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Biomedical subjects

C H Brown

Publications and source records attributed to C H Brown.

At least 55 records · Page 3Linked to original sources
PubMed1997

The role of afferent inputs to supraoptic nucleus oxytocin neurons during naloxone-precipitated morphine withdrawal in the rat.

During prolonged exposure to morphine, oxytocin neurons of the rat supraoptic nucleus develop dependence, shown by hyperexcitation following morphine withdrawal. The present study investigated the role of afferent projections to the supraoptic nucleus in this withdrawal excitation. Rats were made morphine-dependent by continuous intracerebroventricular infusion of morphine at increasing doses (up to 50 microg/h). On the sixth day, rats were anaesthetized with pentobarbitone and morphine withdrawal was precipitated by intraperitoneal injection of naloxone (5 mg/kg). Fos-immunoreactivity in the supraoptic nucleus, and also in the median preoptic nucleus, organum vasculosum of the lamina terminalis and subfornical organ, which project to the supraoptic nucleus, increased following morphine withdrawal. However, retrograde tracing from the supraoptic nucleus showed that, of the neurons in these regions which project to the supraoptic nucleus, only 0.4-7.1% expressed Fos in response to morphine withdrawal. Following morphine withdrawal, Fos-immunoreactivity was present in 39.2% and 19.8% of the tyrosine hydroxylase-immunoreactive neurons of the A1/C1 and A2/C2 cell groups. Of the cells in these regions identified as projecting to the supraoptic nucleus, 11.3% in the region of the A2 cell group and 12.7% in the region of the A1 cell group expressed Fos after morphine withdrawal. In a second study, monoamine release was measured in the supraoptic nucleus of urethane-anaesthetized morphine-dependent and -naive rats. Retrodialysis of naloxone (10[-5] M) into the supraoptic nucleus induced a small increase in plasma oxytocin concentration in morphine-dependent rats (13.5+/-4.8 pg/ml increase) but not in naive rats (1.2+/-5.9 pg/ml decrease), with no significant change in monoamine release in either morphine-dependent or -naive rats. Intravenous injection of naloxone (5 mg/kg) 1 h later produced a further significant increase in plasma oxytocin concentration in morphine-dependent rats concomitant with a significant increase in noradrenaline release from the supraoptic nucleus. Thus, morphine-withdrawal excitation of supraoptic oxytocin neurons occurs concurrently with a modestly increased activity of their input from the brainstem, and very little activation in other known inputs.

Afferent Pathways↗
PubMed1997

Perception of the American English liquid /ra-la/ contrast by humans and monkeys.

Human and monkey perception of the American English liquid /ra-la/ contrast was compared using various synthetic continua in which the normal spectral and temporal cues were higher either complete, partial, or altered in various ways. Two experiments compared human and monkey discrimination of the various continua using a low-uncertainty repeating-standard procedure. Results showed that, while human sensitivity was best at the human phoneme boundary, monkey sensitivity was best inside the /ra/ category. Also, while humans were more sensitive than monkeys to temporal variation in the stimuli, monkeys were more sensitive than humans to spectral variation, particularly for stimuli inside the /ra/ category. Two additional experiments compared human and monkey identification of the /ra-la/ continua using a higher-uncertainty go/nogo identification procedure. Monkeys performed as accurately as humans (including one native Spanish and one native Hindi listener) in identifying the stimuli. However, human and monkey "phoneme boundaries" were in different places, with monkey boundaries shifted more toward /ra/ than human boundaries. These results suggest that human boundaries may be based on some sort of specific linguistic knowledge. Despite these boundary differences, monkeys showed a trading relation comparable to that of humans, indicating that the /ra-la/ trading relation has a psychoacoustic basis and that linguistic knowledge is not a necessary prerequisite for it to occur.

Adult↗
PubMed1997

A multidimensional scaling analysis of vowel discrimination in humans and monkeys.

