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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 91 records · Page 5Linked to original sources
PubMed1999

Effect of diameter of microvascular interposition vein grafts on vessel patency and free flap survival in the rat model.

Interposition vein grafting is an important technique in microvascular free tissue transfer. Studies in rats have demonstrated that the patency rate of vessels is not affected by interposition grafting when the vein grafts and receipt vessels are of similar diameter. Size discrepancy between vein grafts and recipient vessels is frequently encountered in clinical practice and may potentially be an important factor in anastomotic patency. This study was, therefore, designed to assess the effect of vein graft diameter on the patency of arterial repair and survival of a groin free flap in the rat model. Forty-nine Sprague-Dawley rats were used. The inferior epigastric and femoral veins were used to reconstruct the femoral artery in situ (12 rats, 24 anastomoses) and in groin free flaps (30 rats). The vessel patency with inferior epigastric (1:1 size match) and femoral (2:1 size match) veins was 100% in the non free flap model. In the free flap model, flap survival was 30% in the femoral (2:1 size match) vein graft group. This was significantly less than both the free flap epigastric vein graft group (90% survival) and primary anastomoses group (100% survival). The results of this study suggest that size-matched interposition vein grafts can provide a high degree of reliability, but with size mismatch vein grafts are prone to thrombus formation and subsequent free flap failure.

Animals↗
PubMed1999

Cryptosporidium parvum: structural components of the oocyst wall.

Cryptosporidium parvum, an enteropathogenic parasite, infects a wide range of mammals including man and constitutes a substantial veterinary and medical threat due to its ubiquitous distribution and the stability of the oocyst stage. The oocyst wall of C. parvum is known to be extremely resistant to chemical and mechanical disruption. Isolated oocyst walls are shown by both thin sectioning and negative staining transmission electron microscopy to possess a filamentous array on the inner surface. This filamentous array can be greatly depleted by digestion with proteinase K and trypsin, but pepsin has less effect. Ultrasonication of the untreated oocyst walls produced almost no fragmentation, but extension of the suture resulted in inward spiraling of the wall to generate ellipsoid and cigar-shaped multilayer bodies, with the filamentous array still present. When ultrasonicated, proteinase K-digested oocyst walls progressively fragmented into small sheets. These wall fragments, depleted of filaments, are shown by negative staining to possess a pronounced linearity, indicative of an integral highly complex lattice structure.

Animals↗
PubMed1999

Assessment of health risk behaviors. A tool to inform consumers, providers, health care organizations, and purchasers.

INTRODUCTION: Tobacco use, diet and physical activity patterns, and alcohol use are the leading causes of death in the United States. To make major improvements in the health status of the population, behavioral risk factors for disease must be addressed. METHODS: We propose a brief survey of behavioral risk factors for enrollees of health care organizations, employer groups, or other adult populations that can be used to profile the health risk behaviors of a population, assess performance of prevention and risk reduction programs, or make comparisons with other populations. The survey contains questions about tobacco, diet, physical activity, alcohol, firearms, motor vehicle safety, sexual behavior, and drugs. RESULTS: Recommendations for survey items, implementation, and calculation of performance measures are given. CONCLUSIONS: Widespread adoption of this type of survey would be a major step forward in acknowledging the impact that behavior has on health and in furthering individual and organizational accountability for improving health risk behaviors.

Adult↗
PubMed1998

Spatial and temporal expression of AP-1 responsive rod photoreceptor genes and bZIP transcription factors during development of the rat retina.

