Biomedical subjects
D Driscoll
Publications and source records attributed to D Driscoll.
Sarcomas near extremity joints in adults.
BACKGROUND AND OBJECTIVES: There are technical difficulties in resecting soft tissue sarcomas extending to or crossing a joint. The objective of this study was to determine the rate of amputation and local recurrence rate for these sarcomas and compare them with the respective rates for overall extremity sarcomas. METHODS: Retrospective review of 78 patients with sarcoma near a joint compared with 215 patients with extremity sarcomas accrued during the same period, 1977-1994. Of these 78 patients, 64 were in the lower and 14 in the upper extremity. Most common histologic subtypes were malignant fibrous histiocytoma (15/78, 19%), synovial sarcoma (11/78, 14%), liposarcoma (11/78, 14%), and leiomyosarcoma (10/78, 13%). The surgical treatment consisted of local excision in 10 (13%), wide excision in 56 (72%), and amputation in 12 (15%). Adjuvant radiation was given to 26 patients. RESULTS: Local recurrence was noted in 20% (16/78) patients. The incidence of local recurrence in the surgery alone group (n = 52) was 15% (8/52) and in the surgery plus adjuvant radiation group (n = 26) it was 31% (8/26); P = 0.11. Of the 16 patients with local recurrence, 9 (56%) required amputation. The 5-year and 10-year survival rates for the entire group of patients were 68% and 60% respectively. On multivariate analysis survival varied according to grade (P = 0.05) and tumor size (P = 0.02). CONCLUSIONS: Amputation was finally required in 27% (21/78) for local control of the disease. The local recurrence rate was 20%. These rates appear to be somewhat higher than those reported in our overall extremity sarcoma series and those in most modern series of overall extremity sarcomas, but the 5- and 10-year survival rates are similar to those of the latter.
Phenotype and genotype in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is a common disorder in premenopausal women and is characterized by hyperandrogenic chronic anovulation. The cause is unknown. PCOS is associated with significant insulin resistance as well as with defects in insulin secretion. These abnormalities place these women at substantial risk for developing type 2 diabetes mellitus. A defect in insulin-mediated receptor autophosphorylation has been found in a substantial proportion of PCOS women. Both PCOS and the insulin resistance that accompanies it appear to have major genetic components. Family studies of PCOS have supported this, although they suffer from incomplete phenotyping of probands and first-degree relatives. The phenotype in males and nonreproductive age females is uncertain. Despite the shortcomings of the family studies of PCOS, they have consistently indicated familial clustering and suggested that the mode of inheritance is dominant. Our initial studies of 50 families of PCOS probands indicate that 24% of sisters are affected with PCOS. There also appears to be an intermediate phenotype of sisters with regular menstrual cycles who are hyperandrogenic per se (22% of sisters). Additionally, there appears to be a major familial defect, with 50% of first-degree relatives having glucose intolerance (impaired glucose tolerance by oral glucose tolerance test or type 2 diabetes mellitus). These findings suggest that hyperandrogenism in females and glucose intolerance may be genetic traits in PCOS kindreds. Systematic phenotyping will allow assignment of affected status for eventual linkage analysis.
Enlarged Sylvian fissures in infants with interstitial deletion of chromosome 22q11.
Two infants with chromosome 22q11 deletion syndrome were noted to have symmetrically enlarged Sylvian fissures on cranial MRI. We compared the size of the Sylvian fissures in neuroimaging studies from 17 other subjects with del 22q11 to age-matched disease controls. The mean anterior interopercular distance was used as an index of Sylvian fissure enlargement. Symmetric enlargement of the Sylvian fissures was present in 10 of 17 subjects with del 22q11. The age-incidence pattern, as well as follow-up scans in 2 patients, suggests delayed growth of the opercular region in these patients. Subjects with del 22q11 consistently had disproportionate enlargement of the left Sylvian fissure compared to the right. This observation suggests that a gene (or genes) in the deleted region affects the development of the left and right perisylvian cortex in different ways. Abnormal development of the operculum may explain some of the neurodevelopmental features that are common among individuals with 22q11 deletion syndrome.
