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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 91 records · Page 5Linked to original sources

Multifidus spasms elicited by prolonged lumbar flexion.

STUDY DESIGN: The electromyogram of the L1-L7 multifidus muscles of the in vivo cat were recorded while applying a prolonged steady displacement to the lumbar spine through the L4-L5 supraspinous ligament, simulating a moderate anterior flexion. OBJECTIVE: To demonstrate that tension-relaxation and laxity of the viscoelastic structures (ligaments, discs, and capsules) induced by prolonged static flexion of the spine results in loss of reflexive muscular stabilizing activity and in muscular disorders that may lead to or are associated with low back pain. SUMMARY OF BACKGROUND: Epidemiologic data show that prolonged loading of the spine, such as in some occupational activities, can cause low back pain and muscle spasms. Direct experimental evidence linking prolonged loading to a decrease in spinal stability, low back pain, and muscle spasms was not found. It was hypothesized, however, that mechanoreceptors in the viscoelastic structures, when strained, reflexively activate the multifidus muscles to maintain intervertebral stability; that the reflexive muscular activity decreases with stress-relaxation and laxity in the viscoelastic structures; and that when severe strain and possible damage of the viscoelastic structures occurs with time, nociceptive receptors elicit spasms in the musculature and possible pain. METHODS: The lumbar spine of seven in vivo cat preparations was displaced through the L4-L5 supraspinous ligament into moderate flexion that was steadily maintained for 50 minutes while intramuscular electromyograms were recorded from each of the multifidus muscles of L1-L2 through L6-L7. Load and electromyogram were continuously monitored and recorded. Five additional preparations were used as controls, in which dissection and recordings were identical, but the lumbar flexion was excluded. RESULTS: Prolonged flexion of the lumbar spine resulted in initial reflexive electromyogram from the multifidus muscles that decreased to approximately 5% of its initial value as tension-relaxation began in the viscoelastic structures within the first 3 minutes, after which, random and unpredictable electromyogram discharges (i.e., spasms) of high amplitude were recorded from different levels. In some preparations the spasms were present in L1-L4, and in others in all the levels. In other preparations the spasms were recorded only at L5 and L6. The onset of the spasms was also unpredictable, because they were initiated in some cases within 2-3 minutes after the spine was loaded. In other cases, the spasms were observed anytime during the test period and up to 20 minutes after the load was removed. Spasms were also observed in the spinalis and longissimus muscles. CONCLUSIONS: Prolonged flexion of the lumbar spine results in tension-relaxation and laxity of its viscoelastic structures, loss of reflexive muscular activity within 3 minutes and electromyogram spasms in the multifidus and other posterior muscles.

Animals↗

Regulation of integrin alpha vbeta 3-mediated endothelial cell migration and angiogenesis by integrin alpha5beta1 and protein kinase A.

Recent studies indicate that angiogenesis depends, in part, on ligation of integrin alpha(5)beta(1) by fibronectin. Evidence is now provided that integrin alpha(5)beta(1) regulates the function of integrin alpha(v)beta(3) on endothelial cells during their migration in vitro or angiogenesis in vivo. Secretion of fibronectin by endothelial cells leads to the ligation of integrin alpha(5)beta(1), which potentiates alpha(v)beta(3)-mediated migration on vitronectin without influencing alpha(v)beta(3)-mediated cell adhesion. Endothelial cell attachment to vitronectin suppresses protein kinase A (PKA) activity, while addition of soluble anti-alpha(5)beta(1) restores this activity. Moreover, agents that activate intracellular PKA, such as forskolin, dibutyryl cAMP or alpha(5)beta(1) antagonists, suppress endothelial cell migration on vitronectin in vitro or angiogenesis in vivo. In contrast, inhibitors of PKA reverse the anti-migratory or anti-angiogenic effects mediated by alpha(5)beta(1) antagonists. Therefore, alpha(v)beta(3)-mediated endothelial cell migration and angiogenesis can be regulated by PKA activity, which depends on the ligation state of integrin alpha(5)beta(1).

Cell Adhesion↗

European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes.

