sandra andro - Academia.edu (original) (raw)

Papers by sandra andro

Oncology Nursing Forum, 2004

To explore how rural families understand and manage the chemotherapy-induced neutropenia (CIN) ex... more To explore how rural families understand and manage the chemotherapy-induced neutropenia (CIN) experience. Qualitative, inductive approach using family interviews. Family homes in a rural community in the midwestern United States. A convenience sample (7 families [21 people] who had a family member experiencing CIN) recruited from a regional cancer treatment center. Semistructured family interviews that were recorded on audiotape occurred along with constant, comparative analysis over 12 months. An interdisciplinary research team analyzed the transcribed data using grounded theory methodology. The family experience of CIN. An overall family process of turbulent waiting with intensified connections was revealed. Families in the study experienced a sense of vulnerability in response to the diagnosis of CIN. Intensified connections existed within and beyond the families to nurses, physicians, and community members, emphasizing the value of relationships for rural families and highlighting trust in their care providers. Waiting for chemotherapy to resume created a sense of turbulence, an unsettling time described by families as &amp;amp;amp;amp;amp;amp;amp;quot;being on a roller coaster&amp;amp;amp;amp;amp;amp;amp;quot; or &amp;amp;amp;amp;amp;amp;amp;quot;dangling.&amp;amp;amp;amp;amp;amp;amp;quot; To manage the period of waiting and protect the neutropenic patient, families developed family caring strategies, including inquiry, vigilance, and balancing. The process of turbulent waiting with intensified connections led families to a reframed family integrity that included an expanded capacity for caring and protecting. Rural families understand and manage CIN in a context of vulnerability. The threat posed by cancer is heightened by CIN. Family waiting is a rich, interactive process by which families reemphasize relationships to manage neutropenia and is a process that healthcare professionals should acknowledge. Findings suggest the need for further investigation of family caring strategies and for the development of family-level assessment measures in the instance of CIN. Findings contribute to theory development regarding family cancer care and suggest a need to develop an intervention protocol constructed from the perspective of a family-professional partnership.

Molecular Endocrinology, 2002

The porcine gonadal form of aromatase cytochrome P450 (P450arom) exhibits higher sensitivity to i... more The porcine gonadal form of aromatase cytochrome P450 (P450arom) exhibits higher sensitivity to inhibition by the imidazole, etomidate, than the placental isozyme. The residue(s) responsible for this functional difference was mapped using chimeragenesis and point mutation analysis of the placental isozyme, and the kinetic analysis was conducted on native and mutant enzymes after overexpression in insect cells. The etomidate sensitivity of the placental isozyme was markedly increased by substitution of the predicted substrate recognition site-1 (SRS-1) and essentially reproduced that of the gonadal isozyme by substitution of SRS-1 and the predicted B helix. A single isoleucine (I) to methionine (M) substitution at position 133 of the placental isozyme (I(133)M) was proven to be the critical residue within SRS-1. Residue 133 is located in the B&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-C loop and has been shown to be equally important in other steroid-metabolizing P450s. Single point mutations (including residues 110, 114, 120, 128, 137, and combinations thereof among others) and mutation of the entire B and C helixes were without marked effect on etomidate inhibitory sensitivity. The same mutation (I(133)M) introduced into human P450arom also markedly increased etomidate sensitivity. Mutation of Ile(133) to either alanine (I(133)A) or tyrosine (I(133)Y) decreased apparent enzyme activity, but the I(133)A mutant was sensitive to etomidate inhibition, suggesting that it is Ile(133) that decreases etomidate binding rather than Met(133) increasing enzyme sensitivity. Androstenedione turnover and affinity were similar for the I(133)M mutant and the native placental isozyme. These data suggest that Ile(133) is a contact residue in SRS-1 of P450arom, emphasize the functional conservation that exists in SRS-1 of a number of steroid-hydroxylating P450 enzymes, and suggest that substrate and inhibitor binding are dependent on different contact points to varying degrees.

Marine Biotechnology

The discovery of genetic markers linked to physiological traits in wild populations is increasing... more The discovery of genetic markers linked to physiological traits in wild populations is increasingly desired for ecological and evolutionary studies, as well as to inform management decisions. However, identifying such markers often requires a large investment of both time and money. Serendipitously, in a recent microsatellite survey, we discovered three out of 16 microsatellite loci that were correlated to the female sex in Pacific halibut (Hippoglossus stenolepis). These three loci were screened in 550 Pacific halibut to determine their accuracy at identifying sex. Genetic assignment successfully identified sex in 92% of individuals from sample collections spanning 3,000 km and 9 years. All but two of 287 females had one copy of a characteristic allele for at least one of the three microsatellite loci, resulting in consistent heterozygote excess in females. This pattern is consistent with the hypothesis that females are the heterogametic sex in Pacific halibut, which thus may have a different sex-determination pattern than the closely related Atlantic halibut (Hippoglossus hippoglossus). A rapid divergence of sex-determining mechanisms could be either a cause or consequence of speciation between Pacific and Atlantic halibut. In either case, the ability to genetically identify sex in individual Pacific halibut provides a new tool for ecological studies, fisheries management, and insight into the evolution of sex determination in flatfish.

