Biomedical subjects

M Garcia

Publications and source records attributed to M Garcia.

At least 19 recordsLinked to original sources

PubMed2006

Mitochondria-associated yeast mRNAs and the biogenesis of molecular complexes.

The coherence of mitochondrial biogenesis relies on spatiotemporally coordinated associations of 800-1000 proteins mostly encoded in the nuclear genome. We report the development of new quantitative analyses to assess the role of local protein translation in the construction of molecular complexes. We used real-time PCR to determine the cellular location of 112 mRNAs involved in seven mitochondrial complexes. Five typical cases were examined by an improved FISH protocol. The proteins produced in the vicinity of mitochondria (MLR proteins) were, almost exclusively, of prokaryotic origin and are key elements of the core construction of the molecular complexes; the accessory proteins were translated on free cytoplasmic polysomes. These two classes of proteins correspond, at least as far as intermembrane space (IMS) proteins are concerned, to two different import pathways. Import of MLR proteins involves both TOM and TIM23 complexes whereas non-MLR proteins only interact with the TOM complex. Site-specific translation loci, both outside and inside mitochondria, may coordinate the construction of molecular complexes composed of both nuclearly and mitochondrially encoded subunits.

Carrier Proteins↗

PubMed2006

Chordin is underexpressed in ovarian tumors and reduces tumor cell motility.

Ovarian cancers mostly derive from the monolayer epithelium that covers the ovary. There are currently very few molecular clues to the etiology of this cancer. Bone morphogenetic proteins (BMPs) are required for follicular development and female fertility and are expressed in the ovarian surface epithelium (OSE). We previously reported the expression of human chordin (CHRD), a BMP extracellular regulator, in the ovary. Here we show that CHRD is underexpressed in epithelium ovary cancer and epithelial cancer cell lines as compared with normal tissues and OSE, respectively. Besides, we detected BMP expression in all ovarian cell lines analyzed. To determine the functional relevance of the absence of CHRD mRNA in tumors and cancer cell lines, we studied the effects of CHRD on two cancer cell lines, BG1 and PEO14. Migratory and invasive properties were greatly reduced, whereas cell adhesion to the support was enhanced. In addition, we detected chordin (Chrd) expression in OSE of rat ovaries in a pattern similar to that of BMP4. Altogether, these results suggest that CHRD could participate in regulating BMP activity in normal OSE physiology, and that its mis-expression in OSE may facilitate cancer incidence and/or progression.

Animals↗

PubMed2005

Why are many mRNAs translated to the vicinity of mitochondria: a role in protein complex assembly?

The longstanding question of the presence of mitochondria-bound polysomes has been recently revisited using new approaches. Genome-wide analyses provided evidence that many genes are actually translated on mitochondria-bound polysomes and GFP-labeling techniques have shown that, in vivo, the 3'UTR sequence of these genes contains signals which can target hybrid RNA molecules to the proximity of mitochondria. Evolutionary conservation of some of these signals will be presented. Interestingly, class I mRNA which are translated on free polysomes and class II mRNA which are translated on mitochondria-bound polysomes have, mostly, eukaryotic and prokaryotic origins respectively. Using ATP2, a typical prokaryotic-derived gene, as a model for class II mRNA, we showed that its 3'UTR sequence is essential both for a correct addressing of mRNA to mitochondria proximity and to a proper production of functional ATP synthases. These different observations suggest that prokaryotic-derived genes are, like the contemporary mitochondrial genes, translated near mitochondrial membranes. In both cases this locus specific translation process might be connected to a correct complex assembly program and the cases of ATP synthase and cytochrome c oxidase complexes will be considered in this respect.

3' Untranslated Regions↗

PubMed2005

Evolution of the meiotic prophase and of the chromosome pairing process during human fetal ovarian development.

