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D H Johnson

Publications and source records attributed to D H Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1997

Patient, caregiver, and oncologist perceptions of cancer-related fatigue: results of a tripart assessment survey. The Fatigue Coalition.

Although fatigue is the most common symptom reported by cancer patients and has serious adverse effects on quality of life, it remains poorly understood. A survey was designed to characterize the epidemiology of cancer-related fatigue from the perspectives of the patient, primary caregiver, and oncologist. A telephone survey included 419 cancer patients recruited from 100,000 randomly selected households nationwide. Patients provided access to 200 primary caregivers (usually family members) who were also interviewed by telephone. In a separate mail survey, 197 of 600 randomly sampled oncologists (unrelated to the patients) responded to a questionnaire that assessed perceptions and attitudes concerning fatigue in cancer patients who had received chemotherapy or radiotherapy and their caregivers. The median patient age was 65 years, and the principal cancer diagnoses were breast (females) and genitourinary (males). Fifty-nine percent of the patients had received chemotherapy, 63% radiation therapy, and 24% both; 20% of patients received their last treatment within 6 weeks, 31% within 7 weeks to 1 year, and 49% more than 1 year ago. More than three quarters of patients (78%) experienced fatigue (defined as a general feeling of debilitating tiredness or loss of energy) during the course of their disease and treatment. Thirty-two percent experienced fatigue daily, and 32% reported fatigue significantly affected their daily routines. Caregivers reported observing fatigue in 86% of the index patients, and oncologists perceived that 76% of their patients experienced fatigue. Although oncologists believed that pain adversely affected their patients to a greater degree than fatigue (61% v 37%), patients felt that fatigue adversely affected their daily lives more than pain (61% v 19%). Most oncologists (80%) believed fatigue is overlooked or undertreated, and most patients (74%) considered fatigue a symptom to be endured. Fifty percent of patients did not discuss treatment options with their oncologists, and only 27% reported that their oncologists recommended any treatment for fatigue. When used, treatments for fatigue were generally perceived by patients and caregivers to be successful. These data confirm the high prevalence and adverse impact of cancer-related fatigue, although it is seldom discussed and infrequently treated. For patients and oncologists, improving the quality of life of cancer patients requires a heightened awareness of fatigue, a better understanding of its impact, and improve communication and familiarity with interventions that can reduce its debilitating effects.

Aged↗
PubMed1997

Small cell lung cancer in the elderly patient.

Small cell lung cancer (SCLC) is primarily a disease of older individuals. Many physicians and patients believe that lung cancer is less treatable in the elderly because of the presence of comorbid illnesses and an unwarranted concern for the patient's psychological well being. In reality, the prognostic relevance of age is not well defined. Older patients who are able to tolerate standard doses of chemotherapy appear to experience survival that is not substantially different from that achieved in younger patients. However, older patients who cannot tolerate the rigors of standard chemotherapy do less well for reasons that are still incompletely understood. Based on these observations, it has been suggested that specific therapeutic regimens that result in less toxicity but maintain adequate efficacy are needed for older SCLC patients, especially those who have a poor performance status. Single agents such as oral etoposide or carboplatin have been advocated in this setting because of their perceived efficacy and lower toxicity. However, recent randomized studies indicate that older patients should be treated with the same regimens that are used for their younger counterparts. Single agents may be inadequate to achieve optimal results. A more prudent strategy may be one based on an estimate of the individual's likelihood of experiencing toxicity. Parameters for selecting patients who are at high risk for treatment-related complications are reviewed in this article.

Age Factors↗
PubMed1997

Dexamethasone decreases phagocytosis by human trabecular meshwork cells in situ.

PURPOSE: To determine the effect of dexamethasone on the phagocytic capacity of the human trabecular meshwork. A decrease in meshwork phagocytosis has been proposed in the pathogenesis of steroid glaucoma. METHODS: The anterior segments of seven pairs of human eyes were placed in perfusion organ culture. One eye of each pair received dexamethasone, and the fellow eye served as control. After 21 days, latex microspheres labeled with fluorescein isothiocyanate and coated with antibodies were added to the culture medium. Twenty-four hours later, the eyes were fixed, the trabecular meshworks were treated with a rhodamine-labeled secondary antibody and sectioned, and the number of ingested beads was determined using a laser scanning confocal microscope. Nuclei were counted and used to calculate the phagocytic index of each anterior segment (number of ingested beads divided by number of nuclei). RESULTS: Ingested beads appeared green and could be differentiated from noningested beads, which appeared red, using appropriate wavelengths of the laser. Bead ingestion was confirmed with electron microscopy and the use of secondary antibody labeled with horseradish peroxidase. Dexamethasone decreased phagocytosis by 57%, as shown by the fact that trabecular cells in dexamethasone-treated meshworks ingested significantly fewer beads than cells in fellow control meshworks (1.5 +/- 0.6 beads/cell versus 3.5 +/- 1.4 beads/cell; P = 0.008). No evidence of significant migration or loss of trabecular cells was noted; the number of trabecular cells appeared similar in dexamethasone-treated and control meshworks (144 +/- 36 versus 141 +/- 46). CONCLUSIONS: Dexamethasone inhibits phagocytosis by human trabecular meshwork cells in perfusion organ culture.

