Ticket on the Titanic. Perils and pitfalls of junior faculty development.
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Adaptation, Psychological↗
Biomedical subjects
J E Graham
Publications and source records attributed to J E Graham.
Isolation and characterization of Pioneer1, a novel Chlamydomonas transposable element.
During the course of this study a novel family of Chlamydomonas mobile elements has been identified in natural isolate strain 224. The first member of this class to be characterized, a 2.8-kb element named Pioneer1, was trapped in an intron of the nitrate reductase structural gene, NIT1. This element has been cloned and completely sequenced and found to be unusual in structure. Pioneer elements are present in a very low-copy number of three per genome in strain 224. The copy number increased by one upon transposition of Pioneer1. Hybridization of Pioneer1 to a variety of Chlamydomonas strains confirmed that this element differed from previously described Chlamydomonas transposons. It also indicated that related elements are present in low-copy number in natural isolate strains 356 and S1D2, but not in the most commonly used laboratory strains 137c and 21 gr. For these reasons, members of the Pioneer family might prove useful as insertional mutagens.
Animals↗
Recurrence patterns and complications in endometrial adenocarcinoma with cervical involvement.
BACKGROUND: Cervical involvement in endometrial carcinoma is a diverse entity, and the optimal management of these patients is not well understood. METHODS: Recurrence patterns and complications in 202 patients with histologically confirmed endometrial carcinoma with cervical involvement were retrospectively studied. RESULTS: The 5-year actuarial survival rate for all patients was 65%. Recurrences were documented in 80 (40%) of the patients, and the overall long-term survival rate in this group was 4%. Patients treated with radical hysterectomy (n = 33) had a 6% isolated pelvic recurrence rate and the lowest serious complication rate among the five treatment groups despite having the highest frequency of risk factors for recurrence among any of the groups studied. Patients treated with extrafascial hysterectomy alone (n = 37) had a 14% pelvic recurrence rate and very few complications. When radiotherapy preceded extrafascial hysterectomy (n = 37), the frequency of pelvic recurrences was 30%, and 19% experienced serious gastrointestinal or genitourinary tract complications. When radiotherapy followed extrafascial hysterectomy (n = 68), the pelvic recurrence rate was 24%, and 13% experienced serious complications. Overall, 24% of patients (49 of 202) had isolated pelvic recurrences, whereas 10% (21 of 202) had isolated distant recurrences and 5% (10 of 202) were simultaneously diagnosed with both pelvic and distant recurrences. CONCLUSIONS: This large data base suggests that older conventional forms of therapy, particularly those using preoperative radiotherapy, subject the patient to significant morbidity over a 5- to 10-year period and, in terms of local control, are not necessarily superior to therapeutic modalities using primary surgical evaluation, such as radical hysterectomy. Consideration of primary surgery should be given in the appropriate situation, and radical hysterectomy should be considered when gross cervical involvement is encountered and intraoperative exploration does not show obvious extrauterine disease.
Actuarial Analysis↗
Evidence for feedback (trans) regulation of, and two systems for, glycine betaine transport by Staphylococcus aureus.
Previous reports are in conflict as to the number of transport systems for glycine betaine in Staphylococcus aureus. Cells grown in complex medium exhibited a single transport system of moderate affinity. Cells grown in defined medium in the absence of glycine betaine showed a high affinity and a low affinity transport system. Cells grown in the presence of glycine betaine in the presence of osmotic stress in either complex or defined media accumulated large pools of internal glycine betaine. Smaller, but still significant, amounts of glycine betaine were accumulated by cells grown in its presence in either complex or defined media in the absence of osmotic stress. Cells grown in defined medium in the presence of glycine betaine in the presence or absence of osmotic stress showed lower rates of glycine betaine transport than cells grown in its absence. This suggests that glycine betaine transport is subject to feedback or trans inhibition by internal glycine betaine. This can explain the difference in observed kinetics in cells grown in complex or defined media, the high affinity system being predominantly inhibited in cells grown in complex medium.
Betaine↗
Prognostic factors and long-term survival in endometrial adenocarcinoma with cervical involvement.