BACKGROUND: Studies on human oocytes in prophase I are limited due to the difficulty in obtaining the sample. However, a complete study of meiotic prophase evolution and the homologue pairing process is necessary to try to understand the implication of oogenesis in the origin of human aneuploidy. METHODS: A complete analysis of meiotic prophase progression comprising the long developmental time period during which meiotic prophase takes place, based on the analysis of a total of 8603 oocytes in prophase I from 15 different cases is presented. The pairing process of chromosomes 13 and 18 is also described. RESULTS: The findings significantly relate for the first time the evolution of meiotic prophase to fetal development. Although for both chromosomes 13 and 18 a high pairing efficiency is found, pairing failure at the pachytene stage has been observed in 0.1% of oocytes. However, errors at the diplotene stage are substantially increased, suggesting that complete, premature disjunction of the homologues commonly occurs. Moreover, pre-meiotic errors are also described. CONCLUSIONS: Our findings show that homologous chromosomes pair very efficiently, but the high frequency of complete, premature homologue separation found at diplotene suggests that mechanisms other than the pairing process could be more likely to lead to the high aneuploidy rate observed in human oocytes.

Aneuploidy↗

PubMed2005

The importance of clinical parameters when differentiating cholestatic hepatitis C virus from allograft rejection.

BACKGROUND: The exact cause and appropriate treatment for cholestasis following liver transplantation in recipients with hepatitis C virus recurrence (RHCV) are difficult to determine. Our objective was to determine the diagnostic accuracy of clinical and histological parameters in liver transplant recipients with RHCV and concurrent cholestasis. METHODS: A retrospective analysis from June 1996 to May 2003 was performed on adult liver transplant (OLT) recipients with hepatitis C virus. Patients with cholestasis (bilirubin >5 mg/dL, 6 months after OLT) were selected. Demographics, etiology, immune suppression, clinical and histologic outcomes, and virologic features were evaluated. Patients were divided into two groups based on clinical and histological criteria: (1) patients with parameters suggestive of cholestatic HCV; and (2) patients with parameters consistent with acute cellular rejection. RESULTS: Thirty-seven patients met study criteria (20 males). The average age was 54 years (range = 14-72), and time from transplant to jaundice was 769 days (range = 48-2981). The groups were comparable regarding HCV viral load, age, gender, time from transplant, and United Network of Organ Sharing status at time of transplant. Retransplantation was performed in two patients in group 1, neither of whom survived, and in three patients in group 2, all of whom survived. Clinical parameters correlated well with diagnosis of cholestasis (r = 0.85, P < .001) whereas histological evaluation did not (r = 0.11, P = .53). Mortality in group 1 was 78% (7 of 9) vs. 50% (13 of 26) in group 2. Median duration of survival following liver transplantation in group 1 was 132 days versus 435 days in group 2. CONCLUSION: Clinical diagnosis parameters for RHCV with cholestasis appear more accurate than histology parameters and should be the primary consideration in directing therapy. Despite timely diagnosis, cholestatic RHCV LTx recipients have a poor prognosis.

Adult↗

PubMed2005

The effects of drinks made from simple sugars on blood pressure in healthy older people.

The objective of the research was to determine the blood pressure (BP) lowering effects in older people of 50 g carbohydrate drinks with varying carbohydrate content using a randomised, cross-over study with ten (six females) healthy older subjects (mean age 72.20 (sem 1.50) years). BP, heart rate and glucometer-derived blood glucose levels were determined at baseline and following the ingestion of equal volumes (300 ml) of water and carbohydrate drinks with varying nutrient content (glucose, sucrose and fructose). A significant decline in BP over the first 60 min was seen following glucose (systolic BP (SBP) P<0.01, diastolic BP (DBP) P<0.01, mean arterial BP (MAP) P=0.03) and sucrose (SBP P<0.01, DBP P<0.01, MAP P<0.01) ingestion, although the decrease occurred earlier after glucose than sucrose ingestion (SBP 7.33 (sem 2.19) v. 21.00 (sem 4.30) min (P=0.03) and MAP 11.22 (sem 3.10) v. 17.00 (sem 3.78) min (P=0.03)). BP increased after water ingestion (SBP P=0.04, DBP P=0.18, MAP P=0.02) but did not change after fructose ingestion (SBP P=0.36, DBP P=0.81, MAP P=0.34). Post hoc analyses revealed that the BP (SBP, DBP and MAP) decrease following glucose and sucrose ingestion were similar but significantly greater than following fructose or water ingestion. Sucrose, which is used widely (table sugar), reduces BP as much as glucose. In contrast to this, fructose ingestion causes no change in BP. Further studies are required to determine if the substitution of glucose or sucrose with fructose may be beneficial in the medical management of older people with severe symptomatic postprandial hypotension.

