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Biomedical subjects

H Goldman

Publications and source records attributed to H Goldman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Value of methylprednisolone in prevention of the arthralgia-myalgia syndrome associated with the total dose infusion of iron dextran: a double blind randomized trial.

The safety and efficacy of total dose infusion (TDI) of iron dextran has been well documented. In 40% of treated patients, an arthralgia-myalgia syndrome develops. The purpose of this randomized, double-blind, prospective study was to investigate whether intravenous (i.v.) administration of methylprednisolone (MP) prevents this complication. Sixty-five patients, 34 women and 31 men, ages 36 to 80 years, received either normal saline before and after TDI (group 1), 125 mg i.v. MP before and saline after TDI (group 2), or 125 mg i.v. MP before and after TDI (group 3). Patients were observed for 72 hours and reactions were recorded and graded according to severity. Fifty-eight percent of group 1 patients, 33% of group 2, and 26% of group 3 had reactions to TDI. The severity of reactions (minimal, mild, and moderate, respectively) was as follows: group 1--6, 6, and 2; group 2--1, 5, and 0; group 3--5, 1, and 0. Data were analyzed by the two-sided Fisher's exact test using 95% confidence intervals with the approximation of Woolf. These data demonstrate that administration of MP before and after TDI reduces the frequency and severity of the arthralgia-myalgia syndrome. We conclude that 125 mg i.v. MP should be given routinely before and after TDI of iron dextran.

Adult↗
PubMed1998

Comparison of genetic alterations in colonic adenoma and ulcerative colitis-associated dysplasia and carcinoma.

Carcinoma is an important complication of ulcerative colitis (UC) and develops from dysplastic precursor lesions. Genetic changes involved in the malignant transformation have not been fully characterized. We studied 19 cases of UC with high-grade dysplasia (HGD) and eight samples of associated carcinoma (CA). Microdissection of normal epithelium, epithelium at the site of chronic inflammation, HGD, and CA was performed. Polymerase chain reaction (PCR) amplification for loss of heterozygosity (LOH) of the following polymorphic microsatellites of putative tumor suppressor gene loci was done: APC (5q), DCC (18q), p16 (9p), p53 (17p), and 8p12. To compare genetic alterations, 22 typical adenomas of the colon were studied with the markers for APC and pl6 gene loci. The results indicated that LOH of p16 and p53 were present in nondysplastic epithelium, HGD, and CA. However, the LOH in nondysplastic epithelium was detected in some associated HGD, but not all. Whereas LOH of p16 was present in 7 of 14 cases of HGD (50%), it was noted in only 1 of 22 adenomas (5.0%). LOH in the APC and DCC gene loci in UC was noted in HGD with associated CA, but LOH of APC was not present either in cases of nondysplastic epithelium or in HGD alone. Conversely, LOH in APC was present in 4 of 19 colonic adenomas. We conclude that LOH of p53 and p16 in nondysplastic epithelium may be associated with chronic reparative processes. These changes may lead to susceptibility to further genetic damage involving the APC and DCC gene loci in the development of dysplasia and progression of CA in UC. The low frequency of LOH in the p16 gene (9p) in adenomas compared with dysplasia in UC combined with infrequent LOH in APC gene loci in cases of pure dysplasia in UC may support this combination of markers as a clinical test for the differentiation of polypoid dysplasia from adenomas in UC.

Adenoma↗
PubMed1998

Service system integration, access to services, and housing outcomes in a program for homeless persons with severe mental illness.

OBJECTIVES: This study evaluated the hypothesis that greater integration and coordination between agencies within service systems is associated with greater accessibility of services and improved client housing outcomes. METHODS: As part of the Access to Community Care and Effective Services and Supports program, data were obtained on baseline client characteristics, service use, and 3-month and 12-month outcomes from 1832 clients seen at 18 sites during the first year of program operation. Data on interorganizational relationships were obtained from structured interviews with key informants from relevant organizations in each community (n = 32-82 at each site). RESULTS: Complete follow-up data were obtained from 1340 clients (73%). After control for baseline characteristics, service system integration was associated with superior housing outcomes at 12 months, and this relationship was mediated through greater access to housing agencies. CONCLUSIONS: Service system integration is related to improved access to housing services and better housing outcomes among homeless people with mental illness.