Paraffin blocks and clinical data from 521 patients with lymphocyte predominance Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16 European and United States oncological centers to establish the pathologic and clinical characteristics of a large patient cohort, to determine how frequent T-cell-rich large B-cell lymphoma (TCRLBCL) is among LPHD, and to find differential diagnostic criteria distinguishing between the 2 lymphoma categories. For this purpose, conventionally and immunohistologically stained sections were reviewed by a panel of hematopathologists. The diagnosis of LPHD was confirmed in only 219 of the 388 assessable cases (56.5%). This low confirmation rate was due mainly to the presence of a new variant of classical Hodgkin disease (CHD), which resembled, in terms of nodular growth and lymphocyte-richness, nodular LPHD and, in terms of the immunophenotype of the tumor cells, CHD and was designated nodular lymphocyte-rich CHD (NLRCHD). The nodules of LRCHD consisted-as in nodular LPHD-predominantly of B cells but differed from those present in LPHD in that they represented expanded mantle zones with atrophic germinal centers. Clinically, patients with LPHD and NLRCHD showed similar disease characteristics at presentation but differed in the frequency of multiple relapses and prognosis after relapse. Patients with LPHD and NLRCHD clearly differed from patients with CHD with nodular sclerosis or mixed cellularity, as they presented with an earlier disease stage and infrequent mediastinal involvement. As 97% of the LPHD cases showed a complete or partial nodular growth pattern, their differentiation from TCRLBCL was a rare problem in the present series. (Blood. 2000;96:1889-1899)

Adolescent↗

The Eastman Jubilee 1948-1998.

The postgraduate Eastman Dental Clinic and Institute of Dental Surgery were established in 1947. However their roots go back to Rochester in New York State where George Eastman was born in 1854. George Eastman literally changed the image of the world by creating popular photography. In 1914 he was driven by his painful neglected dentition to seek the help of Harvey Jacob Burkhart (pictured, right) who was considered to be the best dentist in the state. Burkhart provided him, for the first time in his adult life, with comfortable dentures, which not only restored function but also his appearance. George Eastman was overwhelmed with his new found comfort and social confidence.

Dental Clinics↗

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Animals↗

Aging affects the retrobulbar circulation differently in women and men.

BACKGROUND: While aging clearly has protean biological effects on every organ system, the differential effects of aging in women and men in the retrobulbar vasculature, to our knowledge, have never been investigated. Because glaucoma and age-related macular degeneration are closely linked to advanced age, we performed a cross-sectional study using color Doppler imaging of 4 retrobulbar vessels in both healthy women and men. OBJECTIVE: To define the influence of aging per se on ocular hemodynamics. METHODS: Women (n = 73) and men (n = 55), aged from 20 to 90 years, free of ocular and systemic disease, and with normal intraocular pressure, were recruited for this study. Postmenopausal women who were not receiving estrogen replacement therapy were also recruited. Studies involved color Doppler imaging analysis of the ophthalmic, central retinal, and nasal and temporal posterior ciliary arteries. Ophthalmic arterial peak systolic and end-diastolic velocities and a Pourcelot resistance index were determined for each vessel. RESULTS: In both sexes, ophthalmic arterial end-diastolic velocity decreased and the Pourcelot resistance index rose with advancing age (each P<. 001); peak systolic velocity in the ophthalmic vessel was age-independent. In contrast, central retinal arterial flow velocities were unaffected by age in both sexes. In the posterior ciliary arteries, in men, flow velocities and the Pourcelot resistance index were independent of age. However, in women, end-diastolic velocity decreased with age in both the nasal and temporal posterior ciliary vessel (each P<.05); peak systolic velocity was constant; the Pourcelot resistance index in each ciliary artery rose with advancing age (each P<.05). CONCLUSION: In healthy women and men, aging-induced changes in retrobulbar hemodynamics are comparable to alterations seen in patients with glaucoma or age-related macular degeneration, suggesting that vascular changes with senescence may contribute to increased risk for these diseases in older age. Arch Ophthalmol. 2000;118:1076-1080

Adult↗

A modified nasopharyngeal tube to relieve high upper airway obstruction.

