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S Greer

Publications and source records attributed to S Greer.

At least 19 recordsLinked to original sources
PubMed2001

Five-chlorodeoxycytidine, a tumor-selective enzyme-driven radiosensitizer, effectively controls five advanced human tumors in nude mice.

PURPOSE: The study's goals were as follows: (1) to extend our past findings with rodent tumors to human tumors in nude mice, (2) to determine if the drug protocol could be simplified so that only CldC and one modulator, tetrahydrouridine (H4U), would be sufficient to obtain efficacy, (3) to determine the levels of deoxycytidine kinase and dCMP deaminase in human tumors, compared to adjacent normal tissue, and (4) to determine the effect of CldC on normal tissue radiation damage to the cervical spinal cord of nude mice. METHODS AND MATERIALS: The five human tumors used were as follows: prostate tumors, PC-3 and H-1579; glioblastoma, SF-295; breast tumor, GI-101; and lung tumor, H-165. The duration of treatment was 3-5 weeks, with drugs administered on Days 1-4 and radiation on Days 3-5 of each week. The biomodulators of CldC were N-(Phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartyl transcarbamoylase, 5-fluorodeoxycytidine (FdC), resulting in tumor-directed inhibition of thymidylate synthetase, and H4U, an inhibitor of cytidine deaminase. The total dose of focused irradiation of the tumors was usually 45 Gy in 12 fractions. RESULTS: Marked radiosensitization was obtained with CldC and the three modulators. The average days in tumor regrowth delay for X-ray compared to drugs plus X-ray, respectively, were: PC-3 prostate, 42-97; H-1579 prostate, 29-115; glioblastoma, 5-51; breast, 50-80; lung, 32-123. Comparative studies with PC-3 and H-1579 using CldC coadministered with H4U, showed that both PALA and FdC are dispensable, and the protocol can be simplified with equal and possibly heightened efficacy. For example, PC-3 with X-ray and (1) no drugs, (2) CldC plus the three modulators, (3) a high dose of CldC, and (4) escalating doses of CldC resulted in 0/10, 3/9, 5/10, and 6/9 cures, respectively. The tumor regrowth delay data followed a similar pattern. After treating mice only 11/2 weeks with CldC + H4U, 92% of the PC-3 tumor cells were found to possess CldU in their DNA. The great majority of head-and-neck tumors from patient material had markedly higher levels of dC kinase and dCMP deaminase than found in adjacent normal tissue. Physiologic and histologic studies showed that CldC + H4U combined with X-ray, focused on the cervical spinal cord, did not result in damage to that tissue. CONCLUSIONS: 5-CldC coadministered with only H4U is an effective radiosensitizer of human tumors. Ninety-two percent of PC-3 tumor cells have been shown to take up ClUra derived from CldC in their DNA after only 11/2 weeks and 2 weeks of bolus i.p. injections. Enzymatic alterations that make tumors successful have been exploited for a therapeutic advantage. The great electronegativity, coupled with the relatively small Van der Waal radius of the Cl atom, may result in CldC's possessing the dual advantageous properties of FdC on one hand and BrdU and IdU on the other hand. These advantages include autoenhancing the incorporation of CldUTP into DNA by not only overrunning but also inhibiting the formation of competing TTP pools in tumors. A clinical trial is about to begin, with head-and-neck tumors as a first target of CldC radiosensitization.

Animals↗
PubMed2001

Morbidity and mortality in rheumatoid arthritis patients with prolonged and profound therapy-induced lymphopenia.