Advanced cutaneous squamous cell carcinoma of the trunk and extremity: analysis of prognostic factors.
BACKGROUND: Patients with squamous cell carcinoma (SCC) of the skin may exhibit locally advanced or metastatic disease and present a challenging management problem. METHODS: A retrospective review of 40 patients with advanced SCC of the trunk or extremity managed at Roswell Park Cancer Institute from 1982 through 1992 was performed to identify clinical and pathologic factors that influenced outcome. RESULTS: There were 27 males and 13 females with a median age of 61 years. Median follow-up was 24 months. Surgical resection to control the primary tumor was often extensive. Amputation was required in nine patients, hemipelvectomy in three patients, and hemicorporectomy in one patient. Median survival was 28 months, and 5-year survival was 43%. Univariate analysis identified stage (P = 0.04), size (P = 0.0001), type of surgical procedure (P = 0.009), and margins of resection (P = 0.005) as having prognostic significance. On multivariate analysis, stage (P = 0.04) and size (P = 0.02) were found to be significant. CONCLUSIONS: Optimum treatment for advanced SCC of the trunk and extremity involves surgical resection with uninvolved margins. The role of elective node dissection remains undefined. Investigation is needed to define the role of neoadjuvant therapy that may improve functional and cosmetic results.
The 22q11.2 deletion: screening, diagnostic workup, and outcome of results; report on 181 patients.
A submicroscopic deletion of chromosome 22q11.2 has been identified in the majority of patients with the DiGeorge syndrome, velocardiofacial syndrome, conotruncal anomaly face syndrome, and in some patients with isolated conotruncal cardiac anomalies, Opitz G/BBB syndrome, and Cayler cardiofacial syndrome. We have evaluated 181 patients with this deletion. We describe our cohort of patients, how they presented, and what has been learned by having the same subspecialists evaluate all of the children. The results help define the extremely variable phenotype associated with this submicroscopic deletion and will assist clinicians in formulating a management plan based on these findings.
Regional localization of over 300 loci on human chromosome 22 using a somatic cell hybrid mapping panel.
A somatic cell hybrid panel, consisting of 25 cell lines, has been developed to localize loci subregionally on chromosome 22. Over 300 markers in the form of STSs or hybridization probes have been assigned to one of 24 unique regions or "bins" using this panel. This ordered collection of markers will aid in the assembly of physical maps and contigs of chromosome 22 and assist in positional cloning of disease loci mapped to chromosome 22.
The curative potential of radiation therapy in the treatment of primary vaginal carcinoma.
The outcome of 55 patients with primary vaginal carcinoma treated with radiation therapy at Roswell Park Cancer Institute was retrospectively reviewed. Forty-four (80%) had a squamous cell carcinoma and 11 (20%) had an adenocarcinoma. The median age was 61 years and the median dose of radiation administered, external beam and brachytherapy, was 7,040 cGy. Fifteen percent of patients developed severe radiation-induced complications, and 36% developed recurrence of disease. The overall 5-year survival and 5-year disease-free survival for the entire group was 49 and 58%, respectively. Variables positively influencing survival included younger age, early stage, involvement of the upper vagina, total radiation dosage > 7,500 cGy, and the use of combination external beam and brachytherapy. However, only age acted as an independent prognostic factor affecting survival. The pelvis was the site of disease in the majority of patients who suffered recurrence.
Critical pathways and mother-baby coupling.
Mother-baby couplet care has been utilized for more than 10 years. Both staff and patients find use of critical pathways in this managed care system to be very effective and efficient.
Selection and treatment of candidates for heart transplantation. A statement for health professionals from the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association.
