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Biomedical subjects

N Anderson

Publications and source records attributed to N Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Severe acute bovine viral diarrhea in Ontario, 1993-1995.

In 1993, noncytopathic bovine viral diarrhea virus (BVDV) strains with enhanced virulence caused unprecedented outbreaks of severe acute bovine viral diarrhea (BVD) in dairy, beef, and veal herds in Ontario (Canada). Fever, pneumonia, diarrhea, and sudden death occurred in all age groups of cattle. Abortions often occurred in pregnant animals. Gross lesions in the alimentary tract were similar to those associated with mucosal disease, especially in animals >6 months of age. Cattle of all age groups had microscopic lesions in the alimentary tract similar to those seen with mucosal disease. The epidemic peaked in the summer of 1993, with 15% of all bovine accessions from diseased cattle presented to the diagnostic laboratory being associated with BVDV. The virus strains involved in the outbreak were analyzed using monoclonal and polyclonal antibodies and the polymerase chain reaction. The virus isolates from these outbreaks of severe disease were determined to be type 2 BVDV. Type 2 BVDV has been present in Ontario at least since 1981 without causing widespread outbreaks of severe acute BVD, which suggests that type 2 designation in itself does not imply enhanced virulence. Cattle properly vaccinated with type 1 BVDV vaccines appear to be protected from clinical disease.

Abortion, Veterinary↗
PubMed1998

Improved detection of infection in hip replacements. A currently underestimated problem.

Our aim was to determine if the detection rate of infection of total hip replacements could be improved by examining the removed prostheses. Immediate transfer of prostheses to an anaerobic atmosphere, followed by mild ultrasonication to dislodge adherent bacteria, resulted in the culture of quantifiable numbers of bacteria, from 26 of the 120 implants examined. The same bacterial species were cultured by routine microbiological techniques from only five corresponding tissue samples. Tissue removed from 18 of the culture-positive implants was suitable for quantitative tissue pathology and inflammatory cells were present in all samples. Furthermore, inflammatory cells were present in 87% of tissue samples taken from patients whose implants were culture-negative. This suggests that these implants may have been infected by bacteria which were not isolated by the techniques of culture used. The increased detection of bacteria from prostheses by culture has improved postoperative antibiotic therapy and should reduce the need for further revision.

Acetabulum↗
PubMed1997

Dose intensity for bolus versus infusion chemotherapy administration: review of the literature for 27 anti-neoplastic agents.

PROBLEM: The dose intensity (DI) and the maximum tolerated dose (MTD) of anti-neoplastic agents is assumed to be a critical factor for achieving optimal therapeutic benefit. Each of these factors may be influenced by the schedule of drug administration, specifically infusional or bolus delivery. OBJECTIVE: To review the literature for selected antineoplastic drugs to analyze the relative DI and MTD for bolus vs. infusional administration schedules. METHODS: Clinical reports of bolus and infusional delivery of chemotherapeutic drugs in the categories of antimetabolites; alkylating agents; antibiotics; plant alkaloids and platinum analogues were collected focusing on phase I studies establishing the MTD per cycle and the DI. Infusional schedules were defined as continuous parenteral administration for more than 24 hours or, in some instances, daily bolus dosing for one hour for 3 to 5 days. Bolus schedules were defined as administration over minutes up to 24 hours and also included daily dosing in some cases. RESULTS: For antimetabolites, the infusional schedule generally decreases the MTD and DI relative to bolus administration but for 5-FU, the MTD and DI both increase. For alkylating agents and the platinum analogues, the MTD and DI for bolus and infusional delivery are generally comparable; but infusional administration results in a slightly increased MTD for thiotepa and for ifosfamide, the MTD is increased depending upon the duration of the infusion. For the antibiotics and the plant alkaloids, the MTD and DI of infusional administration is variable related to the specific agent and the infusion duration and may be increased, decreased or comparable to the MTD of bolus schedules. CONCLUSIONS: The MTD and DI for most cytotoxic agents administered by bolus versus infusional schedules is unpredictable and variable and is influenced by the infusion duration and the interval between treatment cycles (for example three versus four week intervals). The MTD and DI increase substantially with infusional delivery for thiotepa, 5-FU and VM26 (the latter in leukemia specifically) and decrease substantially for the antimetabolites FUDR, ara-C, methotrexate and 6MP. For most other agents and in all four drug categories, the MTD and DI are relatively comparable although for ifosfamide and topotecan, the duration of infusion determines whether the MTD and DI increases, decreases or stays the same relative to bolus administration. The use of cytokines may substantially change the MTD and DI especially for bolus administration since dose limiting toxicity is hematologic for many agents.

