Biomedical subjects
Publications and source records attributed to J Glenn.
Ten patients with metastatic disease to the liver were treated with difluoromethylornithine (DFMO) administered by continuous hepatic arterial infusion. Two of nine evaluable patients had an objective partial response. Stable disease was recorded in three patients. Ototoxicity was encountered in all patients who received a daily dose of DFMO equal to or greater than 1.0 g/m2.
A developmental view may help clarify confusions that exist regarding masochism. Following Loewenstein, I suggest that protomasochism be distinguished from masochism. Protomasochism comprises conditions prior to the oedipal period which may lead to masochism. Preoedipal precursors of masochism are organized and transformed during the oedipal stage and later. A conscious or unconscious genital sexual fantasy in which pain is an integral part may appear at that time. The demonstration of such a fantasy is essential for the definitive diagnosis of masochism. It is overdetermined and may result from a variety of dynamic configurations and genetic origins. In making those suggestions, I assume, following Freud, that erotogenic masochism is basic to all forms of masochism.
Through a review of our experience and the literature, the cases of 56 neutropenic cancer patients requiring urgent abdominal surgery have been studied. The most common underlying diagnosis of malignant disease was leukemia (70%), and the most common intra-abdominal disease discovered at surgery was neutropenic enteropathy (61%). Major postoperative complications occurred in 50% of cases. The 30-day postoperative mortality was 32%, and the determinant 6-month survival was 34%. Abdominal pain in a neutropenic cancer patient calls for a thorough evaluation of its cause and careful serial examinations. Evidence of a surgically treatable disease or failure to respond to medical therapy for a presumed medically treatable disease should prompt surgical intervention.
A prospective cohort study was designed to describe the patterns and to determine the factors associated with the risk of rectal prolapse in a commercial swine herd in California, USA. Thirty (1.0 per cent) of 2862 pigs prolapsed between 12 and 28 weeks of age with the peak incidence occurring in 14- to 16-week-old pigs. The overall prolapse rate was 9.1 cases per 100,000 days at risk. Prolapse rates were highest during the winter and autumn months. Other factors associated with an increased risk of prolapse were maleness (relative risk 2.3) birthweight less than 1000 g (relative risk 3.4) Yorkshire boar A (relative risk 2.8) and dams of litter number 1 (relative risk 14.9), 2 (relative risk 8.2) and 3 (relative risk 9.8). No evidence was found to support the hypothesis that diarrhoea and coughing are factors associated with a risk of prolapse.
DNAs of cell lines derived from human metastatic tumors were transfected into tumorigenic, nonmetastasizing murine cells (BALB 3T12-3) to determine if the capacity to metastasize could be conferred by this transfer of portions of the human genome. Using the calcium phosphate method, whole cell DNA was cotransfected into the murine cells along with a neomycin-resistance gene. Recipient murine cells (10(6] which grew in neomycin, indicating successful transfection, were injected via tail vein into 4- to 6-week-old male athymic nude mice. Animals were sacrificed if they appeared ill or at times up to 24 weeks after injection if they remained healthy. Murine cells transfected with DNA from one cell line derived from a hepatic metastasis of a human pancreatic adenocarcinoma (NCI-ZRY) formed experimental pulmonary metastases in 11 of 13 animals injected. Neither murine cells (unmanipulated BALB 3T12-3 cells) nor murine cells transfected with DNA from the same cell type (BALB 3T12-3 cells transfected with BALB 3T12-3 DNA) produced experimental metastases when each cell type was injected into 20 and 10 animals, respectively (P2 less than 0.0001). The results are consistent with the hypothesis that expression of a structural or regulatory protein encoded on human DNA conferred the metastatic phenotype to the recipient murine cells.
Recent evidence indicates that autocrine/paracrine mechanisms may mediate the mitogenic effect of estradiol (E2) both in human and experimental breast cancer. However, the species-specificity of E2-regulated growth factors with regard to their biologic action has not been evaluated. To test this issue, we examined, in the soft agar clonogenic assay, the colony-stimulating activity in human breast cancers of conditioned media obtained from rat mammary carcinomas exposed to E2 (rat E2-CM). Of 22 primary human breast cancers plated in soft agar in the absence of serum, 18 (82%) successfully grew with a mean colony number of 62.4 +/- 9.8 (S.E.M.) (range 14-193). Rat E2-CM significantly stimulated colony formation in 10/18 (56%) human breast cancers to 155 +/- 11% (S.E.M.) of control. E2 administration (10(-9) M) in these tumors had a virtually identical overall effect (154 +/- 13% of control colony number). In the remaining eight tumors (44%), neither rat E2-CM nor E2 had, in general, a significant colony-stimulating effect. The growth-promoting action of rat E2-CM and E2 was not influenced by the hormone receptor status of the tumor. These results suggest that E2-regulated growth factors may not be species-specific, at least with regard to their colony-stimulating effects in soft agar.
