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Biomedical subjects

H Goldman

Publications and source records attributed to H Goldman.

At least 55 records · Page 3Linked to original sources

Schizophrenia and the life cycle.

We reframe the longitudinal treatment of persons with schizophrenia from the perspective of phases in adult development. This approach articulates the need for different interventions of varying intensities over the person's lifetime. The paper discusses the implications of an adult developmental perspective in managing pharmacologic treatment and psychosocial interventions, and in reallocating financial resources for improved long-term outcomes. This perspective is especially useful in the context of a comprehensive community mental health program permitting access to a continuum of services throughout the lifecycle.

Adolescent↗

Cardiopulmonary complications during laparoscopy: two case reports.

Laparoscopic surgery is growing in popularity. As a result, laparoscopic procedures are being done on a broader and older patient population. These patients may have underlying cardiopulmonary disease that predisposes them to complications not seen in younger patients. Anesthesiologists should be aware of this possibility and of the problems inherent to the pneumoperitoneum necessary for laparoscopy. We present two cases involving elderly patients to illustrate cardiopulmonary complications that can occur during establishment or maintenance of the increased intra-abdominal pressures required for laparoscopic surgery. The first case describes a patient who developed bradycardia and asystole during insufflation for a laparoscopic hernia repair. The second case involves severe hypercarbia and a pneumothorax due to massive subcutaneous emphysema that developed during a laparoscopic colon resection.

Adenocarcinoma↗

Global function scales.

There is a close relationship between impairment of global functioning and mental illness. However valid measurement of global functioning is difficult, and there is no perfect scale. The instruments reviewed in this paper illustrate a range of different approaches. Despite the inherent difficulties the measurement of functioning is a critical domain in mental health evaluative research.

Activities of Daily Living↗

Interpretation of large intestinal mucosal biopsy specimens.

The development of flexible endoscopes has led to a great increase in the examination and mucosal biopsy evaluation of all portions of the large intestine and rectum. Examinations are now performed not only for the determination of diagnosis but also for the monitoring of the course of a wide variety of conditions and for the early detection of complications. This review concentrates on the uses and interpretations of such biopsies in a large number of inflammatory conditions, with special emphasis on the correlations with clinical and functional features. Illustrated are examples of infections, idiopathic inflammatory bowel disease (IBD), vascular disorders, motor and mechanical conditions, toxic and physical reactions, and other inflammatory conditions. Mucosal biopsy specimens also are obtained to identify dysplasia and to evaluate mass lesions, and these subjects are well covered in other articles within this symposium. In patients with chronic disorders multiple examinations are now expected to follow the course of the disease and to detect and correct any complications at an early stage. The exact reasons for the endoscopy and relevant clinical data are essential for the optimal analysis of these mucosal biopsy specimens.

Biopsy↗

alpha-Phenyl-tert-butyl-nitrone inhibits free radical release in brain concussion.

Traumatic brain injury (TBI) is one of the important causes of mortality and morbidity. The pathogenesis of the underlying brain dysfunction is poorly understood. Recent data have suggested that oxygen free radicals play a key role in the primary and secondary processes of acute TBI. We report direct electron spin resonance (ESR) evidence of hydroxyl (.OH) radical generation in closed-head injury of rats. Moderate brain concussion was produced by controlled and reproducible mechanical, fixed, closed-head injury. A cortical cup was placed over one cerebral hemisphere within 20 min of the concussion, perfused with artificial cerebrospinal fluid (aCSF) containing the spin trap agent pyridyl-N-oxide-tert-butyl nitrone (POBN, 100 mM), and superfusate samples collected at 10 min intervals for a duration up to 130 min post brain trauma. In addition, POBN was administered systemically (50 mg/kg body wt.) 10 min pretrauma and 20 min posttrauma to improve our ability to detect free radicals. ESR analysis of the superfusate samples revealed six line spectra (alpha N = 15.4 G and alpha beta H = 2.5 G) characteristic of POBN-OH radical adducts, the intensity of which peaked 40 min posttrauma. The signal was undetectable after 120 min. Administration of alpha-phenyl-tert-butyl-nitrone (PBN), a spin adduct forming agent systemically (100 mg/kg body wt. IP 10 min prior to concussion) alone or along with topical PBN (100 mM PBN in aCSF), significantly (p < 0.001) attenuated the ESR signal, suggesting its possible role in the treatment of TBI.

Animals↗

Histopathologic consequences of moderate concussion in an animal model: correlations with duration of unconsciousness.

