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Biomedical subjects

A M Davis

Publications and source records attributed to A M Davis.

At least 73 records · Page 4Linked to original sources

Treatment of giant-cell tumors of long bones with curettage and bone-grafting.

BACKGROUND: The use of curettage, phenol, and cement is accepted by most experts as the best treatment for giant-cell tumor of bone. The present study was performed to evaluate whether equivalent results could be obtained with curettage with use of a high-speed burr and reconstruction of the resulting defect with autogenous bone graft with or without allograft bone. METHODS: The prospectively collected records of patients who had a giant-cell tumor of a long bone were reviewed to determine the rate of local recurrence after treatment with curettage with use of a high-speed burr and reconstruction with autogenous bone graft with or without allograft bone. All of the patients were followed clinically and radiographically, and a biopsy was performed if there were any suspicious changes. RESULTS: Fifty-nine patients met the criteria for inclusion in the study. According to the grading system of Campanacci et al., two patients (3 percent) had a grade-I tumor, twenty-nine (49 percent) had a grade-II tumor, and twenty-eight (47 percent) had a grade-III tumor. Seventeen patients (29 percent) had a pathological fracture at the time of presentation. The mean duration of follow-up was eighty months (range, twenty-eight to 132 months). Seven patients (12 percent) had a local recurrence. Six of these seven were disease-free at the latest follow-up examination after at least one additional treatment with curettage or soft-tissue resection (one patient). One patient had resection and reconstruction with a prosthesis after a massive local recurrence and pulmonary metastases. CONCLUSIONS: Despite the high rates of recurrence reported in the literature after treatment of giant-cell tumor with curettage and bone-grafting, the results of the present study suggest that the risk of local recurrence after curettage with a high-speed burr and reconstruction with autogenous graft with or without allograft bone is similar to that observed after use of cement and other adjuvant treatment. It is likely that the adequacy of the removal of the tumor rather than the use of adjuvant modalities is what determines the risk of recurrence.

Adolescent↗

Evaluation of the allograft-prosthesis composite technique for proximal femoral reconstruction after resection of a primary bone tumour.

OBJECTIVE: To evaluate clinical and functional outcomes resulting from the allograft-composite technique used for proximal femoral osteoarticular reconstruction in patients who had limb salvage surgery for primary bone tumours. DESIGN: A retrospective review of a prospectively gathered database to provide a descriptive study. SETTING: A tertiary care musculoskeletal oncology unit in a university hospital. PATIENTS AND INTERVENTIONS: Patients treated between 1987 and 1993 were eligible for inclusion in this study if they met the following criteria: they were treated surgically for a primary malignant bone tumour; and a proximal femoral allograft-implant composite technique was used for the reconstruction. MAIN OUTCOME MEASURES: Major postoperative complications with emphasis on mechanical complications in the reconstructive composite implant. Functional outcome in a subset of patients using the 1987 and 1994 versions of the Musculoskeletal Tumor Society instrument, the Short-Form-36 and the Toronto Extremity Salvage Score. RESULTS: There were 5 mechanical and 2 infectious complications requiring surgical intervention. Functional scores were generally low. CONCLUSIONS: Our results suggest that the perceived benefits of the composite technique may accrue only to a few patients, partly owing to the risk of mechanical complications. Although these can be reduced by avoiding the use of cement in the host femur, the generally poor functional outcomes suggest that this technique needs to be studied further in this group of patients and compared with other reconstructive techniques, particularly the prosthetic implant.

Adult↗

d-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia.