Aged↗

PubMed2005

Evolutionary conserved chromosomal segments in the human karyotype are bounded by unstable chromosome bands.

In this paper an ancestral karyotype for primates, defining for the first time the ancestral chromosome morphology and the banding patterns, is proposed, and the ancestral syntenic chromosomal segments are identified in the human karyotype. The chromosomal bands that are boundaries of ancestral segments are identified. We have analyzed from data published in the literature 35 different primate species from 19 genera, using the order Scandentia, as well as other published mammalian species as out-groups, and propose an ancestral chromosome number of 2n = 54 for primates, which includes the following chromosomal forms: 1(a+c(1)), 1(b+c(2)), 2a, 2b, 3/21, 4, 5, 6, 7a, 7b, 8, 9, 10a, 10b, 11, 12a/22a, 12b/22b, 13, 14/15, 16a, 16b, 17, 18, 19a, 19b, 20 and X and Y. From this analysis, we have been able to point out the human chromosome bands more "prone" to breakage during the evolutionary pathways and/or pathology processes. We have observed that 89.09% of the human chromosome bands, which are boundaries for ancestral chromosome segments, contain common fragile sites and/or intrachromosomal telomeric-like sequences. A more in depth analysis of twelve different human chromosomes has allowed us to determine that 62.16% of the chromosomal bands implicated in inversions and 100% involved in fusions/fissions correspond to fragile sites, intrachromosomal telomeric-like sequences and/or bands significantly affected by X irradiation. In addition, 73% of the bands affected in pathological processes are co-localized in bands where fragile sites, intrachromosomal telomeric-like sequences, bands significantly affected by X irradiation and/or evolutionary chromosomal bands have been described. Our data also support the hypothesis that chromosomal breakages detected in pathological processes are not randomly distributed along the chromosomes, but rather concentrate in those important evolutionary chromosome bands which correspond to fragile sites and/or intrachromosomal telomeric-like sequences.

Alouatta↗

PubMed2005

Evolutionary breakpoints are co-localized with fragile sites and intrachromosomal telomeric sequences in primates.

The concentration of evolutionary breakpoints in primate karyotypes in some particular regions or chromosome bands suggests that these chromosome regions are more prone to breakage. This is the first extensive comparative study which investigates a possible relationship of two genetic markers (intrachromosomal telomeric sequences [TTAGGG]n, [ITSs] and fragile sites [FSs]), which are implicated in the evolutionary process as well as in chromosome rearrangements. For this purpose, we have analyzed: (a) the cytogenetic expression of aphidicolin-induced FSs in Cebus apella and Cebus nigrivittatus (F. Cebidae, Platyrrhini) and Mandrillus sphinx (F. Cercopithecidae, Catarrhini), and (b) the intrachromosomal position of telomeric-like sequences by FISH with a synthetic (TTAGGG)n probe in C. apella chromosomes. The multinomial FSM statistical model allowed us to determinate 53 FSs in C. apella, 16 FSs in C. nigrivittatus and 50 FSs in M. sphinx. As expected, all telomeres hybridized with the probe, and 55 intrachromosomal loci were also detected in the Cebus apella karyotype. The chi(2) test indicates that the coincidence of the location of Cebus and Mandrillus FSs with the location of human FSs is significant (P < 0.005). Based on a comparative cytogenetic study among different primate species we have identified (or described) the chromosome bands in the karyotypes of Papionini and Cebus species implicated in evolutionary reorganizations. More than 80% of these evolutionary breakpoints are located in chromosome bands that express FSs and/or contain ITSs.

