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Biomedical subjects

L D Wilson

Publications and source records attributed to L D Wilson.

At least 37 records · Page 2Linked to original sources

Extent of skin involvement as a prognostic indicator of disease free and overall survival of patients with T3 cutaneous T-cell lymphoma treated with total skin electron beam radiation therapy.

BACKGROUND: The goal of this study was to define the prognostic significance of the extent of skin involvement (ESI) with respect to disease free survival (DFS) and overall survival (OS) of patients with T3 cutaneous T-cell lymphoma (CTCL) after total skin electron beam therapy (TSEBT). METHODS: Between 1974 and 1993, TSEBT (36 Gray [Gy], 1 Gy/day for 9 weeks, 6 MeV electrons) was administered to a total of 213 patients. Forty-six of the 213 patients were classified as having T3 CTCL based on the presence of tumor nodules on the skin at diagnosis. Patient records were evaluated retrospectively, and the percentage of total skin surface involved was calculated. Patients were analyzed with respect to response to therapy, disease free and overall survival. The median follow-up was 37.5 months (range, 1.6-93 months). RESULTS: Thirty-six of 46 patients achieved complete clinical response (CCR) by the completion of TSEBT. DFS was 12% at 36 months with approximately 28% OS. When stratified by extent of skin involvement, 100% of patients with 9% or less ESI were disease free at 18 months compared with patients with 10% or greater ESI, all of whom had relapsed by 18 months (78% achieved CCR). Fifty percent of those with 9% or less ESI remained disease free at 36 months; median DFS and OS were not reached at 63 and 65 months, respectively. The median DFS and OS for the 10% or greater ESI group were 4 and 24 months, respectively. These differences were statistically significant (P < or = 0.005). Toxicity of therapy was minimal. CONCLUSIONS: The extent of skin involvement of patients with T3 CTCL is a prognostic indicator of disease free and overall survival for those who have been treated definitively with TSEBT.

Adult↗

Cocaethylene is as cardiotoxic as cocaine but is less toxic than cocaine plus ethanol.

Cocaethylene is a pharmacologically active cocaine metabolite that is produced in the liver by the transesterification of cocaine only in the presence of ethanol. The acute cardiovascular effects of cocaethylene are not known. We compared the acute cardiovascular effects of cocaethylene with cocaine and with cocaine plus ethanol in 18 dogs. We administered cocaethylene 7.5 mg/kg to 6 dogs, cocaine 7.5 mg/kg to 6 dogs, and cocaine 7.5 mg/kg plus ethanol 1 gm/kg to 6 dogs. The dose of each drug was chosen to produce in dogs the concentrations of cocaethylene or cocaine that have been measured in patients who have experienced cardiotoxic reactions to cocaine or cocaine plus ethanol. Arterial, left ventricular (LV), pulmonary artery wedge pressures (PAWP), the maximum rate of LV pressure rise [(dP/dt)max] and fall [(dP/dt)min], and heart rate (HR) were continuously measured. Stroke volume was determined 3 times during the first hour after drug administration then hourly for four hours. The concentrations of cocaethylene and cocaine peaked in the serum at 3717 +/- 651 ng/ml and 4140 +/- 459 ng/ml, respectively, two minutes after each bolus. The median half-life of cocaethylene was 144.3 minutes whereas the median half-life of cocaine was 96.7 minutes (p < 0.01). Cocaethylene maximally decreased (dP/dt)max by 44%, (dP/dt)min by 29%, and stroke volume by 28% (all p < 0.01) and increased the PAWP by 50% (p < 0.02) and the HR by 13% (p = NS) during the first hour. Cocaine maximally decreased (dP/dt)max by 40%, (dP/dt)min by 31%, and the stroke volume by 26% and increased the PAWP by 100% and the HR by 46% (all p < 0.01) during the first hour. Ethanol plus cocaine maximally decreased (dP/dt)max by 68%, (dP/dt)min by 78% and the stroke volume by 49% and increased the PAWP by 118% and the HR by 74% (all p < 0.01) during the first hour. In this last group, (dP/dt)max and stroke volume remained depressed by approximately 20% (p < 0.01) for five hours. We conclude that cocaethylene is as toxic as cocaine to the myocardium but is less toxic than ethanol plus cocaine.

