Beneficial Prognosis Research Articles

IDH1 mutation correlates with a beneficial prognosis and suppresses tumor growth in IHCC

BackgroundIsocitrate dehydrogenase 1/2 (IDH1/2) mutations have been reported in intrahepatic cholangiocarcinoma (IHCC). However, the prognosis of a single IDH1 mutation and impact of mutant IDH1 on IHCC tumor growth remain unclear. MethodsA total of 85 IHCC tumor samples were sequenced. Prognosis and clinicopathological correlation were analyzed. The role of mutant IDH1 in IHCC tumor growth was measured by cell proliferation assay, colony formation assay in soft agar, and xenograft tumor models. Akt, ERK, p38 MAPK, and JNK signaling, which commonly affect tumor growth, were examined by Western blotting to explore the potential mechanism. ResultsIDH1 mutations correlated with a beneficial prognosis and smaller tumor size. Mutant IDH1 exhibited a growth-inhibitory effect on IHCC cell lines in vitro and in vivo. Akt signaling was suppressed in IHCC cell lines expressing a mutant IDH1. The reactivation of Akt signaling by SC79 restored the inhibited growth of cell lines expressing a mutant IDH1 in IHCC. ConclusionsCollectively, we demonstrated that mutant IDH1 correlates with a beneficial prognosis and inhibits tumor growth by suppressing Akt signaling in IHCC. We suggest that patients with IDH1 mutations could be considered for both less-aggressive therapy and therapy tailored to the presence of their mutant enzyme in the future.

Human Papillomavirus Immunity in Oropharyngeal Cancer: Time to Change the Game?

For the first time, human papillomavirus (HPV)-specific immunity has been linked directly to the beneficial prognosis of oropharyngeal squamous cell carcinoma (OPSCC). Those patients lacking HPV immunity fare much worse. These results harbor crucial implications for future management of HPV-driven OPSCC as well as for its definition. Clin Cancer Res; 24(3); 505-7. ©2017 AACRSee related article by Welters et al., p. 634.

Abstract 2989: Expression of immune checkpoints proteins and their prognostic relevance in prostate cancer

Abstract Immune checkpoint proteins including programmed death ligand 1, 2 (PD-L1, PD-L2) and B7-H3 play important roles for immune evasion in many cancer types. PD-L1 is an established therapeutic target in lung cancer and in a growing number of other indications. The clinical success of PD-L1 inhibitors has accelerated the development of drugs also targeting PD-L2 and B7-H3. In prostate cancer, studies on the prevalence and clinical relevance of these proteins have been inconclusive. Here, we performed immunohistochemical analysis of PD-L1, PD-L2 and B7-H3 in our large prostate cancer prognosis tissue microarray (TMA) containing tissue samples from more than 17,000 patients. Normal prostate glands were negative for PD-L1 and B7-H3, but positive for PD-L2. We found that 47% of 12,808 interpretable cancers showed B7-H3 expression, and 92% of 9,463 cancers showed PD-L2 expression, while expression of PD-L1 was virtually absent (0.2% of 17,392 tumors) in epithelial cells. Stroma cells and immune cells were entirely negative for PD-L1 and B7-H3, while some faint staining of lymphocytes was occasionally observed for PD-L2. In cancers, PD-L2 and B7-H3 staining had different prognostic impact, which depended on the ERG status: B7-H3 expression was linked to young patient age, advanced stage, high Gleason grade, lymph node metastasis (p<0.0001 each), presence of PTEN deletion (p<0.0001), and poor prognosis in ERG negative cancers (p<0.0001), while PD-L2 expression was linked to beneficial tumor features and good prognosis exclusively in tumors with ERG fusion (p<0.0001). In a multivariate analysis including pT stage, Gleason grade, nodal stage, resection margin and preoperative PSA level, B7-H3 expression was an independent prognostic factor (p=0.0004). In summary, the results of our study identify a subset of young patients with ERG negative aggressive prostate cancers that might benefit from anti-B7-H3 therapy in the future. PD-L2 expression appears to protect tumors from progression and does not seem to be suitable as a potential target in prostate cancer. PD-L1 expression is extremely rare in this disease, suggesting that only few prostate cancer patients might benefit from PD-L1 inhibitors. Citation Format: Claudia Hube-Magg, Cornelia Schroeder, Ronald Simon, Martina Kluth, Till Krech, Franziska Büscheck, Frank Jacobsen, Doris Höflmayer, Lars Budäus, Hartwig Huland, Markus Graefen, Guido Sauter, Thorsten Schlomm. Expression of immune checkpoints proteins and their prognostic relevance in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2989. doi:10.1158/1538-7445.AM2017-2989

