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Biomedical subjects

G Lieberman

Publications and source records attributed to G Lieberman.

12 recordsLinked to original sources
PubMed2005

Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy.

PURPOSE: The aim of this study was to characterize the prevalence and predictors of central nervous system (CNS) metastasis among women with HER2-overexpressing metastatic breast cancer receiving trastuzumab-based therapy. METHODS: The frequency and time course of isolated CNS progression were characterized among women with HER2-positive metastatic breast cancer, receiving chemotherapy with or without trastuzumab as first-line treatment for metastatic disease in two clinical trials. The first trial was a multicenter randomized phase III study of chemotherapy (doxorubicin/cyclophosphamide or paclitaxel) +/- trastuzumab, and the second was a multicenter phase II trial of vinorelbine + trastuzumab. All patients had measurable disease and were free of symptomatic CNS disease at initiation of study treatment. RESULTS: Nearly 10% of patients receiving trastuzumab in combination with chemotherapy developed isolated CNS metastases as first site of tumor progression. Progression in the CNS tended to be a later event than progression at other sites among women receiving trastuzumab-based therapy. Trastuzumab-based treatment did not substantially delay onset of CNS metastases as initial site of progression. Following diagnosis with primary breast cancer, tumors with HER2 gene amplification tend to be associated with greater risk of isolated CNS progression compared with those lacking gene amplification. CONCLUSIONS: Patients with HER2-overexpressing metastatic breast cancer are at risk for isolated CNS progression, reflecting improved peripheral tumor control and patient survival through use of trastuzumab-based therapy, and a relative lack of CNS activity with trastuzumab. Clinicians should be aware of this association. Better treatments for CNS recurrences are needed.

Antibodies, Monoclonal↗
PubMed2001

Clinical competence assessment in radiology: introduction of an objective structured clinical examination in the medical school curriculum.

RATIONALE AND OBJECTIVES: Traditional oral and written examinations can be limited in predicting future clinical performance. Therefore Objective Structured Clinical Examinations (OSCEs) have been introduced in other specialties. The authors assessed their value in radiology. MATERIALS AND METHODS: The study includes 122 Harvard medical students who undertook 1-month compulsory clerkships at one of three hospitals (A, B, or C) in their 3rd and 4th year and a compulsory OSCE in their 4th year. The OSCE was constructed from five cases. Each had eight or nine standardized questions designed to test, within a set time, the perception of essential findings, their interpretation, and clinical judgment (maximum possible score, 100). Clerkship grades were high honors (score of 3), honors (score of 2), satisfactory (score of 1), and fail (score of 0). Predictors of OSCE scores-clerkship grade and affiliated hospital-were modeled as linear functions. Time elapsed between clerkship and OSCE was modeled as a nonlinear function. RESULTS: Although there was a positive relation between clerkship grade and OSCE grade, it accounted for an increase of only 5.7% in OSCE score per clerkship grade and did not predict performance of individual students. Students who trained in hospital B showed significantly higher OSCE grades. OSCE scores were highest when the examination was taken 8 months after the clerkship. CONCLUSION: The OSCE may be useful to uncover deficits in individuals and groups beyond the ones detected with traditional clerkship evaluations and provide guidance for remediation. The improved performance after additional clinical exposure suggests that the OSCE may be well suited to test the integration of radiologic and clinical knowledge.

Clinical Clerkship↗
PubMed2001

The clinical application of a dual head gamma camera with coincidence detection in 20 women with suspected ovarian cancer.

OBJECTIVE: To assess the effectiveness of a dual head coincidence gamma camera in identifying ovarian cancer as a less expensive alternative to the traditional 2-[18F] fluoro-2-deoxy-D-glucose (18FDG) system using positron emission tomography. DESIGN: Prospective study. POPULATION: Twenty consecutive women suspected of having ovarian carcinoma. Inclusion was based on abnormal serum CA125 (reference range is 0-35 units/L), ultrasound, computerised tomography or clinical findings. METHODS: Women underwent assessment before staging laparotomy. Two nuclear medicine physicians, who were blinded to the pre-operative assessment, reported on 18FDG- dual head coincidence gamma camera imaging. MAIN OUTCOME MEASURES: The histology and operative staging were compared with the 18FDG- dual head coincidence gamma camera findings. RESULTS: Twelve women had pelvic malignancies (nine primary and three recurrences), seven women had benign pathology and one patient had a borderline malignancy. We were able to image accurately all malignant pelvic masses with dual head coincidence gamma camera, as well as accurately demonstrate disease spread. Two of the benign pelvic masses localised 18FDG. The positive predictive value for detecting malignancy was 86%. CONCLUSIONS: Dual head coincidence gamma camera offers accurate and affordable imaging in suspected ovarian masses, with improved specificity over CA125, ultrasound and computerised tomography. These results are similar to those obtained on more expensive dedicated PET systems. We report on a series of patients believed to have primary or recurrent carcinoma and recognise the need to include patients more likely to have benign lesions to assess false positive results. However, we believe that dual head coincidence gamma camera is useful in the pre-operative assessment of women with suspected ovarian cancer.