PURPOSE: The promoter region of the rod-specific beta subunit of cGMP PDE (beta-PDE) and opsin genes contains highly conserved cis-acting elements, which include an AP-1 and/or Nrl response element (NRE: An extended AP-1 like sequence). Transactivation of AP-1 or NRE appears necessary to drive expression of these rod-specific genes during adulthood, however, their role during development is relatively unknown. Therefore, we determined the spatial and temporal relationships between rod morphological and functional development, rod-specific gene expression, and expression of the bZIP transcription factors c-fos, junD and Nrl. METHODS: Retinas from 0-45 day old (PN0-45) dark- and light-adapted Long-Evans rats were used. Morphological development was monitored by light and electron microscopy. Whole retinal trypsin-activated cGMP-PDE activity and rhodopsin content were measured biochemically. The expression of opsin, beta-PDE, c-fos, junD and Nrl mRNAs were determined by Northern blot analysis. The cellular localization of Nrl was examined with in situ hybridization. RESULTS: The mRNAs for opsin, beta-PDE and c-fos were observed at PN0-2, while cGMP-PDE activity and rhodopsin were detected first at PN5: coincident with rod outer segment development. The developmental pattern of cGMP-PDE activity and rhodopsin accumulation paralleled the expression of beta-PDE and opsin mRNA and all reached their maximal levels by PN45. Nrl expression, for all three transcripts found in the rat retina, was low on PN2 and reached its maximal level at PN14. The c-fos and Nrl expression preceded beta-PDE and opsin mRNA expression by 1-2 days. Nrl expression was detected first in the distal post-mitotic retina at PN5 and then in all nuclear layers during retinal development. Maximal expression shifted from the ganglion cells to the outer nuclear layer as the neural retina matured. In contrast, junD expression was highest at PN0 and declined to a stable level by PN10. CONCLUSIONS: Colocalization of Nrl and c-Fos suggests that expression of rod-specific genes, which utilize AP-1 or NRE sites in their promoter, could be regulated through the formation of Nrl-Fos dimers. We hypothesize that Nrl and c-Fos play a fundamental role in the initiation and regulation of the rod-specific gene expression in developing and adult rod photoreceptors.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Correlation of tumor size and axillary lymph node involvement with prognosis in patients with T1 breast carcinoma.

BACKGROUND: The prognosis of patients with T1 breast carcinoma remains controversial. Some studies have shown a low risk of lymph node metastasis and distant failure whereas others have not, possibly due to differences in the definition of tumor size. In this study, the authors assessed the relation between macroscopic tumor size, microscopic invasive tumor size, axillary lymph node involvement, and prognosis in a group of patients with clinically lymph node negative disease. METHODS: Between 1968 and 1986, 1865 women with American Joint Committee on Cancer clinical Stage I or II infiltrating carcinoma of the breast were treated at the Joint Center for Radiation Therapy with conservative surgery and radiation therapy. The study population was limited to 118 patients with clinically negative axillary lymph nodes for whom the macroscopic pathologic tumor size was identified unambiguously as being < or = 2.0 cm, who underwent an axillary lymph node dissection with at least 6 lymph nodes sampled, and for whom the microscopic size of the invasive component could be determined. The median follow-up time for surviving patients was 134 months (range, 90-208 months). No patients with pathologically negative axillary lymph nodes received systemic therapy. RESULTS: Macroscopic and microscopic tumor sizes differed by > 5 mm in 17 patients (14%), by 3-5 mm in 24 patients (20%), and by < or = 2 mm in 77 patients (65%). The macroscopic tumor size was smaller than the microscopic size in 37 patients (31%), larger in 55 patients (47%), and equal in 26 patients (22%). Pathologic axillary lymph node involvement was present in 21% of all patients. The risk of lymph node involvement was not significantly different for those patients with tumors < or = 1 cm compared with patients with tumors > or = 1.1 cm, regardless of whether tumor size was measured by macroscopic or microscopic examination. The 10-year actuarial rate of freedom from distant recurrence (FFDR) was 91% for lymph node negative patients with macroscopic tumors measuring < or = 1.0 cm compared with 77% for patients with macroscopic tumors measuring > or = 1.1 cm (P = 0.07). When measured microscopically, the rates were 96% and 72%, respectively (P = 0.001). CONCLUSIONS: There often is a discrepancy between microscopic tumor size and macroscopic tumor size. T1 tumors have a substantial risk of axillary lymph node metastasis whether measured macroscopically or microscopically. Among those patients with pathologic lymph node negative tumors who are not treated with systemic adjuvant therapy, microscopic invasive tumor size is a better predictor of 10-year FFDR than macroscopic tumor size. There is a substantial risk of distant failure for patients with tumors whose invasive component microscopically measure > or = 1.1 cm, whereas the prognosis for patients with tumors that microscopically measured < or = 1 cm is excellent. These results suggest that the microscopic size of the invasive component of breast carcinomas < or = 2.0 cm routinely should be reported.

