Open reduction,Dega osteotomy and proximal femoral osteotomy in delayed diagnosis of developmental hip dislocation: outcome at 40-year follow-up

PurposeLate-diagnosed dislocated hips underwent open reduction, Dega osteotomy, and proximal femoral osteotomy between 1968 and 1988. The objectives of this study are to assess the survival of hips into adulthood, clinical and radiological outcome, patients’ life perspectives and the risk factors of failure.MethodsAn assessment of 67 hips treated when younger than five years (<age 5yr. group) and 71 hips in the group aged older than five years (+age 5yr.) was performed. All cases were evaluated clinically and radiographically, and survival was assessed, considering hip replacement as endpoints for failure (abbreviation HR+ refers to hips that underwent hip replacement surgery; HR- refers to hips that have not been replaced at the follow-up). The fertility rate and the social security disability benefits (SSDB) recipiency percentage were calculated.ResultsThe 40-year survival rates were 73% (95% confidence (CI) 71% to 76%) in the <age 5yr. group, 54% (95% CI 51% to 57%) in the +age 5yr. group, 70% (95% CI 67% to 73%) in one-sided dislocations and 57% (95% CI 54% to 60%) in bilateral dislocations. At follow-up, the median Harris hip and Western Ontario and McMaster Universities Osteoarthritis scores were 90.0 and 13.0 (<age 5yr. group, HR-), 74.0 and 28.0 (+age 5yr. group, HR-), 90.0 and 16.0 (<age 5yr. group, HR+) and 84.5 and 11.5 (+age 5yr. group, HR+), respectively. The operation normalized the radiological parameters. The correlation between the grade of femoral head avascular necrosis (AVN) at a median 2.6 years after the operation and the grade of osteoarthritis at follow-up was 0.38 (p < 0.001). The fertility rate was 1.54. In total, 16.0% (aged under five years) and 38.5% (aged over five years) of patients were receiving SSDB (p = 0.003).ConclusionEarly failure risk factors are older age at the surgical procedure, high AVN grade and bilateral hip involvement. Still, the results facilitate hip reposition whenever technically manageable, even in teenagers.Level of evidenceIII     

MIR204 n.37C>T variant as a cause of chorioretinal dystrophy variably associated with iris coloboma,early-onset cataracts and congenital glaucoma

Four members of a three-generation Czech family with early-onset chorioretinal dystrophy were shown to be heterozygous carriers of the n.37C>T in MIR204. The identification of this previously reported pathogenic variant confirms the existence of a distinct clinical entity caused by a sequence change in MIR204. Chorioretinal dystrophy was variably associated with iris coloboma, congenital glaucoma, and premature cataracts extending the phenotypic range of the condition. In silico analysis of the n.37C>T variant revealed 713 novel targets. Additionally, four family members were shown to be affected by albinism resulting from biallelic pathogenic OCA2 variants. Haplotype analysis excluded relatedness with the original family reported to harbour the n.37C>T variant in MIR204. Identification of a second independent family confirms the existence of a distinct MIR204-associated clinical entity and suggests that the phenotype may also involve congenital glaucoma.     

Pentoxifylline reduces plasma tumour necrosis factor-alpha concentration in premature infants with sepsis

Increased plasma tumour necrosis factor (TNF) concentration correlates with mortality in sepsis. We suggested that pentoxifylline (PTXF), which is known to inhibit TNF production, may improve survival and attenuate clinical symptoms of sepsis in neonates. Plasma TNF levels were evaluated in 29 newborn infants with sepsis. Patients were randomly assigned into two groups, receiving PTXF in a dose of 5 mg/kg per hour for 6 h or placebo (saline), on 3 successive days. Both groups were subjected to the same conventional therapy. TNF was evaluated before and after PTXF or placebo administration on the 1 st and 3rd days of therapy. There was a statistically significant decrease in plasma TNF level in the PTXF group when the values before the first and after the last PTXF infusion were compared [mean: 671.5 pg/ml; SD: 438; med: 729.6 vs mean: 41.0 pg/ml; SD: 64.1; med: 11.5;P<0.000004]. In the placebo group, decrease was not significant [mean: 633.0 pg/ml SD: 488.6; med: 618.9 vs 246.9 pg/ml; SD: 243.9; med: 191.0]. A significantly higher plasma TNF level, evaluated after the last PTXF infusion, was found in the placebo group [246,9 pg/ml vs 41.0 pg/ml;P<0.001]. Only one of four infants with signs of shock in the placebo group survived, whereas all of five newborns with symptoms of shock in the PTXF group survived [P<0.04]. An increased incidence of metabolic acidosis [P<0.05], necrotizing enterocolitis [P<0.04] and renal insufficiency [P<0.05] was observed in infants in the placebo group.Conclusion PTXF inhibits production of TNF and may have therapeutic value in the treatment of premature infants with sepsis complicatea by shock.     