Adult↗
PubMed1997

Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines.

Somatic mutations in DNA mismatch repair genes have been observed in sporadic tumors as well as cell lines and xenografts derived from such tumors implicating genetic defects of mismatch repair genes in the development of such tumors. However, the proportion of sporadic tumors in which mismatch repair genes have been inactivated has not been determined accurately. We have analyzed 66 sporadic colorectal tumors for the expression of hMLH1 by immunohistochemistry and identified 4 tumors that do not express hMLH1. These four colorectal tumors, a colon tumor cell line (SW48) and an endometrial tumor cell line (AN3CA), did not express hMLH1, despite the absence of mutations in its coding sequence. Cytosine methylation of the hMLH1 promoter region was found in these four colorectal tumors, whereas cytosine methylation of the hMLH1 promoter region was absent in adjacent normal tissue or in nine tumors that expressed hMLH1. In addition, cytosine methylation of the hMLH1 promoter region was observed in the SW48 and AN3CA cell lines that do not express hMLH1 but not in four tumor cell lines known to express hMLH1 mRNA. Our data indicate that DNA methylation is likely to be a common mode of mismatch repair gene inactivation in sporadic tumors.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Topoisomerase II alpha expression in normal, inflammatory, and neoplastic conditions of the gastric and colonic mucosa.

Topoisomerase II alpha (TP) excises and reconnects double-stranded super-coiled DNA during the replicative cell cycle. We studied the localization of TP and Ki-67 in inflammatory and neoplastic mucosal lesions of the stomach and of TP in similar conditions of the colon. TP expression was correlated with tumor stage, grade, and survival time in the colonic tumors to evaluate its potential utility as a predictive marker for clinical outcome. Forty-three sections of chronic gastritis, lesions indefinite for dysplasia, low- and high-grade dysplasia, and gastric adenocarcinomas were immunostained with antibody against TP and Ki-67. For the colon, 71 sections of normal mucosa, chronic colitis, hyperplastic polyps, adenomas, and carcinomas were examined; fresh tissue was analyzed by flow cytometry. Expression of TP in non-neoplastic gastric mucosa was maximal in neck/foveolar cells and focal in surface and deep gland cells. Increased surface and deep gland positivity was found in low-grade dysplasia and a diffuse distribution of positive cells in high-grade dysplasia and carcinoma. The Ki-67 staining pattern was similar. TP in non-neoplastic colon was restricted to the lower crypt zone; it was greatly expanded in the surface/upper crypt region in adenomas and was diffuse in carcinomas. Flow cytometric analysis revealed TP expression mainly in the S and G2/M phase, with higher labeling index in tumors. There was no correlation of TP with stage, grade, or survival times in the colonic tumors. Staining for TP and Ki-67 might help in the distinction of inflammatory and neoplastic lesions of the stomach and colon.

Antigens, Neoplasm↗
PubMed1997

Transforming growth factor-alpha, epidermal growth factor receptor, and MiB-1 expression in Barrett's-associated neoplasia: correlation with prognosis.