Molecular Human Reproduction, 2002

We report for the first time that penile smooth muscle cells (SMC) not only respond to, but also ... more We report for the first time that penile smooth muscle cells (SMC) not only respond to, but also synthesize, endothelin-1 (ET-1), one of the main regulators of SMC activity. Immunohistochemical studies indicated that, beside endothelial cells (EC), SMC of the human adult and fetal penis also express ET-1 and its converting enzyme, ECE-1. Accordingly, cultures of adult penile stromal cells express these genes. We also prepared and characterized penile SMC from human fetuses. These cells express SMC specific markers such as α smooth muscle actin and phosphodiesterase type 5A3 along with hallmarks of androgen-dependent cells (androgen receptor and 5α reductase type 2). Human fetal penile SMC (hfPSMC) are immunopositive for ET-1 and release ET-1.

Activating mutations of the G protein genes have been associated with the development of several ... more Activating mutations of the G protein genes have been associated with the development of several endocrine neoplasms. Such activating mutations, gip2, affecting the ␣-subunit of the G␣ i2 protein were previously described by a single group in 30% of ovarian sex cord stromal tumors. Other activating mutations of the ␣-subunit of the G s (gsp) have been identified in GH-secreting and nonfunctioning pituitary tumors, autonomous thyroid adenomas, and all affected Mc-Cune-Albright tissues, but not in sex cord stromal tumors. In the present study, we investigated the presence of gip2 and gsp mutations in 14 human sex cord stromal tumors. Six Leydig cell tumors (4 ovaries and 2 testes), 2 thecomas, 2 granulosa cell tumors, 3 andro-

Endocrine Reviews, 2005

Aging in men is accompanied by a progressive, but individually variable decline of serum testoste... more Aging in men is accompanied by a progressive, but individually variable decline of serum testosterone production, more than 20% of healthy men over 60 yr of age presenting with serum levels below the range for young men. Albeit the clinical picture of aging in men is reminiscent of that of hypogonadism in young men and decreased testosterone production appears to play a role in part of these clinical changes in at least some elderly men, the clinical relevancy of the age-related decline in sex steroid levels in men has not been unequivocally established. In fact, minimal androgen requirements for elderly men remain poorly defined and are likely to vary between individuals. Consequently, borderline androgen deficiency cannot be reliably diagnosed in the elderly, and strict differentiation between &amp;amp;amp;amp;amp;quot;substitutive&amp;amp;amp;amp;amp;quot; and &amp;amp;amp;amp;amp;quot;pharmacological&amp;amp;amp;amp;amp;quot; androgen administration is not possible. To date, only a few hundred elderly men have received androgen therapy in the setting of a randomized, controlled study, and many of these men were not androgen deficient. Most consistent effects of treatment have been on body composition, but to date there is no evidence-based documentation of clinical benefits of androgen administration to elderly men with normal or moderately low serum testosterone in terms of diminished morbidity or of improved survival or quality of life. Until the long-term risk-benefit ratio for androgen administration to elderly is established in adequately powered trials of longer duration, androgen administration to elderly men should be reserved for the minority of elderly men who have both clear clinical symptoms of hypogonadism and frankly low serum testosterone levels.

Gene expression analysis showed that a human mindin homologue, mindin/RG-1, is expressed selectiv... more Gene expression analysis showed that a human mindin homologue, mindin/RG-1, is expressed selectively in prostate tissues and that its expression level is elevated in some prostate tumors. Mindin/RG-1 protein expression is maintained in >80% of prostate cancers metastatic to bone or lymph nodes as well as in locally recurrent tumors in androgen-unresponsive patients. In contrast, mindin/RG-1 expression in other normal tissues is significantly lower than that seen in the prostate. A fully human antibody, 19G9, was generated against mindin/RG-1 protein and was shown to accumulate at high abundance in LNCaP tumor xenografts. Conjugates of this antibody with the chelator CHX-A 00 -DTPA were generated and radiolabeled with either 111 In, 90 Y, or 86 Y. Small animal positron emission tomography imaging with the 86 Y-radiolabeled conjugate showed very specific accumulation of the antibody in LNCaP tumor xenografts with clear tumor delineation apparent at 4 hours. The therapeutic efficacy of [ 90 Y]-CHX-A 00 -DTPA-19G9 was evaluated in mice bearing LNCaP xenografts. A dose-finding study identified a nontoxic therapeutic dose to be f75 MCi. Significant antitumor effects were seen with a single administration of radiolabeled antibody to animals bearing 200 to 400 mm 3 tumors. Inhibition of tumor growth was observed in all treated animals over a 49-day period. At 49 days posttreatment, slow tumor growth recurred but this could be prevented for an additional 40-day period by a second administration of a 75 MCi dose at day 49. We conclude that [ 90 Y]-CHX-A 00 -DTPA-19G9 is a novel antibody conjugate that has considerable promise for therapy of metastatic prostate cancer in androgen-unresponsive patients. (Cancer Res 2005; 65(18): 8397-405) Requests for reprints: Renate Parry,

