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Biomedical subjects

L A Hansen

Publications and source records attributed to L A Hansen.

138 records · Page 8Linked to original sources

Computer program for comparing total costs of intravenous antibiotic regimens.

A computer program for estimating and comparing the costs of intravenous antibiotic therapy is described, and a cost comparison of two antibiotic regimens using the program is demonstrated. Data unique to each antibiotic (e.g., dosage regimen, duration of therapy, need for pharmacokinetic monitoring, and acquisition cost per dose) are entered into the first part of the program (ABDATA) and combined with preprogrammed hospital-specific data, such as personnel and material costs, to produce an itemized list of the total cost of therapy. With the second part of the computer program (ABCOMP), antibiotic regimen costs that have been entered into ABDATA can be compared. Cost comparisons are made with the assumption that the antibiotic regimens have similar efficacy and toxicity. A sample cost comparison was performed using data from a recent study comparing the use of ceftazidime or tobramycin-ticarcillin therapy in the treatment of nosocomial pneumonia and bacteremia. The computer-generated cost comparison showed that although the unit cost of ceftazidime was more than the combined unit cost of tobramycin and ticarcillin, the total cost of a 10-day course of therapy with ceftazidime (which included personnel and material costs) was less than the cost of therapy with a combination of tobramycin and ticarcillin. A computer program that incorporates hospital-specific personnel and material costs with unit drug costs can be used to facilitate comparisons of the overall cost of intravenous antibiotic regimens.

Anti-Bacterial Agents↗

Isotretinoin teratogenicity. Case report with neuropathologic findings.

Isotretinoin, a drug used for the treatment of acne, has been shown to have teratogenic effects. We report an additional case of isotretinoin teratogenicity in which the patient had agenesis of the cerebellar vermis, multiple leptomeningeal neuroglial heterotopias, hydrocephalus, and abnormalities of the corticospinal tracts. These findings are related to those reported previously.

Abnormalities, Drug-Induced↗

Cost comparison of seven antibiotic combinations as empiric therapy in a simulated febrile neutropenic patient.

Total costs, drug and supply costs, and personnel costs for 14 days of therapy with seven therapeutically equivalent i.v. antibiotic combinations were calculated for a simulated febrile neutropenic patient. The cost for each antibiotic regimen was calculated using a previously developed computerized model that included the cost elements involved in preparation, administration, and pharmacokinetic monitoring of i.v. antibiotic therapy. Comparative costs for the seven antibiotic regimens were determined by inserting the costs of the individual elements into the model. Total costs for the 14 days of therapy varied greatly among the seven regimens, ranging from $908 to $2543. Antibiotics constituted the greatest percentage of total expenditures for each regimen (64-92%). Costs were increased substantially when a third-generation cephalosporin was included in the regimen. Antibiotic costs correlated strongly with total costs, while personnel costs correlated poorly with total costs and accounted for only 6-30% of the total expenditures. Computerized analysis of all costs involved in antimicrobial therapy for this simulated neutropenic patient showed that total costs varied widely in direct proportion to antibiotic costs. In selecting antimicrobial agents for high-risk patients, costs should be considered along with efficacy.

Agranulocytosis↗

Demyelination induced by serum from patients with Guillain-Barré syndrome.

Sera from 16 patients with acute Guillain-Barré syndrome (GBS) and 14 healthy control subjects were injected into rat sciatic nerve and assessed for demyelinating activity by electrophysiological and histological techniques. Only fresh GBS serum, and not GBS serum stored at -20 degrees C or -70 degrees C, blocked conduction to a significantly greater extent than did fresh control serum. Conduction block developed gradually, starting within 24 hours of injection and reaching a maximum between days 3 and 6. Recovery of conduction commenced thereafter, and conduction returned to normal by day 33. Quantitative histological studies on day 6 showed that fresh GBS serum produced significantly more widespread demyelination than did stored GBS serum (p less than 0.01). Stored GBS serum showed residual demyelinating activity when compared with fresh control serum (p less than 0.01). Fresh serum obtained from 4 patients after recovery from GBS did not produce conduction block, despite it having done so during the acute phase of the disease.

Animals↗

An immunohistochemical quantification of fibrous astrocytes in the aging human cerebral cortex.

In order to determine whether cortical fibrous astrocytes increase with age, we studied 25 patients ranging in age from 24 to 100 years with no clinical or pathological evidence of dementia or other cerebral disorder. Paraffin sections of mid-frontal cortex were obtained and stained with the avidin-biotin immunolabeling procedure for glial intermediate filament protein. The resulting immunolabeled fibrous astrocytes were then counted in the molecular and cellular (cortical laminae 2-6) layers. Populations of fibrous astrocytes in both layers varied widely among individuals, and in the molecular layer their numbers were not significantly correlated with advancing age. In the cellular layer, however, despite widely ranging cell counts among individuals within the same decades of life, there was a significant linear increase with age. Our data suggest that the increase occurs or accelerates significantly after age 70, but the case numbers preclude reaching such a conclusion with statistical confidence. However, when the patients are divided into those less than 70 and those older, fibrous astrocytes in the cellular layer are shown to be significantly increased in the latter group compared to the former.

Adult↗

Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients.

Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients. Item scores from the Mattis Dementia Rating Scale (MDRS) and the Mini-Mental State Examination (MMSE) from 389 patients with probable Alzheimer's disease were submitted to principal component analysis with orthogonal rotation. The optimal solution identified four factors that reflected the cognitive domains of attention/registration, verbal fluency/reasoning, graphomotor/praxis and recent memory. A subgroup of patients was identified for whom both the MDRS and the MMSE had been administered within the 12 months before death. Scores were assigned to these patients for the four factors. These cognitive-domain scores were then correlated with postmortem choline acetyltransferase (ChAT) activity in the medial frontal cortex, inferior parietal cortex, and hippocampus. ChAT activity in both the medial frontal and the inferior parietal cortex significantly correlated with scores on the graphomotor/praxis factor. Medial frontal ChAT also correlated significantly with the attention/registration scores. Hippocampal ChAT correlated significantly only with recent memory scores. These results are consistent with current animal research regarding the effect of selective cholinergic lesions on behavior.

