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Biomedical subjects

J W Smith

Publications and source records attributed to J W Smith.

At least 19 recordsLinked to original sources
PubMed1992

Pseudomyxoma peritonei of appendiceal origin. The Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: Pseudomyxoma peritonei is a rare clinical entity in which the peritoneal surfaces and omentum are involved with diffuse gelatinous mucinous implants. It originates from ruptured mucinous tumors of the appendix or ovary. METHODS: The authors examined the experience with 34 patients with pseudomyxoma peritonei seen at Memorial Sloan-Kettering Cancer Center from 1952-1989. Of these, 17 cases were identified to be of appendiceal origin. RESULTS: All patients underwent celiotomy and cytoreduction. The median survival time from diagnosis was 75 months. It was found that long-term survival can be achieved by operation alone. When conditions do recur, chemotherapy may be valuable. CONCLUSIONS: Pseudomyxoma peritonei of appendiceal origin is a rare low-grade malignancy. Initial treatment consists of cytoreduction in an attempt to render the patient locally disease-free. Long-term survival can be obtained by operation alone, even if gross disease is present at the end of the procedure. Systemic chemotherapy should be reserved for patients with proven recurrence.

Adenocarcinoma, Mucinous↗
PubMed1992

Intensive therapy with cisplatin, interleukin-2 and interferon-alpha-2a in patients with metastatic melanoma. A phase II Study.

OBJECTIVE: Based upon their individual clinical activity and combined effects in animal models or in vitro, we wished to evaluate a regimen of cisplatin, interferon-alpha, and IL-2 in patients with metastatic melanoma. DESIGN: Phase II pilot study. SETTING: Referral-based US Government clinical research unit. PATIENTS: Nine patients with metastatic malignant melanoma. INTERVENTION: Cisplatin 75-100 mg/m2 was administered intravenously over 30 minutes on days 1 and 8. Interferon-alpha 2a 5 Mu/m2 body surface area (BSA) was given subcutaneously for 4 days beginning 1 day before each dose of cisplatin. Beginning on day 15 and day 22, IL-2 was administered by intravenous continuous infusion at 3 Mu/m2 BSA/d for 96 hours and by daily intravenous bolus concurrent with daily subcutaneous doses of interferon-alpha 2a. MAIN OUTCOME MEASURES: Antitumor response and toxicities. RESULTS: The study was stopped due to renal and hematopoietic toxicity and severe, delayed nausea and vomiting associated with the cisplatin-interferon treatment. Three of 9 patients achieved a partial response (duration 2.5, 4, 14+ months), and an additional patient had a 50% reduction in measurable tumor volume before undergoing resection of residual disease. Overall response rate was 45%. CONCLUSION: This regimen was associated with excessive toxicity, and the lack of complete responses in a patient cohort with favorable characteristics for response (good performance status, predominance of skin and lymph node metastatic sites) suggests that it had no advantage over less toxic treatment regimens. REGISTRATION: National Cancer Institute/Cancer Therapy Evaluation Program T89-0137.

Adult↗
PubMed1992

Pilot study of interleukin-2 and lymphokine-activated killer cells combined with immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a in patients with metastatic melanoma and renal cell carcinoma.

