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Biomedical subjects

G Whitman

Publications and source records attributed to G Whitman.

18 recordsLinked to original sources
PubMed2004

Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer.

PURPOSE: The goal of this study was to examine the feasibility of developing a multigene predictor of pathologic complete response (pCR) to sequential weekly paclitaxel and fluorouracil + doxorubicin + cyclophosphamide (T/FAC) neoadjuvant chemotherapy regimen for breast cancer. PATIENTS AND METHODS: All patients underwent one-time pretreatment fine-needle aspiration to obtain RNA from the cancer for transcriptional profiling using cDNA arrays containing 30721 human sequence clones. Analysis was performed after profiling, and 42 patients' clinical results were available, 24 of which were used for predictive marker discovery; 18 patients' results were used as an independent validation set. RESULTS: Thirty-one percent of patients had pCR (six discovery and seven validation), defined as disappearance of all invasive cancer in the breast after completion of chemotherapy. We could identify no single marker that was sufficiently associated with pCR to be used as an individual predictor. A multigene model with 74 markers (P <or=.09) was built using data from the discovery samples and tested on the validation samples. Overall, a 78% (14 of 18) predictive accuracy was observed, with a 100% (three of three) positive predictive value for pCR, a 73% (11 of 15) negative predictive value, a sensitivity of 43% (three of seven), and a specificity of 100% (11 of 11). The expected response rate to T/FAC neoadjuvant therapy in unselected patients is 28%. CONCLUSION: Our results suggest that transcriptional profiling has the potential to identify a gene expression pattern in breast cancer that may lead to clinically useful predictors of pCR to T/FAC neoadjuvant therapy.

Adult↗
PubMed2000

Role of specimen radiography in patients treated with skin-sparing mastectomy for ductal carcinoma in situ of the breast.

BACKGROUND: Specimen radiography is an important part of breast conservation surgery for ductal carcinoma in situ (DCIS). The objective of this study was to determine whether mastectomy specimen radiography could help in obtaining negative resection margins in patients with DCIS undergoing skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR). METHODS: Of 95 patients treated at our institution with SSM and IBR for DCIS, 35 had specimen radiography. The mastectomy specimen was first examined grossly and then inked, serially sectioned, and sent for radiographic assessment. Tissue slices containing calcifications were identified for pathologic evaluation. Additional tissue was excised if tumor was found near the inked margins or if calcifications were found near the radiographic margins. RESULTS: Of the 35 patients who had specimen radiography, the radiographic margins were free of calcifications in 30 patients (86%); of these patients, the margins on the final histologic examination were free of tumor in 27 and within 1 mm in 3. The other five patients (14%) had calcifications close to the radiographic margin; four underwent an intraoperative re-excision, but the margin for one of those four patients was still positive on final histologic examination. Margins were found to be negative by both mastectomy specimen radiography and histology in 77% of the patients. Of the 95 patients with DCIS, three patients (3%), none of whom had specimen radiography, developed local recurrences. One of these was successfully re-treated, one died as a result of synchronous distant metastases, and one was lost to follow-up. At a median follow-up time of 3.7 years, 93 patients (98%) were alive and free of disease. CONCLUSIONS: Intraoperative radiography of mastectomy specimens may be useful for assessing margin status and for identifying the location of microcalcifications within tissue slices.

Adult↗
PubMed1996

FK 506 therapy for refractory renal allograft rejection: lessons from liver transplantation.