Previous in vitro and in vivo studies have determined that the d isomer of methadone has N-methyl-D-aspartate (NMDA) receptor antagonist activity. The present studies examined the ability of d-methadone to attenuate the development of morphine tolerance in mice and rats and to modify NMDA-induced hyperalgesia in rats. A decrease in the percentage of mice analgesic (tail-flick response) after 5 days of once-daily morphine (7 mg/kg s.c.) was completely blocked by coadministration of d-methadone given s.c. at 10 mg/kg. Morphine given s.c. to mice on an escalating three times per day dosing schedule resulted in a nearly 3-fold increase in the tail-flick ED50 dose of morphine which was prevented by s.c. coadministered d-methadone at 15 mg/kg. In rats, intrathecal (i.t.) morphine produced a 38-fold increase in the ED50, which was completely prevented by the coadministration of i.t. d-methadone at 160 micrograms/rat. A decrease in thermal paw withdrawal latency induced by the i.t. administration of 1.64 micrograms/rat NMDA was completely blocked by pretreatment with 160 micrograms/rat d-methadone. Thus, systemically coadministered d-methadone prevents systemically induced morphine tolerance in mice, i.t. d-methadone attenuates tolerance produced by i.t. morphine in rats, and i.t. d-methadone, at the same dose which modulates morphine tolerance, blocks NMDA-induced hyperalgesia. These results support the conclusion that d-methadone affects the development of morphine tolerance and NMDA-induced hyperalgesia by virtue of its NMDA receptor antagonist activity.

Analgesics, Opioid↗

Doxorubicin-cisplatin chemotherapy for high-grade nonosteogenic sarcoma of bone. Comparison of treatment and control groups.

OBJECTIVE: To evaluate the role of chemotherapy with a combination of doxorubicin (adriamycin) and cisplatin in high-grade, nonosteogenic, non-Ewing's sarcoma (non-OSA) of bone. DESIGN: A case series comparison with a literature-derived control group. SETTING: A university-affiliated tertiary care centre. PATIENTS: Thirty patients with a diagnosis of non-OSA. Of these, 8 had low-grade disease (grade 1 or 2) and 22 had high-grade disease (grade 3). Eleven of the 22 with high-grade disease had malignant fibrous histiocytoma. Seventeen patients with nonmetastatic high-grade non-OSA were compared with a literature cohort of 37 patients who met the eligibility criteria of nonmetastatic, high-grade non-OSA treated with surgery, with or without radiotherapy. The mean follow-up was 25.2 months. INTERVENTIONS: Eight patients with low-grade tumour underwent surgery alone; 22 patients with high-grade tumour underwent surgery and 6 courses of adriamycin (75 mg/m2 every 3 weeks) and cisplatin (100 mg/m2 every 3 weeks). MAIN OUTCOME MEASURES: Disease-free survival and overall survival in those with high-grade tumours treated with or without chemotherapy. RESULTS: Of 8 patients who had low-grade tumours and underwent surgery alone, 3 had systemic relapse. Of the 22 having high-grade tumours, 4 did not receive chemotherapy because of age and comorbid conditions. Of the other 18, 13 received 3 courses of chemotherapy preoperatively and 3 courses postoperatively, 4 received all 6 courses postoperatively and 1 received all chemotherapy preoperatively to treat metastatic disease. In the 17-patient cohort used for comparison with the literature control group, disease-free survival was 57% at a mean follow-up of 25.6 months and overall survival was 57% at a mean follow-up of 30.1 months. In the control group, disease-free survival was 16% at a mean follow-up of 20.9 months and overall survival was 26% at a mean follow-up of 29.9 months. These differences are significant: p = 0.0000, chi 2 = 41.61 for disease-free survival and p = 0.0000, chi 2 = 46.49 for overall survival. CONCLUSIONS: The findings of this study support the use of adjuvant chemotherapy in patients with high-grade non-OSA, in whom malignant fibrous histiocytoma was the predominant histologic subtype.

Adolescent↗

Evaluating functional outcome in patients with lower extremity sarcoma.

The Short Form 36, The Toronto Extremity Salvage Score, and the 1987 and 1993 Musculoskeletal Tumor Society Rating Scales were compared as measures of functional status for patients with lower extremity sarcoma. The study included 97 patients with lower extremity sarcoma and evaluated each measure on the following measurement properties: conceptual framework; statement of the purpose; feasibility; breadth of content; depth of measurement; cross sectional and longitudinal reliability; and validity and responsiveness. The Short Form 36 represents patients' perceptions of their physical and mental health and is practical to use. However, the validity of the measure is questionable for the patients with sarcoma because the subscale structure could not be reproduced in the current data. The Toronto Extremity Salvage Score meets all standards of measurement with the exception of breadth of content as it measures only physical function. The 1987 and 1993 Musculoskeletal Tumor Society scales do not meet the standards of measurement. In choosing an outcome measure for the extremity sarcoma population, the Toronto Extremity Salvage Score has superior measurement properties when compared with the Short Form 36 or the 1987 and 1993 Musculoskeletal Tumor Society scales. The Toronto Extremity Salvage Score is a reliable and efficient measure for monitoring patients and for use in clinical trials.