Adult↗
PubMed2000

Preoperative diagnosis of ovarian carcinoma with a novel monoclonal antibody.

OBJECTIVE: This study was undertaken to determine whether preoperative radioimmunoscintigraphy of complex ovarian masses with technetium Tc 99m MAb-170 (Tru-Scint AD; Biomira Inc, Edmonton, Alberta, Canada), a murine whole immunoglobulin G monoclonal antibody that has been found to have panadenocarcinoma affinity, would predict surgical findings. STUDY DESIGN: The age range of studied patients was 42 to 83 years (mean, 60.3 years). Planar computed tomographic imaging and single-photon emission computed tomographic imaging were performed at 15 minutes, 6 to 8 hours, and 18 to 24 hours after injection of 1000 MBq technetium Tc 99m MAb-170. Laparotomy was performed within 10 days. RESULTS: Eighteen patients had borderline or invasive ovarian cancers verified by histologic examination. All primary malignancies or deposits (including intrahepatic deposits) yielded positive results on radioimmunoscintigraphic imaging. Radioimmunoscintigraphy was able to identify serosal deposits not seen on computed tomographic or ultrasonographic scans. False-positive localization of the antibody was noted in 6 of the 9 patients with benign pathologic processes. CONCLUSION: It is possible to detect with technetium Tc 99m MAb-170 all patients who have cancer (including sites not seen on computed tomographic or ultrasonographic scan); however, the low specificity (33%) means that patients still require surgical verification of disease.

Adenocarcinoma↗
PubMed1999

Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease.

PURPOSE: Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease. PATIENTS AND METHODS: Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals. RESULTS: Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events. CONCLUSION: Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.

Adult↗
PubMed1996

Acute severe low back pain. A population-based study of prevalence and care-seeking.

STUDY DESIGN: Telephone interviews were conducted with a random sample of adults in 4437 North Carolina households. The response rate was 79%. OBJECTIVE: The prevalence of low back pain and the correlates of care-seeking in a defined population were examined. SUMMARY OF BACKGROUND DATA: Previous research on low back pain has used varying definitions of the illness of low back pain, and has admixed patients with acute and chronic low back pain. Acute low back pain was examined in this study as a distinct phenomenon separate from chronic low back pain. METHODS: Respondents completed a detailed interview regarding the occurrence of and care sought for back pain in 1991. Acute back pain was defined as functionally limiting pain lasting less than 3 months. RESULTS: From this sample, 485 individuals had at least one occurrence of acute severe low back pain in 1991, representing 7.6% of the adult population. Symptoms were reported less commonly in individuals older than age 60 years (5% vs. 8.5%) and in nonwhites compared with whites (5% vs. 8.5%). Thirty-nine percent of those with back pain sought medical care; 24% sought care initially from an allopathic physician, 13% from a chiropractor, and 2% from other providers. More prolonged pain, more severe pain, and sciatica were associated with care-seeking. Gender, income, age, rural residence, and health insurance status did not correlate with the decision to seek medical care. Younger age, male gender, and nonjob-related pain did correlate with the decision to seek care from a chiropractor. CONCLUSIONS: Acute back pain is common. Care is often sought regardless of income and insurance status. Seeing a health care provider for acute back pain may not be discretionary from the perspective of the patient.

Acute Disease↗
PubMed1996

Ocular and cerebral trauma in non-accidental injury in infancy: underlying mechanisms and implications for paediatric practice.