Multidimensional scaling (MDS) was used to compare perceptual maps for 10 synthetic English vowels in humans and Old World monkeys (Macaca fuscata and Cercopithecus albogularis). Subjects discriminated among the vowels using a repeating background procedure, and reaction times were submitted to an MDS analysis to derive measures of perceive similarity. The dimensions that emerged related to the frequencies of the first (F1), second (F2), and third (F3) formants. Human data indicated a good match to previous MDS studies using rating procedures or confusion matrices: The dominant dimension mapped onto vowel F2, the phonetically most important formant, and the second and third dimensions mapped onto F1 and F3, respectively. For monkeys, equal weightings occurred for F1 and F2, and F3 was not clearly represented. Monkey sensitivity to the formants appeared to relate to formant amplitudes. If monkeys are giving an accurate representation of the psychoacoustic relations among the formants, then our human results suggest that species-specific mechanisms, reflecting the salience of the phonetic feature of advancement, may contribute to vowel coding in humans.

Adult↗
PubMed1996

Activation of oxytocin neurones by systemic cholecystokinin is unchanged by morphine dependence or withdrawal excitation in the rat.

1. Morphine inhibits supraoptic nucleus oxytocin neurones directly and presynaptically via inhibition of afferent noradrenergic endings. 2. We studied whether morphine tolerance/dependence (induced by intracerebroventricular (I.C.V.) morphine infusion) alters the responsiveness of oxytocin neurones to systemic cholecystokinin (CCK), a stimulus which activates oxytocin neurones via the release of noradrenaline. 3. CCK (20 micrograms kg-1, i.v.) increased plasma oxytocin concentrations similarly in urethane-anaesthetized morphine-naive and -dependent rats. In naive rats, I.C.V. (10 micrograms) and i.v. morphine (0.5 mg kg-1) reduced CCK-induced oxytocin secretion by 95 +/- 4 and 49 +/- 10%, respectively. In dependent rats, i.v. morphine reduced CCK-induced release by only 8 +/- 9%, indicating tolerance. 4. In urethane-anaesthetized rats, i.v. CCK increased the firing rates of oxytocin neurones similarly in morphine-naive and -dependent rats (by 1.2 +/- 0.2 and 1.4 +/- 0.3 spikes s-1 maximum, respectively, over 5 min). Naloxone did not alter spontaneous or CCK-induced activity in naive rats but increased activity in dependent rats (by 3.4 +/- 0.5 spikes s-1), indicative of withdrawal excitation; however, the response to CCK remained unchanged after naloxone. 5. Systemic CCK did not trigger withdrawal, nor did it have a greater excitatory effect in dependent rats. Thus, morphine withdrawal excitation of oxytocin neurones does not involve supersensitivity to the noradrenergic input, or hypersensitivity of this input to i.v. CCK. Tolerance apparently occurs both at the cell bodies of oxytocin neurones in the supraoptic nucleus and in their noradrenergic input. However, dependence is apparent only at the cell bodies.

Afferent Pathways↗
PubMed1995

Opioid-noradrenergic interactions in the control of oxytocin cells.

The nucleus tractus solitarii (NTS) projects directly to the oxytocin neurones of the supraoptic nucleus (SON), and relays afferent stimuli arising from the birth canal during parturition. About 80% of these projecting neurones are noradrenergic, and these same neurones are activated following systemic administration of cholecystokinin (CCK), which also results in an increased electrical and secretory activity in oxytocin neurones. Oxytocin release in response to CCK is abolished following selective neurotoxic destruction of these noradrenergic neurones. Oxytocin release following CCK (and that during parturition) is potently inhibited by morphine, which blocks the local noradrenaline release in the supraoptic nucleus. This acute opiate action involves presynaptic inhibition of the noradrenergic terminals, and occurs without marked suppression of the activity of noradrenergic cells in the NTS. During chronic exposure to morphine the oxytocin system becomes tolerant to, and dependent upon morphine. In the course of tolerance, oxytocin cell activation in response to CCK recovers from initial inhibition. However, the pathway that mediates this response does not appear to become dependent: the oxytocin cell response to CCK is unchanged by opiate withdrawal induced by naloxone, despite a large increase in the background electrical activity of oxytocin cells provoked by withdrawal. Nevertheless, expression of withdrawal excitation by oxytocin neurones is curiously contingent upon the activity of the noradrenergic input in that prior lesioning of this input has no effect upon the subsequent withdrawal excitation of oxytocin cells. Yet under urethane anaesthesia, acute pharmacological blockade of the noradrenergic input suppresses withdrawal. We discuss how these paradoxical observations might be reconciled, and note that the difference may be related to differing levels of tonic activity in the noradrenergic input. It is possible that dependence relies upon the input when it is there, but not when it is not.