Adult↗
PubMed1997

Paclitaxel/5-fluorouracil/leucovorin in metastatic breast cancer: a Vanderbilt Cancer Center phase II trial.

Fifty-five women with metastatic breast cancer were treated with a regimen consisting of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 administered intravenously over 3 hours on day 1 only plus leucovorin given intravenously over 30 to 60 minutes followed by 5-fluorouracil 350 mg/m2 via intravenous push on days 1 to 3 every 28 days for six cycles. Eight patients were chemotherapy naive. Of 47 previously treated women, 30 had received anthracyclines. Fifty-two patients were evaluable for response. Three (6%) experienced a complete response and 24 (46%) had a partial response, for an overall response rate of 52%. Patients previously exposed to doxorubicin had a response rate similar to those with no prior doxorubicin exposure (50% v 54%, respectively). The median duration of response was 8.6 months and median survival was 17.7 months. Toxicity was modest, with grade 3 or 4 neutropenia observed in only 5.5% (15 of 274) of cycles. Preliminary results indicate that paclitaxel/5-fluorouracillleucovorin is an active, well-tolerated regimen for treating metastatic breast cancer.

Adult↗
PubMed1997

Preliminary analysis of a phase II study of paclitaxel, carboplatin, and hyperfractionated radiation therapy for locally advanced inoperable non-small cell lung cancer.

We conducted a prospective phase II study to determine the response rate, toxicity profile, and survival rate among patients with locally advanced unresectable non-small cell lung cancer receiving concurrent weekly paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), carboplatin, and hyperfractionated radiation therapy followed by two cycles of adjuvant paclitaxel and carboplatin. The weekly paclitaxel/carboplatin regimen was designed to optimize the radiosensitizing properties of paclitaxel during the concurrent phase of treatment. Thirty-two patients with unresectable stage IIIA and IIIB non-small cell lung cancer from Vanderbilt Cancer Center Affiliate Network institutions entered the study from June 1996 until February 1997. Weekly intravenous paclitaxel (50 mg/m2 over 1 hour) and weekly carboplatin (area under the concentration-time curve of 2) plus concurrent hyperfractionated chest radiotherapy (1.2 Gy twice daily [69.6 Gy total]) delivered for 6 weeks were followed by two cycles of paclitaxel (200 mg/m2) and carboplatin (area under the concentration-time curve of 6). Among 22 patients evaluable for response, one (4.5%) achieved a complete response and 16 (72.7%) achieved partial response, for an overall response rate of 77%. Among 23 patients evaluable for toxicity, esophagitis was the principal finding: grade 3 or 4 esophagitis occurred in eight patients (35%). Grade 3 and 4 pulmonary toxicities each occurred in 26% of patients. Thus, weekly paclitaxel/carboplatin plus concurrent hyperfractionated radiotherapy is a well-tolerated outpatient regimen with an encouraging response rate that is at least equivalent to more toxic chemoradiation regimens. These findings indicate that further clinical evaluation of weekly paclitaxel/carboplatin/hyperfractionated radiotherapy is warranted in phase III trials.

Adult↗
PubMed1997

Paclitaxel by either 1-hour or 24-hour infusion in combination with carboplatin in advanced non-small cell lung cancer: preliminary results comparing sequential phase II trials.