OBJECTIVE: Therapies that deplete lymphocytes often improve symptoms in patients with otherwise refractory autoimmune disease but may result in long-term lymphopenia, the consequences of which are uncertain. To assess the impact of prolonged lymphopenia on morbidity and mortality, we studied patients who had previously received lymphocytotoxic monoclonal antibody (mAb) therapy for rheumatoid arthritis (RA). METHODS: Fifty-three patients who received the lymphocytotoxic mAb CAMPATH-1H between 1991 and 1994 in the United Kingdom were assessed for mortality and infectious and malignant morbidity, by interview and case-note review. In addition, patients were monitored via the National Health Service Central Registry, to verify notification of death. Peripheral blood lymphocyte subsets were analyzed by flow cytometry. A retrospective, matched-cohort study of mortality was also performed with 102 control subjects selected from the European League Against Rheumatism database, which comprises patients with rheumatic disorders who have received immunosuppressive drugs. RESULTS: There was profound and persistent peripheral blood lymphopenia in the mAb-treated patients, affecting predominantly the CD4+ subset. Median CD4+, CD8+, and CD19+ peripheral blood lymphocyte counts at 73-84 months after therapy were 185 cells/microl, 95 cells/microl, and 115 cells/microl, respectively. At a median followup of 71 months (range 14-90), 13 patients had died (24.5%), compared with 18% of the matched controls, providing a mortality rate ratio of 1.45 (95% confidence interval 0.65-3.13). During 283 patient-years of followup, there were 36 infections classified as major (12.7 per 100 patient-years). The causes of death and the spectrum of infections documented were similar to those expected in a hospital-based RA cohort. Patients who received more than 1 course of therapy had more severe lymphopenia than did patients who received a single course, but this did not have an impact on mortality or morbidity. CONCLUSION: Despite the occurrence of profound and long-lasting lymphopenia following treatment with antilymphocyte mAb therapy for RA, this therapy is not associated with a large excess of mortality nor with an unusual spectrum of infections, at least during a medium-term period of followup. These data are also relevant to patients receiving lymphocytotoxic mAb therapy for other indications, and to patients receiving other lymphodepleting therapies such as autologous stem cell transplantation.

Aged↗
PubMed2000

Fighting spirit.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed2000

The mode selection trial (MOST) in sinus node dysfunction: design, rationale, and baseline characteristics of the first 1000 patients.

BACKGROUND: More than 200,000 permanent pacemakers will be implanted in the United States in 2000 at a cost of more than $2 billion. Sick sinus syndrome (SSS) will likely account for approximately half of all cases necessitating implantation. Pacemaker technology permits the selection of ventricular (single-chamber) or dual-chamber devices. However, clinical and outcomes data are inadequate to support a clear recommendation that one or the other type of device be used. METHODS: The Mode Selection Trial (MOST) is a single-blind study supported by the National Heart, Lung, and Blood Institute designed to enroll 2000 patients with SSS. All patients will receive a DDDR pacemaker programmed to VVIR or DDDR before implantation. The average time of follow-up will be 3 years. MOST has a >90% power to detect a 25% reduction in the primary end point-nonfatal stroke or total (all cause) mortality-in the DDDR-treated group. Secondary end points will include health-related quality of life and cost effectiveness, atrial fibrillation, and development of pacemaker syndrome. Prespecified subgroups for analysis will include women and the elderly. Enrollment was completed in October 1999, with a total of 2010 patients. RESULTS: The median age of the first 1000 enrolled patients is 74 years, with 25% of patients 80 years or older. Women comprise 49%, and 17% are nonwhite, predominantly black (13%). Before pacemaker implantation, 22% of patients reported a history of congestive heart failure, 11% coronary angioplasty, and 25% coronary bypass surgery. Supraventricular tachycardia including atrial fibrillation was present in 53% of patients. A prior stroke was reported by 12%. Antiarrhythmic therapy was in use in 18% of patients. CONCLUSIONS: MOST will fill the clinical need for carefully designed prospective studies to define the benefits of dual-chamber versus single-chamber ventricular pacing in patients with SSS. The MOST population is typical of the overall pacemaker population in the United States. Thus the final results of MOST should be clinically generalizable.

Aged↗
PubMed2000

What's in a name? Neuroimmunomodulation or psychoneuroimmunology?

Compelling evidence is presented to support the hypothesis that psychological processes affect immune function. Consequently, it is argued that psychological processes should be included in human immunological studies and that neuroimmunomodulation could accurately by called psychoneuroimmunology.