FK 506 has proven to be an effective immunosuppressive agent in liver transplantation, but its role in renal transplantation remains to be defined. Since the initial availability of FK 506 for treatment of refractory renal allograft rejection, we have applied an aggressive approach consisting of institution of rescue therapy at an early point in the rejection process combined with assiduous monitoring of FK 506 blood levels and the histologic response to therapy. A total of 17 adult patients were treated for refractory renal allograft rejection with this approach. Median follow-up was 9 months post-initiation of FK 506 therapy. Median time to first rejection was 26 d post-transplant, and median time to FK 506 rescue therapy was 113 d post-transplant. Sixteen of 17 patients received either ATGAM or OKT3 induction therapy. Prior to FK 506 rescue therapy, patients received the following antirejection therapy: corticosteroids 40 + 21 mg/kg (prednisone or Solumedrol), OKT3 (median 14 d), ATGAM (3 patients, 14 d each). FK 506 rescue therapy was successful in reversing the rejection process in all 17 patients. Fifteen patients (88%) demonstrated rapid reversal of rejection (i.e. reversal within 14 d), whereas three patients demonstrated delayed reversal. Nine month actuarial patient and graft survivals were 92% and 84%. When censored for documented noncompliance, nine month actuarial graft survival was 92%. Good long-term renal function was observed (pre-FK 506 baseline creatinine 2.1 +/- 0.5 mg/dl, current serum creatinine 2.1 +/- 0.6 mg/dl. Six recurrent rejection episodes occurred in 5 patients (29%) with a median time to recurrent rejection of 59 d post-initiation of FK 506 rescue therapy. Each recurrent rejection episode was successfully treated by corticosteroids and/or increased FK 506 dose. CMV disease and lymphoma were not observed. Histologic evidence of FK 506 nephrotoxicity (hyaline necrosis in preglomerular arterioles) was observed in 6 patients 30% (median time to diagnosis 49 d). FK 506 blood levels (whole blood TDX) between 10 and 20 ng/ml provided effective reversal in most patients. Current FK 506 dose and blood levels are 0.18 +/- 0.09 mg/kg/d and 7 +/- 2 ng/dl). FK 506 rescue therapy also allowed aggressive reductions in prednisone dose: (mean current prednisone dose 0.08 +/- 0.05 mg/kg/d). In conclusion, an aggressive approach toward FK 506 rescue: 1) provides prompt, effective reversal of refractory renal allograft rejection, 2) good long-term renal allograft function, 3) balanced immunosuppression with respect to recurrent rejection, opportunistic infection and PTLD, 4) acceptable toxicity, and 5) aggressive reduction in corticosteroid dosing. Based on these findings, FK 506 rescue therapy is now the treatment of choice in our program for renal allograft rejection episodes that occur following antilymphocyte antibody therapy.

Adult↗
PubMed1993

5-Fluorouracil, hydroxyurea and escalating doses of iododeoxyuridine with concomitant radiotherapy for malignant gliomas: a clinical and pharmacologic analysis.

BACKGROUND: Iododeoxyuridine (IUdR) is a known radiation enhancer, and interacts biochemically with 5-fluorouracil (5-FU) and hydroxyurea (HU). PATIENTS AND METHODS: IUdR was added to the previously studied regimen of continuous infusion 5-FU at 300 mg/m2/day for 5 days, HU 500 mg every 12 hours for 11 doses and radiotherapy 200 cGy/day for 5 days, all administered for 7 consecutive weeks to patients with malignant glioma. IUdR was administered as 5-day continuous intravenous infusion during weeks 1 and 4. The IUdR dose was changed in cohorts of patients. IUdR plasma concentrations were determined during weeks 1 and 4, and IUdR incorporation into the DNA of granulocytes was measured on weeks 2 and 5. RESULTS: Two patients treated at the initial IUdR dose of 500 mg/m2/day developed grade 3 or 4 myelosuppression and mucositis. Additional dose levels of IUdR tested were 250 mg/m2/day and 125 mg/m2/day; at the latter dose, severe or life-threatening toxicity was seen in only 3 of 8 patients treated. IUdR incorporation into DNA of granulocytes was 10.5(+/- 2.3)% at an IUdR dose of 500 mg/m2/day but decreased to 0.76(+/- 0.3)% at 125 mg/m2/day. Similarly, IUdR plasma concentrations decreased from 436 (+/- 114) ng/ml to 99 (+/- 29) ng/ml. CONCLUSIONS: The addition of IUdR to 5-FU and HU results in significant systemic toxicity necessitating limitation of the IUdR dose to 125 mg/m2/day. There is a significant biochemical interaction between IUdR, 5-FU and HU leading to increased IUdR incorporation into DNA and to substantial clinical toxicity. Further clinical studies to exploit this interaction at more feasible schedules may be useful.

Adult↗
PubMed1992

Continuous-infusion fluorodeoxyuridine with leucovorin and high-dose interferon: a phase II study in metastatic renal-cell cancer.

