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Biomedical subjects

E Frank

Publications and source records attributed to E Frank.

At least 343 records · Page 19Linked to original sources

A modification of the Brown-Roberts-Wells stereotactic frame for implantation of ventricular access reservoirs.

A ventricular catheter and connected subcutaneous reservoir (ventricular access reservoir) allows easy, repeated access to the cerebrospinal fluid for a multitude of purposes. In situations in which the ventricles are small or displaced, insertion of a ventricular catheter may be difficult. Multiple passes to cannulate the ventricle may damage the brain and manipulation of the catheter and reservoir may cause migration of the catheter, possibly compromising its function. A stereotactic method for insertion of ventricular access reservoirs using a device that attaches to the Brown-Roberts-Wells stereotactic system has been developed. With this device the catheter and reservoir are guided into place as a single unit, utilizing a guide attached to the Brown-Roberts-Wells frame. This technique has been useful in inserting ventricular access reservoirs into patients with small ventricles or in whom there is some abnormality of the brain or skull that renders classical landmarks for ventricular cannulation useless.

Catheterization↗

Role of competition among sensory neurons in regulation of pattern of innervation at their central and peripheral targets.

1. The importance of competitive interactions among muscle sensory afferents on their projections to central and peripheral targets was studied by producing large reductions in the number of afferents during development. Removal of the brachial dorsal root ganglion (DRG2), which normally supplies the entire sensory innervation of the forelimb, in bullfrog (Rana catesbeiana) tadpoles caused a smaller number of neurons in the adjacent thoracic ganglion (DRG3) to sprout into the forelimb and into the brachial spinal cord. 2. Horseradish peroxidase labeling in postmetamorphic animals showed that DRG3 neurons innervating the triceps muscle arborize in a novel but now appropriate area of the spinal cord, the region containing motoneuronal dendrites. These foreign afferents do not arborize in inappropriate regions of the spinal gray matter, and their collaterals have the same rostrocaudal distribution as those of normal DRG2 muscle afferents. 3. After metamorphosis, the number of DRG3 sensory axons in individual triceps muscle nerves was determined. Normally, two-thirds of all triceps afferents project to the medial head alone, even though each of the three heads is of similar size and is contacted by similar numbers of motoneurons. After DRG2 removal, although the total number of DRG3 afferents projecting to the triceps muscle was smaller than normal, the medial head still received approximately two-thirds of the axons, just as in normal frogs. These results suggest that the proportional sensory innervation of the triceps muscle-heads is not dependent on competitive interactions among afferents. 4. DRG3 afferents projecting to the forelimb also sprouted to innervate appropriate brachial motoneurons. The average strength of connection between individual sensory and motor neurons was found to be the same as in normal animals, even though there was presumably more central target space available for each afferent axon. This suggests that the number and/or strength of central connections made by individual fibers may be an intrinsic property of muscle sensory neurons.

Animals↗

Treatment of imipramine-resistant recurrent depression: II. An open clinical trial of lithium augmentation.

Prior studies suggest that the addition of lithium salts may enhance treatment responses in depressions that have not responded to tricyclic antidepressants. The authors report on the efficacy of lithium augmentation in an open-label study of 20 outpatients with recurrent major depression who had not responded to greater than or equal to 12 weeks of treatment with imipramine (mean dosage = 256 mg/day) and psychotherapy. Only 1 patient (5%) responded during the first week of treatment, but the cumulative response rate increased to 65% during the 6-week clinical trial. Improvement in patients receiving lithium augmentation was significantly greater than the improvement observed in a historical control group of imipramine-resistant patients who received continued treatment with the imipramine-psychotherapy combination. The results support the usefulness of a 6-week trial of lithium augmentation in outpatients with resistant depression. It remains unclear whether the effectiveness of lithium augmentation is due to a true potentiation effect, a primary antidepressant effect by lithium, or a combination of both those factors.

Adult↗

Activation of GABAB receptors causes presynaptic inhibition at synapses between muscle spindle afferents and motoneurons in the spinal cord of bullfrogs.

