Unfavorable Progression Research Articles

Metastatic breast cancer detection and therapy monitoring using folate-targeting flow cytometry.

23 Background: Circulating tumor cell (CTC) has emerged as a valuable surrogate tumor marker for cancer diagnosis, prognosis, therapy personalization, and drug discovery. To identify CTCs, EpCAM and/or cytokeratin have been commonly used; however, their expression may diminish for subgroups of breast cancers or during epithelial-mesenchymal transition. A unique approach by targeting folate receptor (FR) on CTCs overcomes the limitation. Cancer cells overexpress FR with high affinity (KD=0.1 nM) to internalize high levels of folate for rapid growth. FR is also found upregulated in most cancers, while at very low levels in normal tissues. Methods: A flow cytometry based in-vitro CTC assay kit (OncoIVDx) was developed by IV Diagnostics Inc to specifically enumerate CTCs which overexpress FRs. 20 mL of 9 metastatic breast cancer (MBC) patients' peripheral blood was collected using CellSave tube before and after the treatment in midst of therapy. CTCs were tagged by fluorescently labeled folate conjugate, while leukocytes were counterstained by anti-CD45. To absolutely count the rare CTCs, a fluorescent bead was added serving internal control. Results: Table. Conclusions: No obvious shift in dot plots was found for patients' leucocytes compared to those in normal sample. Tumor size, histologic grade, nodal involvement and lymphovascular invasion (LVI) did not display a significant association with CTC presence, although more positive nodes with identified LVI might indicate an unfavorable increase in CTC counts. CTC presence was found associated with serum marker CA27.29. A score of 30 and less correlated with CTC response to the treatment. Chemotherapy alone or in combination with hormone therapy did not correlate with the change in CTC counts after treatment, except for hormone therapy alone. Unfavorable progression of cancers could be predicated for the patients with approximately 25 and more CTCs. We would like to thank NIH/NCI for SBIR phase I grant (1R43CA13789301A1). [Table: see text]

Correlation between Inflammation and Fibrinolysis Impairment on Central Obesity: A Study for hsCRP, PAI-1, PAP and TAFI

BACKGROUND: Inflammation in the vascular wall plays an important role in the pathogenesis of atherosclerosis. Current studies have shown that increase of systemic inflammatory marker like the acute phase component C-reactive protein (CRP) are associated with an unfavorable progression of disease and an increased risk for acute cardiovascular events. Recently, a close association of Metabolic Syndrome (MetS) with hemostatic abnormalities has been reported. Among hemostatic abnormalities, an increase in plasminogen activator inhibitor (PAI)-1, a strong inhibitor of fibrinolysis, is considered a core feature of MetS. High PAI-1 concentrations may be associated with thrombus formation, also causing cardiovascular events. Therefore, we investigated the association between markers for chronic inflammation (CRP) and the markers of fibrinolytic impairment (PAI-1, PAP, TAFI) in subjects with central obesity.METHODS: This was a cross-sectional study in 80 male Indonesian subjects, aged 30-60 years old with central obesity, conducted from January to March 2008 in Bandung.RESULTS: The study results showed that there was a difference of PAI-1 levels between MetS and Non-MetS group. There were significant correlations between hsCRP and PAI-1 (r=0.252, p=0.024 ), hsCRP and PAP (r=0.253, p=0.024), and also between PAI-1 and PAP (r=-0.239, p=0.033 ) respectively. But, no correlation found between hsCRP and TAFI.CONCLUSIONS: There was correlation between inflammation and fibrinolysis impairment on central obesity. Concentrations oh hsCRP, PAI-1 and TAFI were significantly higher in MetS.KEYWORDS: inflammation, fibrinolysis impairment, hsCRP, PAI-1, PAP, TAFI

Type B Intramural Hematoma of the Aorta: Evolution and Prognostic Value of Intimal Erosion

