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Biomedical subjects

R M Hansen

Publications and source records attributed to R M Hansen.

At least 55 records · Page 3Linked to original sources

Continuous 5-fluorouracil infusion and alpha interferon in advanced cancers: a report of initial treatment results.

Twenty-four patients with advanced metastatic cancer were treated with continuous intravenous 5-fluorouracil infusion 200-300 mg/m2/day and alpha interferon 3 million units subcutaneously 3 times per week. The average duration of treatment was 87 days (range 22-204 days). 5-fluorouracil could be infused 66% of the planned time on treatment, and patients received an average of 60% of the planned interferon injections. Objective tumor responses were seen in 6 of 17 previously untreated patients (35%). Twenty-two of the 24 patients (92%) experienced toxicity (greater than or equal to ECOG grade II) that required treatment interruption and subsequent dose reduction predominantly for the following reasons: mucositis (67%), hand-foot syndrome (21%), and leukopenia (25%). The incidence of treatment limiting toxicity is higher than previously observed with 5-fluorouracil infusion alone. This suggests true augmentation of 5-fluorouracil effect by interferon. 5-Fluorouracil infusion and alpha interferon is a potentially useful combination that needs further evaluation in future phase II and phase III trials.

Adult↗

Allogeneic bone marrow transplantation for relapsed and refractory lymphoma using genotypically HLA-identical and alternative donors.

Twenty-two patients, ages 16.6 to 43.9 years (median age, 30 years), with relapsed or refractory lymphoma were treated by allogeneic bone marrow transplantation after high-dose chemotherapy with or without total body irradiation (TBI). Seven patients had Hodgkin's disease, four had low-grade histology non-Hodgkin's lymphoma (NHL), seven had intermediate-grade NHL, and four had high-grade NHL. Of the 22 patients, 17 received T-cell (CD-3)-depleted marrow after intensive pretransplant chemoradiotherapy, and five received T-cell-replete grafts after chemotherapy-based preparative regimens. Five patients were transplanted from donors other than genotypically HLA-identical siblings: four from partially HLA-matched relatives, and one from a phenotypically HLA-identical unrelated donor. Acute graft-versus-host disease (GVHD) was less than or equal to grade II in all patients, and chronic GVHD was limited or absent in all but one patient. Of the 21 assessable patients, 17 (80.9%) achieved complete remissions. Death due to transplant-associated complications occurred in five patients, and five patients have relapsed. Thirteen patients are alive, and 12 are continuously relapse-free at a median follow-up of longer than 28 months (range, greater than 10 to greater than 58 months) from transplant. The cumulative probability of treatment failure from relapse or progression of lymphoma was 29% (95% confidence interval [CI], 12% to 51%), while the actuarial lymphoma-free (ie, event-free) survival plateau is 54.6% (95% CI, 34% to 76%). For young patients with advanced malignant lymphoma, allogeneic bone marrow transplantation appears superior to salvage chemotherapy for achievement of long-term, lymphoma-free survival and may be preferable to autologous bone marrow transplantation for selected patients.

Actuarial Analysis↗

The quantity of rhodopsin in young human eyes.

The rhodopsin content of 20 eyes of infants and children ages 27 weeks gestation to 8 years (11 donors) was assayed and compared to the rhodopsin content of adults (36 eyes; 19 donors). Infants have significantly lower rhodopsin contents than adults. On average the rhodopsin content of young infants is about a third of adults. Previously reported full-field b-wave sensitivity of young infants is about 0.5 log units, that is about a third, less than adults. Thus, as previously found in infant rats, photon capture by rhodopsin appears to limit the dark adapted sensitivity of young human infants.

Adolescent↗

Protracted intravenous infusion of 5-fluorouracil in combination treatments. A review.