A Master microRNA miR-508-3p Modulates the Mesenchymal Subtype of Colorectal Cancer by Targeting ZEB1/BMI1/SALL4 Network

OBJECTIVES: The mesenchymal subtype colorectal cancer (CRC) is related to invasive and metastatic disease with poor prognosis in CRC. However, the specific molecular alterations and the driving molecular events behind the mesenchymal subtype of CRC have not been investigated. METHODS: miRNA-mRNA expression profiling studies were performed in The Cancer Genome Atlas (TCGA) CRC samples. Expression and functional analysis of the six key miRNA signatures was investigated in CRC cell lines/tissues and cells were analysed for invasion and migration both in vivo and in vitro. The prognostic significance of miR-508-3p was analysed by univariate and multivariate survival analyses. Expression of miRNA508-3p target genes and EMT markers in CRC cell lines and tissue specimens was validated. RESULTS: Integrated analyses revealed a miRNA-regulatory network that was associated with the mesenchymal subtype in 200 CRC cases from TCGA database. Six key miRNA, including miR-508, miR-506, miR-514 and miR-205 were predicted to regulate 275 mesenchymalrelated genes in this network. Of the six miRNAs, integrated analysis and functional assay highlight a crucial role for miR-508 in CRC Epithelial-mesenchymal transition (EMT). Follow-up functional experiments illustrate that miR-508-3p augmented CDH1 expression, inhibited cell migration, invasion, and prevented TGF b-induced EMT by targeting ZEB1, SALL4 and BMI1 both in vitro and in vivo. MiR508-3p expression was correlated with decreased ZEB1, VIM and N-cadherin, elevated CDH1 and beneficial prognosis in CRC patients. MiR-508-3p may be regulated by methylation in CRC. The associations between miR-508-3p, target genes, EMT markers and the prognosis value of miR-508-3p were validated in paired normal and cancerous colorectal tissues. CONCLUSIONS: MiR-508-3p may be a master microRNA of the mesenchymal subtype of CRC and a promising target to prevent and/or treat CRC invasion and metastasis.

MicroRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma.

Growing evidence indicates that miR-146a is involved in carcinogenesis and tumor progression in several human malignancies. However, the molecular details underlying miR-146a mediated regulation of its target genes and its precise biological function in cancer, especially in hepatocellular carcinoma (HCC) remains unclear.MethodsThe expression levels of genes including miR-146a, APC, VEGF and HAb18G were examined in HCC cell lines and patient specimens were compared with control levels using quantitative reverse transcription-PCR. The functions of miR-146a and HAb18G in migration/invasion and liver metastasis formation were determined by transwell and spleen injection assays, respectively. miR-146a related genes were determined by PCR array. The potential regulatory targets of miR-146a were determined by bioinformatics and prediction tools, correlation with target protein expression, and luciferase reporter assay. DNA methylation status of miR-146a promoter were performed by PCR analysis of bisulfite-modified genomic DNA.ResultsWe demonstrated that miR-146a expression was markedly downregulated in hepatoma cells and hepatoma tissues compared to immortalized normal liver epithelial cells and normal hepatic tissues. DNA methylation of miR-146a promoter correlated with its downexpression and with liver cancer metastasis. The restoration of miR-146a dramatically suppressed HCC cell invasion and metastasis by repressing VEGF expression through upregulating APC, which inhibits β-catenin accumulation in nucleus, and downregulating NF-κB p65 by targeting HAb18G. In human HCC, miR-146a expression was negative correlated with increased HAb18G, VEGF, NF-κB p65 and beneficial prognosis.ConclusionThis study identified a novel target of miR-146a and defined miR-146a as a crucial tumor suppressor in human HCC that acts through multiple pathways and mechanisms to suppress HCC invasion or metastasis.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-14-5) contains supplementary material, which is available to authorized users.

