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PubMed1993

Basal forebrain grafts in the hippocampus and neocortex: regulation of acetylcholine release.

The regulation of acetylcholine (ACh) release from cholinergic neurons transplanted to the hippocampus or neocortex was studied by microdialysis in awake rats. Fetal basal forebrain tissue was implanted as a cell suspension or solid graft into the fimbria-fornix-lesioned hippocampus, or as a cell suspension into the frontal cortex after excitotoxic lesion of the nucleus basalis. Several months after transplantation, microdialysis probes were implanted in areas of the hippocampus or frontal cortex reinnervated by the grafts. The grafts restored lesion-induced deficits in steady-state ACh release up to normal or above normal levels in both hippocampus and frontal cortex. The responses to KCl and tetrodotoxin suggested that the ACh release exhibited normal firing-dependent properties. By applying various behaviorally arousing stimuli that normally activate the basal forebrain projection systems, we wished to investigate the functional integration of the grafts in the host brain. In the hippocampus, sensory stimulation, immobilization stress and motor activity all resulted in increased release of graft-derived ACh amounting to 25-65% of the normal response. Variations in ACh levels during the day-night cycle was, however, not observed in the grafted rats. In the frontal cortex, immobilization enhanced the graft-derived ACh release (60% of normal response), whereas the response to sensory stimulation did not reach significance. Since the activity of the normal basal forebrain projection systems is under influence of monoaminergic brainstem afferents, we investigated the effects of systemic administration of amphetamine or apomorphine on ACh release in the hippocampus. Both drugs produced increases in graft-derived ACh release although the response was variable and less pronounced than normal. In conclusion, the graft-derived ACh release was affected by behavioral manipulations and catecholaminergic drugs that normally modify cholinergic septo-hippocampal and basalo-cortical activity. This strongly suggests a high degree of functional integration of the graft in the host brain allowing for a regulated release of transmitter that can be adjusted during ongoing behavior.

Acetylcholine↗
PubMed2001

Inferior temporal stream for word processing with integrated mnemonic function.

The participation of the inferior temporal cortex in visual word perception and recognition raises several questions: Is there a directed processing stream proceeding anteriorly by continuous cortical processing? How fast are words processed within such an inferior temporal stream? Does this stream support implicit or explicit memory? To answer these questions, we analyzed the spatio-temporal relationship of event-related potentials, recorded directly from the inferior temporal cortex in epilepsy patients performing a continuous visual word recognition paradigm. Event-related potentials elicited an inferior temporal positivity in a strip along the left collateral sulcus. This potential exhibited a linear (r = 0.74) peak latency progression from posterior to anterior inferior temporal regions (approximately 15 cm/sec), indicating a directed, intracortical processing stream. Peak amplitudes and latencies showed reliable old/new effects with smaller amplitudes and shorter latencies for old as opposed to new words. Although the amplitude-old/new-effect occurred for all repeated words (e.g., implicit memory), the latency-old/new-effect occurred for correctly recognized old words only (e.g., explicit recognition). These results seem to dissociate two distinct mnemonic processes. The graded decrease of mean ITP peak amplitudes and latencies, however, does not allow us to exclude a single trace model as assumed for explicit recognition memory based on familiarity (Mandler [1980]: Psychol Rev 87:252-271). Regardless whether there is a dissociation between implicit and explicit memory in inferior temporal cortex or not, our findings are in accordance with an integrated inferior temporal processing stream for words that performs continuously semantic and mnemonic operations supporting both implicit and explicit memory.

Adolescent↗
PubMed2004

Functional magnetic resonance imaging-integrated neuronavigation: correlation between lesion-to-motor cortex distance and outcome.