Assessment of relationship between secretion of melatonin, activity of thyroid, adrenal cortex as well as testes and chosen markers of collagen metabolism in starved rats

In starved rats the mutual interrelations were studied between the secretion of melatonin (MEL), thyroid hormones (TT[_4], FT[_4], TT[_3], FT[_3], rT[_3]), corticosterone (B), testosterone (T) and some markers of collagen metabolism: serum concentrations of carboxyterminal propeptide of type I procollagen (PICP) and aminoterminal propeptide of type III procollagen (PIIINP) (determined by RIA method) as well as urine concentration of hydroxyproline (OH-Pr) (determined by colorimetric method). Starved rats were found to have significantly increased serum MEL, B, and rT[_3] concentrations while serum values of TT[_4], FT[_4], TT[_3], FT[_3], T and PICP as well as urinary OH-Pr were significantly decreased. The concentrations of PICP, PIIINP and OH-Pr correlated negatively with MEL and B values, but positively with TT[_4] and FT[_4]. It was concluded that starving may change the collagen metabolism in rats indirectly via a modulating effect of changes in MEL, thyroxine and corticosterone.     

Serum, salivary and urinary cortisol level in the evaluation of adrenocortical function in-patients with bronchial asthma

56 patients with bronchial asthma (32 women and 24 men) and 31 healthy volunteers (19 women and 12 men) were investigated. The evaluation of the usefulness of salivary and urinary cortisol levels and urinary cortisol metabolites in 24-hr urine was conducted using the correlation coefficient between the cortisol level in the salivary or urine and that in blood serum. Very high correlation was found between the serum and salivary cortisol level (r=0.817). The correlation coefficient between the serum and urinary cortisol level in basal conditions was 0.759, while that between the saliva and urinary level was 0.723. A moderate degree of correlation (r=0.381) was demonstrated between serum cortisol level and 17-OHCS in urine. From these results it was concluded that salivary and urinary free cortisol level estimations may be a useful and non-invasive screening method of evaluating the glucocorticoid function of the adrenal cortex in asthma patients.     

Effect of dietary butylated hydroxyanisole on the mouse hepatic monooxygenase system of nuclear and microsomal fractions

The effect of butylated hydroxyanisole (BHA) administrationon the hepatic monooxygenase system of nuclear and microsomalfraction was investigated in male mice. Addition of BHA to thediet significantly lowered the content of cytochrome P-450 inliver nuclei and increased the specific activity of NADPH-cytochromec reductase and the content of cytochrome b₅ in liver microsomes.Incubation of benzo[a]pyrene (BP) with liver nuclei from BHA-fedmice resulted in inhibition of binding of BP metabolites tonuclear macromolecules by 50% compared with control. However,there was no effect of BHA on the binding of BP metabolitesto macromolecules when BP was incubated with added DNA and livermicrosomes from BHA-fed mice. It has been postulated that modificationof nuclear monooxygenases by BHA may play a role in the inhibitoryeffect of BHA on BP carcinogenesis.     