Our group previously described the activity of carboplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (given as a 24-hour infusion) in 51 patients with advanced non-small cell lung cancer. To facilitate outpatient administration, the regimen was modified to infuse paclitaxel over 1 hour. Between February 1995 and August 1996, 63 patients with advanced non-small cell lung cancer were accrued by the Vanderbilt Cancer Center and its affiliate network. The first four patients received paclitaxel 175 mg/m2; all subsequent patients received paclitaxel 200 mg/m2. The carboplatin dose was determined using the Calvert formula, with a target area under the concentration-time curve of 6. Cycles were repeated every 4 weeks, to a maximum of six cycles. The median age of the patients was 62 years. There were 43 men and 20 women. Ten patients were stage IIIB and 53 were stage IV. Patients with Eastern Cooperative Oncology Group performance status < or =2 were enrolled. There were three complete remissions and 13 partial remissions, for an overall response rate of 25%. Median survival was 32 weeks. This compares with a response rate of 27% and a median survival of 38 weeks observed in our previous study, using 24-hour paclitaxel plus the same dose of carboplatin. Grade 3/4 leukopenia occurred in 47% versus 3% of treatment cycles in the 24-hour versus 1-hour patient groups, respectively. Febrile neutropenia was similar and occurred in 7% versus 4% of treatment cycles. Grade 1 to 3 neurotoxicity occurred in 7% versus 41% of patients in the 24-hour versus 1-hour schedule groups, respectively. Likewise, the incidence of grade 1 to 3 arthralgia/myalgia was greater among patients receiving 1-hour infusion of paclitaxel (3.5% v 28%). Although not randomized, these data suggest that survival may be comparable whether paclitaxel is given by short or prolonged infusion in advanced non-small cell lung cancer. Toxicity profiles differ, however, with greater myelosuppression following 24-hour paclitaxel, but a higher incidence of neurotoxicity and arthralgia/myalgia with the 1-hour infusion.

Adult↗
PubMed1997

Induction paclitaxel/carboplatin in early stage non-small cell lung cancer. Bimodality Lung Oncology Team.

In this feasibility study, a 3-hour infusion of 225 mg/m2 paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was combined with carboplatin dosed to an area under the concentration-time curve of 6 to treat patients with stage T2N0, T1-2N1, or T3N0-1 (excluding superior sulcus tumors) non-small cell lung cancer. Nineteen of a planned 80 patients have been enrolled. To assure that patients meet the study's criteria for inclusion, rigorous physical and laboratory investigations are performed before, during, and after the preoperative chemotherapy and again before the postsurgical chemotherapy. Treatment includes two cycles of preoperative chemotherapy, followed within 3 to 6 weeks with thoracotomy. Up to three cycles of postoperative chemotherapy are planned, commencing 3 to 8 weeks after surgery, as tolerated. To date, 14 patients have completed induction chemotherapy, nine of whom have undergone surgical resection. Three patients have completed postoperative chemotherapy. The study treatment has been well tolerated with no unexpected toxicities. Very preliminary results suggest that perioperative paclitaxel/carboplatin appears to be a feasible and tolerable regimen in patients with early stage non-small cell lung cancer and warrants further investigation. More mature results may provide the basis for an intergroup randomized trial comparing this regimen with surgery alone for patients with early stage disease.

Adult↗
PubMed1997

Correlation of pseudoexfoliative material and optic nerve damage in pseudoexfoliation syndrome.

PURPOSE: To determine whether the severity of glaucomatous damage in eyes with pseudoexfoliative (PEX) glaucoma is related to the amount of PEX material in the trabecular meshwork. METHODS: Trabecular meshwork and optic nerves from 19 eyes (11 donors) with PEX syndrome were studied. Eyes were chosen to represent all stages of severity of disease. Sections from each quadrant around the circumference of each eye were studied with light and transmission electron microscopy. Morphometric measurements were made of Schlemm's canal (SC) and of the components of the cribriform region and were statistically correlated with axonal counts of the optic nerves. Correlations between clinical and histologic data were determined. RESULTS: Pseudoexfoliative material was frequently found in isolated aggregates beneath the inner-wall endothelium of SC. The cribriform region was otherwise normal in structure; disorganization of this region was found only in focal regions of a few eyes. The amount of PEX material was correlated with the maximal intraocular pressure (IOP) and the IOP on treatment and was inversely correlated with the number of axons in the optic nerve. The number of axons was inversely correlated with the maximal IOP and the IOP on treatment, but not with duration of disease. CONCLUSIONS: The severity of glaucoma in PEX is related to the amount of PEX material present in the cribriform region. Elevation of IOP occurs before disorganization of the cribriform region and may be related to the location of the PEX material near the inner wall of SC. Comparison of clinical and histologic findings revealed that the results of visual field examinations fit more closely with the axonal counts than did the clinical assessment of the cup-to-disc ratio.

Aged↗
PubMed1997

The effect of cytochalasin D on outflow facility and the trabecular meshwork of the human eye in perfusion organ culture.