Although duration of unconsciousness is commonly used as a prognostic index following traumatic brain injury (TBI), few controlled studies have statistically evaluated the relationship between unconsciousness and histologic pathology, particularly after moderate head injury. Using a pendulum-striker concussive device, a reproducible model of TBI in rats was developed. This model is uncomplicated by skull fractures, contusions, or experimenter-induced craniotomies. In the present study, the severity of the histopathology observed in this model of moderate closed-head injury at 48 h posttrauma is linearly related to the duration of unconsciousness (p < 0.0001). The pathology, assessed with a silver stain for neurodegeneration, is particularly striking if unconsciousness persists for 4 minutes or more. These data suggest that the initial period of unconsciousness may be a useful predictor of clinical brain histopathology associated with moderate closed-head injury, predicting either the degree of pathology and/or the rate it progresses if left untreated.

Animals↗

Stromal tumors of the stomach: prognostic value of the PCNA index.

Reliable indicators of behavior in stromal tumors of the gastrointestinal tract have yet to be elucidated. Aggressive behavior has been associated with large size, hypercellularity, tumor necrosis, nuclear atypia, and high mitotic rate. Recently, new methods of measuring proliferation have been developed that exploit the phenomenon of cell cycle specific protein synthesis. In this study the expression of the S-phase specific nuclear protein proliferating cell nuclear antigen (PCNA) is tested as an indicator of malignancy. Sixteen stromal tumors of the stomach were reviewed for tumor size, cellularity, nuclear atypia, mitotic rate, necrosis, vascular invasion, and predominant cell type. Local recurrence and/or mortality were ascertained with a minimum follow-up of 5 yr. An immunohistochemical assay for PCNA was performed on a paraffin section of tumor and the percentage of positively stained cells ("PCNA index") was determined. Among the nine men and seven women, age 37 to 80 (median 66) yr, two had local recurrences that were treated surgically with no metastases. Only positive resection margin correlated with local recurrence. Two other patients developed distant metastases at 8 and 15 mo and died. Mortality did not correlate with age, sex, size, cellularity, necrosis, cell type, and vascular invasion. High grade nuclear atypia (2/2 versus 1/14, P = 0.02) and high mitotic rate (20.5 versus 5.5 per 40 hpfs, P = 0.01) did correlate with mortality. PCNA index did not correlate with local recurrence, but was sharply higher in fatal cases (6.4 versus 1.2, P = 0.001). Both fatal tumors had PCNA values above 6.0, and all others had values of 4.0 or less. The PCNA index is a proliferative marker that may have prognostic value in gastric stromal tumors.

Adult↗

Localization of tumor-associated glycoprotein DF3 in normal, inflammatory, and neoplastic lesions of the colon.

BACKGROUND: The expression of DF3 was assessed by a monoclonal antibody in normal, inflammatory, and neoplastic conditions in the large bowel. METHODS: Using immunohistochemistry, expression was examined in formalin-fixed paraffin-embedded biopsy and resection samples of 19 normal colonic mucosal specimens, 49 inflammatory lesions, 34 adenomas, and 38 primary colonic adenocarcinomas. In addition, Western blots of normal colonic mucosa and adenocarcinoma were examined. RESULTS: DF3 expression was detected in 84% of the adenocarcinomas with coarse membrane staining, intense positivity of luminal secretions, and focal cytoplasmic and intracytoplasmic vacuole staining. Nine of 32 areas of transitional mucosa revealed reactivity along apical membranes in crypt cells. Five adenomas containing carcinoma revealed DF3 positivity in the malignant areas only, whereas the remaining 29 were negative. Staining was membrane, luminal, and intracytoplasmic. Two examples of active ulcerative colitis revealed focal reactivity along the apical membrane of crypt cells. No other areas of staining were noted, including 12 cases containing dysplasia. Four of 10 other inflammatory lesions also revealed similar membrane reactivity in crypt cells. Normal colonic mucosa was nonreactive. Examples of normal colonic mucosa were negative for DF3 by Western blot analysis, whereas two carcinoma samples that reacted immunohistochemically were positive. CONCLUSIONS: DF3 is not detectable in normal colonic tissues. It is expressed focally and predominantly along the apical membrane of crypt cells in some inflammatory lesions and in the transitional mucosa of primary adenocarcinomas. Most adenocarcinomas of the colon and adenomas with foci of invasive carcinoma demonstrate reactivity in the cytoplasm and luminal secretions.

Adenocarcinoma↗

Oxypurinol inhibits free radical release from the cerebral cortex of closed head injured rats.

