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Biomedical subjects

M Luna

Publications and source records attributed to M Luna.

At least 19 recordsLinked to original sources

Late cytomegalovirus pneumonia in adult allogeneic blood and marrow transplant recipients.

To assess the impact of antiviral prophylaxis during the first 3 months after transplantation on the frequency, timing, and outcome of cytomegalovirus (CMV) pneumonia during the first year, 541 adult allogeneic blood and marrow transplant recipients were evaluated. Thirty-four patients (6.3%) developed 35 episodes of CMV pneumonia at a mean of 188 days after transplantation, with an associated mortality rate of 76%. Twenty-six episodes (74%) occurred late (after day 100). Of the patients with late CMV pneumonia almost all (92%) had chronic graft vs. host disease or had received T cell-depleted transplants. Fourteen late CMV pneumonias (54%) were associated with serious concurrent infections, and 100% of these episodes were fatal. In conclusion, although the frequency of CMV pneumonia in the early posttransplantation period may be substantially reduced by prophylaxis, CMV continues to be a major cause of morbidity and mortality in the late period. Some subsets of patients need more prolonged surveillance and prophylaxis and/or preemptive therapy.

Adolescent

Infant heart transplantation: improved intermediate results.

OBJECTIVES: Our objectives were to (1) review our experience with heart transplants in infants (age < 6 months), (2) delineate risk factors for 30-day mortality, and (3) compare outcomes between our early and recent experience. METHODS: Records of all infants listed for transplantation in our center before September 1996 were analyzed. Early and recent comparisons were made between chronologic halves of the accrual period. Univariate analysis was used to analyze potential risk factors for 30-day mortality (categorical variables, Fisher's exact test; continuous variables, nonparametric Wilcoxon rank-sum test). Multivariable analysis included univariate variables with p values < or = 0.10. Actuarial survivals were estimated (Kaplan-Meier) and compared by the log-rank test. RESULTS: Fifty-one of the 60 infants listed for transplantation were operated on (waiting list mortality 15%). Thirty-day mortality was 18% overall, 30% in the first 3 years and 10% in the last 3 years (p = 0.07). Sepsis was the commonest cause of early death (4/9). Univariate analysis suggested four potential risk factors for early death: preoperative mechanical ventilation (p = 0.01), prior sternotomy (p = 0.002), preoperative inotropic drugs (p = 0.08), and warm ischemia time (p = 0.08). Multivariable analysis indicated that prior sternotomy (p = 0.01) was an independent risk factor for 30-day mortality. Actuarial survivals were 80%, 78%, and 70% at 1, 2, and 3 years, and these figures improved between early and recent groups (p = 0.05). Late deaths were most commonly due to acute rejection (3/5). CONCLUSIONS: Results of heart transplantation in infancy improve with experience. Prior sternotomy increases initial risk. Intermediate-term survival for infants with end-stage heart disease is excellent.

Case-Control Studies

Mycoflora and naturally occurring mycotoxins in poultry feeds in Argentina.

The purpose of this work was to determine the mycoflora and mycotoxins natural incidence in poultry feeds from 2 factories in Río Cuarto, Córdoba. One hundred and thirty samples were taken from May/1996 to May/1997. The most dominant species isolated of poultry feed samples belonged to the genera Aspergillus spp 85% and Fusarium spp 70%. From Aspergillus genus eleven species were identified and A. flavus was the most frequent. Nine species were identified from the Fusarium genus and the predominant was F. moniliforme. Penicillium ranked third in the number of isolated cases. From this genus twelve species were collected of which P. brevicompactum (15%), P. restrictum (14%) and P. purpurogenum (12%) were the most common. The most significant mycotoxin from poultry feeds was aflatoxin B1 (AFB1) found in 48% of the samples, with levels ranging from 10 to 123 ng/g. For zearalenone (ZEA) the levels were 327 to 5, 850 ng/g and DON was not detected from the samples. Due to the fact that in Argentina there is little information about this topic, these data on poultry feeds in our region would be of worldwide interest.

Aflatoxin B1

Influenza among hospitalized adults with leukemia.