Baclofen, a specific GABAB receptor agonist, was used to study the functional role of activation of GABAB receptors in synaptic transmission between muscle spindle afferents and motoneurons in the isolated spinal cord of bullfrogs. (+/-)-Baclofen (5 microM) reversibly reduced the amplitude of the excitatory postsynaptic potential (EPSP) evoked by simulation of various brachial muscle nerves and recorded extracellularly from the ventral root by 47% without shortening the falling phase of the EPSP. Neither the time course nor the amplitude of the action potentials in the sensory afferents was affected. Thus, baclofen caused synaptic inhibition without reducing either the potential change occurring in the muscle sensory afferents or the motoneuronal membrane resistance. Quantal analysis, performed using a deconvolution technique, of the monosynaptic EPSPs in brachial motoneurons evoked by activity in single triceps muscle spindle afferents showed that transmission at these synapses was quantal, and baclofen lowered the quantal content without altering the quantal size. Furthermore, quantal analysis of the electrical component of these unitary EPSPs showed that it did not fluctuate in amplitude, either in normal saline or with baclofen. The inhibition produced by activation of GABAB receptors is therefore presynaptic but is not likely to be caused by conduction failures in the sensory terminals.

Animals↗

Activation of GABAA receptors causes presynaptic and postsynaptic inhibition at synapses between muscle spindle afferents and motoneurons in the spinal cord of bullfrogs.

The functional role of GABAA receptors in inhibition of synaptic transmission between muscle spindle afferents and spinal motoneurons was studied in the isolated spinal cord of bullfrogs. Extracellular recording from the ventral root showed that activation of GABAA receptors by muscimol (primarily a GABAA receptor agonist) at 50 microM produced a 38% reduction in the amplitude of the excitatory postsynaptic potential (EPSP) evoked by stimulation of triceps muscle sensory afferents and a 66% reduction in the EPSP half-width, suggesting a large increase in the conductance of the motoneuronal membrane. Quantal analysis of unitary triceps EPSPs recorded intracellularly from motoneurons showed that muscimol reduced the quantal content of release (presynaptic inhibition). In addition, muscimol decreased the quantal size (postsynaptic inhibition) when the postsynaptic conductance change was large. Because the effects of muscimol were completely and reversibly blocked by 100 microM bicuculline (a specific GABAA receptor antagonist), both the pre- and the postsynaptic inhibition caused by muscimol were due to activation of GABAA receptors. Activation of GABAA receptors thus causes both pre- and postsynaptic inhibition of synaptic transmission between muscle afferents and spinal cord motoneurons in the frog.

Animals↗

Adequate treatment with imipramine in continuation treatment.

Maintenance treatment studies done with tricyclic antidepressants have used the equivalent of 150 mg or less of imipramine in prophylactic clinical trials. In an ongoing 3-year maintenance trial, the authors are using imipramine in dosages greater than 150 mg/day for both acute and continuation treatment (4 to 6 months) of recurrent depression in order to test the efficacy of this dosage level. Fifty-seven depressed patients who received tricyclic drug treatment and interpersonal psychotherapy during the acute and continuation phases of the study tolerated this dosage level well (mean dose, 217 mg/day of imipramine), reported few adverse effects on a somatic symptom checklist, and demonstrated a high level of compliance as shown by plasma concentration/dosage (L/D) ratios. The authors found that the time course of the L/D ratio is associated with higher steady-state plasma concentrations than those observed with similar dosages in shorter-term tricyclic antidepressant treatment.

Adult↗

Nocturnal penile tumescence in healthy 20- to 59-year-olds: a revisit.

This report presents data on normative nocturnal penile tumescence (NPT), based on a study of 48 healthy men aged 20-59 years, without complaints of erectile dysfunction. In general, the current measures show good concordance with those reported by Karacan and colleagues in 1976. The effect of "pathology-free" aging (from age 20 to 59) on electrographic measures of NPT is relatively modest, accounting for 8.4-14.4% of the variance. Furthermore, no age effect on visual estimates of erectile fullness or on buckling force estimates of penile rigidity were present. Maximum buckling force and maximum erectile fullness showed stability across the four decades of the Pittsburgh sample.

Adult↗

Abdominal candidiasis in surgical patients.