Animals↗

Anterior pitutiary and pitutiary-dependent target organ function in men infected with the human immunodeficiency virus.

To evaluate pituitary and pituitary-dependent target organ function in men infected with the human immunodeficiency virus (HIV), 26 ambulatory HIV-positive men (13 with acquired immunodeficiency syndrome [AIDS]) and nine healthy control men were administered rapid sequential injections of thyrotropin (TSH)-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), ovine corticotropin (ACTH)-releasing hormone (oCRH), and human growth hormone-(GH)-releasing hormone (hGHRH). Blood samples were collected before and for 90 minutes after the injections for immunoassay of pituitary hormones, cortisol, testosterone, and free thyroxine (fT(4)). Data were analyzed for each group of men considering basal, peak, and incremental responses to the releasing hormones, as well as the time course of response of each hormone. Mean basal serum GH concentrations were the same in all groups (control, AIDS, and non-AIDS HIV-positive), but stimulated GH levels were substantially higher at all time points in both groups of HIV-positive subjects. Results for prolactin (PRL) were similar, although stimulated PRL levels were increased significantly only in the AIDS group. The mean basal serum TSH concentration and stimulated TSH levels at 60 and 90 minutes were significantly greater in the AIDS group than in the control group. Basal mean fT(4) concentration in the AIDS group was significantly less than in the control group. Mean basal and stimulated serum (total) testosterone concentrations in all groups were the same. However, basal serum luteinizing hormone (LH) concentrations in both groups of HIV-infected men were significantly greater than in controls; stimulated (peak) LH levels were not different from control levels. Basal and peak stimulated plasma ACTH concentrations were significantly increased in both HIV-infected groups. Basal serum cortisol levels were also greater, on average, in HIV-infected groups, although stimulated (peak) cortisol responses were not different. These results indicate that basal serum concentrations of TSH, LH, ACTH, and cortisol are modestly increased in men with AIDS, and that maximum levels of GH, PRL, TSH, and ACTH stimulated by the releasing hormones are also increased in this group. Measurements obtained in the non-AIDS HIV-infected men showed a pattern generally similar to that obtained in men with AIDS, but less marked. The basis for the increased pituitary activity is unknown; we speculate that it is due to modestly impaired target organ function and to increased hypothalamic stimulation.

Acquired Immunodeficiency Syndrome↗

Additional courses of total skin electron beam therapy in the treatment of patients with recurrent cutaneous T-cell lymphoma.

BACKGROUND: Recurrent cutaneous T-cell lymphoma (CTCL) is managed with a variety of modalities. Repeat treatment with additional courses of total skin electron beam therapy (TSEBT) has not been formally evaluated. OBJECTIVE: Our purpose was to evaluate the efficacy and toxicity of additional TSEBT for recurrent CTCL. METHODS: A total of 14 patients were treated with TSEBT and received at least two courses, with five of those patients receiving a third course. Patients were offered additional TSEBT if they suffered recurrence despite other therapy if the extent of the recurrence precluded localized radiation. The median follow-up was 36 months. RESULTS: The median dose for the entire group was 57 Gy. Thirteen patients (93%) achieved a complete response (CR) after the initial course. After the second course, 12 patients (86%) had a CR; of the five patients who underwent a third course, three (60%) achieved a CR. The median disease-free interval after the first course of therapy for those with a CR was 20 months and 11.5 months after the second course. Median survival after the second course was 15 months. All patients had xerosis, pruritus, desquamation, mild erythema, epilation, and anhidrosis of the skin. CONCLUSION: Patients with recurrent CTCL recalcitrant to other forms of therapy or too diffuse for treatment with localized radiation fields are candidates for additional TSEBT. This therapy is effective and well tolerated with an acceptable risk profile.

Adult↗

Subareolar breast cancer: long-term results with conservative surgery and radiation therapy.