Purpose The prognosis and treatment of type B intramural hematoma (IMH) remain unclear. Intimal erosions could be the target of preventive endovascular treatment, but we have no therapeutic criterion on which to decide preventive treatment. Materials and Methods A prospective multislice computed tomography (CT) study was carried out in 44 patients with type B IMH to assess morphologic evolution and intimal erosion to determine reliable predictive factors that would permit endovascular treatment. Follow-up range was 24–1,440 days. Results Intimal anomalies consisted of intimal erosion and aortic branch artery lesions. Fifty-eight intimal anomalies were seen on initial CT in 38 patients (86%). Twenty-five anomalies in 22 patients were considered as intimal erosions, of which nine (36%) were visible only on delayed-phase CT. Hematoma regressed in 23 patients (53%). Twenty-one patients (47%) showed morphologic progression. Eleven of these (52%) required endovascular treatment. Twenty of the 25 initial intimal erosions (80%) progressed and caused 19 of the 21 morphologic evolutions (90%). Progression was related to initial intimal erosion and to IMH thickness. Intimal erosion measuring greater than 10 mm had unfavorable progression at 1 month (positive predictive value, 100%). Conclusions Complications or morphologic progression were related to a preexisting intimal anomaly visualized on initial CT. Multislice CT with systematically delayed phase and millimetric thin slices could increase the detection rate of intimal anomalies.

Tratamiento quirúrgico del adenocarcinoma pancreático mediante duodenopancreatectomía cefálica (Parte 1). Complicaciones postoperatorias en 204 casos en un centro de referencia

Introduction Cephalic duodenopancreatectomy (CDP) is the treatment of choice in cancer of the head of the pancreas. However, it continues to have a high post-surgical morbidity and mortality. The aim of this article is to define variables that influence post-surgical morbidity and mortality after cephalic duodenopancreatectomy due to pancreatic adenocarcinoma (PA) cancer of the head of the pancreas (CHP). Material and methods The variables were prospectively collected form patients operated on between 1991 and 2007, in order to investigate the factors of higher morbidity. Results A total of 204 patients had been intervened due to PA, of whom 57 were older than 70 years. Of these patients, 119 had a CPD, 11 extended lymphadectomy, 66 with pyloric conservation, and 8 with extension to total pancreatectomy due to involvement of the section margin. Portal or mesenteric vein resection was included in 35 cases. Post-surgical complications were detected in 45% of cases, the most frequent being: slow gastric emptying (20%), surgical wound infection (17%), pancreatic fistula (10%), and serious medical complications (8%). Further surgery was required in 13%, and the over post-surgical mortality was 7%. A patient age greater than 70 years, post-surgical haemoperitoneum, gastroenteric dehiscence, and the presence of medical complications were post-surgical mortality risk factors in the multivariate analysis. Pancreatic fistula was not a factor associated with post-surgical mortality. Conclusions Cephalic duodenopancreatectomy is a safe technique but with a considerable morbidity. Patients over 70 years of age must be carefully selected before considering surgery. Serious medical complications must be treated aggressively to avoid an unfavourable progression.

Surgical treatment of pancreatic adenocarcinoma by cephalic duodenopancreatectomy (Part 1). Post-surgical complications in 204 cases in a reference hospital

IntroductionCephalic duodenopancreatectomy (CDP) is the treatment of choice in cancer of the head of the pancreas. However, it continues to have a high post-surgical morbidity and mortality.The aim of this article is to define variables that influence post-surgical morbidity and mortality after cephalic duodenopancreatectomy due to pancreatic adenocarcinoma (PA) cancer of the head of the pancreas (CHP). Material and methodsThe variables were prospectively collected form patients operated on between 1991 and 2007, in order to investigate the factors of higher morbidity. ResultsA total of 204 patients had been intervened due to PA, of whom 57 were older than 70 years. Of these patients, 119 had a CDP, 11 extended lymphadectomy, 66 with pyloric conservation, and 8 with extension to total pancreatectomy due to involvement of the section margin. Portal or mesenteric vein resection was included in 35 cases. Post-surgical complications were detected in 45% of cases, the most frequent being: slow gastric emptying (20%), surgical wound infection (17%), pancreatic fistula (10%), and serious medical complications (8%). Further surgery was required in 13%, and the over post-surgical mortality was 7%. A patient age greater than 70 years, post-surgical haemoperitoneum, gastroenteric dehiscence, and the presence of medical complications were post-surgical mortality risk factors in the multivariate analysis. Pancreatic fistula was not a factor associated with post-surgical mortality. ConclusionsCephalic duodenopancreatectomy is a safe technique but with a considerable morbidity. Patients over 70 years of age must be carefully selected before considering surgery. Serious medical complications must be treated aggressively to avoid an unfavourable progression.

