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Diagnostic of global coagulation parameters is part of the daily clinical routine practice in conservative as well in operative disciplines. The correct interpretation of in vitro test results in context to the ex vivo influence of anticoagulant drugs and the in vivo hemostatic system of the individual patient is dependent on the doctors clinical and laboratory experience. This article shortly reviews the laboratory interference of oral anticoagulants including the target-specific inhibitors dabigatran, rivaroxaban and apixaban on coagulation parameters and discusses the potential of several methods for measuring the anticoagulant effect of the direct oral anticoagulants.

Narcolepsy-cataplexy is characterised by orexin deficiency, sleep disturbance, obesity and dysautonomia. Ghrelin and obestatin affect both energy intake and sleep. Our aim was to investigate ghrelin, obestatin and metabolic/autonomic function in narcolepsy-cataplexy. Eight narcolepsy-cataplexy patients (seven CSF orexin-deficient) and eight matched controls were studied. The subjects had a fixed energy meal with serial blood samples and measurement of heart rate variability (HRV). Fasting plasma obestatin was more than threefold higher in narcolepsy subjects (narcolepsy 89.6 ± 16 pg/ml vs. control 24.9 ± 3 pg/ml, p0.001). There was no change in HRV total power, but post-prandial low-frequency (LF) power and high-frequency (HF) power were lower in the narcolepsy group [area under the curve (AUC): HF power narcolepsy 1.4 × 10(5) ± 0.2 × 10(5) vs. control 3.3 × 10(5) ± 0.6 × 10(5 )ms(2)/h, p0.001]. On multiple regression analyses, the only significant predictor of plasma obestatin was HF power, which was inversely correlated with obestatin (β = -0.65 R (2) = 38 %, p = 0.009). Fasting and post-prandial plasma ghrelin were similar in both groups (narcolepsy 589.5 ± 88 pg/ml vs. control 686.9 ± 81 pg/ml, p = 0.5; post-prandial AUC-narcolepsy 161.3 ± 22 ng/ml/min vs. control 188.6 ± 62 ng/ml/min, p = 0.4). Only the narcolepsy group had significant suppression of plasma ghrelin after the meal (ANOVA, p = 0.004). In orexin-deficient narcolepsy, fasting plasma ghrelin is unaltered, and post-prandial suppression is preserved. Fasting plasma obestatin is increased and correlates with autonomic dysfunction. As obestatin affects NREM sleep, we suggest that increased plasma levels contribute to the disrupted sleep-state control in narcolepsy.

To describe the radiological signs and demographic characteristics of patients who suffered facial trauma in South-East Asia.This is a retrospective cross-sectional study of a 399 patients who presented with facial trauma over a 2-year period in a tertiary referral centre in South-East Asia. Patients with available CT scan films were included. Demographics, bony and soft tissue radiology characteristics were analyzed.Male to female ratio was 320 (80%):79 (20%). Most of the facial trauma was due to Road Traffic Accident. Of 399 patients, 273 (68%) showed radiological signs of bone or soft tissue trauma. Of these 273 patients, left to right side involvement was 114 (41.7%) / 82 (30.03%), and 77 (28.2%) had bilateral involvement. Floor was the most involved wall (229[83.8%]) and the most involved rim was the inferior rim (164[60.07%]). There were 39 (14.2%) patients with blowout fracture. Bony nasolacrimal duct was broken in 56 (20.5%) patients. Optic canal fracture was found in 7 (2.5%) patients and it was associated with roof and superior rim fracture (P-values were 0.016, 0.046, respectively). Thirty-three (12.08%) patients had radiological signs of extraocular muscle involvement. Traumatic intracranial signs were associated with roof and superior rim fractures (P 0.001 for both).Floor and inferior rim were the most affected orbital structures in facial trauma. We described radiological risk factors association with optic canal, NLD fracture and intracranial involvement. We described extraocular muscle morphological signs, which could alert to the possibility of orbital floor fracture in equivocal cases.

There is an increasing incidence of anaemia in diabetes despite the absence of significant renal impairment.This study set out to determine the prevalence of anaemia in a diabetic population and to explore the relationship between anaemia and urinary albumin excretion in diabetes mellitus. Also, to determine the difference between those with overt nephropathy, microalbuminuria and those without evidence of renal disease.Five hundred and two consecutive diabetes patients were screened for anaemia. Anaemia was defined by World Health Organization criteria (13 g/dl for men and12 g/dl for women). Urinary albumin excretion was determined by urinary albumin creatinine ratio (ACR) from a single urine sample.Anaemia was present in 118 (23.5%) patients. There was a rise in the prevalence of anaemia from 19% in patients with a normal ACR to 29% in those with microalbuminuria and to 41% in macroalbuminuria. This increase in the prevalence of anaemia in microalbuminuria compared to normoalbuminuria was not explained by declining renal function as there was no significant difference in eGFR between the two groups.Anaemia was common in the study population. Early detection and correction of anaemia in diabetes is important for patients at risk of impaired quality of life and increased cardiovascular risk.

