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Biomedical subjects

K Wade

Publications and source records attributed to K Wade.

At least 19 recordsLinked to original sources
PubMed2005

Tissue- and bone cell-specific expression of bone sialoprotein is directed by a 9.0 kb promoter in transgenic mice.

Bone sialoprotein (BSP) is a phosphorylated glycoprotein that is expressed almost exclusively in mineralizing connective tissues. In bone, expression of BSP correlates with the differentiation of osteoblasts and the onset of mineralization. To determine how the tissue- and differentiation-specific transcription of BSP is regulated, various lengths of promoter sequence were ligated to a luciferase reporter and stably transfected into a rat stromal bone marrow cell line, RBMC-D8 and undifferentiated C3H10T1/2 cells. Luciferase transcription of reporter constructs including 5.4 kb (mBSP5.4Luc) and 9.0 kb (mBSP9.0Luc) of the BSP promoter was strongly up-regulated in parallel with endogenous BSP mRNA in differentiating SBMCs, but not in C3H10T1/2 cells. In contrast, 0.1 kb and 1.4 kb BSP promoter constructs did not show selective expression. To determine tissue-specific expression in vivo, transgenic mice expressing reporter constructs for the 9.0 kb promoter and a 4.8 kb promoter lacking two upstream Cbfa1/Runx2 elements (mBSP9.0Luc and mBSP4.8Luc, respectively) were generated. Analysis of various tissues collected from 1-, 4-, 7-, 14-, and 42-day-old mice revealed extremely high levels of luciferase activity in calvaria, mandible, and tibia of the mBSP9.0Luc mice. In contrast, soft tissues showed negligible luciferase expression. Mice harboring the 4.8 kb transgene also showed selective luciferase expression but displayed a significantly lower activity in mineralized tissues. Northern hybridization of endogenous BSP mRNA and immunostaining of BSP in mBSP9.0Luc mice showed a temporo-spatial expression pattern consistent with the luciferase activity. These results indicate that regulatory elements within the 9.0 kb region of the promoter are required for strong, tissue- and differentiation-specific expression of BSP.

Animals↗
PubMed2002

Minimally invasive bar repair for 'redo' correction of pectus excavatum.

BACKGROUND/PURPOSE: A small percentage of patients who have undergone traditional, "Ravitch-type" pectus excavatum repair present with unsatisfactory results and require a second procedure for correction. Reoperative open surgery for pectus excavatum has been associated with extensive dissection and substantial blood loss. The minimally invasive (MIS) bar repair for the correction of pectus excavatum has been gaining acceptance. This study evaluates the authors results with patients who have undergone the MIS bar repair for redo correction of their pectus excavatum. METHODS: A retrospective chart review of all patients undergoing MIS bar repair between December 1997 and August 2001 was performed. Information about demographics, deformity, operative course, complications, and early outcome was recorded. RESULTS: Ninety-two patients underwent MIS repair during this period. Ten patients had redo MIS bar repair for unsatisfactory prior open correction. Operating time was 52 minutes for standard patients and 70 minutes for the redo patients (P <.001). Blood loss and postoperative hospitalization were similar between groups. CONCLUSION: The minimally invasive pectus repair can be performed safely with minimal blood loss and short operating time in patients who have undergone prior unsatisfactory open repair of pectus excavatum and can be an alternative approach to reoperative open repair in these patients.

Child↗
PubMed2001

Minimally invasive repair of pectus excavatum: a single institution's experience.

BACKGROUND: The Nuss repair of pectus excavatum is a relatively new, minimally invasive surgical (MIS) alternative to the traditional open "Ravitch-type" operation. We have one of the larger single-center experiences to date, and we conducted this clinical study to evaluate our early experience, emphasizing initial outcome and technical modifications designed to minimize complications. METHODS: A retrospective chart review was performed on 112 patients who underwent 116 pectus excavatum repairs between January 1995 and January 2001. The Nuss procedure was performed in 80 patients, and open repair was performed in 32 patients. Information about demographics, deformity, operative course, complications, and early outcome was recorded. RESULTS: Operative duration was 143 minutes for the open group and 53 minutes for the Nuss MIS group (P <.001). Blood loss was 6 mL/kg for the open group and 0.5 mL/kg for the MIS group (P <.001). Postoperative hospitalization was 3.2 days for the open group versus 3.7 days for the MIS group (P<.05). CONCLUSIONS: The MIS pectus repair can be performed safely with minimal blood loss and reduced operative time. Short-term analysis of the quality of repair, including absence of preoperative symptoms, patient satisfaction, and cosmetic appearance are encouraging.

Adolescent↗
PubMed2000

Clinical-histopathological correlation of the abnormal retinal vessels in cerebral malaria.