PURPOSE: It has been suggested that patients presenting with breast cancers within 2 cm of the nipple areolar complex represent a relative contraindication to conservative management due to either a compromised cosmetic result associated with sacrifice of the nipple areolar complex, reluctance to include the entire nipple areolar complex in the conedown field, or increased risk of multicentricity. We have reviewed our experience of conservatively treated patients with specific reference to the subset of patients presenting with tumors within 2 cm of the nipple areolar complex. METHODS AND MATERIALS: Between January 1970 and December 1989, 1014 patients with early stage breast cancer were treated at Yale-New Haven Hospital by excisional biopsy with or without axillary lymph node dissection. Of the 1014 charts reviewed, a total of 98 patients fulfilled the criteria of having a central/ subareolar breast cancer. Reexcision was performed on only 16 patients. Following conservative surgery, patients were treated with radiation therapy to the intact breast to a total median dose of 48 Gy with conedown to a total of 64 Gy. adjuvant systemic therapy and regional nodal irradiation were administered as clinically indicated. RESULTS: As of December 1993, the median follow-up for the 98 patients in this study was 9.03 years. The majority of patients had presented with either a palpable mass or a mammographically detected lesion. Three patients presented with Paget's disease, five with nipple discharge, and seven with nipple inversion. Ten of the 98 patients had the nipple areolar complex sacrificed at the time of surgery, while the remaining 88 patients had the entire nipple areolar complex included in the conedown field. Four of these 88 patients had the nipple partially blocked during the electron conedown. There were no significant complications associated with including the entire nipple areolar complex within the conedown field to a median dose of 64 Gy. Six of the 98 patients experienced a local recurrence, three experienced a regional recurrence, and nine experienced distant metastasis. The actuarial 10-year survival (0.79 +/- 0.06), distant disease-free survival (0.88 +/- 0.04) and breast recurrence-free survival (0.84 +/- 0.07) were not significantly different from those patients who presented with cancers in other parts of the breast. CONCLUSIONS: Patients presenting with subareolar breast cancers within 2 cm of the nipple areolar complex are suitable candidates for conservative surgery and radiation therapy. In the majority of patients in this study, the nipple areolar complex did not need to be sacrificed and could be safely included in the electron conedown field with acceptable complications and cosmesis. A subareolar breast cancer does not represent a relative contraindication to conservative management in patients with early stage breast cancer.

Breast Neoplasms↗

Systemic chemotherapy and extracorporeal photochemotherapy for T3 and T4 cutaneous T-cell lymphoma patients who have achieved a complete response to total skin electron beam therapy.

PURPOSE: To evaluate the impact of systemic adjuvant therapies on relapse-free (RFS) and overall survival (OS) of cutaneous T-cell lymphoma (CTCL) patients treated with total skin electron beam therapy (TSEBT). METHODS AND MATERIALS: Between 1974 and 1990, TSEBT (36 Gy at 1 Gy/day; 9 weeks; 6 MeV electrons) was administered with curative intent to a total of 163 CTCL (mycosis fungoides) patients using six fields supplemented by orthovoltage boosts (120 kvp, 1 Gy x 20) to the perineum, soles of feet, and apical scalp (120 kvp, 2 Gy x 3). In this group, all patients who achieved a clinical complete response or a good partial response were offered one of two competing regimens of either adjuvant doxorubicin/cyclophosphamide or adjuvant extracorporeal photochemotherapy (ECP). RESULTS: When the results for the group who achieved a complete response (CR) to TSEBT were analyzed, OS for T1 and T2 patients was excellent (85-90% at 5-10 years) and not improved by either adjuvant regimen. However, T3 and T4 patients who received either adjuvant doxorubicin/cyclophosphamide (75% at 3 years) or adjuvant ECP (100% at 3 years) had better overall survival than those who received neither adjuvant regimen (approximately 50% at 5 years). The difference between the OS curves for those who received ECP vs. those who received no adjuvant therapy approached statistical significance (p < 0.06), while a significant survival benefit from the addition of chemotherapy for TSEBT complete responders was not observed. Neither adjuvant therapy provided benefit with respect to relapse free survival after TSEBT. CONCLUSIONS: These results suggest that an adjuvant nontoxic regimen of extracorporeal photochemotherapy may prolong survival in advanced stage CTCL patients who have achieved a complete remission after TSEBT. The combination of doxorubicin/cyclophosphamide had no significant impact on overall survival in those patients who achieved CR to TSEBT, and neither adjuvant therapy had an impact on relapse free survival for all T-stages. Such results are the basis for the current development of a prospective, randomized trial studying the impact of ECP after TSEBT in patients with advanced stage CTCL.