5-fluorouracil (5-FU) administered by protracted intravenous infusion has been shown to have clinical utility against colorectal cancer and several other advanced tumors. However, additional therapeutic strategies are needed to further improve treatment results. Although the addition of low-dose cisplatin appeared to improve the clinical activity of 5-FU infusion in early phase II studies, subsequent evaluation has failed to substantiate these early reports. In addition, toxicity has been significantly increased. Combinations of cisplatin and other drugs with 5-FU infusion are currently being evaluated. Phase I studies demonstrate that only low doses of concomitant leucovorin are necessary to potentiate 5-FU infusion; phase II studies to evaluate efficacy are underway. Although combinations of 5-FU and biological therapies such as alpha 2a-interferon appear to be very promising, they will require extensive phase II and III testing to define their clinical utility and toxicity.

Antineoplastic Combined Chemotherapy Protocols↗

5-Fluorouracil by protracted venous infusion: a review of recent clinical studies.

The pharmacokinetics of continuous infusion 5-fluorouracil make it an ideal drug to administer as a protracted infusion (continuous infusion more than 30 days). During the last decade numerous clinical studies have been conducted to evaluate the efficacy of 5-fluorouracil (5FU) administered as a protracted venous infusion. Phase II studies in metastatic colorectal cancer in 345 patients have demonstrated an average response rate of 36% (range 15-59%) and a prospective randomized study performed by the Mid-Atlantic Oncology Program (MAOP) has confirmed a higher response rate with 5FU infusion compared with a bolus schedule. Phase II studies in refractory carcinoma of the breast in 177 patients have demonstrated a 30% response rate (range 17-50%); studies in pancreatic, gastric, and refractory prostate cancer have also demonstrated clinical utility. The major toxicities of 5FU infusion are mucositis and hand-foot syndrome; life-threatening myelosuppression is rare and treatment-related deaths have not been reported. 5FU infusion is a useful palliative treatment for many adult patients with advanced malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

Gold induced hepatitis and pure red cell aplasia. Complete recovery after corticosteroid and N-acetylcysteine therapy.

A 54-year-old man developed severe cholestatic jaundice and pure red cell aplasia shortly after beginning treatment with gold sodium thiomalate. Although the hepatic toxicity began to spontaneously improve, the pure red cell aplasia was progressive. Treatment with prednisone and N-acetylcysteine (NAC) infusions was followed by prompt and complete hematologic recovery. Gold induced pure red cell aplasia should be added to the list of gold induced hematologic toxicities that can be potentially reversed with NAC infusion therapy.

Acetylcysteine↗

Hyperopia in complicated Leber's congenital amaurosis.

We studied the refractive status of 13 children with Leber's congenital amaurosis. Seven had the disease complicated by neurological or other systemic abnormalities, while the other 6 patients had only ophthalmic abnormalities. All 13 patients were hyperopic. The magnitude of hyperopia did not differ significantly between the complicated and uncomplicated groups. Therefore, one cannot, as previously suggested, use the presence of high hyperopia to differentiate an uncomplicated form of Leber's congenital amaurosis from one complicated by neurologic or other systemic abnormalities. The concurrence of hyperopia with Leber's congenital amaurosis should not steer the physician away from careful neurologic systemic or biochemical evaluation of the child.

Age Factors↗

5-Fluorouracil infusion and low-dose weekly cisplatin: an analysis of increased toxicity.

It has been suggested that the addition of weekly low-dose cisplatin (DDP) may potentiate the efficacy of continuous infusion 5-fluorouracil (5-FU) without adding significant toxicity. To investigate the extent of added toxicity, an analysis of toxicity was completed in 18 patients with advanced cancers treated with continuous ambulatory 5-FU infusion 300 mg/m2/day and weekly low-dose cisplatin (DDP) 20 mg/m2. Ten of the 18 patients (56%) developed multiple (four or more) toxicities during treatment. In addition, toxicity categorized as severe occurred in 10 patients (56%). Seventeen of the 18 patients (94%) required treatment interruption or dose attenuation due to toxicity and most patients experienced a decline in Eastern Cooperative Oncology Group performance status due to treatment-related toxicity. Compared with historical toxicity patterns when 5-FU infusion is administered alone, the addition of DDP has resulted in significant increases in nausea and vomiting, anorexia, diarrhea, stomatitis, and myelosuppression. The addition of low-dose weekly DDP adds significant toxicity and morbidity to the continuous 5-FU infusion regimen.

