Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial.

BACKGROUND: Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial. OBJECTIVE: To compare the analgesic and cognitive effects of opioids with those of TCA and placebo in the treatment of PHN. METHODS: Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication. RESULTS: Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02). CONCLUSIONS: Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.

Effectiveness of a home intervention for perceived child behavioral problems and parenting stress in children with in utero drug exposure.

OBJECTIVE: To determine if a home-based nurse intervention (INT), focusing on parenting education/skills and caregiver emotional support, reduces child behavioral problems and parenting stress in caregivers of in utero drug-exposed children. DESIGN: Randomized clinical trial of a home-based INT. SETTINGS: Two urban hospital newborn nurseries; homes of infants (the term infant is used interchangeably in this study with the term child to denote those from birth to the age of 36 months); and a research clinic in Baltimore, Md. PARTICIPANTS: In utero drug-exposed children and their caregivers (N = 100) were examined when the child was between the ages of 2 and 3 years. Two groups were studied: standard care (SC) (n = 51) and INT (n = 49). INTERVENTION: A home nurse INT consisting of 16 home visits from birth to the age of 18 months to provide caregivers with emotional support and parenting education and to provide health monitoring for the infant. MAIN OUTCOME MEASURES: Scores on the Child Behavior Checklist and the Parenting Stress Index. RESULTS: Significantly more drug-exposed children in the SC group earned t scores indicative of significant emotional or behavioral problems than did children in the INT group on the Child Behavior Checklist Total (16 [31%] vs 7 [14%]; P =.04), Externalizing (19 [37%] vs 8 [16%]; P =.02), and Internalizing (14 [27%] vs. 6 [12%]; P =.05) scales and on the anxiety-depression subscale (16 [31%] vs. 5 [10%]; P =.009). There was a trend (P =.06) in more caregivers of children in the SC group reporting higher parenting distress than caregivers of children in the INT group. CONCLUSIONS: In utero drug-exposed children receiving a home-based nurse INT had significantly fewer behavioral problems than did in utero drug-exposed children receiving SC (P =.04). Furthermore, those caregivers receiving the home-based INT reported a trend toward lower total parenting distress compared with caregivers of children who received SC with no home visits.

Brain blood flow changes in depressed patients treated with interpersonal psychotherapy or venlafaxine hydrochloride: preliminary findings.

BACKGROUND: Functional brain imaging studies in major depression have suggested abnormalities of areas, including the frontal cortex, cingulate gyrus, basal ganglia, and temporal cortex. We hypothesized that venlafaxine hydrochloride and interpersonal psychotherapy (IPT) might each alter brain blood flow in some or all of these areas on sequential single photon emission computed tomography (SPECT) scans. METHODS: Twenty-eight men and women aged 30 to 53 years with a DSM-IV major depressive episode, a 17-item Hamilton Rating Scale for Depression (HAM-D) rating of 18 or higher, and antidepressant-naive for at least 6 months were studied. After baseline (99m)technetium-hexa-methyl-propylene-amine-oxime scan, 1-T magnetic resonance imaging, and psychometric ratings, patients were assigned to different treatments. Thirteen patients had 1-hour weekly sessions of IPT from the same supervised therapist (E.M.). Fifteen patients took 37.5 mg twice-daily of venlafaxine hydrochloride. Single-photon emission computed tomography scans and ratings were repeated at 6 weeks. RESULTS: Both treatment groups improved substantially, more so with venlafaxine (mean [SD] HAM-D scores at pretreatment: IPT, 22.7 [2.7], and venlafaxine, 22.4 [3.1]; and posttreatment: IPT, 16.2 [7.1], and venlafaxine, 10.9 [8.6]). No patients had structural brain abnormalities. On analysis with statistical parametric mapping 96, the venlafaxine group showed right posterior temporal and right basal ganglia activation (P =.01), while the IPT group had limbic right posterior cingulate and right basal ganglia activation (P =.01). CONCLUSIONS: This preliminary investigation has shown limbic blood flow increase with IPT yet not venlafaxine, while both treatments demonstrated increased basal ganglia blood flow. This was, however, a short trial with a small sample, no control group, and different symptom reduction in the 2 groups.

