Secondary hypercalcemic hyperparathyroidism

Summary A search was made for patients with associated secondary hyperparathyroidism and hypercalcemia: 22 such cases were found in the literature and 22 were recorded among 92 patients operated upon because of parathyroid disease. In the remaining 70 patients the effect of the operation on the serum calcium level was investigated: persisting hypercalcemia after the operation was found in 28 per cent of the cases.The patients reporded in the literature possessed severe renal and skeletary changes and light microscopic evidence of parathyroid adenoma (2 cases), hyperplasia (15 cases), or hyperplasia and adenoma (5 cases).The other 22 patients had histories of long-standing renal disease, most often chronic pyelonephritis, of varying severity. Skeletary roentgenograms were often normal. Morphologic examination of the parathyroids showed adenoma (6 cases) or hyperplasia (16 cases). Postoperatively, normal serum calcium level was found in 9 cases and persisting hypercalcemia in 13 (=59 per cent) cases. One patient possessed also a malignant -cell insuloma and Zollinger-Ellison's syndrome.It is suggested that secondary hyperparathyroidism may develop in patients with only slight or moderate impairment of renal function, that hypercalcemia occurs more often than previously believed in secondary hyperparathyroidism, and that some cases of secondary hyperparathyroidism previously, erroneously have been classified as primary hyperparathyroidism.Supported by grants from the Swedish Medical Research Council (Project No. B72-17X-3499-01), the Swedish Cancer Society (Project No. 552-B71-01P), and the Medical Faculty, University of Umeå.     

Differences in adsorption of serum proteins and production of IL-1ra by human monocytes incubated in different tissue culture microtiter plates

In vitro cell culture models can be of great value in order to further analyze the regulatory mechanisms underlying the inappropriate function of the immune system in diseases such as autoimmunity and cancer. Cell culture conditions have to be well controlled in a way that they mirror the in vivo situation. The objective of this study was to compare tissue culture microtiter plates from different manufacturers with respect to their ability to support monokine production by human monocytes cultured in human serum. Tissue culture ware, made of polystyrene, undergoes treatment by the manufacturers to make the surface more suitable for culture of adherent cell populations. It is possible that quality differences in this treatment can lead to variations in protein binding properties and thereby influence the adherence and functional properties of monocytes. We measured spontaneous interleukin-1 receptor antagonist (IL-1ra) production by peripheral blood monocytes, cultured in human serum, in five different microtiter plates made for adherent cell culture. Culture in plates from two of the five manufacturers resulted in significantly lower amounts of secreted IL-1ra. IL-1ra release by human monocytes can be induced by adherent IgG cross-linking membrane receptors for the Fc part of IgG (FcgammaR). We found that reduced IL-1ra production coincided with a reduced capacity for binding of serum IgG in one case. Furthermore, this brand of microtiter plate also displayed the lowest level of adsorption of human albumin. We conclude that the protein adsorption properties of the plastic tissue culture ware have to be taken into consideration when assessing monokine production by human monocytes in vitro.     

ZK 91296, a partial agonist at benzodiazepine receptors

ZK 91296 (ethyl 5-benzyloxy-4-methoxymethyl--carboline-3-carboxylate) is a potent and selective ligand for benzodiazepine (BZ) receptors. Biochemical investigations indicate that ZK 91296 may be a partial agonist at BZ receptors. Such partial agonism may explain to some extent why ZK 91296 needs higher BZ receptor occupancy than diazepam for the same effect against chemical convulsants and for behavioural effects. The lack of sedatiye effects, and the very potent inhibition of reflex epilepsy, spontaneous epilepsy and DMCM-induced seizures suggest, furthermore, that ZK 91296 may possess pharmacological selectivity for a particular type of BZ receptor interaction, perhaps including topographic as well as receptor subtype differentiation.     

Sex Differences in Voyeuristic and Exhibitionistic Interests: Exploring the Mediating Roles of Sociosexuality and Sexual Compulsivity from an Evolutionary Perspective

Sociosexuality and sexual compulsivity predict sex differences in voyeuristic interest in the population. In this study, we used a sample of 1113 participants from the UK (46% men) to consider whether sociosexuality and sexual compulsivity interacted to explain these sex differences and whether this relationship extended to the related domain of exhibitionism. In doing so, we tested novel predictions derived from an evolutionary perspective which views voyeuristic and exhibitionistic interest as manifestations of a short-term mating strategy. Participants reported their levels of repulsion toward voyeurism and exhibitionism and their interest in performing such acts under different levels of risk. There were clear sex differences in voyeuristic and exhibitionistic repulsion that were partially mediated by the serial combination of sociosexuality and sexual compulsivity. Examining the sexes separately revealed qualitatively different relationships between sociosexuality and sexual compulsivity when predicting exhibitionistic, but not voyeuristic, repulsion. Combined, sociosexuality and sexual compulsivity also mediated the sex difference in willingness to commit acts of voyeurism, but not exhibitionism, which was equally low for both sexes. The results highlight the role sociosexuality plays in voyeuristic and exhibitionistic interest, which coupled with an evolutionary perspective, may have implications for how we view courtship disorders.