Traumatic brain injury (TBI) is a significant cause of mortality and morbidity. Although the sequence of events underlying the resultant neuronal loss is still poorly understood, there are indications that oxygen-free radical generation is critically involved. Free radical generation in the cerebral cortex of closed head injury rats was monitored by measuring free radical release into cortical superfusates containing the spin trap agent 4-pyridyl-1-oxide-N-tert-butylnitrone (POBN, 100 mM). ESR analysis of the superfusates revealed six line spectra (alpha N = 15.4 G and alpha H beta = 2.5 G) characteristic of POBN-OH adducts. Administration of oxypurinol (40 mg/kg) 15 min prior to TBI prevented the formation of these radical adducts.

Animals↗

Allergic proctocolitis in infants: a prospective clinicopathologic biopsy study.

Allergic proctocolitis is a major cause of rectal bleeding in infants, but its clinical features and laboratory results are often nonspecific. Our previous retrospective study demonstrated that large numbers of eosinophils in colonic mucosal biopsy specimens were highly associated with cases of allergic proctocolitis. Therefore, we prospectively examined 60 colonic mucosal biopsy specimens from the same sites (4, 8, and 12 cm from the anal verge) in 20 infants with clinically confirmed allergic proctocolitis to validate this morphologic feature, to characterize its distribution, and to correlate these data with the clinical information. The patients (age range, 4 to 304 days) were fed breast milk or a variety of formulas and all presented with rectal bleeding. Sigmoidoscopic examination was abnormal in 19 cases, typically characterized by focal areas of mucosal erythema. The major histologic finding was a strikingly focal increase in the number of eosinophils in all mucosal compartments, with a predilection to aggregate in close association with lymphoid nodules. Eosinophilic infiltration varied not only between biopsies at different sites, but also within individual biopsy specimens. Only 12 of 20 patients (60%) had all three of their biopsy specimens categorized as abnormal; in the remainder, only one (four patients) or two (four patients) of the three biopsy specimens were abnormal. The average number of eosinophils per high-power field of lamina propria for all cases was 15.6. No significant correlation was identified between the number of eosinophils in the mucosa and the patient's age, length of illness, endoscopic appearance, or type of inciting formula. In summary, eosinophils appear to be an excellent marker for infantile allergic proctocolitis. Given the focal distribution of the eosinophils, multiple mucosal biopsy specimens should be obtained and several levels of each examined to confirm the diagnosis.

Biopsy↗

Dorsal vein sclerosis as a predictor of outcome in penile venous ligation surgery.

We studied the pathological specimens obtained from 24 impotent men who underwent proximal penile vein ligation and 6 potent men who underwent total penectomy as part of male-to-female transsexual surgery to determine if a correlation exists between venous pathology and surgical outcome. Pathology specimens, consisting of cavernosal tissue and penile veins, were independently reviewed by a single uropathologist (V. A.). The degree of vein wall thickness was carefully quantified for each patient. Venous leakage was documented by cavernosometry and cavernosography. Followup ranged from 7 to 19 months (mean 11 months). Within 6 months of the procedure 10 patients (41%) achieved rigid erections while 14 (59%) did not. Although no preoperative index could predict operative success, in the 10 patients with successful outcome histological examination of the excised vein segments revealed normal venous architecture with minimal vein wall thickness (calculated mean per cent vein wall thickness 39.4, range 17.5 to 51.7). In contrast, in the 14 patients in whom ligation failed there was marked vein wall thickness and sclerosis (calculated mean per cent vein wall thickness 68.0, range 55.3 to 85.6). In comparison, the vein segments obtained from the 6 potent patients had a wall thickness of 32.8% (range 8 to 39), which was equivalent to the 10 patients with postoperative erections. These findings suggest that there may be a correlation between vein wall thickness and the prognosis of patients who undergo venous ligation surgery for erectile dysfunction secondary to presumed corporeal venous incompetence.

Erectile Dysfunction↗

Use of adrenocorticotrophic hormone analog to minimize brain injury.

STUDY OBJECTIVES: To investigate the effects of a vasoactive analog of adrenocorticotrophic hormone (GMM2) on time-dependent disturbances in regional cerebral blood flow, permeability-capillary surface area products, and intracranial pressure in a rat model of moderate concussion/brain injury. SETTING AND DESIGN: Regional permeability-capillary surface area products and cerebral blood flow were measured at two hours after trauma. Intracranial pressure was monitored for 120 hours after trauma. SUBJECTS: Male Wistar rats (330 to 430 g) (regional cerebral blood flow studies, n = 35; permeability-capillary surface area product studies, n = 36; intracranial pressure studies, n = 32). INTERVENTIONS: Post-traumatic subcutaneous administration of nanomolar concentrations of GMM2 (31 nmol per rat). MEASUREMENTS AND MAIN RESULTS: Untreated trauma acutely increased average brain permeability-capillary surface area products for sucrose and decreased average brain cerebral blood flow. Moreover, it produced marked and prolonged increases in intracranial pressure. Post-traumatic subcutaneous administration of nanomolar concentrations of GMM2 effectively reduced the early hypoperfusion, blood-brain barrier leakiness, and pathologic elevation of intracranial pressure. CONCLUSION: Post-traumatic administration of GMM2, in nanomolar amounts, can prevent or reverse significantly the serious cerebrovascular sequelae of moderate head injury in this animal model. In view of its potency, low toxicity, and other neuroprotective properties, in both rats and human beings, these data suggest that GMM2 may have considerable clinical benefits in the treatment of central nervous system trauma.

