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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 199 records · Page 11Linked to original sources

Effects of human tumor cell lines on local new bone formation in vivo.

Although some tumors cause osteolytic lesions, there are some that stimulate new bone formation. This is an important phenomenon because the responsible mechanisms probably represent an aberration of normal physiological bone formation, and identifying the factors involved in the process may lead to new therapies for various bone diseases. To clarify our understanding of the potential mechanism responsible, we compared and quantitated the extent of new bone formation stimulated by human tumors (HeLa, Hep-2, AV-3, FL, WISH and KB), some of which have osteogenic activity in vivo [2]. Tumor cells were injected over the calvaria of nude mice to examine formation of new bone. The tumor cells produced three histologically distinct patterns of new bone growth: (1) WISH and KB stimulated appositional bone growth adjacent to periosteal bone surfaces; (2) HeLa and Hep2 induced new bone growth over calvarial surface even when distant from the tumor mass; (3) FL stimulated bone formation adjacent to periosteum as well as ectopic bone formation in sites distant from bone. All tumors except AV3 induced mean new bone thickness >100 microm, and Hep-2 cells produced bone 330 microm thick. PCR and Northern blot analysis of mRNA isolated from cultured tumor cells revealed that all cell lines expressed mRNA for TGFbeta, (fibroblast growth factor) FGF-1, FGF-2, and IGF-I, and most cell lines produced mRNA for PDGF. Only FL expressed large amounts of mRNA for BMP2. In serum-free conditioned media from Hep2 and HeLa cells purified by heparin affinity chromatography, we have identified FGF-I, FGF-2, and PDGF by immunodetection with specific antibodies. Our results show that new bone growth caused by these tumors is likely due to the production of bone growth factors by the tumor cells, and that the overall effects on bone may be due to several factors working in concert.

Animals↗

Facilitated radical perineal prostatectomy with the Brooke Bookwalter retractor blade.

With the resurgent interest in radical perineal prostatectomy, a variety of enhancements have been made to the procedure. We describe herein the use of a retractor blade that allows full mobilization of the seminal vesicles and vasa prior to prostatic apical dissection, thus facilitating bladder neck-sparing radical prostatectomy. This retractor system dramatically improves visualization of the seminal vesicles and prostatic pedicles, allowing a single surgeon to perform this procedure easily.

Humans↗

Infantile myofibromatosis of orbital bone. A case report with computed tomography, magnetic resonance imaging, and histologic findings.

OBJECTIVE: The authors report the clinical, radiographic, histologic, and surgical findings of a rare presentation of infantile myofibromatosis. A mass presenting at the inferolateral orbital rim of a 4-year-old child was imaged with both computed tomography (CT) and magnetic resonance imaging (MRI), excised surgically and analyzed histologically to confirm the diagnosis. Infantile myofibromatosis is a rare benign disorder of childhood consisting of well-demarcated nonencapsulated tumors. The overall prognosis depends on the number and location of tumors. Isolated infantile myofibromatosis of the head and neck is the most common form of this generally benign disease. DESIGN: A case review study is presented and discussed with regard to clinical, radiographic, histologic, and interventional findings. The literature is reviewed and the clinical relevance discussed. INTERVENTION: Surgical extirpation of the tumor was undertaken after sufficient localizing radiographic information was obtained. RESULTS: The tumor showed erosion of the orbital bone and orbital extension with reactive hyperostosis on CT imaging. The MRI finding showed an inhomogeneous well-demarcated dark mass on T1 images with increased signal intensity on T2 images. Gadolinium contrast showed significant vascular enhancement. Histologic sections showed a spindle-cell tumor of whorled myofibroblasts surrounding a hemangiopericytoma-like center. The tumor was excised completely. There has been no evidence of recurrence or adverse ocular sequelae in the first 6 months after surgery. CONCLUSIONS: Cases involving the orbit or cranial bones are particularly rare but can have profound secondary effects on local structures. Isolated tumors can occur in all age groups and can mimic more aggressive or malignant neoplasms. The CT and MRI findings are beneficial in establishing a differential diagnosis, plan of treatment, and prognosis. Early diagnosis is important to rule out other neoplasms. The appropriate treatment is excisional biopsy whenever possible and is considered curative. The authors present what to our knowledge is the first reported case of an isolated infantile myofibroma involving an orbital bone.

Child, Preschool↗

The effect of tramadol on dento-alveolar surgical pain.

