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Biomedical subjects

R E Falk

Publications and source records attributed to R E Falk.

At least 55 records · Page 3Linked to original sources
PubMed1987

Examination of patient selection and outcome for hepatic resection for metastatic disease.

Hepatic resection for metastatic disease is now an accepted therapeutic option in a selected group of patients. A series of 56 patients undergoing hepatic resection at a single institution from 1974 to 1985 are presented. Resection was carried out in 27 women and 29 men who ranged in age from 23 to 87 years (a mean of 56 years). The site of primary disease was: colorectal in 41, adrenal gland in two and other sites in 13. Of the 56 hepatectomies, 21 were done for synchronous secondary disease discovered before or at operation for the primary disease. Metachronous lesions were found in 35 patients, from two months to 17 years (a mean of 34 months) after excision of the primary tumor. Estimated five year survival rates using the Kaplan-Meier method was 25 per cent in the patients with colorectal primaries and 35 per cent in the entire group. No difference was demonstrated between synchronous and metachronous resections. Patients with multiple hepatic lesions did much poorer than those with solitary tumors. Patients with metastatic tumor consisting of one large lesion with surrounding satellite nodule or nodules had an expected survival time resembling that for those with true solitary metastases and were included in that group. No difference in survival time was observed in patients with carcinoma of the colon and rectum who had involvement of regional nodes at the time of the primary resection, as compared with patients with negative nodes. Hepatic resection for a secondary malignant growth can be performed safely with a real chance for cure in selected instances. We continue to recommend an aggressive approach to hepatic metastases, especially those of a colorectal origin.

Adenocarcinoma↗
PubMed1987

The peripheral nerve allograft: an assessment of regeneration in the immunosuppressed host.

Regeneration across the nerve allograft in the immunosuppressed host was assessed using electrical and histologic parameters. The Lewis rat (RTIl) served as the recipient animal, and ACI rats (RTIa) provided the donor nerve allografts. Hydrocortisone and azathioprine were used in various dose schedules as the immunosuppressive agents. Animals were immunosuppressed for either 30 or 100 days. Histologic and electrophysiologic measurements of nerve regeneration were assessed at 30, 100, and 180 days. The degree of nerve regeneration was similar in all experimental groups. Short-term, low-dose immunosuppression was as successful as longer-term, higher-dose immunosuppression therapy. The degree of nerve regeneration in all experimental groups was significantly better than that in the fresh, untreated nerve allograft control group (Lewis/ACI) but was not as good as that seen in the autograft control group (Lewis/Lewis).

Animals↗
PubMed1986

Combination therapy for resectable and unresectable adenocarcinoma of the pancreas.

The current report summarizes our experience with 77 patients with cancer of the pancreas treated over 3.5 years. Patients were not assigned to a definite group of therapy, but through the availability of different drugs and different types of treatment several comparable groups have evolved. All patients have received radiofrequency hyperthermia and chemotherapy, but in addition, some have received selective immune stimulation with one of two low-molecular-weight compounds. The data show that radiofrequency hyperthermia permits the use of a lower dose of chemotherapy, with an apparent response to treatment. This response is enhanced significantly by the addition of selective immune stimulation. A further, more rigorously defined study will be undertaken to confirm this data.

Adenocarcinoma↗
PubMed1986

Polyclonal immunoglobulin production in burned patients--kinetics and correlations with T-cell activity.

Spontaneous and pokeweed mitogen (PWM)-induced polyclonal immunoglobulin production in vitro were estimated in patients with severe burns (28-83% TBSA) immediately following their injury and at intervals of 8 to 14 days thereafter. In parallel, functional activity of patients' T lymphocytes was assessed in the mixed lymphocyte reaction (MLR). PWM-induced immunoglobulin secretion, of both IgG and IgM, was elevated in the first 2 to 3 weeks after burn, followed by a period of relatively suppressed antibody response at 3 to 4 weeks. Immunoglobulin production was then apparently restored to baseline or higher levels in surviving patients. However, in patients whose antibody response continued to be suppressed fatal septicemia developed. The background (spontaneous) immunoglobulin synthesis increased significantly over the normal range in 10/78 tests performed. These alterations in mitogen-induced immunoglobulin production were well correlated with changes in the T-cell alloreactivity in the MLR. Thus thermal injury-associated changes in the patients' humoral responses may be a consequence of changes within the T-cell compartment, especially the T-helper cell subset.

