) cytology samples] were analyzed. EGFR mutation tests were PCR-Invader, peptide nucleic acid-locked nucleic acid PCR clamp, direct sequencing, Cycleave, and Scorpion Amplification Refractory Mutation System (ARMS). Analysis success, mutation status, and concordance rates were assessed. RESULTS: All tests except direct sequencing detected four mutation types at ≥1% mutant DNA. Analysis success rates were 91.4%-100% (FFPE) and 100% (BB and PE cytology), respectively. Inter-assay concordance rates of successfully analyzed samples were 94.3%-100% (FFPE; kappa coefficients: 0.88-1.00), 93.1%-100% (BB cytology; 0.86-1.00), and 85.0%-100% (PE cytology; 0.70-1.00), and 93.1%-96.6% (0.86-0.93) between BB cytology and matched FFPE. CONCLUSIONS: All EGFR assays carried out comparably in the analysis of FFPE and cytology samples. Cytology-derived DNA is a viable alternative to FFPE samples for analyzing EGFR mutations.

Comparison of bone marrow, disseminated tumour cells and blood-circulating tumour cells in breast cancer patients after primary treatment.

The purpose of this study was to determine whether primary breast cancer patients showed evidence of circulating tumour cells (CTCs) during follow-up as an alternative to monitoring disseminated bone marrow tumour cells (DTCs) by immunocytochemistry and reverse transcriptase (RT)-PCR for the detection of micrometastases. We planned to compare CTC and DTC frequency in low-risk and high-risk patients. We identified two cohorts of primary breast cancer patients who were at low (group II, T(1)N(0), n=18) or high (group III, >3 nodes positive (with one exception, a patient with two positive nodes) n=33) risk of relapse who were being followed up after primary treatment. We tested each cohort for CTCs using the CellSearch system on 1-7 occasions and for DTCs by immunocytochemistry and RT-PCR on 1-2 occasions over a period of 2 years. We also examined patients with confirmed metastatic disease (group IV, n=12) and 21 control healthy volunteers for CTCs (group I). All group I samples were negative for CTCs. In contrast, 7 out of 18 (39%) group II primary patients and 23 out of 33 (70%) group III patients were positive for CTCs (P=0.042). If we count only samples with >1 cell as positive: 2 out of 18 (11%) group II patients were positive compared with 10 out of 33 (30%) in group III (P=0.174). In the case of DTCs, 1 out of 13 (8%) group II patients were positive compared with 19 out of 27 (70%) in group III (P<0.001). Only 10 out of 33 (30%) patients in group III showed no evidence of CTCs in all tests over the period of testing, compared with 11 out of 18 (61%) in group II (P=0.033). A significant proportion of poor prognosis primary breast cancer patients (group III) have evidence of CTCs on follow-up. Many also have evidence of DTCs, which are more often found in patients who were lymph node positive. As repeat sampling of peripheral blood is more acceptable to patients, the measurement of CTCs warrants further investigation because it enables blood samples to be taken more frequently, thus possibly enabling clinicians to have prior warning of impending overt metastatic disease.

The uptake and use of the Monospot test in patients with tonsillitis.

The objective of the study was to ascertain the uptake of the Monospot test in St. James's hospital in Dublin over the five years 2002-2006 and to determine the percentage of Monospot tests which had a positive result. Using the HIPE, Electronic Patient Record (EPR) and Patient Access System (PAS) databases in St. James's Hospital, a cohort of 593 patients with a diagnosis of tonsillitis or infectious mononucleosis was identified. Fourteen patients met the exclusion criteria as outlined below leaving a valid pool of 579 patients. It was ascertained whether each patient had a Monospot performed and if so, whether the result was positive or negative. In total, 249 (43.0%) of the included patients had a Monospot test. Of these, 197 (79.1%) were negative and 29 (11.6%) were positive. In 23 (9.2%) cases, no result was available. The uptake of the Monospot increased over the five years studied. A positive Monospot impacts on treatment and follow up. We therefore recommend that one is carried out in all patients presenting with acute tonsillitis.

Antepartum bleeding of unknown origin in the second half of pregnancy and pregnancy outcomes.

OBJECTIVE: The purpose of our investigation was to evaluate factor(s) associated with unexplained antepartum bleeding of unknown origin (ABUO) after 24 weeks of pregnancy and correlate unexplained haemorrhage with maternal and perinatal outcomes. DESIGN: This is a retrospective observational study. SETTING: King Edward Memorial Hospital (KEMH), Subiaco, Western Australia. POPULATION: Singleton pregnancies delivering at KEMH between January 1998 and December 2004. METHODS: ABUO was defined as bleeding after 20 weeks of gestation but before the onset of labour with no cause detected on vaginal examination or abdominal ultrasound. Outcomes of these pregnancies were collated and compared with those of pregnancies without ABUO. MAIN OUTCOME MEASURES: Antepartum complications assessed included pre-eclampsia/eclampsia, gestational diabetes and preterm birth. Intrapartum evaluations included labour inductions, mode of delivery and gestational age at delivery. Neonatal outcomes evaluated included birthweight, Apgar scores, newborn intensive care unit (NICU) admission, neonatal complications and risk of perinatal/neonatal death. RESULTS: Between January 1998 and December 2004, there were 26 583 deliveries without ABUO and 1431 with ABUO. Multivariable analyses of the ABUO effects revealed that ABUO was a simultaneously significant risk factor for term labour inductions (OR = 2.00, 95% CI: 1.72-2.32, P < 0.001), preterm delivery (OR = 4.31, 95% CI: 3.84-4.84, P < 0.001), NICU admission (OR = 1.23, 95% CI: 1.01-1.51, P = 0.042), hyperbilirubinaemia (OR = 1.29, 95% CI: 1.01-1.63, P = 0.041) and reduced birthweight (26 g, 95% CI: 3-50, P = 0.026). CONCLUSION: Women with ABUO are at greater risk of preterm delivery, term labour induction and their neonates are at greater risk for NICU admissions, hyperbilirubinaemia and a reduced birthweight.

