Association of antidepressants and other medications with mortality in the residential-care elderly.

To explore the extent to which treatment of depression affects survival, we evaluated the association between use of antidepressant medications and death rates among the residents of a large residential-care facility for the elderly using a retrospective record-review study (N = 624). One year survival, among those taking antidepressants (10.9%), was 11.8% compared to 11.1% among the remainder of the population. A second study followed a group of 32 patients in the same institution who had participated in a therapeutic trial of nortriptyline treatment for major depression. Patients who experienced adverse medical events during treatment exhibited significantly increased mortality; among treatment completers, there was no significant relationship between mortality and therapeutic response. These findings suggest that the inability to tolerate treatment with an antidepressant can be considered a manifestation of physiologic frailty and increased vulnerability to mortality from disease. The previously reported decrease in survival among residential-care patients with major depression is not paralleled by a similar effect in those taking antidepressants. This may reflect selection factors with respect to the ability to tolerate antidepressants, rather an effect of treatment.

Failure to thrive in the elderly: exploration of the concept and delineation of psychiatric components.

Findings from an exploratory study of the relationships between routine clinical laboratory tests and the clinical status of elderly patients living in a nursing home or congregate housing facility demonstrate that low albumin and anemia are associated with decreased survival and with self-care deficits, cognitive impairment, depression, and summary measures of the severity of medical illness. The interrelationships observed among these variables support the usefulness of the concept of failure to thrive. Although albumin can serve as a nutritional marker, findings on its relationship with sedimentation rate, triiodothyronine uptake, fasting plasma amino acids, and retinol-binding protein levels suggest that the low albumin related to failure to thrive is not a simple reflection of steady-state deficits in protein-calorie nutrition; it appears to be sensitive to more direct effects of disease and inflammation or to the interactions between nutrition and illness.

Development of the cardiovascular system: an interactive video computer program.

The major aim of this project is to provide interactive video computer based courseware that can be used by the medical student and others to supplement his or her learning of this very important aspect of basic biomedical education. Embryology is a science that depends on the ability of the student to visualize dynamic changes in structure which occur in four dimensions--X, Y, Z, and time. Traditional didactic methods, including lectures employing photographic slides and laboratories employing histological sections, are limited to two dimensions--X and Y. The third spatial dimension and the dimension of time cannot be readily illustrated using these methods. Computer based learning, particularly when used in conjunction with interactive video, can be used effectively to illustrate developmental processes in all four dimensions. This methodology can also be used to foster the critical skills of independent learning and problem solving.

Gender differences in neurotransmitter expression in the rat superior cervical ganglion.

Sexual dimorphism of neuron number has been observed in several areas in the central and peripheral nervous system. In many of these areas enhanced neuron survival exists in males during the period of naturally occurring cell death. This has been attributed to high levels of circulating testosterone in the perinatal period. The superior cervical ganglion (SCG) of the rat exhibits this sexual dimorphism. The difference in neuron numbers is established by two weeks postnatally and precedes the differences in body weight and sympathetic target mass between the sexes. At this two week time point, fewer SCG neurons in the female rat must supply neurotransmitter to the same mass of sympathetic target as in the male. The present study examined some of the mechanisms used by neurons in the SCGs of male and female rats to compensate in supplying neurotransmitter to their targets. At birth, the SCGs of male and female rats contain equal numbers of neurons. There is also no sex difference at this time in the content of norepinephrine (NE) in these neurons or in the enzyme activity of tyrosine hydroxylase (TH). However, a sex difference does exist in the expression of TH-mRNA, with SCG neurons in female expressing more TH-mRNA than males. At this time, there is no sex difference in either the total body weight of males and females or in the mass of sympathetic target organs. During the first two postnatal weeks, natural neuron death in the SCG results in the loss of significantly more neurons in females than in males. At the end of the period of cell death, neurons in females continue to express more TH-mRNA, and at this time both TH enzyme activity and NE content per neuron are also higher in females. Since the adult sex difference in body weight and sympathetic target mass has not yet been established, the same amount of target mass is innervated by fewer neurons in females. In the adult, the sex difference in SCG neuron number is maintained. However, both overall body weight and sympathetic target mass are significantly greater in males. At this time expression of TH-mRNA is greater in SCG neurons of males, while both TH enzyme activity and NE content per neuron are equal in males and females. One of the challenges presented to the developing nervous system is to match a population of neurons with its targets.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent regulation of neurotransmitter metabolism in perikarya and terminals of developing sympathetic neurons.

