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Biomedical subjects

D Friedland

Publications and source records attributed to D Friedland.

9 recordsLinked to original sources
PubMed2000

Lymphatic malformation: predictive factors for recurrence.

OBJECTIVE: Although lymphatic malformations are often found to be well circumscribed when surgery is undertaken in early childhood, complete surgical excision can be difficult when the lesion is infiltrative. This study retrospectively evaluates these patients in an attempt to identify prognostic factors that may predict recurrence. STUDY DESIGN AND SETTING: A retrospective chart review was conducted covering the years 1991 to 1998. Seventeen patients were identified having undergone 32 surgical resections of tumors described as lymphatic malformations. Data abstracted from the charts included the site of the lesion, surgical and histologic assessment of encapsulation, and status at follow-up examination. RESULTS: Six of 17 patients developed a recurrence after surgery. Correlation between recurrence and histologic or operative impressions of encapsulation was significant by chi(2) analysis (P<0.01). CONCLUSION: On the basis of the findings of this case series, lymphatic malformations that are found to be nonencapsulated and infiltrative by intraoperative or histologic assessment are more likely to recur.

Adolescent↗
PubMed1999

Phase I clinical/pharmacokinetic and pharmacodynamic trial of the c-raf-1 antisense oligonucleotide ISIS 5132 (CGP 69846A).

PURPOSE: Raf-1 is a protein kinase that plays a broad role in oncogenic signaling and acts as a downstream effector of Ras in the mitogen-activated protein kinase pathway. The present study was designed to determine the maximum-tolerated dose (MTD), toxicity profile, pharmacokinetics, and antitumor activity of the c-raf-1 antisense oligodeoxynucleotide ISIS 5132 (CGP 69846A; ISIS Pharmaceuticals Inc, Carlsbad, CA). The effect of ISIS 5132 on c-raf-1 gene expression in peripheral-blood mononuclear cells (PBMCs) of treated patients was studied using a reverse transcriptase polymerase chain reaction assay. PATIENTS AND METHODS: Patients with refractory malignancies received ISIS 5132 as a 2-hour intravenous infusion three times weekly for 3 consecutive weeks. Pharmacokinetic sampling was performed during the first cycle in all patients; PBMCs for c-raf-1 mRNA analysis were collected at baseline and on days 3, 5, 8, and 15 of cycle 1 and on day 1 of each cycle thereafter. RESULTS: Thirty-one patients received ISIS 5132 at one of nine dose levels ranging from 0.5 mg/kg to 6.0 mg/kg. Clinical toxicities included fever and fatigue, but these were not dose limiting. A clinically defined MTD was not reached. The harmonic mean half-life of ISIS 5132 was 59.8 minutes (range, 35.5 to 107.3 minutes). The area under the concentration-time curve increased linearly with dose, and mean plasma clearance was 1.86 mL/kg/min (range, 1.21 to 2.41 mL/kg/min). Two patients experienced prolonged stable disease lasting more than 7 months, which was associated with persistent reduction in c-raf-1 expression in PBMCs. Significant decreases in c-raf-1 expression were identified at time points after the baseline value (P <.05) at doses >/= 2.5 mg/kg. CONCLUSION: ISIS 5132 is well tolerated at doses up to 6.0 mg/kg when administered as a thrice weekly 2-hour infusion for 3 consecutive weeks. The pharmacokinetic behavior of the drug is reproducible, and suppression of target gene expression is observed in circulating PBMCs.

Adult↗
PubMed1999

A phase II trial of docetaxel (Taxotere) in hormone-refractory prostate cancer: correlation of antitumor effect to phosphorylation of Bcl-2.

Twenty-one patients with hormone refractory prostate cancer were enrolled to receive single-agent docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) 75 mg/m2 intravenously every 21 days. Six patients consented to biopsies of the prostate tumor before and following the first cycle of chemotherapy and 11 patients underwent periodic blood collection for isolation of the mononuclear cell fraction. The toxicities of treatment were moderate but included eight episodes of grade III and two episodes of grade IV nonhematologic toxicity as well as seven episodes of grade III and 11 episodes of grade IV hematologic toxicity (primarily neutropenia, including four episodes of febrile neutropenia). An objective response of more than 50% reduction in prostate-specific antigen was observed in seven patients (38%) and more than half of the patients with symptomatic disease at the initiation of therapy had improvements on treatment. Radiographic or scintigraphic evidence of tumor regression was observed in six patients. Nine patients experienced a prolonged period of stable disease on treatment (median, six cycles). Tumor specimens are currently being analyzed for bcl-2 expression and phosphorylation. The current series confirms the substantial single-agent activity of docetaxel in hormone refractory prostate cancer and may help to further elucidate its mechanism of action at the molecular level.

Aged↗
PubMed1998

Conversation analysis of communication breakdown after closed head injury.