Persistence of Mycoplasma bovis infection in the mammary glands of lactating cows inoculated experimentally.

To study the course of clinical mycoplasma mastitis and investigate its potential for persistence, 10(8) colony-forming units (cfu) of an Irish isolate of Mycoplasma bovis was inoculated aseptically into the right fore teat canal of three lactating cows. M bovis rapidly colonised the infected quarters and grew exponentially to more than 10(10) cfu/ml within the first three days, and spread to other quarters of each of the three cows within five to 10 days. After periods of between 24 and 72 hours the infected quarters became distended and sensitive to touch, and their secretions changed from containing visible particles, to a seropurulent exudate, to an aqueous suspension of fine particles which formed a sediment after a sample was collected. M bovis-specific antibody levels increased to varying degrees in all three cows. Subsequently, the concentrations of mycoplasma decreased to less than 10(7) cfu/ml in two of the cows, but remained at more than 10(8) cfu/ml to the end of the lactation of the other cow. Apparently normal milk was secreted by one of the cows within a month of the challenge, and by the other two cows at the start of their next lactation. However, in two of the cows subclinical M bovis infection persisted through the dry periods and into their next lactations.

p24 and p26, structurally related cell surface molecules identified by monoclonal antibody BA-2.

This paper describes additional structural analyses of the p24 cell surface molecule recognized by monoclonal antibody BA-2. Since BA-2 is broadly reactive with a variety of normal and malignant lymphohematopoietic and nonlymphohematopoietic cells, we examined the structure of p24 expressed on different cell types. Tryptic peptide mapping and 2-dimensional gel electrophoresis of p24 isolated from colon carcinoma cells, fresh leukemic cells, leukemic cell lines, and activated T-cells indicated that p24 exhibits no structural polymorphism within the cells examined. As has recently been demonstrated with several other cell surface molecules, p24 is shown to possess a covalently-attached fatty acid, based on the incorporation of [3H]palmitate. We have also identified an additional protein, designated p26, that is coprecipitated with p24. The p26 molecule is not disulfide-linked to p24, and can be immunoprecipitated from a variety of 125I- or [35S]methionine-labeled cells. V8 protease peptide mapping indicated that p24 and p26 are structurally homologous. Pulse-chase analysis using [35S]methionine and digestion with endoglycosidase-F indicated that p24 and p26 are probably derived from a p23 precursor, but no precursor-product relationship exists between p24 and p26. Based on this data we propose that p24 and p26 are most likely differentially-processed protein products of the same gene.

Enhanced immunogenicity of leucine enkephalin following coupling to anti-immunoglobulin and anti-CD3 antibodies.

Leucine enkephalin (Leu-enk) was coupled to both T and B cell antibodies in order to investigate the possibility of enhanced immunogenicity via targeted immunization. The two antibodies used were Hm x Mo CD3 and Gt x Mo Ig, respectively. The data indicate that while both antibody carriers enhanced the immunogenicity of Leu-enk, the use of the Hm x Mo CD3 antibody resulted in a greater number of mice with positive Leu-enk specific serum titers. 12 Leu-enk cell lines were produced and one, LE4H8, was chosen for characterization.

An mRNA homologous to interleukin-1 receptor type I is expressed in cultured rat sympathetic ganglia.

Interleukin-1 (IL-1) induces substance P (SP) gene expression in cultured rat superior cervical ganglion (SCG) explants. In order to study the molecular mechanism of this action of IL-1, the presence of an interleukin-1 receptor (IL-1R) activity and the identity of an mRNA homologous to known IL-1R sequence was determined in SCG. The SP increase is blocked by recombinant IL-1 receptor antagonist protein, so IL-1 must be interacting with a specific receptor. We have cloned cDNA homologous to IL-1R type I from rat SCG using a reverse transcription-polymerase chain reaction (RT-PCR). The resulting cDNA sequence is strongly homologous with mouse and human IL-1R cDNA of the T cell and fibroblast type (type I; encoding an 80-kDa protein). mRNA specific for IL-1R can be readily detected in intact SCG by quantitative RT-PCR and S1 hybridization. However, the level of IL-1R mRNA increases 3-6-fold by 2 days in culture. This increase is independent of the presence of dexamethasone, IL-1 beta or IL-1 receptor antagonist protein ligands. The increase of IL-1R following explantation, a model of nerve injury, may provide a mechanism linking inflammatory signalling to neuronal phenotypic changes.