Afferent Pathways↗
PubMed1994

Cutaneous malignant melanoma with diffuse intraocular metastases.

A 63-year-old man with a history of cutaneous melanoma and a 3-month history of visual loss in his right eye presented with marked pigmentation of the anterior-segment structures, including trabecular meshwork, iris, and lens surface, with pigment dispersion in the aqueous and anterior vitreous in the right eye. Clinical examination and echography showed no evidence of an intraocular tumor although metastatic melanoma was suspected. Pathologic examination revealed numerous heavily pigmented melanoma cells throughout the anterior segment of the eye, mainly concentrated in the anterior vitreous near the ciliary body. No discrete tumor was found on multiple sections through the globe.

Anterior Eye Segment↗
PubMed1994

Epidemiologic factors correlated with multiple sexual partners among women receiving prenatal care.

A cross-sectional survey methodology was used to respond to the need of a local health department to identify correlates of high-risk behaviors related to human immunodeficiency virus (HIV) transmission among pregnant women attending prenatal care clinics. This study of 488 maternity patients was conducted at two public health clients in Tampa, Florida, in 1991. The prevalence of high-risk behaviors was assessed using a self-administered questionnaire. Out of 428 respondents, 25% reported having had intercourse with two or more male partners in the past year. Following multiple logistic regression analysis, four variables remained consistently and significantly associated (P < 0.05) with having two or more sexual partners: (1) annual household income of less than $10,000/y (prevalence odds ratio (POR) = 4.5; 95% confidence limits (CL): 1.5, 13.1); (2) history of prostitution (POR = 8.1; 95% CL: 1.5, 42.1); (3) history of rape or forcible intercourse (POR = 2.2; 95% CL: 1.0, 4.6); and (4) an expressed desire for confidentiality among women seeking further information about acquired immunodeficiency syndrome (AIDS) prevention (POR = 2.1; 95% CL: 1.1, 4.0). Assessment of these factors may lead to better direction of HIV education programs, as well as identification and counseling of specific individuals at high risk for engaging in behaviors that can lead to HIV infection. Short, self-administered questionnaires provide confidential, rapid, and inexpensive means of generating baseline data for further interventions.

Acquired Immunodeficiency Syndrome↗
PubMed1994

A comparison of two radiotherapy regimens for the treatment of symptoms from advanced bladder cancer.

Pain and haematuria are two of the most distressing symptoms in patients with advanced bladder cancer. The aim of palliative radiotherapy is to relieve these symptoms with the minimum of stress to the patient and with minimal side effects. Two treatment regimens were studied: hypofractionated radiotherapy giving 1700 cGy in two fractions over 3 days and conventional palliative radiotherapy giving 4500 cGy in 12 fractions over 26 days. This study assesses 41 patients, all with Grade II-III T3-4 transitional cell carcinomas of the bladder treated between 1982 and 1989, presenting with haematuria and local pain. Two-fraction (hypofractionated) treatment was given to 22 patients and conventional palliative radiotherapy to 19; patients were selected by performance status. The effect on haematuria was assessed as cleared, intermittent or persistent. Pain was assessed by noting reduction in the need for opiate analgesia. Any side effect was recorded. In the patients receiving two-fraction radiotherapy, 59% had clearance of the haematuria and in 73% there was improvement of their pain, compared with 16% and 37% respectively in those receiving conventional palliation. Survival of the two groups was 9.77 months and 14.47 months respectively. Side effects were trivial in both regimens. Radiotherapy given in two fractions for patients in poor general health is well tolerated and less distressing than the standard palliative regimen with 12 fractions. Haematuria and pain were more effectively palliated than with conventional treatment, though survival was shorter. We conclude that hypofractionated radiotherapy may be the palliative treatment of choice and the study supports the need for a prospective assessment of this treatment approach.