Humans↗
PubMed1999

Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis.

BACKGROUND: Multiple sclerosis results from T-cell-dependent inflammatory demyelination of the central nervous system. Our objective was long-term suppression of inflammation with short-term monoclonal antibody treatment. METHODS: We depleted 95% of circulating lymphocytes in 27 patients with multiple sclerosis by means of a 5-day pulse of the humanised anti-CD52 monoclonal antibody, Campath-1H. Clinical and haematological consequences of T-cell depletion, and in-vitro responses of patients' peripheral-blood mononuclear cells were analysed serially for 18 months after treatment. FINDINGS: Radiological and clinical markers of disease activity were significantly decreased for at least 18 months after treatment. However, a third of patients developed antibodies against the thyrotropin receptor and carbimazole-responsive autoimmune hyperthyroidism. The depleted peripheral lymphocyte pool was reconstituted with cells that had decreased mitogen-induced proliferation and interferon gamma secretion in vitro. INTERPRETATION: Campath-1H causes the immune response to change from the Th1 phenotype, suppressing multiple sclerosis disease activity, but permitting the generation of antibody-mediated thyroid autoimmunity.

Adult↗
PubMed1999

Influence of psychological response on survival in breast cancer: a population-based cohort study.

BACKGROUND: The psychological response to breast cancer, such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease, has been suggested as a prognostic factor with an influence on survival. We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer. METHODS: 578 women with early-stage breast cancer were enrolled in a prospective survival study. Psychological response was measured by the mental adjustment to cancer (MAC) scale, the Courtauld emotional control (CEC) scale, and the hospital anxiety and depression (HAD) scale 4-12 weeks and 12 months after diagnosis. The women were followed up for at least 5 years. Cox's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response, with adjustment for known clinical factors associated with survival. FINDINGS: At 5 years, 395 women were alive and without relapse, 50 were alive with relapse, and 133 had died. There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression (hazard ratio 3.59 [95% CI 1.39-9.24]). There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category (1.55 [1.07-2.25]). There were no significant results found for the category of "fighting spirit". INTERPRETATION: For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect. A high score for depression is linked to a significantly reduced chance of survival; however, this result is based on a small number of patients and should be interpreted with caution.

Aged↗
PubMed1999

Mind-body research in psychooncology.

The biomedical model of disease, though powerful, does not explain all known facts about cancer. It is argued that a broader theoretical framework which includes psychosocial factors is needed. There is empirical evidence that a hopeless/helpless coping style is associated with unfavorable disease outcome in patients with certain cancers. The converse, namely a link between an active, fighting spirit coping style and favorable disease outcome, is under-researched and less clear-cut. The delineation, measurement and psychophysiology of positive states of mind have been sorely neglected. This is a promising area for future research. Psychobiological mechanisms of possible relevance to cancer are considered in terms of psychoneuroimmunology. Despite formidable theoretical and methodological problems, some progress is being made. Recent evidence indicates that psychotherapeutic intervention can augment natural killer cell activity and lymphokine-activated killer cell activity in patients with malignant melanoma and with locally advanced, nonmetastatic breast cancer respectively. These challenging findings, if confirmed, have major implications for our understanding of mind-body interactions in patients with cancer.

Adaptation, Psychological↗
PubMed1999

Mechanism of bone loss after liver transplantation: A histomorphometric analysis.