Animals↗

PubMed2005

Chromosome 18 pairing behavior in human trisomic oocytes. Presence of an extra chromosome extends bouquet stage.

Little is known about the first meiotic prophase stages in the human female because these occur during fetal life, and only a few studies have addressed aneuploid human oocytes. In this paper, the synaptic process in the meiotic prophase in three 47, XX+18 cases is analyzed. A complete study of the dynamics of centromeres and telomeres, cohesin core and synapsis development in aneuploid female meiosis was performed. Investigation of chromosome dynamics in prophase of trisomy 18 oocytes show that these events follow the major patterns seen earlier in euploid oocytes. However, there is a significant delay in the resolution of bouquet topology which could relate to the presence of a surplus chromosome 18 axial element in zygotene oocytes. Pachytene oocytes displayed normal synapsis among the three chromosome 18s. However, in some oocytes the surplus chromosome 18 core was aligned to the bivalent 18. As ataxia telangiectasia and Rad3 related kinase (ATR) has been described as a marker for late-pairing chromosomes in mice, ATR distribution was analyzed in human meiocytes--spermatocytes, euploid oocytes and trisomic oocytes. In contrast to the observations made in mice, no preferential staining for late-pairing chromosomes was observed in humans. In the cases studied, bivalent synapses progressed as in a normal ovary, contrasting with the hypothesis that a surplus chromosome can modify pairing of other chromosomes.

Ataxia Telangiectasia Mutated Proteins↗

PubMed2004

Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors.

OBJECTIVE: To identify potential predictors of and factors associated with early neurologic deterioration (END) in primary intracerebral hemorrhage (ICH). METHODS: Two hundred sixty-six patients with spontaneous supratentorial ICH admitted within 12 hours of stroke onset were investigated in a multicenter, prospective study. Sixty-one clinical, biochemical, and neuroimaging variables were registered on admission, and 37 clinical and neuroimaging variables were registered at 48 hours. The volumes of the ICH and peripheral edema on admission and at 48 hours were measured on CT scan. Stroke severity and functional outcome were evaluated with the Canadian Stroke Scale (CSS) and modified Rankin Scale. END was diagnosed when the CSS score decreased > or =1 points between admission and 48 hours. With use of logistic regression analyses, baseline variables that predicted END and factors measured after the early acute phase and associated with END were investigated. RESULTS: END occurred in 61 (22.9%) patients. Body temperature of >37.5 degrees C (odds ratio [OR] 24.5; 95% CI 4.8 to 125), neutrophil count (by 1,000-unit increase; OR 2.1; 95% CI 1.6 to 2.6), and serum fibrinogen levels of >523 mg/dL (OR 5.6; 95% CI 1.9 to 16.2) on admission were independent predictors of END. Among the factors recorded at 48 hours, early ICH growth (OR 4.3; 95% CI 1.3 to 14.5), intraventricular bleeding (OR 2.6; 95% CI 1.4 to 5.0), and highest systolic blood pressure (by 10-unit increase; OR 1.17; 95% CI 1.02 to 1.32) were associated with END in multivariate analyses. CONCLUSIONS: Clinical and biologic markers of the inflammatory reaction on admission are predictors of subsequent END, whereas early ICH growth, intraventricular bleeding, and high systolic blood pressure within 48 hours are factors associated with END in patients with spontaneous ICH.

Aged↗

PubMed2004

Female-specific features of recombinational double-stranded DNA repair in relation to synapsis and telomere dynamics in human oocytes.