Principle of surgical treatment of adenocarcinoma of the esophagogastric junction

The incidence of adenocarcinoma of the esophagogastric junction (AEG) dramatically increased in the America and Europe.Although some search results on AEG have been reported,it is still difficult to elucidate the clinical status of AEG in China.The consensus of standardized treatment of AEG is gradually formed.For early AEG,endoscopic mucosal resection,endoscopic submucosal dissection,laparoscopic surgery and minimally extent surgery were the main treatment methods; for advanced AEG,transthoracic esophagectomy or mediastinal lymph node dissection can offer beneficial prognosis for patients with Siewert type Ⅰ AEG,while extended total gastrectomy,extended esophagogastrectomy,D2 lymph node dissection are appropriate for patients with Siewert type Ⅱ and Ⅲ AEG. Key words: Adenocarcinoma of the esophagogastric junction; Surgical procedures, operative

Study of lipid profile for psoriatic patients in AL-Anbar governorate.

Psoriasis is a chronic inflammatory skin condition which affects approximately 1-3% of the world's population (1). It appears as red plaques covered with silvery scale that flakes away from the skin.Psoriatic plaques are often found on the elbows, scalp and knees but can also affect other parts of the body such as the face, feet and mucous membranes.Psoriasis is not contagious, nor is it caused by an allergy. However, the tendency to develop the condition can be genetically transmitted. Psoriasis causes itching in 60% to 70% of cases (2). However, the exact etiology of psoriasis is unknown. Abnormalities in lipid metabolism have been proposed because the abnormalities in lipids lead to abnormalities in skin formation which is made from lipids. To evaluate the serum lipids profile in psoriatic patients of Al-Anbar governorate and to compare the results with other external studies. The study group included 60 patients with psoriasis, and 30 healthy volunteers. Blood lipid profile was determined using commercial kits from reliable French and Spain companies. All patients had psoriasis involving less than 30% of body surface. Their ages ranged from 10 to 60 years with a mean of 32 years. Family history of psoriasis was positive in a percentage of (20%) of the patients. The mean levels of serum lipids (total cholesterol, triglyceride, low density lipoprotein, and very low density lipoprotein) in patients with psoriasis were found to be significantly higher than those of healthy individuals. The mean levels of high density lipoprotein were not significant. This study strengthens the relationship between the lipids intake, formation, and metabolism with the pathogenesis of psoriasis. Therefore it is concluded that psoriatic patients should be evaluated for hyperlipidemia and obstructive vascular diseases. Administrating lipid-lowering medicines for patients particularly cases with severe disease may be beneficial prognosis.

Integrated Analyses Identify a Master MicroRNA Regulatory Network for the Mesenchymal Subtype in Serous Ovarian Cancer

Integrated genomic analyses revealed a miRNA-regulatory network that further defined a robust integrated mesenchymal subtype associated with poor overall survival in 459 cases of serous ovarian cancer (OvCa) from The Cancer Genome Atlas and 560 cases from independent cohorts. Eight key miRNAs, including miR-506, miR-141, and miR-200a, were predicted to regulate 89% of the targets in this network. Follow-up functional experiments illustrate that miR-506 augmented E-cadherin expression, inhibited cell migration and invasion, and prevented TGFβ-induced epithelial-mesenchymal transition by targeting SNAI2, a transcriptional repressor of E-cadherin. In human OvCa, miR-506 expression was correlated with decreased SNAI2 and VIM, elevated E-cadherin, and beneficial prognosis. Nanoparticle delivery of miR-506 in orthotopic OvCa mouse models led to E-cadherin induction and reduced tumor growth.

