Cytokine profile in chronic cardiac failure

Elevated tumour necrosis factor alpha (TNF-alpha) has been demonstrated in chronic cardiac failure (CCF) and may relate to severity of CCF and development of cachexia. We measured TNF receptor p55 in addition to TNF-alpha in an attempt to improve the detection rate of TNF-alpha activation, and simultaneously measured interleukin 6 (IL-6), interleukin 8 (IL-8) and C-reactive protein. Thirty-four patients with CCF and 24 control subjects were studied. Only TNF receptor p55 [6.95 (0.77-42.3) vs. 5.52 (1.50-13.36) ng mL-1 (median (range)] and IL-6 [0.335 (0-9.79) vs. 0(0-14.71) pg mL-1) were significantly elevated in patients compared with control subjects (both P < 0.05). All inflammatory markers were more frequently elevated in patients, but none correlated with any of the clinical parameters studied. Reasons for inflammatory marker elevation in CCF are uncertain, but future studies should measure the p55 TNF receptor and IL-6 in addition to TNF-alpha, to improve detection of cytokine activity.     

Intrauterine devices: learning from the past and looking to the future

This paper reviews the historical development of the IUD, describing the challenges and successes, and attempts to offer a balanced perspective for family planning service workers today. Modern IUDs are an important component of family planning services and an excellent contraceptive choice for properly screened women, providing contraception that is safe, effective, long lasting and cost effective. Potential research strategies for the future are also discussed.     

Progesterone induces calcitonin gene expression in human endometrium within the putative window of implantation

The human endometrium acquires the ability to implant the developing embryo within a specific time window that is thought to open between days 19-24 of the secretory phase of the menstrual cycle. During this period the endometrium undergoes pronounced structural and functional changes induced by the ovarian steroids, estrogen and progesterone, that prepare it to be receptive to invasion by the embryo. The identification of reliable biochemical markers to assess this critical receptive phase in the context of the natural cycle remains one of the major challenges in the study of human reproduction. Our previous studies in a rat model system demonstrated that the expression of calcitonin, a peptide hormone involved in calcium homeostasis, is transiently induced by progesterone in the glandular epithelium at the onset of implantation. Attenuation of calcitonin synthesis in the uterus during the preimplantation phase by administration of calcitonin antisense oligodeoxynucleotides severely impairs implantation of rat embryos, suggesting that this peptide hormone plays a critical role in uterine receptivity. To investigate whether calcitonin is also expressed in the human endometrium during implantation, we monitored the spatio-temporal expression of calcitonin on various days of the menstrual cycle. Our studies employing RT-PCR showed that calcitonin messenger ribonucleic acid is expressed in human endometrium during the postovulatory midsecretory phase (days 17-25) of the menstrual cycle, with maximal expression occurring between days 19-21. Very little calcitonin expression was detected in the endometrium in either the preovulatory proliferative (days 5-14) or the late secretory (days 26-28) phase. In situ hybridization and immunocytochemical analyses localized the calcitonin expression predominantly in the glandular epithelial cells of the endometrium. Our studies further showed that calcitonin expression in the human endometrium is under progesterone regulation. Treatment of women with an antiprogestin, mifepristone (RU-486), drastically reduced calcitonin expression in the endometrium. Collectively, these findings reveal that progesterone-induced expression of calcitonin in the secretory endometrium temporally coincides with the putative window of implantation in the human.     

Effects of growth hormone secretagogues on prolactin release in anesthetized dwarf (dw/dw) rats

In addition to stimulating GH release, GH secretagogues such as GH-releasing peptide-6 (GHRP-6) stimulate small amounts of ACTH and PRL release. Although the effects on ACTH have recently been studied, there is little information about the effects of GHRP-6 on PRL. We have now studied GHRP-6-induced GH and PRL release and their regulation by estrogen (E2) in anesthetized male and female rats and in GH-deficient dwarf (dw/dw) rats that maintain high pituitary PRL stores and show elevated hypothalamic GH secretagogue receptor expression. Whereas GHRP-6 (0.1-2.5 microg, i.v.) did not induce PRL release in normal male or female rats, significant PRL responses were observed in dw/dw females. These responses were abolished by ovariectomy and could be strongly induced in male dw/dw rats by E2 treatment. These effects could be dissociated from GHRP-6-induced GH release in the same animals, but not from PRL release induced by TRH, which was also abolished by ovariectomy and induced in males by E2 treatment. However, the effects of GHRP-6 on PRL were unlikely to be mediated by TRH because in the same animals, TSH levels were unaffected by GHRP-6 whereas they were increased by TRH. The increased PRL response could reflect an increase in GH secretagogue receptor expression that was observed in the arcuate and ventromedial nuclei of E2-treated rats. Our results suggest that the minimal PRL-releasing activity of GHRP-6 in normal rats becomes prominent in GH-deficient female dw/dw rats and is probably exerted directly at the pituitary; these GHRP-6 actions may be modulated by E2 at both hypothalamic and pituitary sites.     

