Micro- and macrocirculatory effects of apheresis in patients with familial hyperlipidemia

High lipid levels have been shown to coexist with a disturbed vascular endothelial function. Thus, acute lipid lowering could be expected to improve vascular reactivity. Patients with familial hyperlipidemia (FH) have substantial and rapid decreases in lipid levels after low-density lipoprotein apheresis. Thus, an opportunity exists to study acute effects of lipid lowering on vascular reactivity. Flow mediated vasodilation (FMD) is commonly used to assess endothelial function in conduit vessels, whereas vital capillary microscopy during the post-reactive hyperemia (PRH) phase is used to assess response at the microvascular level. It is not known whether endothelial dysfunction is a general phenomenon in all kinds of vessels or if there are differences between micro- and macrovessels. In the present study, we were not able to demonstrate an improved vascular response after acute lipid lowering in FH patients. This was true both in the microcirculation (PRH) and in the conduit vessels (FMD). However, the two methods gave concordant results, demonstrating disturbed vascular reactivity in the patients as compared with healthy subjects. We have found no previous report with parallel assessments at the microcirculatory and macrocirculatory levels.     

Irradiation Induces Marked Immunohistochemical Expression of Vasoactive Intestinal Peptide in Colonic Mucosa of Man

Vasoactive intestinal peptide (VIP) is known tomodulate inflammatory reactions, to have trophiceffects, and to contribute to diarrhea and has beenimplicated as an important factor in severalinflammatory conditions in the human gut. The aim of thepresent study was to investigate the effects ofirradiation on the expression of VIP in the colon ofpatients operated on for adenocarcinoma. Some of thepatients had received preoperative irradiation (25 Gy)within one week before the operation. Specimens ofsigmoideum, 10 cm cranial to the margin of the cancer,were examined, by using antiserum against VIP and immunohistochemistry. There were numerous nervefibers showing VIP-like immunoreactivity in the damagedmucosa, including the regions showing ulcerations. Therewas a higher degree of expression of VIP in the ganglion cells in the submucous plexusesin irradiated than nonirradiated patients. The studyshows that there is a marked immunohistochemicalexpression of VIP concomitant with the occurrence of inflammatory and repair processes in theirradiationdamaged human colonic mucosa.     

Metabolic and hormonal responses to exercise in type 1 diabetic patients during continuous subcutaneous, as compared to continuous intraperitoneal, insulin infusion

This study was performed to determine whether metabolic and hormonal responses during moderate exercise differ between continuous intraperitoneal insulin infusion (CIPII) and continuous subcutaneous insulin infusion (CSII). In seven Type 1 diabetic patients, treatment was changed from CSII to CIPII. Prior to the change, these patients performed an ergometer exercise at 60% of VO2max for 40 min followed by a 200-min rest. About one year later, when the procedure was repeated during CIPII, HbA1c had improved from 8.5 to 7.1%. Arterial blood glucose, venous lactate and hormonal responses were analysed. Although a regimen with a higher basal insulin infusion rate was applied during the exercise test on CIPII, corresponding venous insulin levels were lower (28.0 +/- 2.2 vs. 48.1 +/- 7.9 pmol L-1, p = 0.04). Exercise caused a more marked decline in blood glucose during CIPII, with nadir blood glucose at the end of exercise (3.6 +/- 0.4 vs. 5.1 +/- 0.4 mmol L-1, p = 0.005). Both exercise tests yielded significant and similar increases in plasma levels of adrenaline, noradrenaline, cortisol and growth hormone. A significant rise in plasma glucagon (15.1 +/- 4.5 pg mL-1, p = 0.01) was observed during CIPII, but not during CSII (7.4 +/- 3.5, pg mL-1, n.s.). It is concluded that patients on CIPII should reduce their insulin infusion rate during exercise. CIPII appears to have favourable effects on counterregulatory capacity; in particular, a more prominent glucagon response to exercise may prove important.     

Radiosensitizing effect of estramustine in malignant gliomain vitro andin vivo

Summary Estramustine-phosphate (EMP), a combination of nornitrogen mustard and 17-estradiol, has been demonstrated to exert specific antiproliferative effects on human glioma cellsin vitro. The cytotoxic effect is, at least partially, mediated by inhibiting microtubule function. In this study the combined effect of EMP and radiation was evaluated in the human glioma cell-lines, 251-MG and 105-MG,in vitro, and in the rat glioma BT4Cin vitro andin vivo. In all cell-lines an additive effect of EMP and radiation was obtainedin vitro. Assuming equal effect of EMP is obtained in subsequent radiation fractions, the cell kill will be increased from 2–3 to 5–10 logs if delivering 30 fractions of 2 Gy combined with EMP. In the BT4C rat model the combined effect was found to be synergistic. Flow cytometry demonstrated an arrest in G2/M phase in all cell-lines after EMP treatment. This block in G2/M phase in addition to the previously demonstrated induction of free oxygen radicals, and the increase of blood flow with an assumed subsequent increase of oxygenation, might provide an explanation for the observed radiosensitizing effect of estramustine.     