OBJECTIVE: The integration of functional magnetic resonance imaging (fMRI) data into neuronavigation is a new concept for surgery adjacent to the motor cortex. However, the clinical value remains to be defined. In this study, we investigated the correlation between the lesion-to-fMRI activation distance and the occurrence of a new postoperative deficit. METHODS: fMRI-integrated "functional" neuronavigation was used for surgery around the motor strip in 54 patients. During standardized paradigms for hand, foot, and tongue movements, echo-planar imaging T2* blood oxygen level-dependent sequences were acquired and processed with BrainVoyager 2000 software (Brain Innovation, Maastricht, The Netherlands). Neuronavigation was performed with the VectorVision(2) system (BrainLAB, Heimstetten, Germany). For outcome analysis, patient age, histological findings, size of lesion, distance to the fMRI areas, preoperative and postoperative Karnofsky index, postoperative motor deficit, and type of resection were analyzed. RESULTS: In 45 patients, a gross total resection (>95%) was performed, and for 9 lesions (low-grade glioma, 4; glioblastoma, 5), a subtotal resection (80-95%) was achieved. The neurological outcome improved in 16 patients (29.6%), was unchanged in 29 patients (53.7%), and deteriorated in 9 patients (16.7%). Significant predictors of a new neurological deficit were a lesion-to-activation distance of less than 5 mm (P < 0.01) and incomplete resection (P < 0.05). CONCLUSION: fMRI-integrated neuronavigation is a useful concept to assess the risk of a new motor deficit after surgery. Our data suggest that a lesion-to-activation distance of less than 5 mm is associated with a higher risk of neurological deterioration. Within a 10-mm range, cortical stimulation should be performed. For a lesion-to-activation distance of more than 10 mm, a complete resection can be achieved safely. The visualization of fiber tracks is desirable to complete the representation of the motor system.

Adult↗
PubMed1997

Sperm head decondensation, pronuclear formation, cleavage and embryonic development following intracytoplasmic injection of mitochondria-damaged sperm in mammals.

The objective of this study was to investigate the influence of sperm mitochondrial destruction on sperm head decondensation, male pronuclear formation, cleavage and embryonic development. In the study two models were used: heterologous (hamster ICSI assay: human sperm injected into a hamster oocyte) for evaluation of sperm head decondensation and pronuclear formation, and homologous (mouse model) for the study of fertilisation and development. Destruction of mitochondria of the sperm was achieved by exposure to cyanide, a respiratory poison. Rhodamine 123 was used to evaluate the functional integrity of mitochondria. Sperm head decondensation was found to be not statistically significantly affected by mitochondrial damage (p = 0.8), with 62.8% and 67.9% condensation in the experimental and control groups respectively. Male pronucleus formation was seen in 40.2% and 44.4% of the injected oocytes in the experimental and control groups respectively. In the mouse experiments 45.5% and 49.7% of the injected oocytes were fertilised in the mitochondria-damaged and live-intact sperm groups respectively (p = 0.53). Development to blastocyst was achieved in 53.5% and 59.4% of the experimental and control groups respectively; the difference was not significant (p = 0.71). Inner cell mass (ICM) cell number were 15.7 +/- 4.12 and 43.1 +/- 11.3 respectively in the mitochondria-damaged group; the equivalent numbers were 14.12 +/- 4.02 and 39.3 +/- 12.6 in the control group. However, the differences in ICM and total cell counts between these two groups were not significant. Of the blastocysts transferred to pseudopregnant mice, 51.3% (20/36) implanted and 33.4% (12/36) developed to live fetuses in the mitochondria-damaged group. These rates were 60.5% (23/38) and 39.5% (15/38) in the control group. In conclusion, this study shows that functional integrity of the sperm mitochondria is not necessary in the process of fertilisation and development when the sperm is deposited into the ooplasm. Fertilisation and development can be achieved by injection of sperm at the very early stage of necrosis in which only the mitochondria have been destroyed and the rest of the cell including the plasma membrane is still intact.

Animals↗
PubMed1997

Effect of spinal cord and peripheral nerve injury on human cutaneous sensory corpuscles. An immunohistochemical study.

