Prenatal diagnosis of congenital malformations and parental psychological distress--a prospective longitudinal cohort study.

OBJECTIVE: To test whether postnatal psychological distress in parents of babies with congenital malformations is reduced by prenatal diagnosis. METHODS: A prospective observational longitudinal cohort study was conducted at two Norwegian hospitals. We included 293 parents of babies with congenital malformations (prenatal detection rate: 36.5%) referred for neonatal surgery and 249 parents of healthy babies (comparison group). Parental psychological responses were assessed on three postnatal occasions by psychometric instruments (GHQ-28, STAI-X1, and IES). RESULTS: Significantly increased psychological distress (GHQ-28) was reported by parents who received prenatal diagnosis as compared to postnatal diagnosis; acutely 28.9 versus 24.4, P = 0.006 (comparison group: 19.6); at 6 weeks 26.8 versus 21.5, P < 0.001 (comparison group: 17.7); and at 6 months 22.6 versus 18.7, P = 0.015 (comparison group: 16.6). Mothers consistently reported higher levels of distress than fathers. Multiple linear regression analysis showed that prenatal diagnosis and being a mother significantly predicted severity of acute psychological distress. At 6 weeks and 6 months, mortality and associated anomalies were significant independent predictors of psychological distress. CONCLUSION: Controlling for other covariates, we found that prenatal diagnosis of congenital malformations was a significant independent predictor of acute parental psychological distress after birth.

Consequences of prenatal ultrasound diagnosis: a preliminary report on neonates with congenital malformations.

OBJECTIVE: The aim of the present study was to examine the sensitivity of prenatal ultrasound diagnosis in neonates referred for surgery, and to test whether a prenatal versus postnatal diagnosis influenced mode of delivery and neonatal outcome of these infants. PATIENTS: Thirty-six consecutive neonates with congenital diaphragmatic hernia, abdominal wall defects, bladder exstrophy and meningomyelocele were included. RESULTS: The sensitivity of prenatal ultrasound for diagnosis of the congenital malformations was 7/36 (19%) at 17-18th week of gestation, and overall 13/36 (36%). Overall sensitivity was 2/8 in neonates with congenital diaphragmatic hernia, 6/12 in neonates with abdominal wall defects, 5/13 in neonates with meningomyelocele, whereas none of three cases with bladder exstrophy were detected prenatally. No significant improvement in neonatal morbidity was found comparing the prenatally and postnatally diagnosed groups. The neonatal survival rate was 10/13 (77%) in the prenatally diagnosed group and 22/23 (96%) in the postnatally diagnosed group (p=0.12). CONCLUSIONS: The sensitivity of prenatal ultrasound in diagnosing the congenital malformations under study in a low risk population was 19% at 17-18th week of gestation and 36% throughout the pregnancy. Prenatal diagnosis altered management of labor, but caused no improvement in neonatal outcome.

Amplification of kinin-induced hypotension by nitric oxide synthesis in spontaneously hypertensive rats.

We studied the role of nitric oxide and adrenergic activation in the blood pressure (BP) response to exogenous bradykinin in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto rats (WKY). Rats were pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the alpha-adrenergic receptor antagonist phentolamine together with L-NAME, or phentolamine alone. Sham-injected rats were used as controls. All rats subsequently received bradykinin (3, 6, and 30 micrograms/kg i.v.). Bradykinin induced a concentration-dependent fall in BP in both WKY and SHR (P < .0005). The change in BP was greater in SHR than WKY (P < .0001). BP before bradykinin administration was elevated in the L-NAME group in both strains. In WKY, L-NAME or L-NAME plus phentolamine did not alter the delta BP concentration-response curve to bradykinin (P = NS), whereas in SHR, the delta BP concentration-response curve was attenuated (P < .0048). The attenuation was observed for the two lower bradykinin doses (P < .0005) but not the highest. In SHR, phentolamine alone reduced BP before bradykinin to the same level as in WKY controls, and its delta BP concentration-response curve was not different from that of the normotensive controls or L-NAME and L-NAME plus phentolamine SHR groups. No difference was observed in the duration of the hypotensive response in SHR compared with WKY. The present results confirm that in normotensive rats, the hypotensive effect of bradykinin was mediated by an unknown mechanism other than through the release of nitric oxide. However, in SHR, this mechanism was amplified by additional activation of nitric oxide synthesis. This bradykinin-activated nitric oxide production may be a pressure-induced mechanism to counteract the hypertensive condition.