Aged↗

Position paper on diagnostic criteria for Alzheimer disease.

The lesions of Alzheimer disease (AD) consist of synapse and neuron loss associated with progressive deposition of amyloid as diffuse and neuritic plaques and accumulating tau abnormalities in the form of neurofibrillary tangles and neuropil threads. Diagnostic criteria for Alzheimer disease constitute arbitrary cut-off levels above which AD is deemed to exist, and below which lesser amounts of the same abnormalities are relegated to the nebulous category of aging changes. Demanding neocortical tangles for a diagnosis of AD sacrifices sensitivity on the altar of specificity, since, while such lesions usually represent an advanced stage in the orderly evolution of AD, lighter burdens of plaque-predominant AD pathology with tangles confined to the medial temporal lobe can cause dementia when associated with concomitant synapse loss. Such muted AD pathology typifies the Lewy body variant of AD, and it serves to segregate it from pure Lewy body disease. We endorse the semiquantitative neuritic-plaque based criteria from CERAD for routine diagnosis, and Braak staging with descriptive profiling of AD lesions in a research context.

Aged↗

TGF alpha is dispensable for skin tumorigenesis in Tg.AC mice.

Alterations in growth factor signaling pathways frequently accompany the development and maintenance of epithelial neoplasia. Transforming growth factor alpha (TGF alpha) and its epidermal growth factor receptor have been thought to play an especially important role in epithelial neoplasia. In this study, mice were derived genetically deficient (null) in functional TGF alpha expression and carrying the Tg.AC/v-Ha-ras transgene. The goals were to determine if (a) papillomagenesis was dependent on TGF alpha and (b) progression to malignancy was dependent on TGF alpha expression. Groups of male and female mice heterozygous or homozygous for the TGF alpha null allele and hemizygous for the Tg.AC transgene were treated twice weekly for 10 or 15 wk with doses of 12-O-tetradecanoylphorbol-13-acetate (TPA) known to produce papillomas in Tg.AC mice. Papillomas were readily induced in both male and female TGF alpha null mice. Malignant progression of papillomas was observed in all TGF alpha null treatment groups. Additionally, we examined the response of TGF alpha null mice to full thickness dorsal wounds, a stimulus known to promote papillomagenesis in Tg.AC mice. As in the TPA study, papillomas were induced in both male and female TGF alpha null mice. These studies indicate that TGF alpha is not required for the induction and maintenance of papillomas nor is it essential for the malignant conversion of papillomas in Tg.AC mice.

Animals↗

Treatment of gestational trophoblastic tumors.

A brief discussion of the definition, etiology, epidemiology, classification, and prognosis of the gestational trophoblastic tumor (GTT) is presented. Current therapeutic options are summarized. GTTs arise from fetal tissues and can be divided into three histologic categories, hydatidiform mole, chorioadenoma destruens, and choriocarcinoma. Clinically, it is classified as nonmetastatic, metastatic-low risk, or metastatic-high risk. Diagnosis is based on clinical signs and symptoms, ultrasound and X-ray examinations, and the presence of elevated serum levels of the B-subunit of human chorionic gonadotropin (hCG). Primary therapy for hydatidiform mole is evacuation of the uterine contents. Prophylaxis for metastases with actinomycin D sometimes is performed, but generally is not recommended. For persistent disease that is classified as nonmetastatic or low-risk metastatic, a methotrexate-leucovorin rescue protocol is preferred, with actinomycin D used in patients who show resistance to the regimen. Standard therapy for high-risk metastatic disease involves triple agent therapy with methotrexate, actinomycin D, and chlorambucil, but toxicity is significant. Other alternatives include the modified Bagshawe protocol, a VBC (vinblastine, bleomycin, cisplatin) regimen, cisplatin in combination with vincristine and high-dose methotrexate, and VP16-213 (etoposide) in combination with other agents. Other treatment modalities include radiation and surgery. Use of the most appropriate therapies can maximize the survival of a patient with gestational trophoblastic disease.

Adult↗

Cost comparison of ceftazidime versus tobramycin/ticarcillin therapy in three hospitals.

A retrospective review of 114 patient charts was conducted at three geographically different hospitals to compare the costs of ceftazidime (CTZ) with the combination of tobramycin and ticarcillin (T/T) in the treatment of hospital-acquired pneumonias and/or septicemias. Variables analyzed to determine the cost of the therapy included duration of treatment, dosage and number of doses administered, side effects, and laboratory tests. Time and motion studies were also performed and the results included in the algorithm. In two of the three hospitals, the computer-calculated cost of CTZ therapy was significantly less than for T/T therapy ($1194 vs. $1668 and $93 vs $629). In the third hospital there was no significant difference in the costs of the two treatments ($1079 for CTZ vs. $1066 for T/T). The cost of each regimen per patient day followed a similar pattern, with CTZ therapy being significantly less expensive in the same two hospitals. Patients receiving CTZ therapy realized an average cost savings of $29.70 per day at the three institutions. These savings appeared to be due to a reduction in laboratory and administration costs resulting from the decreased frequency of CTZ administration. We conclude that CTZ therapy was less costly than T/T therapy at three geographically different institutions when the cost of supplies, laboratory tests, and personnel time were taken into account.

Ceftazidime↗