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Biomedical subjects

D Goldstein

Publications and source records attributed to D Goldstein.

At least 19 recordsLinked to original sources
PubMed2002

Elevated alpha-foetoprotein and hepatic metastases--it's not always what it seems!

Gastric cancers that secrete alpha-foetoprotein (AFP) are a rare but well defined entity. These tumours tend to be aggressive with a poor prognosis. Recognition and identification of this group of patients is important in influencing prognosis, treatment options and further clinical research into this entity. We report three cases of gastric cancers associated with elevated AFP. This entity should be considered in patients with hepatic lesions and an elevated AFP without risk factors for hepatocellular carcinoma or in patients with associated gastric symptoms.

Aged↗
PubMed2001

S-nitrosothiols do not induce oxidative stress, contrary to other nitric oxide donors, in cultures of vascular endothelial or smooth muscle cells.

Nitric oxide (NO) has been described to exert various anti-atherogenic actions. However, NO, in some cases, has been shown to stimulate the oxidation of low-density lipoprotein (LDL), which constitute an important triggering event in atherosclerosis. Thus, some NO donors, despite their advantages, might also induce oxidative stress. Therefore, the purpose of this study is to examine the effect of three different NO donors on LDL oxidation, in acellular system as well as in cultures of normal endothelial cells or smooth muscle cells, which constitute the two major cellular components of the arterial wall. Sodium nitroprusside oxidized strongly LDL in medium alone as well as in endothelial or smooth muscle cell cultures. Sydnonimine-1 (SIN-1) oxidized LDL already in the absence of cells and enhanced clearly the LDL oxidation in the cultures. S-nitroso-N-acetylpenicillamine was unable to oxidize LDL in synthetic medium alone as well as in the presence of cells, showing that the amount of superoxide and other reactive oxygen species released by these cells did not suffice, contrary to those liberated by macrophages, to combine to NO providing oxidant activity.

Animals↗
PubMed2001

Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: a Phase II trial for the Trans-Tasman Radiation Oncology Group.

PURPOSE: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. METHODS AND MATERIALS: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. RESULTS: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. CONCLUSION: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications.

Adenocarcinoma↗
PubMed2001

Phase II study of paclitaxel and oral etoposide in patients with locally advanced or metastatic non-small cell lung cancer.

The combination of paclitaxel and etoposide was evaluated in a phase II study in patients with locally advanced or metastatic non small-cell lung cancer (NSCLC). Thirty-five patients, median age 61, received treatment with paclitaxel 200 mg/m (2) intravenous over 3 h on day 1, and oral etoposide, 100 mg daily on days 1-5. Cycles were repeated every 21 days for a maximum of nine cycles, or until progression occurred. Twenty-eight patients had stage IV disease, and seven patients had stage IIIA or B disease. There was one complete and seven partial responses (overall response rate, 23%). Two of these responses were in patients with stage III disease (29%) and six in patients with stage IV disease (21%). Median survival was 8.7 months, and 36% of patients were alive at 1 year. There were no treatment-related deaths and little grade 3 or 4 non-haematological toxicity although grade 3 or 4 neutropenia occurred in 60% of patients (33% of cycles). There were four episodes of febrile neutropenia. The combination of paclitaxel and oral etoposide is active in advanced NSCLC and can be delivered with acceptable toxicity.

Administration, Oral↗
PubMed2001

Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT).

OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy of type 1 diabetes mellitus reduces the risk of development and progression of microvascular complications. The Epidemiology of Diabetes Interventions and Complications (EDIC) study assessed whether these benefits persisted after the end of DCCT. Results for the adolescent DCCT cohort are reported here. STUDY DESIGN: Of the DCCT adolescent cohort (n = 195), 175 participated in EDIC, 151 had fundus photography, and 156 had albumin excretion rate measured at year 3 or 4. The odds of progression of retinopathy and albuminuria from closeout of the DCCT until EDIC year 4 were assessed. RESULTS: In contrast to the 7.4 years of the DCCT, during which mean hemoglobin A(1c) levels were significantly lower with intensive therapy than conventional therapy (8.06% vs 9.76%; P <.0001), the subsequent first 4 years of EDIC had mean hemoglobin A(1c) levels that were similar between the former intensive and the former conventional groups (8.38% vs 8.45%). However, the prevalence of worsening of 3 steps or more in retinopathy and of progression to proliferative or severe nonproliferative retinopathy were reduced by 74% (P <.001) and 78% (P <.007), respectively, in the former intensive therapy group compared with the former conventional group. CONCLUSIONS: These findings provide further support for the DCCT recommendation that most adolescents with type 1 diabetes receive intensive therapy aimed at achieving glycemic control as close to normal as possible to reduce the risk of microvascular complications.