Adult↗
PubMed1998

Placental endogenous retrovirus (ERV): structural, functional, and evolutionary significance.

That endogenous retrovirus (ERV) is present within the placenta of humans and other mammals has been known for the past 25 years, but the significance of this observation is still not fully understood. Much molecular biological data have emerged in recent years to support the earlier electron microscopic data on the presence of placental ERV. The evidence for ERV in animal and human placental tissue is presented, then integrated with data on the presence of ERV in a range of other tissues, in particular teratocarcinoma cells. Placental invasiveness and maternal immunosuppression are then discussed in relation to metalloproteinase secretion, the immunosuppressive potential of retroviruses, and placental growth factors, while the evidence for a functional link between placental protooncogenes and trophoblast malignancy is reviewed. Finally, placental development, structure, and life span are discussed within an evolutionary context. The hypothesis that one or more ancient trophoblastic ERVs could have played a role in the evolution and divergence of all placental mammals is evaluated.

Animals↗
PubMed1998

Isradipine combined with naltrexone persistently reduces the reward-relevant effects of cocaine and alcohol.

Previous studies have revealed that the combination of small doses of isradipine and naltrexone (ISR&NTX) blocks the ability of cocaine to enhance pressing for rewarding, lateral hypothalamic brain stimulation. Further, such combinations also reduce rats' intakes of alcoholic beverages. Here, we asked whether ISR&NTX would lose its ability to reduce the reinforcing effects of cocaine and alcohol when given daily. Specifically, after almost 2 months of daily injections, ISR&NTX blocked the expression of a cocaine-induced conditioned place preference (CPP). By themselves, ISR and NTX were not effective at blocking cocaine's effects. Subsequent to the CPP procedures, the rats continued to receive daily injections for another 3 weeks. During this time, they were given access to water and an alcoholic beverage for 2 h a day. As expected, placebo controls gradually increased their daily intakes until they were taking about 2 g/kg of ethanol daily. ISR, NTX, and ISR&NTX blocked the typical pattern of intakes. At the end of the 3-week period, the rats had received 80 consecutive daily injections. The data suggest that the salient effects of ISR&NTX do not wane. The data support the idea that ISR&NTX would be a useful pharmacotherapy for poly drug abuse.

Animals↗
PubMed1998

Male genital pain syndrome.

Patients who present with concerns that they suffer from sexually transmitted infection frequently suffer from other problems. Occasionally it is simply not enough just to demonstrate that the patient has no evidence of sexually transmitted disease, but it is important to diagnose the cause of their symptoms and to refer them to the appropriate specialty physician for care and attention.

Diagnosis, Differential↗
PubMed1998

Is there a consequence for fetal growth of having an unlike-sexed cohabitant in utero?

BACKGROUND: There is evidence to suggest a masculinizing effect on female intrauterine development in unlike-sexed twins. The purpose of the present report was to examine the possible effects of male presence on fetal growth in females by comparing mean birthweights in members from dizygotic unlike-sexed (DZU) pairs with those from dizygotic like-sexed (DZL) pairs. METHODS: The sample consisted of 1087 DZU and 1089 DZL twin pairs from the New Norwegian Twin Panel, which was established by identifying all twin births from 1967 to 1974 through the population-based Medical Birth Registry. RESULTS: The mean birthweight of females from DZU pairs was 2684+/-15 g (+/-SEM), as opposed to 2647+/-19 g in females from DZL pairs (P = 0.06). For males, the mean birthweight was 2812+/-16 g in DZU pairs and 2805+/-20 g in DZL pairs (P= 0.78). CONCLUSION: We found a tendency for the birthweight in females to be influenced by the presence of a male co-twin. This observation may have a biological significance and should lead to a close follow-up of DZU and DZL females with respect to hormone-sensitive disorders and reproductive ability.