The clinical, surgical, and histopathologic data from 202 patients with endometrial adenocarcinoma with cervical involvement are presented. One hundred fifty-one (75%) had histopathologically confirmed cervical involvement at the time of their definitive surgery, while in 51 (25%) no cervical involvement was conclusively identified. The 5-year actuarial survival for patients with true surgical stage II endometrial carcinoma (N = 24) was 76%. Extrauterine disease was documented in 32% (27/84) of patients in which the primary treatment modality was surgical. The 5-year actuarial survival was 65% for all patients with clinical surgical stage II disease. There appeared to be a survival advantage for patients treated by radical surgery as compared with more conventional treatments, especially in patients with numerous high-risk factors. The subgroup of patients (N = 53) having tumor grossly involving the cervix had a 5-year survival of 48%. In this subgroup of patients, radical hysterectomy offered improved 5-year survival over more traditional forms of treatment, particularly compared with simple hysterectomy or combined treatment with radiation and surgery. Multivariate analysis positively correlated myometrial invasion, grade, uterine serosal involvement, lower uterine segment involvement, adnexal metastasis, pelvic metastasis, aortic node metastasis, and peritoneal cytology, with disease-free survival. Clinical and surgical findings correlated poorly; therefore, primary surgical evaluation is recommended when possible.
Adenocarcinoma↗
Choline transport activity in Staphylococcus aureus induced by osmotic stress and low phosphate concentrations.
Uptake of [14C]choline upon hyperosmotic stress of exponential-phase Staphylococcus aureus cultures in a complex medium occurred after a delay of 2.5 to 3.5 h. This uptake could be prevented by chloramphenicol, suggesting that it occurred via an inducible transport system. Radioactivity from [14C]choline was accumulated as [14C]glycine betaine. However, neither choline nor glycine betaine could act as the major carbon and energy source for the organism, suggesting that choline was not metabolized beyond glycine betaine. Assay of choline transport activity in cells grown under different conditions in defined media revealed that osmotic stress was mainly responsible for the induction, but choline gave a further increase in induction. The system was not induced in anaerobically grown cells. Choline transport activity was repressed by glycine betaine and proline betaine, suggesting that these compounds are corepressors. Choline transport activity was not induced in cells osmotically stressed by 1 M potassium phosphate or 0.5 M sodium phosphate, but was induced in cells grown in low-phosphate medium in the absence of osmotic stress. This suggests that there is a connection between the phosphate and osmotic stress regulons. Choline transport was energy and Na+ dependent and had a Km of 46 microM and a maximum rate of transport (Vmax) of 54 nmol/min/mg (dry weight). The results of competition studies suggested that N-methyl and an alcohol group or aldehyde groups at the ends of the molecule were important in its recognition by the system. Glycine betaine was not a highly effective competitor, suggesting that its transport system and the choline transport system were distinct from each other. Choline transport was highly susceptible to a variety of inhibitors, which may be related to the greater dependence on respiratory metabolism of cells grown in the presence of high NaC1 concentrations.
Biological Transport↗
Egocenter location in children with strabismus: in the median plane and unchanged by surgery.
PURPOSE: Previous studies have shown that there are spatial localization shifts after horizontal strabismus surgery when a patient performs an open-loop pointing task. After monocular enucleation, an adult will also show a shift in the pointing response. Other studies have shown that in children who underwent enucleation, the egocenter location shifts toward the remaining eye. Is the pointing shift after surgery in children with strabismus the result of a shift in egocenter location? METHODS: Using a modified Roelofs' method for measuring the egocenter, eight children were tested before and after horizontal strabismus surgery to see if there were any shifts in egocenter location. One control group consisted of six children undergoing surgery for correction of vertical strabismus in which the horizontal muscles would be unaltered. RESULTS: Presurgery measurements of egocenter location in the people with strabismus were the same as those found in the other control group of 12 normal children. Postsurgical measurements of eye position showed horizontal rotations of 14.5 degrees for the horizontal group and 2.4 degrees for the vertical group. Egocenter measurements showed no postoperative shift for either strabismus group. CONCLUSIONS: Thus, the pointing shift seen in the previous studies is not from a shifting egocenter location but from a change in the registered position of the eye in the orbit.
Child↗
Staphylococcus aureus osmoregulation: roles for choline, glycine betaine, proline, and taurine.
Choline, glycine betaine, and L-proline enhanced the growth of Staphylococcus aureus at high osmolarity (i.e., they acted as osmoprotectants) on various liquid and solid defined media, while an osmoprotective effect of taurine was shown only for cells growing on high-NaCl solid medium that lacked other osmoprotectants. Potassium pool levels were high, and there was little difference in levels in cells grown at different osmolarities. Glycine betaine accumulated to high levels in osmotically stressed cells, and choline was converted to glycine betaine. Proline and taurine also accumulated in response to osmotic stress but to lower levels than glycine betaine.
Amino Acids↗
Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study.