Overexpression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) occurs in Barrett's esophagus, particularly the specialized type, which is at an increased risk for malignant transformation. We performed this study to evaluate the immunohistochemical expression and prognostic significance of these growth factors, as well as MiB-1, the Ki-67 proliferation-associated nuclear antigen, in Barrett's-associated neoplasia. Monoclonal antibodies for TGF-alpha, EGFR, and MiB-1 were evaluated in 25 cases of Barrett's-associated adenocarcinoma (BAA) and in adjacent areas of Barrett's metaplasia and dysplasia. The data were correlated with the pathologic features (grade, stage, depth of invasion, lymph node metastasis) and the clinical outcome of the patients. Of the BAAs, 100% and 64% were positive for TGF-alpha and EGFR, respectively. TGF-alpha and EGFR expression did not correlate with any of the pathologic features of the tumors. By univariate analysis, a higher degree of EGFR immunostaining was significantly associated with poorer patient survival (P = 0.004). After stratified analysis, however, EGFR expression correlated with poor survival only in patients with pathologic Stage II cancer (P = 0.03). There was significant (P < 0.001) increase in the MiB-1 proliferation index (PI) associated with neoplastic progression: Barrett's metaplasia, 22.0% +/- 6.4; dysplasia, 56.5% +/- 21.6; and BAA, 70.0% +/- 17.7. In a separate comparison of the luminal (upper half) and basal (lower half) crypt MiB-1 PI, dysplastic epithelium revealed a significant increase in the luminal crypt MiB-1 PI in comparison with Barrett's metaplastic epithelium (50.7 +/- 24.6 versus 1.2 +/- 1.9, P < 0.001). EGFR expression might have prognostic value for patients with BAA, particularly those with Stage II cancer. The MiB-1 PI pattern supports the metaplasia-dysplasia-adenocarcinoma pathogenetic sequence in these tumors. Furthermore, the pattern of MiB-1 immunostaining might help to distinguish dysplastic from regenerative metaplastic epithelium of Barrett's esophagus in uncertain cases.

Adenocarcinoma↗
PubMed1996

Alterations in CNS gene expression in a rodent model of moderate traumatic brain injury complicated by acute alcohol intoxication.

The combined effects of acute alcoholic intoxication and moderate traumatic brain injury (TBI) on zif/268, glial fibrillary acidic protein (GFAP), and preproenkephalin (PPE) mRNA expression were examined. Adult male Wistar rats received ip injections of a 5% alcohol solution (2.4 g/kg in a final volume of 20 ml isotonic saline) 10 min prior to fixed-head, mechanical injury. Using Northern analysis, a transient three- to fourfold induction of zif/268 mRNA levels was observed 45 min after injury in both TBI and alcohol-treated rats. This induction occurred in regions close to the impact site, namely, the olfactory bulb (OB) and frontal cortex (FTCTX) but not in the more distal piriform/amygdala cortex (P/A). No PPE mRNA changes were observed at 45 min for any experimental group. By 6 h, zif/268 transcript levels returned to or fell below basal levels in the OB and FTCTX while GFAP mRNA levels began to increase in TBI rats. At 24 h, GFAP mRNA levels were greatly increased in all three brain regions of TBI rats. However, alcohol inhibited the temporal induction of GFAP mRNA in the FTCTX and P/A triggered by TBI at 6 and 24 h. These results suggest that although acute alcohol intoxication prior to TBI does not influence gene expression patterns immediately after injury, it may minimize the transcriptional activation of astrocytes particularly in more distant brain regions that were influenced by the impact in nonintoxicated rats.

Alcoholic Intoxication↗
PubMed1996

Oral administration of a bacterial immunomodulator enhances the immune response to cholera toxin.

