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Biomedical subjects

S Kramer

Publications and source records attributed to S Kramer.

At least 37 records · Page 2Linked to original sources

The outcome of treatment of 313 patients with T-1 (UICC) prostate cancer treated with external beam irradiation.

Three hundred and thirteen patients with UICC T-1 N-0 M-0 prostate cancer were treated with external beam irradiation in 1973 and 1974 or in 1978, and their outcome determined 3-10 years after treatment. Survival over the first 5 years was comparable to that expected for a group of age matched normal males (77% vs. 81%), but during the second 5-year interval, there was a decrease in survival below that expected (51% vs 62%), a reflection of death in patients who developed metastasis as a first recurrence (18%). Overall, 72% of patients were free of any recurrence at 5 years and, 88% free of infield recurrence. The development of metastatic recurrence was significantly related to grade; at 5 years 87% of grade I, 79% of grade II and 69% of grade III patients were free of metastasis. There was a trend for increased local recurrence with increasing grade, but it was not statistically significant. There was a dose/response relation for complications, and radiation doses above 6500 cGy are associated with an increase in complication from 6% to 11% (p = .09). Complications requiring hospitalization for evaluation or management occurred in 30 (10%) of 313 patients. There were no deaths from complications and less than 2% of patients required surgical correction of complications. External beam radiation offers the patient with early prostate cancer a favorable opportunity for cure without the morbidity of impotence, incontinence, and occasional death experienced following LND and radical prostatectomy. Lymph node dissection does not seem necessary for most patients with T-1 prostate cancer as the positive yield in those with Grades I and II cancers is less than the complications of the procedure, and extensive involvement can be detected by non-invasive means.

Adult

The developmental context of internalized preoedipal object relations. Clinical applications of Mahler's theory of symbiosis and separation-individuation.

Mahler's theory of symbiosis and separation-individuation demonstrates the essential unity of drive, ego, and object relations psychologies. By highlighting the role that early dyadic relations play in psychic structure formation, her theory expands the understanding of human psychic development and its failures. This paper reviews Mahler's propositions and underscores their clinical importance by describing two cases where much preoedipal reconstructive work preceded the emergence of an analyzable oedipal transference neurosis.

Adult

Radiation Therapy Oncology Group (RTOG) studies in head and neck cancer.

Since its foundation in 1971, the RTOG has conducted a successful clinical research program in head and neck mucosal squamous cell carcinoma with 22 treatment protocols and one registry study which combined have accumulated data on over 5,500 patients. The RTOG was the first multicenter group to evaluate neoadjuvant chemotherapy before definitive radiation with its methotrexate study. Although the study was negative, RTOG has since conducted five pilot or phase II studies of neoinduction or concurrent chemotherapy with radiation therapy in patients with inoperable tumors. The last study showed that radiation concurrent with cisplatinum was tolerable with a suggestion of increased antitumor effect. In patients with potentially resectable tumors, RTOG has completed a pilot study of combination chemotherapy administered either before or after the surgery with radiotherapy. Based upon its findings, the treatment sequence, surgery-chemotherapy-radiotherapy, was chosen as the experimental arm for a new phase III study. This study was subsequently adopted by the head and neck intergroup mechanism as its study (INT 0034/RTOG 8503). RTOG has investigated the optimal timing of radiotherapy with surgery. The 7303 study established that postoperative radiotherapy achieved significantly better locoregional control but not improved absolute survival. Approximately 30% of the patients on each arm failed to complete both modalities. Even when comparison is restricted to patients who completed both modalities, postoperative radiotherapy still produced the better locoregional control. Efforts to overcome the limitations imposed by tumor hypoxia through use of carbogen (95% O2 and 5% CO2) breathing or the radiosensitizer misonidazole during radiotherapy have been unsuccessful. In a phase I study, RTOG showed that 15 to 18 sessions of sensitized radiation can be safely delivered with the new radiosensitizer SR 2508 in contrast to only six such sessions with misonidazole. This promising radiosensitizer is now being tested in a phase III trial. RTOG has also investigated variations in fraction size, fraction number, and total radiation dose. In the 7102 study, split-course irradiation achieved equivalent antitumor results as compared to continuous daily irradiation but with less social alteration and cost to the patient. In the hyperfraction pilot study 7703, twice a day irradiation with 120 cGys up to 6,000 cGys proved to be tolerable.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged

Purification of bovine protoporphyrinogen oxidase: immunological cross-reactivity and structural relationship to ferrochelatase.