Steady-state levels and turnover of the neurotransmitter, norepinephrine (NE), were measured in sympathetic perikarya and in two sympathetic target organs in the rat at various times during postnatal development. NE content in sympathetic perikarya in the superior cervical ganglion (SCG) increases 15-fold from birth to reach adult levels by 60 days. This increase in NE content parallels the increase in total protein in the ganglion. The rate of turnover of NE in the sympathetic perikarya increases slightly from birth to adulthood. Since the perikarya in the SCG project to a variety of different targets in the head and neck, NE metabolism was also examined in two terminal sympathetic plexuses, in the iris and in the submandibular gland (SMG). The terminal noradrenergic plexuses within these target organs do not mature with the same time course. In the iris, levels of NE increase 24-fold from birth until 90 days postnatally. Turnover of NE in sympathetic terminals in the iris at the time of birth is equivalent to that in the adult. In contrast, both the content and turnover of NE in sympathetic terminals in the SMG are very low at birth, and increase dramatically in the first month postnatally. Deafferentation of the SCG at birth impairs the development of normal levels of NE in sympathetic perikarya by approximately 40%, and total ganglionic protein is similarly affected. NE turnover in sympathetic perikarya deafferented at birth is only slight reduced from normal. The response to neonatal deafferentation differs in the two terminal sympathetic plexuses. In neurons that project to the iris, no detectable NE turnover could be measured, although the content of transmitter attains 64% of control values after deafferentation.(ABSTRACT TRUNCATED AT 250 WORDS)

Dendritic development in the rat superior cervical ganglion.

Previous studies from our laboratory have shown that synaptogenesis in the superior cervical sympathetic ganglion (SCG) of the rat occurs predominantly during the first weeks after birth. The purpose of the present study was to examine the normal development of dendrites of the ganglion neurons, and to assess the importance of the afferent input in shaping this development. Two independent methods for examining dendritic morphology were used. One was to label neurons in the SCG by injecting a conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA) into a target of the SCG neurons (the submandibular gland). This procedure results in a 'Golgi-like' filling of the retrogradely labelled cell bodies and their dendrites. The second method was stereologic analysis (point-counting) of electron micrographs of sections of the SCG. At birth, the ganglion neurons give rise to an average of 2.4 primary dendrites and 1.2 secondary branches. No tertiary branches are observed at this age. The total dendritic length is 15.3 microns. Electron microscopic stereology reveals that the mean volume occupied by dendrites in the newborn SCG is 0.0093 mm3. In the adult, there is an average of 5.2 primary, 6.3 secondary, 4.8 tertiary and 1.9 quaternary dendrites. The total dendritic length is increased 23-fold to 347 microns. The mean volume occupied by dendrites is 0.0771 mm3, representing an 8-fold increase. In ganglia from adult rats which were deafferented at birth, an essentially normal dendritic form is attained. There are 4.5 primary, 6.2 secondary, 2.8 tertiary and 2.2 quaternary dendrites, and the total dendritic length is 297 microns. The mean volume of dendrites is 0.0571 micron3.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurotransmitter synthesis, storage, and turnover in neonatally deafferented sympathetic neurons.

In the superior cervical sympathetic ganglion (SCG) of the rat, a significant amount of morphological and biochemical maturation occurs in the first few postnatal weeks. The specific activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of norepinephrine (NE), increases during this time and is subject to transsynaptic regulation by the preganglionic inputs. In the present study, we examined the normal postnatal development of NE stores in sympathetic neurons and the transsynaptic regulation of this development. NE content undergoes an 8-fold increase from the time of birth, and stabilizes at adult levels at one month. Following neonatal deafferentation, there is a temporary stunting of NE accumulation in sympathetic neurons and a permanent reduction in the activity of TH, whether or not regeneration of the afferents occurs. When regeneration is prevented, the turnover of NE is significantly reduced, while NE levels rise to near normal levels. When regeneration is permitted, however, both the stored amount and turnover of NE attain normal levels. These data suggest that there is a critical period during the first two postnatal weeks when transsynaptic influences from afferents are necessary for the induction of TH in sympathetic neurons. Levels and turnover of transmitter do not have this critical period, but appear to depend solely on the functional integrity of the system.