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Biomedical subjects

J Berlin

Publications and source records attributed to J Berlin.

At least 19 recordsLinked to original sources
PubMed2005

A phase II trial of gefitinib with 5-fluorouracil, leucovorin, and irinotecan in patients with colorectal cancer.

Inhibition of epidermal growth factor receptor (EGFR) signalling contributes to the therapy of colorectal cancer. Gefitinib, an oral EGFR tyrosine kinase inhibitor, shows supra-additive growth inhibition with irinotecan and fluoropyrimidines in xenograft models. We designed a study to determine the tolerability and efficacy of gefitinib in combination with irinotecan, infusional 5-fluorouracil (5-FU) and leucovorin (LV), on a 2-week schedule. Among 13 patients with advanced colorectal cancer, 10 required dose reductions of irinotecan and 5-FU because of dehydration, diarrhoea, and neutropenia, seven of whom required hospitalisation, three with neutropenic fever. One patient achieved partial response and seven had disease stabilisation. The combination of this standard chemotherapy regimen with gefitinib is associated with excessive toxicity, suggesting an interaction at a pharmacokinetic or pharmacodynamic level.

Adenocarcinoma↗
PubMed2001

Predictors of improvement in health-related quality of life among elderly patients with depression.

BACKGROUND: Depression is the most prevalent disabling psychiatric syndrome of aging and may lead to important decrements in the elderly depressed patient's health-related quality of life (HRQL). The goal of this study was to determine whether severity of chronic illness at admission, severity of depressive symptoms at admission, or living alone before admission was associated with lack of improvement in HRQL at 3 months postdischarge among elderly depressed inpatients. METHODS: Subjects were 100 consecutive patients admitted to a 26-bed inpatient geriatric psychiatry unit from 1994 through 1997, who were residing in the community and were not demented. At admission, severity of depressive symptoms was assessed using the Geriatric Depression Scale and severity of chronic physical illness was measured using the Cumulative Illness Rating Scale (Geriatrics). HRQL was assessed at admission and again at 3 months postdischarge using the Medical Outcomes Study (MOS) 6-Item General Health Survey. RESULTS: This study found large improvements in all MOS items between admission and 3 months postdischarge. Severity of chronic physical disease was negatively associated with the probability of improvement in three MOS items (role functioning, psychological functioning, and general health perceptions) whereas the severity of depressive symptoms on admission was negatively associated with the probability of improvement in role functioning, social functioning, and bodily pain. Living alone was negatively associated with social functioning but not with any of the other MOS items. CONCLUSION: The results of this study suggest that the inpatient treatment of depression in the elderly brings about improvements in quality of life that persist for at least 3 months following discharge. The patient's initial level of depression and initial level of physical health may be important factors to be considered when evaluating a patient's prognosis.

Aged↗
PubMed2001

A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma.

BACKGROUND: A phase II study testing the safety and efficacy of irinotecan (CPT-11). 5-fluorouracil (5-FU), and leucovorin (LCV) was conducted in patients with advanced gastric adenocarcinomas. PATIENTS AND METHODS: Patients with metastatic or recurrent adenocarcinoma of the gastroesophageal junction (GEJ) or stomach were entered onto this study. Previous chemotherapy for metastatic disease was not allowed. Treatment consisted of repeated 6-week cycles comprising CPT-11 125 mg/m2 intravenously (i.v.) followed immediately by LCV 20 mg/m2 i.v. and 5-FU 500 mg/m2 i.v., all given weekly for four weeks followed by a two-week rest. RESULTS: Thirty-eight patients were enrolled and 36 eligible patients received protocol therapy. Grade 3-5 toxicities consisted primarily of neutropenia (36%) and diarrhea (28%). Neutropenic infection was observed in 14% of patients, with 3 (8%) dying of neutropenic sepsis. The overall response rate was 22% (95% confidence interval [CI] 8.5% to 35.5%). Median survival was 7.6 months, and median time to progression was 4.4 months. CONCLUSION: This weekly regimen of CPT-11 with bolus 5-FU/LCV is active in patients with advanced adenocarcinomas of the stomach or gastroesophageal junction. While rates of grade 3-4 neutropenia and diarrhea were similar to those observed historically in patients receiving this regimen for colorectal cancer, neutropenic fever/sepsis appeared to be more frequent, and dose modifications were substantial. Future trials of this combination in patients with gastric cancer should decrease the absolute starting drug doses and/ or employ altered scheduling that better accommodates the pattern of toxicity.