The aim of the study was to assess the analgesic effect of tramadol in the relief of pain after dentoalveolar operations that involve the removal of bone and suturing. Four-hundred and fifty-two patients over the age of 18 years who were to undergo removal of impacted teeth (n = 362), removal of root (n = 79), or alveolectomy, enucleation of cysts, or removal of soft tissue (n = 11) under local anesthesia were studied. Patients were randomly allocated to receive tramadol 100 mg or 50 mg four times daily, or 50 mg twice daily, or placebo. Median pain scores on the day of operation in the three tramadol groups were similar (2 in each group, ranges 1-5, 1-4.8, and 1-5 respectively) and were all significantly lower than that in the placebo group (2.3 range 1-4.2). The median number of Paracetamol tablets taken by patients in the three tramadol groups was 2 (ranges 0-8, 0-12 and 0-8 respectively), and were all significantly less than in the placebo group (4, range 0-12). More patients given tramadol reported complete pain relief than the placebo group. The advantages of tramadol continued over the next 2 days. There were no serious or unexpected adverse effects. It is concluded that tramadol is an effective analgesic after dentoalveolar operations.

Acetaminophen↗

The role of oxygen free radicals in idiopathic facial pain.

Patients with chronic facial pain including those with facial arthromyalgia (TMJ dysfunction syndrome) were investigated for evidence of abnormal systemic and intra-articular free radical activity. Chronic facial pain patients showed significantly raised serum 2,3-dihydroxybenzoic acid after an oral dose of 1.2 g of aspirin which indicates increased systemic free radical activity. This was reflected in the TMJ aspirates of the facial arthromyalgia patients which contained thiobarbituric acid-reactive substance (TBA-RS) which is also a product of free radical activity. The synovial aspirates also contained high levels of the hyperalgesic eicosanoid 15-HETE. However, there was no difference between the painful and symptom-free joints, which suggested that in part the clinical features are probably determined by asymmetrical masticatory function or as yet unknown algesic factors such as local cytokine production.

Administration, Oral↗

The stimulation of bone formation in vitro by therapeutic ultrasound.

A controlled study was performed to evaluate the effects of different ultrasound (US) intensities on 5-day-old mouse calvaria bone in tissue culture. A special technique to apply the US was developed, and the following parameters were measured: collagen and noncollagenous protein (NCP) synthesis (bone formation), and temperature change. It was found that ultrasound at 0.1 W/cm2 (SATA), pulsed 1:4, 3 MHz, 5 min, significantly stimulates bone formation (i.e., the synthesis of collagen and NCP) (p < 0.001 and p < 0.01). However, pulsed ultrasound at higher doses (1.0-2.0 W/cm2 (SATA), pulsed 1:4, 3 MHz, 5 min) significantly inhibited the synthesis of both collagen and NCP (p < 0.05). The temperature measurements showed a maximum rise of 1.8 degrees C [at 2.0 W/cm2 (SATA)] and no detected rise at 0.1 W/cm2 (SATA), suggesting that the effects in this study were primarily nonthermal. These results may reflect the healing effect of US on fractures and osteoradionecrosis and reinforces the use of low intensity US regimens [0.1 W/cm2 (SATA)] in clinical practice.

Animals↗

Atypical facial pain: a double-blind placebo-controlled crossover pilot study of subcutaneous sumatriptan.

A double-blind placebo-controlled crossover pilot study involving 19 patients was undertaken to evaluate the efficacy of subcutaneous sumatriptan, a selective 5-hydroxytryptamine (5-HT)-like receptor agonist, in the treatment of atypical facial pain (AFP). A reduction in total pain was found 120 min post injection in the sumatriptan group. Most patients, however, described the medication as ineffective overall, despite significant pain score reduction. The temporary improvement of pain scores with the active drug was thought to be too small to be of any clinical benefit, but suggests that vascular or neurogenic mechanisms may be involved in the aetiology of AFP. Sumatriptan is not an appropriate therapeutic option for patients with AFP, but could prove a valuable drug in experimental clinical pharmacology.

Adolescent↗

Citrobacter freundii and fatal neutropenic enterocolitis following adjuvant chemotherapy for breast cancer.

Neutropenic enterocolitis is increasingly being recognized as a life-threatening complication of chemotherapy, mainly for haematological and lymphoproliferative malignancies. It is under-recognized clinically, with the diagnosis often being made on post-mortem examination. Although active medical management is generally preferred, surgical intervention may be indicated. We report a case of fatal neutropenic enterocolitis, secondary to Citrobacter freundii, following adjuvant chemotherapy for breast cancer. We also review the literature, examining the aetiology, diagnosis and management of this often fatal entity.