Twelve-gel slide format optimised for comet assay and fluorescent in situ hybridisation

The comet assay is widely used to measure DNA damage and repair in basic research, genotoxicity testing and human biomonitoring. The conventional format has 1 or 2 gels on a microscope slide, 1 sample per slide. To increase throughput, we have designed and tested a system with 12 smaller gels on one slide, allowing incubation of individual gels with different reagents or enzymes. Thus several times more samples can be analysed with one electrophoresis run, and fewer cells and smaller volumes of test solutions are required. Applications of the modified method include treatment with genotoxic agents at different concentrations; simultaneous analysis of different lesions using a range of enzymes; analysis of cell extracts for DNA repair activity; and fluorescent in situ hybridisation (FISH) to comet DNA with specific labelled probes.     

Nerve conduction velocity, laser Doppler flow, and axonal caliber in galactose and streptozotocin diabetes

In an initial study, the effects of galactose intoxication on nerve laser Doppler blood flow (NLDF) and nerve conduction velocity (NCV) were assessed after 1–16 weeks of galactose feeding in pentobarbital-anesthetized rats. NLDF was not significantly changed at any time point. NCV was significantly reduced after 16, but not 1 or 4, weeks of galactose feeding. In a second study, NLDF was not significantly changed by 4 weeks of galactose intoxication, but streptozotocin-diabetic NLDF was significantly reduced compared to both control (P<0.001) and galactose-intoxicated rats (P<0.05). Compared to control animals, sciatic motor NCV was significantly (P<0.001) reduced in the galactose group, while sciatic and saphenous sensory NCVs were not significantly changed. In the streptozotocin-diabetic rats, motor and sensory NCVs were all significantly reduced (P<0.001). In contrast to the NCV findings, mean caliber of myelinated axons in both the saphenous and sciatic nerves was reduced in galactose-intoxicated, but not streptozotocin-diabetic rats. The observed sequence of changes associated with these two models of diabetic neuropathy is not consistent with the proposed roles of ischemia and axonal dwindling in the reported nerve conduction deficits.     

Orchidectomy versus oestrogen for prostatic cancer: cardiovascular effects

One hundred consecutive patients aged up to 75 with newly diagnosed cancer of the prostate suitable for hormonal treatment were included in a controlled study of the cardiovascular effects of oestrogen versus orchidectomy. In all cases pre-existing cardiovascular morbidity was excluded. Of the 100 patients, 91 were strictly randomised to receive either oestrogen (n = 47) or orchidectomy (n = 44) and 9 (6 given oestrogen, 3 orchidectomy) either chose their own treatment (five cases) or had it selected for them by the urologist (four). Oestrogen was given in the lowest recommended dosage in Sweden--namely, as 160 mg polyestradiol phosphate intramuscularly every month for the first three months, then 80 mg monthly, plus ethinyloestradiol 1 mg by mouth daily for the first two weeks, then 150 micrograms daily. At entry to the study the two treatment groups showed no difference in demographic characteristics or conventional risk factors for cardiovascular disease. During the first year, however, 13 (25%) of the patients given oestrogen suffered major cardiovascular events as compared with none of the patients after orchidectomy. Patients in the oestrogen treatment group who did not have minor signs of atherosclerosis at entry to the study suffered a similar incidence of cardiovascular complications to those who did have these signs at entry. The substantially increased risk of cardiovascular complications in patients given oestrogen for prostatic cancer warrants careful consideration when choosing treatment for this disorder.     

Psychosocial factors and completed suicide in personality disorders

The aim of the present study was to investigate the relationships between personality disorders (PD) and various psychosocial factors in a random sample (n= 229) of suicides with psychological autopsy-based DSM-III-R diagnoses representing the total 1-year suicide population in Finland. Background social factors and social interaction factors for 56 suicide victims with a PD diagnosis were compared with those of 56 age- and sex-matched non-PD suicide victims. The groups were similar with regard to marital status, socio-economic status, parental divorce, broken home before the age of 16 years, parental suicide attempts, and proportion of subjects living with parents. The PD suicide victims had more commonly had a companion of the opposite sex, lived alone, and resided in an urban area, but had less often experienced parental psychiatric hospitalization during their childhood. Although the groups did not differ with regard to complaints of loneliness before suicide, the lonely PD suicide victims had experienced more interpersonal loss and/or conflict than the lonely non-PD suicide victims. The PD suicide victims were very similar with regard to psychosocial factors, irrespective of sex, age, Axis-I comorbidity, or the cluster type of the PD. Only living alone was more common in young PD suicide victims, and male PD subjects had less often had confidants or friends with whom they shared common interests.