Adult↗

Cocaethylene causes dose-dependent reductions in cardiac function in anesthetized dogs.

Twelve million Americans abuse both cocaine and ethanol each year because this drug combination produces a pronounced and prolonged euphoria. However, these substances in combination are substantially more toxic than either drug alone. This toxicity may be due to cocaethylene, which has been detected in the serum of patients who have used cocaine and ethanol and two require emergency treatment. Cocaethylene is a pharmacologically active cocaine metabolite formed in the liver only in the presence of ethanol. To investigate the cardiovascular effects of cocaethylene, we randomized 15 mongrel dogs to receive 11.25 mg/kg (n = 4), 7.5 mg/kg (n = 6), or 3.75 mg/kg (n = 5) of cocaethylene as an intravenous (i.v.) bolus. These doses were chosen to achieve serum concentrations of cocaethylene consistent with those observed in patients with cocaine and ethanol toxicity. The ECG and the femoral arterial, left ventricular (LV), and pulmonary artery pressure were measured continuously, and cardiac output (CO) and serum levels of cocaethylene were monitored at specific intervals before and after drug administration. The maximal rate of increase and decrease in LV pressure (LVP), i.e., (dP/dt)max and (dP/dt)min, were determined as our indexes of ventricular contractility and relaxation. Cocaethylene concentrations peaked 2-4 min after each bolus and then decreased in a curvilinear manner. Cocaethylene's half-life (t1/2) was 150 +/- 15.1 min (mean +/- SEM). The greatest hemodynamic changes occurred at the peak cocaethylene serum concentrations in each group. In comparison with control measurements, cocaethylene in concentrations of 11.25 and 7.5 mg/kg decreased (dP/dt)max by 81 and 43% and decreased (dP/dt)min by 80 and 36%, respectively. In these two groups, cocaethylene decreased stroke volume (SV) by 29 and 33% and reduced mean arterial pressure (MAP) by 65 and 30%, respectively. Cocaethylene increased pulmonary artery wedge pressure (PAWP) by 70 and 67% in the 11.25- and 7.5-mg/kg groups. These hemodynamic changes persisted for 60 min after the bolus administration. In each of the three groups, cocaethylene increased the QRS interval duration by 60, 32, and 44% and the QTc interval by 38, 21, and 17%. These ECG changes persisted for 120 min. These experiments suggest cocaethylene depresses the myocardium. Cocaethylene may be a major contributor to the delayed but substantial cardiotoxicity that occurs in individuals who use both cocaine and ethanol.

Animals↗

Cocaine-associated myocardial infarction. Clinical safety of thrombolytic therapy. Cocaine Associated Myocardial Infarction (CAMI) Study Group.