Influenza is one of the most important respiratory diseases of mankind, yet scant data exist concerning the frequency and clinical course of influenza in severely immunocompromised adults. From October 1993 to September 1994, we cultured the respiratory secretions of all adults with leukemia who were hospitalized with an acute respiratory illness at The University of Texas M.D. Anderson Cancer Center in Houston. During a 9-week period from 29 November 1993 to 29 January 1994, influenza virus type A (H3N2) was isolated from 15 (33%) of these 45 hospitalized adults. Twelve (80%) of the cases of influenza were associated with pneumonia, and four patients (33%) with pneumonia died. Patients who died tended to have received chemotherapy more recently and to be more myelosuppressed. Autopsy examination in two cases revealed histopathologic changes consistent with viral pneumonia. During community outbreaks, influenza is a frequent cause of serious respiratory disease in hospitalized adults with leukemia. Effective prophylactic and therapeutic regimens need to be defined for immunocompromised patients.

Adult

Stress and coping among parents of children awaiting cardiac transplantation.

Psychosocial support during the waiting period for pediatric transplant recipients and their families is vital. This study describes the stress levels and coping techniques among parents of children awaiting cardiac transplant. Twenty-six parents of 18 children demonstrated a range of stress with 77% scoring at a moderate stress level. They perceived transplantation neutrally and used a similar number of coping mechanisms as did a normative group of adults. Use of coping mechanisms significantly decreased over the 3-month study period. A moderate correlation between a negative perception of transplantation and parental stress was found. Parents of girls viewed transplant more negatively than did boys' parents. This study provides a beginning for assisting families during the waiting period.

Adaptation, Psychological

The induction of benign epithelial neoplasms of the ovaries of guinea pigs by testosterone stimulation: a potential animal model.

We studied the effects of different hormones on the epithelial cells of the ovaries of 11 guinea pigs. Three received testosterone, two received estrone, three megestrol, and three chorionic gonadotropin. Three control guinea pigs received sterile water. Benign epithelial cysts larger than 1.5 mm were found in six guinea pigs, three who received testosterone, one who received megestrol, and two who received chorionic gonadotropin. In one of the three guinea pigs who received testosterone, 2.5-cm bilateral cysts were grossly identified. Papillary excrescences were found on the ovarian surface in four guinea pigs, three who received testosterone and one who received megestrol. The proliferating epithelial cells also formed benign glands in the ovarian stroma in two guinea pigs who received testosterone, the most exuberant epithelial proliferations, including large bilateral cystadenomas, papillary excrescence that formed a small papillary neoplasm, and glands in the ovarian stroma that formed adenomatous areas, were seen in the guinea pig who received an intermediate dose of testosterone for the longest time. By radioimmunoassay, the serum level of testosterone was 22 ng/dL in one of the controls and 10,000, 12,000, and 15,000 ng/dL in the three guinea pigs who received testosterone. In the guinea pig with the most exuberant epithelial proliferation, the level of testosterone in the uterus was similar to that in the serum (13,860 ng/mg), but in the wall of the ovarian epithelial cyst, it was three times higher than it was in the serum (44,000 ng/mg). Our study shows that testosterone stimulates the growth of epithelial cells in the ovaries of guinea pigs, resulting in benign cysts, small adenomas in the ovarian parenchyma, and papillomas on the ovarian surface. The study also shows that guinea pigs can be used as an animal model for epithelial tumors of the human ovary.

Animals

p53, Rb, and cyclin D1 expression in human oral verrucous carcinomas.

BACKGROUND: The verrucous carcinoma (VC), a tumor with low grade malignancy, appears to be associated with tobacco and human papillomavirus. The pathobiology of these tumors has not been extensively studied, and molecular genetic alterations have not been reported. In this study we investigated by immunohistochemistry the expression of p53, Rb, and cyclin D1 in a series of well-defined oral VC. Changes in the expression of these genes have been commonly reported in a variety of human tumors. METHODS: We studied 29 cases of VC, fixed in formalin and embedded in paraffin. Immunohistochemistry was carried out using the avidin-biotin immunoperoxidase technique. Polyclonal antibody CM-1 was used for p53, a rabbit polyclonal human RB antibody, Rb-WL-1 antibody for Rb and a rabbit polyclonal human cyclin D antibody for cyclin D1. RESULTS: Positive p53 expression (protein accumulation) was detected in 15 of the 29 VC analyzed. In some cases, p53-positive areas were small foci but in most of the cases extensive positive areas were observed. None of the cases studied showed alterations of Rb protein. The expression of cyclin D1 was determined in 18 cases of VC. Positive nuclear immunostaining was seen in 11 cases. CONCLUSIONS: p53 protein accumulation is frequently observed in these tumors suggesting possible mutations of this gene in VC. Overexpression of cyclin D1 but no alterations of Rb staining were also observed in this low grade tumor suggesting that Rb may be functionally inactivated by overexpression of cyclin D1 or HPV infection.