Adolescent↗

The effect of ionic strength on liposome-buffer and 1-octanol-buffer distribution coefficients.

The distribution of salmeterol and proxicromil between unilamellar vesicles of dioleoylphosphatidylcholine (DOPC) and aqueous buffer at pH 7.4 has been studied, using an ultrafiltration method, as a function of compound concentration, DOPC concentration, and buffer ionic strength. The binding of these ionized lipophilic compounds to neutral DOPC vesicles induces a surface charge, which causes the observed membrane distribution coefficient D(mem)obs to vary significantly with bound compound to DOPC ratio and with ionic strength. This variability is shown to be well-described with use of the Gouy-Chapman theory of the ionic double layer and is contrasted with the ideal behavior shown by the neutral compound clofibrate. Increasing ionic strength is also shown to increase the observed 1-octanol-buffer distribution coefficients D(o/w)obs of proxicromil but through a very different mechanism involving the extraction of ion pairs. This study highlights the experimental difficulty in determining concentration-independent liposome distribution coefficients of ionized lipophilic compounds and describes when deviations will be significant and how observed values may be corrected for such effects. The general effect of ionic strength on membrane-buffer distribution and 1-octanol-buffer distribution is discussed with particular reference to the very different propensity for ion pair formation shown by the two systems, and the most suitable experimental conditions that should be used with each system.

1-Butanol↗

The long QT syndrome and seizures in childhood.

Children with the long QT syndrome (LQTS) are prone to life threatening ventricular arrhythmias. These arrhythmias may result in syncope and seizures that are often attributed incorrectly to a seizure disorder or to common fainting. The untreated mortality for symptomatic children with the LQTS is high but is improved significantly with therapy. Paediatricians should be aware of the presentations of the syndrome. Recommendations for screening for the syndrome are given.

Child↗

Hypocaloric oral therapy during an episode of diarrhea and vomiting can lead to severe malnutrition.

BACKGROUND: Malnutrition associated with diarrhea and vomiting can be prevented if the focus of treatment is on nutritional requirements. Some pediatricians inappropriately continue to recommend clear liquids followed by dilute feedings or hypocaloric diets until the diarrhea clears. METHODS: Medical records were retrospectively reviewed, and the literature was reviewed. RESULTS: Severe malnutrition occurred in two children with diarrhea and vomiting who were treated with clear liquids followed by restricted nutrient intake. CONCLUSION: Severe malnutrition associated with diarrhea and vomiting can occur when the prescribed treatment is bowel rest followed by hypocaloric diets until diarrhea clears. Malnutrition can be prevented if the focus of treatment is on nutritional requirements. Current American Academy of Pediatrics recommendations for treatment of diarrhea and vomiting are discussed.

Child, Preschool↗

Function after subtotal scapulectomy for neoplasm of bone and soft tissue.

We describe the functional results in 14 patients (7 men, 7 women) after subtotal scapulectomy for primary bone and soft-tissue tumours at a specialist musculoskeletal oncology unit. Eight had chondrosarcomas, two Ewing's sarcomas, one aggressive fibromatosis and three soft-tissue sarcomas. The mean follow-up was 52 months (6 to 120). Analysis of residual symptoms and of range and strength of movement by physicians used the Musculoskeletal Tumour Society rating scale (MSTS). Physical disability was measured by the patients using the Toronto Extremity Salvage Score (TESS). All 14 patients are still alive, two with systemic disease. Nine had more than 80% of their scapula resected but the glenohumeral joint was preserved in all cases. Eight had full movement and another two achieved 90 degrees of flexion. The mean functional results were good to excellent in all except three patients (mean MSTS = 71.6 and TESS = 79.9). Two of these three patients had considerable pain as a result of brachial neuropathy. Scapulectomy gives an excellent functional result if the glenohumeral joint is preserved. The rotator cuff could be removed without a severe functional deficit provided that the deltoid was reattached to the scapular remnant and the trapezius.