Adenocarcinoma↗
PubMed2001

New directions in the treatment of advanced colorectal cancer.

As the chemotherapy horizons have expanded in colorectal cancer with development of oxaliplatin (Eloxatin) and irinotecan (CPT-11, Camptosar), so too have our approaches to therapy. Numerous immunotherapy and gene therapy approaches are undergoing initial study. These methods are founded on increased knowledge of tumor biology. That same knowledge has led to the identification of new molecular targets for anticancer chemical therapies. This article highlights some of these developments with focus on epidermal growth factor receptor and angiogenesis.

Colorectal Neoplasms↗
PubMed2000

Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: a regimen with unexpected early toxicity.

PURPOSE: We performed a phase I trial of protracted venous infusion (PVI) fluorouracil (5-FU) plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer to determine the maximum-tolerated dose of gemcitabine that could be safely administered. We also sought to identify the toxicities associated with this treatment protocol. PATIENTS AND METHODS: Seven patients with locally advanced pancreas cancer were treated with planned doses of radiation (59.4 Gy) and PVI of 5-FU (200 mg/m(2)/d) with gemcitabine doses of 50 to 100 mg/m(2)/wk. RESULTS: Two of three patients at the 100-mg/m(2)/wk dose level experienced dose-limiting toxicity (DLT), as did three of four at the 50-mg/m(2)/wk dose level. One patient experienced a mucocutaneous reaction described as a Stevens-Johnson syndrome that was attributed to chemotherapy. Three patients developed gastric or duodenal ulcers with severe bleeding requiring transfusion. One patient developed severe thrombocytopenia lasting longer than 4 weeks. Three of the five episodes of DLT developed at radiation doses < or = 36 Gy. CONCLUSION: Based on this experience, we cannot recommend further investigation of regimens incorporating gemcitabine into regimens of radiation with PVI 5-FU. The mechanism of this synergistic toxicity remains to be determined.

Adenocarcinoma↗
PubMed2000

Effects of external beam radiation on the allograft dermal implant.

OBJECTIVE: The purpose of this study was to define the effects of external beam radiation (EBR) on AlloDerm (LifeCell Corp) through the analysis of graft thickness, fibroblast recellularization, and neovascularization as a function of time. METHODS AND MATERIAL: Thirty-six male Sprague-Dawley rats (n = 36) were randomly assigned to 1 of 4 groups (A, B, C, and D). AlloDerm was implanted subcutaneously into the hind legs of each rat, and 20 Gy of EBR was administered to one side. Grafts harvested 1, 2, 4, and 12 weeks after radiation were subjected to blinded histologic analysis. RESULTS: In groups A, B, and C, the irradiated grafts showed a significant decrease in recellularization versus nonirradiated (P < 0.001). At 12 weeks (group D), recellularization equalized, but neovascularization was significantly less (P = 0.048) in the irradiated group. Graft thickness was unaffected. CONCLUSIONS: In the rat model, EBR of the implanted AlloDerm graft hinders recellularization in the early posttreatment period. However, EBR did not adversely affect graft thickness, recellularization or ultimate graft survival.

Animals↗
PubMed2000

Ipsilateral and contralateral thalamic hypometabolism as a predictor of outcome after temporal lobectomy for seizures.