Attempts to achieve IgA responses in the intestine by oral immunization with non replicating antigens have been characterized by ineffective responses of short duration unless long term dosages are administered. Cholera toxin (CT) is an exception in that it is able to produce a high secretory and systemic immune response. We study the effects of a bacterial immunomodulator [3 x 10(10) Propionibacterium granulosum ml-1 and lipopolysaccharide (LPS) 5 mg ml-1] on the immune response to CT orally administered to Wistar rats. The immunomodulator was orally administered as follows: in schedule 1 during 7 days prior to the first dose of CT; and in schedule 2, 2 days before, together, and 3 days after the first dose of CT. Schedules 1 and 2 were effective in increasing the specific IgA in the intestinal fluid and specific IgG in serum (P < 0.001) when compared to controls. Besides, schedule 2 was more effective than schedule 1 when the levels of specific IgG in serum or specific IgA in intestinal fluid was measured (P < 0.05). Total IgA in the intestinal fluid was increased in rats receiving the immunomodulator (P < 0.01). However, the ratio of specific IgA per total IgA was higher in rats receiving treatment 1 or 2 when compared to controls (P < 0.01). The number of antitoxin antibody producing cells was not increased in the Peyer patches, but a significant increase was observed in the mesenteric lymph nodes and spleen when compared to controls (P < 0.05). The administration of LPS alone produced an increase in the antitoxin immune response when compared to controls, but it was lower than those produced by the administration of the immunomodulator. These results indicate that this immunomodulator is an effective adjuvant of the mucosal and systemic immune response to CT. The mechanisms of action possibly involve nonespecific and specific modulations of the immune response.

Adjuvants, Immunologic↗
PubMed1996

Effects of alcohol on blastocyst implantation site blood flow in the rat.

The effect of alcohol on blood flow at sites of blastocyst implantation versus adjacent intersites was measured in conscious unrestrained rats on day 5 of pregnancy. Alcohol (0.75 ml of 100% ethanol diluted 1:2, v/v) was injected into the femoral vein (1 g/kg body wt); controls received an equivalent volume of vehicle (physiological saline). Implantation sites were rendered visible by intravenous injection of Evans Blue dye. Blood flow was measured at 15 min after alcohol injection by the 86Rb fractionation method. In controls, blood flow was significantly greater (P < 0.05) at implantation sites (0.77 +/- 0.04 ml/min/g) than at intersites (0.43 +/- 0.03 ml/min/g). Alcohol markedly increased (P < 0.05) perfusion at both sites (2.17 +/- 0.22 ml/min/g) and intersites (1.74 +/- 0.15 ml/min/g) vs respective controls. Blood alcohol levels exceeded 100 mg/dl at 10 min post-injection. Mean cardiac output and haematocrit values did not differ significantly between control and treated rats. The data indicate that alcohol enhances uterine vascular perfusion and that the vascular bed of implantation sites is susceptible to the haemodynamic effects of alcohol. Enhanced uterine blood flow may contribute to the alcohol-induced changes in embryo development, blastocyst implantation and endometrial decidualization observed in the rat.

Animals↗
PubMed1996

Are thyroid function tests necessary in patients with suspected sleep apnea?

Thyroid evaluation is frequently performed in patients with sleep apnea because of a suspected causal relationship between hypothyroidism and obstructive sleep apnea (OSA). The aim of this study was to determine the actual prevalence of hypothyroidism in patients referred for polysomnography and evaluate whether its rate was higher in patients with OSA than those without OSA. Ultrasensitive thyroid stimulating hormone (TSH) was performed on 255 of 279 consecutive patients referred for polysomnography from the neurology service of a large HMO. Hypothyroidism was detected in 1.6% (4/243) of all patients, 1.5% (3/194) of patients referred to evaluate OSA, and 2.0% of patients referred to evaluate the presence of periodic leg movement disorder (PLMD)/narcolepsy/parasomnia. There was no significant difference in rates of hypothyroidism in patients with documented OSA (2.9%, 3/103) compared to those without OSA (0.7%, 1/135). Two of the four patients with elevated TSHs had previously documented hypothyroidism and were on thyroxine replacement. Rates of hyperthyroidism were as high or higher than those of hypothyroidism in all groups. We conclude that thyroid screening does not appear to be appropriate for patients with suspected, or confirmed, OSA in the absence of signs or symptoms consistent with hypothyroidism or unless they are in a high risk group (women over the age of 60).

Adult↗
PubMed1996

Gastric and esophageal intraepithelial lymphocytes in pediatric celiac disease.