Background amd Objective: Periodontitis is a multifactorial disease in which environmental and genetic determinant factors contribute to individual subject’s susceptibility. A DNA polymorphism in the regulating region of adhesion molecule genes is suggested to modulate the molecule’s physiological effects. The aim of this study was to investigate the genetic association between the E-selectin Ser128Arg and L-selectin Phe206Leu polymorphisms and periodontitis. Material and Methods: DNA was isolated from the whole blood of 88 patients with periodontitis and 139 healthy individuals. All samples were genotyped for the E-selectin Ser128Arg and L-selectin Phe206Leu polymorphisms using the polymerase chain reaction with sequence specific primers. Results: Our findings revealed a significant difference in the Ser128Arg polymorphism of E-selectin, but not in the L-selectin polymorphism, between periodontal patients and controls. The 128Arg allele was present more frequently in patients than in healthy individuals (31.25% vs. 12.2%, p

Both for diagnosis of congenital and acquired platelet dysfunction as well as for therapy monitoring after application of platelet function inhibitors various methods have been established for evaluation of platelet function. In contrast to the gold standard of platelet function testing, the light transmission aggregometry in platelet rich plasma the Point-of-care (POC) analyzers allow fast analysis of platelet function without extensive laboratory work up. The conditions of the pre-analytical phase, however, are still of enormous importance in the prevention of medical errors. There is increasing clinical data in monitoring the effect of platelet aggregation inhibitors, showing that quantitative determination of the platelet function degree correlates with risk of increased bleeding or stent thrombosis. However, it is still unclear, which is the optimal test system, to predict the clinical outcome of these patients.

Ghrelin inhibits sympathetic nervous system (SNS) activity in rodents. We studied the effect of ghrelin on healthy humans, in obesity and in vagotomized subjects.Randomized, double-blinded, placebo-controlled crossover.Seven lean [mean body mass index (BMI) 23·6 ± 0·9 kg/m(2) ], seven morbidly obese (mean BMI 50·9 ± 4·4 kg/m(2) ) and seven post-gastrectomy subjects (mean BMI 22·0 ± 1·1 kg/m(2) ).Subjects were randomized to intravenous ghrelin (5 pmol/kg/min) or saline over 270 min. Subjects had a fixed calorie meal and a free choice buffet during the infusion. Heart rate variability (HRV) was measured. Total power (TP) represents overall autonomic function, low-frequency (LF) power represents sympathetic and parasympathetic activity, and high-frequency (HF) power represents parasympathetic activity. Very low (VLO) frequency represents the frequency band associated with thermogenesis.Preliminary anova analysis, looking at all three subject groups together, showed that ghrelin had an overall highly significant inhibitory effect on TP (P = 0·001), HF power (P = 0·04), VLO power (P = 0·03) and no effect on LF (P = 0·07). Further subset analysis revealed that ghrelin had a significant effect on TP (P = 0·03), borderline effect on LF power (P = 0·06) and no effect on HF power (P = 0·1) in healthy controls. By contrast in obese subjects, ghrelin had no effect on TP (P = 0·3), LF (P = 0·5) and HF (P = 0·06) and also no effect in the vagotomized subjects on TP (P = 0·7), LF (P = 0·7) and HF (P = 0·9). Ghrelin had no effect on the LF/HF ratio.Ghrelin inhibits SNS activity in healthy controls with a moderate effect on parasympathetic nervous system activity but had no effect on obese subjects. Vagotomized subjects also did not respond to ghrelin, suggesting the vagus nerve is important for the effects of peripheral ghrelin on the SNS.

Numerous laboratory tests are in use to detect congenital or acquired platelet function disorders. Platelet aggregometry, using ADP, collagen, arachidonic acid or ristocetin as inductor is the standard test system for diagnosis. It is also used to detect platelet non-response to antiplatelet therapy. Studies have demonstrated that laboratory assessment of platelet non response to aspirin or clopidogrel is associated with adverse outcomes, and they indicate the importance of adjusting antiplatelet therapy in patients with a low degree of platelet inhibition. Nevertheless, a standardized method for identifying these patients is still missing.