Adolescent↗
PubMed1986

Allogeneic hepatocyte transplantation in the rat spleen under cyclosporine immunosuppression.

An innovative approach for stimulating the rapid growth of allogeneic hepatocytes implanted into splenic tissue with maintenance of the structural integrity is described. Single cell suspensions of hepatocytes from normal male ACI-strain rats (RTIa) were injected (2 X 10(6) cells) into the spleen of allogeneic male Fischer (RTI1) recipient rats. A 70% partial hepatectomy (PH) was performed at the same time as hepatocyte transplantation. Animals were treated for 4 days prior to, and 1 day after, transplantation with a feeding regimen containing 0.05% 2-acetylaminofluorene (AAF) to inhibit regeneration of the residual host liver. Animals received cyclosporine (CsA) 3 mg/kg/day s.c. posttransplantation. Histological examination of a standard longitudinal section of the recipient spleen two days posttransplant revealed an approximately 0.54-mm2 area replaced by hepatocytes. By 7 days this had increased to 0.97 +/- .15 mm2. Without CsA administration, hepatocytes were undetected at 7 days. Both PH and AAF treatment were necessary for successful colonization and sustained proliferation. Withdrawal of CsA treatment at 10 days after transplantation resulted in rapid rejection of established hepatocytes. This study demonstrates that rapid colonization of the rat spleen with allogeneic hepatocytes can be achieved, and that the viability and structural integrity of these transplanted cells can be maintained for at least 14 days using cyclosporine immunosuppression.

2-Acetylaminofluorene↗
PubMed1986

Excision of abdominal wall tumours and reconstruction with Marlex mesh.

Because metastatic abdominal wall tumours are rare and their biologic activity is unpredictable, they must be managed aggressively (a) for potential cure of isolated recurrences and (b) to obtain good palliation, as fetid exophytic lesions alter the patient's self-image and life-style. An aggressive surgical approach often leaves a large abdominal wall defect. The authors describe 19 patients (10 men, 9 women) with these tumours who had their abdominal wall reconstructed with Marlex mesh. All patients received antibiotics preoperatively, but 16 had either mechanically unprepared bowel due to obstruction or abdominal contamination from the intestine intraoperatively. The commonest complication was wound abscess in 10 patients; it was controlled without removing the Marlex mesh. The majority of patients had prolonged palliation with greatly reduced symptoms, a reasonable quality of life and acceptable cosmesis. Potentially life-threatening intra-abdominal complications were reduced. One patient was considered cured. The authors believe that there is a definite role for aggressive surgical management of abdominal wall metastases and that Marlex mesh may be used for reconstruction even when there has been peritoneal contamination.

Abdominal Muscles↗
PubMed1986

Impairment of T cell activation in burn patients: a possible mechanism of thermal injury-induced immunosuppression.

In the burn patient, the mechanisms leading to impaired T lymphocyte activity are unclear. The capacity for T cell proliferation and the expression of Tac antigen (IL-2 receptor) was assessed during the post-burn period in patients with injuries ranging from 5-68% total body surface area. T cell-dependent (polyclonal) immunoglobulin synthesis, mixed lymphocyte reaction and Interleukin-2 production were also determined in these patients and correlated with survival. Surviving patients demonstrated a transient reduction while terminal patients exhibited a permanent reduction in the number of Tac (+) lymphocytes, unrelated to the absolute number of T cells, during the post-burn period. The reduced percentage of IL-2 receptor-expressing T cells coincided with the suppressed antibody response and reduced alloreactivity. Although the concentration of IL-2 was decreased in all patients throughout the hospitalization period, surviving patients showed a gradual increase in its production while terminal patients gradually decreased to undetectable levels. Exogenous recombinant IL-2 induced a significant enhancement of in-vitro polyclonal immunoglobulin production and blastogenesis in the mixed lymphocyte reaction in immunosuppressed patients who demonstrated up to 50% reduction in the percentage of IL-2 receptor positive cells. Thus, the reduced capacity for production of and response to IL-2 after thermal injury may lead to the immunosuppression due to a lack of T lymphocyte clonal expansion. The permanent nature of this defect in patients who died from fatal sepsis may suggest a causative relationship.