UNLABELLED: FDG PET is often used to help localize the seizure focus before surgery in patients with medically refractory temporal lobe epilepsy. However, the ability of certain patterns of metabolic landscape to predict postsurgical seizure outcome has not been well characterized. The purpose of this retrospective study was to determine whether FDG PET abnormalities elsewhere in the brain, in combination with those in the temporal lobes, can be used to predict seizure outcome after surgery. METHODS: Eighty patients with refractory temporal lobe seizures were imaged with PET after intravenous administration of 115 microCi/kg FDG. Images were interpreted without knowledge of clinical information by an experienced reviewer to determine seizure focus and regional metabolic changes in the brain. Metabolic activity scores were assigned for cortical and subcortical structures using the following criteria: 4 = normal activity, 3 = mildly decreased activity, 2 = moderately decreased activity, 1 = severely decreased activity, and 0 = no activity. A laterality index for each region was calculated using the equation 100 x [right - left]/[1/2 x (right + left)]. Seizure focus localization was based on the laterality of temporal lobe metabolic activity and was compared with that determined by scalp and depth electrodes and MRI results. Comparisons were made between asymmetries in metabolic activity in various brain structures and postoperative seizure frequency. Postoperative outcome was determined on the basis of cessation (complete disappearance of seizures) or continuation of seizure activity, regardless of frequency, compared with the preoperative state. RESULTS: All 64 patients who were free of seizures postoperatively had either no thalamic asymmetry or reduced metabolism on the side from which the temporal lobe was removed. In contrast, 5 of 16 patients (31%) with postoperative seizures of any frequency had hypometabolism in the thalamus contralateral to that of the removed temporal lobe. All 5 patients with reverse thalamic asymmetry had postoperative seizures. Patients with thalamic hypometabolism ipsilateral to the removed temporal lobe also had an increased risk of postoperative seizures, but this risk was not as high as in patients with the contralateral abnormality. In these patients, the temporal lobe (which appeared hypometabolic on PET) was determined to be the site of the seizure on the basis of information besides that provided by PET before surgery. CONCLUSION: This study indicated that, in patients with temporal lobe epilepsy, thalamic metabolic asymmetry, particularly in the reverse direction to that of the temporal lobe asymmetry, was associated with a poor postsurgical outcome compared with no or matched asymmetry. This determination may be important in evaluating patients for, and selecting optimal candidates for, surgical intervention.

Adolescent↗
PubMed2000

Second-line therapy in colorectal cancer.

Second-line therapy is a relatively new concept for gastrointestinal oncologists. Although retreatment with fluorouracil (5-FU) is common, offering colorectal cancer patients a different chemotherapeutic agent as second-line therapy is a fairly recent strategy. The focus of this article is on the use and efficacy of oxaliplatin (Eloxatin) as second-line therapy for colorectal cancer. As such, this article will present very limited data on the toxicity of oxaliplatin regimens.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Immunohistochemistry with pancytokeratins improves the sensitivity of sentinel lymph node biopsy in patients with breast carcinoma.

BACKGROUND: Sentinel lymph node (SLN) biopsy is being investigated as a staging procedure for breast carcinoma. The authors evaluated whether immunohistochemical (IHC) analysis improves the sensitivity of this procedure. METHODS: Forty-four women with breast carcinoma were recruited for SLN biopsy. Preoperative lymphoscintigraphy was followed by intraoperative localization using a handheld gamma probe and blue dye. After SLN identification, an immediate complete axillary lymph node dissection was performed in all patients. All lymph nodes were subjected to routine histology (hematoxylin and eosin [H&E]) and IHC using antibody to cytokeratins. RESULTS: The SLN was identified in 41 of 43 patients (95%). Successful SLN identification was independent of biopsy technique (open surgical [95%] vs. fine-needle aspiration/core needle biopsy [96%]). Twelve of 41 patients (29%) had evidence of lymph node metastasis in the SLN by routine histology. Of the twenty-nine patients with H&E negative SLN, 3 were found to have metastasis by IHC for a conversion rate of 10%. Fifteen of 41 patients (37%) had evidence of metastasis in SLN. All 26 patients with H&E and IHC negative SLN had negative nonsentinel lymph nodes by routine histology and IHC (100% negative predictive value). All patients with tumors < 2 cm and micrometastasis to the SLN had no additional lymph node disease, in contrast to patients with lesions > 2 cm or patients with macrometastasis to the SLN (P = 0.007). CONCLUSIONS: These results confirm that SLN biopsy is extremely accurate for patients with breast carcinoma, even after open surgical biopsy. IHC analysis or serial sectioning of SLN improves the sensitivity of this staging technique.

Adult↗
PubMed1999

Phase II evaluation of treatment of complete resection of hepatic metastases from colorectal cancer and adjuvant hepatic arterial infusion of floxuridine: an Eastern Cooperative Oncology Group Study (PB083).