Improved outcome of heart failure in response to medical therapy, coupled with a critical shortage of donor organs, makes it imperative to restrict heart transplantation to patients who are most disabled by heart failure and who are likely to derive the maximum benefit from transplantation. Hemodynamic and functional indexes of prognosis are helpful in identifying these patients. Stratification of ambulatory heart failure patients by objective criteria, such as peak exercise oxygen consumption, has improved ability to select appropriate adult patients for heart transplantation. Such patients will have a poor prognosis despite optimal medical therapy. When determining the impact of individual comorbid conditions on a patient's candidacy for heart transplantation, the detrimental effects of each condition on posttransplantation outcome should be weighed. Evaluation of patients with severe heart failure should be done by a multidisciplinary team that is expert in management of heart failure, performance of cardiac surgery in patients with low left ventricular ejection fraction, and transplantation. Potential heart transplant candidates should be reevaluated on a regular basis to assess continued need for transplantation. Long-term management of heart failure should include continuity of care by an experienced physician, optimal dosing in conventional therapy, and periodic reevaluation of left ventricular function and exercise capacity. The outcome of high-risk conventional cardiovascular surgery should be weighed against that of transplantation in patients with ischemic and valvular heart disease. Establishment of regional specialized heart failure centers may improve access to optimal medical therapy and new promising medical and surgical treatments for these patients as well as stimulate investigative efforts to accelerate progress in this critical area.
Human steroidogenic acute regulatory protein: functional activity in COS-1 cells, tissue-specific expression, and mapping of the structural gene to 8p11.2 and a pseudogene to chromosome 13.
Steroidogenic acute regulatory protein (StAR) appears to mediate the rapid increase in pregnenolone synthesis stimulated by tropic hormones. cDNAs encoding StAR were isolated from a human adrenal cortex library. Human StAR, coexpressed in COS-1 cells with cytochrome P450scc and adrenodoxin, increased pregnenolone synthesis > 4-fold. A major StAR transcript of 1.6 kb and less abundant transcripts of 4.4 and 7.5 kb were detected in ovary and testis. Kidney had a lower amount of the 1.6-kb message. StAR mRNA was not detected in other tissues including placenta. Treatment of granulosa cells with 8-bromo-adenosine 3',5'-cyclic monophosphate for 24 hr increased StAR mRNA 3-fold or more. The structural gene encoding StAR was mapped using somatic cell hybrid mapping panels to chromosome 8p. Fluorescence in situ hybridization placed the StAR locus in the region 8p11.2. A StAR pseudogene was mapped to chromosome 13. We conclude that StAR expression is restricted to tissues that carry out mitochondrial sterol oxidations subject to acute regulation by cAMP and that StAR mRNA levels are regulated by cAMP.
Severe radiation morbidity in carcinoma of the cervix: impact of pretherapy surgical staging and previous surgery.
PURPOSE: The purpose of this study is to delineate the factors which (a) contribute to an increase in the severe, radiation induced complication rate and (b) have a significant effect on survival in patients with International Federation of Gynecologists and Obstetricians (FIGO) Stage I-IVA cervical cancer undergoing pretherapy surgical staging. METHODS AND MATERIALS: From 1971-1991, 189 patients underwent pretherapy surgical staging via a retroperitoneal approach (67) or transperitoneal approach (122). Seventy-nine patients had previously experienced a laparotomy. Patients subsequently received a median of 85 Gy to point A. In patients receiving paraaortic radiation, a median of 45 Gy was administered. One hundred and thirty-two (69.8%) patients received hydroxyurea as a radiation sensitizer. RESULTS: Pretherapy surgical evaluation revealed that 21 of 89 (23.6%) Stage II patients and 32 of 85 (37.6%) Stage III patients had paraaortic lymph node metastases. Multivariate logistic regression analysis detailed the significant factors favorably influencing the radiation-induced complication rate to be a retroperitoneal approach of pretherapy surgical staging and no previous laparotomy. Survival was significantly prolonged in patients receiving hydroxyurea, evaluated via a retroperitoneal incision, with negative paraaortic lymph nodes, and with an early stage of disease. CONCLUSION: A retroperitoneal approach to pretherapy surgical staging and absence of previous surgery reduced the incidence of subsequent radiation-induced complications. Despite improvements in the detection of occult disease, prolonged survival is impaired when the therapeutic measures currently available are used.