OBJECTIVE: To determine the safety of thrombolytic use in patients with cocaine-associated myocardial infarction. DESIGN: Retrospective cross-sectional survey. SETTING: Twenty-nine acute care institutions. PATIENTS: Patients who sustained cocaine-associated myocardial infarction from 1987 to 1993 were identified through medical record review. Those who received thrombolytic therapy (n = 25) were compared with those who met electrocardiographic TIMI criteria but did not receive thrombolytic therapy (n = 41). INTERVENTIONS: None. RESULTS: Both groups of patients were similar with respect to age, gender, race, cardiac risk factors, time from last cocaine use until presentation, and duration of chest pain at the time of presentation (p > 0.20). There were no major complications or deaths in patients who received thrombolytic therapy (95% confidence interval, 0 to 12%). Minor complications occurred in only two patients. The presence or absence of clinical criteria for reperfusion was noted in the charts of 21 patients who received thrombolytic therapy: 67% were believed to reperfuse. The patients who did and did not receive thrombolytic therapy had similar median peak creatine kinase-MB (CK-MB) levels (180 vs 154 mg/dL, p = NS) and time until peak CK-MB (11.3 vs 13.6 h; p = NS). CONCLUSION: Thrombolytic therapy for cocaine-associated myocardial infarction appears to be safe. It remains unclear whether thrombolytic therapy is an important therapeutic intervention for patients with cocaine-associated myocardial infarction. Further study on efficacy is recommended prior to routine use.

Adult↗

Malignant melanoma and other second cutaneous malignancies in cutaneous T-cell lymphoma. The influence of additional therapy after total skin electron beam radiation.

BACKGROUND: Previous large studies have shown that patients with cutaneous T-cell lymphoma are at increased risk for basal cell carcinoma and squamous cell carcinoma, and anecdotal case reports have suggested an association with malignant melanoma. It has been postulated that the exposure of cutaneous structures to potentially carcinogenic therapies, such as ionizing radiation or alkylating agents, might be causally associated with the development of these second cutaneous malignancies, but, to date, no study has directly addressed this issue. The purpose of this study was to evaluate the occurrence of second cutaneous malignancies in a group of patients with cutaneous T-cell lymphoma treated with total skin electron beam therapy and to examine the additional effects of oral psoralen with UV-A phototherapy, topical mechlorethamine hydrochloride therapy, and further radiation therapy. One hundred sixty-four patients with cutaneous T-cell lymphoma who had received total skin electron beam therapy between 1974 and 1990 were identified, and information was abstracted from their records. RESULTS: Six patients developed malignant melanoma 12 to 95 months after total skin electron beam therapy. Of the six patients, three had received oral psoralen with UV-A as additional therapy and two had received topical mechlorethamine. None had received additional radiation therapy. Twenty-four patients developed more than 37 basal cell carcinomas and 34 squamous cell carcinomas from 11 months to more than 10 years after total skin electron beam therapy. Of the 24 patients, 15 had received oral psoralen with UV-A and 12 had received mechlorethamine as additional therapy. Additional radiation therapy had been administered to nine patients. During a median follow-up of 6 years, no patients died of any second cutaneous malignancy. CONCLUSION: We found a high rate of both melanoma and nonmelanoma skin cancer. The additional use of mechlorethamine or oral psoralen plus UV-A, but not radiation, was significantly associated with the development of basal cell carcinoma and squamous cell carcinoma, but not malignant melanoma.

Adult↗

Location of the prostatic apex and its relationship to the ischial tuberosities.

PURPOSE: Although modern computerized tomography scans have revolutionized the three-dimensional treatment planning for external beam radiation therapy for prostate cancer, the prostate apex is often difficult to precisely define. Some institutions routinely use the ischial tuberosities to define the lower border of external beam fields for prostate cancer, while others recommend a retrograde urethrogram. This study was undertaken to estimate the accuracy of using the bottom of the ischial tuberosities to define the lower border of the external beam fields for Stages T1, T2, and T3 prostate cancer. METHODS AND MATERIALS: The anatomic location of the apex of the prostate was determined in 153 implant patients either by direct surgical exposure of the prostate (133 patients) or by using transrectal ultrasound (20 patients). The prostate apex position relative to the ischial tuberosities was determined and plotted on a schematic of the bony pelvic structures drawn to scale. RESULTS: There was excellent agreement in the estimate of the location of the prostate apex between the two methods (surgery vs. ultrasound) used. The prostate apex was located above the ischial tuberosities in 152 of the 153 patients studied (99.3%). Seven of the 153 patients (4.6%) had a prostate apex which was less than 1.5 cm above the ischial tuberosities and 3 of the 153 patients (2%) had an apex-tuberosity distance of less than 1 cm. CONCLUSION: This study indicates that locating the inferior border of the external beam fields at the ischial tuberosity adequately treats at least 95.4% of all prostate patients with a margin of 1.5 centimeters or more below the prostate apex. In addition, the external beam policy of locating the inferior border at the ischial tuberosities has produced: (a) excellent 10-year clinical local control rates of 88% for Stage T1 and T2 patients and 82% for Stage T3 patients, and (b) 5-year and 10-year biochemical (normal prostate specific antigen) and clinical disease free survival rates for T1 and T2 patients which are similar to surgery.

