Biomedical subjects
Publications and source records attributed to W L Marsh.
The knowledge of the potential clinical significance of alloantibodies to blood group antigens is essential for selecting appropriate red blood cell (RBC) products for transfusion. This article provides a summary of clinical and technical aspects of many alloantibodies.
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The vascular actions of the lipophilic gap junction inhibitors 18alpha-glycyrrhetinic acid (18alpha-GA), 18beta-glycyrrhetinic acid (18beta-GA) and the water-soluble hemisuccinate derivative of 18beta-GA, carbenoxolone, were investigated in preconstricted rings of rabbit superior mesenteric artery. EDHF-type relaxations to acetylcholine (ACh), observed in the presence of 300 microM NG-nitro-L-arginine methyl ester (L-NAME) and 10 microM indomethacin, were attenuated by preincubation with 18alpha-GA (to 100 microM), 18A-GA (to 10 microM) or carbenoxolone (to 300 microM) in a concentration-dependent fashion. By contrast, none of these agents affected responses to sodium nitroprusside, an exogeneous source of NO, and relaxations evoked by ACh in the absence of L-NAME were attenuated by only approximately 20%. 18alpha-GA exerted no direct effect on vessel tone, whereas 18beta-GA and carbenoxolone caused relaxations which were maximal at approximately 1 and approximately 10 mM, respectively. Relaxations to carbenoxolone were attenuated by endothelial denudation and by incubation with L-NAME, whereas those to 18beta-GA were unaffected. In conclusion, all three agents inhibit EDHF-type relaxations evoked by ACh, providing further evidence for the involvement of gap junctions in such responses. Unlike 18alpha-GA, carbenoxolone and 18beta-GA possess intrinsic vasorelaxant activity which in the case of carbenoxolone involves functional enhancement of NO activity in addition to direct effects on vascular smooth muscle.
Extranodal Hodgkin disease presenting as a primary localized neoplasm is uncommon, with rare case reports describing primary sites other than lymph nodes. The gastrointestinal tract is the most frequent site of involvement by extranodal Hodgkin disease, typically involving the stomach or small bowel. To date, we have been able to find only one fully documented case of Hodgkin disease of the sigmoid colon confirmed by immunohistochemical studies. We report a case of extranodal Hodgkin disease involving the transverse colon, presenting as inflammatory bowel disease and documented by light microscopic, immunohistochemical, cytogenetic, and molecular studies.
OBJECTIVE: The investigation of attention-deficit/hyperactivity disorder (ADHD) in girls raises complex questions of referral bias and selection criteria. The authors sought to determine whether they could recruit a research sample of comparably affected girls using a combination of sex-independent diagnostic criteria and sex-normed cutoffs on teacher ratings. They also report on the largest placebo-controlled crossover comparison of methylphenidate and dextroamphetamine in girls with ADHD. METHOD: Subjects were 42 girls with DSM-III-R/DSM-IV ADHD (combined type) contrasted to 56 previously studied boys with ADHD on comorbid diagnoses, behavioral ratings, psychological measures, psychiatric family history, and stimulant drug response. RESULTS: Girls with ADHD were statistically indistinguishable from comparison boys on nearly all measures. Girls exhibited robust beneficial effects on both stimulants, with nearly all (95%) responding favorably to one or both drugs in this short-term trial. Dextroamphetamine produced significantly greater weight loss than methylphenidate. CONCLUSIONS: This highly selected group of ADHD girls was strikingly comparable with comparison boys on a wide range of measures. The results confirm that girls with ADHD do not differ from boys in response to methylphenidate and dextroamphetamine and that both stimulants should be tried when response to the first is not optimal.
Although the etiology of attention-deficit/hyperactivity disorder (ADHD) is likely multifactorial, family, adoption, and twin studies suggest that genetic factors contribute significantly. Polymorphisms of the dopamine 4 receptor (DRD4) affect receptor binding, and one allele with seven tandem repeats in exon 3 (DRD4*7R) has been associated with ADHD. We examined this putative association in 41 children with severe ADHD and 56 healthy controls who were group matched for ethnicity and sex. The frequency of the DRD4*7R allele did not vary by diagnosis (0.220 vs 0.205 in patients and controls, respectively). Behavioral and brain anatomic MRI measures, previously found to discriminate patients from controls, did not differ significantly between subjects having and those lacking a DRD4*7R allele. These data do not support the reported association between DRD4*7R and the behavioral or brain morphometric phenotype associated with ADHD.