BACKGROUND: Experiments in animal tumor models suggest that the antitumor effects of interleukin-2 (IL-2) or IL-2 in combination with lymphokine-activated killer (LAK) cells can be enhanced by chemotherapy agents such as cyclophosphamide or doxorubicin or by the biologic agent interferon alpha. PURPOSE: We determined the toxicity and clinical response rate of an IL-2-LAK cell regimen modified by the addition of moderate, immunomodulatory doses of chemotherapy and sequenced with interferon alfa-2a (IFN alpha-2a) in patients with metastatic melanoma and renal cell carcinoma. METHODS: IL-2 (3-6 million units/m2 per day) was administered by continuous infusion on days 0-5 and days 11-16. LAK cells were infused on days 11 and 12 or on days 11, 12, and 14. Low doses of cyclophosphamide (300 mg/m2) and doxorubicin (25 mg/m2) were given on day 9 before the LAK cell infusions. Following the IL-2-LAK cell infusion, IFN alpha-2a (12 million units/m2) was administered for a total of nine doses to complete a cycle of treatment. A total of 89 patients were enrolled in the study. RESULTS: For each histology, there were eight partial responses in 40 assessable patients, for an overall response rate of 20% (90% confidence interval = 10%-33%). The median response duration was 5 months, although two patients with renal cell carcinoma and one patient with metastatic melanoma had almost complete disappearance of tumor and are still responding after 26+, 22+, and 26+ months, respectively. Toxic effects were severe in patients receiving the highest dose of IL-2 administered in this study and similar to those reported with other high-dose IL-2-LAK cell regimens. Although toxic effects were completely reversible in most patients, there were four treatment-related deaths. CONCLUSIONS: This regimen is active in patients with metastatic melanoma and renal cell carcinoma and produces meaningful responses in a small percentage of these patients; however, it is not clear whether cyclophosphamide, doxorubicin, and IFN alpha-2a as used in this protocol appreciably augmented the antitumor activity of the IL-2-LAK cell regimen.

Adult↗
PubMed1992

Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects.

We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment.

Antigens, CD↗
PubMed1992

Anti-CD3 monoclonal antibody treatment of patients with CD3-negative tumors: a phase IA/B study.

Anti-CD3 monoclonal antibodies induce the proliferation of human T-cells in vitro and activate specific and nonspecific cytolysis by human T-cell clones and human peripheral blood lymphocytes. In vivo administration of anti-CD3 prevents tumor growth of a UV-induced mouse fibrosarcoma. We conducted a phase I trial to determine the toxicity and immunomodulatory properties of low doses of anti-CD3 in 36 patients with cancer. In 23 patients, anti-CD3 was given i.v. over 3 h at 1, 10, 30, and 100 mcg/patient. Five other patients received anti-CD3 at 30 mcg by i.v. bolus. Patients were treated every 3 days for a total of four doses. An additional eight patients received anti-CD3 daily for 14 days at 3 mcg by i.v. bolus, 3-h infusion, or 24-h infusion. Dose-limiting toxicity was headache. Headache was often accompanied by signs and symptoms of meningeal irritation leading to performance of a lumbar puncture in nine patients. The opening pressure was usually elevated, and six patients had a cerebrospinal fluid lymphocytosis with an elevated protein. Increased levels of interleukin 6 were identified in the cerebrospinal fluid. The maximum tolerated dose by 3-h infusion was 30 mcg. There were no objective tumor responses. There was a dose-related increase in the number of peripheral blood lymphocytes expressing the T-cell activation antigen CD69 (Leu 23), but no changes were seen in CD25 (interleukin 2 receptor) expression, and no changes were observed in the serum levels of the soluble interleukin 2 receptor. Even at these low doses of anti-CD3, 8 of 16 patients tested developed human anti-mouse antibodies.

Adult↗
PubMed1992

Thrombocytopenia caused by passive transfusion of anti-glycoprotein Ia/IIa alloantibody (anti-HPA-5b).

We describe a patient who developed transient and moderately severe thrombocytopenia (platelet count nadir 35 x 10(9)/L) after the transfusion of plasma. Using the technique of direct radioimmunoprecipitation, we showed that during the thrombocytopenia episode, the patient's platelets had IgG specifically bound to the glycoprotein (GP) Ia/IIa complex. Indirect radioimmunoprecipitation using serum from the plasma donor confirmed that anti-HPA-5b (anti-Zava) was the cause of GP Ia/IIa sensitization. The relatively mild thrombocytopenia, compared with passive alloimmune thrombocytopenia caused by anti-HPA-1a (anti-P1A1), may reflect the low copy number of HPA-5 compared with HPA-1. Direct radioimmunoprecipitation permits the detection of the GPs carrying the known platelet alloantigen systems, and this study suggests that this technique can be used to diagnose passive alloimmune thrombocytopenia.

Humans↗
PubMed1992

Alcohol and other substance abuse and impairment among physicians in residency training.