Nursing Management (springhouse), 1987

The health care environment has undergone major changes in recent years, and hospitals have had t... more The health care environment has undergone major changes in recent years, and hospitals have had to adjust their operating philosophies. The hospitals that survive as providers of inpatient care will be those best able to produce services efficiently and effectively. Efforts ...

Endocrinology, 2004

By real-time RT-PCR and Western blot analysis, we found that phosphodiesterase type 5 (PDE5) mRNA... more By real-time RT-PCR and Western blot analysis, we found that phosphodiesterase type 5 (PDE5) mRNA and protein abundance was several fold higher in human male than in female reproductive tracts. The highest mRNA level (>1 ؋ 10 7 molecules/g total RNA) was detected in human corpora cavernosa (CC), where PDE5 protein was immunolocalized in both muscular and endothelial compartment. The possible role of androgens in regulating PDE5 expression was studied using a previously established rabbit model of hypogonadotropic hypogonadism. In this model, hypogonadism reduced, and testosterone (T) supplementation restored, CC PDE5 gene and protein expression. In addition, T supplementation completely rescued and even enhanced cyclic GMP conversion to metabolites, without changing IC 50 for sildenafil (IC 50 ‫؍‬ 2.16 ؎ 0.62 nM). In control CC strips, sildenafil dose-dependently increased relaxation induced by electrical field stimulation, with EC 50 ‫؍‬ 3.42 ؎ 1.7 nM. Hypogonadism reduced, and T increased, sildenafil effect on electrical field stimulation, again without changing their relative EC 50 values. CC sensitivity to the NO-donor NCX4040 was greater in hypogonadal rabbit strips than in control or T-treated counterparts. Moreover, sildenafil enhanced NCX4040 effect in eugonadal rabbit strips but not in hypogonadal ones. This suggests that androgens up-regulate PDE5 in rabbit penis. We also measured PDE5 gene expression and metabolic activity in human CC from male-to-female transsexual individuals, chronically treated with estrogens and cyproterone acetate. Comparing the observed values vs. eugonadal controls, PDE5 mRNA, protein, and functional activity were significantly reduced. In conclusion, we demonstrated, for the first time, that androgens positively regulate PDE5, thus providing a possible explanation about the highest abundance of this enzyme in male genital tract.

BMC Health Services Research, 2010

Background Interventions to improve blood pressure control in hypertension have had limited succe... more Background Interventions to improve blood pressure control in hypertension have had limited success in clinical practice despite evidence of cardiovascular disease prevention in randomised controlled trials. The objectives of this study were to evaluate blood pressure control and antihypertensive pharmacotherapy patterns in a population of Eastern Central Region of Portugal, attending a hospital outpatient clinic (ambulatory setting) for routine follow-up. Methods Medical data of all patients that attended at least two medical appointments of hypertension/dyslipidemia in a university hospital over a one and a half year period (from January 2008 to June 2009) were retrospectively analysed. Demographic variables, clinical data and blood pressure values of hypertensive patients included in the study, as well as prescribing metrics were examined on a descriptive basis and expressed as the mean ± SD, frequency and percentages. Student's test and Mann-Whitney rank sum test were used to compare continuous variables and χ2 test and Fisher exact probability test were used to test for differences between categorical variables. Results In all, 37% of hypertensive patients (n = 76) had their blood pressure controlled according to international guidelines. About 45.5% of patients with a target blood pressure <140/90 mmHg (n = 156) were controlled, whereas in patients with diabetes or chronic kidney disease (n = 49) the corresponding figure was only 10.2% (P < 0.001). Among patients initiating hypertension/dyslipidemia consultation within the study period 32.1% had stage 2 hypertension in the first appointment, but this figure decreased to 3.6% in the last consultation (P = 0.012). Thiazide-type diuretics were the most prescribed antihypertensive drugs (67%) followed by angiotensin receptor blockers (60%) and beta-blockers (43%). About 95.9% patients with comorbid diabetes were treated with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Conclusions Clinically important blood pressure decreases can be achieved soon after hypertension medical appointment initiation. However, many hypertensive patients prescribed with antihypertensive therapy fail to achieve blood pressure control in clinical practice, this control being worse among patients with diabetes or chronic kidney disease. As pharmacotherapy patterns seem to coincide with international guidelines, further research is needed to identify the causes of poor blood pressure control.