Aged↗
PubMed1994

Perception of chirps by Sykes's monkeys (Cercopithecus albogularis) and humans (Homo sapiens).

Four Sykes's monkeys (Cercopithecus albogularis) and 4 humans (Homo sapiens) discriminated among 12 chirps presented in a repeating background paradigm. The test stimuli consisted of sets of 4 chirps recorded from Sykes's monkeys, red-tailed monkeys (C. ascanius), and small East African birds. Reaction times were submitted to a multidimensional scaling analysis. All monkey listeners perceived the bird chirps as similar to each other and distinct from the monkey calls, whereas 3 of the 4 human listeners had difficulty distinguishing the bird chirps from the monkey calls. Both human and monkey subjects tended to perceive Sykes's and red-tailed monkey calls as very similar to one another, but the degree of perceived similarity was greatest for the monkey listeners. The data suggest that the perceptual map of these calls is influenced by their biological significance in nature.

Animals↗
PubMed1993

The effect of corticosteroids for acute optic neuritis on the subsequent development of multiple sclerosis. The Optic Neuritis Study Group.

BACKGROUND: Optic neuritis is often the first clinical manifestation of multiple sclerosis, but little is known about the effect of corticosteroid treatment for optic neuritis on the subsequent risk of multiple sclerosis. METHODS: We conducted a multicenter study in which 389 patients with acute optic neuritis (and without known multiple sclerosis) were randomly assigned to receive intravenous methylprednisolone (250 mg every six hours) for 3 days followed by oral prednisone (1 mg per kilogram of body weight) for 11 days, oral prednisone (1 mg per kilogram) alone for 14 days, or placebo for 14 days. Neurologic status was assessed over a period of two to four years. The patients in the first group were hospitalized for three days; the others were treated as outpatients. RESULTS: Definite multiple sclerosis developed within the first two years in 7.5 percent of the intravenous-methyl-prednisolone group (134 patients), 14.7 percent of the oral-prednisone group (129 patients), and 16.7 percent of the placebo group (126 patients). The adjusted rate ratio for the development of definite multiple sclerosis within two years in the intravenous-methylprednisolone group was 0.34 (95 percent confidence interval, 0.16 to 0.74) as compared with the placebo group and 0.38 (95 percent confidence interval, 0.17 to 0.83) as compared with the oral-prednisone group. The beneficial effect of the intravenous-steroid regimen appeared to lessen after the first two years of follow-up. Signal abnormalities on magnetic resonance imaging (MRI) of the brain were a strong indication of risk for the development of definite multiple sclerosis (adjusted rate ratio in patients with three or more lesions, 5.53; 95 percent confidence interval, 2.41 to 12.66). The beneficial effect of treatment was most apparent in patients with abnormal MRI scans at entry. CONCLUSIONS: In patients with acute optic neuritis, treatment with a three-day course of high-dose intravenous methylprednisolone (followed by a short course of prednisone) reduces the rate of development of multiple sclerosis over a two-year period.

Acute Disease↗
PubMed1993

Analyzing preventive trials with generalized additive models.

Described a new class of nonparametric regression procedures called generalized additive models (Hastie and Tibshirani, 1991) for assessing intervention effects in mental health preventive field trials. Such models are often better than analysis of covariance models for examining intervention effects adjusted for one or more baseline characteristics and for assessing potential interactions between the intervention and baseline characteristics. Because of these advantages, generalized additive models are important tools analysts should consider in evaluating preventive field trials. We apply generalized additive models as well as more standard linear models to data from a preventive trial aimed at improving mental health and school performance outcomes through a universal intervention in first and second grades. Practical guidance is given to researchers regarding when generalized additive models would be beneficial.

Community Mental Health Services↗
PubMed1993

Effects of intrapartum stress on fetal adrenal function.