Cognitive changes 5 years after coronary artery bypass grafting: is there evidence of late decline?

OBJECTIVE: To determine the long-term (preoperative to 5 years postoperative) and late (1-5 years postoperative) changes in cognitive test performance in patients after coronary artery bypass grafting. SETTING: The departments of surgery and neurology at The Johns Hopkins University School of Medicine, Baltimore, Md. PATIENTS: A group of 102 patients who completed preoperative and follow-up cognitive testing up to 5 years after coronary artery bypass grafting. MAIN OUTCOME MEASURES: A battery of neuropsychological tests, assessing 8 cognitive domains (attention, language, verbal and visual memory, visuoconstruction, executive function, and psychomotor and motor speed), was administered preoperatively and at 1 month, 1 year, and 5 years postoperatively. RESULTS: Significant changes in neuropsychological test scores from baseline to 5 years were observed in only 3 of the 8 domains: there were declines in visuoconstruction and psychomotor speed and an improvement in executive function. When the period from baseline to 5 years was divided into 2 intervals, we found that cognitive test scores generally improved from baseline to 1 year. By contrast, between 1 and 5 years, there was significant decline in all cognitive domains except for attention and executive function. Some potential explanatory covariates (demographic, medical history, and surgery variables) were associated with changes from baseline to 5 years in some cognitive domains, but few covariates were statistically significant in more than 1 cognitive domain. CONCLUSIONS: The change in cognitive test performance between baseline and 5 years is likely related to several factors, including low baseline performance and practice effects. The significant decline in performance between 1 and 5 years, however, raises the possibility that a late cognitive decline may be occurring in this population. Additional studies, with the use of a nonsurgical control group, are needed to determine if the observed cognitive decline is related to bypass surgery itself, normal aging in a population with cardiovascular risk factors, or some combination of these and other factors.

Effects of pathway and neuronal aging on the specificity of motor axon regeneration.

Youth is a strong predictor of functional recovery after peripheral nerve repair, while adulthood is commonly associated with poor outcome. Identification of the factors responsible for this difference could form the basis for strategies to improve regeneration in adults. Preferential reinnervation of motor pathways by motor axons (PMR) occurs strongly in young rats, but is often absent in older animals, and thus parallels the overall trend for superior results in young individuals. These experiments evaluate the individual contributions of peripheral nerve age and motoneuron age to the decline in regeneration specificity (PMR) which accompanies the aging process. The femoral nerves of young and old Lewis rats were removed as inverted "Y" grafts from the femoral trunk proximally to the terminal muscle and cutaneous branches distally. These grafts were transferred from (1) old to young, (2) young to old, (3) old to old, and (4) young to young bilaterally in 10 individuals per group. After 8 weeks of regeneration, reinnervation of cutaneous and muscle branches was assessed by dual labeling with HRP and Fluoro-Gold. Motor neuron regeneration was random in old to old (mean muscle branch (M) = 159, mean cutaneous branch (C) = 168), but PMR was seen when young pathways were used in old animals (M = 163, C = 116). PMR was vigorous when either type of graft was used in young animals (young graft, M = 218, C = 134; old graft, M = 204, C = 127). In this model, motoneuron age appears to be the primary determinant of specificity. However, the pathway also makes significant contributions, as shown by the ability of young pathways to generate specificity in old animals. Manipulation of graft Schwann cell behavior might therefore be an appropriate strategy to improve outcome in older individuals.

Contributions of pathway and neuron to preferential motor reinnervation.

