Olfactory dysfunction in behavioral variant frontotemporal dementia.

OBJECTIVE: Several neurodegenerative disorders show olfactory dysfunction. In patients with frontotemporal dementia (FTD), olfactory impairment is probably due to the involvement of the temporal and orbitofrontal lobes. We hypothesized that due to the disrupted areas in FTD, there would be an impairment in smell identification, differentiation and association. Moreover, we hypothesized that there would be a correlation between the severity of FTD and the severity of odor dysfunction. METHODS: In the current study, we compared odor identification, discrimination and association of nine patients with behavioral variant FTD with eleven healthy controls using the Brief Smell Identification Test and the Odor Perception and Semantics Battery. RESULTS: The results showed significant differences in the odor association test, but not in the identification or discrimination test. There was no correlation between disease severity and the performance in the odor tests. CONCLUSION: We showed impairment of odor association that is most likely due to disruption of specific associative areas involved in olfactory processing. Specifically, we propose that the impairment may well be due to disrupted areas in the temporal lobe and amygdala.

Retrograde amnesia for autobiographical memories and public events in mild and moderate Alzheimer's disease.

Patients with mild to moderate Alzheimer's disease and normal controls were tested on two retrograde memory tests, one based on public events, and the other querying autobiographical memory. On both tests, patients showed strong decrements as compared to normal controls, pointing to retrograde amnesia. Evidence for a gradient in retrograde amnesia was conflicted, with analyses of variance revealing no gradient beyond the most recent period, and more sensitive analyses pointing to shallow Ribot gradients on both tests. A literature review shows that this is the case in most published studies. In autobiographical remote memory patients generated many incorrect answers, a tendency correlated with the number of false alarms on an anterograde memory test administered several months earlier. This suggests a stable, possibly executive, factor underlying memory errors.

The role of visual discrimination disorders and neglect in perceptual categorization deficits in right and left hemisphere damaged patients.

This study was designed to investigate the role of visual sensory deficits and neglect in perceptual categorization deficits in a group of 35 patients with unilateral cerebral lesions. From theoretical point of view, it was expected that right hemisphere lesions would play a critical role in eliciting perceptual categorization deficits which could not be accounted for by visual sensory deficits or neglect. The results revealed that perceptual categorization deficits were not confined to RHD patients, but they were also found in LHD patients. RHD patients were impaired regardless of the nature of the task (verbal vs. nonverbal), while LHD patients were impaired on nonverbal tasks, and in a lesser degree on verbal tasks. In both braindamaged groups, perceptual categorization deficits were highly associated with visual sensory deficits, however, perceptual categorization deficits were also found without impairments in the visual sensory system. Neglect to be less important determinant of perceptual categorization deficits. The present findings are discussed in the light of Warrington's model of object agnosia.

The treatment of uterine bleeding with vasopressin hormonogen (glypressin)--a pilot study.

In a pilot study 12 women with severe uterine bleeding received an intravenous injection of 0.2 mg of a vasopressin hormonogen, glypressin. In 11 of the patients a rapid reduction or cessation of blood loss were observed. Two patients had facial pallor following the injection but no other side effects occurred. Five of the older women with long histories of menorrhagia were placed on a regime of one injection of glypressin on the first day of menstruation for six months; in all of them the duration of bleeding was reduced to three days and the monthly blood loss became very slight. On the basis of these results more extensive clinical trials in menorrhagia and metrorrhagia are recommended.

Skin and nail infection by Scytalidium hyalinum sp. nov.

Eight cases of fungal infection are described in which an arthrosporic hyphomycete has been isolated from patients of Jamaican and West African origin. In most cases the organism was the only one isolated and in one case it was isolated 3 times over a 5 month period. The fungus is described as a new species of Scytalidium (S. hyalinum).

Action of the triglycyl hormonogen of vasopressin (glypressin) in patients with liver cirrhosis and bleeding esophageal varices.

Seven patients with compensated liver cirrhosis and esophageal varices, all with a base line wedge hepatic vein pressure greater than 20 cm H2O, received 1-mg doses of vasopressin hormonogen (tGLVP) intravenously. There was a significant mean decrease in wedge pressure of 32%, which lasted for at least 20 min (the duration of measurement), with no change in cardiac output measured. The only cardiac response was a 10 to 20% bradycardia at the height of the moderate pressor response-otherwise the ECG was without change. In 5 patients who received the same tGLVP dose during surgery, direct measurements of portal venous pressure showed the same degree of decrease within 10 min of intravenous injection. Fifteen patients with liver cirrhosis and severe bleeding from esophageal varices were treated conservatively with blood transfusion and tGLVP as the only major drug aside from antibiotics. A nonrandomized control group of 13 patients with the same age distribution, stage of disease, number of previous bleeds, etc., was treated conservatively in the same manner, except that they received either no hemodynamically active drugs or short acting neurohypophysial peptide preparations such as Pitressin. In the control group there was a 61.5% total mortality, a 53.8% mortality directly related to uncontrollable bleeding, and a mean duration of the bleeding episode of 11 days. In the tGLVP-treated group total mortality was 20%, mortality directly related to uncontrollable bleeding was 13.3%, and mean duration of the bleeding episode was 2.9 days. These results appear to justify a large scale clinical trial of the vasopressin hormonogen in this disease.

Role of the disulfide bridge and the C-terminal tripeptide in the antidiuretic action of vasopressin in man and the rat.