Although abdominal candidiasis in critically ill surgical patients is becoming increasingly common, optimal management has not been defined. We treated 16 patients with abdominal candidiasis over a 36 month period. Violation of the gastrointestinal tract mucosa was the most common precipitating event (13 patients). Predisposing factors included: CVP catheters, broad spectrum antibiotics, and parenteral hyperalimentation in all patients, H2-blockers/antacids in 14 patients, as well as malnutrition (7 patients), DM (3 patients), alcoholism (3 patients), and steroids/chemotherapy (3 patients). Candida was isolated from an abscess in seven patients, peritoneal fluid in six patients and both in three patients. In four patients abdominal candidiasis was preceded by positive cultures from blood or two peripheral sites which had not been treated. All patients were treated with amphotericin B (146-4000 mg) without any major adverse effects. Fungal infection was eradicated in ten patients; three patients succumbed to candidiasis. Patients treated within seven days required less Amphotericin B and appeared to have a better outcome than those having delayed treatment. The authors conclude that abdominal candidiasis is a potentially lethal infection in critically ill surgical patients that should be aggressively treated. Amphotericin B can be safely administered and concurrent antibiotics need not be stopped.

Abdomen↗

Specificity of sensory projections to the spinal cord during development in bullfrogs.

Sensory neurons in dorsal root ganglia of frogs project to areas of the spinal cord they do not normally innervate following removal of adjacent ganglia at tadpole stages (Frank and Westerfield, J. Physiol. (Lond.) 324:495-505, '82b). A possible explanation of this phenomenon is that sensory neurons project to wider areas of the spinal cord in tadpoles than in adult frogs and that partial deafferentation causes the retention of these widespread projections. Therefore, the specificity of sensory projections to the spinal cord in tadpoles was assessed by staining individual dorsal roots with horseradish peroxidase. Thoracic sensory neurons project to thoracic segments of the spinal cord and to the brainstem in tadpoles, like thoracic sensory neurons in adult frogs. They rarely arborize in the brachial region even at stages when no other sensory fibers arborize at this level. Furthermore, their projections are restricted to the dorsal horn at all stages. Conversely, hypoglossal sensory neurons, which project into the intermediate gray matter in the adult, also project to this area in tadpoles. The finding that sensory neurons in tadpoles only project to areas of the spinal cord that they innervate in the adult suggests that the novel projections observed following partial deafferentation of the spinal cord are actually induced by the operation. An additional finding was that forelimb afferents, which project to an area extending from the obex to midthoracic levels in adult frogs, arborize at rostral spinal levels and at thoracic levels several stages before they form projections to the region around their own dorsal root. These differences in the stages at which projections to different levels of the spinal cord develop suggest that local properties of the spinal cord may control the timing of sensory fiber arborization.

Afferent Pathways↗

Electroencephalographic sleep profiles in recurrent depression. A longitudinal investigation.

The electroencephalographic sleep profile of a group of recurrent depressives who had been depressed for less than four weeks was compared with their sleep profile in a prior episode of depression. The findings in these 19 cases indicate that early in the episode, rapid eye movement (REM) sleep findings are more abnormal, including shortened REM latency, REM sleep percent, and REM activity. Other sleep variables, such as sleep continuity measures and decreased delta-wave sleep, are abnormal in a similar fashion in both episodes. The results are not explainable on the basis of clinical severity or number of episodes and call for increased attention to the potential relationships between the psychobiological pattern and duration and course of the depressive episode.

Adult↗

Social zeitgebers and biological rhythms. A unified approach to understanding the etiology of depression.

Results of biological and psychosocial studies of depression completed in the last decade have stimulated the need for new hypotheses that synthesize these findings in a unified etiologic theory. The importance of disruption of biological rhythms on the one hand, and psychosocial losses on the other, in the causation of depressive episodes suggest one possible unifying hypothesis. The concept of loss of "social zeitgebers," ie, persons, social demands, or tasks that set the biological clock, may provide the link between biological and psychosocial theories of etiology. We suggest that a disruption of social rhythms, which may result in instability in biological rhythms, could be responsible for triggering the onset of a major depressive episode in vulnerable individuals.

Biological Clocks↗

Anatomical specificity of regenerated muscle sensory afferents in the spinal cord of the bullfrog.