This study was designed to evaluate hepatic arterial infusion of floxuridine (FUDR) in patients with resected hepatic metastases from colorectal cancer. Patients who met eligibility criteria had an Infusaid pump (Infusaid Corporation, Sharon, MA, U.S.A.) implanted for intraarterial administration of chemotherapy. After complete surgical resection of hepatic metastases, FUDR (0.2 mg/kg/day) was given in 28-day cycles consisting of 14 days of treatment followed by 14 days of rest. Of 11 patients enrolled, one was ineligible, one received no treatment because of a blocked pump, and nine were treated per protocol. Of the nine treated patients, all are dead: one from hepatic toxicity, one from unrelated causes, and seven from progressive disease. Grade 3-4 toxicity included three cases of gastritis and two cases of hepatotoxicity from FUDR. Although this regimen was not successful, in part because of toxicity, the patient population studied here should be considered for future studies of adjuvant therapy.

Adult↗
PubMed1998

Phase I clinical and pharmacokinetic trial of penclomedine using a novel, two-stage trial design for patients with advanced malignancy.

PURPOSE: A novel phase I trial design was used to determine the maximum-tolerated dose (MTD) and pharmacokinetics for penclomedine when administered as an intravenous (i.v.) infusion over 1 hour daily for 5 days, repeated every 28 days. This study also tests the feasibility of a novel two-stage design for phase I trials. PATIENTS AND METHODS: Twenty-eight patients with advanced malignancy who met standard eligibility criteria were treated with i.v. penclomedine. The initial daily dose was 50 mg/m2. Dose escalations were planned using a modified Fibonacci sequence. One patient was enrolled on each dose level during the first stage of this trial. In the second stage, patients were enrolled in cohorts of three, proceeding in an up-and-down manner based on toxicities observed. MTD was determined by logistic regression analysis. Pharmacokinetic assessment was performed during the first cycle of treatment. RESULTS: Dose-limiting toxicities (DLT) observed during this trial were principally neurologic and were self-limited. Although hematologic toxicity was rare, the few patients with significant hematologic changes experienced late nadirs with prolonged time to recovery. The MTD was estimated as 381 mg/m2 (80% CI, 343 to 415 mg/m2). Although there was a long elimination half-life, accumulation of penclomedine over the 5 days of administration was negligible. CONCLUSION: The novel trial design used in this study was safe and appeared effective in limiting the numbers of patients treated at lower-dose levels. Reversible neurotoxicity was dose-limiting. Although the estimated MTD was 381 mg/m2, any dose within the CI would be reasonable for phase II study.

Adult↗
PubMed1997

Phase I clinical and pharmacokinetic study of oral carboxyamidotriazole, a signal transduction inhibitor.

PURPOSE: We conducted a phase I trial of carboxyamidotriazole (CAI, NSC 609974), designed to determine the maximum-tolerated dose (MTD), toxicity profile, and pharmacokinetic characteristics of CAI gelatin capsule (gelcap) formulation administered daily as a single oral dose. PATIENTS AND METHODS: Twenty-nine patients with advanced malignancy who met standard eligibility criteria were treated with once-daily CAI given in cycles of 28 days. Pharmacokinetic sampling was performed on days 1 and 29 and trough plasma CAI levels were assessed weekly. RESULTS: Patients were entered at dose levels of 50, 75, and 100 mg/m2. All three patients at the 100-mg/m2 level experienced dose-limiting neurocerebellar toxicity. Other neurotoxicities were mild. Gastrointestinal side effects were common, but generally mild, with 23 patients experiencing nausea and/or vomiting of any grade. Fatigue was a frequent complaint, with 19 patients experiencing mild to moderate symptoms. Six patients with nausea and vomiting and five with fatigue experienced relief of symptoms with a change to nocturnal administration of CAI. Peak plasma concentrations (Cp) occurred at 2.4 +/- 1.5 hours after administration of the oral gelcap dose. Patients approached steady-state trough plasma concentrations (Css) by days 8 to 15 and maintained a relatively constant Css throughout the course of treatment. For all patients, the mean variation in weekly CAI Cp was 12.4% +/- 5.3%. CONCLUSION: The MTD for the gelcap formulation was 75 mg/m2 with dose-limiting neurocerebellar toxicity (ataxia) seen at 100 mg/m2. Other prominent side effects, including nausea, vomiting, and fatigue, were partially alleviated through altering the administration schedule to nighttime dosing.