Infants with high upper airway obstruction (UAO) are managed with a variety of techniques to relieve their UAO. Among these techniques, the least invasive and safest is the nasopharyngeal tube (NPT). However, the traditional NPT is not always satisfactory, and tracheostomies need to be done. We recently described a modified NPT technique that, in contrast to the traditional tube, does not add airway dead space and resistance, is easy to use, is well-tolerated, has proven highly successful, and allows the simultaneous use of oxygen nasal prongs. This modified NPT has many advantages over the traditional NPT as a temporary management of high UAO that resolves with growth of the infant. This report highlights the respiratory care of 10 infants with high UAO (Pierre Robin syndrome, Down syndrome, Goldenhar syndrome, isolated microngathia, and idiopathic hypotonia) who were managed with a modified NPT. The modified NPT described potentially reduces the need for surgical intervention to relieve high UAO in infants.

Airway Obstruction↗

Biexponential recovery model of lumbar viscoelastic laxity and reflexive muscular activity after prolonged cyclic loading.

OBJECTIVES: To determine the rest duration required for full recovery of reflexive muscular activity and laxity/creep induced in the lumbar viscoelastic structures (e.g., ligaments, discs, etc.) after 50 min of cyclic loading, and to develop a model describing such recovery. BACKGROUND: It is well established that steady, cyclic or vibratory loading of the lumbar spine induces laxity/creep in its viscoelastic structures. It was also shown that such viscoelastic creep does not fully recover when subjected to rest equal in duration to the loading period. Rest periods of 24 h, however, were more than sufficient to allow full recovery. The exact period of time allowing full recovery of viscoelastic laxity/creep, and its pattern is not known. It is also not known what is the duration required for full recovery of reflexive muscular activity lost due to the laxity/creep induced in the spine during cyclic loading. METHODS: The lumbar spine of 'in vivo' feline preparations was subjected to 50 min of 0.25 Hz cyclic loading applied v ia the L4/5 supraspinal ligament. At the end of the loading period the spine was subjected to prolonged rest, interrupted by a single cycle loading applied hourly for measurement purposes until the laxity was fully recovered (>90%). Reflexive EMG activity was recorded with wire electrodes from the L-1-L-7 multifidus muscles. A biexponential model was fitted to the load and EMG recorded in the recovery period in order to represent viscous and elastic components of structures with different architecture (e.g., disc vs. ligament). RESULTS: Full recovery of the laxity induced by 50 min of cyclic loading at 0.25 Hz required 7 h and was successfully fitted with a biexponential model. Similarly, EMG activity was fully recovered in 4 hours, and often exceeded its initial value during the following 3 h. CONCLUSIONS: Full recovery of laxity induced in the lumbar viscoelastic structures by a given period of cyclic loading requires rest periods, which are several folds longer than the loading duration. Similarly, reflexive muscular activity requires 4 h of rest in order to be restored. Meanwhile, significant laxity can be present in the joints, exposing the spine to potential injury and low back pain. Increased EMG activity at the end of the recovery period may indicate that pain was possibly induced in the spinal structures, inducing hyperexcitability of the muscles during passive loading. RELEVANCE: Although the data was derived from a feline model, and its extrapolation to the human model is not straightforward, the general pattern of decreasing reflexive muscular activity with cyclic loading is expected in both species. Therefore, workers who subject their spine to periods of cyclic loading may be exposed to prolonged periods of laxity beyond the neutral zone limits, without protection from the muscles and therefore the risk of possible injury and low back pain. Pain and muscle hyperexcitability could also be a factor associated with cyclic loading, being expressed several hours after work was completed.

Animals↗

Oral submucous fibrosis patients have altered levels of cytokine production.