Antineoplastic Agents↗
PubMed1997

Effects of phosphodiesterase inhibitors on human lung mast cell and basophil function.

1. The non-hydrolysable cyclic AMP analogue, dibutyryl (Bu2)-cyclic AMP, inhibited the stimulated release of histamine from both basophils and human lung mast cells (HLMC) in a dose-dependent manner. The concentrations required to inhibit histamine release by 50% (IC50) were 0.8 and 0.7 mM in basophils and HLMC, respectively. The cyclic GMP analogue, Bu2-cyclic GMP, was ineffective as an inhibitor of histamine release in basophils and HLMC. 2. The non-selective phosphodiesterase (PDE) inhibitors, theophylline and isobutyl-methylxanthine (IBMX) inhibited the IgE-mediated release of histamine from both human basophils and HLMC in a dose-dependent fashion. IBMX and theophylline were more potent inhibitors in basophils than HLMC. IC50 values for the inhibition of histamine release were, 0.05 and 0.2 mM for IBMX and theophylline, respectively, in basophils and 0.25 and 1.2 mM for IBMX and theophylline in HLMC. 3. The PDE 4 inhibitor, rolipram, attenuated the release of both histamine and the generation of sulphopeptidoleukotrienes (sLT) from activated basophils at sub-micromolar concentrations but was ineffective at inhibiting the release of histamine and the generation of both sLT and prostaglandin D2 (PGD2) in HLMC. Additional PDE 4 inhibitors, denbufylline, Ro 20-1724, RP 73401 and nitraquazone, were all found to be effective inhibitors of mediator release in basophils but were ineffective in HLMC unless high concentrations (1 mM) were employed. 4. Neither 8-methoxymethyl IBMX (PDE 1 inhibitor), zaprinast (PDE 5 inhibitor) nor a range of PDE 3 inhibitors (siguazodan, SKF 94120, SKF 95654) were effective inhibitors of mediator release from either basophils or HLMC. 5. In basophils, rolipram acted to potentiate the inhibitory effects of the adenylate cyclase activator, forskolin, whereas in HLMC, rolipram failed to potentiate the inhibitory effects of forskolin. 6. Extracts of purified HLMC and basophils hydrolysed cyclic AMP. IBMX (100 microM) inhibited the PDE activity in basophil extracts by 67 +/- 7% (P < 0.0001) and in HLMC extracts by 63 +/- 9% (P < 0.0005). The hydrolysis of cyclic AMP by basophil extracts was inhibited by the selective PDE inhibitors (all at 10 microM), rolipram (56 +/- 8%, P < 0.0001) and the mixed PDE 3/4 inhibitor, Org 30029 (47 +/- 9%, P < 0.01), whereas 8-methoxymethyl IBMX, siguazodan and zaprinast were ineffective. In HLMC, rolipram, Org 30029, 8-methoxymethyl IBMX, siguazodan and zaprinast all inhibited the hydrolysis of cyclic AMP by extracts to a significant (P < 0.05) and similar extent (approximately 25% inhibition at 10 microM). 7. In total, these data suggest that modulation of the PDE 4 isoform can regulate basophil responses whereas an association of the PDE 4 isoform with the regulation of HLMC function remains uncertain.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Cerebellar vermis measurement at cranial sonography for assessing gestational age in the newborn weighing less than 2000 grams.

Prognosis of the very low birth weight infant depends more on gestational age than birth weight, but clinical assessment of gestational age of very low birth weight infants is inaccurate. We wished to determine how well cerebellar vermis dimensions might predict gestational age in infants of birth weight less than 2000 g. We obtained suitable midline sagittal images of the cerebellar vermis at cranial sonography, performed via the anterior or posterior fontanelle, in 41 infants, from the regional neonatal intensive care unit whose gestational age was known. We measured the cerebellar vermis area and diameter on the hard-copy image provided the margins of the vermis were clearly visible, the cerebellar tonsils were excluded from the image, and the anterior and posterior divisions of the corpus medullare were visible on the image. Vermis diameter was measured from the base of the fourth ventricle to the junction of folium and tuber vermis. Vermis area was calculated using a stereological method using a test system of regularly spaced points randomly placed over a magnified image of the cerebellar vermis. We generated regression equations for estimating gestational age using combinations of birth weight, vermis area, or vermis diameter for the 26 infants with birth weight of less than 2000 g for whom the cerebellar vermis measurements were obtained within one week of birth. Vermis area and diameter correlated very highly. They both can be used for predicting gestational age. The addition of either vermis area or diameter to birth weight improves accuracy of gestational age assessment. If birth weight was presumed to be unknown, cerebellar vermis area or diameter allow prediction of gestational age to within +/- 1.3 weeks (1 standard error) or +/- 2.5 weeks, using a 95% prediction interval. If the same method of reporting is applied to the New Ballard Score, the New Ballard Score predicts gestational age +/- 1.7 weeks (1 standard error) or +/- 3.4 weeks, using a 95% prediction interval.