The role of endogenous bradykinin in blood pressure homeostasis in spontaneously hypertensive rats.

1. The role of endogenous bradykinin in mean arterial blood pressure (BP) homeostasis was studied in spontaneously hypertensive (SHR) and normotensive (WKY) rats by the use of a bradykinin B2-receptor antagonist (BKant; Hoe 140, 11.6 micrograms kg-1) and converting enzyme (kininase II) inhibitor (captopril, 10 mg). To obtain a response to captopril that was induced through inhibition of kinin-degradation only and not through inhibition of angiotensin II-formation, the studies were performed on binephrectomized male rats to eliminate the renin-angiotensin system. 2. The role of the nitric oxide (NO) and the adrenergic systems were evaluated by the use of NO-synthase inhibitor (L-NAME, 0.3 g kg-1) and phentolamine (2 mg kg-1), respectively. 3. The rats were anaesthetized and pretreated with two injections of vehicle (PBS) or drugs spaced 5 min apart: PBS + PBS; BKant + PBS; PBS + L-NAME; BKant + L-NAME; or phentolamine + L-NAME. All rats were given captopril 15 min later. Time-control groups were treated with L-NAME but not captopril. 4. In WKY rats, captopril did not significantly alter BP in any of the groups. In the SHR-PBS + PBS group, on the other hand, captopril induced an immediate fall in BP (delta BP = -23 +/- 4 mmHg, P < 0.0017) which was completely blocked by BKant (delta BP = 2 +/- 2 mmHg) (P < 0.0011). L-NAME did not significantly alter the immediate hypotensive response to captopril but disclosed a later hypertensive reaction. In L-NAME + BKant-treated rats, both the hypotensive response and the late hypertension was abolished. In rats treated with phentolamine + L-NAME, the immediate fall in BP was not different from the controls whereas the late hypertension was absent. 5. BKant itself had no effect on basal BP in either WKY or SHR even when a 10 times higher dose was tested in a separate set of experiments. This was true also for conscious, nonnephrectomized SHR rats. 6. It was concluded that endogenous production of bradykinin was demonstrable through kininase II-inhibition in hypertensive but not in normotensive rats. However, this endogenous bradykinin did not play a role in basal BP homeostasis. The captopril-induced hypotension depended on kinin but, under the present conditions, not on NO as a mediator. The fall in BP induced a compensatory adrenergic hypertensive response which was revealed when the continuous NO-synthesis was blocked by L-NAME.

The role of nitric oxide, adrenergic activation and kinin-degradation in blood pressure homeostasis following an acute kinin-induced hypotension.

1. Nitric oxide (NO) has been suggested as the mediator of the vascular response to bradykinin. In the present study, we found that NO did not mediate the hypotensive response to bradykinin. In addition, the significance of kininase II in terminating a kinin-induced hypotension and the role of the adrenergic system in compensating for the acute fall in blood pressure (BP) was established. 2. In normal rats, the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) induced a rise in basal BP (delta BP = 40 +/- 6 mmHg, P < 0.0014) which was not altered by pretreatment with phentolamine (delta BP = 50 +/- 6 mmHg, NS). L-NAME did not attenuate the acute fall in BP in response to bradykinin (3-30 micrograms kg-1) or kallikrein (6-300 micrograms kg-1). However, a significant decrease was observed in the duration of the hypotensive response (P < 0.027). This shorter duration was not observed after pretreatment with phenotolamine in addition to L-NAME. Phentolamine alone prolonged the hypotensive response to bradykinin (P < 0.04). These experiments confirm the role of NO-formation as a hypotensive component in BP homeostasis but not the role of NO as a mediator in kinin-induced hypotension. It further shows that the continuous NO-release also impedes the compensatory adrenergic hypertensive response following the acute fall in BP induced by bradykinin. 3. The hypertensive response to intravenously administered phenylephrine was found to be unchanged by preadministration of L-NAME (NS) thus showing that L-NAME did not change the sensitivity to the adrenergic response. In a separate protocol on L-NAME-treated rats we found no difference in heart rate (NS) during the recovery period following bradykinin before as compared to after administration of phentolamine. It was therefore concluded that the observed alterations in the duration of the hypotensive response were most probably due to changes in peripheral vascular resistance.4. To confirm further that NO is not a mediator in kinin-induced hypotension, we used an experimental model where the response to bradykinin was prolonged by preventing kinin degradation by kininase II-converting enzyme inhibitor (CEI). To produce a hypotensive response purely dependent on kinin, the studies were performed after removal of the renin-angiotensin system by nephrectomy (Nx). In this model, bradykinin (6 microg kg-1, i.v.) induced a prolonged hypotensive response. Pretreatment with LNAME did not alter the magnitude or the progression of the hypotensive response to bradykinin, thus confirming that NO was not a mediator in BK-induced hypotension.5. To study the mechanisms involved in terminating the hypotensive response to bradykinin, the results from the Nx CEI-treated rats were compared with Nx animals not treated with CEL. In the latter group,bradykinin induced a short hypotensive response, i.e. 0.5 +/- 0.1 min as compared to the 17 +/- 1 min after CEI (P<0.003). After kininase II-inhibition (and L-NAME), BP recovery was totally dependent on the adrenergic system, since phentolamine prevented a recovery in BP during the experimental period(P<0.01, compared to the CEI/L-NAME group). These results demonstrate the importance of kininase II as the major agent in terminating a bradykinin-induced hypotension, whereas the adrenergic system plays a small, although significant role in compensating for the fall in BP. The continuous release of NO therefore not only lowers basal BP but also impedes the compensatory adrenergic response.