This single case study investigated the use of Conversation Analysis (CA) in assessing pragmatic language difficulties after closed head injury (CHI). The aim was to see if CA captures the types of communication breakdown observed after CHI and whether results from CA can be directly related to scores on formal tests more typically applied after CHI. The results suggested that CA was a sensitive tool for identifying and investigating pragmatic deficits in this case. It facilitated an exploration of whether language impairments identified on formal tests manifest themselves in functional communication; it revealed how different interlocutors adapt to these language difficulties in conversation and also explained why some conversational partners were more successful than others. Considered together, formal test results and CA insights facilitated an in-depth analysis into the precise nature of the communicative impairments of the speaker in this exploratory study, suggesting that CA is a promising approach to the assessment of pragmatic impairments in the CHI population.

Adaptation, Psychological↗
PubMed1997

Spread of the Spanish multi-resistant serotype 23F clone of Streptococcus pneumoniae to Seoul, Korea.

Multi-resistant serotype 23F pneumococcal strains from an outbreak in a day-care centre in South Africa and strains from sporadic cases in Korea were analysed for their relatedness, by means of arbitrarily-primed PCR (AP-PCR), repetitive extragenic palindromic PCR (rep-PCR) and penicillin-binding protein (PBP) gene profiles. The South African strains previously shown to be identical to the 23F Spanish clone had identical AP-PCR and rep-PCR patterns to 13 Korean isolates. PBP gene analysis of strains from this cluster showed identical fingerprints, suggesting clonality. Isolates, identical genotypically to the 23F clone appeared to have acquired the type 19F and 14 capsular serotypes, respectively, a result that suggests horizontal transfer of capsular biosynthetic genes. These same techniques revealed three serotype 9V isolates not closely related to the 23F clone but which harbour PBP genes identical to the 23F clone. The data presented suggests that a clone of S. pneumoniae serotype 23F related to isolates from Spain and South Africa has become disseminated in Korea.

Cloning, Molecular↗
PubMed1996

Phase II trial of all-trans retinoic acid in metastatic non-small cell lung cancer.

The toxicity and marginal effectiveness of cytotoxic chemotherapy in metastatic non-small cell lung cancer (NSCLC) necessitates the search for new agents. Preliminary data in lung cancer and other malignant and premalignant disorders have identified retinoid compounds as potentially useful antitumor agents. Twenty-eight patients with metastatic NSCLC were treated with oral all-trans retinoic acid in a phase II trial. The study population consisted of patients with excellent performance status and minimal weight loss. Toxicities were generally mild and included cutaneous effects, headache, and myalgia. A significant number of patients developed elevations of hepatic transaminases or hyperlipidemia and 3 patients had treatment-related leukocytosis. Two patients (8%) achieved a partial response, and 1 had a mixed response. The duration of remission in the 2 responders was 7 and 13 months and the median survival of all patients 7 months. Therefore, all-trans retinoic acid has minimal activity as a single agent in NSCLC but warrants further study in combination with biological agents and chemotherapy.

Adult↗
PubMed1994

First hints in non-small cell lung cancer (NSCLC).

All-trans retinoic acid was evaluated in metastatic measurable non-small cell lung cancer. All-trans retinoic acid was given at 175 mg/m2 orally on a daily basis. Twenty-eight patients (median age 58, 16 males, 12 women) had an ECOG performance status of 0 (26 patients) and 1 (two patients). Sixteen of the 28 had no weight loss. Eleven had between 5 and 10% and only one had greater than 10% weight loss at time of entry. Toxicities included cutaneous (cheletis 25/28), fatigue (10/28), myalgias/anthralgias (9/28), and headache (17/28). Alterations in triglycerides and hepatic transaminases were noted in a majority of patients. Two partial responses occurred in patients with adenocarcinoma. Both responses were 7 months in duration. Activity of all-trans retinoic acid in metastatic non-small cell lung cancer is minimal, but due to its low toxicity profile it should be tested in setting with other agents.

Adenocarcinoma↗
PubMedDate not supplied

Verbal fluency in elderly bilingual speakers: normative data and preliminary application to Alzheimer's disease.

This study investigated verbal fluency abilities in 30 healthy elderly English-Afrikaans bilingual speakers, and 6 bilingual subjects with Alzheimer's disease. Three 1-min semantic verbal fluency tasks (animals) were obtained in the bilingual mode, Afrikaans and English. Results were analysed in terms of total correct, and semantic clusters. There was no significant difference between monolingual and bilingual performance. Some healthy bilingual subjects used code switching as a strategy but with no direct increase in the number of exemplars generated, and there was no relationship between age of acquisition, pattern of use and verbal fluency scores. In comparison, subjects with Alzheimer's disease did not make use of code switching strategies, and there was some relationship between age of acquisition, pattern of use and verbal fluency scores.

Aged↗