The effects of peripherald-amphetamine, 4-OH amphetamine, and epinephrine on maintained discharge in the locus coeruleus with reference to the modulation of learning and memory by these substances

d-Amphetamine, 4-OH amphetamine, and epinephrine have been shown in many behavioral studies to facilitate memory when given post-training. The effect of these drugs on the maintained discharge of cells in the locus coeruleus (LC) was investigated using a route of administration (intraperitoneal) and a log-dose range of these drugs comparable to those used in the behavioral experiments.d-Amphetamine profoundly suppressed maintained discharge: an inhibitory effect was observed at every dose (0.1, 1.0, 10.0 mg/kg). In contrast, only the highest dose of 4-OH amphetamine (8.2 mg/kg) inhibited activity in the LC, and this effect was a modest one. Unlike the amphetamines, epinephrine (500 μ/kg) elevated maintained discharge. These results are discussed in the contex of the hypothesized involvement of the LC in the enhancement of memory by these drugs.     

Effect of high hematocrit and high blood flow rates on transmembrane pressure and ultrafiltration rate in hemodialysis.

Removal of prescribed ultrafiltration volumes in hemodialysis requires knowledge of both the ultrafiltration coefficient of the dialyzer and the average transmembrane pressure (TMP) in the dialyzer. While it has been a fairly common practice to assume that the TMP is constant along the length of the dialyzer, it actually decreases linearly from a maximum value at the blood inlet to a minimum value at the blood outlet. In the past, ignoring the difference between arterial and venous TMPs when calculating the dialysate pressure setting did not result in significant errors in ultrafiltration volume. However, with the introduction of erythropoietin therapy and the trend toward high-efficiency dialysis, increases in hematocrit and blood flow rate have led to axial variations in TMP which, if ignored, can lead to inaccurate fluid removal. The goals of this paper are to provide an understanding of how high hematocrits and high blood flow rates affect TMP and ultrafiltration rate, and to provide simple guidelines for ensuring accurate fluid removal. Sample calculations are given on the last page for easy reference.     

Application of fluorescence in situ hybridization techniques in clinical genetics: use of two alphoid repeat probes detecting the centromeres of chromosomes 13 and 21 or chromosomes 14 and 22, respectively

Two cloned DNA fragments, one derived from an alpha satellite subfamily common to chromosomes 13 and 21, and the other derived from a similar subfamily common to chromosomes 14 and 22, have been used as biotinylated probes in in situ hybridization studies. Under high stringency conditions, chromosome specific centromeric labelling can be obtained. The applications of this technique in clinical situations are illustrated on metaphases from a fetus with trisomy 21, a fetus with trisomy 13, and a child with clinical features of cat-eye syndrome.     

Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations.

Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr respectively) whereas differences in AUC, t1/2 and Cmax were not significant. The AUC (mean +/- S.D.) values following single dose administration of Cardil and Cardizem were 678.4 +/- 321.5 and 948.6 +/- 580.6 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.89 and 0.44-1.34 respectively. At steady-state a significant difference between Cmax/Cmin and tmax was seen Cmax/Cmin being 4.9 and 3.2 respectively and Tmax being 2.7 +/- 2.0 and 6.0 +/- 2.8 hr respectively, whereas Cmax and AUC did not differ significantly. The AUC (mean +/- S.D.) values in steady state of Cardil and Cardizem were 880.1 +/- 399.8 and 1056.8 +/- 509.8 ng.ml-1.hr respectively. The mean and the 95% confidence limits for the observed ratio AUCCardil/AUCCardizem are 0.96 and 0.66-1.26 respectively. Although the observed ratios AUCCardil/AUCCardizem in both the single-dose and the steady-state study do not differ significantly from 1.0, the confidence limits exceed the acceptable values given by Poulsen & Juul (personal communication 1990) (a 20% decrease or increase of the ratio to 0.8 or 1.2).     

Comparison studies of HPV detection in areas at different risk for cervical cancer.