Brachytherapy↗

Impact of non-CTCL dermatologic diagnoses and adjuvant therapies on cutaneous T-cell lymphoma patients treated with total skin electron beam radiation therapy.

PURPOSE: To evaluate the impact of pre-cutaneous T-cell lymphoma dermatologic diagnoses and adjuvant therapies on the relapse-free and overall survivals of patients treated with total skin electron beam therapy. METHODS AND MATERIALS: Between 1974 and 1990, 164 patients were evaluated by members of Yale University School of Medicine departments of Dermatology and Therapeutic Radiology and treated with total skin electron beam therapy to a total dose of 3600 cGy. Patients who achieved a clinical complete response were offered doxorubicin/cyclophosphamide chemotherapy, extracorporeal photopheresis, or no systemic adjuvant therapy. The effects of TNM stage, antecedent non-T-cell lymphoma dermatologic diagnoses, and systemic adjuvant therapies were analyzed for their impact on relapse-free and overall survival. RESULTS: In this cohort of patients, an antecedent dermatologic diagnosis of follicular mucinosis or lymphomatoid papulosis was significantly associated with a shorter relapse-free survival for T1 and T2 patients, while antecedent "non-specific" dermatitides were associated with a somewhat better relapse-free survival. When the impact of systemic adjuvant therapies was analyzed, neither systemic doxorubicin/cyclophosphamide chemotherapy nor systemic extracorporeal photopheresis were found to delay cutaneous relapse. CONCLUSION: Our results suggest that antecedent follicular mucinosis and lymphomatoid papulosis may be associated with short relapse-free survival in T1 and T2 patients treated with total skin electron beam therapy. They also imply that neither adjuvant chemotherapy nor extracorporeal photopheresis delay cutaneous relapse after total skin electron beam therapy.

Adult↗

Cocaine plus ethanol is more cardiotoxic than cocaine or ethanol alone.

OBJECTIVES: The purpose of this study was to determine the hemodynamic effects of recreational/toxic doses of ethanol, or cocaine, or ethanol followed by cocaine. DESIGN: Prospective, randomized study. SETTING: University research laboratory. SUBJECTS: Eighteen healthy, adult mongrel dogs. INTERVENTIONS: Dogs were randomized to receive ethanol (1 g/kg iv) over 20 mins and a 10-mL bolus of 0.9% sodium chloride, or 5% dextrose in water, over 20 mins, and then a cocaine bolus (7.5 mg/kg), or ethanol (1 g/kg iv), over 20 mins, and then a cocaine bolus (7.5 mg/kg). MEASUREMENTS AND MAIN RESULTS: Arterial, left ventricular, and pulmonary arterial pressures, mixed venous blood oxygen saturation, and heart rate (HR) were continuously recorded in each dog. The maximal rate of left ventricular pressure increase (dP/dtmax) and decrease (dP/dtmin), stroke volume, HR, pulmonary artery occlusion pressure (PAOP), and plasma concentrations of ethanol and cocaine were measured at baseline, after ethanol or placebo infusions, and then after a cocaine or placebo bolus at specific time intervals over a 5-hr study period. The plasma ethanol concentration increased to 160 +/- 8 mg/dL at 30 mins after the start of the infusion, and then decreased to 30 +/- 8 mg/dL at 180 mins. The plasma cocaine concentration increased to 4587 +/- 383 ng/mL within 2 mins of the bolus injection, and then decreased and approached the baseline at 240 mins. Immediately after injection, ethanol plus cocaine synergistically decreased dP/dtmax by 70% and dP/dtmin by 81% (both p < .001). In addition, immediately after injection, ethanol plus cocaine maximally decreased the stroke volume by 34% (p < .05) and maximally increased the HR by 89% and PAOP by 127% (both p < .002). The dP/dtmax and the stroke volume remained decreased by 15% to 20% for 5 hrs (p < .05). Cocaine alone, immediately after injection, maximally decreased dP/dtmax and dP/dtmin by 40% (p < .02), and caused a 26% decrease in stroke volume (p = .05), a 48% increase in HR (p < .02), and a 75% increase in PAOP. The decrease in dP/dtmax persisted for approximately 60 to 90 mins. Ethanol alone produced transient 6% to 13% decreases in dP/dtmax, dP/dtmin, and stroke volume (NS) and small (9%) increases in the HR (NS) during the first hour after injection. CONCLUSION: Cocaine combined with ethanol produces a significant synergistic depression of ventricular contraction and relaxation that substantially exceeds the arithmetic sum of the depressive effects of either cocaine or ethanol alone.