Adult

Cellular targets and molecular responses associated with photodynamic therapy.

The positive clinical results associated with photodynamic therapy (PDT) have led to an expanded need to identify the cellular targets and molecular responses associated with this treatment. Increased knowledge regarding the mechanisms of action associated with PDT-mediated cytotoxicity should contribute to the continued advancement of this therapy. This report focuses on recent studies analyzing PDT resistance and examining stress protein and early response gene activation induced by photosensitizer mediated oxidative stress. Recurring observations from these studies indicate that subcellular targets and cellular responses associated with PDT can vary significantly for different photosensitizers.

Animals

Respiratory disease due to parainfluenza virus in adult bone marrow transplant recipients.

We reviewed the frequency and clinical course of parainfluenza virus (PIV) infections in 1,173 adult bone marrow transplant (BMT) recipients cared for at The University of Texas M.D. Anderson Cancer Center (Houston). Between January 1991 and September 1994, PIV was isolated from the respiratory secretions of 61 (5.2%) of these patients. Thirty-four (56%) of the 61 patients had uncomplicated upper respiratory tract illnesses and survived. The remaining 27 patients (44%) developed pneumonia, and the associated mortality was 37% (10 of 27 patients). Twenty-three (85%) of the patients with pneumonia had had preceding upper respiratory illnesses. Of the 10 patients who died, nine died within 100 days after transplantation. Histopathologic examination of lung tissue from seven patients revealed intracytoplasmic viral inclusions in six, a finding consistent with invasive PIV pneumonia, and viral changes in the seventh patient. Seven of the 10 patients who died had other serious concurrent infections. Of 42 patients who developed PIV infection early after transplantation (i.e., < 100 days), the frequency of pneumonia was higher among the 18 allogeneic BMT recipients (61%) than among the 24 autologous BMT recipients (42%), and the associated mortality was also higher (55% vs. 30%, respectively). PIVs are an important cause of life-threatening pneumonia in adult BMT recipients, particularly patients who have recently undergone allogeneic bone marrow transplantation.

Adult

Causes of initial remission induction failure in patients with acute myeloid leukemia and myelodysplastic syndromes.

We analyzed 144 of 475 previously untreated patients with acute myeloid leukemia (AML, n = 87) and 'high-risk' myelodysplastic syndromes (MDS, n = 57) who failed to achieve a complete remission with fludarabine- and high-dose cytarabine-containing regimens between 1991 and 1994. The AML and MDS groups were comparable with regard to age, major prognostic indicators, supportive care received, type of antileukemia response and causes of death and were considered together. The causes of death of 118 evaluable patients were compared to a series of 123 AML initial remission induction failures previously reported from our institution. The induction failure rate was significantly lower (30 vs 43% P <0.001). We found a significant decrease in fatal infections (autopsied patients, P = 0.001) and a reduction in bacterial (autopsied and non-autopsied patients, P <0.005) but not fungal (non-autopsied patients, P = 0.93; autopsied patients P = 0.15) infections as causes of induction death. Pulmonary hemorrhage was twice as common in the present report (P < 0.005, with pulmonary hemorrhage almost three times as common as fatal cerebral hemorrhage. A comparison restricted to the AML patients in the present study yielded similar results. We conclude that the mortality profile in AML remission induction has undergone substantial changes at our institution since our last report, probably as a consequence of the introduction of new chemotherapy regimens and supportive care modalities.

Acute Disease

Osteosarcoma hybrids can preferentially target alkaline phosphatase activity to matrix vesicles: evidence for independent membrane biogenesis.