Extrême prématurité : comparaison du devenir à 5 ans en fonction de l’âge gestationnel inférieur ou supérieur à 26 semaines d’aménorrhée

Is it reasonable to care for children born under 26 gestational weeks (GW)? To answer this question, we compared outcome at 5 years of 2 groups of children:less or equal to 25 GW+6 days (group 1) and 26-27 GW+6 days (group 2). Retrospective study on extremely preterm children hospitalized in our center between 1999 and 2001. Perinatal data were obtained from medical reports. Five-year outcome was evaluated by questionnaire sent to Centers for Early Medicosocial Intervention, pediatricians or the child's parents. The children were classified according to their disability: none, minor or major. Progression was considered favorable if the child survived with or without minor disability and unfavorable if the child had died or had major disability. One hundred and sixty-six preterm babies were recorded. In group 1 (n=63), mortality was higher (58% vs 29%; p=0.0002), a neurologic cause was often responsible for death (36% vs 19%; p=0.018), a high level of intracranial hemorrhage was more frequent (35% vs 19%; p=0.002), and a decision to stop healthcare more often made (35% vs 18%; p=0.01) than in group 2 (n=103). Among the 99 survivors, 78 were being followed up at 5 years of age. In terms of disability, no difference was observed between group 1 (n=21) and group 2 (n=57). Including deaths, the risk for unfavorable progression was higher in group 1 (64% vs 41%; p=0.008). The progression of under 26-GW preterm babies is more often unfavorable than the progression of babies born 26-27 GW+6 days. However, given the low number of patients, no significant difference was made concerning the prognosis at 5 years between the survivors of the 2 groups.

Pneumonie nécrosante à Staphylococcus aureus secréteur de la toxine de panton valentine

Necrotizing pneumonia caused by Staphylococcus aureus producing Panton Valentine Leukocidine (PVL) has been described recently and is associated with a high mortality (75%).We report a case of pneumonia due to PV secreting Staphylococcus aureus in a healthy young adult, complicated by multiple necrotizing lung lesions and major cystic changes, with a favourable final outcome. Acute respiratory failure with haemodynamic failure and ARDS developed a few days after an influenza-like illness. The appearances at fibreoptic bronchoscopy were atypical, consisting of a purulent, necrotic tracheo- bronchitis with desquamation. The initial unfavourable progress despite broad spectrum antibiotic therapy and, finally, the identification of PV leukotoxin in blood cultures and tracheal aspirate, led to the diagnosis. During the clinical course there were repeated pneumothoraces (8 drains) due to multiple bilateral cystic lesions. Ultimately progress was favourable following treatment with antibiotics (flucloxacillin and clindamycin) and steroids.It is important to consider pulmonary complications of the Panton-Valentine leukotoxin in a healthy young adult who presents with necrotizing pneumonia and an unfavourable outcome in spite of broad spectrum antibiotics. Treatment is difficult on account of the extent of the necrotizing lesions and the need to use antibiotics effective against both the bacterium and its toxin.

Les lymphomes T des fosses nasales et des sinus

Introduction Extra-nodal T lymphomas of the ear, nose, and throat (ENT) are unusual in Western countries, with differential diagnosis from other destructive and necrotizing lesions of the sino-nasal tract often difficult. Material and methods Eleven cases of extra-nodal lymphomas of the upper aerodigestive tract tract managed in the ENT department of F. Hached hospital in Sousse, Tunisia, were retrieved over a 10-year period (1995–2004). The aim of our study was to report the clinical and pathological data and the outcome for each patient. Results The median age of patients was 41-years. The most frequent site of involvement was the nasal cavity. Clinically, the symptoms were not specific. Histological examination identified two cases of T/NK lymphoma and nine cases of T-lymphoma not otherwise specified. Immunohistochemistry and in situ hybridization techniques positively detected Epstein-Barr virus in tumoral cells, in seven cases. Tumor staging, in 10 patients, found distant metastasis in three. Nine patients underwent the following treatment: exclusive radiotherapy (one patient), radiochemotherapy (three patients), and exclusive polychemotherapy (five patients). The two remaining patients had no treatment because of a rapidly unfavorable progression. After a median follow-up of 11-months, clinical outcome consisted in death in seven patients and remission in three patients; one patient was lost of follow-up. Conclusion Extra-nodal lymphomas of the ORL tract are rare in Tunisia. Clinical presentation is not specific, depending on the lymphoma location. Diagnosis relies on clinical presentation and immunophenotypic and molecular characteristics; morphological features are not specific. These are aggressive lymphomas, often requiring multidisciplinary management.