Analysis of Variance↗

Long-term intermittent intravenous insulin therapy and type 1 diabetes mellitus.

An important defect in insulin-dependent diabetes mellitus (IDDM) is that the liver does not meet its full fuel-processing function, because many of the enzymes involved depend on high insulin concentrations in the portal vein. We tried to reactivate the liver by long-term treatment of IDDM patients with intravenous insulin in pulses, with the aim of achieving high portal-vein concentrations during and after a glucose meal. We studied 20 IDDM patients with brittle disease; despite use of a four-injection regimen with manipulation of insulin doses, diet, and physical activity, and frequent clinic visits for at least a year, these patients still had wide swings in blood glucose and frequent hypoglycaemic reactions. The intermittent therapy consisted of 7-10 pulses of intravenous insulin, infused while the patient was ingesting carbohydrate, primarily glucose, during the first hour of a 3 h treatment; three treatments were given in a day. After 2 consecutive days' treatment, patients were treated for 1 day per week. No patient was withdrawn from the study. At the time of this analysis the duration of intermittent treatment ranged from 7 to 71 months (mean 41 [SE 5] months). Haemoglobin A1C concentrations declined from 8.5 (0.4)% at the end of the stabilisation phase to 7.0 (0.2)% at the analysis point (p = 0.0003). During the same time the frequencies of major and minor hypoglycaemic events also fell significantly (major 3.0 [1.1] to 0.1 [0], minor 13.0 [2.6] to 2.4 [0.8] per month; both p < 0.0001). Because the use of saline rather than insulin pulses would have led to unacceptable hyperglycaemia we opted for a historical control design. The absence of a true control group limits the interpretation of these preliminary results, but we believe further studies of hepatic and muscle metabolism before and after long-term intermittent intravenous insulin therapy would be worth while.

Adolescent↗

Conservative surgery and radiation in the treatment of synchronous ipsilateral breast cancers.

BACKGROUND: Conservative surgery (CS) and radiation therapy (RT) as an alternative to mastectomy is controversial in patients with two or more lesions in the same breast. The authors reviewed their experience with CS and RT in the management of patients with synchronous ipsilateral breast cancer (SIBC). METHODS: Of 1060 patients treated with CS and RT at the authors' facilities before December 1988, 13 (1.2%) presented with SIBC. All lesions were identified macroscopically and confirmed microscopically as carcinoma. After excision, patients were treated with radiation to the breast for a median tumor bed dose of 65 Gy, and regional lymphatics were treated as clinically indicated to a median dose of 48 Gy. These cases were retrospectively reviewed. RESULTS: As of February 1992, with a median follow-up of 71 months, the 5-year actuarial survival rate of the 13 patients was 81%. Three of the 13 (23%) had an ipsilateral breast recurrence, resulting in a 72-month actuarial breast recurrence rate of 25%, compared with a rate of 12% in our singular lesion population. Two of these patients remain alive, no evidence of disease at 135 and 93 months after diagnosis. The third patient had chest wall progression and died with metastatic disease at 64 months. Invasive lobular histology and three separate lesions were identified in two of the three patients with subsequent local recurrence. CONCLUSIONS: The local recurrence rate in conservatively treated patients with SIBC is greater than that seen in patients with single lesions, but because of the small sample size, significant conclusions are not possible. Although the data are limited on this subject, these results support consideration of CS and RT as an option in the management of selected patients who favor a breast conservation management approach.

