HER2 and tau expression as potential markers for response and survival to first line taxane plus cisplatin therapy in non-small cell lung cancer

Aim:   The aim of this study was to assess the role of various HER2 , tau and bcl2 as prognostic markers of responsiveness to taxane and cisplatin therapy in patients with advanced NSCLC.
Methods:   Amplification of HER2 gene determined by chromogenic in situ hybridization (CISH) and HER2 , tau and bcl2 protein expression determined by immunohistochemistry were assessed in 49 patients with NSCLC enrolled in our four clinical trials of taxane plus cisplatin chemotherapy.
Results:   The patients were classified as responders or non-responders, a negative tau expression was associated with a significantly higher rate of response compared to a positive tau expression ( OR 3.33, 95% CI 1.01–10.97, P  = 0.043). Patients with more than stable disease compared to those with progressive disease showed that negative amplification of the HER2 gene was associated with a significantly higher rate of disease control compared to positive amplification ( OR 7.35, 95% CI 0.83–65.21, P  = 0.048). Furthermore, HER2 gene amplification was strongly associated with the overall survival: 20 months (95% CI 9.007–30.993) in patients with negative amplification of the HER2 gene versus 12 months (95% CI 6.584–17.416) in patients with positive amplification of the HER2 gene ( P  = 0.040). A multivariate analysis with the Cox proportional hazards model confirmed that HER2 gene amplification was a significant independent prognostic factor with a hazard ratio of 2.334 (95% CI 1.060–5.142, P  = 0.035).
Conclusion:   Tau protein expression and HER2 gene amplification are the prognostic factors in NSCLC patients treated with a taxane and cisplatin combination.     

Immunohistochemical analysis of Fas and FLIP in prostate cancers

Fas‐mediated apoptosis is considered a principal pathway for apoptosis induction in normal and cancer cells. Expression of Fas has been reported in prostate tissues several times, but the data were not consistent. Expression of FLICE‐like inhibitory protein (FLIP), an inhibitor of Fas‐mediated apoptosis, has not been studied by immunohistochemistry in prostate tissues. The aim of this study is to explore whether alterations of Fas and FLIP expression occur in prostate cancer tissues. We analyzed the expression of Fas and FLIP in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray approach. Normal glandular cells of the prostates strongly expressed both Fas and FLIP proteins. Prostate intraepithelial neoplasm also showed a strong Fas immunoreacitity. Fas expression was strongly positive in 60 cancers (56.1%), but the remaining 47 cancers showed no (6.5%) or markedly decreased (37.4%) Fas immunostaining compared with the normal glandular cells of the same patients. By contrast, FLIP expression was strong in most (103/107; 96.3%) of the cancers, and only four cancers (3.7%) showed decreased immunoreactivities compared with the normal cells. The decreased expression of Fas was not associated with pathologic characteristics, including FLIP expression, size of the cancers, age, Gleason score and stage. The decreased expression of Fas in a large fraction of prostate cancers compared with their normal cells suggested that loss of Fas expression might play a role in tumorigenesis in some prostate cancers possibly by inhibiting apoptosis mediated by Fas.     

The outcome of cementless total hip arthroplasty in haemophilic hip arthropathy

Summary.  Total hip arthroplasty (THA) in haemophilic arthropathy is reported to be less successful than in non-haemophilic indications. Although preliminary results are encouraging, the survival and functional outcome of cementless THA in haemophilia are not known. The aim of this study was to analyse mid-term results of cementless THA in haemophilia. Twenty-seven consecutive cementless THAs with 23 patients performed between June 1995 and June 2003 were reviewed. Mean age at time of operation was 36 years and mean follow-up period was 92 months (range, 60–156). Radiographic assessment was done for fixation of components, loosening, osteolysis, wear and bone responses around the implants. The factor requirements, amount of transfusion and complications associated with bleeding were studied. The mean preoperative Harris hip score changed from 57 to 95.9 at the latest follow-up. The survival at mean follow-up was 95.2%. One patient with osteolysis around acetabular cup was re-operated with bone-grafting and change of polyethylene liner. One loose cup was revised with a cemented cup. All other components were deemed stable at the latest follow-up. A standardized management protocol and dedicated team approach comprising of haematologist, physicians, physical therapist, nurses and coordinators is needed for excellent results. The present retrospective study shows that the functional results of cementless THA in haemophilia are satisfactory as it happens in osteoarthritic patients according to the current literature, mainly the younger. Thus, taking into account that the majority of haemophilia patients requiring a THA are relatively young, cementless THA is currently recommended.     