Substance abuse and impairment are serious societal problems. Physicians have historically had high rates of substance abuse, which has been viewed as an occupational hazard. Most authorities agree that the rate of alcoholism among practicing physicians is similar to that among control populations and that the rates of other substance abuse are greater, although some studies have shown no difference. Data about substance abuse among residents in training are limited but suggest that the use of benzodiazopines is greater than that among age-matched peers, whereas the use of alcohol is similar between the two groups. Medical institutions, including those with teaching programs, have legal and ethical responsibilities concerning substance abuse among current and future physicians. Many training programs, however, do not provide educational programs on this subject, do not have faculty trained in substance abuse medicine, and do not have a formal system to address the problem of residents who are suspected or known to be substance abusers. This position paper examines the extent of substance abuse, including alcohol abuse, among physicians in residency training. It outlines approaches to the problem and delineates responsibilities of institutions and residency program directors. Recommendations are made to establish an informational program and a clearly defined, organized process to address the problems of substance abuse among residents. Careful and humane approaches can be used to identify and treat residents with substance abuse problems and thus allowing them to complete their training as competent and drug-free professionals.

Alcoholism↗
PubMed1992

A human monoclonal autoantibody to platelet glycoprotein IIb derived from normal human lymphocytes.

Tonsillar lymphocytes from an otherwise healthy nonthrombocytopenic male child were fused with the lymphoblastoid cell line GM 4672. Twenty of 472 (4%) hybridomas had antiplatelet reactivity detected using intact platelets in an enzyme-linked immunosorbent assay. One hybridoma (STO 171) reacted to platelet glycoprotein IIb (integrin alpha IIb) as determined by radioimmunoprecipitation and immunoblotting. Antibody specificity was confirmed using immunodepletion experiments with isotypic antibodies derived from a mutlitransfused Glanzmann's thrombasthenic patient. The antibody reactivity was restricted to platelets and did not react with other integrin alpha-chain proteins expressed on granulocytes or cultured human brain-derived microvascular endothelial cells. These studies indicate that lymphocytes of normal, nonthrombocytopenic individuals have the genetic potential to produce antiplatelet autoantibodies.

Antibodies, Monoclonal↗
PubMed1992

Comparison of serum amyloid A and C-reactive protein as indicators of lung inflammation in corticosteroid treated and non-corticosteroid treated cystic fibrosis patients.

Serum amyloid A (SAA) and C-reactive protein (CRP) levels were compared in 830 serum samples from 155 cystic fibrosis (CF) patients. Correlation coefficients were calculated for all samples (r = 0.73), for samples from non-corticosteroid treated (CFNS) patients (n = 698, r = 0.80), and for samples from corticosteroid treated (CFS) patients (n = 132, r = 0.35). SAA was the more sensitive indicator of pulmonary inflammation when SAA and CRP were compared to pulmonary function tests of 49 hospitalized patients at admission and discharge. CRP levels were significantly (p less than .05) lower at admission in CFS patients than in CFNS patients, whereas SAA levels were not significantly different between the two groups. All nine CFS patients hospitalized had elevated SAA levels (average 22 times above normal limits) at admission, while only six had elevated CRP levels (average 3.7 times above normal limits) at admission. In the 40 CFNS patients both SAA and CRP levels were significantly elevated at admission. In each case SAA and CRP levels declined as pulmonary functions improved with effective antimicrobial therapy. In three instances SAA levels increased during hospitalization while CRP levels did not. In each case, rising SAA levels indicated clinical deterioration associated with evolving resistance of P. aeruginosa which required a change in antibiotic therapy.

Adolescent↗
PubMed1992

Antithrombotic benefit of subendothelium-bound urokinase: an experimental study.