Sustained Viral Response Hematological Markers During The Treatment of Chronic Hepatitis C Infection in Children

Dear Editor, We read with interest the paper by Pawlowska et al. (1) and we would like to add some comments. They conducted a retrospective cohort study of children with chronic hepatitis C (CHC) infection who completed treatment with ribavirin (RBV) plus pegylated IFN (peg-IFN) or recombinant IFN, and concluded that a mild decrease in hemoglobin levels , leukocyte and platelet counts during treatment may be the responsible factors for sustained viral response (SVR) induction. One of the interesting data in this paper is the non-discussed main result: SVR was achieved with a non-statistically significant different rate in the two groups of treated children (RBV plus peg-IFN or IFN). In a previous article by Pawlowska et al. (2), the authors concluded that treatment with peg-IFN and RBV was effective, showing the same SVR percentage that appears in the current article, but without comparing it to another group treated with recombinant IFN and RBV. Manns MP et al. (3) and other adult population studies showed that therapy with peg- IFN and RBV was better than monotherapy with IFN or therapy with IFN plus RBV. Current guidelines recommend children are treated for hepatitis C virus (HCV) using the same principles applied in adults. However, few published studies in the pediatric population for HCV treatment assessed the effectiveness of these two treatments. A systematic review of the literature by Hu J et al. (4) found only four randomized controlled trials (RCTs) and 31 non-randomized studies, all involve IFN, peg-IFN, or combinations of these drugs with RBV. The SVR rate could not be directly compared as the populations and interventions differed across studies. Nevertheless, the results were comparable to studies in adults. The therapy must be avoided in children younger than two years of age because of the risk of neurotoxicity. The decision of start therapy time must account for the estimated or known duration of infection, genotype, and degree of fibrosis. On the other hand, the main question discussed in the paper is if the decrease in hematological parameters could be a response marker or simply a side effect. Agreeing with some previous studies (4, 5), anemia during treatment with peg-IFN and RBV in patients with HCV genotype 1 is associated with superior virologic responses. The results show that hemoglobin value, leukocyte and platelet counts decrease in both groups, but hemoglobin level and leukocyte count decrease more in the peg-IFN one. The authors show that the reduction was lower in children who achieved SVR than in those who did not, and peg-IFN had a more marked influence on the decrease in hemoglobin value and leukocyte count. They also suggest that the amount of this decrease could be a marker of beneficial prognosis in children same as in adults and that it may not be indicator for withholding or reducing the dose of IFN. According to the results of this study, it seems reasonable to recommend a close monitoring of different hematological parameters during treatment of children with CHC including IFN plus RBV, as possible side effects and surrogate markers of treatment response. However, according to (4), we conclude that current guidelines for the treatment of HCV in children are based on limited data and further research is needed to define the optimal therapy for HCV in children.

Expression of circadian gene Per2 and VEGF in NSCL tissue and its clinical significance

Objective To detect the expression of Per2 and VEGF in NSCLC tissue,and analyze its clinical significance.Methods The expression of Per2 and VEGF was measured in 60 NSCLC and 20 normal lung tissue by immunohistochemistry assay,then the relation with clinicopathological parameters was analyzed.Results The positive expression rate of Per2 in NSCLC and in normal lung tissue were 71.7％ and 95.0％ ( x2 =4.683,P ＜0.05 ),while the positive expression rate of VEGF were 58.3％ and 15％ (x2 =11.295,P ＜ 0.01 ).The negative expression of Per2 in NSCLC was correlated with pathological differentiation or TNM stage( x2 =4.413,6.179,all P ＜0.05),while the positive expression of VEGF in NSCLC was correlated with pathological differentiation or lymphatic metastasis (x2 =6.524,P ＜ 0.05 ).The expression of Per2 was negatively correlated with the expression of VEGF in NSCLC (r =-0.381,P ＜ 0.01 ).Conclusion The overexpression of VEGF in NSCLC may contribute to invasion and metastasis,while Per2 may be a beneficial prognosis factor in patients with NSCLC. Key words: Cancer, non-small-cell lung; Circadian gene Per2; Vascular endothelial growth factor; Immunohistochemistry