Antineoplastic Combined Chemotherapy Protocols↗

Quality assessment in contracting for tertiary care services by HMOs: a case study of three markets.

BACKGROUND: Few studies have examined the provision of tertiary care services by managed care organizations (MCOs). Moreover, little is known about the role of quality assessment and quality assurance mechanisms in the contracting process. Site visits were conducted in 1995 in three geographic areas to describe and evaluate the contracting processes for tertiary care services, especially neonatal intensive care and coronary artery bypass graft surgery, of health maintenance organizations (HMOs). METHODS: Three market areas in the United States, each with differing levels of "maturity", as primarily defined in terms of managed care penetration, were selected for study. Interviews were conducted with HMO and hospital managers about the processes for identifying potential tertiary care hospitals and mechanisms for quality assessment and quality improvement (QI) that are considered in the contracting process. FINDINGS: The most sophisticated contracting arrangements were found in the most mature market-where HMOs select hospitals for tertiary care services based on both the price and quality of services, with quality assessed through both objective and subjective data. Yet in all three markets, quality assessment was the least well-developed component of tertiary care contracting. Even in the mature market, we found inconsistent use of even validated quality or outcomes measures in hospital contracting. CONCLUSION: The potential of MCOs to increase quality depends on their ability to identify high-quality hospitals and their willingness to direct enrollees to those hospitals. Yet inconsistent evidence was found that mechanisms for evaluating and rewarding quality are being fully adopted in the three markets studied.

Catchment Area, Health↗

The relationship between violence dimensions and symptom severity among homeless, mentally ill women.

Little is known about the relationship between violence and symptomatology in the lives of homeless, mentally ill women. This study investigates the possibility that specific dimensions of violence-frequency, recentness and type-may be associated with severity of psychiatric symptomatology in this population. Results indicate that each of the abuse dimensions is associated with a broad range of psychiatric symptoms and, in combination with substance abuse, account for almost one third of the variance in overall distress. These findings suggest the possibility that intensity of exposure to violence contributes to the severity of psychiatric symptoms even in women who already suffer an overwhelming number of intrapsychic and social difficulties; and that multiply traumatized women do not become desensitized to the impact of new violence. This article discusses the clinical and policy implications of these conclusions.

Adult↗

Angiotropic lymphoma with endocrine involvement.

AIMS: Two cases of angiotropic high-grade B-cell lymphoma are described in which involvement of endocrine glands was a prominent feature. METHODS AND RESULTS: One patient had marked unilateral adrenomegally due to lymphoma within adrenal blood vessels. He is alive 5 years after presentation following combination chemotherapy. The diagnosis was made at autopsy in the second patient who presented with pyrexia of unknown origin and had hypothyroidism and a thyroid nodule. The thyroid gland and pituitary showed striking involvement by angiotropic lymphoma and the thyroid nodule was a cavernous haemangioma heavily colonized by lymphoma cells. CONCLUSIONS: Our cases illustrate endocrine organ manifestations of this rare disease. The condition may respond to combination chemotherapy.

Adrenal Gland Neoplasms↗

Clinicopathological characteristics of peripheral primitive neuroectodermal tumour of skin and subcutaneous tissue.

AIMS: To study the clinical and pathological features of primary malignant peripheral primitive neuroectodermal tumours (PNETs) of the skin and subcutaneous tissue, to discuss the differential diagnosis, and to review the existing literature on these tumours. METHODS AND RESULTS: Eight cases of PNETs presenting in the skin and subcutaneous tissue were identified from the pathology records of the Christie Hospital, Manchester. Detailed immunohistochemical studies were performed on all cases and seven tumours were subjected to electron microscopic examination. Detailed clinical and follow-up information was obtained on seven cases. Six tumours occurred in children and adolescents and two were seen in young adults (age range, 8-36 years). No sex or site predilection was observed. Five tumours occupied the dermis and subcutis and three were entirely located in the subcutaneous tissue. Microscopically, they were composed of small round cells and seven tumours contained glycogen. Only one tumour focally exhibited Home-Wright rosettes and neuropil. Two tumours contained rhabdoid or plasmacytoid cells in places and all cases showed microcystic and pseudovascular spaces. Immunostains revealed MIC2 (8/8), NSE (7/8), PGP9.5 (7/8), beta 2 microglobulin (7/8), neurofilament protein (6/8), S100 protein (3/8), synaptophysin (2/8) and Leu-7 (1/8) positivity. Anomalous cytokeratin (4/8), desmin (2/8), myoglobin (2/8), NKIC3 (4/8) and GFAP (1/8) staining was also noted. Ultrastructurally, neuroendocrine granules were detected in five cases and one case exhibited microtubules in processes. Adequate follow-up information was available in four cases. One patient died of metastatic disease. One child developed axillary lymph node metastasis but is alive with no evidence of disease 96 months after treatment. Two other patients are alive with no residual or recurrent disease 44 and 52 months after excision and radio/chemotherapy. CONCLUSION: PNETs are rare malignant small round cell tumours of the skin and subcutaneous tissue which are probably underdiagnosed. A correct diagnosis can be made on light microscopic features, demonstration of neuroendocrine granules on electron microscopy and a combination of MIC2, beta 2 microglobulin, and more than one neural marker positivity. These neoplasms should be differentiated from other cutaneous neoplasms composed of small round cells. The number of cases of cutaneous PNETs studied so far is rather small, and no firm conclusion can be drawn about their behaviour but long-term survival is possible in some cases.