This study was aimed at analyzing the changes in cutaneous sensory corpuscles from the territory of lesioned nerves and clinically denervated skin of patients with spinal cord injury using immunohistochemical methods. The morphological and biochemical characteristics of the Schwann-related cells of the mature sensory corpuscles (lamellar cells of Meissner corpuscles and inner-core of Pacinian corpuscles) depend upon the axon. To clarify whether this dependence requires structural and/or functional integrity of sensory axons we analyzed immunohistochemically some axonal, Schwann cell and perineurial cell antigens in cutaneous sensory corpuscles from i) the underlesional levels of patients with spinal cord injury affecting dorsal and lateral funiculi; ii) peripheral nerve entrapment, iii) sectioned and grafted nerves. Skin biopsy samples from the hand or feet were processed for peroxidase-antiperoxidase immunohistochemistry using monoclonal antibodies directed against neurofilament proteins (to label the axons), S-100 protein (to label Schwann-related cells), epithelial membrane antigen (to label the perineurial derivatives), vimentin (to label both Schwann cell and perineurial derivatives). Meissner and Pacinian corpuscles of subjects suffering from spinal cord lesions showed an immunohistochemical profile close to normality, although in many of them S-100 protein was unevenly distributed or absent. Sensory corpuscles of the cutaneous territory of entrapped nerves were in most cases similar to those of normally innervated skin. The most striking finding in these subjects was the hyperinnervation of blood vessels and sweat glands. Finally, nerve section and subsequent unsuccessful graft repair resulted in absence of immunostaining for all the assessed antigens in sensory corpuscles. The present results suggest that structural, but not functional, integrity of the axon is essential in maintaining some immunohistochemical characteristics of the human cutaneous sensory corpuscles. Morphological findings are correlated and discussed in relation to the clinical evaluation of the sensitivity.

Adult↗
PubMed1992

Photosystem II function and integrity in spite of drastic protein changes in a conserved region of the D2 protein.

D1 and D2 are structurally related proteins forming the core of the photosystem II reaction center. The two proteins have several loop regions including an extended stroma-exposed loop between transmembrane helix D and parallel helix de. This loop (the D-de loop) is phylogenetically conserved in both proteins. The role of the D-de loop in photosystem II was studied in Synechocystis sp. PCC 6803 by constructing a chimeric D2 protein in which the stroma-exposed loop of D1 replaced that of D2. In one of the transgenic lines, a single-base deletion shifted the reading frame of the chimeric gene leading to loss of D2 accumulation and photosystem II assembly. Selection for spontaneous reversion to photoautotrophy yielded several suppressor mutants, five of which were analyzed. In all, further frameshifts in the inserted loop piece restored the original reading frame allowing readthrough to the normal carboxy terminus. However, the sequences in the restored D-de loop varied widely among the mutants. Changes ranged from a deletion of one amino acid residue to an insertion of 31, while the net charge of the D-de loop increased by up to 12 units. Mutant electron transfer rates and photoautotrophic growth were only mildly affected as compared to wild type. Nevertheless, in all mutants, the hydropathy profile of the stroma-exposed D-de loop region maintained its hydrophilic character including turns in similar locations. We conclude that the stroma-exposed, D-de loop of the D2 protein can accommodate drastic composition and size changes without extensive functional consequences in photosystem II.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Tier-2 studies on monocrotaline immunotoxicity in C57BL/6 mice.

Monocrotaline (MCT) is a member of a class of naturally occurring phytotoxins known as pyrrolizidine alkaloids, and is a toxicological concern to both man and his livestock. The purpose of these studies was to evaluate the effect of a 14-day oral MCT (0-100 mg/kg per day) exposure on the functional integrity of various immunocyte effector systems in C57BL/6 mice, as well as to investigate potential mechanisms for its immunotoxicity. Decreases in lymphoid organ weights and cellularity, and resident peritoneal exudate cell (PEC) number were only observed after exposure to the highest dose of 100 mg/kg MCT. This dose also inhibited NK cell cytotoxicity, while the total number of NK lytic units per spleen was decreased (-53%) after exposure to 50 mg/kg MCT. Following i.p. injection of SRBC, the percentage of PEC macrophages containing engulfed SRBC was significantly increased in MCT-exposed mice, while the percentage of large vacuolated (activated) macrophages was decreased in a dose-dependent manner. Exposure to MCT significantly decreased the total number of Ig+ cells without altering the number of CD4+ and CD8+ cells. The antibody responses (PFC/10(6) spleen cells) to two T cell-independent antigens, TNP-LPS and DNP-Ficoll, were significantly decreased at all MCT doses, and the degree of suppression of both responses was identical at coincident doses. MCT exposure (25 mg/kg) significantly suppressed the blastogenic response to the T cell mitogen concanavalin A (-38%), and to the B cell mitogen lipopolysaccharide (-58%). These results indicate that exposure to MCT can alter the functional integrity of various immune effector responses in a dose-dependent manner, and suggest that the B cell may be a relatively more sensitive target of MCT immunotoxicity compared to T cells, macrophages and NK cells.