AIMS: To determine the sites, mechanisms, and clinical significance of injuries to the eyes and brains of children with non-accidental injuries in relation to differing levels of trauma. METHODS: A forensic pathological study of injuries in the eyes and brains of 23 consecutive children dying of non-accidental injuries over a 4 year period (1988-92) under the jurisdiction of Yorkshire and Humberside coroners. RESULTS: Sixteen children died from cerebral injuries and seven died from non-cerebral causes. There were high incidences of retinal detachment (63%) and subhyaloid (75%), intraretinal (75%), and perineural (68%) haemorrhages in CNS deaths. Local subhyaloid haemorrhages and retinal detachment were more common at the periphery and optic disc than at the equator. There was a strong correlation between CNS and eye trauma scores in all 23 children (r = 0.7551, p < 0.0001). Ranking of injuries by severity suggests progressively more trauma required for (a) subdural haemorrhage, (b) subhyaloid, intraretinal, perineural haemorrhages, and (c) retinal detachment. At highest trauma levels choroidal and vitreous haemorrhages were associated with additional cerebral lacerations, intracerebral and subarachnoid haemorrhages. CONCLUSIONS: In non-accidental (and probably accidental) infantile head injury the earliest eye injuries (coinciding with subdural haemorrhage) could be missed if indirect ophthalmoscopy is not performed. Retinal detachment and multiple (particularly choroidal/vitreous) haemorrhages may indicate additional cerebral lacerations and/or intracerebral haemorrhage. Vitreous traction is the likely cause of intraocular pathology.

Battered Child Syndrome↗
PubMed1985

Evaluation of the Quantum II yeast identification system.

We compared three methods for identifying clinical yeast isolates: Abbott Quantum II, API 20C, and a modified BBL Minitek system. The API 20C and modified Minitek systems agreed on the identification of 243 of 245 yeasts (99.2%). The Quantum II system correctly identified 197 (80.4%), incorrectly identified 19 (7.8%), and did not identify 29 (11.8%) of the yeasts. Most of the misidentifications with the Quantum II occurred because assimilation or biochemical results were false-positive. Sixteen different species of yeasts and 16 different Quantum II substrates contributed to the discrepancies. On retesting with the Quantum II, 31% of the discrepant strains were correctly identified, while the remaining 69% were incorrectly identified or were not identified. Erroneous biochemical and assimilation results were also noted with yeasts that were correctly identified by the Quantum II system.

Candida↗
PubMed1983

Development of preimplantation embryos of the golden hamster in a defined culture medium.

Eight-cell embryos were recovered from mated golden hamsters that had been superovulated with pregnant mare's serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Embryos were cultured for 24 or 32 h in a defined medium (modified Tyrode's solution) designed for fertilization of hamster oocytes in vitro. This medium was supplemented in some experiments with amino acids (glutamine, phenylalanine, methionine and isoleucine) and with vitamins (Eagle's Minimum Essential Medium vitamin supplement). At the end of the culture period, the numbers of embryos developing to the blastocyst stage were recorded. In other experiments, the effects of varying the osmotic pressure (225, 250, 275 and 300 m0smol/kg) and the pH (6.8 and 7.4) of the culture medium on blastocyst formation were examined. A difference was found between the ability of early 8-cell embryos (approx. 54 h post-egg activation) and late 8-cell embryos (approx. 62 h post-egg activation) to develop in culture. In the unsupplemented culture medium, only 2% of early 8-cell embryos developed to the blastocyst stage compared with 22% of late 8-cell embryos. A marked effect of the four amino acids on development was found. In the presence of amino acids 36% of early 8-cell embryos developed into blastocysts (18-fold increase). The amino acids also increased the percentage of late 8-cell embryos that developed into blastocysts from 22% to 66%. These data suggest that an important metabolic change may occur in hamster embryos during a critical period at the 8-cell stage of development. No additional effect on development was observed when vitamins were included in the culture medium. No significant effect of either osmotic pressure of pH of the culture medium on development was found. When blastocysts formed from cultured 8-cell embryos were transferred surgically to pseudopregnant hamsters, about 25% developed into normal-looking fetuses and 5 normal-looking young were born, 4 of which have survived. These results represent an approach towards achieving complete preimplantation development of hamster embryos in vitro.

Amino Acids↗
PubMedDate not supplied

Operative treatment of metacarpal and phalangeal shaft fractures.

Diaphyseal fractures of the metacarpals and phalanges are common injuries that can lead to impairment of hand function. The fracture pattern and soft-tissue injury vary with the mechanism of injury. The imbalance of the flexor and extensor forces created by displaced fractures will often produce a secondary angulatory deformity. Nonoperative treatment is indicated for reducible and stable fracture configurations. Irreducible or unstable fracture patterns require open or closed reduction and fixation. Reduction must be assessed in flexion and extension to ensure correct rotatory alignment. Fracture fixation can be achieved with the use of Kirschner wires, interfragmentary screws, or plates. The outcome after surgery is greatly influenced by the condition of the surrounding soft tissues; therefore, surgical trauma should be minimized to optimize the result.

Adult↗