Adult↗
PubMed1985

Beta-glucuronidase deficiency. A heterogeneous mucopolysaccharidosis.

We studied two cases of beta-glucuronidase deficiency. One patient's disease was present at birth and the other patient's disease appeared in early childhood. The symptoms observed in both patients, although of differing severity, included peculiar facies, cloudy cornea, hepatosplenomegaly, hernia, kyphosis, recurrent infections, short stature, and developmental delay, as well as increased excretion of urinary chondroitin sulfate A/C and decreased levels of beta-glucuronidase activity. We reviewed all of the reported cases and examined the biochemical and clinical heterogeneity observed in this disorder.

Child↗
PubMed1985

Hyperthermia for cancer: a practical perspective.

A causal relationship between hyperpyrexia and tumor regression was first suggested in 1866, when Busch reported the cure of a histologically diagnosed sarcoma in a middle-aged woman, following a bout of erysipelas. Over the years, interest in the effect of heat on cancer has remained alive, but this interest has increased dramatically in recent years. The literature on this subject is broadly reviewed and the clinical results discussed. It is apparent from clinical studies thus far that it is a relatively simple undertaking to treat superficial neoplasms with hyperthermia. However, the major challenges in clinical thermotherapy pertain to patients with deeply situated tumors. The lack of safe and reliable methods of monitoring temperature in deep tissues is a major impediment to a thorough understanding of thermal dosimetry in clinical hyperthermia, and routine thermal dosimetry in clinical hyperthermia will have to await the development of reliable noninvasive thermometry. As responses have been reported with modest levels of hyperthermia, the need for thermometry is somewhat lessened, given that invasive monitoring is imperfect and somewhat risky when used in deeply seated tumours. The eventual place of thermotherapy in the treatment of malignant tumours in man is as yet unclear and must be rigourously and thoroughly assessed in well-designed, prospective, randomized patient trials.

Animals↗
PubMed1985

Enhanced survival in antibiotic-treated murine fecal peritonitis by administration of copovithane, a selective immunostimulative polymer.

The purpose of this study was to determine the effect of an immunostimulative polymer, Copovithane (Cpv), plus antibiotics (netilmicin and clindamycin) in a murine model of fecal peritonitis. Cpv augments humoral immunity with little effect on T cells and is nontoxic. Cpv 100 mg/kg iv administered at the onset of sepsis increased median survival time (MST) by 40-55% over untreated controls. Four experiments were performed. Cpv in combination with antibiotics when given at the time of onset of sepsis was significantly more effective than antibiotics alone (MST 235 vs 105 hr, P less than 0.05 at 144, 168, 192, 216 hr). In the second and third experiments Cpv alone and with antibiotics was administered 15 hr after the onset of sepsis. Cpv significantly augmented survival over controls in the second experiment (MST 87 vs 60 hr, P less than 0.025 at 96 hr). Cpv plus antibiotics was significantly better than antibiotics alone in the third experiment (MST 111 vs 64 hr, P less than 0.05 at 72 hr, P less than 0.005 at 120 hr). In the final experiment, Cpv did not inhibit growth of 20 bacterial species in agar and liquid media. Cpv significantly enhances survival in murine fecal peritonitis even when administered after the onset of sepsis; furthermore Cpv plus antibiotics in established peritonitis produces longer survival than antibiotics alone. Synthetic immunomodulators such as Cpv could eventually play a significant role in the management of peritoneal infection in humans.

Animals↗
PubMed1985

The nerve allograft response--an experimental model in the rat.

The nerve allograft response in a rat model is presented. The Lewis rat (RTI1) served as the recipient animal while Fischer rats (RTI1) and ACI rats (RTIa) provided the donor nerve allografts. A Lewis/Lewis autograft group was used as the control group. Histological and electrophysiological measurements of nerve regeneration were assessed at five months. While good regeneration was noted in the autograft and matched allograft groups, regeneration across the unmatched allograft was poor. The degree of nerve regeneration (as measured with histological and electrophysiological values) correlated well with previous immunological studies and would support the use of this model for future investigation of the nerve allograft response in the rat.