12E7 Antigen↗

Correlation of virus load in plasma and lymph node tissue in human immunodeficiency virus infection. INCAS Study Group. Italy, Netherlands, Canada, Australia, and (United) States.

The impact of long-term changes in plasma viremia, produced by effective combination antiretroviral therapy, on human immunodeficiency virus (HIV) burden within tissue reservoirs is unknown. Fifteen patients who had received at least 1 year of therapy with two or three drug combinations of zidovudine, didanosine, and nevirapine had suitable samples of lymph node tissue obtained by ultrasound-guided core needle biopsy. HIV RNA was extracted from homogenized tissue samples and quantitated using a modified branched DNA assay. Results were correlated with antiretroviral treatment effect on the basis of plasma virus load measurements over the preceding 12-18 months. A statistically significant negative correlation was observed between magnitude of treatment effect on plasma viremia and lymph node virus load. These data suggest that combinations of antiretroviral drugs that produce sustained suppression of plasma HIV RNA may also be able to reduce the virus burden in lymphoid tissues.

Biopsy↗

Learning to look in the right place: a comparison of attentional behavior in deaf children with deaf and hearing mothers.

Eleven 18-month-old children with profound prelingual hearing loss were video-recorded in a free-play session with their mothers. Five of the mothers were profoundly deaf and fluent users of British Sign Language (BSL) or Auslan. The other six were hearing and had enrolled in a signing program. Ten-minute segments from each session were analyzed to determine the number of switches in attention shown by each child. Switches in attention were subdivided into three categories: spontaneous (where the child spontaneously looked to the mother); responsive (where the child responded to some maternal action such as moving an object); and elicited (where the mother made a direct attempt to gain the child's attention. Failed attempts to gain attention were also noted. A comparison of deaf and hearing mothers revealed no difference in the proportion of spontaneous or responsive switches in attention shown by their children. Responsive switches were by far the most frequent category for both groups, but these most commonly focused on objects and did not provide an opportunity for maternal signing. Successful perception of signing typically followed from spontaneous or elicited attentional switches. Deaf mothers were generally more insistent on their children turning to look at them, and they were more successful in eliciting attentional switches although they also had more failed attempts. These overall differences between the two groups were overshadowed by large individual differences within the groups. Within the sample there were both deaf and hearing mothers who achieved successful signed communication with their children.

Journal Article↗

Clinical isolates of Staphylococcus aureus have osteolytic surface proteins and a proportion of the population have antibodies that block this activity: is this of prognostic significance?

Staphylococcus aureus is directly implicated in the bone destruction associated with infected orthopaedic implants and bacterial arthritis. The Oxford (laboratory) strain of this organism has surface-associated proteins (SAPs) which have potent osteolytic activity. In this study, we have examined the osteolytic activity of SAPs from clinical isolates and also investigated the role of the humoral immune response to such proteins. Nine patients with infected orthopaedic prostheses or infective arthritis, and six volunteers not suffering from overt S. aureus infection, were examined. The sera from 5/9 patients and 4/6 volunteers were able to neutralize the osteolytic activity of the SAPs. The SAPs were extracted from four clinical isolates and were found to have osteolytic activity, but with a wide range of efficacies and potencies. All four patients from whom the clinical isolates were obtained had serum IgG antibodies to the surface proteins from their autologous isolates as determined by ELISA. In conclusion, clinical isolates of S. aureus contain osteolytic SAPs which may be responsible for bone destruction. Apparently disease-free individuals and patients have antibodies able to block this activity. However, since the capacity of patients' sera to neutralize the activity of the SAPs derived from their own S. aureus isolate was not investigated, it is unclear whether these findings are of prognostic value.

Antibodies, Bacterial↗