Motor axons regenerating after transection of mixed nerve preferentially reinnervate distal muscle branches, a process termed preferential motor reinnervation (PMR). Motor axon collaterals appear to enter both cutaneous and muscle Schwann cell tubes on a random basis. Double-labeling studies suggest that PMR is generated by pruning collaterals from cutaneous pathways while maintaining those in motor pathways (the "pruning hypothesis"). If all collaterals projecting to muscle are saved, then stimulation of regenerative sprouting should increase specificity by increasing the number of motoneurons with at least one collateral in a muscle pathway. In the current experiments, collateral sprouting is stimulated by crushing the nerve proximal to the repair site before suture, a maneuver that also conditions the neuron and predegenerates the distal pathway. Control experiments are performed to separate these effects from those of collateral generation. Experiments were performed on the rat femoral nerve and evaluated by exposing its terminal cutaneous and muscle branches to HRP or Fluoro-Gold. Crush proximal to the repair site increased motor axon collaterals at least fivefold and significantly increased the percentage of correctly projecting motoneurons, consistent with the pruning hypothesis. Conditioning the nerve with distal crushes before repair had no effect on specificity. A graft model was used to separate the effects of collateral generation and distal stump predegeneration. Previous crush of the proximal femoral nerve significantly increased the specificity of fresh graft reinnervation. Stimulation of regenerative collateral sprouting thus increased PMR, confirming the pruning hypothesis. However, this effect was overshadowed by the dramatic specificity with which predegenerated grafts were reinnervated by fresh uncrushed proximal axons. These unexpected effects of predegeneration on specificity could involve a variety of possible mechanisms and warrant further study because of their mechanistic and clinical implications.

Industry-wide study of mortality of pulp and paper mill workers.

A study of pulp and paper mill workers indicated low risks of death from all causes (standardized mortality ratio (SMR) = 0.74) and all cancers (SMR = 0.81) compared with U.S. rates. The leukemia death rate in workers was not higher than the U.S. rate but was higher than the rate in county populations surrounding mills. Workers whose last jobs were in the finishing areas of the mills had an elevated SMR for liver cancer. An internal comparison of occupational characteristics indicated that workers employed in mills using other chemical pulping operations had significantly elevated mortality from all causes, all cancers, heart disease, lymphomas, and brain cancers. Lung cancer mortality was elevated in mills using kraft pulping. The internal comparisons confirmed the association between work in finishing and the risk of liver cancer. This study was designed to investigate whether pulp and paper mill workers have any risks that would indicate the need for studies detailing exposures.

Improving stereological estimates for the volume of structures identified in three-dimensional arrays of spatial data.

Investigators frequently measure the volumes of anatomic structures. These volumes can answer important scientific questions such as whether a structure differs between two groups, which structures a disease affects, or how the size of a structure relates to its function. Magnetic resonance (MR) imaging, X-ray computed tomography and confocal microscopy are used more and more frequently in anatomic studies; each yields information that is spatially organized as a three-dimensional array. We describe how to improve an efficient stereological technique for estimating the volumes of structures that are identifiable in these arrays. As an example, we apply the technique to measuring brain volumes by MR imaging. We then show how the results of the technique may be used for solving a typical problem in experimental design. This technique is applicable to a wide range of experimental problems. We discuss its limitations and offer some suggestions and observations relating to its use.

Planum temporale asymmetry reversal in schizophrenia: replication and relationship to gray matter abnormalities.

OBJECTIVE: The planum temporale, the posterior superior surface of the superior temporal gyrus, is a highly lateralized brain structure involved with language. In schizophrenic patients the authors previously found consistent reversal of the normal left-larger-than-right asymmetry of planum temporale surface area. The original subjects plus new patients and comparison subjects participated in this effort to replicate and extend the prior study. METHOD: High-resolution magnetic resonance imaging of 28 schizophrenic patients and 32 group-matched normal subjects was performed. The authors measured planum temporale surface area, gray matter volume underlying the planum temporale, and gray matter thickness. Asymmetry indices for areas and volumes were calculated. RESULTS: Overall gray matter and total brain volume were not significantly smaller in the patients than in the comparison subjects. As previously reported, there was striking reversal of the normal asymmetry for planum temporale surface area in the male and female schizophrenic subjects. Bilaterally, gray matter volume beneath the planum temporale was smaller in the schizophrenic patients, and the gray matter thickness of the right planum temporale was only 50% of the comparison value. Volume of planum temporale gray matter did not show significant asymmetry in either group. CONCLUSIONS: This study extends the finding of reversed planum temporale surface area asymmetry in schizophrenic patients and clarifies its relationship to underlying gray matter volume. Although right planum temporale surface area is larger than normal in schizophrenia, gray matter volume is less than the comparison value; thus, gray matter thickness is substantially less than normal.