Adult↗

Plasma cell leukemia and hyperviscosity syndrome.

A 56-year-old man had dyspnea, weight loss, hemoptysis, and a generalized bleeding diathesis. Physical examination disclosed hepatosplenomegaly, congestive heart failure, and multiple sites of bleeding. Severe anemia, thrombocytopenia, rouleaux formation, and a leukocytosis with circulating immature plasma cells were observed, along with azotemia, hyperuricemia, and marked elevation of total proteins with a monoclonal IgG kappa spike. The finding of increased serum viscosity confirmed the clinical impression of the hyperviscosity syndrome. Emergency plasma exchange produced marked improvement in the clinical manifestations of hyperviscosity syndrome. Systemic chemotherapy resulted in a partial remission of the disease, but the patient ultimately died of complications of treatment. In this review, we discuss the diagnosis and management of the hyperviscosity syndrome.

Blood Proteins↗

Systemic therapy in metastatic colorectal cancer.

Fluorouracil-based chemotherapy regimens have been utilized in metastatic colorectal cancer for more than 30 years. Early attempts at defining an optimal treatment schedule and use in combination with other drugs failed to significantly improve results. In contrast, the clinical effectiveness of fluorouracil has been improved by continuous infusion administration and modulation with folinic acid. Both approaches have increased the response rate compared with results achieved with traditional bolus schedules; the effect on survival has been less significant. Unfortunately, expense and, in some instances, toxicity have also been increased, which detracts from their overall usefulness. Clinical studies that evaluate fluorouracil chemotherapy in combination with biological-response modifiers are ongoing and will be areas of intense research during the next few years.

Antineoplastic Combined Chemotherapy Protocols↗

Electrophysiologic testing techniques for children.

This practical article for clinical electrophysiologists discusses the evaluation of infant and child patients' visual systems using electroretinographic (ERG), electrooculographic (EOG), and visually evoked potential (VEP) techniques. These techniques not only help to secure specific diagnoses, but by systematic assessment of function along the visual pathways can also localize dysfunction underlying visual deficits of pediatric patients. Among children, development as well as disease can affect electrophysiological parameters. Therefore diagnosis of normal or abnormal depends critically on an adequate description of normal responses for age. Procedures that the authors have found feasible, reliable, and valid are summarized. Standardization of pediatric testing appears to be an important next step. The power of ERG, EOG and VEP recordings to demonstrate the neurophysiological basis for pediatric visual impairment is predicted to stimulate further research in this area.

Adult↗

Psychophysical estimates of ocular media density of human infants.

The ocular media densities of eleven 10-week-old infants and of 10 adults were estimated from dark adapted thresholds measured using a two alternative forced choice preferential looking method. The estimated media density at 400 nm derived from these thresholds ranged from 0.55 to 1.00 (median 0.75) log units for infants, and from 1.35 to 1.69 (median 1.46) log units for young adults. This indicates media density increases significantly (0.71 log units) between infancy and adulthood. These data allow more complete specification of the retinal stimulus for quantitative analysis of infants' retinal function.

Adult↗

5-Fluorouracil by protracted venous infusion. A review of current progress.

5-Fluorouracil (5FU) administered by prolonged intravenous infusion may more effectively treat advanced, slow-growing tumors with low growth fractions and long doubling times. Protracted infusion provides continual cancer cell exposure to 5FU; limitations due to cell cycle specificity and a short plasma half-life are theoretically circumvented. Advances in catheter composition and pump technology now make ambulatory infusion therapy widely available. Clinical trials suggest that prolonged infusion may improve the response rate in colorectal cancer. In addition, preliminary results suggest clinical activity against gastric, pancreatic and refractory breast cancers with minimal toxicity. Despite the potential logistic problems of infusion chemotherapy, many patients report improved quality of life. Increased costs incurred from infusion therapy are probably justifiable if survival is prolonged and quality of life maintained.