To improve the outcome of extremity replantation, microsurgeons have administered systemic antithrombotic agents (e.g., heparin, aspirin, dextran). To obviate the risks associated with systemic anticoagulation, we have investigated the use of topically applied urokinase for its binding capacity to arterial subendothelium and for its ability to prevent subsequent thrombosis. An arterial model of thrombosis associated with intimal deendothelialization was developed. Donor rat carotid arteries were everted and mechanically deendothelialized with a scalpel blade. The vessels were next subjected to one of several treatments, which included 30-minute incubation with urokinase, heparin, or vehicle (lactated Ringer's solution). The vessels were then washed, reinverted to normal orientation, sectioned into 5 mm lengths, and grafted into the femoral arteries of recipient rats. Two-hour patency rates were 25% for controls (n = 20), 10% for heparin-treated vessels (n = 10), and 55% for urokinase-treated vessels (n = 20); this last was significantly greater than the other two groups. In vitro investigations revealed that urokinase has a high capacity for binding to subendothelium, with a release half-life of approximately 20 minutes. Surface-bound urokinase was found to have proteolytic activity similar to that of urokinase in solution. These results indicate that urokinase may be a more beneficial irrigating solution additive than heparin for repair of traumatized vessels.

Administration, Topical↗
PubMed1992

Inoculated mouse model of Pneumocystis carinii infection.

A transtracheally inoculated mouse model of Pneumocystis carinii has been developed using BALB/c mice. The advantage of this strain of mice include that they are widely available, inexpensive, and were not infected with Pneumocystis before inoculation. Inoculated mice that were not treated had a mean infectivity score of 4.1 compared with inoculated mice treated with the effective anti-Pneumocystis drug combination of trimethoprim plus sulfamethoxazole, which had a mean infectivity score of 0.1, an approximately 4 log difference. The inoculated BALB/c mouse provides a model to serve as a valuable addition to rat models currently used, providing a source of organisms from a different host for cross-species comparisons and for studies of drug efficacy for therapy and prophylaxis. The inoculated mouse is especially cost effective and allows testing of compounds in short supply.

Aminoquinolines↗
PubMed1992

One-year follow-up after multimodal inpatient treatment for cocaine and methamphetamine dependencies.

Of a randomly selected sample of 214 patients treated with aversion therapy for cocaine dependence in four chemical dependency units operated by Schick Shadel Hospitals, 156 were followed up 12 to 20 months posttreatment (average 15.2 months). Significant other validation was obtained in 33%. Total abstinence from cocaine for the group overall was 53% at one year post treatment, and current abstinence of at least 6 months at follow-up was 68.6%. Those treating with aversion for cocaine alone had a one-year abstinence of 39% and a current abstinence of 62.4%. Those treating with aversion for alcohol and cocaine had a one-year total abstinence from cocaine of 69% and a current abstinence of 76%. Those treating with aversion for cocaine and marijuana had a one-year total abstinence from cocaine of 50% and a current abstinence of 65%. Those treating with aversion for alcohol, cocaine, and marijuana had a one-year total abstinence from cocaine of 73% and a current abstinence of 73%. One-year total abstinence from alcohol was 54% for those receiving aversion for both alcohol and cocaine and 77% for those receiving aversion for alcohol, cocaine, and marijuana. Current abstinence from alcohol at follow-up was 68% and 81%, respectively. One-year total abstinence from marijuana was 42% for those treating with aversion for cocaine and marijuana and 64% for those treating with aversion for alcohol, cocaine, and marijuana. Current abstinence at follow-up from marijuana was 61% and 81%, respectively. The use of aversion therapy for both alcohol and cocaine in alcoholics who were also using cocaine was associated with higher total abstinence rates (88% vs. 55%) from cocaine when compared with alcoholics who used cocaine but received no aversion as part of their program. The conclusion is tentative since the follow-up rate in this study was lower than that of the previous study (64% vs. 84%). Being around other users accounted for 49% of relapse situations. Family/Work stress was associated with relapse in 33% of cases and unpleasant feelings in 24% of cases. The use of both reinforcement treatments and the use of support following treatment were associated with improved abstinence rates from cocaine. Those patients who reported losing all urges for cocaine after treatment had a total abstinence from cocaine of 90%, those who reported losing all the uncontrollable urges had a total abstinence of 64%, and those who reported still having the urge reported only 33% total abstinence from cocaine.

Adult↗
PubMed1992

Alcoholism in relatives of primary cocaine-dependent patients.