The specificity of central projections made by regenerated muscle sensory fibers in the brachial spinal cord was studied with anatomical tracing methods. Sensory fibers were interrupted by freezing dorsal roots in postmetamorphic bullfrogs. After several months, regenerated sensory fibers were labeled with horseradish peroxidase applied to the triceps brachii muscle nerve, and their arborizations within the spinal cord were reconstructed from serial cross sections. Most of the regenerated projections from triceps muscle sensory afferents ended in or near their normal terminal field. A few branched and appeared to terminate more dorsally than normal, however, sometimes within the region where cutaneous afferents normally terminate. In contrast to the normal pathway followed by muscle afferents within the spinal cord, many regenerated afferents grew along the circumference of the spinal cord, just under the pial surface, and then turned abruptly toward the midline and into their appropriate terminal region. This suggests that regenerating afferents may actively seek out their appropriate targets and are not simply passively guided to them.

Afferent Pathways↗

Nocturnal penile tumescence is diminished in depressed men.

Although depressed individuals commonly report decreased libido, it was not known if such changes are accompanied by neurophysiological alterations. Preliminary studies suggest that some depressed men may manifest diminished nocturnal penile tumescence (NPT), an objective measure of erectile capacity. We report NPT findings in 34 male outpatients with major depression (SADS/RDC) and an age-matched group of 28 healthy controls. A 3-night electroencephalographic (EEG) sleep/NPT protocol was utilized, with penile rigidity (buckling force) determined on night 3. Analysis of night 2 data by MAN-COVA revealed significant effects for age, the covariate (F = 2.86, p = 0.002), and diagnosis (F = 2.32, p = 0.02). Depressed men had significantly diminished NPT time (F = 16.8, p less than 0.001), even when adjusted for sleep time (F = 13.4, p less than 0.001) or rapid eye movement (REM) time (F = 7.2, p less than 0.01). NPT time was reduced by greater than or equal to 1 SD below the control mean in 40% of depressives and was comparable to the level seen in 14 nondepressed patients with a clinical diagnosis of organic impotence. An intermediate proportion of depressed patients (38%) had maximum buckling forces less than or equal to 500 g, indicating diminished penile rigidity, when compared to controls (16%) and men with presumed organic impairment (93%) (p less than 0.001). Diminished NPT time and low buckling force were associated with a history of erectile dysfunction within the index depressive episode (p less than 0.001). These findings suggest that depression in men is associated with a potentially reversible decrease in erectile capacity, which may be associated with significant sexual dysfunction.

Adult↗

Diagnostic performance of nocturnal penile tumescence studies in healthy, dysfunctional (impotent), and depressed men.

Nocturnal penile tumescence (NPT) studies were evaluated in 17 men with a clinical diagnosis of organic erectile dysfunction in comparison to age-matched healthy controls (n = 17) and depressed men (n = 17). The dysfunctional group had significantly fewer NPT episodes and reduced maximal penile tip changes when compared to healthy controls and depressed patients. Further, the dysfunctional group had significantly diminished erectile fullness and reduced penile rigidity. Diagnostic performance of polygraphic (night 1) and visual inspection (nights 2 or 3) components of the NPT protocol were examined in these criterion groups. A diagnostic classification based on polygraphic measures successfully discriminated 73.5% of dysfunctional and healthy control subjects, but classified 47% of depressives in the dysfunctional range. Use of visual inspection indices correctly identified 88% of the dysfunctional sample and 94% of normal controls, and reduced the "false-positive" rate in depression to only 18%. Results support the diagnostic utility of NPT studies, particularly when enhanced by visual inspection procedures. Nevertheless, the presence of major depression may confound interpretation of such studies.

Circadian Rhythm↗

Assessment of sexual function in depressed, impotent, and healthy men: factor analysis of a Brief Sexual Function Questionnaire for men.

We report a study of sexual function in outpatient men with major depressive disorder (n = 42), compared with healthy control men (n = 37) and a clinic sample complaining of erectile dysfunction (n = 13). A principal-components factor analysis of the Brief Sexual Function Questionnaire confirmed differences in the clinical dimensions of sexual activity/performance, interest, satisfaction, and physiological competence. The four factors accounted for 72% of the variance in the analysis. Acceptable test-retest reliability, construct validity, and concurrent validity (with the Derogatis Sexual Function Inventory and a self-report behavioral log) were demonstrated. Parallel observations with findings from previous nocturnal penile tumescence studies in these same men are discussed.

Adult↗