PURPOSE: To determine the effect of cytochalasin D on outflow facility in the human anterior segment, and the histologic changes that accompany the effect. METHODS: Human anterior segments were studied in perfusion organ culture. The anterior segment from one eye received cytochalasin D, and that from the fellow control eye received vehicle; doses ranged from 0.06 mg/ml to 27.7 mg/ml. The duration of action and the effect of repeated doses were studied, and the accompanying histologic changes were assessed in 12 pairs of anterior segments. RESULTS: Cytochalasin D in concentrations of 0.6 mg/ml and 1.1 mg/ml caused increases in outflow facility of 42% and 37%, respectively (P < 0.05), with a peak effect 2 to 6 hours after infusion and a duration of action of approximately 14 hours. Anterior segments were not responsive to repeated doses (24 hours apart). Compared with the effect of vehicle in control anterior segments, cytochalasin D caused scattered breaks in the inner wall endothelial lining of Schlemm's canal (4.6 +/- 2.5% versus 0.7 +/- 0.6%; P = 0.02; anterior segments fixed during maximum drug effect). No increase in the amount of optically empty space within the juxtacanalicular tissue was seen. Inner wall breaks persisted, even in eyes in which the outflow facility had returned to baseline; the basement membrane and subendothelial matrix of the inner wall remained intact. Final intraocular pressure was inversely correlated with the length of optically empty space immediately adjacent to the inner wall. CONCLUSIONS: Cytochalasin D can increase outflow facility in the anterior segment of the human eye and causes ruptures of the inner wall of Schlemm's canal. These breaks persist, even when interocular pressure returns to baseline; the basement membrane and subendothelial matrix of the inner wall appear to remain intact. The final intraocular pressure was inversely correlated with the length of optically empty space immediately adjacent to the inner wall.

Aged↗
PubMed1997

A phase I trial of retroviral BRCA1sv gene therapy in ovarian cancer.

Gene transfer of BRCA1sv (a normal splice variant of BRCA1) into ovarian cancer cells produces growth inhibition in vitro and tumor suppression in nude mouse xenografts. As an initial step toward gene replacement therapy for ovarian cancer, we conducted a Phase I trial to assess the pharmacokinetics and toxicity of i.p. BRCA1sv retroviral vector therapy. Following placement of an indwelling Port-a-Cath in patients, a dose escalation study was performed of four daily i.p. infusions spanning doses from 3 to 300 ml (i.e., 10(10) viral particles) at half-log intervals (23 cycles in 12 patients). Gene transfer and expression were documented by PCR, Southern blot, reverse transcription-PCR, and nuclease protection assays. Pharmacokinetics were assessed by PCR and Southern blots detecting vector DNA, and toxicity was evaluated by clinical exam and fluid analysis. Three of 12 patients developed an acute sterile peritonitis, which spontaneously resolved within 48 h. Plasma and peritoneal antibodies to the retroviral envelope protein were detected only in patients treated with the highest dose levels but not in others, despite repeat dosing for an interval of up to 4 months. Eight patients showed stable disease for 4-16 weeks, and three patients showed tumor reduction with diminished miliary tumor implants at reoperation (two patients) and radiographic shrinkage of measurable disease (one patient). The vector-related complication of peritonitis was observed in three patients but resolved quickly as in preclinical mouse studies. Ovarian cancer may provide an important model for retroviral gene therapy studies due to vector stability, minimal antibody response, and access to tumor by i.p. therapy.

Adult↗
PubMed1997

Phase I study of the antineovascularization drug CM101.

CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fifteen patients with refractory malignancies received CM101 i.v. by a 15-min infusion every other day, three times in 1 week, at doses ranging from 1 unit (7.5 microgram)/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly. Plasma levels of inflammatory cytokines, including tumor necrosis factor alpha, interleukin 8, interleukin 10, MIP-1alpha, and soluble E-selectin, were analyzed from -15 min to 12 h during each treatment. Dose-limiting toxicities, including grade IV dyspnea and arrhythmia, were encountered at the 5-unit/kg level. Toxicities occurred primarily within the first 12 h after therapy and included mild-to-moderate fever and chills, nausea, cough, headache, facial flushing, dyspnea, myalgias, and acute tumor-related pain. No patient developed detectable antibodies to CM101. All patients experienced marked time- and dose-dependent elevations in all cytokines studied. Three patients experienced tumor shrinkage. The results show that CM101 can be safely administered at doses that produce evidence for severe, and possibly tumor-specific, inflammation. Further study is necessary to better characterize the mechanism of action and determine the optimal dose and schedule of this new agent.

Adult↗
PubMed1996

Voluntary ethanol intake in the rat: effects of nicotinic acetylcholine receptor blockade or subchronic nicotine treatment.

