Caring relationships with patients suffering from dementia--an interview study.

The aim of the study reported in this paper was to describe and analyse care-givers' caring relationships with patients suffering from dementia. The theoretical perspective was caring science. Data were collected through interviews with six care-givers in a ward for patients with severe dementia. From the qualitative analysis of the narratives, the following factors emerged as important for the caring relationships: 'touching', mutual 'confirmation', and the care-givers' 'values in the caring culture' in the ward. We conclude that communication skills are very important in a ward where patients with severe dementia reside, and that there is always a need for formulating the basic values. Theoretical education and clinical supervision are examples of means to improve competence and skills.

Histopathological and hemodynamic studies supporting hypoxia and vascular disruption as explanation to phenytoin teratogenicity.

The limb plates and craniofacial regions in rabbit fetuses were examined shortly after the last dose of phenytoin on day 16 after daily administration by gavage with either 150 mg/kg on days 14-16 or 300 mg/kg on days 15-16. Both treatment regimens resulted in similar changes. Histologically, the digital areas of the limb plates showed extensive edema and dilated blood vessels within 2 h. After 8 h, vascular disruption occurred with hemorrhages. At 24-48 h after dosing, mesenchymal necrosis and, on some occasions, amputation of digits was observed. In the craniofacial region, well-defined superficial hemorrhage was seen in the frontal and nasal region at 8 h. Histologically, subectodermal hemorrhage caused by vascular disruption and microfocal mesenchymal necrosis was observed. At 48 h, some fetuses showed severe diffuse intracranial and superficial hemorrhage, resulting in massive tissue damage, also in the central nervous system (CNS). Maternal heart rate, blood pressure, PO2, and PCO2 were also measured in awake pregnant rabbits 6 h after the last dose on day 16 after daily administration with 150 mg/kg during gestational days 14-16. An attempt was also made to measure fetal heart rate in anesthetized rabbits. The maternal heart rate and blood pressure decreased with about 15% in phenytoin-treated animals, resulting in a decrease in PO2 (approximately 15%) and an increase in PCO2 (approximately 15%). A decrease in fetal heart rate was also registered. The results thus indicate that phenytoin exerts its teratogenic effects by inducing fetal hypoxia, leading to vascular disrupture and necrosis of existing and developing structures.

Identical phalangeal defects induced by phenytoin and nifedipine suggest fetal hypoxia and vascular disruption behind phenytoin teratogenicity.

In previous experimental studies in rabbits, we have shown that vasodilating drugs (including nifedipine) cause distal digital defects. These defects were preceded by edema, hemorrhage, and finally necrosis of the developed cartilage in the phalanges. The underlying mechanism is most likely a fetal hypoxic response, secondary to maternal hypotension and decreased uteroplacental blood flow. Since phenytoin is known to cause distal digital defects both in man and rabbits, we decided to compare the defects provoked by oral administration of phenytoin (100 mg/kg) versus nifedipine (8.3 mg/kg) to New Zealand White rabbits on days 6-18 of gestation. In order to investigate phase-specificity, phenytoin (150 mg/kg) was given on days 14-17. The result of single dose administration on day 16 of phenytoin (300 mg/kg) versus nifedipine (33.2 mg/kg) was also studied. In this latter experiment maternal heart rate was measured up to 21 hours after phenytoin administration. Phenytoin induced digital defects identical with those produced by nifedipine and caused marked maternal cardiodepression. The defects consisted of a reduction, absence, or abnormal structure of the distal phalanges. The distal phalanx of the fourth digit on the hindpaw was the first to be affected, with inclusion of other phalanges, both on the hind- and forepaws, with increasing dose. The sensitive period for induction and histological appearance of these defects was identical for phenytoin and nifedipine. These results suggest that vascular disruption due to a fetal hypoxic response lies behind phenytoin teratogenicity, as has been shown for vasodilators. A cardiodepressive action on the maternal and fetal hearts, possibly in combination with decreased uteroplacental blood flow, is discussed as a probable factor behind phenytoin teratogenicity.

Histological and in vitro studies supporting decreased uteroplacental blood flow as explanation for digital defects after administration of vasodilators.