Československá ekonomika v osmdesátých letech 20. století

Studie analyzuje vývoj ekonomiky Československa v období osmdesátých let, poslední dekádě existence socialismu. Ukazuje, že Československo nezachytilo podněty, které v západních zemích akcelerovaly dva ropné šoky, jež vedly k technické revoluci ve sféře energetické náročnosti výroby, ke komputerizaci a automatizaci. Dokládá na číslech, že tempa růstu československé ekonomiky se v osmdesátých letech zpomalila a byla nižší než v západní Evropě. To vedlo k tomu, že rozdíly v úrovni československé ekonomiky se oproti srovnatelným zemím západní Evropy začaly opět zvětšovat.Zapojení do mezinárodní dělby práce bylo nízké. Směrem na Západ to ovlivňovala zvláště studená válka, směrem na Východ velmi nízká efektivnost integračního procesu socialistických zemí. Dokumentuje to např. nepříznivý vývoj směnných relací (terms of trade). Struktura československé ekonomiky byla formována podle "poptávky" socialistických zemí. Byl zde nadměrný podíl palivo-energetického a hutního průmyslu a nízký podíl odvětví a oborů, které jsou nositeli pokroku v ekonomice a společnosti. Životní úroveň obyvatelstva se vyvíjela podle modelu založeného na počátku orientace země na socialismus. Celý hospodářský mechanismus byl tomuto modelu přizpůsoben a postupem doby se jeho logika vzdalovala potřebám doby. Dále studie věnuje pozornost otázce vyrovnání Slovenska na úroveň České republiky, které vstoupilo v roce 1918 do Československa jako nepříliš rozvinutá země,. Ukazuje se, že přes značné úspěchy na tomto poli to nevedlo k upevnění Československa. 1. 1. 2003 se Československo rozpadlo na Českou republiku a Slovenskou republiku.

PKC inhibitor Go6976 induces mitosis and enhances doxorubicin-paclitaxel cytotoxicity in urinary bladder carcinoma cells

Protein kinase C (PKC) α/βI isoenzyme inhibitor Go6976 has been suggested to be a G2 checkpoint abrogator by direct Chk1 inhibition. In the present study, we demonstrate that Go6976 induces mitosis in doxorubicin treated G2-arrested 5637 urinary bladder transitional cell carcinoma cells and interestingly also in non-synchronized 5637 cells. Importantly, the results demonstrated that both doxorubicin treated and non-synchronized cancer cells are forced to mitosis by Go6976. However, part of the cells avoid the death in mitosis and continue in the cell cycle which may increase the probability of genomic instability. Cytotoxicity of Go6976 alone and in combination with chemotherapeutic agents was further studied. Go6976 treatment alone induced apoptotic cell death. Cytostatic doxorubicin pre-treatment induced G2 arrest and inhibited the cytotoxic effects of mitosis specific drug paclitaxel. Cytotoxicities of doxorubicin-paclitaxel and doxorubicin-Go6976 sequences could be markedly enhanced by combining Go6976 with paclitaxel after doxorubicin pre-treatment. In doxorubicin-Go6976+paclitaxel sequence, paclitaxel arrested the cells to mitosis and unfavourable progression of the cell cycle was inhibited. Analyzes of the molecular mechanisms underlying Go6976 induced mitosis showed that PKC inhibiting concentrations of Go6976 induced cdc2 activation concentration-dependently in non-synchronized and in DNA damaged cells. Simultaneously, Chk1/2 became deactivated and cdc25C activated in DNA damaged cells, indicating regulatory events upstream. In non-synchronized cells, activation of cdc25C, but not Chk1/2, was observed, suggesting inactivation of c-TAK1. The results of the current study suggest that Go6976 has a synergistic cytotoxic effect when combined with doxorubicin and paclitaxel.