Adolescent↗
PubMed2001

Cultural aspects of cancer genetics: setting a research agenda.

BACKGROUND: Anecdotal evidence suggests that people from non-Anglo-Celtic backgrounds are under-represented at familial cancer clinics in the UK, the USA, and Australia. This article discusses cultural beliefs as a potential key barrier to access, reviews previous empirical research on cultural aspects of cancer genetics, draws implications from findings, and sets a research agenda on the inter-relationships between culture, cancer genetics, and kinship. METHODS: The CD-ROM databases MEDLINE, PsychLIT, CINAHL, and Sociological Abstracts were searched from 1980 onwards. RESULTS: Cultural aspects of cancer genetics is the focus of an emerging body of publications. Almost all studies assessed African-American women with a family history of breast cancer and few studies included more diverse samples, such as Americans of Ashkenazi Jewish background or Hawaiian- and Japanese-Americans. Our analysis of published reports suggests several directions for future research. First, an increased focus on various Asian societies appears warranted. Research outside North America could explore the extent to which findings can be replicated in other multicultural settings. In addition, control group designs are likely to benefit from systematically assessing culture based beliefs and cultural identity in the "majority culture" group used for comparative purposes. CONCLUSION: More data on which to base the provision of culturally appropriate familial cancer clinic services to ethnically diverse societies are needed. Empirical data will assist with culturally appropriate categorisation of people from other cultures into risk groups based on their family histories and provide the basis for the development of culturally appropriate patient education strategies and materials.

Black or African American↗
PubMed2001

Sertraline treatment of posttraumatic stress disorder: results of 24 weeks of open-label continuation treatment.

BACKGROUND: Posttraumatic stress disorder (PTSD) is typically associated with a high degree of chronicity, comorbidity, and psychosocial disability. The efficacy of sertraline in the acute treatment of PTSD has been confirmed based on the results of 2 large, placebo-controlled studies, but almost no prospective long-term treatment studies have been reported. METHOD: One hundred twenty-eight patients who completed 12 weeks of double-blind, placebo-controlled, acute-phase treatment for DSM-III-R-defined PTSD with sertraline were continued into a 24-week open-label continuation phase. Efficacy was evaluated using the endpoint change in the 17-item Clinician Administered PTSD Scale Part 2 (CAPS-2) severity score, the 15-item patient-rated Impact of Event Scale, and the Clinical Global Impressions-Improvement and -Severity of Illness scales as primary outcome measures. Treatment response was defined as > or =30% decrease in the CAPS-2 total severity score (compared with acute-phase baseline score) and a Clinical Global Impressions-Improvement score of 1 or 2. RESULTS: Ninety-two percent of acute-phase responders maintained their response during the full 6 months of continuation treatment. In addition, 54% of acute-phase nonresponders converted to responder status during continuation therapy. Over the 36-week course of acute and continuation therapy, 20% to 25% of the improvement in the CAPS-2 severity score occurred during the continuation phase. Sertraline was well tolerated, with 8.6% of patients discontinuing due to adverse events. A high pretreatment CAPS-2 score (> 75) predicted a longer time to response and a greater likelihood that response occurred after 12 weeks of acute treatment. CONCLUSION: The acute efficacy of sertraline is sustained in the vast majority of patients, and at least half of nonresponders to acute treatment will eventually respond to continued treatment.

Adult↗
PubMed2001

Alzheimer's disease. To tell or not to tell.

OBJECTIVE: To evaluate reasons for telling or not telling patients about a diagnosis of Alzheimer's disease and to assess the effect of such a decision on patients, families, physicians, and the health care system. QUALITY OF EVIDENCE: MEDLINE was searched from January 1966 to December 1999 using the key words "Alzheimer's disease" or "dementia" and "truth disclosure" or "attitude to health." There were no randomized controlled trials (level I evidence) in the literature. Articles identified provided level II evidence (case-controlled and cross-sectional studies) or level III evidence (expert opinion). All articles identified were chosen for this study. MAIN MESSAGE: In attempting to determine whether or not to communicate a diagnosis of Alzheimer's disease, physicians face a predicament: the desire to communicate honestly and directly with a patient is sometimes at variance with the equally compelling desire to concur with the patient's family's reluctance to disclose the diagnosis. Most Alzheimer's patients should be told of their diagnosis, but the timing of the discussion and the way it occurs are crucial to a good outcome. Most patients accept the information without a catastrophic response. Physicians must gain support from patients' families because it could take time for them to accept disclosure of what is perceived as a "hopeless" diagnosis. CONCLUSION: We must continue to support Alzheimer's patients and promote hope.