     

Genotoxic activity of chlorohydroxyfuranones in the microscale micronucleus test on mouse lymphoma cells and the unscheduled DNA synthesis assay in rat hepatocytes

Chlorohydroxyfuranones (CHFs) are mutagenic disinfection by-productsfound in chlorine-treated drinking water. In the current study,the genotoxicity of four CHFs, 3,4-dichloro-5-hydroxy-2(5H)-furanone(MCA), 3-chloro-4-methyl-5-hydroxy-2(5H)-furanone (MCF), 3-chloro-4-(chloromethyl)-5-hydroxy-2(5H)-furanone(CMCF) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone(MX), was determined. Two in vitro assays, the microscale micronucleusassay on L5178Y mouse lymphoma cells and the unscheduled DNAsynthesis assay on a hepatocyte primary culture from FisherF344 rats, were carried out. All four CHFs demonstrated genotoxiceffects in both assays. In the two systems used, CMCF was themost genotoxic compound, followed by MCA, MX and MCF, respectively.This work was the first study of the DNA damaging propertiesof all four CHFs in two in vitro genotoxicity tests. These newdata expand the range of genetic damages induced by this groupof compounds. ² To whom correspondence should be addressed. Tel: +33 3 20 8779 14; Fax: +33 3 20 87 73 10; Email: daniel.marzin{at}pasteur-lille.fr     

The effect of lithium on amphetamine-induced locomotor stimulation

Rats were treated chronically with -methyl-p-tyrosine methyl-ester HCl (-MT) twice daily for 0–14 days. At 1 h after the (last) -MT injection, d-amphetamine sulphate was given and motor activity was measured in an ANIMEX activity meter for 4 h. Amphetamine-induced excitatory and stereotyped behaviour was scored according to a rating scale in a separate experiment. A single dose of -MT markedly reduced the activity response after amphetamine. After 1–3 days of -MT treatment, tolerance to its amphetamine-antagonistic affect started to develop, reaching a maximal degree after 7–14 days. The pattern of the amphetamine response, monophasic in control rats, became biphasic in the -MT tolerant rats with an early (at 0–1 h) and a late (2–4 h) peak of motor activity. The late peak appeared within 3 days, while the early peak appeared after 7 days of -MT treatment. The results on amphetamine-induced excitatory and stereotyped behaviour in essence agreed with the motor-activity data. It is concluded that tolerance to the amphetamine-antagonistic action of -MT is not complete. Its rate of development varies in a complex pattern, indicating the presence of more than one mechanism of tolerance.     

Visual cortex activation recorded by dynamic emission computed tomography of inhaled xenon 133

Regional cerebral blood flow (CBF) was studied tomographically with ¹³³Xe administered by inhalation over a 1-min period at a concentration of 10 mCi/l. A fast rotating (dynamic) single-photon emission computed tomograph with four detector heads was used, an instrument that has been found to be well suited for detecting focal ischemia. In the present study its ability to detect focal hyperemia was investigated in 13 normal subjects studied during rest and during visual stimulation. A flickering light seen with eyes open and closed, increased blood flow in the visual cortex by 35% and 22% respectively. Looking at different pictures displayed on a screen raised regional CBF by 26%. The most complex task, reading and copying a text, increased blood flow by 45%. Averaging the different tasks resulted in a mean regional CBF increase in the visual cortex of 35%. The result is comparable with that obtained by positron emission tomography. Both forms of isotope tomography offer unique possibilities for the study of brain function in health and disease, possibilities not matched by X-ray tomography. The low cost and ready availability of appropriate single-photon radionucleides (¹³³Xe and ¹²⁷Xe) are mentioned.Supported by the Danish Medical Research Council, the Danish Sclerose Association, and the Johann and Hanne Weimann Foundation.     

Electron microscopy and X-ray microanalyses of uterine epithelium from lead-injected mice in an experimental delay of implantation

Mice in experimental delay of implantation were injected intravenously with 75 g · g^–1 body weight of lead chloride, corresponding to a dose of lead of about 56 g · g^–1 body weight. Delay of implantation was obtained by ovariectomy 3 days after mating followed by a depot dose of progesterone every fifth day. Electron microscopy showed that the uterine lumen, which was closed in control mice, was opened in lead-injected mice. This morphology suggested that lead caused an increase in uterine secretion. X-ray microanalysis of pyroantimonate precipitates in the uterine epithelium of injected mice demonstrated lead in the precipitates, suggesting that lead could have a direct effect on the function of the uterine epithelium and that lead also could be secreted into the uterine lumen and affect the blastocysts.     

Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity: A Latent Class Trajectory Approach

OBJECTIVEIn a large, multiethnic cohort of youths with obesity, we analyzed pathophysiological and genetic mechanisms underlying variations in plasma glucose responses to a 180 min oral glucose tolerance test (OGTT).RESEARCH DESIGN AND METHODSLatent class trajectory analysis was used to identify various glucose response profiles to a nine-point OGTT in 2,378 participants in the Yale Pathogenesis of Youth-Onset T2D study, of whom 1,190 had available TCF7L2 genotyping and 358 had multiple OGTTs over a 5 year follow-up. Insulin sensitivity, clearance, and β-cell function were estimated by glucose, insulin, and C-peptide modeling.RESULTSFour latent classes (1 to 4) were identified based on increasing areas under the curve for glucose. Participants in class 3 and 4 had the worst metabolic and genetic risk profiles, featuring impaired insulin sensitivity, clearance, and β-cell function. Model-predicted probability to be classified as class 1 and 4 increased across ages, while insulin sensitivity and clearance showed transient reductions and β-cell function progressively declined. Insulin sensitivity was the strongest determinant of class assignment at enrollment and of the longitudinal change from class 1 and 2 to higher classes. Transitions between classes 3 and 4 were explained only by changes in β-cell glucose sensitivity.CONCLUSIONSWe identified four glucose response classes in youths with obesity with different genetic risk profiles and progressive impairment in insulin kinetics and action. Insulin sensitivity was the main determinant in the transition between lower and higher glucose classes across ages. In contrast, transitions between the two worst glucose classes were driven only by β-cell glucose sensitivity.