Between June 20, 1977 and February 5, 1983, the Gynecologic Oncology Group entered 1180 women with clinical stage I or II (occult) endometrial carcinoma into a surgical-pathological staging study. Eight hundred ninety-five patients with endometrioid or adenosquamous carcinoma were evaluable for this study which relates surgical-pathological parameters and postoperative treatment to recurrence-free interval and recurrence site. Proportional hazards modeling of time to recurrence was performed. For patients without metastasis determined by surgical-pathological staging the greatest determinant of recurrence was grade 3 histology adenocarcinoma grade 3, relative risk (RR) = 15; adenosquamous carcinoma grade 3, RR = 8.1; all adenocanthomas, RR = 1.0). Of 48 patients with histologically documented aortic node metastases, 47 had one or more of the following features: (1) grossly positive pelvic nodes, (2) grossly positive adnexal metastasis, or (3) outer one-third myometrial invasion. Pelvic radiation was administered to 48.0% and vaginal brachytherapy alone to 10.2% of patients postoperatively; 41.8% received no adjuvant radiation therapy. None of three recurrences in the vaginal implant group were vaginal or pelvic; 7.4% (7 of 95) of recurrences in the pelvic radiation therapy (RT) group were vaginal and 16.8% were pelvic; 18.2% (8 of 44) of recurrences in the no adjuvant radiation group were vaginal and 31.8% pelvic. Because of the high degree of selection bias no valid comparisons can be made of recurrence-free interval in these groups. The 5-year recurrence-free interval for patients with negative surgical-pathological risk factors (other than grade and myoinvasion) was 92.7%; involvement of the isthmus/cervix 69.8%; positive pelvic cytology 56.0%; vascular space invasion 55.0%; pelvic node or adnexal metastases 57.8%; and aortic node metastases or gross laparotomy findings 41.2%. It is not clear that cervix invasion per se diminishes survival, because it is more often associated with poor tumor differentiation (34.7% versus 24.0%, grade 3) and deep myoinvasion (47.0 vs 18.6%) than cases without cervix invasion. The relapse rate among cervix-positive and -negative cases with grade 3 lesions and deep myoinvasion is not dramatically different (48.8% vs 39.8%). The proportion of failures which were vaginal/pelvic (34.6% for the surgery only group compared to 12.5% of the RT group) appears to favor the use of adjuvant radiation for patients with more than one-third myoinvasion and grade 2 or 3 tumor. There were 97 patients in the study group with malignant cytology of which 29.1% had regional/distant failure, which compares to 10.5% of the cytology-negative patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenocarcinoma↗
Results of radiotherapeutic management of primary carcinoma of the vagina.
Forty-five previously untreated patients with primary carcinoma of the vagina were treated with curative radiotherapy from 1965 through 1985. All patients were staged according to the FIGO system. One patient was classified as Stage 0, 15 as Stage I, 22 as Stage II, 6 as Stage III, and 1 as Stage IV. Treatment consisted of intracavitary irradiation alone in Stage 0 patients. Stage I patients received intracavitary/interstitial irradiation alone or in combination with external irradiation and an implant when feasible. When treated with an implant only, the total tumor dose delivered was between 65-70 Gy. External irradiation consisted of delivering a dose of 45-50 Gy over a period of 4 1/2-5 weeks to the whole pelvis to treat the regional lymph nodes. An additional dose of 20-25 Gy was delivered to the site of original involvement using an implant when feasible. If not technically feasible, as in advanced stages, the patient was treated with additional external irradiation to a total dose of 65-70 Gy by a shrinking field technique. All patients except one were followed either until death or for a minimum of 2 years. The actuarial 5-year survival rates were 100% for Stage 0, 78% for Stage I, and 71% for Stage II patients. None of the patients with Stage III or IV disease survived. Of the patients who recurred, all but two did so within 16 months after diagnosis. Pelvic recurrence as the first site of recurrence occurred in 86% of the patients who recurred. Distant recurrence as a component occurred in 20% of all failures. Complications as a consequence of therapy occurred in 18% of the patients. Vaginal necrosis that healed with conservative treatment was seen in four patients and the other four patients had rectal complications of varying severity. Thus, curative radiotherapy is an effective method of treatment, with acceptable morbidity, in patients with early stage primary carcinoma of the vagina.
Adult↗
Small area analysis shows differences in utilization.
Adjusted admission rates for respiratory distress (COPD, asthma, bronchitis, and pneumonia) varied up to 3.09-fold between the highest and lowest hospital market areas in 1986 for the state of Ohio. Reasons for the variability can be determined through small area analysis techniques with the help of area physicians. Substantial improvements in the availability, delivery, and cost of respiratory care would reasonably be anticipated as a result of such analysis and feedback.
Aged↗
Infectious morbidity in gynecologic oncology.