Murine T-lymphocytes express vasoactive intestinal peptide receptor 1 (VIP-R1) mRNA.

Vasoactive intestinal peptide (VIP), a neuropeptide present in primary and secondary lymphoid organs has been previously reported to inhibit IL-2 and IL-4 production as well as the proliferation of mitogen- or antigen-stimulated T-cells. Binding studies suggested that the immunoregulatory effects of VIP are mediated through specific VIP-binding sites present on lymphocyte subpopulations. Here we report on the expression of VIP-R1 mRNA in various murine lymphocyte subpopulations. By using RT-PCR. RNase protection assay, cDNA cloning, and sequence analysis, we show that stimulated and unstimulated murine spleen cells, thymocytes. CD4+ and CD8+ T-cells express VIP-R1. The VIP-R1 fragment amplified from murine brain, thymocytes, spleen cells and CD4+ T-cells share identical nucleotide sequences, and a high degree of homology with the corresponding nonlymphoid rat and human VIP-R1 sequences. The expression of VIP-R1 in thymocytes and peripheral lymphocytes, and especially in the CD4+ T-cell subset supports the idea that VIP produced or released locally in the lymphoid microenvironment could directly affect cytokine production and proliferation of T-lymphocytes.

Mitochondrial DNA polymorphism: its role in longevity of the Irish population.

The mtDNA genome has been implicated as playing a pivotal role in determining the longevity and success of the human lifespan. A PCR-RFLP methodology was used to identify polymorphic restriction enzyme sites within a 2643 bp region of the mtDNA genome and a table of genetic haplotypes for a healthy aged and a younger control cohort of patients was constructed. Forty-six different mtDNA haplotypes and 11 groups of related haplotypes were identified across the two age groups but statistical analysis failed to show any significant associations. The European J haplogroup, previously reported to be associated with longevity, was not found at an increased frequency within the Irish aged population (P=0.36). However, the haplotypes comprising the J haplogroup could be differentiated into two distinct branches by the presence or absence of the two polymorphic restriction sites, 16,389g and 16,000g. The branch of haplotypes defined by 16,389g displayed a significant increased frequency in the aged samples (8%) compared to the controls (1%), P=0.015. Inversely, the branch of haplotypes defined by 16,000g displayed a significant decreased frequency in the aged samples (4%) compared to the controls (13%), P=0.011. The polymorphism (mt5178A) associated with longevity in the Japanese was not found in the Irish population, while the polymorphism (mt9055A) associated with successful ageing in the French centenarians was found at an increased frequency in the Irish aged population (9%) compared to the younger control group (5%), but failed to reach a level of statistical significance, P=0.164.

The malignancy of bronchial adenoma.

The literature on bronchial adenoma has been reviewed and controversy found to exist about certain aspects of these tumors, particularly their malignancy. A retrospective study of 79 cases managed in Edinburgh since 1946 is presented. Seventy-one were of the carcinoid type, 7 were adenoid cystic carcinomas, and there was a single example of mucoepidermoid carcinoma. All types show a definite malignant potential, greatest in the rare mucoepidermoid tumor and least in the common carcinoid variety. Adenoid cystic carcinoma occupied an intermediate position in frequency and malignancy.

Regression of multiple pulmonary varices after mitral valve replacement.

A 30-year-old woman with severe mitral insufficiency had large, rounded opacities at the right hilus as seen on her chest x-ray film. These were shown to be varicosities of the right pulmonary veins by pulmonary angiography and by direct injection of contrast medium from a Brockenbrough catheter, which entered the varices from the left atrium. A year after mitral valve replacement there was complete regression of the venous dilatations. When a pulmonary varix is detected there is associated heart disease in 40% of cases. Mitral valve disease (usually mitral insufficiency) is the cardiac abnormality in 27%. This would indicate that pulmonary varix is a complication of mitral insufficiency. Four patients who have undergone valve replacement for mitral reflux have shown regression of the caricosities, suggesting that relief of mitral insufficiency will reduce or eliminate the risk of varix rupture.

Molecular forms of prostate-specific antigen and the human kallikrein gene family: a new era.

Without question, much has been learned about the glycoprotein PSA in recent years. By increasing our understanding of this tumor marker's biochemical and physiologic properties, we will be able to improve its clinical utility. The discovery of the various molecular forms of PSA represents a significant advancement. Knowing the concentration and ratio of these PSA forms will be valuable in deciding which patients require further evaluation with transrectal ultrasound and prostate biopsy and which men can be monitored safely without undergoing further invasive testing. This information will be most valuable in treating the patient with a mildly elevated serum PSA level. Although assays are not yet available to detect specifically hK2, the striking similarities of hK2 to PSA, including selective expression in the prostate, suggest that this marker may also prove useful in prostate cancer management. Indeed, a new era of PSA testing has been entered, and the entire field of prostate cancer will benefit.