Nuclear Pedigree Criteria for the Identification of Individuals Suspected to Be at Risk of an Inherited Predisposition to Gastric Cancer

Gastric cancer is the second most frequently diagnosed malignancy worldwide and therefore represents a significant healthcare burden. Environmental and genetic factors are involved in the development of gastric cancer. To date only one clear genetic predisposition has been identified involving mutations in the E-cadherin gene. The disease phenotype in patients harbouring E-cadherin mutations appears to be specifically related to diffuse gastric cancer. Little is known genetically about the other forms of gastric cancer. Since there is a growing awareness about the necessity of early intervention criteria have been developed that aid the identification of hereditary forms of gastric cancer. The aim of the current study was to identify minimal inclusion criteria so that nuclear pedigree families can be provided with risk assessment and/or genetic testing.The results reveal that inclusion features described herein such as (a) gastric cancer diagnosed before 46 years of age; (b) two gastric cancers among first degree relatives diagnosed over the age of 50 are useful in identifying suspected hereditary gastric cancer patients.     

Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer

Background Despite curative resection, 50%–90% of gastric cancer patients die of disease relapse. Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities, more recent studies have not been able to define the standard treatment for advanced gastric cancer. The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG (bacille Calmette-Guérin) and FAM (5-fluorouracil, adriamycin, mitomycin C) chemotherapy on the survival of patients with locally advanced resectable gastric cancer.Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were randomly assigned to three treatment groups: BCG + FAM (immunochemotherapy), FAM (chemotherapy), and control (surgery only). Treatment was continued for 2 years or until death. Further postsurgical follow up was carried on for up to 10 years.Results Overall 10-year survival was 47.1% for the immunochemotherapy group (P < 0.037 vs FAM and P < 0.0006 vs control), 30% for the chemotherapy group (vs control, NS), and 15.2% for the control group. In patients with pT2/T3 primary tumors, 10-year survival was 55.3% for BCG + FAM vs 28.2% for FAM (P < 0.01) and 14.6% for the control group (P < 0.00018). BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer. Immunochemotherapy was well tolerated.Conclusion This study, based on a limited number of patients, indicates that adjuvant immunochemotherapy (BCG + FAM) may prolong the survival of gastric cancer patients after curative gastrectomy; in particular, in patients with pT2/T3 tumors and intestinal-type primary tumors. There was no survival benefit from FAM adjuvant chemotherapy.     

Interleukin 12-based immunotherapy improves the antitumor effectiveness of a low-dose 5-Aza-2'-deoxycitidine treatment in L1210 leukemia and B16F10 melanoma models in mice.

PURPOSE: Recent findings indicating that many genes related to cancer development are silenced by an aberrant DNA methylation suggest that inhibitors of this process may be effective cancer therapeutics. In this study we investigated the efficacy of low-dose 5-aza-2'-deoxycitydine (DAC), a methylation inhibitor, with interleukin (IL) 12, one of the most potent cytokines with antitumor activity. Experimental Design: Mice inoculated with L1210 leukemia cells or with B16F10 melanoma cells were treated with 7 daily injections of low-dose DAC (0.2 mg/kg) and/or 7 daily doses of IL-12 (100 ng/dose). Scid/scid mice as well as monoclonal antibodies against CD4, CD8, and NK1.1 were used to investigate the mechanisms of the antitumor effects of the combination treatment. The activity of murine lymphocytes was measured with enzyme-linked immunospot and (51)Cr release assays. RESULTS: Treatment with DAC or IL-12 given alone produced moderate antitumor effects. In both tumor models combined treatment resulted in potentiated antitumor effects and produced 70% long-term survivors among mice inoculated with L1210 cells. The antitumor efficacy of combined treatment was abrogated in scid/scid mice, and after depletion of CD4(+) and CD8(+) T cells. Mice inoculated with B16F10 melanoma cells had significantly delayed tumor growth after combined treatment with DAC and IL-12. Strong antitumor effect correlated with a significant activation of lymph node-derived CD8(+) and CD4(+) cells. Transient neutropenia was observed in mice under treatment of DAC alone, but remarkably this effect was not potentiated by IL-12. CONCLUSIONS: This study provides the first evidence that antitumor effects of DAC can be strongly potentiated by IL-12 and could be beneficial in an effective low-dose-based antitumor therapy.