For many neoplasms, the status of regional lymph nodes is a critical prognostic factor with direct therapeutic implications. Despite the importance of lymph node status, there is no consensus on whether lymph nodes from node dissections should be submitted in their entirety. To study this issue, for a 4-month period, all lymph nodes from node dissections were submitted in their entirety. The larger nodes were submitted systematically to determine whether the additional tissue blocks contained metastases that were not identified in the initial tissue block. We also analyzed the cost of submitting, processing, and interpreting these extra blocks. During the study period, 149 patients underwent lymph node dissections, yielding a total of 2,915 lymph nodes. Submitting the larger nodes in their entirety resulted in processing 808 additional tissue blocks that demonstrated a total of 9 additional metastases in 7 patients. In 2 of these patients, the additional metastases changed the stage of the neoplasm and may have contributed to an alteration in therapy. By using median salary figures, the estimated cost for submitting, processing, and interpreting the additional blocks was $5,935.62. Whether the additional positive nodes justify this cost should be determined by individual pathology practices.
Posttransplantation lymphoproliferative disorder occurs in 1.5% to 13% of heart transplant recipients and rarely involves the allograft. We report a case of posttransplantation lymphoproliferative disorder restricted to the mitral valve in a heart transplant recipient. Thirteen cases of cardiac allograft involvement by posttransplantation lymphoproliferative disorder are reported in the literature. None are restricted to the allograft. Five specify sites of cardiac involvement. Valvular masses without infection necessitate evaluation for posttransplantation lymphoproliferative disorder involvement of the cardiac allograft valve.
OBJECTIVE: To examine the relation between specific frontostriatal structures (prefrontal cortex and basal ganglia) and response inhibition deficits observed in attention-deficit/hyperactivity disorder (ADHD). METHOD: Children with ADHD and age-matched normal controls were scanned using magnetic resonance imaging (MRI) and tested on three response inhibition tasks. Behavioral performance was correlated with MRI-based anatomical measures of frontostriatal circuitry (prefrontal cortex and basal ganglia) implicated in ADHD. RESULTS: First, significant differences in performance by children with ADHD and normal volunteers were observed on all three response inhibition tasks. Second, performance on these tasks correlated only with those anatomical measures of frontostriatal circuitry observed to be abnormal in children with ADHD (e.g., the region of the prefrontal cortex, caudate, and globus pallidus, but not the putamen) in the authors' previous study. Third, significant correlations between task performance and anatomical measures of the prefrontal cortex and caudate nuclei were predominantly in the right hemisphere, supporting a role of right frontostriatal circuitry in response inhibition and ADHD. CONCLUSION: The data suggest a role of the right prefrontal cortex in suppressing responses to salient, but otherwise irrelevant events while the basal ganglia appear to be involved in executing these behavioral responses.
OBJECTIVE: To determine the effects of methylphenidate (MPH) and dextroamphetamine (DEX) on tic severity in boys with attention-deficit/hyperactivity disorder (ADHD) comorbid with Tourette's syndrome. METHOD: A 9-week, placebo-controlled, double-blind crossover using a wide range of doses was completed by 20 subjects in three cohorts. RESULTS: Relatively high doses of MPH and DEX in the first cohort produced significant increases in tic severity which were sustained on higher doses of DEX but which attenuated on MPH. Overall, 14 of 20 subjects continued stimulant treatment for 1 to 3 years, generally in combination with other psychotropics. Stimulant-associated adverse effects, including tic exacerbations, were reversible in all cases. CONCLUSION: A substantial minority of comorbid subjects had consistent worsening of tics on stimulants, although the majority experienced improvement in ADHD symptoms with acceptable effects on tics. MPH was better tolerated than DEX.
Deficits in sensorimotor gating, defined by prepulse inhibition (PPI), have been associated with subcortical dopaminergic overactivity in animal and clinical studies. Utilizing supraorbital nerve electrical stimulation, we produced adequate blink responses and measured decreases in amplitude resulting from electric prestimuli just above sensory threshold. Seven boys comorbid for attention-deficit hyperactivity disorder (ADHD) and a tic disorder had significantly reduced PPI, compared to 14 screened controls and seven boys with ADHD alone. If independently replicated, these results may reflect greater neurologic immaturity in these comorbid subjects. Alternatively, these findings, together with other converging lines of evidence, suggest that deficient pallidal inhibition may be etiologically related to tic and movement disorders.
BACKGROUND: Anatomic magnetic resonance imaging (MRI) studies of attention-deficit hyperactivity disorder (ADHD) have been limited by small samples or measurement of single brain regions. Since the neuropsychological deficits in ADHD implicate a network linking basal ganglia and frontal regions, 12 subcortical and cortical regions and their symmetries were measured to determine if these structures best distinguished ADHD. METHODS: Anatomic brain MRIs for 57 boys with ADHD and 55 healthy matched controls, aged 5 to 18 years, were obtained using a 1.5-T scanner with contiguous 2-mm sections. Volumetric measures of the cerebrum, caudate nucleus, putamen, globus pallidus, amygdala, hippocampus, temporal lobe, cerebellum; a measure of prefrontal cortex; and related right-left asymmetries were examined along with midsagittal area measures of the cerebellum and corpus callosum. Interrater reliabilities were .82 or greater for all MRI measures. RESULTS: Subjects with ADHD had a 4.7% smaller total cerebral volume (P = .02). Analysis of covariance for total cerebral volume demonstrated a significant loss of normal right > left asymmetry in the caudate (P = .006), smaller right globus pallidus (P = .005), smaller right anterior frontal region (P = .02), smaller cerebellum (P = .05), and reversal of normal lateral ventricular asymmetry (P = .03) in the ADHD group. The normal age-related decrease in caudate volume was not seen, and increases in lateral ventricular volumes were significantly diminished in ADHD. CONCLUSION: This first comprehensive morphometric analysis is consistent with hypothesized dysfunction of right-sided prefrontal-striatal systems in ADHD.