Prevalence of the hemochromatosis gene mutation in patients with nonalcoholic steatohepatitis and correlation with degree of liver fibrosis

Nonalcoholic steatohepatitis is a chronic liver disease with a high prevalence in the general population and a potential to evolve into cirrhosis. It is speculated that iron overload could be associated with liver injury and unfavorable progress in affected patients. To evaluate the prevalence of mutation of the hemochromatosis gene (HFE) in patients with nonalcoholic steatohepatitis and to correlate it with histological findings in liver specimens. Twenty-nine patients with nonalcoholic steatohepatitis were evaluated. The presence of mutation in the hemochromatosis gene (C282Y and H63D) was tested in all patients and its result was evaluated in relation to hepatic inflammatory activity, presence of fibrosis, and iron overload in the liver. The control group was composed of 20 patients with normal liver function tests and 20 patients infected with the hepatitis C virus, with elevated serum levels of aminotransferases and with chronic hepatitis as shown by biopsy. Mutation of the hemochromatosis gene (C282Y and/or H63D) was diagnosed in 16 (55.2%) patients with nonalcoholic steatohepatitis, in 12 (60%) patients with hepatitis C and in 8 (40%) patients with no liver disease. No association was found between the presence of mutation and inflammatory activity, nor with the presence of fibrosis in patients with nonalcoholic steatohepatitis. An association was found between the presence of mutation and the occurrence of iron overload in liver, but there was no association between liver iron and the occurrence of fibrosis. The findings suggest that iron does not play a major role in the pathogenesis and progression of nonalcoholic steatohepatitis, and routine tests of the hemochromatosis gene mutation in these patients should not be recommended.

Fatal Long-term Immunosuppressive Therapy With Uncontrolled Repeat Prescription

A case of nephrotic syndrome treated with associated cyclophosphamide and corticosteroids came to our attention after over 2 years of self-administered immunosuppressive therapy which remained unchanged and uncontrolled during this period. The self-administered therapy resulted in a severe cell-mediated immunodeficiency (as expressed by a nadir CD4 lymphocyte count of 2 cells/muL). This led to a rapid unfavorable progression of hepatitis B, which was recently acquired and subsequently evolved into a severe cholestatic and fibrosing chronic hepatitis, causing multiple end-organ failure, and ultimately, death. This process was not reversed by lamivudine therapy, hemodialysis, and the use of a Molecular Adsorbent Recirculating System. The role played by repeated drug prescriptions from general practitioners without appropriate clinical and laboratory controls, and that of our patient's depression are discussed. Current literature related to the presented case and the ongoing debate regarding repeated prescriptions are considered in this study.

A Longitudinal Model for Non-Monotonic Clinical Assessment Scale Data

Clinical assessment scales, where subitem ratings are added and summarized as a total score, are convenient tools for monitoring disease progression and often used to measure the effect of drug treatment in clinical trials. Statistical evaluation of any beneficial treatment effects tends to focus on single-valued summary measures, for example, the difference between the score at the end of treatment and the score at baseline. Such analyses ignore potentially important features of the data, e.g. early vs. late recoveries. It is therefore of interest to develop longitudinal models that make more efficient use of the information present in non-monotonic clinical assessment scale data. We propose a two-part modeling approach for the modeling of this type of data. Non-monotonicity is managed by regarding score changes as Markovian transition events. A set of probabilistic models are used to describe the occurrences of the transitions. Continuous models are used to describe the magnitude of the scale score change, given the observed transition. In this manner, a non-monotonic disease progression is handled more efficiently than if other available methods are used. We illustrate this approach using data from a recent phase II study of a drug used in the treatment of stroke, where stroke severity was measured on the Scandinavian Stroke Scale (SSS). This scale consists of nine subitems: consciousness, eye movements, hand/arm/leg motor performance, orientation, speech, facial palsy, and gait. The data were non-monotonic, since there was at any time a risk of a score decline, despite a general tendency towards healing. The two-part probabilistic/continuous model fit the data well and proved to be robust in model-checking procedures such as posterior predictive checks and bootstrapping. The models derived using this approach could potentially accommodate drug effects, not only in terms of score improvement at end of study, but also on the onset of recovery, on dropout and on the probability of unfavorable progression patterns. In addition, it is possible to use the resulting for simulation of the prospective outcome of future studies. We conclude that this approach has considerable potential for more efficient use of information in longitudinal modeling of non-monotonic clinical assessment scale data.