Inherited susceptibility is believed by some to be a factor in cocaine dependence. In this study, nonalcoholic cocaine-dependent patients (N = 175) were screened to identify alcoholic first-degree relatives. One or more first-degree relatives are also reported to be alcoholic by 25% to 50% of alcoholic patients. Approximately the same percentage of these cocaine patients (34%) also report having an alcoholic first-degree relative. This lends credence to the hypothesis that the apparent inherited susceptibility to alcoholism may be a more general susceptibility to addictive disease. A much higher proportion of females than males have an alcoholic first-degree relative.

Adult↗
PubMed1992

Resection of hepatic and pulmonary metastases from colorectal cancer.

Resection of hepatic metastases of colorectal origin has gained wide acceptance, but when patients have synchronous or metachronous pulmonary metastases, they are often considered incurable and are offered systemic therapy only. We performed a retrospective review of the patients at Memorial Sloan-Kettering Cancer Center who underwent resection of both hepatic and pulmonary metastases of colorectal origin between 1970 and 1990. Ten patients were identified who met the above criteria. Median survival after hepatic and pulmonary resections were 34 and 18 months, respectively. Actuarial 1-, 3- and 5-year survivals are 89%, 78% and 52%, respectively. With a median of 18 months after second operation, three patients have no evidence of disease (NED), four are alive with disease (AWD) and three are dead of disease (DOD). In the absence of effective chemotherapy, selected patients with hepatic and pulmonary metastases of colorectal origin should be considered for resection as it offers the only possibility for long-term survival.

Actuarial Analysis↗
PubMed1992

Surgical treatment of gastric cancer. Proximal, mid, and distal stomach.

At present, only radical surgical resection of gastric cancer offers a chance for cure. The objective of an operation for patients with disease that is confined locally is to maximize the potential for cure. The objective for patients with advanced incurable disease, obstruction, hemorrhage, and intractable pain is to provide the best palliation. The evaluation, staging, and surgical management of gastric cancer are described.

Humans↗
PubMed1992

Isolation gowns: a false sense of security?

BACKGROUND: Isolation gowns have traditionally been used in health care situations to protect against microbial contamination. There is now concern over protection of the health care worker from contamination by patients' blood and body fluids. We quantitatively determined the effectiveness of commercially available isolation gowns against human blood leakage or strike through. METHODS: More than 1200 samples of 11 types of disposable gown and one type of reusable gown (new and washed 40 and 80 times) were tested at five different pressures (0.25 to 2 psi) and six durations (1 second to 2 minutes) by means of an apparatus designed to simulate pressures generated during gown usage. RESULTS: In all studied conditions, testing showed significant differences (p less than 0.0001) in the amount of strike through allowed by the gowns and demonstrated important differences in the gowns' protective capabilities. CONCLUSION: Although traditional thought assumes that isolation gowns protect the wearer from contamination, our data show this belief may provide a false sense of security.

Diffusion↗
PubMed1992

Efficacy of intermittent dosage of 8-aminoquinolines for therapy or prophylaxis of Pneumocystis pneumonia in rats.

Experimental 8-aminoquinolines from Walter Reed Army Institute for Research are effective for prophylaxis or therapy of Pneumocystis carinii pneumonia in rat models. In the present study, primaquine, WR6026, and WR238605 were tested in prophylaxis and treatment models of P. carinii pneumonia to compare the effectiveness of continuous versus intermittent dosing. For treatment of P. carinii pneumonia, the drugs showed detectable effects when given once every 4 days (primaquine and WR6026 at doses greater than 8 mg/kg; WR238605 at doses greater than 2 mg/kg). For prophylaxis, WR6026 and WR238605 were effective given alone daily (WR6026 at doses greater than 0.25 mg/kg; WR238605 at doses greater than 0.57 mg/kg). WR6026 and WR238605 at 4 mg/kg given once every 4 days for prophylaxis were as effective as daily trimethoprim-sulfamethoxazole. These studies suggest that higher doses of 8-aminoquinolines administered at appropriate intervals may be as effective as continuous dosing for prophylaxis of P. carinii pneumonia.

Aminoquinolines↗