Oral submucous fibrosis (OSF) is a pre-malignant fibrotic lesion of the mouth in betel quid chewers and is characterised by dense bands of collagen in the juxta-epithelial region preceded by inflammation. We have investigated the spontaneous and stimulated production of cytokines by peripheral blood mononuclear cells (PBMC) from OSF patients and compared them with genetically-related relatives, Indian and Caucasian control subjects. The cytokines studied included: interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). The results show: a) significant differences in the stimulated versus non-stimulated levels of IL-1beta, IL-6, IL-8 and TNF-alpha but not of IFN-gamma production by patients, and in the relatives' stimulated versus non-stimulated levels of IL-1beta, IL-6 and IFN-gamma; b) no difference in the spontaneous cytokine production between any two groups; and c) significant increases in the patients' stimulated cytokines compared to the Caucasian and Indian controls (P< or =0.050). These results demonstrate increased levels of proinflammatory cytokines and reduced anti-fibrotic IFN-gamma in patients with OSF, which may be central to the pathogenesis of OSF.

Areca↗

Risk perceptions among patients and their relatives regarding prostate cancer and its heredity.

We performed a qualitative study to examine how prostate cancer (PC) patients and their spouses and relatives take into account family history when considering susceptibility to PC. Semi-structured interviews were conducted with 20 participants. All interviews were tape-recorded, transcribed and content analyzed. Patients' and spouses' views concerning the seriousness of PC were different. Wives viewed PC as a serious disease because it has affected their marital relationships; patients found PC to be less serious because it can be treated. All participants viewed PC as a male disease that can be passed on from fathers to sons. Furthermore, participants were aware of PC clustering in their families. However, this awareness did not encourage (healthy) male relatives to seek early detection. Additionally, participants perceived age, high-fat diet, and less exercise as important risk factors, while socioeconomic status, ethnic origin and a family history of PC were viewed as less important. We recommend that health educators pay special attention to these findings when planning to teach patients, spouses and their relatives about PC, its heredity and risks. Prostate Cancer and Prostatic Diseases (2000) 3, 176-185

Journal Article↗

Morphological and immunophenotypic variations in malignant melanoma.

A variety of cytomorphological features, architectural patterns and stromal changes may be observed in malignant melanomas. Hence, melanomas may mimic carcinomas, sarcomas, benign stromal tumours, lymphomas, plasmacytomas and germ cell tumours. Melanomas may be composed of large pleomorphic cells, small cells, spindle cells and may contain clear, signet-ring, pseudolipoblastic, rhabdoid, plasmacytoid or balloon cells. Various inclusions and phagocytosed material may be present in their cytoplasm. Nuclei may show bi- or multi-nucleation, lobation, inclusions, grooving and angulation. Architectural variations include fasciculation, whorling, nesting, trabeculation, pseudoglandular/pseudopapillary/pseudofollicular, pseudorosetting and angiocentric patterns. Myxoid or desmoplastic changes and very rarely pseudoangiosarcomatous change, granulomatous inflammation or osteoclastic giant cell response may be seen in the stroma. The stromal blood vessels may exhibit a haemangiopericytomatous pattern, proliferation of glomeruloid blood vessels and perivascular hyalinization. Occasionally, differentiation to nonmelanocytic structures (Schwannian, fibro-/myofibroblastic, osteocartilaginous, smooth muscle, rhabdomyoblastic, ganglionic and ganglioneuroblastic) may be observed. Typically melanomas are S100 protein, NKIC3, HMB-45, Melan-A and tyrosinase positive but some melanomas may exhibit an aberrant immunophenotype and may express cytokeratins, desmin, smooth muscle actin, KP1 (CD68), CEA, EMA and VS38. Very rarely, neurofilament protein and GFAP positivity may be seen.

Diagnosis, Differential↗

A doxorubicin-based regimen used in the treatment of elderly patients with high-grade non-Hodgkin's lymphoma.

A retrospective analysis was performed on 66 patients, aged 70 years or older, who received treatment with a weekly doxorubicin-containing regimen (VAPEC-B) for high grade non-Hodgkin's lymphoma (NHL). Two dosing schedules were employed. The choice of regimen was at the discretion of the treating clinician and reflected the performance status of the patient and the predicted tolerance to chemotherapy. Forty-nine patients received a half-dose schedule and 17 the full-dose schedule. Those receiving the half-dose regimen had a lower median performance status and received a lower dose intensity of chemotherapy (45% versus 83%). However, the outcomes of the two groups were similar: complete remission rate 41% versus 47%, and 5-year overall survival 36% versus 23%, for the half- and full-dose groups, respectively. A similar proportion of patients (51% versus 59%) completed each regimen, although there were more delays in treatment delivery experienced in those receiving the full dose. Half-dose VAPEC-B is an effective treatment option for elderly patients with high-grade NHL and has comparable efficacy with other published regimens. The use of such low-dose doxorubicin-containing regimens in elderly patients with high-grade NHL requires further investigation.