Background and Objective: Periodontitis is a multifactorial disease and immunologic and genetic factors have an important role in its pathogenesis. Mutation in the promoter regions of the interleukin-4 and interferon-γ genes has been reported to modify the protein expression. The objective of this study was to evaluate the possible role of interleukin-4 (C-590T) and interferon-γ (G5644A) polymorphisms in the susceptibility to periodontitis. Material and Methods: In this case–control study, 53 patients (36 women and 17 men), comprising 27 patients with aggressive periodontitis and 26 patients with chronic periodontitis, and 56 healthy volunteers, were enrolled. DNA was isolated from all subjects, and the polymerase chain reaction-sequence specific primer method was used to study the interleukin-4 (C-590T) and interferon-γ (G5644A) gene polymorphisms. Results: Our results showed no significant difference in the allele and genotype frequencies of interleukin-4 (C-590T) and interferon-γ (G5644A) gene polymorphisms between patients with periodontal disease and controls. Conclusion: The results suggest that the interleukin-4 (C-590T) and interferon-γ (G5644A) gene polymorphisms may not be associated with the susceptibility of Iranian individuals to periodontitis.

Pelvic lymphadenectomy is the final staging procedure before institution of therapy patients with clinically locally confined adenocarcinoma of the prostate, a normal acid phosphatase and a bone scan free of metastatic disease. The pathologic information it provides cannot be accurately acquired at the present time by any other method. Extraperitoneal lymphadenectomy is associated with some morbidity intraoperatively and in the early postoperative period. We enumerate our results with 284 extraperitoneal lymphadenectomies.

Resistance to acetylsalicylic acid (ASA) or clopidogrel is understood from the clinical point of view as failure of the drugs to prevent recurrent vascular occlusions. Non-response to ASA and clopidogrel is defined from the laboratory aspect as an inability to cause in vitro detectable platelet function inhibition. It would be beneficial to monitor non-response to ASA or clopidogrel with platelet function methods, which detect the specific effect of these drugs, and thus prevent clinical events caused by failure of therapy. Non-response to ASA and clopidogrel are detected with different platelet function methods, which are not always clinically standardized and are assessing only the global platelet function and not the specific drug effect. Although various studies reporting 5 to 59% non-response for both drugs, support a clinical relevance of ASA and clopidogrel non-response, well-designed clinical prospective trials are required to identify patients with antiplatelet drug resistance. Furthermore, mechanisms explaining this phenomenon of drug resistance are still unknown.

In India general surgical pathologists report on all tissue types, and subspecialty training is an exception. We undertook an internal audit of gastric biopsy reporting in a large teaching hospital to assess need for subspecialty training. In a first phase, 228 consecutive gastric biopsies (two antral + one body bits in each) undertaken in our institution over six months were objectively evaluated by three experienced histopathologists, based on the updated Sydney classification.1 The three histopathologists were “trained” over four to five sessions at a multihead microscope, each session lasting 20 to 30 minutes (less than two hours cumulative time). Thereafter each …

Background: It is still not clear whether native or platelet count adjusted platelet rich plasma (PRP) should be used for platelet aggregation measurements. Aim: To evaluate the necessity of using adjusted PRP in platelet function testing. Methods: Platelet aggregation with native PRP and adjusted PRP (platelet count: 250/nl, obtained by diluting native PRP with platelet poor plasma) was performed on the Behring Coagulation Timer (BCT®) using ADP, collagen, and arachidonic acid as agonists. Healthy subjects, patients on antiplatelet treatment, and patients with thrombocytosis (platelet counts in PRP > 1250/nl) were investigated. Results: No significant differences in the maximum aggregation response were seen when using either native or adjusted PRP from healthy subjects and patients on antiplatelet treatment. Nevertheless, some patients taking aspirin or clopidogrel showed reduced inhibition of ADP and arachidonic acid induced aggregation in adjusted PRP but not in native PRP. The maximum velocity of healthy subjects and patients on antiplatelet treatment varied significantly as a result of the degree of dilution of the adjusted PRP. Surprisingly, the BCT provided good results when measuring platelet aggregation of native PRP from patients with thrombocytosis, whereas commonly used aggregometers could not analyse platelet aggregation of native PRP in these patients. Conclusion: The time consuming process of PRP adjustment may not be necessary for platelet aggregation measurements. Moreover, using adjusted PRP for monitoring aspirin or clopidogrel treatment may falsify results. Therefore, it may be better to use native PRP for platelet aggregation measurements, even in patients with thrombocytosis.