Early course of illness in first episode schizophrenia with long duration of untreated illness - a comparative study

When a long duration of untreated illness (DUI) is correlated with an unfavourable progression of schizophrenia in the same way as that of a long duration of untreated psychosis (DUP), the characteristics of patients with a long DUI are of particular interest for early recognition and early intervention programmes. With this background, demographic data and early symptoms were collected from 82 first time in-patients with schizophrenia using the IRAOS (Interview for the Retrospective Assessment of the Onset of Schizophrenia). In the total sample, the average DUI was almost 5.9 years. On the basis of the DUI median (5.2 yrs), the random sample was divided into two groups: one with long (n = 41) and one with short (n = 41) DUI. When comparing both groups in terms of socio-demographic data, no significant differences could be found (with the exception of age at first admission: 28 - 32 yrs). On a psychopathological level, patients with long DUI were prone to depressive moods, anxiety, compulsive symptoms and showed early signs of disturbances in bodily perception. An educational campaign should sensitize both employees working in primary care and experts who diagnose and treat psychological illnesses, to the fact that these symptoms could point to a prodrome even when the patient has passed the typical age of being at risk from schizophrenia.

Effect of Intrauterine Growth Retardation on the Progression of Nephrotic Syndrome

Background/Aim: Neonates with intrauterine growth retardation (IUGR) experience higher morbidity and mortality rates than appropriate-for-gestational-age (AGA) neonates. The purpose of our study was to clarify whether IUGR has any influences on the progression of nephrotic syndrome in children. Methods: We performed a retrospective review of 56 children with nephrotic syndrome. IUGR was defined as a birth weight less than the tenth percentile for gestational age. Among 56 patients having nephrotic syndrome, 8 had IUGR, and 48 were AGA. Results: The 24-hour urinary protein level in children with IUGR was significantly higher than that in children who were AGA (7.61 ± 6.75 vs. 3.92 ± 3.70 g/day, p < 0.05). There was a statistically significant difference in the incidence of steroid resistance (62.5 vs. 10.4%, p < 0.05) and in the time to remission (median 60 vs. 13 days, p < 0.05) between the children with IUGR and those being AGA. Also, there was a significant difference in the incidences of treatment with cytotoxic agents (75 vs. 29.2%, p < 0.05) and complications such as hypertension. Conclusions: Our report indicates that IUGR predicts an unfavorable progression of nephrotic syndrome. So, it is important for nephrologists to pay attention to the clinical course of nephrotic syndrome in neonates with IUGR.

Squamous cell carcinoma on both palms

A dramatic case of squamous cell carcinoma (SCC) on both palms in a 70-year-old is presented. The lesion appeared on the palms simultaneously and no causal factors were found. During his work, he came into contact with liquid acid from car batteries. The diagnosis of SCC on both palms was confirmed histologically. Because of its unfavorable progress, a new surgical stage was performed to excise a left metastatic axillary tumor involving the brachial plexus.

Corium kinematic viscosity measurement

Viscosity is one of the important properties which along with thermal conductivity and coefficient of volumetric expansion, determines convection in molten corium in the case of unfavourable progress of a severe accident in nuclear reactors. The viscosimetric attachment has been designed, developed and built for the purpose of measurement of corium kinematic viscosity with the technique of torsional oscillations. The created experimental devices and procedure for measurement of liquid corium viscosity have been tested and refined over temperature range up to 2800°C. The experimental data of 62UO 2+38ZrO 2 (mol%) melt viscosity have been obtained at temperature ranging from 2600 to 2800°C. The viscosity of 62UO 2+8ZrO 2+30Zr (mol%) melt has been measured at temperatures from 2400 to 2700°C. This work has been performed within OECD RASPLAV Project. The Management Board approves publication of this paper.