[Glutaric aciduria type I]. / Glutarsyreuri type I.

Glutaric aciduria type I is a congenital metabolic disease caused by an enzymatic defect in the degradation of the amino acids lysine and tryptophane. This article presents five Norwegian patients with this condition. Early clinical features may be similar to those of encephalitis. The further clinical course is dominated by choreoathetosis, hyperkinesis and spasticity. The diagnosis is made by tracing enhanced glutaric acid in the urine. The treatment is a low protein diet containing only small quantities of lysine and tryptophane. Four of our patients underwent a neuropsychological examination. Despite the fact that such patients are difficult to test, our examination indicates that the condition has a greater effect on motor than on cognitive functions.

Identification of proteins of the kallikrein family by isoelectrofocusing and immunoblotting.

We have found that kallikrein-like proteins differ in their isoelectric point but share antigenic determinants. For identification of kallikrein-like proteins an initial separation was carried out in flat-bed isoelectrofocusing gels. The kallikrein-like nature was demonstrated by an immunological similarity to kallikrein-like proteins by immunoblotting using antiserum against a kallikrein family member for staining. We used this system to identify different kallikrein-like proteins during purification of both known as well as new enzymes.

A group-based training programme for general practitioners: a Norwegian experience.

There are approximately 3000 general practitioners in Norway, serving a population of slightly above four million people. A three year postgraduate education scheme for general practitioners has been in effect since 1973, to be replaced by a five year vocational training programme from January 1985, making general practice a fully recognized specialty from that date. The educational requirements consist of one year of hospital training, four years of training in general practice, and a total of 400 hours of course education, mainly in clinical subjects. The core element of the training is attendance at a group-based structured educational programme of two years' duration. This article describes the concepts and content of this decentralized group-based education, as well as some of the conflicting considerations which eventually led to this new Norwegian model of general practice training. The first evaluation studies indicate that the educational programme has met a long standing need among general practitioners.

Patient management problems in general practice using a medical journal for self-assessment exercises.

A series of six patient management problems, with clinical case histories from the authors' own practices, was presented in a Norwegian medical journal (Utposten) during 1981 and the spring of 1982. The readers were asked to respond to a number of statements which related to each case history, using a 5-point rating scale. The answers were prepared from return forms mailed anonymously to the authors, leaving the doctors with copies of their own answers. The following issue of the journal then presented the distribution of all incoming answers by giving histograms and mean values of the ratings for each question. In addition, the case history author gave his own ratings, a review of the answers, and more details about the case. In this way the respondents were given a possibility of comparing their own diagnostic skills and management decisions with those of their colleagues. There was a total of 406 incoming answers from 243 different participants, among whom 210 were general practitioners or district physicians. Background characteristics of these doctors are discussed, as well as the results of an evaluation questionnaire. This experiment with problem solving by mail was well received by the readers, mainly as a supplement to their continuing medical education. The method in this study, which permits quantification of clinical decision, may be a useful tool for medical audit activities.