Comparative quantitative analysis of macrophage populations defined by CD68 and carbohydrate antigens in normal and pathologically altered human liver tissue

Liver macrophages, which are involved in the different types of hepatitis, may indirectly induce hepatic fibrogenesis, since they have the possibility to activate hepatic stellate cells and fibroblasts by secretion of TGF-beta, TNF-alpha and IL-1. To evaluate variations of the number of liver macrophages and their subpopulations, a quantification was carried out in normal human liver tissue, fatty liver, fatty liver hepatitis and hepatitis B. Identification was performed by the mab PG-M1 (anti-CD68) and, comparatively, four lectins, Griffonia simplicifolia agglutinin I (GSA-I), Erythrina cristagalli agglutinin (ECA), peanut agglutinin (PNA) and soybean agglutinin (SBA). A slight decrease in the frequency of macrophages in pericentral fields was observable in fatty liver and fatty liver hepatitis as compared to normal liver tissue. On the other hand, the number of CD68+ cells was significantly enhanced in hepatitis B with moderate and severe inflammatory activity. The highest incidence of macrophages was found in portal tracts of liver with fatty liver hepatitis and, particularly, hepatitis B. The fraction of cells stained by ECA, PNA or SBA did not increase significantly under pathological conditions. In contrast, the percentage of GSA-I binding macrophages was higher in liver parenchyma of hepatitis B and in portal tract macrophages in fatty liver hepatitis and also hepatitis B. In conclusion, our results indicate that GSA-I may aid in the detection of the subpopulation of activated macrophages which are assumed to play a pivotal role in liver pathology.     

Design of HIV viral dynamics studies

HIV viral dynamics studies involve repeated measurement of viral load in HIV-infected individuals, to assess short-term rates of viral load change in response to interventions such as initiation or withdrawal of antiviral therapy. Such studies are an important source of information on HIV pathogenesis. This paper concerns some statistical issues arising in their design. Using a linear random-effects model to incorporate between-patient differences in rates of viral load change, I discuss the choice of number of individuals and frequency of observation per individual. I suggest an approach for calculating the optimal sample size and observation frequency, based on minimizing the total number of viral load measurements that one needs to undertake. The conclusion, using this approach, is that over a period of linear change in viral load, three to five measurements per individual is generally appropriate. I also examine the observation frequency when the number of available individuals is limited, in which case it is shown that one can use a higher frequency of measurement per individual to achieve adequate power or precision. Finally, I consider sources of data for prior specification of variance components, together with conservative designs that are insensitive to a lack of prior information about between-patient differences.     

Renal hypertension secondary to ureteropelvis junction obstruction. Unusual presentation and new therapeutic modality

We recently have treated an infant with a ureteropelvic junction obstruction believed to be the first reported case of nonrenovascular renal hypertension presenting as a cerebrovascular accident. A new role for the percutaneous nephrostomy as a predictive, diagnostic, and therapeutic tool is illustrated. Pitfalls in the preoperative assessment of ureteropelvic junction obstructions are discussed, and possible mechanisms for reno-prival hypertension are suggested.     

Effects of increased O2-N2 pressure and breathing apparatus on respiratory function

The ventilatory response of four subjects was measured at rest and various intensities of exercise. Experiments were conducted in a dry pressure chamber (1) at 1 ATA and 4 ATA with the subjects breathing from a low-resistance mouthpiece, and (2) at ATA with the subjects breathing from open-circuit breathing apparatus (Royal Naval Swimmers' Air Breathing Apparatus). At 4 ATA there was significant hypoventilation and hypercapnia, together with an increased tidal volume and lower respiratory frequency. The use of the breathing apparatus tended to amplify these changes in ventilatory response. In addition, the extent of hypercapnia at 4 ATA was related to the exercise intensity. When subjects breathed from a low-resistance mouthpiece, oxygen uptake was significantly greater at 4 ATA than at the surface for the same ergometric work load, but when they breathed from the breathing apparatus, the increase in oxygen uptake was not significant in comparison to surface values. At 4 ATA bradycardia was evident at all levels of exercise but was not affected significantly by the presence of the breathing apparatus.