Alkaline phosphatase is the marker enzyme for matrix vesicles, extracellular organelles that play a major role in primary bone formation and calcification. Recently, we developed osteosarcoma x fibrosarcoma hybrids in which alkaline phosphatase expression was greatly reduced, a phenomenon known as extinction. In the present study, we used to cell hybrids, LTA-1 and LTA-5, constructed from a human osteoblast-like osteosarcoma. TE85, and a mouse fibrosarcoma, La-t-, to examine the differential distribution of alkaline phosphatase between matrix vesicles and the plasma membrane, postulated to be the parent membrane from which matrix vesicles are derived. While alkaline phosphatase in plasma membranes was extinguished, enzyme activity in matrix vesicles from LTA-1 hybrid cells was 34.2% of that present in matrix vesicles from the TE85 parent cells and 200 times that found in La-t- matrix vesicles. Matrix vesicles from LTA-5 had alkaline phosphatase levels similar to La-t-. When other membrane enzymes (phospholipase A2, 5'-nucleotidase, and Na+/K+ ATPase) were examined, hybrid matrix vesicle and plasma membrane levels were similar to those of TE85 and significantly higher than in La-t- membrane fractions. Northern analysis detected mRNA for alkaline phosphatase in TE85 cells, but not in the hybrids or La-t- cells. In contrast, reverse transcription-polymerase chain reaction (RT-PCR) revealed alkaline phosphatase mRNA in the hybrid cells, but at very low levels. Taken together, the data indicate that regulation of plasma membrane and matrix vesicle alkaline phosphatase is independent and suggest that matrix vesicle biogenesis is independent and distinct from that of plasma membrane biogenesis. Analysis of 1B- and 1L-type alkaline phosphatase mRNA by RT-PCR showed that alternate promoter usage of the alkaline phosphatase gene was not responsible for the differential localization of this enzyme in matrix vesicle. Thus, it is likely that matrix vesicle and plasma membrane alkaline phosphatase are regulated differently at a post-transcriptional level.

5'-Nucleotidase

Heart transplantation in children and young adults: early and intermediate-term results.

The purpose of this article is to report our short- and intermediate-term follow-up of cardiac transplantation for congenital heart disease and cardiomyopathy in children (age greater than 6 months), adolescents, and young adults. Thirty patients (ages 8 months to 24 years) with end-stage heart failure have undergone cardiac transplantation in our program: 12 (40%) for postoperative end-stage heart failure, 9 (30%) as primary treatment for congenital heart disease, 5 (17%) for dilated cardiomyopathy, and 4 (13%) for restrictive/hypertrophic cardiomyopathy. Nineteen patients (63%) had undergone prior operations; 4 patients received transplants for failed Fontan procedures. Induction therapy with antithymocyte therapy was used routinely, and long-term immunosuppression was by cyclosporine and azathioprine alone. Rejection surveillance/diagnosis was based on echocardiographic criteria. Posttransplantation follow-up ranges from 3 to 78 months. Operative mortality was 3.3% (1/30). No patients have been diagnosed with either accelerated allograft atherosclerosis or posttransplantation lymphoproliferative disease. We conclude that cardiac transplantation may be performed with excellent early and intermediate-term results.

Adolescent

Markers of primary mineralization are correlated with bone-bonding ability of titanium or stainless steel in vivo.

Critical events in the adaptation of osseous tissues to implant materials involve initial calcification of the newly synthesized bone. Previous studies indicated that bone-bonding but not nonbonding glass ceramics increase the matrix vesicle number, thereby compensating for delayed maturation of the extracellular organelles. The present study assessed whether this was also true for metal implants commonly used in orthopaedics and oral medicine. Bone-bonding titanium (Ti) or nonbonding stainless steel (SS) implants were placed in the right tibias of Sabra rats following ablation of the marrow. At 3, 6, 14, and 21 days postinjury, newly formed endosteal bone in the treated and contralateral limbs was removed and matrix vesicle-enriched membranes isolated. Alkaline phosphatase and phospholipase A2 specific activities and phosphatidylserine (PS) content were determined and compared with those of a nonsurgical control group. Results show that matrix vesicle alkaline phosphatase and phospholipase A2 activity and PS content was increased in the Ti-implanted limbs at 6 (peak), 14, and 21 days, although at levels less than observed in normal healing. Alkaline phosphatase activity remained elevated throughout the healing period. In contrast, these parameters were markedly inhibited in the SS-implanted limbs with respect to Ti or to normal healing. Both implants altered the systemic response associated with marrow ablation, but in an implant-specific manner. The results support the hypothesis that cells adjacent to bone-bonding materials can compensate for negative effects on primary mineralization during osteogenesis, whereas cells adjacent to nonbonding materials either do not compensate or are further depressed. The data support the use of the rat marrow ablation model as a tool for rapid, initial assessment of biomaterials in bone.