Differentiation and tumor response to retinobenzoic acid RE-80 in a malignant conversion model.
The synthetic retinobenzoic acid RE-80 was evaluated for its potential as an inductor of tumor cell differentiation and as a chemopreventive agent. A minimally toxic dose of RE-80 in vitro produced morphologic changes typical differentiation in epidermal tumor cell colonies. Indirect immunofluorescence indicated induction of a differentiation-associated keratin of internal stratified epithelia, K13, and inhibition of the differentiation-associated epidermal keratin K1. Cultured cells were skin-grafted to athymic nu/nu mice to evaluate RE-80 effects on early stage malignant progression in vivo. When tumors had grown to 3 to 4 mm in diameter, mice were treated by intraperitoneal injection with RE-80 (67 micrograms, 170 mmol, i.p., two times per week) or vehicle (100 microliters 20% ethanol). Papillomas (benign) and moderately differentiated squamous cell carcinomas were reduced in volume about 4-fold by RE-80 treatment. Larger, poorly differentiated squamous cell carcinomas were unaffected. RE-80 resulted in a lower proportion of proliferative cells (detectable by bromodeoxyuridine incorporation) and a higher proportion of moderately to well differentiated tumors after 40 days of treatment compared with control tumors, which were mainly poorly differentiated squamous cell carcinomas. K13 induction in vitro was correlated with response to retinoid in vivo. Induction of differentiation may be mechanism of the response to RE-80 in vivo since carcinoma cells expressing K13 did not incorporate bromodeoxyuridine and were on a terminal pathway.
Evaluation of survival after second-line intraperitoneal cisplatin-based chemotherapy for advanced ovarian cancer.
BACKGROUND: The authors sought to evaluate survival of patients with ovarian cancer treated with second-line intraperitoneal cisplatin-based chemotherapy. METHODS: From August 1985 to September 1991, 63 patients with recurrent or persistent ovarian cancer after first-line cisplatin-based chemotherapy were on a protocol and treated with cisplatin, cytarabine, with or without bleomycin. Eligibility included Stage III/IV invasive adenocarcinoma of the ovary, documentation of the size of residual disease at reoperation, and prior treatment with first-line intravenous cisplatin-based chemotherapy. RESULTS: The median survival from intraperitoneal chemotherapy was 29 months. For patients who responded to first-line chemotherapy and second-line intraperitoneal chemotherapy, the 5-year survival was 60%, but for patients with response to first-line chemotherapy but no response to intraperitoneal chemotherapy the 5-year survival was only 17%, and no patient survived 5 years who did not have a response to first- or second-line therapy (P < 0.0001). There was significant improvement in the 2-year survival from initiation of intraperitoneal chemotherapy for patients with < or = 5 mm residual tumor in greatest dimension (74%), compared with patients with residual tumor larger than 5 mm and smaller than or equal to 2 cm (38%), and patients with residual tumor larger than 2 cm (0%) (P < 0.0001). CONCLUSION: Survival was increased for patients who (1) had a response to first-line intravenous chemotherapy and second-line intraperitoneal chemotherapy and (2) who had residual tumor 5 mm or smaller at the initiation of intraperitoneal therapy. The conclusion that the prolonged survival is secondary to cisplatin-based chemotherapy administered intraperitoneally must be made with caution because survival may have been secondary to the small residual disease at initiation of second-line chemotherapy or the systemic effect of cisplatin.
Human sciatic nerve phospholipid profiles from non-diabetes mellitus, non-insulin-dependent diabetes mellitus and insulin-dependent diabetes mellitus individuals. A 31P NMR spectroscopy study.
