Frontal impairment and hypoperfusion in neuroacanthocytosis

Cerebral blood flow tomography, by xenon 133 inhalation or HMPAO (99mTc-d, l-hexamethyl-propylene amine oxime) technetium Tc 99m injection, revealed a severe hypoperfusion in both frontal lobes of a 40-year-old woman with confirmed neuroacanthocytosis. This finding occurred in conjunction with neuropsychological deficits consistent with selective frontal lobe dysfunction. This observation is the first documentation of this type of dementia in neuroacanthocytosis.     

Randomized double-blind study of fluvoxamine and maprotiline in treatment of depression

In a six-week double-blind randomized trial, preceded by a one-week period of single-blind placebo treatment, the efficacy and the side-effects of fluvoxamine (100-300 mg/d) (n = 24) and maprotiline (50-150 mg/d) (n = 24) were compared in moderately depressed outpatients with DSM-III Major Depression (n = 22) or Dysthymic Disorder (n = 26). Efficacy was measured by means of the Hamilton Depression Rating Scale, the Zung Depression Selfrating Scale, and a Clinical Global Impression of Severity Scale. Side-effects were evaluated by an Adverse Event Inventory and a Psychosomatic Symptom Scale. A statistically significant improvement was achieved in both treatment groups but success rates were modest: in both groups, 29% of the patients achieved a clinically significant improvement after six weeks of treatment. After six weeks of treatment, no difference in efficacy was found between fluvoxamine and maprotiline. Nausea was the most common complaint in the fluvoxamine group, while in the maprotiline group, it was dry mouth and constipation. One maprotiline-treated patient developed a convulsive attack.     

Tight nuchal cord and neonatal hypovolaemic shock.

Two neonates who went into acute hypovolaemic shock due to a tight nuchal cord were successfully resuscitated. The occurrence of this life threatening complication in two low risk pregnancies emphasises the importance of having staff trained in resuscitation immediately available in the delivery unit.     

The maturation of the central auditory conduction in preterm infants until three months post term. III. The middle latency auditory evoked response (MLR)

Middle latency auditory evoked responses (MLRs) were recorded in 64 premature infants; serially in 54 of them. The last recording sessions occurred at 50-52 weeks conceptional age (CA), defined as the gestational age (GA) added to the chronological age. The MLRs were analyzed for the components PO, Na and Pa, and the interpeak latency difference (IPLD) Na-PO. The detectability rate of PO and Na reached 80-90% at about 30 weeks CA. Pa reached the highest rate of about 60% at 52 weeks CA. The degree of prematurity did not result in clear differences with respect to the parameter values. Also, the side of stimulation did not influence the MLR parameter values. The latency values of the MLR components are strongly age dependent. Topographic differences were found between the sides ipsi- and contralateral to stimulation. They are, however, different for PO, Na and Pa. The influence of the state of vigilance on the parameter values could generally only be established at CA levels of about 32 and 52 weeks CA. The amplitude values at 52 weeks CA are especially sensitive for sleep or awake state. The particular pattern of age dependency of the different components and their topographic differences are consistent with a differential generation of bilateral nature. The early appearance of the response supports the generation of an early functioning subcortical structure in the auditory pathway.     

In vitro modulation of cisplatin cytotoxicity by sparsomycin inhibition of protein synthesis

Inhibition of protein synthesis can alter cellular responsiveness to the classical anticancer drugs. The in vitro response of Chinese hamster ovary (CHO) cells to cisplatin with or without sparsomycin (Sm) was studied with the use of [3H]leucine and [methyl-3H]thymidine incorporation and clonogenic assay. Pretreatment of exponentially growing CHO cells with 1 microgram Sm/ml for 3 or 5 hours decreased [3H]leucine incorporation by 20% and resulted in significant resistance to cisplatin (P = .005). Sm in a concentration of 10 micrograms/ml reduced [3H]leucine and [methyl-3H]thymidine incorporation after 3 hours by 92 and 84%, respectively, and resulted in potentiation of the cisplatin cytotoxicity (P = .004). This effect was the same in the case of nonproliferating cells (P = .005), while protection due to Sm (1 microgram/ml) was seen only during cell proliferation. Simultaneous incubation and postincubation with Sm proved to have much less or no potentiating effect on cisplatin. The mechanisms of both protection and potentiation are still not clear, but our data indicate that Sm is a promising drug for further studies on the modulation of the cancer cell response to classical anticancer drugs.     

Comparison of bronchial washing,brushing and biopsy for diagnosis of pulmonary tuberculosis

The diagnostic yields of bronchial washings, bronchial brushings and lung biopsy specimens were compared in 50 patients with positive Mycobacterium tuberculosis cultures. The number of positive results obtained with cultures of bronchial brushings was significantly higher than that with bronchial washings (p < 0.001). The histological study of biopsy lung material improved the rate of immediate or rapid diagnosis of tuberculosis (p<0.001).     

Mixture Toxicity Indices in acute lethal toxicity tests

The use of Mixture Toxicity Indices (MTI's) is one of the more attractive approaches for describing and predicting the effects of mixtures of toxicants. For an MTI to apply to all possible mixtures of the compounds in question, it must summarize information from a model describing all possible responses of interest. A method of obtaining MTI's from response surface equations or from tolerance models similar to the toxic units model is presented. Methods of calculating several MTI's with desirable properties from multivariable probit response surfaces are demonstrated.     

