Effects of psychotropic agents on the physical properties of platelet membranes in vitro

Normal platelet membranes were exposed in vitro to a variety of psychotropic medications commonly used in the treatment of patients with psychiatric disorders. Changes in structural order at the hydrocarbon region of the drug-exposed membranes were determined by steadystate fluorescence polarization measurements employing the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Chlorpromazine, an aliphatic phenothiazine, produced a significant increase in DPH fluorescence polarization at concentrations from 2–200 M. Thioridazine, a piperidine phenothiazine, and three piperazine derivatives, perphenazine, trifluoperazine, and fluphenazine, produced significant increases in this parameter at concentrations from 20–200 M. The other agents tested, including thiothixene, lithium, antidepressants, anxiolytics, and anticonvulsants, were without effect in the concentration ranges examined. The phenothiazine-induced increase in DPH fluoresence polarization apparently depended on the structure of the phenothiazine nucleus; changes in side-chain structure appeared to modulate this effect, most likely by altering the inherent membrane solubility of the agents.     

Studies in gastric carcinogenesis. II. Absence of elevated concentrations of N-nitroso compounds in the gastric juice of Greek hypochlorhydric individuals

The concentrations of nitrate, nitrite, N-nitrate compoundsand bacteria were measured in 96 samples of fasting gastricjuice, pH 0.90–8.50, obtained from 56 individuals justbefore or at various times (8 days –1 year) after gastricoperation. The mean pH of the post-operative samples [4.66 ±0.39 (SEM)] was significantly higher than that of the pre-operativeones [3.29 ± 0.33 (SEM]. A positive correlation withpH was observed for the concentrations of total and nitrate-reducingbacteria (median values 5.0 x 10⁵ organisms/ml and 9.2 x 10⁴organisms/ml, respectively, for samples with pH6.5, and 1.2x 10³ organisms/ml and 0 organisms/ml, respectively, for sampleswith pH 2.5) and nitrite [mean values 22.5 ± 3.1 (SEM)µM and 3.20 ± 0.5 (SEM) uM for samples with pH6.5 and pH 2.5, respectively]. No correlation with pH was seenfor the concentrations of nitrate [mean value 0.48 ±0.06 (SEM) mM] or N-nitroso compounds [mean value 0.30 ±0.06 (SEM) µM]. The concentrations of bacteria and nitrite,although increased in hypochlorhydric individuals, were lowerthan those reported for corresponding individuals in other,primarily British, studies. It is suggested that the relativelylow concentrations of nitrite observed in our hypochlorohydricpopulation may account for the absence of elevated concentrationsof N-nitroso compounds and that the latter phenomenon may berelated to the relatively low frequency of gastric cancer inGreece.     

Fast neutron radiotherapy for locally advanced prostate cancer: results of an RTOG randomized study

Between June 1977 and April 1983, the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized study investigating fast neutron radiation therapy in the treatment of patients with locally advanced (Stage C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation therapy or fast neutron irradiation used in a mixed-beam treatment schedule (neutron/photon). A total of 91 analyzable patients were entered in the study; 78 of them were treated without major protocol deviations. The two treatment groups were balanced in regard to all major prognostic variables. Actuarial curves for "overall" survival, "determinantal" survival and local/regional control are presented both for the entire group of 91 patients and the 78 patients treated within protocol guidelines. The overall local/regional tumor recurrence rate is 7% for the mixed-beam treated group of patients and is 22% for the photon (X ray) treated group of patients. The difference is statistically significant at the p = 0.05 level. For the entire group of 91 evaluable patients, the 5-year "overall" survival rate is 62% for the mixed-beam-treated group and 35% for the photon-treated group. This difference is also statistically significant (p less than 0.05). However, this statistical significance is lost when the smaller number of patients treated strictly within protocol guidelines is considered. The significance is regained (p less than 0.02) when one looks at "determinantal" survival, which uses active cancer at time of death as the failure endpoint. This study demonstrates that a regional treatment modality, in this case mixed-beam irradiation, can influence both local/regional tumor control and survival in patients with locally-advanced adenocarcinoma of the prostate gland.     

Extrapelvic colon--areas of failure in a reoperation series: implications for adjuvant therapy

A total of 230 patients had planned single or multiple reoperative procedures following "curative" resection of colorectal cancer at the University of Minnesota. The site of the primary lesion was extrapelvic in 91, and later evidence of cancer was found in 58 patients (64%) at re-operation and/or other follow-up. Eight of the 58 (14%) were converted to disease-free status. Incidence and patterns of failure were correlated with initial operative-pathologic extent of disease (87 of the 91 at risk had initial tumor extension beyond the bowel wall, involved nodes or both) and comparisons were made with the previously analyzed rectal reoperation patients. While a component of local-regional failure was more common with rectal lesions (48/74 at risk, 65%), it was not uncommon with extrapelvic primaries (44/91-48%). The incidence of hematogenous metastasis (DM) was equal, but the pattern of initial DM differed (extrapelvic colon--primarily liver; rectum--liver and lung). Peritoneal seeding was a more common component of failure with the extrapelvic primaries (19/91--21% vs 3/74-4%). Since surgery alone is inadequate treatment for many patients with colon as well as rectal cancer, the rationale of adjuvant radiation and systemic therapy, alone or in combination, is discussed.     