BACKGROUND: Clinically abnormal retinal vessels unique to cerebral malaria have previously been shown to be associated with a poor outcome in African children. There have been no studies of the histopathological correlates of these vessels. DESIGN: This is a descriptive study of the clinical-histopathological correlates of the retinal vessels of 11 children who died with cerebral malaria. RESULTS: The retinal vessels in children with cerebral malaria contained many parasitized red blood cells; these cells tended to cluster at the periphery of vessels or, in the case of capillaries, to fill the vessel. Those with late-stage parasites had markedly reduced amounts of hemoglobin. The pattern of dehemoglobinization corresponds to the pattern of clinically abnormal vessels. CONCLUSIONS: The sequestration of late-stage parasitized red blood cells with reduced amounts of hemoglobin accounts for the unique white and pale orange retinal vessels seen in cerebral malaria. Clinical examination of these "marked" vessels offers a method to monitor a basic pathophysiological process of cerebral malaria in vivo. Arch Ophthalmol. 2000;118:924-928

Animals↗
PubMed1996

Inhibition of 5-lipoxygenase-activating protein (FLAP) reduces pulmonary vascular reactivity and pulmonary hypertension in hypoxic rats.

Chronically elevated shear stress and inflammation are important in hypertensive lung vessel remodeling. We postulate that 5-lipoxygenase (5-LO) is a molecular determinant of these processes. Immunohistology localized the 5-LO to macrophages of normal and chronically hypoxic rat lungs and also to vascular endothelial cells in chronically hypoxic lungs only. In situ hybridization of normal and chronically hypoxic lungs demonstrated that 5-LO mRNA is expressed in macrophages. Rats hypoxic for 4 wk-developed pulmonary hypertension increased translocation of the lung 5-LO from the cytosol to the membrane fraction and increased levels of lung tissue 5-lipoxygenase-activating protein (FLAP). A FLAP ligand, 3-[l-(4-chlorobenzyl)-3-t-butyl-thio-t-isopropylindol-2-yl]-2,2- dimethylpropanoic acid (MK-886), inhibited the acute angiotensin II and hypoxia-induced pulmonary vasoconstriction in vitro and the development of chronic hypoxic pulmonary hypertension in rats in vivo. Mice bred with the deletion of the 5-LO enzyme (5-LO knockout) developed less right heart hypertrophy than age-matched 5-LO competent mice. Our results support the hypothesis that the 5-LO is involved in lung vascular tone regulation and in the development of chronic pulmonary hypertension in hypoxic rodent models.

5-Lipoxygenase-Activating Proteins↗
PubMed1996

An economic analysis of two models of hospital care for AIDS patients: implications for hospital discharge planning.

The development of cost effective models of hospital care and discharge planning for people with HIV is a vital policy issue. However, almost no data exist evaluating cost and quality differences in alternate hospital models of care. This empirical study retrospectively evaluates social work discharge planning for patients with HIV disease in two hospital care models: a cluster AIDS unit and general inpatient site beds. The independent effect of each hospital model of care on length of stay is assessed in a multivariate analysis, controlling for level of care needs and other social and clinical factors. Results reveal that the cluster AIDS unit, where a specialized AIDS social work staff works in collaboration with the interdisciplinary AIDS team, is associated with a significant reduction in hospital length of stay for persons with HIV disease and complex discharge planning needs. These results support the hypothesis that discharge planning services, performed by specialized social workers, are a cost effective investment for hospitals treating patients with complex chronic conditions, such as AIDS. Further research should be developed to systematically evaluate the cost effectiveness of hospital-based social workers, using prospective experimental designs, in order to establish the net impact of social work discharge planning services on patient and family outcomes and institutional and social costs.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Bryostatin 1, a novel antineoplastic agent and protein kinase C activator, induces human myalgia and muscle metabolic defects: a 31P magnetic resonance spectroscopic study.

Bryostatin 1, a novel antineoplastic agent and protein kinase C (PKC) activator, has been found to induce myalgia (muscle pain) 48 h after administration in clinical trials. This is the dose-limiting toxicity and has restricted the duration of therapy in phase I trials. To investigate the mechanisms and try to increase toleration of the drug, we studied calf muscle metabolism of 14 patients at rest and during exercise and subsequent recovery using 31P magnetic resonance spectroscopy (MRS) before and 4 h, 48-72 h and 1-2 weeks following bryostatin therapy. In resting muscle there was a significant (P < 0.001) increase in the phosphodiester/adenosine 5'-triphosphate (PDE/ATP) ratio 48 h post bryostatin and in patients with myalgia compared with pre-bryostatin control studies. Following exercise, patients with myalgia showed significantly slower phosphocreatine (PCr) and ADP recovery half-time (P < or = 0.05) suggesting impaired mitochondrial (oxidative) energy production, possibly due to a direct effect on the mitochondria or secondary to reduced blood flow. The apparent proton efflux rate following exercise was significantly reduced 4 h after bryostatin (P < or = 0.05), suggesting reduced blood flow. The rate of post-exercise reoxygenation was studied in four patients by near-infrared spectroscopy 4 h post bryostatin. In three of these the rate was reduced, consistent with reduced muscle blood flow. Bryostatin 1 appeared to cause a long-lasting impairment of oxidative metabolism and proton washout from muscle, consistent with a vasoconstrictive action. Thus these studies provide evidence for two mechanisms of the dose-limiting toxicity for bryostatin. Prospective studies on the use of vasodilators to improve the tolerance of the drug should be carried out.