Chromosome segregation errors are a significant cause of aneuploidy among human neonates and often result from errors in female meiosis that occur during fetal life. For the latter reason, little is known about chromosome dynamics during female prophase I. Here, we analyzed chromosome reorganization, and centromere and telomere dynamics in meiosis in the human female by immunofluorescent staining of the SYCP3 and SYCP1 synaptonemal complex proteins and the course of recombinational DNA repair by IF of phospho-histone H2A.X (gamma-H2AX), RPA and MLH1 recombination proteins. We found that SYCP3, but not SYCP1, aggregates appear in the preleptotene nucleus and some persist up to pachytene. Telomere clustering (bouquet stage) in oocytes lasted from late-leptotene to early pachytene-significantly longer than in the male. Leptotene and zygotene oocytes and spermatocytes showed strong gamma-H2AX labeling, while gamma-H2AX patches, which colocalized with RPA, were present on SYCP1-tagged pachytene SCs. This was rarely seen in the male and may suggest that synapsis installs faster with respect to progression of recombinational double-strand break repair or that the latter is slower in the female. It is speculated that the presence of gamma-H2AX into pachytene highlights female-specific peculiarities of recombination, chromosome behavior and checkpoint control that may contribute to female susceptibility for aneuploidy.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Oral anti-pneumococcal activity and pharmacokinetic profiling of a novel peptide deformylase inhibitor.

OBJECTIVE: BB-81384, a novel peptide deformylase (PDF) inhibitor, was characterized in terms of enzyme inhibition profile, antibacterial activity, rodent pharmacokinetics and oral efficacy in murine infection models. METHODS: MICs were determined by standard NCCLS broth microdilution. Selectivity of metalloenzyme inhibition was determined with a limited panel of enzymes via standard biochemical assays. Profiling of the pharmacokinetics and select tissue disposition in mice was determined and compared with that of the macrolide, azithromycin. In vivo murine efficacy studies using Streptococcus pneumoniae were conducted using a peritonitis model, as well as lung and thigh burden models of infection. RESULTS: BB-81384 selectively inhibited PDF with an IC(50) approximately 10 nM and with MICs < 0.5 mg/L against most S. pneumoniae pathogens. Pharmacokinetic analysis revealed good oral bioavailability and moderate clearance and volume of distribution. BB-81384 partitioning to lung tissue was similar in terms of magnitude and kinetics to that of the plasma compartment. Single-administration oral efficacy in a mouse peritonitis model was evident with an ED(50) of 30 mg/kg. BB-81384 reduced the bacterial load by approximately 5 and 3 log units in organ-burden models of lung and thigh infection, respectively. CONCLUSION: BB-81384, a novel PDF inhibitor with good activity against S. pneumoniae in vitro, was the first compound of this class to be profiled for oral pharmacokinetics and tissue disposition and to demonstrate oral anti-pneumococcal efficacy in mice.

Amidohydrolases↗

PubMed2004

CD44 and hyaluronic acid regulate in vivo iNOS expression and metalloproteinase activity in murine air-pouch inflammation.

OBJECTIVE: To evaluate the effects of anti-CD44 IM7.8.1 antibody, HMW-HA and LMW-HA on leukocyte migration and adhesion, and the induction of proinflammatory mediators, in mouse air-pouch inflammation induced by zymosan. METHODS: Leukocytes were obtained from zymosan-air pouches after the intra-pouch injection of anti-CD44 IM7.8.1, isotype control, HMW-HA, LMW-HA or PBS. TNF-alpha, IL-1beta and iNOS mRNA were estimated in leukocytes by semi-quantitative RT-PCR. Matrix metalloproteinases (MMPs) from exudates were evaluated by zymography and Western Blot. Adhesion and migration of leukocytes were evaluated in HA-coated plates and Boyden chambers respectively. RESULTS: IM7.8.1 decreased iNOS mRNA levels and the activity of both MMP-9 and MMP-2 eight h after injection into zymosan air pouch while IM7.8.1, HMW-HA and LMW-HA had no effect on IL1-beta or TNF-alpha mRNA levels. Leukocytes from air pouch adhered to and migrated in vitro against both HMW-HA and LMW-HA. LMW-HA increased the number of leukocytes in the air pouch and iNOS mRNA levels as compared to PBS injection. In contrast, HMW-HA decreased leukocyte count and reduced iNOS mRNA levels. Paradoxically, the activity of both MMP-9 and MMP-2 was increased by HMW-HA and decreased by LMW-HA. CONCLUSIONS: Both CD44 and HA can modulate leukocyte migration and induction of proinflammatory mediators in mouse zymosan air pouch inflammation. IM7.8.1 had consistent anti-inflammatory effects, reducing iNOS, MMP-9 and MMP-2. HMW-HA and LMW-HA were able to modulate both the induction of proinflammatory mediators and leukocyte count in the air pouch.