Cardiovascular risk factors related to the PPARγ Pro12Ala polymorphism in patients with type 2 diabetes are gender dependent

The interaction of the PPARγ Pro12Ala polymorphism with diabetes and cardiovascular risk is controversial. We studied 173 women and 309 men in the observational CARDIPP trial in which determination of left ventricular mass, carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were performed. Blood pressures were measured with 24-h ambulatory technique (ABP). Heterozygotes and homozygotes of Ala were defined as Ala in the analyses. Men with Ala-isoform displayed higher waist circumference (Ala: 107 ± 14 cm, Pro: 104 ± 11 cm, p = 0.045) and body weight (Ala: 95.7 ± 18 kg, Pro: 91.6 ± 14 kg, p = 0.042) than Pro-homozygotes. Men with ALA-isoform also showed higher systolic ABP levels (Ala: 134 ± 15 mmHg, Pro: 130 ± 14 mmHg, p = 0.004), whereas left ventricular mass index, IMT and PWV were unrelated to isoforms. In contrast, carotid–radial PWV was lower in women with the Ala-isoform (Ala: 7.9 ± 1.0 m/s, Pro: 8.5 ± 1.3 m/s, p = 0.01) and levels of apolipoprotein A1 were higher (Ala: 1.43 ± 0.27 g/l, Pro: 1.35 ± 0.17 g/l, p = 0.03). In conclusion, we found that men with type 2 diabetes having the Ala-isoform of PPARγ Pro12Ala had an unfavorable cardiovascular risk profile, whereas women with this isoform had lower carotid–radial PWV and higher apolipoprotein A1 levels suggesting a beneficial prognosis. These differences according to gender of the ALA isoform in type 2 diabetes deserve further attention.

Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor

The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1–4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3–12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eight-gene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score ≥7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score ≤4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31–1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P=0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53–6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.

COMPARATIVE EFFECTS OF AMLODIPINE AND CILNIDIPINE ON SYMPATHETIC NERVOUS MODULATION IN PATIENTS WITH HYPERTENSION: PP.32.265

Objective: Sympathetic nervous activity may be augmented with the calcium channel blocker (CCB) treatment as a result of decreased blood pressure despite the advent of long-acting CCBs. A dihydropyridine CCB, cilnidipine blocks not only L type but also N type of calcium channels. Accordingly, we compared the effects of amlodipine and cilnidipine on autonomic nervous activity in hypertensive patients. Design and Methods: Eighteen hypertensive patients under the treatment of amlodipine monotherapy for at least 6 months were randomized to the 2 treatment arms. In 8 patients (70±9 (SD) years, 1 man and 7 women), amlodipine monotherapy was further continued for 6 months. In 10 patients (70±4 years, 3 men and 7 women), amlodipine treatment was switched to cilnidipine treatment. Before and after 6-month treatment with amlodipine or cilnidipine, each patient underwent 30 min resting electrocardiographic recording in the morning after an overnight fasting. By using spectral analysis of heart rate variability, frequency-domain measures were calculated. The low frequency (LF: 0.04 to 0.15 Hz)/high frequency (HF: 0.15 to 0.40 Hz) power ratio was used as an index of sympathovagal balance, and HF/total power (TP) ratio was used as an index of vagal activity. Plasma norepinephrine levels were measured by radioimmunoassay. Results: In patients with continuous amlodipine treatment, systolic and diastolic blood pressures (SBP, DBP) and heart rate (HR) remained unchanged. LF/HF and HF/TP ratios also remained unchanged (LF/HF 1.77±1.05 vs. 1.83±1.22, HF/TP 0.419±0.122 vs. 0.402±0.116). Plasma norepinephrine levels were comparable (370±88 pg/ml vs. 491±137 pg/ml). In patients switched to cilnidipine, SBP, DBP and HR were similar before and after switching. Interestingly, LF/HF ratio decreased significantly (p = 0.012) from 2.37±1.56 to 1.89±1.42, and HF/TP ratio increased significantly (p = 0.049) from 0.366±0.132 to 0.417±0.156, despite the comparable HR. Plasma norepinephrine concentrations decreased significantly (p = 0.009) from 359±65 pg/ml to 282±72 pg/ml. Conclusions: These findings suggest that cilnidipine may provide beneficial prognosis for hypertensive patients because it suppresses sympathetic nervous activity.