Aged↗
PubMed2000

Diagnosis of pyogenic pelvic inflammatory diseases by 99mTc-HMPAO leucocyte scintigraphy.

Pelvic inflammatory disease (PID) is one of the major health problems of women of child-bearing age. Among the most serious complications of PID is the formation of a tubo-ovarian abscess (TOA). Early diagnosis of this condition may prevent serious surgical complications such as peritonitis and sepsis, which may be fatal. The purpose of this study was to investigate the efficacy of technetium-99m hexamethylpropylene amine oxime (HMPAO) leucocyte scintigraphy in the diagnosis of TOA. Twenty women with high clinical suspicion of TOA underwent 99mTc-HMPAO leucocyte scintigraphy. The labelling of leucocytes with 99mTc-HMPAO was performed according to a standard protocol. Scans were obtained at 1, 3 and 24 h following the injection of the labelled leucocytes. In eight cases the early and/or late scan was positive, in 11 cases it was negative, and in one case of ovarian cyst torsion, confirmed by laparoscopy, it showed slight uptake in the capsule of the cyst (false-positive). The sensitivity of 99mTc-HMPAO leucocyte scintigraphy was 100%, specificity 91.6%, positive predictive value 89%, negative predictive value 100% and overall accuracy 95%. It is concluded that leucocyte scintigraphy is a non-invasive, safe, physiological and accurate procedure for the diagnosis of TOA. The 24-h scan is crucial, since in some cases the abscess was not clearly visualized on the early scan. Leucocyte scintigraphy may reduce the need for CT, diagnostic laparoscopy and unnecessary invasive surgical procedures.

Adult↗
PubMed2000

Metastatic secretory breast cancer. Non-responsiveness to chemotherapy: case report and review of the literature.

Secretory carcinoma of the breast is a rare and indolent tumour originally described in children but occurring equally in the adult population. The principal management problems following primary surgical treatment are local recurrence and axillary lymph node metastases. Distant metastases are extremely rare. We present the case of a 27-year-old woman with pulmonary metastases from a secretory breast cancer treated by mastectomy and axillary lymph node dissection 12 years previously. There was no response to chemotherapy; however, the patient remained alive and active two years from presentation with metastatic disease and one year from cessation of all cytotoxic chemotherapy. She eventually died of respiratory failure two and a half years after presentation. To our knowledge, this is only the fourth reported case of distant metastases from secretory breast cancer and the second reported case in which current active chemotherapy has been used. We review the literature and discuss the apparent chemoresistance of this tumour including the lack of membrane staining for Her2/neu. In the absence of any proven effective chemotherapy we believe that symptom control becomes the focus of management and offers patients with metastatic secretory breast cancer the greatest chance of a functional and good quality existence.

Adult↗
PubMed2000

A unique form of mental retardation with a distinctive phenotype maps to Xq26-q27.

We report a novel X-linked mental retardation (XLMR) syndrome, with characteristic facial dysmorphic features, segregating in a large North Carolina family. Only males are affected, over four generations. Clinical findings in the seven living affected males include a moderate degree of mental retardation (MR), coarse facies, puffy eyelids, narrow palpebral fissures, prominent supraorbital ridges, a bulbous nose, a prominent lower lip, large ears, obesity, and large testicles. Cephalometric measurements suggest that the affected males have a distinctive craniofacial skeletal structure, when compared with normative measures. Obligate-carrier females are unaffected with MR, but the results of cephalometric skeletal analysis suggest craniofacial dysmorphisms intermediate between affected males and normative control individuals. Unaffected male relatives show no clinical or cephalometric resemblance to affected males. The blood-lymphocyte karyotype and the results of DNA analysis for fragile-X syndrome and of other routine investigations are normal. Linkage analysis for polymorphic DNA markers spanning the X chromosome established linkage to Xq26-q27. Maximum LOD scores were obtained at marker DXS1047 (maximum LOD score = 3.1 at recombination fraction 0). By use of haplotype analysis, we have localized the gene for this condition to an 18-cM genetic interval flanked by ATA59C05 and GATA31E08. On the basis of both the clinical phenotype and the mapping data, we were able to exclude other reported XLMR conditions. Therefore, we believe that a unique recessive XLMR syndrome with a distinctive and recognizable phenotype is represented in this family.

Abnormalities, Multiple↗