Animals↗
PubMed2002

Correlation between severity of clinical signs and motor evoked potentials after transcranial magnetic stimulation in large-breed dogs with cervical spinal cord disease.

OBJECTIVE: To evaluate use of transcranial magnetic motor evoked potentials for assessment of the functional integrity of the cervical spinal cord in large-breed dogs with cervical spinal cord disease. DESIGN: Randomized, controlled, masked study. ANIMALS: 10 healthy large-breed control dogs and 25 large-breed dogs with cervical spinal cord diseases. PROCEDURE: Affected dogs were allocated to 3 groups on the basis of neurologic status: signs of neck pain alone, ambulatory with ataxia in all limbs, or nonambulatory. Transcranial magnetic stimulation was performed on each dog with the same standard technique. Motor evoked potentials (MEP) were recorded from electrodes inserted in the tibialis cranialis muscle. Following the procedure, each dog was anesthetized and cervical radiography, CSF analysis, and cervical myelography were performed. The MEP latencies and amplitudes were correlated with neurologic status of the dogs after correction for neuronal path length. RESULTS: Mean MEP latencies and amplitudes were significantly different between control dogs and dogs in each of the 3 neurologic categories, but were not significantly different among dogs in the 3 neurologic categories. A linear association was evident between MEP latencies and amplitudes and severity of neurologic deficits; the more severe the neurologic deficits, the more prolonged the latencies and the more decreased the amplitudes. CONCLUSIONS AND CLINICAL RELEVANCE: Transcranial magnetic MEP are useful to assess severity of cervical spinal cord disease in large-breed dogs. Impairment of the functional integrity of the cervical spinal cord was found even in dogs with neck pain alone.

Animals↗
PubMed1993

Acute lymphoid leukemia. No evidence of consistent chemotherapy-induced intestinal malabsorption.

PURPOSE: The impact of chemotherapeutic agents on intestinal functional integrity was assessed in 16 consecutive children treated for acute lymphoid leukemia (ALL) and in remission on maintenance therapy. PATIENTS AND METHODS: Measurements of height, weight, nutrient intake, fecal fat, D-xylose absorption, and lactose absorption were obtained at diagnosis and every 6 months during therapy. RESULTS: At diagnosis all children were age appropriate for height and weight. A decrease in height velocity occurred in 73% at 12 months and 29% at 24 months. A reduced weight velocity was seen in 40% at 12 months and 14% at 24 months. Nutrient intake was more than two thirds the recommended nutrient intake (RNI) for energy in 70% of the children and > 100% RNI for protein in all but one child. Gastrointestinal investigations at diagnosis were normal, and no child had symptoms suggestive of malabsorption. Fecal fat excretion was abnormal in only one child, after therapy-induced pancreatitis, and returned to normal with pancreatic enzyme supplementation. D-xylose absorption became abnormal in two children at 6 months on therapy, normalized at 12 months, and remained normal on further evaluations. Intestinal lactose absorption was abnormal in four of 12 children. CONCLUSIONS: These results suggest that habitual nutrient intake is adequate and that there is no generalized malabsorption in children during treatment for ALL that might interfere with their overall nutritional status. However, mild to moderate alteration in intestinal functional integrity may occur transiently in some children.

Adolescent↗
PubMed1994

Sympathetic neural blockade by thoracic epidural anesthesia suppresses renin release in response to arterial hypotension.