In a recent study, the vasodilating drugs nifedipine, nitrendipine, felodipine, and hydralazine induced phalangeal defects in rabbits, when given on day 16 of pregnancy. Histologically, the changes were characterized by disturbed chondrogenesis. In order to elucidate mechanisms behind the defects, the fetal concentration of felodipine was measured, and the fetal limb plates were examined histologically, at 0, 2, 4, 8, 12, and 24 hours after single oral administration of felodipine (12 mumol/kg) on day 16 in pregnant rabbits. The effects of nifedipine, nitrendipine, and felodipine were also investigated in an in vitro system, in which chick embryonic mesenchymal limb bud cells differentiated into chondrocytes. In this system, no inhibition of chondrogenesis was observed below concentrations 3 x 10(5) M. At this concentration, unspecific cytotoxicity was found. The highest fetal concentrations of felodipine were more than 500 times lower than what was required for in vitro toxicity. Histologically, the digital areas of the limb plates showed extensive edema and dilatation of marginal sinus within 2 hours. After 8 hours, rupture of the thin-walled vessels occurred with hemorrhages. Finally, small necroses and blisters were observed. Similar early changes have been reported in experiments where digital defects were induced by clamping uterine vessels. This study thus indicates that the phalangeal defects after administration of high doses of vasodilators are secondary to pharmacological action (associated with a significant reduction in the uteroplacental blood flow), and not a direct effect on fetal chondrogenesis.

Digital defects induced by vasodilating agents: relationship to reduction in uteroplacental blood flow.

The effects of nifedipine (40-100 mumol/kg), nitrendipine (40 and 80 mumol/kg), hydralazine (381 and 763 mumol/kg), felodipine (12 mumol/kg), and the pharmacologically inactive first-step metabolite of felodipine, H152/37 (80 mumol/kg) were studied in rabbits (New Zeeland White) after oral administration on day 16 of gestation. The vasodilating drugs--nifedipine, nitrendipine, felodipine, and hydralazine--all induced digital defects in the fetuses. The defects consisted of a reduction, absence, or abnormal structure of the distal phalanx of especially the fourth digit on the hind paw(s). Histologically, a disturbed differentiation of the cartilage, and secondarily also of the ossification centre and joint structure of the distal phalanx, was observed. In contrast, no digital abnormalities were observed after administration of vehicle or H152/37. The findings that vasodilators with different structures, like dihydropyridines and hydralazine, induced the same type of digital defects strongly suggest that the observed phalangeal defects are secondary to pharmacological action, and not related to chemical structure. A decrease in uteroplacental blood flow, caused by excessive hypotension, is discussed as the most probable mechanism underlying the observed defects.

Comparison between lysine vasopressin and a long-acting analogue (N alpha-triglycyl-lysine vasopressin) used as local hemostatic agents for conization.

Lysine vasopressin and a long-acting analogue N alpha-triglycyl-lysine vasopressin were compared in a prospective randomized double-blind study including 71 women undergoing cold knife conization of the uterine cervix. Hemodynamic and hemostatic variables were studied. N alpha-triglycyl-lysine vasopressin had the following advantages over lysine vasopressin: it gave significantly less skin pallor, becoming evident at a later stage during the operation. The diastolic blood pressure was significantly lower, as also was the incidence of postoperative hemorrhages. Factor VIII related antigen was lower. On the other hand reduction in heart rate (values before conization compared with values during conization) was more pronounced when N alpha-triglycyl-lysine vasopressin was used, but there was no difference in absolute values between the two groups during conization.

Treatment of pelvic varicosities causing lower abdominal pain with extraperitoneal resection of the left ovarian vein.

Fifteen women with chronic pelvic pain in whom left sided renal phlebography had demonstrated pelvic varicosities were operated upon with extraperitoneal resection of the left ovarian vein during an eight year period. At follow-up eight patients were completely cured and three were considerably improved, but in four women no improvement occurred. Mean period of follow-up was 5.6 years (range 0.5 to 8 years). All but two women were followed for at least three years. The complication rate was low. One case of wound infection and one case with bleeding from a subcutaneous artery necessitating resuture were the only complications.