Metabolic requirement for the inotropic effects of digitalis and BAY K 8644

The positive inotropic effects of ouabain and of BAY K 8644 are not apparent in rabbit atria suspended in substrate free medium or in a medium containing 5 mM pyruvate. Addition of glucose in graded concentrations (1-11 mM) during continued exposure of the preparations to the inotropic agents yields graded inotropic effects. The possible involvement of the glycolytic pathway to the development of the inotropic effect of ouabain and BAY K 8644 was tested by using inhibitors of glycolysis that act at two different steps. Iodoacetic acid completely blocks the inotropic effect of ouabain in atria at 0.1 mM and papillary muscles at 0.05 mM. The inotropic effect of BAY K 8644 was blocked partially in atria and papillary muscles. Iodoacetic acid did not change the inotropic effects of isoproterenol and Ca2+. Addition of 1 mM fluoride did not affect significantly the inotropic effect of either ouabain or BAY K 8644 in atria but partially blocked the effect of BAY K 8644 in papillary muscles. The response of atria to ouabain was not changed significantly when glyceraldehyde (10 mM) was substituted for glucose. We suggest that glycolytic ATP may be important for the full inotropic effect of ouabain and BAY K 8644.     

Dual-isotope SPECT imaging of striatal dopamine: first episode, drug naïve schizophrenic patients

OBJECTIVE: The aim of this investigation was to evaluate the usefulness of a dual-isotope SPECT technique to assess simultaneously striatal dopamine binding structures - presynaptic dopamine transporter (DAT) and postsynaptic dopamine D(2) receptor - in first-episode, drug-naive schizophrenic patients compared to healthy control persons. Additionally, relations between radioligand binding to DAT and D(2) and positive symptoms were assessed. METHODS: Twenty acutely ill inpatients suffering from a first acute schizophrenic episode and 12 healthy control persons participated in the study. Patients were na?ve with respect to neuroleptic or antidepressant medication. A dual-isotope SPECT protocol was performed using combined application of [99mTc]TRODAT-1 and [123I]IBZM. On the day of SPECT, psychopathology was assessed in the patient group by PANSS rating. RESULTS: In the patient but not in the healthy control group there was a significant correlation between DAT and D(2) receptor availability. Patients with predominant positive symptoms (n=12) had a significantly higher DAT availability compared to the healthy control group. An inverse correlation between DAT and D(2) availability and the extent of "delusions", "conceptual disorganization", and "hallucinatory behaviour" could be demonstrated. DISCUSSION: The data obtained with this dual-isotope SPECT technique show a change in interaction between striatal DAT and D(2) receptor in first-episode, never-treated schizophrenic patients. Additionally, an association between dopamine transmission and the core symptoms of the acute psychotic syndrome was found.     

Increase of striatal dopamine transmission in first episode drug-naive schizophrenic patients as demonstrated by [I]IBZM SPECT

Acute psychotic exacerbation in schizophrenia is associated with a “striatal hyperdopaminergic state”. The aim of this investigation was to test this hypothesis by assessing striatal dopamine D₂ receptor availability using single photon emission computed tomography (SPECT) and the specific D₂ radioligand [¹²³I]IBZM in first episode, drug-naïve, schizophrenic patients and compare it with that in healthy control subjects. Additionally, D₂ radioligand binding was correlated with the extent of psychopathology assessed by specific rating scales including Positive and Negative Syndrome Scale (PANSS). Twenty-three acutely ill, treatment-naïve, inpatients suffering from a first acute psychosis were studied. Patients were assigned to a psychopathological syndrome-type according to PANSS positive and negative subscale results. The PANSS items delusions, conceptual disorganization, and hallucinatory behaviour were chosen to assess the extent of the acute psychotic syndrome. Patients showed a significantly lower specific [¹²³I]IBZM binding compared with the control group. Positive and negative syndrome type patients differed significantly with respect to specific IBZM binding. There was a significant negative correlation between IBZM binding and the PANSS item ‘hallucinatory behaviour’ in patients with pronounced positive symptoms. The data obtained show a significant difference between acute psychotic patients, patients with predominant negative syndrome, and healthy controls, according to the concept of a “hyperdopaminergic state” in psychotic exacerbation.     

18F-FDG PET/CT for staging of penile cancer.

The value of PET or PET/CT with (18)F-FDG for the staging of penile cancer has yet to be determined. The objective of this study was to investigate the pattern of (18)F-FDG uptake in the primary malignancy and its metastases and to determine the diagnostic value of (18)F-FDG PET/CT in the staging and restaging of penile cancer. METHODS: Thirteen patients (mean +/- SD age, 64 +/- 14.0 y) with suspected penile cancer or suspected recurrent disease were examined with a Gemini PET/CT system (200 MBq of (18)F-FDG). The reference standard was based on histopathologic findings obtained at biopsy or during surgery. RESULTS: Both the primary tumor and regional lymph node metastases exhibited a pattern of (18)F-FDG uptake typical for malignancy. Sensitivity in the detection of primary lesions was 75% (6/8), and specificity was 75% (3/4). On a per-patient basis, sensitivity in the detection of lymph node metastases was 80% (4/5), and specificity was 100% (8/8). On a nodal-group basis, PET/CT showed a sensitivity of 89% (8/9) in the detection of metastases in the superficial inguinal lymph node basins and a sensitivity of 100% (7/7) in the deep inguinal and obturator lymph node basins. The mean +/- SD maximum standardized uptake value for the 8 primary lesions was 5.3 +/- 3.7, and that for the 16 lymph node metastases was 4.6 +/- 2.0. CONCLUSION: According to our results, the main indication for (18)F-FDG PET in the primary staging or follow-up of penile cancer patients may be the prognostically crucial search for lymph node metastases. With the use of a PET/CT unit, the additional information provided by CT may be especially useful for planning surgery. Implementing (18)F-FDG PET and PET/CT in future staging algorithms may lead to a more precise and stage-appropriate therapeutic strategy. Furthermore, invasive procedures with a high morbidity rate, such as general bilateral lymphadenectomy, may be avoided.     

Meckel cave lesions: percutaneous fine-needle-aspiration biopsy cytology

The authors describe the novel combination of two traditional methods to facilitate diagnosis of Meckel cave lesions, which may otherwise require craniotomy to obtain adequate tissue samples. Fine-needle-aspiration biopsy cytology was performed on tissue obtained with a percutaneous approach via the foramen ovale with use of fluoroscopic guidance and intravenous analgesia during an outpatient procedure. This new application of fine-needle-aspiration biopsy cytology results in decreased patient morbidity and significant cost reduction.     

Neurohormonal modulation of natural resistance to a murine lymphoma

The hypothesis that neuroendocrine stimulation after aversive handling can alter natural resistance was examined in the tail electroshock (TES) model, a procedure that can activate pituitary neuropeptide secretion. Immediately after a brief TES session, the resistance of DBA/2J mice was suppressed in proportion to the intensity of the shock. Initial suppression of the natural resistance was rapidly reversed in longer treatment protocols, and repeated aversive stimulation augmented the antitumor response, leaving the mice more resistant to lymphoma than unhandled animals. Corticosterone was released into the serum after all acute handling procedures, and hydrocortisone inoculation suppressed antitumor responses. However, serum corticosterone levels did not quantitatively correlate with the alterations in natural resistance. The observation that TES-induced suppression of natural resistance could be reversed by the opiate receptor antagonist naltrexone suggested that endogenous opiated released after TES stimulation were immunosuppressive.