Organ transplantation is associated with increased bone loss and high fracture risk, but the pathophysiological mechanisms responsible have not been established. We have performed a histomorphometric analysis of bone remodeling before and 3 months after liver transplantation in 21 patients (14 male, 7 female) aged 38-68 years with chronic liver disease. Eight-micrometer undecalcified sections of trans-iliac biopsies were assessed using image analysis. Preoperatively, bone turnover was low with a tendency toward reduced wall width and erosion depth. The bone formation rate increased from 0.021 +/- 0.016 (mean +/- SD) to 0.067 +/- 0.055 microm2/microm/day after transplantation (p < 0.0002) and activation frequency from 0.24 +/- 0.21/year-1 to 0.81 +/- 0. 67/year-1 (p < 0.0001). No significant change was observed in wall width, but there was a trend toward an increase in indices of resorption cavity size. There was a small increase in osteoid seam width postoperatively (p< 0.02) and decrease in mineralization lag time (p < 0.001). No significant changes in indices of cancellous bone structure were observed in the postoperative biopsies. These results demonstrate a highly significant and quantitatively large increase in bone turnover in the first 3 months after liver transplantation. Although no significant disruption of cancellous bone structure was demonstrated during the time course of the study, the observed changes in bone remodeling predispose to trabecular penetration and may thus result in long-term adverse effects on bone strength.

Adult↗
PubMed1998

Living and working with latex allergies: personal perspectives from a nurse.

Living with the limitations of latex sensitivity can be devastating. Even more devastating is when the diagnosis can end a career. For a registered nurse, latex allergy can be a career ender, or it can spur the individual to become increasingly clever in coping with the allergy while maintaining a productive personal and professional life. This article describes the personal struggle an individual registered nurse has overcome to maintain her position in nursing.

Adaptation, Psychological↗
PubMed1997

Adjuvant psychological therapy for cancer patients.

Adjuvant psychological therapy (APT), a brief, problem-focused, cognitive-behavioural treatment for patients with cancer, is described. A previously published randomized trial demonstrated a significant reduction in cancer-related emotional distress. APT is recommended for cancer patients suffering from such distress.

Adult↗
PubMed1996

Early increase in plasma parathyroid hormone levels following liver transplantation.

BACKGROUND/AIMS: The pathogenesis of post-transplantation bone loss is poorly understood, although glucocorticoid therapy is believed to play an important role. In the present study we have measured plasma parathyroid hormone concentrations in the first few months after orthotopic liver transplantation, in order to examine the potential contribution of hyperparathyroidism to bone disease. PATIENTS AND METHODS: Twenty-seven patients aged 32-54 years, 12 male, undergoing liver transplantation were studied prospectively before and for 3 months after operation. Plasma parathyroid hormone and serum 25-hydroxyvitamin D concentrations were measured by radioimmunoassay. RESULTS: Plasma parathyroid hormone levels were normal in all but two patients prior to transplantation. There was a highly significant increase in plasma parathyroid hormone concentrations at 1 and 2 months (p < 0.0005 and 0.001, respectively, versus baseline); by 3 months, values were close to those obtained preoperatively. Serum 25-hydroxyvitamin D concentrations showed no significant change over the study period. However, 74% of the patients had subnormal values at baseline. CONCLUSIONS: An early and transient increase in plasma parathyroid hormone after liver transplantation may be responsible for the high rates of bone loss which occur during the first few post-operative months. Prevention of post-transplantation bone disease is most likely to be achieved by peri-operative intervention with an anti-resorptive agent.

Adult↗
PubMed1995

Five-chlorodeoxycytidine and biomodulators of its metabolism result in fifty to eighty percent cures of advanced EMT-6 tumors when used with fractionated radiation.