By radioimmunoassay we determined circulating levels of a tumor-associated antigen, CA 19-9, in 47 patients with pancreatic adenocarcinoma, to learn if serial testing was useful in predicting prognosis or in detecting disease progression. Before treatment, 42 (89%) had an abnormal serum level, and 45 (96%) had an abnormal level at some time during the disease course. A pretreatment value of less than 1,000 U/mL (normal, less than or equal to 37 U/mL) was found in 38 patients; 20 (53%) had resectable disease. One of nine patients (11%) with a pretreatment value greater than 1,000 U/mL had resectable disease (P2 = .05). Among 14 patients who underwent pancreatectomy and were studied serially, the CA 19-9 level normalized in eight; seven (88%) survived greater than or equal to 18 months. Six patients whose levels did not normalize after pancreatectomy all died in less than 12 months (P2 less than .005). Greatly elevated levels occurred in 11 patients after pancreatectomy 1 to 7 months before clinically apparent recurrence. The other three patients without significant elevations remain clinically free of disease. The data suggest that serial determination of serum CA 19-9 levels are useful as a prognostic indicator and in detecting disease recurrence following pancreatectomy. Concurrent determinations of carcinoembryonic antigen (CEA) levels showed abnormal preoperative values in 28 of 46 patients tested (61%). Concurrent serial postoperative determinations of CEA were available in ten patients. Whereas CA 19-9 values clearly indicated eight recurrences, CEA was helpful in only four. In this small group of patients, CA 19-9 was a better predictor of recurrence.
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We reviewed records of 18 patients with external duodenal fistula. Fourteen patients developed duodenal fistulas following an operation, two following abdominal trauma, and two as a complication of other diseases. Copious drainage of intestinal juice from the abdomen was the most common presenting sign. Contrast fistulography, upper gastrointestinal tract roentgenography, and T-tube cholangiography were useful diagnostic studies. Nine patients were treated nonoperatively; nine patients required at least one operation. Complications occurred frequently; of special interest were three patients who developed postoperative acute cholecystitis. Six patients died (33% mortality). Factors associated with mortality were advanced age (greater than 65 years), uncontrolled infection and multiple organ failure, high-output fistula, malnutrition, delay in diagnosis (more than three days), and multiple reoperations to treat the fistula or complications. External duodenal fistula continues to be a life-threatening problem whether it is postoperative, posttraumatic, or secondary to a disease process.
In this study, we determined the sensitivity and specificity of the new serum assay CA19-9 in detecting adenocarcinoma of the pancreas and compared the results with those of the serum assay to carcinoembryonic antigen (CEA). Thirty-seven patients with biopsy-proven adenocarcinoma (14 patients with resectable disease and 23 patients with unresectable disease) were compared with 157 controls (48 patients with benign pancreatic disease, 34 patients with nonpancreatic sources of abdominal pain, 58 patients with benign jaundice, 7 patients with nonpancreatic malabsorption, and 10 patients with renal failure on dialysis). It was determined that a cutoff of 75 U/ml enhanced the diagnostic efficiency (sensitivity + specificity) of CA19-9 over the manufacturer's recommended cutoff of 37 U/ml. The sensitivity of CA19-9 (greater than 75 U/ml) in detecting cancer was greater than that of CEA (greater than 5 ng/ml) (86.5% vs. 48.4%) (p less than 0.01, McNemar test). The sensitivity of CA19-9 was 78.6% in resectable and 91.3% in unresectable disease. The specificity of CA19-9 was also greater than CEA (92.5% vs. 87.3%), although this difference was not statistically significant. The higher the CA19-9 or CEA level, the greater the specificity of either assay; at CA19-9 levels greater than 600 U/ml and CEA levels greater than 20 ng/ml the specificity is approximately 99%. The combination of an elevated CA19-9 level (greater than 75 U/ml) and an elevated CEA level (greater than 5 ng/ml) also enhanced specificity to 99%. It is concluded that CA19-9 used alone is superior to CEA used alone in detecting cancer of the pancreas and that the combination of mild elevations of both assays improves their specificity. Although the CA19-9 marker can be elevated with other intraabdominal adenocarcinomas (e.g., gastric, biliary, or colonic), CA19-9, together with CEA, will be useful to the clinician in differentiating benign from malignant pancreatic processes and in alerting the clinician to the possible presence of an intraabdominal neoplasm in the proper clinical setting.