BACKGROUND: The renin-angiotensin and vasopressin systems, in addition to the sympathetic system, are important backup mechanisms for maintaining arterial blood pressure during circulatory challenges. We tested the hypothesis that preganglionic sympathetic blockade by thoracic epidural anesthesia interferes with the functional integrity of the renin-angiotensin system. METHODS: Renin concentrations were assessed in awake non-sedated patients in response to induced arterial hypotension both before and during sympathetic blockade by thoracic epidural anesthesia (n = 10). Heart rate (electrocardiogram) and mean arterial blood pressure (electromanometry) were recorded continuously. Active renin (radioimmunoassay), vasopressin (radioimmunoassay), and osmolality (osmometry) in arterial blood were measured intermittently: (1) at baseline, (2) during a hypotensive challenge (15 min) induced by sodium nitroprusside (titrated to decrease mean arterial blood pressure by at least 25%) with the sympathetic system intact, (3) during recovery, (4) with epidural anesthesia alone (sensory blockade T1-T11), and (5) during a second hypotensive challenge and sympathetic blockade with sodium nitroprusside titrated to the same mean arterial blood pressure as with the sympathetic system intact. RESULTS: With the sympathetic system intact hypotension almost doubled renin concentration (34 +/- 32 SD to 60 +/- 58 pg.ml-1, P = 0.019), while vasopressin concentration remained unchanged. In contrast, during sympathetic blockade and despite identical hypotension (mean arterial blood pressure 68 +/- 8 vs. 67 +/- 5 mmHg), renin concentration did not change (35 +/- 27 vs. 35 +/- 29 pg.ml-1, P = 0.5), whereas vasopressin concentration increased (4.6 +/- 2.5 to 13.4 +/- 9.4 pg.ml-1, P = 0.01). Osmolality remained unchanged. CONCLUSION: Our results indicate a key role of renal sympathetic fibers in mediating renin release during hypotension in humans, and that epidural anesthesia interferes with the functional integrity of the renin-angiotensin system.

Adult↗
PubMedDate not supplied

Coronary vascular hemodynamic and permeability changes during reperfusion after no-flow ischemia in isolated, diltiazem-treated rabbit hearts.

Effects of diltiazem on coronary vascular functional integrity were assessed in isolated rabbit hearts during reperfusion after 30 min of global, no-flow ischemia. External detection of radiolabeled albumin, [125I]bovine serum albumin ([125I]BSA), and compartmental-model analysis were used to estimate the mean transit time of [125I]BSA (tBSA), vascular volume (V1), and vascular into extravascular space clearance (F21) for [125I]BSA. Perfusion pressure, left ventricular (LV) end-diastolic pressure, LV developed pressure, maximum +dP/dt, and V1 remained constant during 5 h of continuous perfusion, while tBSA and F21 gradually increased (1.5 and 2.4 times baseline, respectively). Diltiazem, 4 microM, increased total water content (8.5%) and decreased perfusion pressure (11%), LV developed pressure (22%), and +dP/dt (24%) in nonischemic control experiments, but did not significantly affect estimates of V1, extracellular space, tBSA, or albumin permeation. During reperfusion after 30 min of ischemia, V1 increased 40% and perfusion pressure increased 60%, while tBSA and F21 increased three and eight times baseline, respectively. LV developed pressure and +dP/dt returned to control levels, even though the water content and extracellular space of ischemic hearts were increased significantly. Diltiazem, 4 microM, blocked ischemia-reperfusion-induced increases in water content, extracellular space, vascular resistance, V1, and vascular permeability to [125I]BSA, without reducing LV developed pressure or +dP/dt relative to nonischemic diltiazem controls. These results suggest that protection of ischemic myocardium by diltiazem is mediated, at least in part, by preservation of vascular functional integrity.

Animals↗
PubMed1997

[Microinvasive cervical cancer].

While the rate of invasive carcinoma of the cervix is relatively constant among women under 40 years of age, the rate of microinvasive carcinoma (MIC) appears to increase steadily in this young age group. The definition of MIC is not universally established and if the probability of dissemination of the disease is low, it is not unconceivable and calls for an adequate surgical treatment that should respect the anatomic and functional integrity of these young women. The diagnosis of MIC relies primarily on conisation that is indicated in severe dysplasia and cervical neoplasia with no evidence of invasion on colposcopic directed biopsies. Conisation is the standard approach that requires a rigorous surgical technique and a thorough histological evaluation of the surgical sample by a skilled pathologist. This pathologic examination should be particularly attentive to the depth of stromal invasion, the width and volume of the lesion and the magnitude of LVI. While the dissemination within the parametrium cannot be well assessed, it appears that the likelihood of pelvic lymph node involvement approximates the depth of stromal invasion of the MIC with a threshold limit of 3 mm. LVI also carries the risk of poor prognosis, particularly in the early stages of the disease, and has been taken into consideration by the Society of Gynecologic Oncologists (SGO). The standard treatment of MIC is also conisation under the condition that the surgical limits are not diseased. If the depth of stromal invasion exceeds 3 mm or if LVI is reported by the pathologist, the lesion should then be treated like an invasive carcinoma of the cervix (i.e.: colpohysterectomy and pelvic lymphadenectomy). In some instances however (e.g.: early invasion with LVI), a laparoscopy directed pelvic lymphadenectomy could be suggested as a first line investigation associated with conisation. Since early invasive carcinoma of the cervix can now be defined and carries a reduced spreading potential we can propose an adequate treatment allowing functional integrity in these patients in a particularly young age group.