Adrenocorticotropic Hormone↗

An ACTH analog minimizes cerebrovascular damage in an animal model of moderate brain injury.

An ACTH1-14-related analog (GMM2) was tested for efficacy in reducing the cerebrovascular pathology that follows moderate, closed-head injury in our rat model. Posttraumatic subcutaneous administration of nanomolar amounts of GMM2 significantly minimized both the hypoperfusion and the increased blood-brain permeability observed 2 h following a concussion. Posttraumatic administration of the peptide also reduced the elevated brain water content observed at 24 and 48 h postinjury to nonsignificant levels. These findings complement previously described observations that GMM2 treatment prevents dangerous elevations of ICP (> 25 mm Hg) at 24 to 72 h in this model of head injury. In view of the potency and low toxicity of GMM2 these observation suggest that the peptide may have considerable clinical application in interrupting pathologic sequelae of traumatic brain injury.

Animals↗

Effect of topical 5-aminosalicylic acid (5-ASA) therapy on rectal mucosal biopsy morphology in chronic ulcerative colitis.

Classic teaching emphasizes that chronic ulcerative colitis is characterized morphologically by the presence of fixed architectural and cellular mucosal changes that categorize the process as chronic. To examine the effect of topical 5-aminosalicylic acid (5-ASA) enemas on the presence of six histological features of chronicity in established chronic ulcerative colitis, 123 mucosal biopsies were taken prospectively at 1-month intervals, all from the same anatomic location (10 cm), from 14 patients treated with either 5-ASA or placebo enemas. The biopsies were evaluated for the presence of mixed inflammation in the lamina propria, crypt architectural abnormalities, basally located lymphoid aggregates, basal plasmacytosis, villiform surface epithelial configuration, and Paneth cell metaplasia. Overall, 29% of biopsies from 64% of patients were histologically normal (no chronic features, no active disease). Compared with patients treated with placebo enemas, patients treated with 5-ASA enemas showed a significantly higher percentage of normal biopsies (36% ASA group vs. 12% placebo group; p = 0.005) and a lower percentage occurrence of each individual histological feature of chronicity. In addition, patients treated with 5-ASA had a higher average number of normal biopsies per patient (3.0) than those treated with placebo enemas (1.3). Therefore, histologically normal-appearing mucosal biopsies do occur in established cases of chronic ulcerative colitis, and this finding is enhanced by treatment with 5-ASA enemas. Awareness of these results should prevent the presence of normal rectal mucosal biopsy findings in chronic ulcerative colitis patients from being misinterpreted as either evidence against this diagnosis or as representing focal skip areas characteristic of Crohn's disease.

Administration, Topical↗

Effect of 3'-azido-3'-deoxythymidine on human immunodeficiency virus type 1 replication in human fetal brain macrophages.

We investigated whether cells derived from the fetal central nervous system can support productive infection by a human immunodeficiency virus type 1 (HIV-1) isolate termed UHC-1, produced by a cellular clone derived from HIV-1 strain HIV-IIIB chronically infected U-937 promonocytic cells, and what the effect of nucleoside analogs might be on viral replication in this system. Fractionation of human fetal brain tissue into two different populations, enriched for either astrocytes or macrophages, showed that only the latter were able to support productive UHC-1 replication and generation of detectable progeny virus. Pretreatment of fetal brain macrophages with either of two nucleoside analogs, 3'-azido-3'-deoxythymidine (AZT) or the (-) enantiomer of 2'-deoxy-3'-thiacytidine, efficiently blocked production of progeny virus. Generation of unintegrated proviral DNA and HIV-1 transcripts were inhibited by pretreatment of fetal brain macrophages with 1 microM AZT. Administration of AZT at 24 h postinfection led to a slight reduction in viral transcript levels and viral progeny production by day 15 postinfection; however, brain macrophages under these conditions did not contain detectable amounts of unintegrated viral DNA. These results suggest that AZT may interfere with the accumulation of unintegrated HIV-1 DNA in brain macrophages. This is the first demonstration that nucleoside analogs are able to block HIV-1 replication in primary cultures of brain cells.

Acquired Immunodeficiency Syndrome↗