Aged↗

General practice recruitment for schizophrenia prevention studies.

OBJECTIVE: To examine the barriers and incentives that may exist for Australian general practitioners (GPs) to screen for and detect individuals at risk of developing schizophrenia and to participate in studies aimed at assessing screening procedures. METHOD: Examination of literature, existing procedures in general practice, informed by experience in the GP Integration Support, Evaluation and Resource Unit during 1995-1999 and the General Practice Integration Research Programme and the reports arising from this. RESULTS: The attitudes and responses of GPs to research proposals and to working with researchers will be influenced by their overall relationship with mental health services. As the average GP will only have a small caseload of patients with schizophrenia, it is important to provide some incentive to encourage GP involvement in schizophrenia prevention studies. Key incentives include: the availability of specialist support from mental health practitioners; systems development in general practice; inclusion in the research team; and Quality Assurance points. CONCLUSIONS: General practitioners have shown willingness to engage in a diversity of research projects, including mental health research. Divisions of General Practice are increasingly interested in evaluation and research and may be a useful entry point for approaching GPs as a group.

Attitude of Health Personnel↗

Mesotheliomas with deciduoid morphology: a morphologic spectrum and a variant not confined to young females.

Deciduoid mesotheliomas are rare with only four previously reported cases, all affecting the peritoneum of young females. We describe another six cases (three men and three women; age range 52-65 yrs, median 55 yrs; five peritoneal and one pleural). Three patients had an occupational history of asbestos exposure. The deciduoid appearance predominated in four cases, whereas in two it represented a minor component within conventional tubulopapillary epithelioid mesothelioma. All tumors were strongly cytokeratin-positive (including CK5/6) and all showed at least focal staining for thrombomodulin, HBME-1, and calretinin. All were negative for epithelial mucin (D/PAS), CEA, BerEP4, LeuM1 (CD15), CD21, CD35, and S100 protein. Five of six cases (83%) were vimentin-positive and two (33%) were focally positive for alpha-smooth muscle actin. A differential diagnosis of gastrointestinal autonomic nerve tumor (GANT) had been initially considered from the morphology of one case, and we found positivity for some of the "neuronal" markers described in GANTs. This prompted us to apply such a panel to the other five tumors, accepting that the cytokeratin positivity encountered in all of our cases would exclude GANT. All cases of deciduoid mesothelioma (100%) were positive for PGP 9.5 and NSE and four of six (66%) were positive for NKI/C3. Weak focal staining (<5% cells) for synaptophysin was seen in two of six tumors. All cases were chromogranin-negative. All cases examined by electron microscopy showed desmosomes and smooth microvilli without rootlets but no neuroendocrine granules. In conclusion, a deciduoid morphology appears to be part of the histopathologic spectrum encountered in epithelioid mesothelioma. This variant is not confined to female patients and occurs over a wider age range than previously recognized. The overlapping immunophenotype with GANTs illustrates that caution should be exercised when interpreting positivity for "neuronal" markers in this context. An immunohistochemical panel that includes cytokeratins should always be used.

Aged↗

Extraskeletal myxoid chondrosarcoma with neuroendocrine differentiation: a pathologic, cytogenetic, and molecular study of a case with a novel translocation t(9;17)(q22;q11.2).

A case of extraskeletal myxoid chondrosarcoma (EMC) in which there was histochemical, immunohistochemical, and ultrastructural evidence of neuroendocrine differentiation is reported. Genetic investigations showed the recently described novel translocation t(9;17)(q22;q11.2) and associated fusion of the CHN and RBP56 genes, contrasting with the translocation t(9;22)(q22;q12) and EWS/CHN gene fusion found in the majority of EMCs.

Biomarkers, Tumor↗