Protoporphyrinogen oxidase, the penultimate enzyme in the haem biosynthetic pathway has been purified to apparent homogeneity from bovine liver mitochondria, by a published method (Dailey, H.A. and Fleming, J.E., (1983)), with an additional ion-exchange chromatography step, using a Mono Q column on an FPLC-system. This gave a product with a 68% yield and 870-fold purification. Protoporphyrinogen oxidase (EC 1.3.3.4) has an apparent Mr of 57,000 and the Km for protoporphyrinogen IX was 16.6 microM. Activity of the isolated enzyme was increased by 66% in the presence of oleic acid, and evidence was obtained for a FAD prosthetic group. Ferrochelatase (EC 4.99.1.1) was purified and antibodies were raised in rabbits against ferrochelatase and protoporphyrinogen oxidase, respectively. Anti-protoporphyrinogen oxidase IgG showed marked cross-reactivity with ferrochelatase and anti-ferrochelatase IgG cross-reacted with protoporphyrinogen oxidase. In addition, radiolabelled peptides of both enzymes, generated by chymotrypsin, demonstrated common peptides when analysed by two-dimensional chromatography.

Animals

Gestational risk factors for Wilms' tumor: results of a case-control study.

Gestational risk factors for Wilms' tumor were investigated in a pair-matched case-control study. Cases who were under 15 years of age at diagnosis during 1970-1983 were identified through the registries of the three main hospitals treating childhood cancer in the greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone area code and exchange. Because of a low participation rate among nonwhites, results are reported only for the 88 white matched pairs whose parents were interviewed by telephone. Of the hypothesized risk factors, maternal use of hair-coloring products in the year prior to the index child's birth (odds ratio, 3.6; P = 0.003) and hypertension or fluid retention during pregnancy (odds ratio, 5.0, P = 0.01) were significantly associated with increased risk of Wilms' tumor. Use of hair-coloring products was strongly associated with cases in which Wilms' tumor was diagnosed before 2 years of age (odds ratio, 15; P = 0.001). For two other gestational factors, tea drinking and vaginal infection, the odds ratios were significantly elevated for all cases and the effects were concentrated among the nongenetic cases. Bilateral cases had a significantly higher mean birth weight than did their controls. Older maternal age was significantly associated with the genetic form of Wilms' tumor. Adjustment for possible confounders and consideration of the time interval between the index pregnancy and the interview did not substantially alter the findings.

Female

Antisecretory activity of misoprostol, its racemates, stereoisomers and metabolites in isolated parietal cells.

Inhibition of histamine-stimulated acid secretion by misoprostol was compared to its racemates, stereoisomers and metabolites in isolated canine parietal cell preparations. The concentration of misoprostol required to inhibit 50% of maximal histamine-stimulated acid secretion (IC50) was 3.8 +/- 0.3 nM. One racemate of misoprostol was at least 1000 times more potent than the other. Of the four misoprostol stereoisomers, the 11R, 16S isomer exhibited the most potent activity against histamine with an IC50 value of 1.4 +/- 0.1 nM. The acid metabolite of misoprostol was equally potent as misoprostol. In contrast to the acid metabolite, the beta-oxidation metabolites of misoprostol lacked significant activity at 1 microM. The results indicate that: 1) the acid metabolite of misoprostol may play a significant role in the antisecretory activity of misoprostol, and 2) the high degree of stereo-specificity associated with the antisecretory effects indicates that the activity of misoprostol may be receptor mediated.

Alprostadil

A contribution to the concept "the exception" as a developmental phenomenon.

The sense of "entitlement" or of being an exception has been noted in people who have suffered from severe childhood deformities or from other forms of severe deprivation. In such cases it constitutes a restitution for earlier suffering. In this vignette from the treatment of a patient who, because of sexual abuse by her mother, did not feel that she owned her own genitals, the sense of entitlement represented a developmental step toward ownership of her own body.

Adult

A ten year follow-up of 682 patients treated for prostate cancer with radiation therapy in the United States.