A circadian variation in the observed duration of labor

The distribution of the duration of labor during the day was analyzed. A one-year material consisting of 1,881 deliveries at the Department of Obstetrics, Regional Hospital of Trondheim, Norway. Only singleton pregnancies with spontaneous onset of contractions and intended vaginal delivery were included. Duration of labor was routinely recorded by the midwife. Stepwise multiple regression. Logarithmic transformation of the dependent variable (duration measured in hours) was applied. Parity (0/1+) and hour of birth were the independent variables. The variable indicating delivery during the night (0 to 08) contributed significantly to explain the variation in the duration of labor, in terms of a decrease in the median duration. The effect is substantial, median duration of labor 1.2 h shorter than for deliveries during the day. The variable indicating delivery during the evening (16-24) did not reach the required level of significance (0.05). This reflects a clustering of cases with longer duration of labor, unfavourable progress and less good prognosis during the latter half of the day, which has practical implications for the obstetrical staff. This may explain the similar circadian pattern in perinatal mortality which has been repeatedly documented, the etiology of which has remained enigmatic.

Progressive tubulointerstitial nephropathy with hepatic involvement in an infant

We describe an infant with renal and liver disease who died at the age of 10 months from chronic renal failure. Hepatosplenomegaly was present along with biochemical findings of cholestasis and cytolysis. The diagnosis of tubulointerstitial nephropathy with cortical microcysts associated with hepatic fibrosis was based upon laboratory, radiological, and histological data. This rarely described disorder is characterized by an early clinical onset and unfavourable progression to end-stage renal failure before the age of 2.

Morphological Parameters in Lupus Nephritis: Their Relevance for Classification and Relationship with Clinical and Histological Findings and Outcome

One hundred and sixty-seven renal biopsies from 147 patients with lupus nephritis were studied retrospectively to assess the contribution to morphological classification by features assessed with immunofluorescence and electron microscopy, together with pathological indices obtained by scoring specific histologic changes. The prognostic relevance of the histologic scoring was also evaluated. The biopsies were assigned to the following classes: I, absence of glomerular lesions; II, mesangial proliferation; III, focal segmental proliferation; IVa, diffuse (more than 50 per cent of the glomeruli) but segmentally distributed proliferation; IVb, diffuse and generalised proliferation; IVc, extracapillary proliferation; Va, pure membranous changes; Vb, membranous changes with slight mesangial proliferation; VI, association of class V and class III or IV. The incidence and degree of some glomerular and non-glomerular 'active' and 'sclerotic' changes as assessed by light microscopy were evaluated in the different classes. Both the activity and sclerosis indices obtained by scoring these lesions were found to be significantly higher in classes with glomerular proliferative changes. Eighteen patients had a second biopsy and two of these had a third; more severe changes were observed in nine and improvement in four. In 146 biopsies light microscopy findings were compared with immunofluorescence patterns (negative, mesangial, mesangial and peripheral, peripheral, membranous). The mesangial pattern was mainly present in class II with a few examples in classes I and III; in the last two the mesangial-peripheral pattern was most common; the peripheral pattern was by far the most common in class IV (a, b and c) and frequent in class VI; a membranous pattern was the rule in class V and occasionally found in class VI. Immunoglobulins (Igs) and complement (C) fractions were simultaneously present in most cases, IgG, C3 and C1q being the commonest in all classes. Except for IgM and fibrinogen, the differences in distribution of Igs and C fractions among the various classes were statistically significant. The deposits most commonly found by electron microscopy in all biopsies were mesangial; subendothelial deposits were mainly found in classes with active glomerular changes, frequently associated with deposits at the other sites in the most severe cases. A highly significant correlation was found between the activity index and the sclerosis index and severity of the clinical picture at biopsy. An unfavourable progress was confined mainly to classes with extensive intracapillary proliferation and correlated significantly with the highest activity and sclerosis indices.(ABSTRACT TRUNCATED AT 400 WORDS)