1. Human sciatic nerve phospholipids obtained from non-diabetes mellitus (NDM), non-insulin-dependent diabetes mellitus (NIDDM), and insulin-dependent diabetes mellitus (IDDM) patients, after lower extremity amputation, were studied by 31P NMR spectrometry. 2. Nine phospholipids resonances in NDM and NIDDM groups were identified as followed: Ethanolamine plasmalogen (Eplas, Chemical shift = 0.07 delta); phosphatidylethanolamine (PE, 0.03 delta); phosphatidylserine (PS, -0.05 delta); sphingomyelin (SM, -0.09 delta); lysophosphatidylcholine (LPC, -0.28 delta); phosphatidylinositol (PI, -0.30 delta); alkylacylphosphorylcholine (A1.PC, -0.78 delta); phosphatidylcholine (PC -0.84 delta), and an unknown resonance (U, 0.13 delta). 3. In the IDDM group a resonance of lysophosphatidylinositol (LPI, 0.01 delta) was detected in addition to the nine phospholipids listed above. 4. IDDM showed that PI and A1.PC were elevated and U was lower when compared with NDM; also, Eplas was lower when compared with NIDDM. PC was elevated and PS was lower when compared with both NDM and NIDDM. 5. Indices calculated from this data, showed that the choline ratio and choline/ethanolamine ratio were elevated; while ethanolamine ratio, and myelin ratio were lower in IDDM group, when compared with both NDM and NIDDM groups. 6. Inactivation of the cholineacethyltransferase enzyme (ChAT) and enhancement of the phospholipidmethyltransferase enzyme (PLMT), secondary to an insulin deficiency, are proposed as an interpretation of these findings.
Thick cutaneous melanoma of the trunk and extremities: an institutional review.
The objective of this study was to review our experience with thick cutaneous melanoma of the trunk and extremities and to identify subgroups of long-term survivors. Ninety-one patients admitted between the years 1977 and 1987, with cutaneous melanoma of the trunk or extremities, Breslow thickness > or = 4.0 mm, or a Clark's level V lesion form the basis of this review. Node positive clinical stage II patients had a 5-year survival rate of 32%. Five-year survival for node positive clinical stage III patients was 0% (P < 0.0001). Node negative clinical stage II patients, and those found to be histologically node positive, had no survival difference, P = 0.88. Sixty per cent of node negative patients with an extremity primary survived 5 years, while patients with a node positive truncal primary had a survival of 14%, P = 0.005. In conclusion, most patients present with local-regional disease. Patients with node negative extremity lesions have the best chance for cure.
Guidelines for evaluation and management of common congenital cardiac problems in infants, children, and adolescents. A statement for healthcare professionals from the Committee on Congenital Cardiac Defects of the Council on Cardiovascular Disease in the Young, American Heart Association.
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Pulmonary complications in patients undergoing thoracotomy for lung carcinoma.
One hundred three consecutive patients undergoing 106 thoracotomies for primary lung carcinoma were reviewed to determine factors associated with the development of postoperative pulmonary complications. Pulmonary complications occurred in 40 of 104 (39 percent) patients. Minor complications occurred in 17 of 104 (16 percent) patients and major in 23 of 104 (22 percent). There were six deaths in the entire series of 103 patients (6 percent), two of which were directly caused by a pulmonary complication and one where it was a contributing factor. Extended surgical resections were associated with an increased risk of complications. Pulmonary complications occurred in 9 of 11 (82 percent) patients undergoing extended resections involving chest wall resection. The use of neoadjuvant chemotherapy also was associated with an increase in the rate of major complications. Poor nutritional status as measured by a history of weight loss and preoperative serum albumin levels also was associated with an increased risk of any pulmonary complication. Cardiac complications were significantly increased in the group of patients having pulmonary complications. Pulmonary complications continue to present a major source of morbidity and mortality for patients undergoing thoracotomy for lung carcinoma. Determination of factors associated with increased risk is important in order to identify patients who might be predisposed to the development of these complications.