Adolescent↗

Alleles of the cholesterol 7 alpha-hydroxylase (CYP7) gene in pigs selected for high or low plasma total cholesterol.

Crossbred pigs were selected for high (HTC) or low (LTC) plasma total cholesterol (TC). Pigs from the seventh (n = 51) and eighth (n = 92) generations were used to determine restriction fragment length polymorphisms (RFLP). Using TaqI restriction enzyme digestion, the frequencies of two alleles (2.8- or 5.0-kb fragments) of the cholesterol 7 alpha-hydroxylase (CYP7) gene were determined in the two populations as a potential indicator of TC concentration at 8 weeks of age. Only the 2.8-kb fragment allele was present in the 26 HTC pigs tested in Generation 7. In the LTC pigs both the 2.8- and 5.0-kb alleles were present in 12 pigs, and only the 5.0-kb allele was present in 13 pigs. The allele frequencies of the 2.8 and 5.0 fragments, respectively, were .26 and .74 in LTC pigs and 1.00 and 0 in HTC pigs. There was an association (P < .001) between the 5.0- and 2.8-kb CYP7 alleles, respectively, and low and high TC concentrations. In Generation 8, all HTC pigs were homozygous for the 2.8-kb allele. The 5.0 kb allele was present in all LTC pigs tested and was homozygous in 57% of LTC pigs. Mean plasma TC was 105.0 mg/dl in 30 pigs homozygous for the 2.8-kb allele in Generation 8; means for LTC pigs were 53.5 and 60.4 mg/dl in 35 pigs homozygous for the 5.0-kb allele and in 27 heterozygous pigs, respectively. High TC was associated with the presence of the 2.8-kb allele, and low TC was associated with the presence of the 5.0-kb allele in both Generations 7 and 8. We conclude that TaqI RFLP analysis of the CYP7 gene is a reliable indicator for TC in these swine.

Alleles↗

Hindquarter amputation for pelvic tumors. The importance of patient selection.

Twenty-two patients underwent hindquarter amputation with curative intent for malignant or locally aggressive tumors of the pelvis (21 cases) or proximal thigh (one case). In all cases, the ilium was resected, and in seven cases an osteotomy of the sacrum was done to achieve negative surgical margins. Only six wounds healed without complications. The worst wound problems occurred in patients requiring ligation of the common iliac vessels and in those requiring a sacral osteotomy. Twelve patients have died of disease, two are alive with extensive pulmonary metastases, and one remains well after excision of a local tumor recurrence. Thirteen of 14 patients with high grade sarcoma had metastases develop, compared with only one of eight patients with low grade sarcoma. Eight patients (all with high grade sarcoma) died within 1 year of surgery. Seven patients have remained disease free at a mean of 39 months after surgery. Given the poor prognosis and high morbidity after amputation in high grade sarcoma, the authors think that consideration should be given to pursuing nonoperative management in patients with large, high grade sarcomas and significant medical extension to the sacroiliac joint or sacrum.

Adolescent↗

Cognitive aspects of recalling and reporting health-related events: Papanicolaou smears, clinical breast examinations, and mammograms.

This paper reports an examination of cognitive processes used by 178 women aged 50 years and older in retrieving information about the frequency with which they received Papanicolaou smears, mammograms, and clinical breast examinations. Women were selected from a health maintenance organization in which they had been enrolled for at least 5 1/2 years. The literature suggested that reporting of regular events such as these kinds of tests is likely to be based on schemas, which is an estimation technique in which events are reported in a format with generic content. Thus, if the procedure is believed to occur annually, the respondent will report receiving five tests in 5 years. The study attempted to evaluate whether use of episodic recall, in which respondents are forced to report individual events, would be more accurate than reports based on estimation using a schema format. The results indicated that most of the errors occurred in Papanicolaou smear reporting, which is consistent with the literature, and that the fewest errors occurred with mammograms. Regardless of the questionnaire format, respondents persisted in using schemas based on the date of annual physical examination. Most reporting errors occurred because the interval between examinations was estimated incorrectly.