A portable mouth pressure meter.

The design and function of a device for bedside measurement of maximum static respiratory pressures is reported. The ability to measure maximum inspiratory and expiratory pressures allows a simple means of monitoring respiratory muscle weakness in both acute and chronic conditions.

Racial differences in the cause-specific prevalence of blindness in east Baltimore.

BACKGROUND: Bilateral blindness unrelated to simple refractive error is twice as prevalent among blacks as among whites, although the difference narrows among the elderly. The reasons for this race- and age-related pattern are uncertain. METHODS AND RESULTS: A randomly selected, stratified, multistage cluster sample of 2395 blacks and 2913 whites 40 years of age and older in East Baltimore underwent detailed ophthalmic examinations by a single team. We identified 64 subjects who were blind in both eyes. The leading causes of blindness were unoperated senile cataract (accounting for blindness in 27 of the total of 128 eyes), primary open-angle glaucoma (17 eyes), and age-related macular degeneration (16 eyes). Together, these three disorders accounted for 47 percent of all blindness in this sample. Unoperated cataract accounted for 27 percent of all blindness among blacks, among whom it was four times more common than among whites; whites were almost 50 percent more likely than blacks to have undergone cataract extraction before the age of 80 (P less than 0.002). Primary open-angle glaucoma accounted for 19 percent of all blindness among blacks; it was six times as frequent among blacks as among whites and began 10 years earlier, on average. By contrast, age-related macular degeneration resulting in blindness was limited to whites, among whom it was the leading cause of blindness (prevalence, 2.7 per 1000; 95 percent confidence interval, 1.2 to 5.4); it affected 3 percent of all white subjects 80 years of age or older. CONCLUSIONS: The pattern of blindness in urban Baltimore appears to be different among blacks and whites. Whites are far more likely to have age-related macular degeneration, and blacks to have primary open-angle glaucoma. The high rate of unoperated cataracts among younger blacks and among elderly subjects of both races suggests that health services are underused. Half of all blindness in this urban population is probably preventable or reversible.

Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey.

OBJECTIVE: --To compare the prevalence of primary open-angle glaucoma between black and white Americans. DESIGN, SETTING, AND PARTICIPANTS: --The design was a population-based prevalence survey of a noninstitutionalized black and white population aged 40 years or older from the eastern and southeastern health districts of Baltimore, Md. A multistage random sampling strategy was used to identify 7104 eligible participants, of whom 5308 (2395 blacks, 2913 whites) received an ophthalmologic screening examination. Those with abnormalities were referred for definitive diagnostic evaluation. MAIN OUTCOME MEASURE: --Primary open-angle glaucoma was defined based on evidence of glaucomatous optic nerve damage, including abnormal visual fields and/or severe optic disc cupping, and was independent of intraocular pressure. MAIN RESULTS: --Age-adjusted prevalence rates for primary open-angle glaucoma were four to five times higher in blacks as compared with whites. Rates among blacks ranged from 1.23% in those aged 40 through 49 years to 11.26% in those 80 years or older, whereas rates for whites ranged from 0.92% to 2.16%, respectively. There was no difference in rates of primary open-angle glaucoma between men and women for either blacks or whites in this population. Based on these data, an estimated 1.6 million persons aged 40 years or older in the United States have primary open-angle glaucoma. CONCLUSIONS: --Black Americans are at higher risk of primary open-angle glaucoma than their white neighbors. This may reflect an underlying genetic susceptibility to this disease and indicates that additional efforts are needed to identify and treat this sight-threatening disorder in high-risk communities.

Blindness and visual impairment in an American urban population. The Baltimore Eye Survey.