Enhanced dispersion of atrial refractoriness as an electrophysiological substrate for vulnerability to atrial fibrillation in patients with paroxysmal atrial fibrillation.

Atrial electrical remodeling plays a part in recurrence of atrial fibrillation (AF). It has been related to an increase in heterogeneity of atrial refractoriness that facilitates the occurrence of multiple reentry wavelets and vulnerability to AF. AIM: To examine the relationship between dispersion of atrial refractoriness (Disp_A) and vulnerability to AF induction (A_Vuln) in patients with clinical paroxysmal AF (PAF). METHODS: Thirty-six patients (22 male; age 55+/-13 years) with > or =1 year of history of PAF (no underlying structural heart disease--n=20, systemic hypertension--n=14, mitral valve prolapse--n=1, surgically corrected pulmonary stenosis--n=1), underwent electrophysiological study (EPS) while off medication. The atrial effective refractory period (AERP) was assessed at five different sites--high (HRA) and low (LRA) lateral right atrium, high interatrial septum (IAS), proximal (pCS) and distal (dCS) coronary sinus--during a cycle length of 600 ms. AERP was taken as the longest S1-S2 interval that failed to initiate a propagation response. Disp_A was calculated as the difference between the longest and shortest AERP. A_Vuln was defined as the ability to induce AF with 1-2 extrastimuli or with incremental atrial pacing (600-300 ms) from the HRA or dCS. The EPS included analysis of focal electrical activity based on the presence of supraventricular ectopic beats (spontaneous or with provocative maneuvers). The patients were divided into group A--AF inducible (n=25) and group B--AF not inducible (n=11). Disp_A was analyzed to determine any association with A_Vuln. Disp_A and A_Vuln were also examined in those patients with documented repetitive focal activity. Logistic regression was used to determine any association of the following variables with A_Vuln: age, systemic hypertension, left ventricular hypertrophy, left atrial size, left ventricular function, duration of PAF, documented atrial flutter/tachycardia and Disp_A. RESULTS: There were no significant differences between the groups with regard to clinical characteristics and echocardiographic data. AF was inducible in 71% of the patients and noninducible in 29%. Group A had greater Disp_A compared to group B (105+/-78 ms vs. 49+/-20 ms; p=0.01). Disp_A was >40 ms in 50% of the patients without A_Vuln and in 91% of those with A_Vuln (p=0.05). Focal activity was demonstrated in 14 cases (39%), 57% of them with A_Vuln. Disp_A was 56+/-23 ms in this group and 92+/-78 ms in the others (p=0.07). Using logistic regression, the only predictor of A_Vuln was Disp_A (p=0.05). CONCLUSION: In patients with paroxysmal AF, Disp_A is a major determinant of A_Vuln. Nevertheless, the degree of nonuniformity of AERP appears to be less important as an electrophysiological substrate for AF due to focal activation.     

Adrenal function under long-term raloxifene administration.

The aim of the present study was to evaluate the effect of long-term (12 months) administration of raloxifene hydrochloride (60 mg/day) on the steroid production of the adrenal cortex and on the hypothalamic-pituitary-adrenal axis in postmenopausal women. We performed a basal evaluation, a corticotropin releasing factor (CRF) (100 microg i.v. bolus) test and a dexamethasone (DXM) (0.25 mg) suppression-adrenocorticotropic hormone (ACTH) (10 microg i.v. bolus) stimulation test in 11 postmenopausal women, before and after 3, 6 and 12 months of raloxifene treatment. Raloxifene administration significantly modified circulating levels of adrenal steroids, decreasing cortisol (-24%), dehydroepiandrosterone (DHEA) (-36%), and its sulfate (DHEAS) (-41%), and androstenedione (-29%), and increasing circulating allopregnanolone (+39%) levels. Progesterone and 17OH-progesterone levels remained unmodified, while estradiol and estrone levels showed a significant decrease (-51% for estradiol and -61% for estrone). We also observed an increase in circulating ACTH (+58%) and beta-endorphin (+120%). No modifications in the hormonal responses to CRF were observed during the treatment. DXM significantly suppressed circulating steroids at any time with a lower suppression of cortisol from the third month and a higher suppression of DHEA at 12 months. ACTH administration was associated with a significantly blunted cortisol response from the sixth month and a significantly increased response of allopregnanolone from the third month. The present data exclude a raloxifene effect on pituitary sensitivity to CRF and demonstrate a reduced adrenal sensitivity to ACTH, sustained by the opposite changes in basal cortisol and Delta5 androgens, which were reduced, and in ACTH and beta-endorphin, which were increased, as well by the reduced response of cortisol to the direct ACTH stimulus. The reduction of circulating cortisol levels and cortisol response to the ACTH challenge suggests that raloxifene protects against the neurotoxic effects of endogenous glucocorticoids. Furthermore, the progressive increase in basal allopregnanolone and its increased response to ACTH indicate that chronic raloxifene administration exerts direct effects on the pattern of adrenal enzymes, leading to specific changes in the circulating levels of this anxiolytic progesterone metabolite. The important reduction in the circulating levels of estradiol and estrone under long-term raloxifene administration may represent a further mechanism by which this molecule may exert a protective effect against breast and endometrial malignancies.