Antineoplastic Agents↗
PubMed1997

Fluorine-18-FDG evaluation of crossed cerebellar diaschisis in head injury.

UNLABELLED: This study investigates the phenomenon of crossed cerebellar diaschisis in head injury patients. METHODS: We visually compared fluorine-18-fluorodeoxyglucose (FDG)-PET images to radiograph computed tomography or magnetic resonance images in 19 patients with head injury. RESULTS: We found that of 68 focal unilateral lesions, 40% were associated with contralateral cerebellar hypometabolism and 19% were associated with ipsilateral cerebellar hypometabolism. Of supratentorial, extraparenchymal lesions (n = 20), 45% were associated with contralateral cerebellar hypometabolism, whereas 15% had ipsilateral cerebellar hypometabolism. Intraparenchymal lesions were associated with contralateral cerebellar hypometabolism in 38% of the patients and with ipsilateral cerebellar hypometabolism in 21% of the patients. Of the cortical lesions that were the patients' most severe injury, 69% were associated with contralateral cerebellar hypometabolism, whereas only 8% were associated with ipsilateral cerebellar hypometabolism. In patients with focal supratentorial lesions alone, 50% of all focal lesions were associated with contralateral cerebellar hypometabolism and 13% had ipsilateral hypometabolism. Of patients with both focal and diffuse brain injuries, 27% of the focal lesions had contralateral cerebellar hypometabolism and 27% had ipsilateral cerebellar hypometabolism to the most severe focal injury. CONCLUSION: Crossed cerebellar diaschisis is seen more often in patients with focal cortical or extraparenchymal injuries and is not seen in patients with multiple or diffuse brain injuries. Furthermore, this predominance is more pronounced with lesions of the greatest severity.

Adult↗
PubMed1996

Improved metabolic action of a bacterial lysine decarboxylase gene in tobacco hairy root cultures by its fusion to a rbcS transit peptide coding sequence.

The gene of a bacterial lysine decarboxylase (ldc) fused to a rbcS transit peptide coding sequence (tp), and under the control of the CaMV 35S promoter, was expressed in hairy root cultures of Nicotiana tabacum. The fusion of the ldc to the targeting signal sequence improved the performance of the bacterial gene in the plant cells in many respects. Nearly all transgenic hairy root cultures harbouring the 35S-tp-ldc gene contained distinctly higher lysine decarboxylase activity (from 1.5 to 30 pkat LDC per mg protein) than those which had been transformed with constructs in which the gene had been directly cloned behind the CaMV 35S promoter. The higher enzyme activity led to the accumulation of up to 0.7% cadaverine on a dry mass basis. In addition, part of the cadaverine pool was used for increased biosynthesis of anabasine, an alkaloid which was hardly detectable in control cultures. The best line contained anabasine levels of 0.5% dry mass, which could be further be enhanced by feeding of lysine.

Anabasine↗
PubMed1996

Does treatment of asymptomatic bacteriuria in older ambulatory women reduce subsequent symptoms of urinary tract infection?

OBJECTIVE: To determine whether treatment of symptomatic bacteriuria in older ambulatory women affects the subsequent development of symptoms of urinary tract infection. DESIGN: A controlled clinical trial. PARTICIPANTS: Older women not having urinary catheters. MEASUREMENTS: Urine cultures every 6 months (the same organism at 10(5) colony-forming units or more per mL on two midstream urine specimens defined asymptomatic bacteriuria) and questionnaire surveys for the new development of symptoms of urinary tract infection (dysuria, frequency, urgency, low back pain with fever) 1, 3, and 6 months after the initial survey. RESULTS: Of the 23 initially culture-positive participants receiving antibiotic treatment for symptomatic bacteriuria, nine were culture positive at 6 months, which contrasts with 18 of 27 who received no treatment or placebo, P = .05. However, symptoms of urinary tract infection were more common in the antibiotic-treated group. CONCLUSION: Antibiotic therapy effectively reduced the subsequent occurrence of positive urine cultures, but symptoms were not reduced. Based on this study of morbidity, previous studies failing to show any relation to mortality, and the cost and complications of antibiotic therapy in the older population, treatment of asymptomatic bacteriuria in older women is contraindicated.

Activities of Daily Living↗