OBJECTIVE: Our purpose was to characterize the fetal adrenal response to acute intrapartum stress in otherwise uncomplicated pregnancies. STUDY DESIGN: Term infants (n = 61) diagnosed as having fetal distress during labor, as indicated by heart rate abnormalities, and delivered of women having normal pregnancies were pair-matched with 61 infants showing no signs of fetal distress or acidemia (controls) on the basis of gestational age and delivery method. Umbilical cord serum dehydroepiandrosterone sulfate and cortisol were measured, and the data were analyzed by two-tailed t test, Fisher's exact test, analysis of variance, and Tukey's multiple range test. RESULTS: Distressed infants had lower serum levels of dehydroepiandrosterone sulfate (3992 +/- 246 nmol/L, mean +/- SE) than control infants (4853 +/- 283 nmol/L); distressed infants also had higher levels of cortisol (412 +/- 17 nmol/L) than did control infants (299 +/- 16 nmol/L). The dehydroepiandrosterone sulfate/cortisol ratios in control infants (17.7 +/- 1.2) were almost twice those of distressed infants (10.8 +/- 0.9). These same relationships also were noted when the infant pairs were segregated according to whether delivered vaginally (21 pairs) or by cesarean section (40 pairs). The abnormalities in steroid levels in the distressed infants were independent of the presence or absence of acidemia. CONCLUSION: Intrapartum stress acutely alters fetal adrenal steroidogenesis, leading to increased production of cortisol and decreased secretion of dehydroepiandrosterone sulfate.

Adrenal Glands↗
PubMed1993

Effects of varying signal and noise levels on pure-tone frequency discrimination in humans and monkeys.

This study examined the effects of presenting various signal and noise levels on pure-tone frequency difference limens (FDLs) in humans and monkey. Signal levels for two frequencies of 500 Hz and 4 kHz were varied both in quiet and in noise. For the lower frequency of 500 Hz, the two species exhibited qualitatively divergent FDLs as level increased in quiet: FDLs decreased at high levels for humans, but increased for monkeys. In noise, differences between human and monkey FDLs were less pronounced. At 500 Hz, monkeys exhibited slightly lower FDLs in noise than in quiet. At the higher frequency of 4 kHz, under all conditions, FDLs for both species were qualitatively similar. Results are discussed in relation to (1) different use of "temporal" coding mechanisms by humans and monkeys at 500 Hz, and (2) similar use of "rate-place" coding mechanisms at 4 kHz.

Adult↗
PubMed1993

Effects of varying signal duration on pure-tone frequency discrimination in humans and monkeys.

This study examined the effects of varying signal duration and pulse repetition rate on pure tone frequency difference limens (FDLs) at 500 Hz and 4 kHz in humans and monkeys. Two experiments examined FDLs as a function of tone duration from 12-400 ms, using stimuli presented either with a constant pulse rate, or with a constant interstimulus interval. In both cases, at 500 Hz, human FDLs increased more than monkey FDLs as duration decreased from 400 to 12 ms. This effect resulted in monkey FDLs that were about 14 times larger than human FDLs at 400 ms, but only about 4 times larger at 12 ms. At 4 kHz, human and monkey FDLs showed more similar rates of increase as duration decreased. A third experiment examined FDLs at 500 Hz for a 100-ms tone as a function of pulse rate (1 per 250-2000 ms). Here, FDLs for humans and monkeys varied in a similar fashion, indicating that both species' sensitivity was similarly affected by manipulating temporal variables relating to memory load, rather than sensory coding. These data provide evidence that, at 500 Hz, humans have a qualitatively different pure tone frequency analyzing mechanism from monkeys, possibly based on better access to phase-locking mechanisms.

Acoustic Stimulation↗
PubMed1993

The use of hamstring tendons for anterior cruciate ligament reconstruction. Technique and results.

We feel that some of the current prejudice against use of hamstring tendon grafts for ACL reconstruction has not been justified if one critically reviews the literature. In this article, we have tried to provide the reader with our current indications, present our current surgical technique, and review some of the outcome studies involving use of the hamstring tendons for ACL reconstruction. We also feel that some of the poor results of hamstring tendon ACL reconstructions previously reported resulted from the use of inadequate strength grafts (single-stranded grafts) and lack of rigid fixation on both ends of the graft (usually secondary to inadequate graft length). We feel that the technique described in this article addresses both of these issues. It is our clinical impression that, in appropriately selected patients, this technique produces stability and functional outcome similar to that obtained with patellar tendon grafts but results in less postoperative pain, a quicker return of quadriceps muscle function, and less donor site morbidity.

Animals↗