Animals↗

PubMed2004

Expanded huntingtin activates the c-Jun terminal kinase/c-Jun pathway prior to aggregate formation in striatal neurons in culture.

Huntington's disease (HD) is an autosomal neurodegenerative disorder, caused by expansion of a glutamine repeat in the Huntingtin protein. Pathogenesis in HD includes the cytoplasmic cleavage of Huntingtin and release of an amino-terminal fragment capable of nuclear localization, where expanded-Huntingtin (Exp-Htt) might lead to aberrant transcriptional regulation, neuronal dysfunction and degeneration. Recent evidence, from hippocampal cell lines, also implicates altered interaction of Exp-Htt with components of the c-Jun N-terminal kinase (JNK) cascade. However, there is yet no proven implication of the JNK/c-Jun module in degeneration of striatal neurons, the more vulnerable cell population, in HD. In the present study, we used primary striatal neurons in culture to analyze c-Jun activation by Exp-Htt. Green fluorescent protein (GFP)-tagged exon 1 of human Huntingtin either in its normal (25Q, normal-Htt) or expanded (103Q, Exp-Htt) version was transiently transfected in these cells. We first set out, in our conditions, the time course of striatal degeneration produced by Exp-Htt, and found it occurred rapidly. At 48 h post-transfection, 60% of striatal neurons expressing Exp-Htt had apoptotic characteristics including DNA fragmentation and neuritic retraction. Most of these neurons also showed nuclear aggregates of GFP-Exp Htt. Kinetics of c-Jun activation were tested in transfected cells using immunocytochemical detection of phospho-c-Jun. We found a significant activation and induction of c-Jun in Exp-Htt but not normal-Htt-transfected neurons. Of interest, these events occurred prior to nuclear translocation of Exp-Htt. Finally, overexpression of a dominant negative version of c-Jun, as well as pharmacological inhibition of JNK strongly protected against DNA fragmentation and neuritic retraction induced by Exp-Htt. Thus our data suggest that c-Jun activation and induction, is an early event in the pathogenesis of HD, occurring prior to formation of nuclear aggregates of Exp-Htt.

Animals↗

PubMed2004

Immunoenzymatic and morphological detection of epithelial cell apoptotic stages in gastrointestinal allografts from multivisceral transplant patients.

Acute allograft rejection (AR) is a major contributor to morbidity and mortality among patients who undergo multivisceral transplantation. Critical to the assessment of AR is detection of apoptosis in the glandular epithelium of the gastrointestinal allograft. We utilized the TUNEL stain (TdT-mediated biotin 16-dUTP nick-end labeling) to test whether this method improved detection of apoptosis compared to standard slide evaluation. TUNEL and H&E stains were performed on paraffin-embedded tissue sections to estimate the number of apoptotic bodies per 10 high power fields, as determined by independent pathologists in blinded fashion. Both methodologies showed similar numbers and distributions of apoptotic foci present among the epithelial cells. There was a correlation between the number of apoptosis and the grade of rejection (P <.001). This is the first use of the TUNEL stain in gastrointestinal allograft biopsies to our knowledge. The similarity in pattern and sensitivity of TUNEL with standard morphology confirms that biopsy assessment with routine H&E staining allows an accurate appraisal of epithelial cell apoptosis. Therefore, current staining protocols for endoscopically derived mucosal biopsies of gastrointestinal allografts are sufficiently accurate to enumerate the critical feature of epithelial apoptosis as a determinant of the grade of acute rejection.

Apoptosis↗

PubMed2004

Lymphoplasmacytic hyperplasia (possibly pre-PTLD) has varied expression and appearance in intestinal transplant recipients receiving Campath immunosuppression.