Alkaline Phosphatase

Neuroendocrine regulation of adrenal gland and hypothalamus 5'deiodinase activity. II. Effects of splanchnicotomy and hypophysectomy.

This study analyzes the role of the autonomic nervous system, the pituitary gland, ACTH, dexamethasone (DEX), and thyroid hormones in the regulation of 5'deiodinase (5'D) in the hypothalamus (HP) and adrenal gland (AG) of the rat. 5'D activity was analyzed in rats under basal conditions (22 C) and during cold exposure (4 C, during 15, 30, 60, and 120 min). Several experimental groups were formed: intact animals (INT), unilateral (left) splanchnicotomized, sham splanchnicotomized, hypophysectomized (HPX), and sham hypophysectomized. Results in the hypothalamus were: 1) independent of the experimental group, the HP 5'D activity increased during the first 15-30 min of cold exposure; however, this increase was greater in operated animals than in INT rats; and 2) basal 5'D activity was increased in HPX rats and was also regulated by thyroid hormones. Results in the adrenal gland were: 1) INT rats exhibited a biphasic pattern of 5'D activation during cold stress (30 and 60 min of exposure); 2) the splanchnic nerve exerted a tonic-stimulatory effect on basal AG 5'D activity; 3) the denervated gland preserved its ability to respond to cold; 4) in INT animals DEX but not ACTH had a stimulatory effect on basal activity; 5) the high 5'D activity post-HPX was reverted to basal values by T4 and DEX administration; 6) SHAM-HPX also was followed by a large increase in basal 5'D activity, and 7) this hyperresponse was abolished by acute ACTH and DEX administration. In conclusion, our results demonstrate that the mechanisms that participate in the regulation and activation of 5'D in the adrenal gland and the hypothalamus are of a neuroendocrine nature. Also, in both organs, but mainly in the HP, 5'D activity is T4-dependent. In addition to the tonic-stimulatory influence conveyed by the splanchnic nerve, AG 5'D activity is influenced by thyroid hormones, glucocorticoids, and probably extrapituitary factors whose nature is unknown yet.

Adrenal Glands

The relationship between the thrombotic and infectious complications of central venous catheters.

OBJECTIVES: To assess the frequency of thrombotic and infectious complications of long-term use of vascular catheters in cancer patients and to determine whether the two types of complication are related. DESIGN: Case series. SETTING: A 500-bed tertiary cancer center. PATIENTS: Seventy-two cancer patients. INTERVENTIONS: During a 16-month period, postmortem examinations of catheterized veins and contralateral uncatheterized veins were done on all patients with indwelling central venous catheters who met study criteria. MAIN OUTCOME MEASURES: Catheter-related septicemia determined by clinical and microbiological data as well as postmortem pathology; venous pathological changes such as mural hemorrhage, thrombosis, calcification, ulceration, and inflammation. RESULTS: Premortem clinical and microbiological data were obtained retrospectively on all patients. Pathological changes were noted in 35 catheterized veins (49%) compared with five contralateral control veins (9.2%) (P < .001). Mural thrombi were noted in 27 catheterized veins (38%) compared with only one contralateral control vein (1.4%) (P < .001). Other pathological changes consisted of four central venous catheter-related mural thrombi (5.6%) in the right atrium and four instances (5.6%) of nonbacterial thrombotic endocarditis, three involving the tricuspid and one the mitral valves. Seven patients had catheter-related septicemia. Of the 31 patients with mural thrombosis of the catheterized vein or right atrium, seven developed catheter-related septicemia, whereas none of the 41 patients with normal catheterized veins and atria developed catheter-related septicemia (P < .01). CONCLUSIONS: Thrombotic complications are common in catheterized veins and are often associated with catheter sepsis.

Adolescent