DNA-flow cytometry of 207 pituitary adenomas: ploidy, proliferation, and prognosis

The principal factors involved in pituitary adenoma formation are unknown. DNA-flow cytometry is a useful study providing an estimation of a tumor proliferative rate. In this study, DNA-flow cytometry was performed to evaluate its capability to both assess prognosis and predict recurrence. Two hundred and seven fresh pituitary adenoma specimens were assessed by flow cytometry. Pre-operative endocrine function, previous medical treatment, radiographic appearance, surgical findings and immunohistochemistry were recorded for each patient. Patient outcomes were assessed at a mean follow-up of 5.3 +/- 3.1 yr. Endocrinologically inactive pituitary adenomas were predominantly euploids (50.8%). The highest proliferation rates occurred in Nelson's syndrome and the lowest in Cushing's disease. A significant difference in proliferation was observed with prolactinomas and acromegaly when a medical treatment was performed before primary surgery. Massive histological invasiveness was directly associated with a significant increase in proliferation rate. Radiotherapy did not affect the recurrence rate (4.4%) statistically. In conclusion, DNA-flow cytometry was found to be useful for determining ploidy and obtaining an overview of cell cycle status. It was helpful in identifying patients requiring closer follow-up, such as those with invasive adenomas and Nelson's syndrome. No single parameter revealed by DNA-flow cytometry could predict tumor prognosis or recurrence in the follow-up of 7.5 +/- 1.3 yr.     

Feasibility and efficacy of extracorporeal shock-wave lithotripsy using a new modified lateral position for the treatment of renal stones in obese patients

The aim of our study was to evaluate the efficacy and safety of ESWL using a modified lateral position in obese patients with renal stones. Nineteen obese patients with renal stones were enrolled (group A). The mean stone diameter was 1.3 cm (0.7-1.9 cm). The mean BMI was 35.1 kg/m2 (31-41 kg/m2). Patients were placed in the lateral position, with the energy source facing their body posteriorly and the site where the stone was located in direct contact with the water cushion. Success rate (defined as the percentage of patients who were stone-free or with insignificant fragments after 3 months), mean number of ESWL sessions, mean duration of ESWL session and complications were recorded. The results were compared with those of 17 obese patients (Group B) with similar baseline characteristics treated in the standard supine position. All ESWLs were performed using the Dornier lithotripter SII. Both success rate (68.4 vs. 64.7% for groups A and B, respectively) and mean number of sessions (2.2 vs. 2.6) did not differ significantly between the two groups (p = 0.5). Interestingly, the time required to complete ESWL was significantly shorter for group A patients (56 min) compared to group B (73 min) (p = 0.001). No severe complications (including hematoma, pyelonephritis) were recorded. Our data indicate that ESWL in the modified lateral position for renal calculi in obese patients seems to be feasible and safe. In addition, it is faster than in the supine position since it overcomes technical difficulties. Further studies with a large number of patients are required to support our findings.     

Effect of BRCA1 immunohistochemical localizations on prognosis of patients with sporadic breast carcinomas

Our purpose was to investigate the expression pattern of BRCA1 protein in sporadic breast carcinomas, as well as the clinicopathological and prognostic value of its subcellular localizations. Immunohistochemistry was performed on paraffin embedded tissue specimens from 111 sporadic, invasive breast carcinomas to detect the expression of the proteins BRCA1, ER, PR, erbB2, p53 and Ki67. BRCA1 protein was detected in the nuclei and the cytoplasm of the tumor cells. Nuclear BRCA1 immunoreactivity showed no relation with the classic clinicopathological markers and the expression of cerbB2, p53 and Ki67. Reduced expression of nuclear BRCA1 protein was found to exert an independent favorable impact on both the overall and relapse-free (RF) survival of the patients (p = 0.019 and p = 0.043, respectively). Cytoplasmic BRCA1 was associated with none of the classic histomorphological indices, except from the lymph node metastasis, with which its relation was found to be inverse (p = 0.05), prolonging the RF survival of the patients (p = 0.05). Our findings suggest that BRCA1 protein depicts different prognostic significance, according to its subcellular distribution. Nuclear detection of the protein was associated with a worse prognosis, while the cytoplasmic one was related to fewer recurrences as a result of fewer lymph node metastases.     

Precision of the preoperative axial tomography in local TN staging in colon cancer

Aim-Background

This study investigates the diagnostic accuracy of preoperative axial tomography in colon cancer. The parameters studied are local infiltration (T) and local lymphadenopathy (N).

Patients-Methods

Forty-one patients diagnosed with colon cancer were included in this study. All patients underwent preoperative abdominal axial tomography with the use of intravenously administered paramagnetic substance. Axial tomography was reconstructed with sections of 5–7 mm thickness. The staging deduced by axial tomography was compared with histopathological staging.

Results

Based on the histopathological evaluation, ten patients were staged as having T2 tumours, twenty-three as T3, and eight as T4 tumours. As concerns N staging, twenty-five patients were classified as N0, seven as N1, and nine as N2. The accuracy of axial tomography in T staging was 90% for T2 tumours, 78% for T3 and 75% for T4. The precision of N staging was 48% for N1, 71% for N2 and 78% for N3 lymph node infiltration.

Conclusion

In terms of local tumour infiltration, the diagnostic precision of preoperative abdominal axial tomography in patients with colon cancer is high. However, the technique is not as accurate as regards lymph node infiltration.     