Insulin-like growth factors (IGFs) are important mitogens and are involved in normal and malignant cellular proliferation. IGFs and IGF binding proteins (IGFBPs) regulate the prostatic cell growth and reduction/blocking of IGFs has been suggested to be of therapeutic value in prostate cancer. beta,beta-dimethyl acryl shikonin, an extract from the roots of plant Arnebia nobilis has been shown to have anticancer properties but was found to be toxic. Subsequently, several analogoues of beta,beta-dimethyl acryloyl shikonin were synthesized and one of them shikonin analogue 93/637 (SA) was significantly less toxic compared to beta,beta-dimethyl acryloyl shikonin.We have investigated the effect of SA on prostate cancer cell (DU 145, LNCaP and PC-3) growth and expression of IGFs (IGF-I, IGF-II and IGF-I receptor (IGF-IR)), IGFBP-3 and vascular endothelial growth factor (VEGF).SA had growth inhibitory effect on PC-3 cells in a dose dependent manner. It also showed slight inhibitory effect on the growth of DU 145 and LNCaP cells at low doses ranging from 250 nM to 1 microM and has moderate inhibitory effect at concentrations 2.5 microM and above. Lactate dehydrogenase (LDH) activity assays indicated cellular damage, only at higher concentrations of SA that are greater than 1 microM. Gene expression studies by RT-PCR have demonstrated a decrease in mRNAs of IGF-II in DU 145, IGF-I, and IGF-IR in LNCaP, and IGF-II and VEGF in PC-3 cells and an increase in IGFBP-3 in both DU 145 and PC-3 cells by treatment with SA.The results demonstrate the inhibitory effect of SA on cellular growth and IGFs specifically in PC-3 cells and suggest a potential therapeutic use in treatment of prostate cancer.

A 65-year-old man had been followed by a family doctor for the treatment of hypertension and chronic hepatitis (type C) for about 20 years. Although he was pointed out to have impaired glucose tolerance and primary aldosteronism in 1995, he refused an adrenal tumor operation. He was admitted to our hospital on December, 1997 for further evaluation of general malaise, pitting edema of the legs, and positive urinary protein. A diagnosis of nephrotic syndrome was made on admission and a renal biopsy was performed. Histological findings indicated that he was at the early phase of diabetic nephropathy and hypertensive renal sclerosis. It is commonly believed that diabetic nephropathy develops after ten years of diabetic history and under poor control conditions. The diabetic history of this patient was only several years and the disease was under good control. In contrast to blood glucose, hypertension was not well-controlled with any antihypertensive drug, because he had a primary aldosteronism. Unfortunately, he could not take a spironolactone because of side effects. After removal of his adrenal tumor, his blood pressure was normalized gradually, and concomitantly his urinary protein was reduced and plasma protein and albumin were restored. Hypokalemia also disappeared. These findings suggest that uncontrolled hypertension may have accelerated the condition of diabetic nephropathy. The data indicates that the control of hypertension is important for inhibiting the progression of diabetic nephropathy.

We studied a Malian family with parental consanguinity and two of eight siblings affected with late-childhood-onset progressive myoclonus epilepsy and cognitive decline, consistent with the diagnosis of Lafora disease. Genetic analysis showed a novel homozygous single-nucleotide variant in the NHLRC1 gene, c.560A>C, producing the missense change H187P. The changed amino acid is highly conserved, and the mutation impairs malin's ability to degrade laforin in vitro. Pathological evaluation showed manifestations of Lafora disease in the entire brain, with particularly severe involvement of the pallidum, thalamus, and cerebellum. Our findings document Lafora disease with severe manifestations in the West African population. Electronic supplementary material The online version of this article (doi:10.1007/s10048-009-0190-4) contains supplementary material, which is available to authorized users.

We describe a new method for fixation of dislocated posterior chamber lenses. The closed eye technique involves externalizing the haptics through the pars plana and suturing the loops to the scleral wall. There were no complications in our two patients, and the implants have remained well positioned.

Pelvic lymphadenectomy has become a recognized staging procedure in patients with locally confined adenocarcinoma of the prostate prior to therapy for cure. Our study of 343 patients shows that the grade of the primary tumor does definitely affect the results of pelvic lymphadenectomy. As the grade worsens in each clinical stage, the incidence of positive nodes increases. The result of the pelvic lymphadenectomy often directs the selection of the therapy for the patient and definitely influences the results of that therapy.

Of 343 patients who underwent pelvic lymph node dissection during treatment for carcinoma of the prostate 25 had persistently elevated serum enzymatic acid phosphatase levels preoperatively: 15 (60 per cent) had metastases to the pelvic lymph nodes and 10 (40 per cent) had negative nodes. Bone metastases occurred in 10 of 12 (83 per cent) and 5 of 7 patients (71 per cent), respectively, who were followed for a minimum of 2 years. Of the 318 patients with normal serum enzymatic phosphatase levels 70 (22 per cent) had positive nodes. A persistently elevated serum enzymatic acid phosphatase level in patients with proved carcinoma of the prostate, with elimination of infrequent causes of enzyme elevation, indicates metastases and has significant implications regarding staging and, thus, therapy of this disease.