Posttransplant lymphoproliferative disorders (PTLD) are a frequent complication in bowel transplant recipients. Histological changes in PTLD range from expansile lymphoplasmacytic (LP) hyperplasia to frank lymphoma. Small bowel allograft biopsies obtained in the first 250 days posttransplant were retrospectively graded after patients had received induction immunosuppression with either anti-CD52 (Campath) or anti-CD25 (Zenapax) monoclonal antibodies. The biopsies were analyzed with respect to the onset intensity of lymphoplasmacytic infiltrates and presence of in situ EBV hybridization (EBER) positivity. We observed that lymphoplasmacytic infiltrates were a frequent change in all bowel transplant patients over the examined period. Campath-treated patients developed earlier LP infiltrates of mild to moderate intensity between day 1 and 100 posttransplant, thereafter decreasing to mild. No EBER positivity was detected in this group. Zenapax-treated patients presented with LP infiltrates later of mild to moderate intensity through day 100 posttransplant. However, more persistent and intense LP infiltrates was observed after day 101 in this group, including a case of lymphoma and two cases of EBER positivity. We conclude that Campath immunosuppression results in an earlier appearance of LP lesions that are generally less intense than those evident with Zenapax. We attribute these findings to the more profound immunodeficiency and cell targeting following Campath treatment.

Alemtuzumab↗

PubMed2004

Campath-1H immunosuppressive therapy reduces incidence and intensity of acute rejection in intestinal and multivisceral transplantation.

Campath-1H, an anti-CD52 antibody, is being used at our institution as immunosuppression in multivisceral and intestinal transplantation. We reviewed the pathologic findings of 1696 small bowel allograft biopsies obtained in the first 250 days posttransplant from 78 patients who underwent isolated intestinal or multivisceral transplantation and received induction immunosuppression with Campath (n = 30) or Zenapax (n = 57). We found an overall reduced incidence of acute cellular rejection (ACR) in patients receiving Campath (19.1%) compared with those on Zenapax (32.8%). The majority of Campath patients showed no rejection or was indeterminate for rejection over the period of measurement. The frequencies of mild and moderate ACR were approximately twice and three times more common, respectively, in Zenapax-treated patients. The mean grade of ACR in Campath patients compared with Zenapax patients was significantly lower (P <.01) during the first 6 weeks posttransplant. Thereafter, the grade of rejection in both patient groups showed fluctuation, with Zenapax patients sometimes having lower values (eg, at 2 to 4 months) than Campath patients. Patient and graft survival was not significantly different between the two groups. These data suggest that the incidence of ACR is significantly reduced with Campath during the first 2 months posttransplant, when compared with Zenapax. However, the incidence and intensity of ACR following this initial time period shows vacillation with both types of immunosuppression.

Alemtuzumab↗

PubMed2004

Erectile dysfunction in heart disease patients.

Atherosclerosis is a general health problem that not only affects the coronary arteries but also (in men) the penile arteries, thus contributing to organic causes of erectile dysfunction (ED) in heart disease patients. These organic causes are intertwined with psychological and pharmacological causes because medication prescribed for heart disease patients may also cause ED. The incidence of ED after myocardial infarction ranges from 38 to 78%. As sexual intercourse involves physical exertion, the medical history, ventricular function determined through echocardiography, and stress testing are used to classify patients into various groups where coital activity represents a greater or lesser cardiovascular risk. The energy requirements for intercourse are not high, ranging from 3.7 metabolic equivalents (METs) of energy expenditure at resting state during the preorgasmic phase to 5 METs during orgasm. The Bruce protocol for exercise stress testing is a six-stage protocol with changes in the slope and speed of the treadmill. As a general rule, a patient who completes the first two stages of the Bruce protocol has a functional capacity greater than 7 METs, which is considered sufficient for sexual intercourse. The physician or cardiologist concerned should institute first-line treatment with oral drugs according to the indications listed below. If sexual activity is not contraindicated, the treatment of choice for ED in heart disease patients is oral therapy with sildenafil, except in those cases in which its use is contraindicated. Specific recommendations are discussed.

Arteriosclerosis↗