Adenosine Triphosphate↗
PubMed1995

Tuberculosis and AIDS: the impact on the hospital social worker.

The second decade of the AIDS epidemic is marked by increasing numbers of people being diagnosed with HIV infection as well as mycobacterium infection (pulmonary tuberculosis). The convergence of these two epidemics presents new challenges for social workers. Serious threat of HIV infection from occupational exposure was diminished by the knowledge of roots of disease transmission. TB, on the other hand, is an airborne infectious disease. Social workers working with patients over long periods of time in confined spaces can be at risk for contracting TB. Hospital social workers must struggle and advocate for full information regarding the incidence of risk and risk precaution. They must find ways of coping with their own emotional responses to the resurgence of TB and their own fear of exposure to avoid physical and emotional withdrawal from their HIV infected patients. This paper will address the unique impact on the worker's personal safety, the impact on the therapeutic relationship with the patient, and provide action steps for workers facing these challenges.

AIDS-Related Opportunistic Infections↗
PubMed1994

The Lactational Amenorrhea Method (LAM): a postpartum introductory family planning method with policy and program implications.

It is well accepted that breastfeeding contributes significantly to child survival and child nutrition. Healthful child spacing is associated with improved birth outcomes and maternal recovery. On a population basis, breastfeeding may contribute more to birth spacing than all family planning use combined in many countries. However, while breastfeeding does provide a period of infertility, until recently, there was no reliable way for an individual woman to capitalize on this lactational infertility for her own efficacious child spacing. The Lactational Amenorrhea Method (LAM) is a new introductory family planning method that simultaneously promotes child spacing and breastfeeding, with its optimal nutrition and disease preventive benefits for the infant. LAM, as it is called, is based on the utilization of lactational infertility for protection from pregnancy and indicates the time for the introduction of a complementary family planning method. LAM is recommended for up to six months postpartum for women who are fully or nearly fully breastfeeding and amenorrheic, and relies on the maintenance of appropriate breastfeeding practices to prolong lactational infertility, with the concomitant delay in menses return. A recent clinical trial confirmed the theoretical 98% or higher effectiveness of the method and field trials are demonstrating its acceptability. Nonetheless, some demographers and family planning organizations continue to debate its value. The development, efficacy, and sequelae of the method are presented using data from several studies by the authors.

Amenorrhea↗
PubMed1993

Survival bonding: a response to stress and work with AIDS.

There is ample literature describing the ongoing stressors and tremendous emotional impact on health care professionals caring for patients with AIDS. This paper is a report of a research study which explored collegial relationships and staff retention to determine factors that reduced staff burnout. The study explored an observed phenomenon of pairing among staff members of various disciplines, working with patients with AIDS, in a tertiary care hospital. The authors called this phenomenon "survival bonding." These informal but intense relationships offered staff a mutually supportive environment which reduced their anxiety, stress, and helped prevent burnout. Given the growing volume of HIV infected persons, and the increased work load of many health care professionals in the aids field, it is important to understand the complex emotional and social support needs of staff to prevent burnout and to improve staff recruitment and retention.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Release of cholecystokinin from rat midbrain slices and modulatory effect of D2DA receptor stimulation.

Cholecystokinin octapeptide (CCK-8) is colocalized within a majority of dopamine (DA)-containing neurons of the rat midbrain. Exogenous CCK-8 can modulate the electrophysiological activity of DA neurons, at least in part, by direct actions on the somatodendritic region of these cells. If CCK-8 is somatodendritically released from DA neurons, it may influence DA cell function as has been shown for DA itself. In the present study, radioimmunoassay was used to determine if CCK-8 is released in vitro from slices of rat midbrain under basal and depolarizing (30 mM potassium) conditions. Low levels of CCK-8 were detected in the basal incubation medium. Thirty mM potassium caused about a 3-fold increase in the release of CCK-8. This stimulated release was abolished in calcium-free medium. The D2 receptor agonist quinpirole, but not the D1 agonist SKF 38393, attenuated the potassium-stimulated release of CCK-8 but did not affect basal release. These results show that CCK-8, like DA, can be released from midbrain slices, presumably from DA/CCK-8-containing neurons. This finding is in accordance with the possibility that CCK-8 plays a role in the regulation of DA neuronal function at the level of the cell body, where it might influence the excitability of the DA cell membrane.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Clinical support groups that work.

A support group for nurses who care for patients with AIDS has been meeting at a major teaching hospital in New York City for the past year. The authors believe its success has been determined by three components: the group's ability to first, express feelings; second, do a needs assessment and plan programs to meet those needs; and third, participate in the organizational development system of the hospital. Management recognizes the importance of the group, endorses it, and supports it verbally and behaviorally.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Uterine sarcoma: steroid receptors and response to hormonal therapy.

Seventy-three patients with uterine sarcomas were treated between 1976 and 1987. Steroid receptors were analyzed in 60 cases; 48% were estrogen receptor (ER) positive, and 30% progesterone receptor (PR) positive. Only 1 of 28 patients with residual or recurrent disease showed a response to hormonal therapy. Neither receptor status of the primary tumor nor use of adjuvant hormonal therapy affected survival.

Adult↗