Breast Neoplasms↗

Sensory perceptual alteration. Diagnosis, prediction, and intervention in the hospitalized adult.

This article proposed the nursing diagnosis SPA as the appropriate term for a phenomenon that has been frequently studied, described, and discussed by nurses and physicians using various diagnostic and descriptive labels. SPA affects patients, significant others, and nurses. SPA results in inflated health care costs because it prolongs hospitalization and increases the vigilance required by the nursing staff to maintain patient safety. It is also a source of emotional distress for the patient and his or her significant others. It has been proposed that alteration in NF is the primary cause of SPA. Physiologic, psychological, and environmental alterations represent barriers to adequate NF, thereby interfering with accurate perception of stimuli. A temporary adverse response characterized by impaired cognition and inappropriate behavior occurs. A review of nursing and medical literature during the last 30 years has identified a multitude of conditions that may precipitate SPA, thus supporting the theory that SPA has a multivariate. Yet, a consistent pattern or cluster of risk factors has not been identified. Recent data on the incidence of SPA in hospitalized patients are sparse, and previous research reveals inconsistency in data regarding incidence in all of the populations studied. This inconsistency reflects differences in the settings and demographic characteristics of the subjects studied. In addition, differences in reported incidence can also be attributed to methodological variations brought about by differences in terminology and criteria used to define and diagnose the phenomena associated with SPA. Future research should include reestablishing the incidence of the phenomenon in various populations of hospitalized patients. Populations previously overlooked in the investigation of SPA should also be studied. Examples include organ transplant patients and patients treated with cardiac-assist devices. The behavioral sequelae of SPA have been adequately established in the literature. Therefore, future research should focus on identifying those patients at risk rather than continuing to describe behaviors associated with SPA. The importance of risk identification has been discussed. Identifying patients most at risk for SPA by systematically screening them with a risk tool would facilitate allocation of resources and preventative interventions. Predictive tools need to be developed and tested. A risk-assessment tool could be included with the admission nursing history, and a daily risk assessment could be incorporated into the assessment documentation system. To develop risk prediction tools, it may be necessary to further investigate the barriers to accurate NF. Replication of prior descriptive studies on the causes of SPA should be attempted.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Disseminated intravascular coagulation and excessive fibrinolysis in a patient with metastatic prostate cancer. Response to epsilon-aminocaproic acid.

BACKGROUND: Disseminated intravascular coagulation (DIC) and primary fibrinolysis have both been reported in association with prostate carcinoma. The correct diagnosis of the coagulopathy can be difficult and the appropriate management controversial. METHODS: A case is presented of a man in whom DIC and soft tissue hemorrhage developed after prostatic biopsy. The results of therapy and a review of the literature are discussed. RESULTS: Fibrinogen levels continued to decrease despite high-dose estrogen therapy, but they rapidly returned to normal after therapy with epsilon-aminocaproic acid. Although routine coagulation tests were suggestive of primary fibrinolysis, the results of the D-dimer assay confirmed that the patient had DIC associated with excessive fibrinolysis. CONCLUSION: A review of the literature suggests that most cases of primary fibrinolysis are probably DIC with excessive secondary fibrinolysis. In cases in which bleeding is the primary manifestation of DIC and there is a significant reduction in alpha-2-plasmin inhibitor activity, a trial of epsilon-aminocaproic acid and low-dose heparin should be considered. The failure in this case of estrogen therapy to correct the coagulopathy, despite a later good tumor response, is consistent with the delay in which anorchid testosterone levels are obtained after initiating treatment.

Adenocarcinoma↗