Data on the prevalence of blindness and visual impairment in multiracial urban populations of the United States are not readily available. The Baltimore Eye Survey was designed to address this lack of information and provide estimates of prevalence in age-race subgroups that had not been well studied in the past. A population-based sample of 5300 blacks and whites from east Baltimore, Md, received an ophthalmologic screening examination that included detailed visual acuity measurements. Blacks had, on average, a twofold excess prevalence of blindness and visual impairment than whites, irrespective of definition. Rates rose dramatically with age for all definitions of vision loss, but there was no difference in prevalence by sex. More than 50% of subjects improved their presenting vision after refractive correction, with 7.5% improving three or more lines. Rates in Baltimore are as high or higher than those reported from previous studies. National projections indicate that greater than 3 million persons are visually impaired, 890,000 of whom are bilaterally blind by US definitions.

Health and mental health problems of homeless men and women in Baltimore.

A study of homeless people in Baltimore, Md, focused on their health and other characteristics, with special emphasis on their needs for services. In the first stage, 298 men and 230 women were randomly selected from the missions, shelters, and jail in Baltimore to respond to a baseline interview that provided extensive sociodemographic and health-related data. In the second stage, a subsample of 203 subjects was randomly selected from the baseline survey respondents to have systematic psychiatric and physical examinations. Data are presented from both stages. Data from the first stage demonstrate, among other things, the high levels of disaffiliation of this population and their heavy involvement in substance abuse. Data from the clinical examinations demonstrate the high prevalence of mental illnesses and other psychiatric disorders and of a wide range of physical disorders and confirm the high prevalence of alcohol abuse disorders. The high rates of comorbidity of these conditions is demonstrated and data are provided on the subjects' needs for mental health and substance abuse services.

Evidence and scientific research.

This commentary reviews the arguments for and against the use of p-values put forward in the Journal and other forums, and shows that they are all missing both a measure and concept of "evidence." The mathematics and logic of evidential theory are presented, with the log-likelihood ratio used as the measure of evidence. The profoundly different philosophy behind evidential methods (as compared to traditional ones) is presented, as well as a comparative example showing the difference between the two approaches. The reasons why we mistakenly ascribe evidential meaning to p-values and related measures are discussed. Unfamiliarity with the technology and philosophy of evidence is seen as the main reason why certain arguments about p-values persist, and why they are frequently contradictory and confusing.

Micturition detection switch.

Micturating renograms often need to be carried out on children, with whom difficulty may be experienced in synchronizing onset of micturition with camera and computer acquisition. A flow detection system has been developed which will automate these acquisitions, resulting in far fewer false starts or lost studies. The unit was developed specifically for the camera/computer system in our department (IGE 400T and DEC 11/34) but with only minor modifications would be suitable for interfacing to other equipment. It is a free standing unit which requires no modifications of the camera or computer circuitry apart from access to the remote start buttons.

A rate pressure product meter. A new module for use with the Simonsen & Weel System 8000 monitors.

A prototype rate pressure product module has been constructed for use with Simonsen and Weel Series 8000 monitors. The importance of method of display of rate pressure product is stressed.

Heparin-associated thrombocytopenia: a comparison of three heparin preparations.

We performed a prospective, double-blind study of the incidence of thrombocytopenia in 149 patients randomly assigned to treatment with one of three heparin preparations--from bovine lung from intestinal-mucosa A, or from intestinal-mucosa O. Thrombocytopenia developed in 21 patients (platelets, < 100 x 10(9) per liter): 13 of the 50 receiving bovine lung heparin, four of 45 receiving intestinal-mucosa-A heparin, and four of 54 receiving intestinal-musoca-O heparin (P < 0.005). There was a significantly increased incidence of thrombocytopenia in the bovine-lung group (P < 0.002); estimated incidence rates after nine days of treatment were 24 per cent in this group and 7 per cent in the combined intestinal-mucosa A and O groups. Thrombocytopenia appeared in the bovine-lung group on days 3 to 16, in the intestinal-mucosa-A groups on Days 4 to 12, and in the intestinal-mucosa-O group on Days 3 to 7; it disappeared in all groups three to eight days after discontinuation of heparin. A total of 121 patients were subsequently given warfarin for four to six months, and thrombocytopenia was not observed.