The hypothesis of a geographical correlation between HPV detection rates and incidence of cervical cancer has been investigated in studies of various types. However, results from these studies are equivocal, in contrast to findings concerning other suspected risk factors which seem to correlate well with the cervical cancer incidence. Possible explanations include (1) greater sensitivity of ecological studies to cumulative exposures such as lifetime number of sexual partners, lifetime smoking and seroprevalence of herpes simplex virus type 2, than to HPV DNA prevalence which does not reflect cumulative exposure to HPV and (2) misclassification in the HPV diagnosis leading to wrong prevalence estimates. In future research, it will be important to establish the sensitivity and specificity of the different methods and conduct intra- and interlaboratory validation studies in order to standardize methods. In spite of the limitations of cross-sectional studies, the measurement of HPV prevalence and its correlation with, for example, sexual behaviour is still valuable for our understanding and interpretation of the role of HPV infections.     

Nimodipine treatment of subarachnoid hemorrhage

In a pilot study of 6 patients with subarachnoid hemorrhage caused by a ruptured intracranial (grade IV (Hunt and Hess) aneurysm the hemodynamics and plasma-nimodipine concentrations have been observed during a 3-week period of treatment. We found that 3 patients developed reversible hypotension during the nimodipine treatment and that the hypotension tendency could be related to the plasmanimodipine level and not to a more or less severe sensitivity to nimodipine.

Repeated measurements of blood pressure, plasma-nimodipine and regional cerebral blood flow (rCBF) are necessary for the purpose of obtaining the optimum treatment and for evaluating the effect of treatment.     

Role of sucralfate in peptic disease.

Sucralfate, a basic aluminum salt of sucrose, was the first successful drug with a major cytoprotective mechanism of action. It binds bile acids and pepsin and adheres to both ulcerated and nonulcerated mucosa. Sucralfate stimulates the synthesis and release of gastric mucosal prostaglandins as well as bicarbonate and the epidermal growth factor which stimulates healing. Sucralfate is the safest drug available today in the treatment of dyspeptic symptoms and compared to ranitidine and cimetidine it has the following characteristics. (2) The short-term healing of duodenal ulcers is the same for sucralfate, cimetidine and ranitidine. (3) Sucralfate-treated patients have a lower recurrence rate of duodenal ulceration after healing when compared with cimetidine and the recurrence rate is not connected with the presence or absence of Campylobacter pylori.     

Sympathetic preganglionic neurons projecting to the adrenal medulla and aorticorenal ganglion in the rabbit.

The distribution of sympathetic preganglionic neurons (SPN) projecting to the adrenal medulla and the aorticorenal ganglion in the rabbit was studied using a dual retrograde transport technique. The B subunit of cholera toxin (CTB) was injected into the left adrenal medulla and wheatgerm agglutinin-apo-horseradish peroxidase-7 nm gold (WGA-apo-HRP-gold) was injected into the left aorticorenal ganglion. Retrogradely transported CTB was detected by immunohistochemistry, while gold particles were detected by silver intensification. SPN projecting to the adrenal medulla were observed in segments T2-L2 of the spinal cord in 5 rabbits, with the majority of cells within segments T6-T11 (79%). SPN projecting to the aorticorenal ganglion were seen in segments T2-L1 of the spinal cord in 5 rabbits, with the greatest number of the cells within T6-T11 (81%). Only a small number of doubly labelled cells (1%) were found in two rabbits. The results suggest that despite their similar segmental distribution SPN projecting to the adrenal medulla or the aorticorenal ganglion belong to separate populations and few, if any, individual SPN have axonal projections to both locations.     

Obsessive-compulsive disorder: admission patterns and diagnostic stability

All first-time admissions from 1970 to 1986 with obsessive-compulsive neurosis (OCD) (ICD-8 diagnosis number 300.39) or obsessive-compulsive personality disorder (OCPD) (ICD-8 diagnosis number 301.49) were analyzed based on an extract from the nationwide Psychiatric Case Register in Denmark. All patients with secondary diagnoses other than neurotic disorders or personality disorders (including “neuroses characterogenes”) were excluded from the study. A total of 284 patients were first-time admitted with a main diagnosis of OCD during the period. The sex ratio was 0.67 (males/females). A total of 126 were first-time admitted with a diagnosis of OCPD, with a sex ratio of 1.18 (males/females). Seventy-seven percent of the readmitted patients with a first-time diagnosis of OCD kept a diagnosis within the “emotional spectrum” at the last admission. About half kept OCD as a main diagnosis, whereas only 15% shifted to a severe psychiatric diagnosis such as schizophrenia or manic-depressive psychosis. Of the readmitted patients with OCPD. 13% later developed a diagnosis of manic-depressive psychosis.