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Early advances in psychoanalytic knowledge, profound though they were, were incomplete structures to be built upon, modified, and partially discarded. In addition to errors due to insufficient knowledge, Freud's difficulties with Dora stemmed from countertransference. Dora's transference included an identification with a governess/maid. Important oedipal role played by a nursemaid in Freud's life made him vulnerable to being left by Dora. The maid, Monika, "the prime originator" of Freud's neurosis, seduced him, chastised him, and taught him of hell. In his self-analysis she was associated with Freud's mother who left him when she gave birth to his sister. When he was two and a half years old, Monika was discharged and jailed for stealing. I suggest that Freud's attraction to Dora revealed itself in his libidinal imagery of the treatment and his premature sexual interpretations, the effects of which he misjudged. Defending against his attraction, he pushed her away from him, did not act to keep her in analysis or allow her to reenter analysis later. In addition, since Dora had left him as he must have felt his childhood nursemaid had, he reacted as if she were that maid. Hurt, saddened, and angered, he used reversal and deserted her, thus damping his feelings.
The role of prolactin (PRL) in supporting the growth of human breast cancer is still unclear. The ability to grow primary breast cancer specimens in the soft agar clonogenic assay in the absence of serum gave us the opportunity to evaluate the growth-promoting effect of PRL and to compare it to that of estradiol in the same tumor samples. PRL was tested both at physiological concentrations (20 ng/ml) as well as in pharmacological amounts (200 ng/ml) comparable to circulating blood levels in hyperprolactinemic states. Estradiol was simultaneously tested in physiological amounts (10(-8)M). In 17 infiltrating ductal carcinomas, the lower dose of PRL stimulated colony formation to 126 +/- 5.2% (SE) of control, while the higher dose increased colony number to 159 +/- 10.4% of control. This latter effect was comparable to that observed with estradiol (159 +/- 8.5% of control). The effect of PRL was more pronounced in estrogen receptor-positive tumors. Nine of ten estrogen receptor-positive tumors were PRL sensitive, while three of seven estrogen receptor-negative tumors exhibited a clear response to PRL administration. PRL did not stimulate colony formation in a malignant cystosarcoma phylloides and in two benign lesions (fibroadenoma and fibrocystic disease). We conclude that, at least under the conditions of the soft agar clonogenic assay, PRL exerts a dose-dependent growth-promoting effect on human breast cancer. Such effect is comparable to that of estradiol when PRL is added in concentrations similar to circulating blood levels in hyperprolactinemic patients.
An 18-week field trial was conducted on a sheep ranch to evaluate the therapeutic and prophylactic effect of a commercial foot rot vaccine. Two hundred sheep were included in the study, 100 with detectable foot rot lesions and 100 without. Approximately 50 sheep from each group were selected randomly and vaccinated twice against foot rot at a 6-week interval in the late spring 1984; the remaining sheep acted as nonvaccinated controls. Therapeutic effect of the vaccine was demonstrated by a cure rate of 53% in vaccinated, foot rot-affected sheep vs a cure rate of 19% in nonvaccinated, foot rot-affected sheep. Prophylactic effect of the vaccine was demonstrated by a foot rot prevalence at the end of the 18-week period of 9% for vaccinated sheep vs 53% for nonvaccinated sheep. Associations of foot rot lesions and vaccination with body condition were found to be significant, as was the association between foot rot lesions and mortality.
Since 1977, 31 patients were entered in a randomized, prospective study testing the efficacy of adjuvant chemotherapy after aggressive local treatment of high-grade sarcomas of the head, neck, breast, and trunk (excluding retroperitoneal sarcomas). All patients had complete resection of gross tumor and underwent postoperative radiotherapy (6000-6300 rads over 7-8 weeks). Seventeen patients received adjuvant chemotherapy consisting of doxorubicin (less than or equal to 550 mg/m2), cyclophosphamide (less than or equal to 5500 mg/m2), and methotrexate (less than or equal to 1000 mg/kg). Three-year actuarial disease-free survival in the chemotherapy arm was 77%, compared to 49% in the no-chemotherapy arm (P = 0.075). Three-year overall actuarial survivals in the two treatment arms, however, were 68% and 58%, respectively (P = 0.38). Considering only patients with tumors of the trunk (22 patients), 3-year actuarial disease-free survival in the chemotherapy arm was 92%, compared to 47% in the no-chemotherapy arm (P = 0.006). Actuarial 3-year overall survival in the chemotherapy arm was 82%, compared to 61% in the no-chemotherapy arm (P = 0.18). An additional 26 patients were treated in an identical fashion, but were not part of the randomized trial because of contraindications to chemotherapy, refusal to enter the randomized trial, or because they were treated before 1977 in a trial in which all patients received chemotherapy. Considering the entire group of 57 patients, follow-up ranged from 10 to 86 months (median, 35 months). Local control was achieved in 46 patients (81%); 3-year actuarial disease-free and overall survivals were 67% and 77%, respectively. A tendency toward improved disease-free survival was apparent among patients treated with chemotherapy (P = 0.018), but there was no statistically significant improvement in overall actuarial survival (P = 0.46). The subgroup of patients with sarcomas of the trunk (39 patients) demonstrated the greatest benefit from chemotherapy, with regard to disease-free survival (P less than or equal to 0.001). The most significant toxicity associated with chemotherapy was doxorubicin-induced cardiomyopathy, which resulted in clinically apparent congestive heart failure in five patients. Thus, the use of chemotherapy when combined with aggressive local measures appears to improve disease-free survival, but additional patients and longer follow-up are necessary to determine if improved overall survival will result.