Birth Weight↗
PubMed1998

Radiation therapy and breast cancer.

The role of radiation therapy in the management of breast cancer is well established. Questions remain, however, regarding: 1) which patients derive the most benefit from the addition of radiation in breast conservation for ductal carcinoma in situ (DCIS) and after mastectomy for node-positive invasive cancer; 2) what is the role of brachytherapy in the management of invasive disease, either as primary therapy or as a boost after external beam therapy; and 3) whether radiation fields can be modified given the low rates of local-regional recurrence reported after breast conserving therapy in patients receiving systemic therapy.

Brachytherapy↗
PubMed1998

Managed care and public health.

Both public health and managed care organizations share an interest in ensuring the health status of a defined population. We explore the existing and potential relationships between managed care organizations and public health in several major public health areas, specifically clinical preventive services, prevention-oriented social and political policies, and core public health functions. The latter include health information, health education, personal health services provision, work force and research, community partnerships, and evaluation of health care. We believe there is much potential to improve the population's health through the collaboration of these two sectors of the health care system.

Government Agencies↗
PubMed1998

Papillomavirus assembly requires trimerization of the major capsid protein by disulfides between two highly conserved cysteines.

We have used viruslike particles (VLPs) of human papillomaviruses to study the structure and assembly of the viral capsid. We demonstrate that mutation of either of two highly conserved cysteines of the major capsid protein L1 to serine completely prevents the assembly of VLPs but not of capsomers, whereas mutation of all other cysteines leaves VLP assembly unaffected. These two cysteines form intercapsomeric disulfides yielding an L1 trimer. Trimerization comprises about half of the L1 molecules in VLPs but all L1 molecules in complete virions. We suggest that trimerization of L1 is indispensable for the stabilization of intercapsomeric contacts in papillomavirus capsids.

Capsid↗
PubMed1998

HIV enteropathy: comparative morphometry of the jejunal mucosa of HIV infected patients resident in the United Kingdom and Uganda.

AIMS: To compare jejunal mucosal morphometry in HIV infected patients resident in London and Uganda. PATIENTS: Twenty HIV positive patients from London and 16 from Uganda were studied, and compared with HIV negative control subjects from both sites. METHODS: Stools and biopsy specimens were examined for enteropathogens. Surface area to volume (S:V) ratio was estimated morphometrically, mean crypt length of jejunal biopsy specimens was measured, and HIV infected cells detected immunohistochemically were quantified. RESULTS: Enteric pathogens were detected in none of the London patients, and in three Ugandan patients. S:V ratio was lower, and mean crypt length higher, in the specimens of London patients than in normal subjects, but there was no difference in S:V ratio or mean crypt length between Ugandan patients and controls. A negative correlation was present between S:V ratio and mean crypt length in all biopsy specimens analysed. HIV infected cells were detected only in lamina propria. CONCLUSION: Infection of cells in the lamina propria of the jejunum with HIV stimulates crypt cell proliferation, and a fall in villous surface area. The mucosal response to HIV is masked by other pathogens in the African environment.

Adult↗
PubMed1998

Skin recurrences after breast-conserving therapy for early-stage breast cancer.