Aged↗

A generic method for the production of cell lines expressing high levels of 7-transmembrane receptors.

G-protein-coupled or 7-transmembrane receptors (7TMRs) are often studied after heterologous expression in mammalian cells such as COS-7, CHO-K1, or HEK-293s. In this paper, we describe the development of a rapid and generic method for producing stable Chinese hamster ovary cell lines expressing high levels of recombinant 7TMRs by N-terminal tagging these proteins with the hemagglutinin (HA) sequence. To illustrate the broad applicability of this technique, we have presented data from cell lines expressing a glycoprotein hormone receptor for follicle-stimulating hormone (FSHR), CXC- (CXCR-2), and CC-chemokine (CCR-1) receptors and peptide receptors from the somatostatin (SSTR1, 2, 5) and neuropeptide Y (NPY-Y2, -Y4 Rs) families. Typically, cell lines with a receptor density of 1 to 15 pmol/mg protein are produced with this method. The presence of the HA tag does not adversely affect the binding or functional activity of the receptors.

Amino Acid Sequence↗

Peptide agonist of the thrombopoietin receptor as potent as the natural cytokine.

Two families of small peptides that bind to the human thrombopoietin receptor and compete with the binding of the natural ligand thrombopoietin (TPO) were identified from recombinant peptide libraries. The sequences of these peptides were not found in the primary sequence of TPO. Screening libraries of variants of one of these families under affinity-selective conditions yielded a 14-amino acid peptide (Ile-Glu-Gly-Pro-Thr-Leu-Arg-Gln-Trp-Leu-Ala-Ala-Arg-Ala) with high affinity (dissociation constant approximately 2 nanomolar) that stimulates the proliferation of a TPO-responsive Ba/F3 cell line with a median effective concentration (EC50) of 400 nanomolar. Dimerization of this peptide by a carboxyl-terminal linkage to a lysine branch produced a compound with an EC50 of 100 picomolar, which was equipotent to the 332-amino acid natural cytokine in cell-based assays. The peptide dimer also stimulated the in vitro proliferation and maturation of megakaryocytes from human bone marrow cells and promoted an increase in platelet count when administered to normal mice.

Amino Acid Sequence↗

Spinal gabapentin is antinociceptive in the rat formalin test.

Gabapentin is a novel anticonvulsant that may be of value for the relief of clinical pain. To determine whether gabapentin is antinociceptive after spinal administration, the drug was given via an intrathecal catheter in doses from 6 to 200 micrograms/rat 10 min prior to intraplantar formalin. Five percent formalin injected subcutaneously in the right hind paw produced a biphasic reaction consisting of flinching and licking behaviors (phase 1, 0-10 min; phase 2, 10-60 min). Gabapentin dose-dependently reduced the numbers of flinches and the duration of licking during phase 2 of the formalin test. The highest dose of gabapentin (200 micrograms/rat) did not affect the tail-flick response. These results demonstrate that spinal gabapentin is antinociceptive in the formalin test.

Acetates↗

The impact of residual disease on local recurrence in patients treated by initial unplanned resection for soft tissue sarcoma of the extremity.

BACKGROUND AND OBJECTIVES: "Unplanned excision" in soft tissue sarcoma (STS) is defined as the gross removal of tumor without preoperative staging or consideration of the need for removal of normal tissue around the tumor. This study evaluated whether unplanned excision in patients with extremity STS would have an impact on local relapse (LR), even if reexcision of the tumor bed was undertaken. METHOD: Two hundred thirty-nine (239) patients with primary, extremity STS treated with limb salvage surgery were included in this study. Of the 239, 78% were treated with surgery and irradiation. Forty-seven tumors were low-grade and 192 high grade. Mean tumor diameter was 7.5 cm. Twenty had local recurrences and 64 relapsed systemically. RESULTS: Only margin and prior surgery were significant in univariate analysis (P < 0.05, log-rank test). The Cox multivariate analysis revealed that both margin of resection (P < 0.001) and the status of the local tumor site (P < 0.05) at definitive surgery were significant predictors of local relapse. CONCLUSIONS: These results suggest that the presence of microscopic disease in the reexcised specimen following unplanned resection is a risk factor for local disease recurrence.

Adolescent↗