From July 1975 to December 1982, 563 patients were referred to the Surgery Branch of the National Cancer Institute with the diagnosis of soft-tissue sarcoma. Three hundred and seven of these patients had fully resectable, localized high-grade soft-tissue sarcomas and were treated at the National Cancer Institute using standard protocols with surgery alone, or in combination with chemotherapy and/or radiotherapy. An aggressive surgical approach was undertaken in the management of patients who subsequently developed recurrent disease. These 307 cases have been reviewed, with a median duration of follow-up of 30 months, to determine the frequency of recurrent disease, the patterns of recurrence, and the impact of surgery on the survival of patients who developed recurrent disease. Disease recurred in one hundred seven patients (107/307, 35%), with a median disease-free interval of 18 months (range, 0.5 to 72.0 months). The frequency of recurrence by site of primary sarcoma was extremity, 31% (65/211); head and neck, 33% (4/12); trunk, 40% (17/42); retroperitoneum, 47% (17/36); and breast, 67% (4/6). Isolated pulmonary metastatic disease was the most common pattern of initial recurrence (56/107, 52%) followed by isolated local recurrence (21/107, 20%). Single other sites of recurrence and multiple concurrent sites of recurrence each accounted for 14% (15/107) of all initial recurrences. The relative frequency of each of these four patterns of recurrence varied with the site of the primary sarcoma. The outcome for patients with recurrent disease depended on the site of recurrence, rather than on the site of the primary sarcoma. Sixty-six patients (66/107, 62%) with recurrent disease were rendered surgically disease-free with the first recurrence, including 40 (40/56, 72%) patients with isolated pulmonary metastases, 20 patients (20/21, 96%) with isolated local recurrences, five patients (5/15, 33%), with isolated other sites of recurrence and one patient (1/15, 7%) with multiple sites of initial recurrence. Following surgical resection, the actuarial three-year survival for the 66 patients rendered disease-free was 51%. The median survival for the 41 patients not rendered surgically disease-free with the first recurrence was only 7.4 months. Thirty of the sixty-six patients (30/66, 45%) rendered disease-free with the first recurrence remained disease-free at follow-up, with a median follow-up of 28 months from the time of resection of the first recurrence. The remaining 36 patients (36/66, 55%) subsequently recurred, with a median disease-free interval of 7.3 months.(ABSTRACT TRUNCATED AT 400 WORDS)
Thirty-seven patients with resectable retroperitoneal sarcomas were studied prospectively to determine the efficacy of aggressive multimodality treatments. No patients was lost to follow-up, which ranged from 11 to 85 months (median 29 months). All patients received radiotherapy and some received postoperative chemotherapy (doxorubicin, cyclophosphamide, and high-dose methotrexate). A subset of 15 patients were entered into a prospective, randomized study testing the efficacy of adjuvant chemotherapy (eight received chemotherapy; seven did not). Two-year actuarial survival rates were inferior in the chemotherapy arm (100% versus 47%; p = 0.06), but the small number of patients precluded drawing definitive conclusions from this randomized study alone. Among the entire 37 patients (21 received chemotherapy; 16 did not) the actuarial 3-year survival rate was 43% and appeared unaffected by chemotherapy. Two patients suffered doxorubicin infiltration, three sustained cardiac toxicity, two developed cyclophosphamide-induced cystitis, and three withstood transient, severe bone marrow suppression. Eight patients suffered severe radiation enteritis, and one patient died after bowel resection for this problem. Thus the chemotherapy regimen we administered did not appear to improve survival but was associated with major morbidity. Radiotherapy was also associated with major complications, and since all patients received radiotherapy, it remains to be established if this modality is beneficial in improving survival.