Animals↗
PubMed1985

Reversal of cyclosporine-induced mortality with a synthetic polymeric immunostimulant in a murine model of fecal peritonitis.

We have been investigating the effects of a synthetic immunostimulative polymer known as copovithane (Cpv). This agent appears to enhance humoral immunity in untreated and cyclosporine-immunosuppressed mice and is nontoxic in rodents and man. The purpose of this study was to determine whether cyclosporine (CsA) is deleterious to survival in a murine cecal ligation, puncture, and excision (CLPE) model of fecal peritonitis, and--if so--whether this effect could be ameliorated by Cpv without interfering with skin allograft acceptance. Cpv significantly prolongs survival in the CLPE model; the optimal dose for this effect was found to be 100 mg/kg. CsA was found to have a significant and deleterious effect on survival at several dosage levels when administrated 48 and 24 hr before cecal ligation, and immediately before and 16 hr after cecal ligation. Using a dose of CsA sufficient for skin allograft acceptance and the same schedule of administration outlined above, Cpv 100 mg/kg was administered 48 hr prior to cecal ligation. Mice treated with CsA plus Cpv had significantly longer survival than mice treated with CsA alone; furthermore, the survival of CsA-plus-Cpv-treated animals was not significantly different from that of saline-treated controls. Acceptance and survival of H-2 incompatible skin allografts in mice treated with CsA were not affected by Cpv 100 mg/kg/week. We conclude that CsA-induced mortality in the CLPE model can be abrogated by Cpv without adversely affecting skin allograft survival. It may eventually be possible to reduce the incidence of septic complications in clinical allotransplantation by prophylactically administering Cpv to patients on CsA immunosuppression.

Animals↗
PubMed1985

False-positive amniotic fluid acetylcholinesterase results: the need for a multifacet approach to the prenatal diagnosis of neural tube defects.

Two cases are presented with false-positive amniotic fluid alpha-fetoprotein and acetylcholinesterase results for the prenatal diagnosis of neural tube defects. Stage II ultrasound revealed no lesions of the fetal spine in both cases. The alpha-fetoprotein and acetylcholinesterase results returned to normal on subsequent taps. Both pregnancies resulted in normal outcomes. A protocol is presented for managing pregnancies with abnormal alpha-fetoprotein and acetylcholinesterase results.

Acetylcholinesterase↗
PubMed1985

Pelvic exenteration for advanced primary and recurrent adenocarcinoma.

The authors report on 45 patients who have undergone pelvic exenteration for adenocarcinoma since 1979. Three patients underwent exenteration as the initial treatment for their disease but all others had had previous surgery, radiotherapy or chemotherapy. Operating time and blood loss were lower in previously irradiated patients. There were seven in hospital deaths (15.5%). The number of complications and length of postoperative hospital stay have decreased significantly as experience with pelvic exenteration has been acquired. Symptoms have been controlled in a high proportion of patients. Exenterative surgery is an effective method of treatment in selected patients with pelvic adenocarcinoma but should be undertaken only by experienced surgeons who have access to a wide range of supportive facilities for optimal perioperative management.

Adenocarcinoma↗
PubMed1984

Congenital pernicious anemia: report of seven patients, with studies of the extended family.

Seven children ages 1 1/2 to 12 years with congenital pernicious anemia were detected in an extended Mexican family. All affected children had megaloblastic anemia accompanied by low serum B12 and normal serum folate levels. Gastric fluid analysis in six patients revealed normal gastric acidity and absent intrinsic factor. Serum antibodies to intrinsic factor or parietal cells were also absent. Schilling tests performed in six of the seven patients yielded abnormal results. Of the three patients in whom gastric biopsy was done, two had normal histologic findings (including examination by electron microscopy) and one had mild atrophy. All patients responded rapidly to parenterally administered vitamin B12 therapy. In addition, 170 family members were screened for the defect with complete blood counts and serum B12 levels. Such screening detected pernicious anemia in two of the children, but no other abnormalities that could be attributed to pernicious anemia were found in other family members. Based on the family pedigree, autosomal recessive inheritance is likely. The variability of age of presentation in this family is noteworthy and suggests that expression may be modified by still undefined factors.

Anemia, Pernicious↗