Penile erectile responses to electric stimulation are enhanced by a new phosphodiesterase type-5 inhibitor

AIM: This study was conducted to investigate the effect of DA-8159, a new phosphodiesterase type-5 (PDE5) inhibitor, on electrostimulation-induced penile erection in rats. METHODS: Intracavernous pressure (ICP) and arterial blood pressure (BP) were simultaneously recorded through electric pelvic-ganglion stimulation (2-10 Hz) after the oral administration of DA-8159 (3 or 10 mg/kg) in normal and streptozotocin-induced diabetic rats. Statistical analysis was performed on the maximal intracavernous pressure (ICP), detumescence time, maximal intracavernous pressure/blood pressure (ICP/BP) ratio, and the area under the curve (AUC) of the ICP/BP ratio. RESULTS: In normal and diabetic rats, electrical stimulation of the pelvic ganglion induced a frequency- and dose-dependent increase in the intracavernous pressure. The ICP/BP ratio and the corresponding AUC values were also significantly and dose-dependently increased after DA-8159 administration. In addition, the detumescence time significantly increased after DA-8159 administration compared to that of the controls. CONCLUSIONS: These results show that the DA-8159 significantly increased the intracavernous pressure response and prolonged the decay period induced by electrical stimulation of the pelvic ganglion, and suggest that DA-8159 might be a potential therapeutic agent for the treatment of erectile dysfunction.     

Characterization of Sinoatrial Parasympathetic Innervation in Humans

INTRODUCTION: The response to sinoatrial parasympathetic nerve stimulation (shortened atrial refractoriness) was used to determine the atrial distribution of these nerve fibers in humans. We hypothesized that, in humans, parasympathetic nerves that innervate the sinoatrial node also innervate the right atrium and that the greatest density of innervation is near the sinoatrial nodal fat pad. METHODS AND RESULTS: Temporary epicardial wire electrodes were sutured in pairs in the sinoatrial nodal fat pad, high right atrium, and right ventricle by direct visualization during coronary artery bypass surgery in nine patients. Appropriate electrode placement was confirmed by electrically stimulating the fat pad in the operating room to prolong sinus cycle length by 50%. Experiments were performed in the electrophysiology laboratory 1 to 5 days after surgery. Programmed atrial stimulation was performed via an endocardial electrode catheter advanced to the right atrium. The catheter tip electrode was moved in 1-cm concentric zones around the epicardial wires by fluoroscopic guidance. Atrial refractoriness was determined in the presence and absence of sinoatrial parasympathetic nerve stimulation at each catheter site. In 8 of 9 patients, parasympathetic nerve stimulation reproducibly prolonged sinus cycle length by 50%. There was no effect on AV nodal conduction (no prolongation of PR interval) and no change in AV nodal refractoriness. Atrial effective refractory periods reproducibly shortened in response to parasympathetic nerve stimulation in 1-cm zones up to 3 cm surrounding the fat pad, by a mean (+/- SEM) of 26.6+/-4.3 msec (zone 1), 11.4+/-1.8 msec (zone 2), and 10.0+/-2.5 msec (zone 3), respectively (P = 0.0001). At distances > 3 cm from the fat pad, the effective refractory period did not shorten. CONCLUSION: Stimulation of parasympathetic nerves that innervate the sinoatrial node shortened atrial refractoriness in humans.     

Pigmented nail with atypical melanocytic hyperplasia

We report two cases showing black discoloration of the thumb nail which were histologically found to be acral lentiginous melanoma (ALM) in situ. A pigmented subungual lesion is more frequently malignant than benign and it is generally believed that diagnosis of subungual melanoma during the radial-growth phase is very difficult. Our cases are particularly interesting because atypical melanocytic hyperplasia was confined to the epidermis despite the lesion being present for a long time.     

Anaesthetic requirement and stress hormone responses in patients undergoing lumbar spine surgery: anterior vs. posterior approach

Background: The intensity of nociceptive stimuli reflects the severity of tissue injury. The anaesthetic requirement and stress hormonal responses were determined to learn whether they differ according to different surgical approaches (anterior vs. posterior) during the spinal surgery.
Methods: Patients undergoing lumbar spine surgery without neurological deficits were divided into two groups: one having posterior ( n =13) and the other having anterior fusion ( n =13). The end-tidal sevoflurane concentrations (ET_SEVO) required to maintain the bispectral index score at 40–50 were determined. Mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), serum osmolality and plasma concentrations of catecholamines, cortisol and vasopressin (AVP) were measured.
Results: There were no differences in MAP, HR, CVP and serum osmolality between the groups. ET_SEVO was higher in the anterior than in the posterior group ( P <0.05). The plasma concentrations of norepinephrine and cortisol increased in both groups during the surgery, whereas those of epinephrine remained unchanged. AVP concentrations increased during the surgery in the anterior group, and remained unaltered in the posterior group. The anterior group needed more analgesics ( P <0.01) during the first 1 h after the operation.
Conclusions: The anterior approach required a deeper level of anaesthesia while undergoing spinal surgery and more use of post-operative analgesics than the posterior approach. It was also associated with a more pronounced AVP release during the surgery.