Ethical Considerations of Refusing Nutrition After Stroke

The aim of this article is to analyse and discuss the ethically problematic conflict raised by patients with stroke who refuse nutritional treatment. In analysing this conflict, the focus is on four different aspects: (1) Is nutritional treatment biologically necessary? (2) If necessary, is the reason for refusal a functional disability, lack of appetite or motivation, misunderstanding of the situation or a genuine conflict of values? (3) If the latter, what values are involved in the conflict? (4) How should we deal with the different kinds of refusal of nutritional treatment? We argue that patients' autonomy should be respected as far as possible, while also considering that those who have suffered a stroke might re-evaluate their life as a result of a beneficial prognosis. However, if patients persist with their refusal, health care professionals should force nutritional treatment only when it is clear that the patients will re-evaluate their future life.

Serum lipids abnormalities and psoriasis

<b>Context:</b> Psoriasis is a chronic proliferative inflammatory skin disease with unknown etiology. The loss of scale from the surface observed in the course of psoriasis may be related to lipid disorders in epidermis and in serum. Moreover a predisposition to occlusive vascular disease and increased cardiovascular morbidity has been reported. <b> Aims:</b> In this study, the serum lipid levels of psoriatic patients were investigated to detect any relation in this respect. <b> Materials and Methods:</b> 60 psoriatic and 120 nonpsoriatic individuals were included in this case control study and were analogized for sex, age and body mass indices. Total cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels were measured. <br><b> Statistical Analysis Used:</b> Collected data were analyzed by statistical tests of Chi square, Mann Whitney and Kruskal Wallis applying SPSS software. <b> Results:</b> Total cholesterol, triglyceride and LDL-C were found to be significantly higher than in normal control group (<i> P</i> <0.05). No significant statistical difference was observed between HDL level of the two groups. <b> Conclusions:</b> We concluded that psoriatic patients should be evaluated for hyperlipidemia and obstructive vascular diseases. Administrating lipid-lowering medicines for patients particularly cases with severe disease may be beneficial prognosis.

Renal function in proteinuric glomerular diseases correlates to the changes in urine IgM excretion but not to the changes in the degree of albuminuria.

Renal function in proteinuric glomerular diseases correlates to the changes in urine IgM but not to the changes in the degree of albuminuria. Albuminuria is believed to correlate to the progression of renal failure in glomerular diseases. Nevertheless, many patients with glomerular disorders maintain their renal function despite persistent albuminuria. In previous studies, we found that the baseline urine excretion of IgM, rather than the degree of albuminuria, predicts the renal outcome in glomerulopathies. In the present study, we examine correlations between changes in the content and in the amount of urine proteins and renal survival during a follow-up time of 3.5 years. An observational study of a mean of 44 (+/- 3.6) months was conducted in 37 proteinuric patients (21 males and 16 females) with biopsy-verified primary glomerular disease. The patients were subdivided, according to the findings at the end of the study, into 3 groups, 1 group with decreasing albuminuria (by more than 50%), 1 group with persisting albuminuria and low (< 0.04 mg/mmol creatinine) urinary IgM excretion and 1 group with persisting albuminuria and with high (> or = 0.04 mg/mmol) urinary IgM excretion. All patients that showed remission of albuminuria had also low IgM excretion at the end of the study. All these patients, except 1, maintained their renal function. Patients with persistent albuminuria and high urinary IgM excretion showed a decrease in the glomerular filtration rate (GFR) of a mean of 9.6 ml/min/year compared to a mean GFR increase by 1.5 ml/min/year in patients with low IgM excretion and the same degree of albuminuria (p < 0.01). Seven out of the 9 patients in the former group fall in GFR by more than 5 ml/min/year compared to only 1 of the 10 patients in the latter group. Furthermore, the GFR alterations that occurred during follow-up time correlated in a higher degree to the changes in urinary IgM excretion (r = 0.6, p < 0.01) than to the changes in the degree of albuminuria, (r = 0.4, p < 0.05). A stepwise regression analysis indicated that increased urine IgM excretion is a strong predictor of the GFR decline (r = 0.73, p < 0.001). High urinary IgM excretion correlates to decreased GFR in primary glomerular diseases regardless of the degree of albuminuria. In parallel, low urinary IgM excretion indicates beneficial prognosis in these diseases. Since IgM passes the glomerular barrier entirely through large shunts or defects in the glomerular capillary wall, decreased urine content of IgM might be considered as a sign of recovery in the glomerular damage.