PURPOSE: To assess the frequency and prognosis of skin recurrences after breast-conserving therapy (BCT) compared with other breast recurrences. MATERIALS AND METHODS: From 1968 to 1986, 1,624 patients with unilateral stage I or II breast cancer treated with BCT at the Joint Center for Radiation Therapy (Boston, MA) underwent gross tumor excision and received a dose of > or = 60 Gy to the tumor bed. Skin recurrences (SR) were defined as breast recurrences without associated parenchymal disease. An invasive breast recurrence with any parenchymal disease noted clinically or radiographically was scored as an other breast recurrence (OBR). Median follow-up for survivors was 137 months. RESULTS: SR represented 8% (18 of 229) of all breast recurrences and occurred in 1.1% of all patients. The outcome after local recurrence was different for patients with SR and invasive OBR. Patients with SR more frequently had uncontrolled local failure (50%; 9 of 18) than did patients with OBR (14%; 26 of 188) (P = .0007). Forty-four percent (8 of 18) of patients with SR had distant metastasis simultaneously or within 2 months of the recurrence compared with 5% (9 of 188) of invasive OBR patients (P < .0001). For patients without distant metastasis at the time of recurrence, the 5-year actuarial rate of development of distant metastasis was 60% for SR patients compared with 39% for invasive OBR patients (P = .07), and the corresponding 5-year actuarial survival rates beyond the time of local failure were 51% and 79%, respectively (P = .06). CONCLUSION: In contrast to other types of invasive breast recurrence after breast-conserving therapy, skin recurrences are rare and are associated with a significantly higher rate of distant metastasis and uncontrolled local disease as well as a lower rate of survival.

Adult↗
PubMed1998

Cost-effectiveness of routine radiation therapy following conservative surgery for early-stage breast cancer.

PURPOSE: To examine the cost-effectiveness of radiation therapy following conservative surgery for early-stage breast cancer. METHODS: Using a Markov model, a cost-utility analysis was performed to compare a strategy of radiation therapy versus no radiation therapy in a hypothetical cohort of 60-year-old women following conservative surgery. Local recurrence, distant recurrence, and survival rates used in the model were derived from randomized trial data. Utilities for the nonmetastatic health states were collected from actual patients. Direct medical costs were estimated using data from a single institution. Transportation and time costs were also estimated. Years of life, quality-adjusted life-years (QALYs), costs, and incremental cost/QALY over a 10-year time horizon were calculated by the model for each strategy. RESULTS: The addition of radiation therapy results in a cost increase of $9,800 per patient, no change in life expectancy, and an increase of 0.35 QALYs per patient, which leads to an incremental cost-effectiveness ratio of $28,000/QALY, which is well below $50,000/QALY, a commonly cited threshold for cost-effective care. Sensitivity analysis shows the ratio to be heavily influenced by the cost of radiation therapy and the quality-of-life benefit that results from decreased risk of local recurrence. CONCLUSION: Radiation therapy following conservative surgery is cost-effective compared with other accepted medical interventions. This study illustrates the importance of considering an intervention's effect on quality of life, as well as survival in defining cost-effectiveness.

Breast Neoplasms↗
PubMed1998

No long-term increase in cardiac-related mortality after breast-conserving surgery and radiation therapy using modern techniques.

PURPOSE: To determine whether left-breast irradiation using modern techniques after breast-conserving surgery leads to an increased risk of cardiac-related mortality. METHODS: Between 1968 and 1986, 1,624 patients were treated for unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA, with conservative surgery and breast irradiation. Seven hundred forty-five patients with a potential follow-up of at least 12 years were analyzed. Clinical, pathologic, and treatment characteristics were compared between the 365 patients (49%) who received left-sided irradiation and the 380 patients (51%) who received right-sided irradiation. The relationship between left-sided breast irradiation and the risk of nonbreast cancer- and cardiac-related mortality was examined. RESULTS: There was no significant difference in the distribution of clinical, pathologic, or treatment characteristics between the two groups, with the exception of a small difference in pathologic tumor size (medians, left, 2.0 cm, right, 1.5 cm; P = .007). At 12 years, a majority of patients still were alive. Slightly more patients with left-sided tumors had died of breast cancer (31% v 27%; P = NS). Equivalent proportions from each group died of nonbreast cancer causes (11%), including nine patients (2%) from each group who died from cardiac causes. The risk of cardiac mortality did not increase as time after treatment increased for patients who received left-sided irradiation compared with right-sided irradiation. A model that controlled for clinical, pathologic, and treatment differences showed no significant increase in any category of cause of death (breast, cardiac, or other) for patients who received left-sided irradiation. CONCLUSION: These results suggest that modern breast radiotherapy is not associated with an increased risk of cardiac-related mortality within at least the first 12 years after treatment.

Breast Neoplasms↗