Infectious complications are the most frequent cause of death in cancer patients. Broad-spectrum antibacterial therapy is dictated by the polymicrobial nature of infections encountered in gynecologic oncology and is imperative in the empiric therapy of febrile granulocytopenic patients. In addition, the potential for infectious complications after radical pelvic surgery to remove malignancies has influenced most gynecologic oncologists to recommend prophylactic antibiotics. However, the choice of appropriate antibacterial therapy in gynecologic oncology patients is complicated frequently by impaired renal function secondary to cancer chemotherapy or associated with age in this generally elderly population. In addition, the potential cost- and time-saving advantages of simplified antibacterial regimens have resulted in a reexamination of the standard aminoglycoside-containing multiple-drug regimens. The efficacy and safety of monotherapy with broad-spectrum beta-lactam antibiotics or beta-lactam-antibiotic/beta-lactamase-inhibitor combinations, such as ticarcillin/clavulanate, remain to be confirmed in gynecologic oncology patients. The broad spectrum of ticarcillin/clavulanate, including gram-negative and -positive aerobic and anaerobic bacteria, seems plausible for the treatment of these potentially devastating infections.
Agranulocytosis↗
Intra-operative radiation therapy in the treatment of pelvic malignancies: a preliminary report.
Local control of advanced pelvic malignancies, particularly when complete surgical resection is not feasible, is often impeded by dosage limitations in radiation therapy and the intolerance to radiation of normal tissues. This is a preliminary report on the feasibility of improved local control in pelvic malignancies treated by intra-operative radiation therapy, as a radiation boost, in addition to conventional surgical resection and external beam radiation therapy. Fifteen gynaecological malignancies (five cervix, five uterus, four ovary, and one vulva) from Rush Medical College and the University of Navarre, as well as 36 other pelvic malignancies (32 colorectal, 4 genito-urinary) from Rush Medical College were reviewed. All tumours were advanced or recurrent, and all patients were felt to be at high risk of local failure. IORT was administered at a dose range of 10-26 Gy. Our data suggest that the probability of local control improves when IORT is used for primary and for microscopic disease, when the tumour is at least partially resectable, and when the total dose given in IORT and external beam radiation exceeds 70 Gy.
Brachytherapy↗
Surgical pathologic spread patterns of endometrial cancer. A Gynecologic Oncology Group Study.
The surgical pathologic features of 621 patients with Stage I carcinoma of the endometrium are presented. All patients were treated with primary surgery consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and paraaortic lymphadenectomy and peritoneal cytology. An appreciable number of patients (144-22%) with Stage I cancers have disease outside of the uterus (lymph node metastasis, adnexal disease, intraperitoneal spread and/or malignant cells in peritoneal washings). Multiple prognostic factors particularly grade and depth of invasion are related to extrauterine disease. This study adds credence to the primary surgical approach with individualized postoperative therapy as indicated.
Female↗
Radiation therapy in primary carcinoma of the vagina.
A retrospective analysis of 32 patients with carcinoma of the vagina treated with curative radiotherapy between 1965 and 1981 is presented. Squamous cell carcinoma was the most common histologic type, found in 78% of the patients. Patients were staged according to the FIGO system. Stage I and II disease was found in 8 and 18 patients, respectively. Six patients had either Stage III or IV disease. The absolute survival rate was 100% for Stage I and 72% for Stage II patients. The pattern of failure was analyzed. All patients who failed had done so within 14 months of completion of treatment. Treatment failure in the pelvis occurred only in 16% of the patients with early disease (Stages I and II) while 81% of the patients with late stage had failed in the pelvis.
Adult↗
Coronary revascularization in patients with bilateral internal carotid occlusions.
Coronary revascularization that is neurologically uneventful in patients with bilateral totally occluded internal carotid arteries has not been previously reported. We performed saphenous vein coronary artery bypass grafting on three such patients and observed them for 6 to 23 months. Preoperatively two of our patients had chronic stable symptoms of cerebrovascular insufficiency, and one had received cerebral revascularization via a superficial temporal-to-middle cerebral artery bypass. Controversy exists regarding proper cerebral protective maneuvers during coronary revascularization for patients with advanced cerebrovascular disease. Cerebral protection for our patients during cardiopulmonary bypass included hypothermia and high perfusion flows and pressures. Two patients also received prophylactic sodium thiopental. None of these three patients had a stroke perioperatively or during the follow-up period. We believe that these case histories strongly suggest that the functional state of the cerebral collateral circulation, as judged by preoperative neurological symptoms, predicts neurological outcome after coronary revascularization better than the specific occlusive anatomy of the extracranial carotid arteries.
Arterial Occlusive Diseases↗
Significant improvement in flow through a potential internal mammary graft after partial approximation of the sternum.
A large internal mammary artery provided inadequate flow on testing, but its use was fortunately not abandoned until after partial closure of the sternal retractor. Reassessment following this maneuver identified ample flow.
Coronary Artery Bypass↗
Pain from bone metastases as the admitting complaint in cervical cancer.
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Adult↗