Central dopaminergic activity has been assumed to play a role in the efficacy of stimulant drugs in attention deficit/hyperactivity disorder (ADHD), although supporting evidence has been scant. This study examined baseline cerebrospinal fluid (CSF) of boys with ADHD in relation to response to three different stimulant drugs. Forty five boys with DSM-III-R-diagnosed ADHD had a lumbar puncture before double-blind trials of methylphenidate, dextroamphetamine, and placebo. Sixteen also received pemoline as part of a subsequent open trial. Stepwise linear regressions determined significant predictors of drug response. Our prior report of a positive significant correlation between CSF homovanillic acid (HVA) and ratings of hyperactivity on placebo was replicated in a new sample of 20 boys. After baseline symptom severity, CSF HVA was the best predictor of stimulant drug response, with significant independent contribution to four of the ten measures of hyperactivity that changed significantly with medication. Higher HVA predicted better drug response, and lower HVA was associated with worsening on some measures. This supports the mediating role of central dopaminergic activity in stimulant drug efficacy in childhood hyperactivity.
Recently there have been several editorials suggesting that breast biopsies with small or nonpalpable lesions should not be subjected to frozen section examination. In this study, the approach of routinely performing frozen sections on all breast biopsies was compared to the recommended approach of performing frozen sections only on cases with gross lesions < 1.0 cm. From July 1, 1992 through June 30, 1993, there were 444 breast biopsies submitted. Nearly all of these (98%) had frozen sections performed. Among these cases, there were 14 false-negative frozen section diagnoses equating to a frozen section sensitivity of 84%, and a frozen section false-negative rate of 3.3%. From July 1, 1994 through June 30, 1995, there were 601 breast biopsies submitted. Of these cases, 310 contained a gross lesion > 1.0 cm and were subjected to frozen section examination. The remaining 291 cases contained either no distinct lesion or a gross lesion < 1.0 cm. These cases were not frozen. Among the 310 cases that were frozen, there were 3 false-negative frozen section diagnoses equating to a frozen section sensitivity of 96%, and a frozen section false-negative rate of 1.0%. These findings indicate that careful gross examination combined with selective freezing of only cases containing a gross lesion > 1.0 cm improves frozen section accuracy. This study provides statistical support for previous recommendations that frozen section examination should be limited to cases with distinct gross lesions > 1.0 cm.
Three separate groups, using MRI, have reported basal ganglia abnormalities in Tourette's syndrome (TS). We found similar abnormalities in boys with attention-deficit/hyperactivity disorder (ADHD). Because TS and ADHD are frequently comorbid, we contrasted ADHD boys with and without TS along with control subjects. As expected, we found a significant loss of the normal globus pallidus asymmetry in the patients, but presence or absence of TS did not differentiate the ADHD groups. We conclude that accounting for ADHD comorbidity will be important in future TS morphometric studies.
BACKGROUND: As part of a broader series of studies on unwanted repetitive behaviors, DSM-IV stereotypic movement disorder (SMD) was examined in an intellectually normal population. Repetitive nonfunctional behaviors, or stereotypies, are expressed during early normal development but have not been described in adults without severe psychiatric or intellectual impairment. METHOD: Lifetime and current psychiatric Axis I diagnoses were determined by structured and clinical interviews in subjects who responded to a newspaper advertisement that specifically mentioned rocking and head banging. RESULTS: Of 52 potential subjects who were screened by telephone, 32 had been previously diagnosed with an Axis I psychiatric disorder, which presumably accounted for the repetitive behavior, or were otherwise excluded. Of 20 who were interviewed in person, 12 met DSM-IV criteria for SMD; rocking or thumb sucking was present in 8 of these 12. Four of 8 rockers had a first-degree relative who had a lifetime history of a similar repetitive behavior. A lifetime history of an affective or anxiety disorder was found for 11 of 12 SMD subjects. CONCLUSION: DSM-IV stereotypic movement disorder can be diagnosed in intellectually normal individuals. Although sampling bias was probable, prominent stereotypies in individuals meeting the DSM-IV criteria for stereotypic movement disorder, which are narrower than the DSM-III-R criteria for stereotypy/habit disorder, seem likely to include rocking and thumb sucking. The likelihood of persistence of these behaviors, which are developmentally appropriate in infancy, may be enhanced by comorbidity with anxiety or affective disorders.