Influence of oestrogen on spontaneous and diazepam-induced exploration of rats in an elevated plus maze

An elevated plus-maze, used to identify anxiolytic effects of drugs (Pellow et al., 1985), reflected as increased open-arm exploration, was employed in cycling and ovariectomised rats, to determine the effect of diazepam on the cycle and, after ovariectomy, to investigate possible influences of treatment with oestradiol (10 or 100 micrograms/kg, s.c.) (acute: 1 day or subchronic: 3 days) to ovariectomised rats on the effect of diazepam (1 mg/kg, i.p.), studied 3, 24 and 72 hr after cessation of treatment. Cycling females, exhibiting 3 consecutive 4-day oestrous cycles and ovariectomised rats, 15 days after surgery, were used. There was a tendency for increased open-arm exploration by rats in proestrous and diestrous, as compared to the other phases of the cycle and to ovariectomised rats. Rats treated 24 hr after subchronic treatment with oestradiol also exhibited increased open-arm exploration. The anti-anxiety effect of diazepam was clearly shown in oestrous and metestrous but not in proestrous, diestrous or in ovariectomised rats. The effect of diazepam was abolished in rats tested 3 hr after acute small doses of estradiol and attenuated in rats tested 24 hr after subchronic administration of the hormone. The results suggest that oestradiol, administered in physiological doses, may have an inhibitory effect on the diazepam-induced anxiolysis.     

Cardiac tamponade due to post–cardiac injury syndrome in a patient with severe haemophilia A and HIV-1 infection

An 18-year-old man with severe haemophilia A (FVIII:C < 1%) and human immunodeficiency virus 1 (HIV-1) infection was admitted to the hospital with fever and chest pain for 7 days. Eight weeks prior to his admission he had an accident for which he underwent, at another hospital, clinical and laboratory examination that revealed bone fractures of the nose cavity, and he was given factor VIII concentrates for seven days due to nasal bleeding. On admission, chest roentgenogram showed a large cardiac silhouette and echocardiography confirmed the presence of a large quantity of pericardial fluid. A presumptive diagnosis of the post-cardiac injury syndrome was made and he was given anti-inflammatory drugs plus infusion of recombinant factor VIII concentrate (35 units kg-1 b.i.d.). On the seventh day he exhibited cardiac tamponade for which he underwent subxiphoid pericardiotomy with drainage of approximately 1500 mL of bloody exudate. He had an uncomplicated recovery and 10 days later he left hospital. He was given a continuous prophylactic treatment of 15 units kg-1 of recombinant FVIII every 2 days for 6 months, and 30 months after this episode the patient is free of any symptom.     

Activation of sympathetic fibres in the pulp by electrical stimulation of rat incisor teeth

Previous of the sympathetic nerve supply of the rat mandibular incisor pulp have shown conflicting results. Here, the neurovascular control of the rat lower incisor pulp was investigated by stimulating the tooth crown and the cervical sympathetic trunk electrically and monitoring blood-flow changes in the pulp by laser Doppler flowmetry. In addition the presence of noradrenaline (NA) in the pulp and gingiva was examined biochemically in untreated and sympathectomized animals by high-performance liquid chromatography. The tissue concentrations of NA in the pulp were 11-fold greater than those of gingiva. Surgical sympathectomy significantly reduced the NA content in the pulp by 76%. Monopolar electrical stimulation of teeth (25–50 μA) for 1 min resulted in a frequency-dependent reduction followed by an increase in pulpal blood flow. At 16 Hz the reduction in blood flow was 65% and the subsequent increase was 9%. After intravenous administration of the -adrenoceptor antagonist phentolamine, the stimulation-induced reduction in pulpal blood flow was diminished by 94% while the increase was significantly enhanced (from 9 to 40%). Infusion of the β-adrenoceptor antagonists propranolol and timolol significantly reduced this increase in blood flow by 53 and 55%, respectively. Preganglionic sympathetic nerve stimulation also induced a frequency-dependent reduction followed by a slight increase in pulpal blood flow. This reduction in blood flow was almost abolished after -adrenergic blockade and there was no subsequent increase. These findings suggest that there are sympathetic nerve fibres in rat incisor pulp and that they are activated upon monopolar electrical stimulation of teeth resulting in -and β-adrenoceptor mediated blood-flow responses.     

Enhancement of endocannabinoid neurotransmission through CB1 cannabinoid receptors counteracts the reinforcing and psychostimulant effects of cocaine

Cannabinoids, in contrast to typical drugs of abuse, have been shown to exert complex effects on behavioural reinforcement and psychomotor function. We have shown that cannabinoid agonists lack reinforcing/rewarding properties in the intracranial self-stimulation (ICSS) paradigm and that the CB1 receptor (CB1R) agonist WIN55,212-2 attenuates the reward-facilitating actions of cocaine. We sought to determine the effects of the endocannabinoid neurotransmission enhancer AM-404 (1, 3, 10, 30 mg/kg) on the changes in ICSS threshold and locomotion elicited by cocaine and extend the study of the effects of WIN55,212-2 (0.3, 1, 3 mg/kg) on cocaine-induced hyperlocomotion. AM-404 did not exhibit reward-facilitating properties, and actually increased self-stimulation threshold at the highest dose. Cocaine significantly reduced self-stimulation threshold, without altering maximal rates of responding. AM-404 (10 mg/kg) attenuated this action of cocaine, an effect which was reversed by pretreatment with the selective CB1R antagonist SR141716A. WIN55,212-2 decreased locomotion at the two highest doses, an effect that was blocked by SR141716A; AM-404 had no effect on locomotion. Cocaine caused a significant, dose-dependent increase in locomotion, which was reduced by WIN55,212-2 and AM-404. SR141716A blocked the effects of WIN55,212-2 and AM-404 on cocaine-induced hyperlocomotion. SR141716A alone had no effect on ICSS threshold or locomotion. These results indicate that cannabinoids may interfere with brain reward systems responsible for the expression of acute reinforcing/rewarding properties of cocaine, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for the treatment of psychostimulant addiction and pathological states associated with psychomotor overexcitability.