It has been suggested that the mesolimbic dopamine activating and the reinforcing properties of ethanol involve activation of central nicotinic acetylcholine receptors. To test this hypothesis, the effects of two nicotinic receptor antagonists and of subchronic nicotine treatment on voluntary ethanol consumption (ethanol 6% v/v or water) were studied in ethanol low-, medium- or high-preferring Wistar rats. After systemic mecamylamine (2 mg/kg) but not hexamethonium (0 mg/kg) high- but not low-preferring rats decreased their ethanol intake but, however, not their ethanol preference. When subchronically exposed to nicotine (0.35 mg/kg, s.c. daily) medium-preferring rats markedly increased their ethanol intake and preference. This effect lasted for more than 1 week after interrupting nicotine administration. Ethanol intake levels did not correlate with locomotor activity scores after nicotine challenge (0.35 mg/kg, s.c.) or with exploratory locomotor activity. However, exploratory locomotor activity correlated with locomotor activity scores both after nicotine (0.35 mg/kg, s.c.) and ethanol (0.125 g/kg i.p.) challenge. Dopamine release, as indicated by accumulation of 3-methoxytyramine after monoamine oxidase inhibition, was increased in the limbic forebrain (including the nucleus accumbens, the olfactory tubercles, the amygdala and the septum) after acute nicotine (0.35 mg/kg s.c.) or ethanol (2.5 g/kg i.p.) in animals subchronically exposed to nicotine compared to subchronically vehicle-treated controls. The present results further implicate central nicotinic receptors in the molecular events mediating the reinforcing properties of ethanol, and suggest that subchronic nicotine enhances the responsiveness of mesolimbic dopamine neurons both to nicotine and to ethanol. Clinical implications are discussed.

Alcohol Drinking↗
PubMed1996

Acebutolol overdose treated with hemodialysis and extracorporeal membrane oxygenation.

A case involving a 27-year-old woman who ingested an overdose of acebutolol is presented. Extracorporeal membrane oxygenation was initiated to stabilize the patient's condition before commencing hemodialysis. S-diacetolol (the N-acetelation product of acebutolol) was cleared with hemodialysis. It is suggested that extracorporeal membrane oxygenation may be of short-term benefit in the treatment of overdoses with beta-adrenergic agents such as acebutolol when accelerated clearance with hemodialysis is anticipated.

Acebutolol↗
PubMed1996

Point process models of single-neuron discharges.

In most neural systems, neurons communicate via sequences of action potentials. Contemporary models assume that the action potentials' times of occurrence rather than their waveforms convey information. The mathematical tool for describing sequences of events occurring in time and/or space is the theory of point processes. Using this theory, we show that neural discharge patterns convey time-varying information intermingled with the neuron's response characteristics. We review the basic techniques for analyzing single-neuron discharge patterns and describe what they reveal about the underlying point process model. By applying information theory and estimation theory to point processes, we describe the fundamental limits on how well information can be represented by and extracted from neural discharges. We illustrate applying these results by considering recordings from the lower auditory pathway.

Animals↗
PubMed1996

Drug fever.

Drug fever is the febrile response to a drug without cutaneous manifestations. Although the exact incidence of drug fever remains unknown, it has been estimated to occur in approximately 10% of inpatients. The recognition of drug fever is of great clinical importance because, if drug fever is not recognized diagnostically, patients may be subjected to prolonged hospitalization and unnecessary testing or medications. Early diagnosis and treatment of drug fevers are essential in maintaining cost-effective, high-quality medical care.

Body Temperature Regulation↗
PubMed1996

Arthroscopy assisted operative management of tibial plateau fractures.

In recent years the treatment of fractures has evolved from extensive open reduction and internal fixation to minimally invasive surgery and biologically benign internal fixation. The ultimate goal of treatment for tibial plateau fractures is to prevent the late development of degenerative osteoarthritis. Surgery is often required to restore joint congruity and alignment, to stabilize the knee, and to allow early joint motion. In most cases, these goals can be achieved through arthroscopic reduction and internal fixation. Arthroscopic reduction and internal fixation offers the advantage of direct visualization of the fracture and its subsequent reduction without a formal arthrotomy or detachment of the anterior horn of the lateral meniscus. Not all types of fractures are amenable to arthroscopic reduction and internal fixation, such as severe bicondylar fractures. This technique is now evolving and some Schatzker Type 6 fractures have been treated with traction on the fracture table, arthroscopy assisted reduction, limited internal fixation of the articular surface, followed by rigid external fixation.

Adult↗