The antidiuretic action of a number of vasopressin analogues has been measured in the rat and man in water diuresis. These analogues had the following categories of structural alteration: a) substitution of -CH2CH2-(dicarba) and -SCH2-(6-monocarba) for the natural -SS- bridge between residues 1 and 6, b) changes in the nature of the C-terminal tripeptide produced by substitution of D-arginine and L-Nalpha-methylarginine for L-arginine in sequence position 8 and L-leucine for proline in position 7, and c) combinations of a and b. In addition, a highly active analogue which results when valine is substituted for glutamine in position 4 was tested. Trained, unanesthetized rats and normal human volunteers were complemented by a volunteer patient with posttraumatic diabetes insipidus (DI) in the total group of experimental subjects. The only change in the C-terminal tripeptide which was associated with a high antidiuretic action was D-Arg substitution. The meArg and Leu analogues showed low to very little activity and no signs of antidiuretic antagonist action. All of the carba analogues showed both high potency and prolongation of antidiuretic action in the following order (for both potency and duration): monocarba + 8-D-Arg greater than 4-Val + 8-D-Arg greater than 8-D-Arg alone, all in deamino form. None of the 8-D-Arg analogues had any side effects on the cardiovascular system, gut, uterus, bladder, etc. The prolongation was such that even with a DI patient refractory to the action of lysine-vasopressin and relatively resistant to deamino-[8-D-Arg]-vasopressin, water turnover could be reduced from untreated levels of 20 to 30 liters/day to less than 2 liters/day with only a single administration of deamino-6-carba-[8-D-Arg]-vasopressin as nose drops. The significance of these structural alterations in the vasopressin molecule for interaction with both antidiuretic and smooth muscle receptors was discussed.

[The action of triglycylvasopressin on control subjects and patients with upper gastrointestinal bleeding (author's transl)]. / Die Wirkung von Triglycyl-Lysin-Vasopressin auf Kontrollpersonen und Patienten mit Blutungen des oberen Gastrointestinaltraktes

Nalpha-glycyl-glycyl-glycyl-(8-lysine)-vasopressin, a hormone analogue with prolonged pharmacological action due to slow release of active nonapeptide by enzyme action in vivo, has been administered to 5 control subjects and to 14 patients actively bleeding from upper gastrointestinal sites. The control subjects showed a prolonged pressor response to 100mug/kg body weight associated with a rise in cardiac output, with no ECG signs of myocardial toxicity. 13 of the 14 bleeding patients showed not only pressor responses and haemodynamic and clinical improvement when administering doses of 20-100 mug/kg, but clear signs of standstill of upper gastrointestinal bleeding.

Regional and systemic haemodynamic effects of some vasopressins: structural features of the hormone which prolong activity.

Cardiac output and regional blood flows to myocardium, gut, uterus and kidney were determined in anaesthetised female rats by a single injection of 86RbCl. The haemodynamic responses were measured at various time intervals up to 2 h after single I.V. injections of lysine-vasopressin and the following of its analogues: a) with extended peptide chains at the N-terminal (including "hormonogens") Nalpha-glycyl-glycyl-lysine-vasopressin, Nalpha-glycyl-glycyl-glycyl-arginine-vasopressin and Nalpha-D-valyl-lysine-vasopressin, b) "carba" modifications desamino-carba6-arginine-vasopressin, desamino-carba6-D-arginine8-vasopressin, desamino-carba6-ornithine8-vasopressin, desamino-dicarba-arginine-vasopressin and c) other steric alterations - desamino-D-arginine8-vasopressin and desamino-N-methylarginine8-vasopressin. Sub-pressor doses of lysine-vasopressin were followed by marked reductions in gut and uterus blood flows which reached a peak at 10 min. and had completely receded by 60 min. The presence of steric alterations in the C-terminal tripeptide of the molecule- D-arginine or N-methylarginine in sequence position 8 - practically completely eliminated vascular activity. The same was true for Nalpha-D-valyl-lysine-vasopressin. None of the latter three analogues showed any inhibitor properties to the action of lysine-vasopressin. The two hormonogens (triglycyl N-terminal extensions) had to be given in doses 10 times greater to obtain a vasoconstrictor effect in gut and uterus equivalent in amplitude to that of a lysine-vasopressin, but this effect was still present to the same degree 2 h later with the hormonogen of lysine-vasopressin, and was only starting to return to baseline values at the same time with the arginine-vasopressin hormonogen. The vascular potency of both mono-carba L-analogues was higher than that of lysine-vasopressin, and the effect was as prolonged as with the hormonogens. The dicarba analogue also showed a prolonged action, but with much reduced potency. No significant changes in renal or myocardial blood flows were observed at all. Molecular features of vasopressin smooth muscle activity were discussed, and a receptor model was proposed. It was suggested that the -S-S-, -CH2CH2-bridges in the above analogues are not directly bound in the peptide-receptor complex and constitute the limiting factor determining complex duration, or persistence of the active peptide in the "receptor compartment". These results provide an experimental basis for possible clinical application of triglycyl-vasopressin and carba-vasopressin in bleeding from both gut and uterus and for induction of menstruation.

The use of a short-lived radionuclide in the investigation of acute bleeding in the upper gastrointestinal tract.

A method is described for the detection and monitoring of bleeding in the upper gastrointestinal tract. A short-lived radionuclide (113In-m) is used. Acute bleeding in the upper gastrointestinal tract in patients without signs of shock and preshock usually stopped within a short time after onset.