A total of 25 patients with metastatic renal cancer were treated on a phase II protocol with 5 days of continuous-infusion fluorodeoxyuridine (FUDR), (0.1 mg/kg daily) together with high-dose oral leucovorin (100 mg 4 h) and daily x6 high-dose interferon-alpha 2b (30 x 10(6) IU/m2). Despite the good performance status of the patients and the inclusion of 14 previously untreated patients in the cohort, no response was observed among the 20 evaluable patients. Toxicities included high fever, moderate anemia, transient leukopenia, transient and mild elevations of transaminases, and moderate to severe nausea, vomiting, diarrhea, and mucositis. There were also two episodes each of confusion, fluid retention, and pancreatitis and one episode of increased creatinine levels. During the study three deaths occurred, two of which were possibly therapy-related. Despite previous reports of activity of FUDR in metastatic renal cancer, the present regimen cannot be recommended.

Administration, Oral↗
PubMed1990

Improved cannulation method for extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation has been shown to be useful for patients in reversible cardiogenic shock. Effective arterial cannulation techniques for infants have been developed that are simple to use and require minimal subsequent vascular repair or reconstruction after removal. Groin cannulation in adults frequently requires bidirectional arterial cannulation to ensure adequate distal perfusion as well as frequent complex arterial repairs after discontinuation. We describe a simple arterial cannulation technique using a single right-angle, high-flow arterial cannula. With this technique adequate bidirectional arterial perfusion is maintained with a single arterial cannula while the need for vascular repairs or reconstruction is minimized.

Catheterization, Peripheral↗
PubMed1990

Bronchial anomaly of the right upper lobe.

This case report presents a rare anomaly of right upper lobe bronchial anatomy. During routine right upper lobe resection for carcinoma, a common right upper and middle lobe bronchus was found. The resection was completed as a right upper and middle bilobectomy. Knowledge of this uncommon variant was beneficial in performing the pulmonary resection. A review of the literature is presented.

Adenocarcinoma↗
PubMed1988

Influence of human chorionic gonadotropin (hCG) and hCG internalization by granulosa cells on the rate of in vitro fertilization and embryonic development of human oocytes.

Follicular fluids and granulosa cells were obtained from 28 aspirated follicles of nine women undergoing laparoscopy in an in vitro fertilization program. Follicular growth was stimulated by a human menopausal gonadotropin regimen and laparoscopy was performed 32 hours after human chorionic gonadotropin (hCG) administration. Follicular fluid 17 beta-estradiol (E2) levels were higher and hCG levels were lower in follicles with oocytes that fertilized and cleaved beyond two blastomeres (greater than two-cell group) than in those with nonfertilizable oocytes (NF group) (P less than 0.05). Compared to those from the NF group, granulosa cells from the greater than two-cell group secreted less progesterone (P) in vitro and had a fourfold increase in percentage of cells with internalized hCG. These results demonstrate that the steroidogenic capacity of granulosa cells from follicles whose oocytes fertilize and undergo accelerated embryonic development in vitro differs from the capacity of granulosa cells from NF follicles. This difference may be due to their enhanced ability to bind and subsequently internalize hCG.

Chorionic Gonadotropin↗
PubMed1987

A comparison of thermal injury, healing patterns, and postoperative adhesion formation following CO2 laser and electromicrosurgery.

To further define the role of CO2 laser in infertility surgery, the authors compared the immediate tissue damage and the subsequent healing patterns that followed the randomized use of CO2 laser and electrocautery on opposite sides of the reproductive tracts of 20 mature, female rabbits. Blind histopathologic evaluations were performed on the ovarian and uterine tissues immediately to compare the extent of the acute thermal damage, and 4 weeks postoperatively to compare the healing patterns. There were no differences in the depth of thermal damage, extent of collagen deposition, or in postoperative adhesion formation between CO2 laser and electrocautery. However, the mean depth of the acute thermal damage was significantly less on the ovary than on the uterus, and the area of fibrosis was significantly less when the incised uterine surfaces were approximated.

Animals↗
PubMed1985

Quinidine photosensitivity.

