THE FIMBRIA-FORNIX/CINGULAR BUNDLE PATHWAYS: A REVIEW OF NEUROCHEMICAL AND BEHAVIOURAL APPROACHES USING LESIONS AND TRANSPLANTATION TECHNIQUES

Extensive lesions of the fimbria-fornix pathways and the cingular bundle deprive the hippocampus of a substantial part of its cholinergic, noradrenergic and serotonergic afferents and, among several other behavioural alterations, induce lasting impairment of spatial learning and memory capabilities. After a brief presentation of the neuroanatomical organization of the hippocampus and the connections relevant to the topic of this article, studies which have contributed to characterize the neurochemical and behavioural aspects of the fimbria-fornix lesion “syndrome” with lesion techniques differing by the extent, the location or the specificity of the damage produced, are reviewed. Furthermore, several compensatory changes that may occur as a reaction to hippocampal denervation (sprouting, changes in receptor sensitivity and modifications of neurotransmitter turnover in spared fibres) are described and discussed in relation with their capacity (or incapacity) to foster recovery from the lesion-induced deficits. According to this background, experiments using intrahippocampal or “parahippocampal” grafts to substitute for missing cholinergic, noradrenergic or serotonergic afferents are considered according to whether the reported findings concern neurochemical and/or behavioural effects. Taken together, these experiments suggest that appropriately chosen fetal neurons (or other cells such as, for instance, genetically-modified fibroblasts) implanted into or close to the denervated hippocampus may substitute, at least partially, for missing hippocampal afferents with a neurochemical specificity that closely depends on the neurochemical identity of the grafted neurons. Thereby, such grafts are able not only to restore some functions as they can be detected locally, namely within the hippocampus, but also to attenuate some of the behavioural (and other types of) disturbances resulting from the lesions. In some respects, also these graft-induced behavioural effects might be considered as occurring with a neurochemically-defined specificity. Nevertheless, if a graft-induced recovery of neurochemical markers in the hippocampus seems to be a prerequisite for also behavioural recovery to be observed, this neurochemical recovery is neither the one and only condition for behavioural effects to be expressed, nor is it the one and only mechanism to account for the latter effects. © 1997 Elsevier Science Ltd. All Rights Reserved.     

Norethisterone concentration in breast milk and infant and maternal plasma during ethynodiol diacetate administration

Twelve women with established lactation of 4–8 weeks duration were given a low-dose progestogen-only contraceptive, ethynodiol diacetate 0.5 mg (Femulen) daily. On the seventh and eighth day of the study, prior to the mother's taking the pill, a blood sample was taken from her and from the infant. Further blood samples were collected from the mother 4 and 12 hours later. Breast milk samples were collected at every feed on day 7 and day 8.

Ethynodiol diacetate is rapidly metabolised in humans, changing into the metabolite norethisterone which is found in both blood and milk. Hence, norethisterone concentrations were estimated.

On day 7 and day 8, four hours after ingestion of the pill, the median norethisterone maternal plasma concentration was 1.60 ng/ml and it fell to a median level of 0.30 ng/ml prior to the next dose of the pill. At this time the median infant concentration was 0.10 ng/ml but the maximum observed level was 0.50 ng/ml.

In the breast milk the norethisterone concentration appears to peak at around 4–8 hours following the ingestion of the pill. The maximum observed concentration in breast milk was 0.84 ng/ml. The amount of norethisterone ingested by the infant averaged 0.02% (6.65 μg) of the dose of ethynodiol diacetate ingested by the mother. The maximum observed on any one day was 0.07% (27.52 μg).

The above results indicate that the amount of progestogen ingested by the infant from its mother's milk is small and is unlikely to pose a risk to the infant.     

Serum Neopterin and β2-Microglobulin Concentrations in Monoclonal Gammopathies

ABSTRACT Serum neopterin and β₂-microglobulin concentrations were investigated in 46 patients with multiple myeloma and in 28 patients with asymptomatic monoclonal gammopathy followed for long periods (median 9.6 years) and showing an absence of evolution. Seventy-two per cent of the patients with multiple myeloma showed β₂-microglobulin concentrations higher than 3 mg/1 with a mean of 6.84 mg/1, whereas all the patients with asymptomatic monoclonal gammopathies had concentrations lower than 3 mg/1 with a mean of 1.64 mg/1. Concerning serum neopterin concentrations, 91% of the patients with multiple myeloma had values with in pathological limits (>8 nmol/1) with a mean of 34 nmol/1, whereas all but one of the patients with asymptomatic monoclonal gammopathy had normal values with a mean of 5.19 nmol/1. The differences thus observed in these two groups of patients are highly significant (p<0.001). Serum neopterin concentration, unrelated to renal insufficiency, seems to be useful in the differentiation of malignant or benign asymptomatic monoclonal gammopathies.     

Duodenal obstruction after repair of abdominal aortic aneurysm

Two cases are reported of obstruction of the transverse duodenum within the first 2 weeks after repair of an abdominal aortic aneurysm. Abdominal radiography, upper gastrointestinal examination, and computed tomography all aid in the diagnosis.