Birth Weight↗
PubMed1996

The effects of alcohol consumption on laboratory-induced panic and state anxiety.

BACKGROUND: This study tested whether alcohol consumption reduces anxiety and panic associated with a panic-challenge procedure. METHODS: Subjects with panic disorder were randomly assigned to consume either a moderate dose of alcohol or a nonalcoholic placebo. All subjects were told that they were drinking alcohol to control beverage expectancies. Following the beverage administration, subjects underwent a panic challenge (35% carbon dioxide) and a series of anxiety symptom assessments. RESULTS: Subjects who consumed alcohol reported significantly less state anxiety both before and after the challenge. In response to the challenge, subjects who consumed alcohol experienced significantly fewer panic attacks when applying liberal panic criteria; however, this effect only approached significance when applying conservative panic criteria. CONCLUSIONS: These findings suggest that alcohol acts acutely to reduce both panic and the anxiety surrounding panic, and they lend support to the view that drinking behavior among those with panic disorder is reinforced by this effect. We suggest that this process may contribute to the high rate at which alcohol-use disorders co-occur with panic disorder.

Adult↗
PubMed1996

Effect of supplemental L-arginine in a chemical-induced model of colorectal cancer.

L-Arginine inhibits the development of spontaneous, transplantable solid tumors and chemically induced mammary tumors. The aim of the present study was to investigate the effect of l-arginine on chemically induced colorectal cancer in male Wistar rats. Colorectal cancer was induced in all animals by weekly subcutaneous injections of the colonic procarcinogen 1,2-dimethylhydrazine (DMH) at a dosage of 20 mg/kg body weight. Arginine was given in a 1% solution of drinking water. Group I was the DMH control; group II, arginine for 22 weeks; group III, arginine for the first 10 weeks only. Lymphocyte function was evaluated by measuring the thymic lymphocyte proliferative response to the T cell mitogen phytohemagglutinin. The results show that tumor incidence and tumor burden (tumors/rat and tumors/tumor-bearing rat) were significantly reduced in both groups of animals receiving arginine compared to DMH controls (p < 0.05). The tumor areas and volumes were also reduced in both arginine groups (p < 0.05). Thymic lymphocyte stimulation indices were significantly increased by arginine supplementation (p < 0.05). These results would be in keeping with the reduction in colorectal tumor production due to a "nonspecific" stimulation of the host immune system by L-arginine.

1,2-Dimethylhydrazine↗
PubMed1996

Pilot study of ambulatory infusional delivery of a multidrug regimen: ifosfamide, carboplatin and etoposide (ICE).

PURPOSE: To determine the feasibility for administering ICE (ifosfamide, carboplatin, and etoposide) using an ambulatory infusional schedule for each of the three agents in a design that sequentially alternates those agents that are not compatible as an admixture. PATIENTS AND METHODS: Forty-one patients received ICE administered as follows: ifosfamide (500 mg/M2/day) without mesna days 1 to 7 and 14 to 21; carboplatin (30 or 40 mg/M2/day) and etoposide (30 to 40 mg/M2/day) admixed as a single solution infused day 7 to 14. Patients were monitored weekly and cycles repeated at five-week intervals. RESULTS: Seventy-nine courses of therapy were analyzed. Forty-one patients received a median of two cycles with a range of one to five cycles. The only significant toxicity was hematologic with 11 patients experiencing grade III neutropenia and 7 patients grade III thrombocytopenia (18%). Eleven patients did develop significant anemia requiring transfusion and/or the use of erythropoietin. Tumor responses were observed in 7 of 24 evaluable patients, 4 of whom had lung cancer, 2 with small cell with no prior therapy and 2 with nonsmall cell with prior chemotherapy. CONCLUSION: Ambulatory infusion of ICE using an alternating sequence is feasible, and although the dose per cycle of carboplatin and etoposide is less than that of conventional bolus schedules for either single agent or combination programs, the ability to deliver this combination of agents in an ambulatory setting and without mesna substantially reduces the cost. Phase II studies of ambulatory infusion ICE in nonsmall cell lung cancer, lymphoma, and sarcoma are a reasonable next step.