PURPOSE: To extend our findings in previous radiation and biochemical studies with five rodent tumors, in which we used one and occasionally two or three irradiations. The extent of control of the EMT-6 mammary adenocarcinoma was determined using fractionated radiation (12 irradiations) over a 3-week period using the radiosensitizer 5-chloro-2'-deoxycytidine (CldC) and biomodulators of its metabolism: N-(Phosphonacetyl)-L-aspartate (PALA), tetrahydrouridine and 5-fluoro-2'-deoxycytidine (FdC). METHODS AND MATERIALS: Mammary adenocarcinoma EMT-6 tumors implanted 1 week prior to therapy in BALB/c mice were subjected to single daily doses of focused radiation, not exceeding a total of 60 Gy, on days 2-5 of each week. N-(Phosphonacetyl)-L-aspartate (PALA) was administered on the first day of therapy. Five-fluoro-2'-deoxycytidine and CldC were administered in the morning and afternoon, respectively, of the next 2 days, and CldC was administered on the fourth day. Tetrahydrouridine was always coadministered with FdC or CldC. Drug and radiation treatments overlapped for 3 weeks. RESULTS: Fifty to 80% cures (usually 70%) were obtained with no apparent morbidity and the same moderate weight loss that occurs with radiation alone. Neither tumor regrowth delay nor cures were obtained with drugs or radiation alone. An apparent threefold dose increase effect was obtained with the end point: "days to reach 4 times initial tumor volume." Increasing the radiation dose threefold (without drugs) resulted in four out of five deaths; increasing the dose twofold (without drugs) resulted in extensive weight loss and hair loss in the entire ventral area and no cures. Increasing the dose of drugs or radiation 1.5-fold, in the complete protocol, did not result in increased morbidity. Comparative studies with Iododeoxyuridine demonstrate the heightened efficacy of CldC. CONCLUSIONS: One cannot achieve the same results obtained with CldC and the modulators by merely increasing the dose of radiation. There is a significant window of safety in this approach. The evidence we have obtained with EMT-6, the fifth rodent tumor we have studied with CldC, as well as the demonstrated and proposed reasons for its superior efficacy over 5-Iododeoxyuridine (and 5-Bromodeoxyuridine), drugs in current use, indicate that CldC will allow more aggressive treatment of human tumors with radiation than is now feasible.

Adenocarcinoma↗
PubMed1995

Improving quality of life: adjuvant psychological therapy for patients with cancer.

The present paper describes a psychological treatment programme--Adjuvant Psychological Therapy (APT)--that has been developed specifically for patients with cancer-related psychosocial disorders. APT is brief (average six sessions), directed at current problems and conducted with individual patients together with their partners or spouses, if possible. Therapy focuses on the personal meaning of cancer to the patient and his or her coping strategies. An outline of APT together with a clinical illustration is given. A randomised trial has demonstrated that APT produces significant improvement in psychological distress and thus in the quality of life of patients with cancer.

Adaptation, Psychological↗
PubMed1995

Viral serology and detection.

Viral detection is an important part of clinical hepatology. For many years practical clinical tests have been serological but recently newer molecular techniques have become available for virus detection, although these have yet to become routine and some, such as PCR of viral nucleic acid in blood or tissue are not yet consistently reliable. Serology remains the mainstay at present for routine diagnosis. Hepatitis A testing in clinical practice is entirely serological, the IgM response representing acute infection and the IgG response immunity, although more sophisticated molecular techniques have been applied experimentally. A second agent of epidemic enteral hepatitis, the hepatitis E virus, has recently been cloned and sequenced and serological tests for this virus are available, although experience in their use is necessarily limited and a commercial IgM assay has yet to be produced. Serological tests for the hepatitis B virus are well developed. The IgM anticore response differentiates acute infection from chronic, the latter being characterized by the persistence of hepatitis B surface antigen for over six months. Chronic carriers are at risk of liver damage and this risk is best assessed by the amount of viral DNA circulating, which can be determined using a hybridization assay. More sensitive techniques such as the branched chain DNA assay or PCR can detect lower levels of viral DNA but their clinical relevance remains to be established. The hepatitis D virus is defective and relies on hepatitis B to replicate. Serology for antibody and antigen is well established although PCR for circulating viral genome may come to supplant hepatic viral antigen as a test for hepatitis D replication. For hepatitis C serology is feasible only for antibodies, not antigens; although early tests were prone both to false positives and false negatives, current versions are more reliable. PCR has been much used for detection of hepatitis C RNA in blood and tissues and a bDNA assay is now commercially available. Cytomegalovirus detection is confounded by the problem of distinguishing asymptomatic viral replication from disease. Serology is helpful, especially in primary infections, but viral culture is a widely used method. PCR (especially quantitative modifications) or the pp65 antigenaemia assay are experimental approaches which may prove specific enough for general use.

Hepatitis Viruses↗