Early course and long-term follow-up after automated percutaneous lumbar discectomy.

In this prospective study, the clinical outcome in the early course as well as the long-term results were analyzed after automated percutaneous lumbar discectomy (APLD). Thirty consecutive patients are included, all with a contained lumbar disc herniation on magnetic resonance imaging. There was a significant reduction in the sciatic pain and straight leg raising (SLR) test postoperatively at all the different measurements in the early course except for the sciatic pain at 2 weeks. On the same occasions, there was no change in the back pain or the Oswestry score. Ten patients needed subsequent open surgery. For the remaining patients, the long-term result showed a significant and unchanged improvement in the sciatic pain and SLR. In addition, the Oswestry score had now significantly improved. The failure rate of APLD turned out to be unacceptably high in this study, because 38% of the patients needed subsequent open surgery. However, an early satisfactory course also seemed to imply a beneficial long-term prognosis.

MR diffusion tensor imaging of white matter tract disruption in stroke at 3 T.

Recent advances in MR diffusion weighted imaging (DWI) enable the identification of anisotropic white matter tracts with diffusion tensor imaging (DTI). We aimed to use a novel DTI technique to safely study patients with recent stroke in a high field (3 T) MR machine with its intrinsically higher spatial resolution and signal-to-noise ratio. Of ten patients studied, six had disruption of white matter tracts as determined by DTI. A further patient had distortion of white matter tracts around an infarct rather than actual disruption of the tracts themselves. The lack of tract destruction may imply a beneficial prognosis, information that is not available with conventional DWI.

Flow and compartmental weight in relation to the cours of stroke.

Using a scintillation camera system, hemispheric and regional cerebral blood flow was measured repeatedly during the course after a stroke. In 20 patients who improved clinically mean hemispheric and regional flow and relative weight of rapidly perfused compartment increased, while these values decreased in 15 patients, on an average, whose clinical condition deteriorated or did not change. The changes of flow and relative weight were significantly different between the two groups. Futhermore, the relationship between changes in clinical condition, scored according to a rating scale, and changes in flow and compartmental weight was proved by significant Spearman rank correlation coefficients. In six cases hyperperfused areas in locations of disturbed neurological function were observed; these areas were found to be ischemic at measurements done early and late in the cours after the stroke. This type of hyperperfusion was related to beneficial prognosis. The results indicate a shift of tissue form fast to slowly cleared compartment after a cerebrovascular attack. If tissue morphology is not entirely destroyed, recovery might occur; this results in an increase of recorded weight of rapidly clearing compartments, which correlates to the clinical course.

The pancreatic function of obstructive jaundice

The diagnostic procedures of carcinoma of the pancreas were studied from morphological and functional points of view. The diagnostic efficiencies of the carcinoma of the pancreas was low by individual procedure in each self, but it was able to become higher by combined diagnostic procedures. However, the results of therapy, surgical or non-surgical, were still very low, even when the correct diagnosis was made. Same thing was noted in the case of carcinoma of the gall bladder and of the bile duct and choledotholithiasis. It was stressed that the early diagnosis of the malignant tumor with jaundice was necessary for beneficial prognosis of the disease.