Adenocarcinoma↗
PubMed1996

Pilot study of ambulatory infusional delivery of a multidrug regimen: cisplatin, 5-fluorouracil and leucovorin (PFL) +/- etoposide.

PURPOSE: To determine the feasibility of ambulatory infusional administration 24 hours per day, 7 days per week of a three-drug regimen of cisplatin or carboplatin, leucovorin, and 5-fluorouracil (5-FU) (PLF) utilizing an alternating weekly sequential design and to introduce infusional etoposide as PLEF to the regimen. PATIENTS AND METHODS: Forty-three patients with diverse malignancies received a sequential infusion of 5-FU 200 mg/M2/day on days 1 to 14 and 21 to 35 with leucovorin admixed for day 1 to 7 and 21 to 28. Cisplatin (20 patients) or carboplatin (23 patients) infusion was administered at a dose of 10 mg/M2/day or 30 mg/M2/day, respectively, day 7 to 14 and 35 to 42. Cycles were planned to be repeated consecutively in the absence of toxicity in patients with stable or responding disease. Sixteen patients also received etoposide 30 mg/M2/day as an admixture concomitant with administration of the platinum analogue. Therefore, the distribution of therapies was PLF 19, CLF 8, PLEF 14, and CLEF 2. RESULTS: A total of 63 courses of PLF +/- E was administered as outlined above. Hematologic toxicity was minimal with or without the addition of etoposide. Sixteen percent of patients developed an elevated creatinine with a median of 1.6 and a range of 1.6 to 3.2 mg %. Tumor responses were observed in seven of fourteen evaluable patients with squamous cell carcinoma of the lung (all of whom received concomitant etoposide). In addition, one patient with metastatic gallbladder cancer achieved a complete clinical response. CONCLUSION: Ambulatory infusional PLF with carboplatin or cisplatin using sequentially alternating delivery of the component antineoplastic agents is feasible and active with minimal toxicity. The addition of infusional etoposide to the PLF regimen does not substantially increase hematologic toxicity. Extended phase II studies in aerodigestive cancers are ongoing and a phase III trial comparing this ambulatory regimen to short-term PLF infusion (5-day) may be justified to compare the relative cost and benefits of the two schedules.

Adult↗
PubMed1995

Overexpression of the tumour suppressor gene p53 is not implicated in neuroendocrine tumour carcinogenesis.

The tumorigenesis of neuroendocrine tumours remains poorly understood, although a minority, the familial multiple endocrine neoplasia (MEN 1 and MEN 2), are known to be of uncommon genetic origin. Mutation of the tumour suppressor gene, p53, is now known to be a common genetic alteration in about half of all types of non-endocrine cancers. In the present study, immunocytochemistry using the monoclonal anti-p53 antibody, DO-7, has been employed to investigate the accumulation of p53 immunoreactivity in a wide range of primary neuroendocrine tumours. Tumours (n = 109) were fixed and processed to paraffin wax according to a constant protocol. Sections were subjected to microwave antigen retrieval prior to immunostaining for p53. Positive nuclear immunostaining was observed in one medullary carcinoma of the thyroid (MCT), one lung carcinoid, and five small cell carcinomas of the lung (SCCL). All other tumour samples were consistently negative. As the neoplasia investigated in this study comprised a wide spectrum of neuroendocrine tumour types and ranged from minute, relatively benign lesions to malignant metastasizing disease and as there was no relationship between the presence of p53 overexpression and clinico-pathological features, the present study suggests that p53 gene mutation may be relatively unimportant in the genesis of neuroendocrine tumours.

Antibodies, Monoclonal↗
PubMed1995

Ulnar club-hand and constriction-ring syndrome.

An infant presented with ulnar club hand and constriction ring syndrome involving all four limbs. The former abnormality was diagnosed by ultrasound at 23 weeks gestation. This association has not been previously described.

Abnormalities, Multiple↗
PubMed1995

Use of pedicled fat pad graft as an adjunct in the reconstruction of palatal cleft defects.

The purpose of this article is to provide the rationale for the use of pedicled buccal fat pad grafts as an adjunct to the reconstruction of palatal or dentoalveolar clefts in cases when healing by secondary intention may need to be considered and integrated into the initial treatment plan because of the size of the defect or qualitative or quantitative tissue constraints. Four representative cases are presented in which a pedicled buccal fat graft was adjunctively used in conjunction with pedicled mucosal flaps to gain closure of large oroantral or oronasal cleft deformity.

Adipose Tissue↗