This report extends the follow-up of patients studied in the Patterns of Care Survey of Prostate Cancer treated in the United States between 1973 and 1975 from a maximum of 5 years to a maximum of 10 years. Survival for 60 Stage A patients was the same as expected for their age distribution (83% at 5 years and 62% at 10 years). Survival for 312 Stage B patients was 73% at 5 years and 46% at 10 years and for 296 Stage C patients was 58% at 5 years and 38% at 10 years. Infield recurrence was determined by clinical means, at 5 years 97% of Stage A patients, 86% of Stage B patients, and 74% of Stage C patients were free of local recurrence. At 10 years 97% of Stage A patients, 74% of Stage B patients, and 69% of Stage C patients remained free of local recurrence. Patients with Stage B and C cancer who developed their first failure infield show a long-term survivorship after recurrence of 40% and 20% respectively. This is in contrast to Stage B and C patients who develop a first recurrence at a metastatic site where the rate of progress to death was slower in Stage B patients than for those with Stage C disease (mean survival 32 months versus 19 months), but eventually all are dead by 7 years after recurrence. Complications were infrequent, actuarial analysis shows 93% of patients free of serious complications at 5 years and 89% free at 10 years. There were 14 patients (2%) whose complications required surgical correction and 2 of the 682 patients died of complications.

Actuarial Analysis

Failure of misonidazole-sensitized radiotherapy to impact upon outcome among stage III-IV squamous cancers of the head and neck.

As part of the RTOG research effort in the treatment of advanced, inoperable squamous cancer of the head and neck region, the hypoxic cell sensitizer, misonidazole, was selected for investigation as an adjuvant to definitive irradiation. Based upon a pilot experience (78-02) showing a 67% complete response rate among 36 AJC Stage III-IV patients receiving full-dose irradiation and 6 weekly p.o. doses of misonidazole, a phase III trial was carried out from '79-'83. Three hundred and six patients were entered, 42% of whom had oropharyngeal primaries and with 78% of all cases representing T3 or T4 (inoperable) lesions. Only 16% of the entire series presented with N0 necks. Fractionation was altered among the misonidazole-receiving patients, in contrast to "standard" 5 treatments per week among "control" patients, such that 2 separate treatments were given on each day of p.o. misonidazole administration (2.0 gm/m2/wk X 6 doses, 2.5 Gy in a.m., 2.1 Gy in p.m.). Total tumor doses were identical among the two treatment arms except that a limitation of 40.0 Gy to spinal cord was specified for sensitized radiotherapy vs. 45.0 Gy for "control" patients. Primary tumor clearance was observed to be 55-60%, with minor variations according to tumor stage and site. The local regional control rate among radiotherapy-alone patients was 26% at 2 years compared to 22% (2 years) within the misonidazole-receiving group. Analysis of survival revealed no advantage to the sensitized patients, with 55 +/- 2% surviving 1 year and 22 +/- 1% living 3 years following treatment in both treatment categories. Distant metastases as first site of failure (12-13%) and the local failure among initial complete responders (46%) showed no advantage to the misonidazole group. Although a misonidazole dosage of 2.0 gm/m2/wk X 6 (12 gm/m2 total) is well tolerated, no clinical benefit was demonstrated in this randomized trial. Other nitroimidazole analogs (e.g. SR-2508) are now being investigated.

Aged

Medical and drug risk factors associated with neuroblastoma: a case-control study.

A matched case-control study of prenatal risk factors for neuroblastoma was conducted, including 104 cases diagnosed over the period 1970-79 in the Greater Delaware Valley. Significantly elevated odds ratios (ORs) were associated with maternal use of a neurally active drug during pregnancy (OR = 2.83), sex hormone exposure 3 months prior to or during pregnancy (OR = 2.25), frequent alcohol consumption during pregnancy (OR = 9.0), and maternal use of diuretic drugs during pregnancy (OR = 5.75). Significantly more case mothers than control mothers reported use of hair coloring products during pregnancy (OR = 3.0). No association was found between cigarette smoking, coffee consumption, or medical irradiation and case-control status.

Alcohol Drinking

Protoporphyrinogen oxidase in porphyria variegata. A report of the findings in 7 families.