Catheterization↗

Pneumatosis intestinalis in bone-marrow transplantation patients: diagnosis on routine chest radiographs.

We report seven cases of pneumatosis intestinalis that was initially detected on routine chest radiographs made in adult bone-marrow transplantation patients. The cases were collected over a 13-month period. The chest radiographs generally underestimated the extent of the pneumatosis, as subsequently seen on plain abdominal films. However, the portions of bowel most extensively involved were those seen on the chest radiographs (transverse colon, hepatic and splenic flexures, stomach). One patient had pneumoperitoneum also. Pneumatosis developed within 6-293 days after transplantation. The cause of pneumatosis intestinalis was multifactorial. Three patients were asymptomatic. Clinical management of all seven patients was altered because of the detection of pneumatosis. The dose of steroids was increased in three patients to treat graft-vs-host disease, antibiotic drugs were given to three patients for enteric pathogens, and bowel rest was prescribed for one patient with mucosal injury from intense chemotherapy and radiation therapy. These cases show that the chest radiograph makes early diagnosis of pneumatosis intestinalis possible in posttransplantation patients.

Adult↗

Dark adaptation in hyperprolactinemic women.

In a study to test the hypothesis that hyperprolactinemia is caused by subclinical zinc deficiency, dark-adaptation curves of seven women with primary hyperprolactinemia and seven normal women were measured to assess tissue zinc status. Although plasma zinc levels, final dark-adapted thresholds, and the time courses of rod dark-adaptation did not differ significantly between patients and normal subjects, the median cone plateau of the hyperprolactinemic patients was significantly higher (0.66 log units) than that of normal subjects. It appears unlikely that derangements of vitamin A metabolism, for which zinc is a cofactor, explains this unanticipated and subtle abnormality in dark adaptation of the hyperprolactinemic women.

Adult↗

Computerized tomography in metastatic evaluation.

A case is presented in which a radionuclide liver-spleen scan suggested multiple space-occupying lesions compatible with multiple metastases. Computed axial tomography, however, demonstrated more generalized hypodensity without focal defects, and liver biopsy confirmed the presence of fatty infiltration and cirrhosis. The sensitivity and specificity of liver spleen scans and computed axial tomography scans compared to liver biopsy are reviewed. In the evaluation of hepatic metastases, computed axial tomography scanning should be the diagnostic imaging procedure of choice.

Aged↗

Visual acuities and dark-adapted thresholds of children with Bardet-Biedl syndrome.

We studied the visual acuities and dark-adapted sensitivities of 12 children with Bardet-Biedl syndrome. All except one child, who was seen only once, were tested serially. In the first decade of life, all visual acuities were within 2 octaves of normal. All but two final visual acuities obtained from patients in their second and third decades were more than 2 octaves poorer than normal. Dark-adapted sensitivities of all patients were, or became, significantly less than normal even in those patients whose period of follow-up was limited to the first decade of life. Of the 11 patients measured serially, seven showed decreases in dark-adapted sensitivities of at least 0.5 log unit during the follow-up period, and the last measured sensitivities of all patients were at least 2 log units less than the normal mean.

Child, Preschool↗

The relation of rhodopsin and scotopic retinal sensitivity in sector retinitis pigmentosa.

We used reflection retinal densitometric, psychophysical, and electroretinographic techniques to study the scotopic retinal function of a mother and her three daughters who had clinical evidence of a sectoral type of retinitis pigmentosa. Retinal regions with, and those without, ophthalmoscopic signs of degeneration were investigated. During dark adaptation, the time courses of rhodopsin regeneration and recovery of scotopic sensitivity were similar to normal as was the relation of rhodopsin to scotopic threshold. In dark-adapted eyes, threshold increases were not proportional to rhodopsin loss. The results of psychophysical tests of background adaptation and temporal summation, and analysis of the relation of electroretinographic a- to b-wave amplitudes, led to the conclusion that abnormalities of photoreceptor cell function central to the rhodopsin-bearing outer segments accounted for the increased thresholds.

Adult↗