Celiac disease (CD) is associated with marked mononuclear cell inflammation in the small intestinal mucosa. This study was performed to evaluate analogous changes in the gastric and esophageal mucosa of pediatric patients with CD, with emphasis on epithelial lymphocytosis. We evaluated intraepithelial lymphocytes (IELs) in 23 gastric (no.IELs/100 epithelial cells) and 14 esophageal mucosal biopsy specimens (IELs/hpf) from 23 pediatric cases of CD and 10 nonceliac matched controls. Four patients had postgluten withdrawal biopsy specimens reviewed, and one of these had further postgluten challenge biopsy specimens evaluated as well. Gastric specimens from the CD cases showed a significantly increased IEL count (20.5 +/- 14.4; range, 4-50) compared to controls (3.4 +/- 1.9; range, 1-8; p < 0.001), which also correlated directly with the histologic severity of the small intestinal disease as assessed by the degree of villous shortening. Sixteen (69.5%) of 23 gastric specimens showed > 8 IELs, which was the highest value obtained in control specimens. The four posttreatment specimens showed a significant reduction in the gastric IEL counts from a mean of 19.8 to 3.5 IELs/100 epithelial cells (p < 0.001). The single case that had a further postgluten challenge biopsy showed a return to the pregluten withdrawal IEL count. However, the degree of gastric intraepithelial lymphocytosis did not correlate with any of the clinical data, such as age, gender, presenting symptoms, or serum antibody levels (antigliadin, antireticulin, or antiendomysium). Furthermore, no differences were observed in the IEL count in CD esophageal specimens (5.3 +/- 2.6; range, 2-10) compared to controls (5.2 +/- 1.5; range, 3-8; p = 0.935). These findings suggest that an immune-mediated lymphocytic response linked to gluten occurs in the gastric epithelium, similar to that seen in the small intestine of pediatric patients with CD. Therefore, gastric intraepithelial lymphocytosis may represent a concurrent manifestation of CD rather than a separate entity in the pediatric population.

Biopsy↗
PubMed1996

Effects of mental health services reform on clinical practice in the United Kingdom.

In the last few years, the British National Health Service, local government social services departments, the welfare benefits system, and the organization of primary health care in the United Kingdom have undergone major reforms that have had significant effects on mental health services. Local social service departments were given the lead role in purchasing and coordinating community supports for persons with mental illness, but were not given enough funds to arrange adequate services. In the National Health Service, an internal-market approach, in which local health authorities could contract with any provider or group of providers, was introduced. This purchaser-provider split has created a climate of competition in a traditionally collaborative environment and has reduced staff morale. Similar but separate case management models were introduced in both the health service and the social service departments, which has led to inefficiency in planning care for individual patients. Opportunities were created for general practitioners to use capitated funds to purchase specialty care directly from providers. This arrangement resulted in an initial emphasis on care for less severely mentally ill patients, although some general practitioners are beginning to explore new approaches for supporting severely ill patients in the community. On the positive side, the reforms have led to greater involvement of patients and their families in planning service delivery. However, the authors suggest that policy makers in the U.K. seem to be repeating many of the mistakes made by American mental health systems in the 1960s and 1970s.

Cost-Benefit Analysis↗
PubMed1995

Effect of recent health and social service policy reforms on Britain's mental health system.

The introduction of new policies in health and social services in Britain has changed the way community care is provided to seriously mentally ill people. Britain is creating the same problems that have existed in the United States, whereby clinicians struggle to provide services in an environment with multiple payers and perverse incentives. A simple system in Britain has been replaced with complicated organisational and financial structures that require almost impossible feats by local health and social service staff to coordinate care for patients for whom continuity of care is critical for their survival in the community and their wellbeing. Seriously mentally ill people are in the middle of these complicated problems. The creation of a local mental health authority that could be held responsible for community care, as exists in some American states, may be one solution.

Community Mental Health Services↗