Electrophysiologic and histopathologic correlations in a case of permanent form of reciprocating tachycardia

A case of permanent junctional reciprocating tachycardia withpost-mortem documentation of an accessory atrioventricutar pathwayas the substrate of the arrhythmia is reported. Tachycardiahad lasted for 15 years and showed a retrograde P wave (P')and R–P' longer than P'–R interval. The tachycardiacircuit utilized a concealed posterior septal accessory pathwayas the retrograde limb. Because the arrhythmia was disablingand unresponsive to pharmacological treatment, the patient underwentclosed chest ablation of the His bundle. After the procedure,no anterograde or retrograde conduction over the normal conductionsystem was observed; anterograde conduction over the anomalouspathway showed decremental properties. Because of previous myocardialinfarction, the patient developed a ventricular aneurysm anddied suddenly 5 months after His bundle ablation. Histologicalexamination of the heart revealed a group of tiny fibromuscularbundles joining the lower rim of the coronary sinus outlet tothe summit of the interventricular septums; the anomalous atrioventricularconnection pursued a sinuous, tortuous path. The geometricaldisposition of the accessory pathway may have been responsiblefor the decremental properties of conduction observed duringlife.     

Familial cavernous malformations of the central nervous system and retina

We studied a family in which 4 persons from three generations had multiple cavernous malformations ("angiomas") of the central nervous system (CNS) and/or retina and found accounts in the literature of sixteen other families with this condition. In these families with familial cavernous malformation of the CNS and retina, 92% of pathologically documented vascular malformations were cavernous; 50% of those subjects affected had multiple CNS and/or retinal vascular malformations and 68% (excluding probands) were symptomatic. Cutaneous vascular lesions were an inconsistant manifestation. Autosomal dominant inheritance with high penetrance was confirmed.     

BLOOD PLASMA PEPTIDES OF RATS AFTER ADMINISTRATION OF ETHANOL OR ACETALDEHYDE

The blood plasma peptide fractions labelled with ³H-leucineafter chronic administration of ethanol or acetaldehyde in ratshave been analysed. Total ³H-leucine radioactivity in peptidefraction calculated per millilitre of plasma in both study groupswas significantly decreased. The amount of peptide spots obtainedby tlc in the ethanol-treated group or acetaldehyde-treatedgroup was reduced in comparison with the control group. Analysisof amino acid composition of atypical spots occurring in bothtest groups revealed the presence of aromatic amino acids andmethionine, but was associated with the absence of branched-chainamino acids, such as valine, leucine and isoleucine. These findingssuggest a change in protein metabolism in hepatic dysfunctionin rats receiving ethanol or acetaldehyde.     

ANTIGENEMIA HBs AND OTHER SEROLOGICAL MARKERS OF HEPATITIS B VIRUS INFECTION IN PATIENTS WITH ACUTE AND CHRONIC ALCOHOLISM

Serological markers of hepatitis B virus infection were studiedin a group of recently presenting alcoholic out-patients andcompared with a group of long-stay in-patients suffering fromchronic alcoholism. All markers of infection were increasedin the chronic group and Were thought to be related to admissionto the Alcohol Unit. Although both groups had normal liver functiontests, the patients with the longer alcohol history had evidenceof two coexisting causes of liver disease and may, therefore,have a much poorer prognosis.     

Evaluation of urethral pressure profilometry for the diagnosis of genuine stress incontinence

Summary Given the expense of radiographic imaging facilities and the reproducibility of urethral pressure measurements with microtransducers, the use of urethral pressure profilometry (UPP) has been gaining widespread popularity for the diagnosis of genuine stress incontinence (GSI). However, the clinical usefulness of the technique has not been adequately evaluated against the best available technique, namely videocystourethrography. Using the latter technique as the Gold Standard, the UPP results of 114 normal women and 95 GSI patients have been compared. In order to determine the most diagnostic UPP measure, 25 parameters were examined for each patient. With the use of the Kappa statistic it was found that the area under the stress profile was the most discriminatory of the UPP parameters. Even using this measure, the overlap between normal and GSI is so great as to make accurate diagnosis impossible. It is therefore concluded that UPP is useless for the diagnosis of GSI.     

Effect of vibration on red cell metabolism

Summary In investigating the influence of vibrational energy on the metabolism of the erythrocyte, it was hypothesized that under conditions of normal PaO₂ and SaO₂ in arterial blood, vibration induced vasoconstriction would decrease local blood flow and induce hypokinetic hypoxia. This decreased blood flow and therefore decreased delivery of oxygen to the tissue would markedly lower tissue PO₂ (hypokinetic hypoxia), which would influence the energetics and metabolism of the erythrocyte. The metabolism of the red blood cell (RBC) was evaluated by measuring the enzymatic activities of PFK (2.7.1.11), PGI (5.3.1.9), PK (2.7.1.40), and aldolase (4.1.3.13) from the anaerobic glycolytic cycle and D-G-6-P (1.1.1.49) from the pentose cycle. Also measured were the levels of ATP and 2,3 DPG and the in-vitro production of lactic acid. In the group of workers showing early changes (vibration angioneurosis) associated with the vibration syndrome, changes in RBC metabolism were demonstrated. Statistically significant were increases of PFK, PK and the production of lactic acid, indicating the activation of anaerobic glycolysis. Furthermore statistically significant were the increased 2,3 DPG and decreased ATP levels.