A 55-year-old woman developed a dermatitis confined to light-exposed areas while taking quinidine gluconate, warfarin sodium, furosemide, spironolactone, and digoxin after cardiac surgery. Phototesting indicated a normal erythematous response to 290- to 320-nm ultraviolet radiation, but she developed erythema from 6 joules/sq cm of 320- to 400-nm radiation (ultraviolet A [UV-A]), a much lower dose than needed to produce a reaction in normal individuals. Two days after she discontinued quinidine and warfarin, phototesting showed no reaction to as much as 20 joules/sq cm of UV-A. One week after resuming quinidine (but not warfarin), she again reacted to 8 joules/sq cm of UV-A. No reactivity was elicited when the preparation was applied to the skin or injected into the dermis either with or without subsequent UV-A irradiation.

Dose-Response Relationship, Radiation↗
PubMed1984

The influence of infused calcium on the postischemic myocardium.

Despite evidence for calcium-induced damage in the postischemic myocardium, calcium remains a frequently used inotropic agent following cardiopulmonary bypass surgery with cardioplegic arrest. The purpose of this study was (1) to challenge the postischemic myocardium with incremental doses of ionized calcium, and (2) to relate postischemic calcium reperfusion concentration to final recovery of left ventricular contractile function. Rabbit hearts (N = 38) were perfused and equipped with a ventricular balloon to monitor developed pressure (DP) +/- dp/dt, and left ventricular end diastolic pressure (LVEDP). Hearts underwent 40 min of global ischemia. Hearts were then assigned to one of four groups to receive a variable calcium concentration (0.6, 1.2, 2.5, 5.0 mM) for the initial 5 min of reperfusion followed by 55 min of reperfusion (Ca+2 = 1.25 mM). No differences were found between groups for final recovery of DP +/- dp/dt, or final LVEDP. It was concluded that: (1) within the physiologic range, variable calcium infusions during the first 5 min of postischemic reperfusion do not impair final recovery of LV contractile function, (2) irreversible partial recovery of left ventricular function appears due to mechanisms other than mitochondrial or myofibrillar calcium loading during reperfusion, and (3) infused calcium is a safe inotropic agent even in the postischemic myocardium.

Animals↗
PubMed1983

The relationship between global myocardial ischemia, left ventricular function, myocardial redox state, and high energy phosphate profile. A phosphorous-31 nuclear magnetic resonance study.

UNLABELLED: The onset of global myocardial ischemia was related to mechanical function (intraventricular pressure), cellular redox state (NADH fluorophotography), and high energy profile (phosphorous-31 nuclear magnetic resonance). Ten rabbit hearts were excised and perfused on a modified Langendorff apparatus (37 degrees C; pO2 480 Torr). Developed pressure and positive and negative dp/dt were determined at control, 1-10, 15, 30, 45, and 60 sec of acute global ischemia. NADH fluorophotographs were taken at control, 1-10, 15, 20, 30, 60 sec, and 5, 10, and 30 min. P-31 NMR spectra in 14 guinea pig hearts under identical conditions were obtained at control, 1, 5, 10, 20, 40, and 60 min of acute global ischemia. LV contractility diminished within 1 sec (P less than 0.01) of ischemia and dropped to less than 35% of control by 1 min. Reduction of mitochondria was detected by epicardial NADH fluorophotography at 2 sec of ischemia. Cellular pH diminished 0.3 pH units by 5 min. Adenosine triphosphate (ATP) concentration remained at control levels while phosphocreatine (PCr) dropped to 63 +/- 8.5% of control by 1 min of ischemia. CONCLUSIONS: After the onset of global ischemia (1) mitochondrial electron transport ceases by 2 sec; (2) acidosis develops immediately; (3) LV contractility diminishes by 1 sec; (4) ATP concentration appears to be buffered by PCr, and is dissociated from myocardial function.

Adenosine Triphosphate↗
PubMed1982

Vascular ring: left cervical aortic arch, right descending aorta, and right ligamentum arteriosum.

A rare form of vascular ring is presented consisting of a left cervical aortic arch, a right descending aorta, and a right ligamentum arteriosum in a symptomatic infant. The planning of its surgical interruption was complicated by absence of the left pulmonary artery and hypoplasia of the left lung. This case provides an exception to the surgical axiom that all vascular rings can be divided through the left side of the chest. It reveals the difficulty in evaluation of these lesions by barium swallow alone and emphasizes the importance of preoperative angiography to correctly define the anatomy. The surgical approach to a patient with an absent left pulmonary artery and hypoplastic lung requiring a contralateral thoracotomy is presented.

Aorta, Thoracic↗