Protoporphyrinogen oxidase (PPO) activity was determined in 7 families with porphyria variegata (PV). Enzyme activity was reduced by 50% in 8 propositi and in 8 out of 16 prepubertal children. These results are in keeping with the concept that PV is inherited as an autosomal dominant disease. Enzyme activity was also reduced in the fathers of 2 of the propositi, who were suspected on family history of carrying the PV trait, but who had no clinical manifestations. Determination of PPO activity provides a reliable means of identifying PV and of identifying offspring who could, at puberty, become PV patients.

Adult

Quantitation of the monoclonal plasma cell component in bone marrow from patients with serum paraproteinemia and nondiagnostic marrow morphology.

Twenty-one patients with serum monoclonal gammopathy but lacking acceptable morphological evidence of myelomatosis were studied with reference to the degree, if any, of monoclonal plasma cell expansion in aspirated marrow samples, enriched for plasma cells and analysed with respect to light chain distribution. Four of these patients had a biopsy-proven plasmacytoma of bone. Bone marrow aspirated from sites distant to the tumor showed clear evidence of infiltration by monoclonal plasma cells in two of the cases studied; the other two patients had normal results. Of the 17 other cases, 14 showed evidence of a monoclonal plasma cell component qualitatively concordant with the serum paraprotein as one would expect. These cases could be subdivided into those with myeloma (six cases) and those with monoclonal gammopathy of undetermined significance (eight cases) on the basis of conventional biochemical and radiological criteria. Three of the 17 patients, however, did not show evidence of monoclonal plasma cell infiltration, despite the presence of lytic lesions. It is important to recognize this minority group that simulates myeloma but that may well reflect alternative pathology that has not been identified.

Bone Marrow

Prognostic factors for loco/regional control and metastasis and the impact on survival.

For the identification of predictive factors for local (head and neck) control and metastases and impact on survival in squamous cell cancer of the head and neck, we have used data from over 2000 patients from the Patterns of Care Study (PCS) and the Radiation Therapy Oncology Group (RTOG) studies. Complete local response (C.R.) is significantly related to T stage, N stage, general performance status (Karnofsky), and site of primary tumor. There is a strong association between T and N stage. T1N0 tumors showed a C.R. of 99%, whereas, T1N3 had a C.R. of 57%. T4N0 showed a C.R. of 75%, but this went down to 31% in the T4N3 lesions. Glottic tumors showed a C.R. of 96% versus the other sites, which ranged from 81% for the nasopharynx to 59% for the hypopharynx. Patients with a performance status (KPS) of less than 90% showed a C.R. of 60% versus 88% for AKPS 90% or higher. Absence of local recurrence after C.R. is significantly related to T stage, N stage, and the site of primary tumor (glottis versus the rest). The appearance of distant metastases is significantly related only to N stage and primary site. This relationship persists in control of loco/regional tumors. In Stages III & IV in non-glottic head and neck cancer, metastases as the cause of death play an increasingly important role. This can be as high as 30%. The appearance of new malignant tumors and death unrelated to cancer, that is, death related to lifestyle, assumes an important role in patients with advanced head and neck cancer. The number of advanced glottic larynx was too small to examine this question. The use of a surgical procedure in carcinomas of the anterior tongue and floor of the mouth was associated with a smaller percentage of infield recurrences at 2 years, than when radiation therapy alone was used (27% versus 88% p less than .01). The same observation was noted at 3 years in the glottic and supraglottic Stage III & IV tumors (p less than .01).

Carcinoma, Squamous Cell

Patterns of Care Study. Analysis of outcome survey data-anterior two-thirds of tongue and floor of mouth.

The Patterns of Care Study, begun in 1973, carried out its second outcome survey from December 1978 through April 1979. The review of patients with epidermoid carcinomas of the anterior two-thirds of tongue and floor of mouth included patients treated between January 1973 and June 1975 so that a minimum follow-up period of 2 years was evaluable. Records of 434 patients from 96 facilities were available for analysis, although not every patient could be evaluated for every variable. Almost three-fourths (320) were treated with radiation alone. In these data, four patient and disease characteristics were strongly related to recurrence rates including stage at presentation, deep ulceration, deep infiltration, and age. Treatment variables significantly affecting recurrence included use of interstitial therapy in Stages I and II, use of surgery in Stages III and IV, and a facility's best equipment.

Brachytherapy