Biopsy↗
PubMedDate not supplied

Characterization of cystine uptake in cultured astrocytes.

Glutathione is involved in the maintenance of the structural and functional integrity of membrane proteins, in protection against free radicals and oxidative stress, and in the detoxification of xenobiotics. The cellular uptake of cystine is the rate limiting step in the biosynthesis of glutathione. The precise mechanism for such uptake is not clear as some reports indicate that the uptake occurs through a glutamate-cystine antiporter (system X(c)(-)), whereas, others suggest that it is taken up by the glutamate transporter (system X(AG)). Our studies in cultured astrocytes derived from neonatal rats showed that glutamate, D- and L-aspartate inhibited cystine uptake; that factors that increased intracellular glutamate levels, which would have enhanced the activity of the antiporter, did not stimulate cystine uptake; that the uptake was sodium dependent and partially chloride dependent; that the b(o,+) and ASC systems, which have been shown to carry cystine in some cells, did not mediate cystine uptake in astrocytes; that glutamate uptake blockers such as L-aspartate-beta-hydroxamate (AbetaH) and L-trans-pyrrolidine-2,4-dicarboxylate (PDC), as well as cystine uptake inhibitor L-alpha-aminoadipate (AAA) potently reduced cystine uptake. Additionally, deferoxamine (100 microM) as well as ammonium chloride (5 mM), both of which inhibit glutamate uptake, also inhibited cystine uptake. Taken together, our findings indicate that astrocytes take up cystine through a similar, if not identical, system used to take up glutamate. Interference of cystine uptake by astrocytes through the glutamate transport system may have profound effects on the redox state and the structural and functional integrity of the CNS.

Amino Acids↗
PubMed2006

Cystometric and in vitro muscle studies of cystoplastic appendiceal segments in the rat.

AIMS: The functional integration of the smooth muscle of enterocystoplasties into the detrusor muscle was investigated in an awake-rat cystometry model and in vitro. METHODS: The upper fourth of the bladder was removed, and a detubularized appendiceal segment (7 x 7 mm), with preserved vasculature, was incorporated into the bladder. After 1 or 3 months, a catheter was fixed to the top of the bladders. After a 3-day recovery, cystometries were performed. In separate experiments, agonist and nerve-induced responses were evaluated on isolated bladder strips. RESULTS: Cystometries revealed reduced basal pressure and micturition pressure in enterocystoplasty (ECP) bladders. Bladder capacity and micturition volume were increased. Threshold pressure (pressure immediately before micturition) was significantly lower at 1 month, but not at 3 months. Bladder compliance was significantly higher in the operated at 1 month but not at 3 months. Threshold tension did not differ between control and corresponding operated groups. Residual urine was significantly higher in the operated groups. ECP strips showed increased maximal contractions to nerve stimulation, to levels similar to those of detrusor strips. Maximal responses to carbachol increased to levels between those of intestine and detrusor. The inhibitory effect of scopolamine on nerve induced contractions increased to levels similar to those for detrusor. Purinergic activation had no effect on intestinal or ECP strips, but contracted detrusor muscle. CONCLUSIONS: The smooth muscle of the bowel segment in rat ECP bladders underwent a partial change in the response to nerve stimulation from that of intestine towards that of detrusor. The cystometry experiments suggested a partial functional integration of the ECP segment into the detrusor.

Animals↗
PubMed1999

Will stentless valves be durable? The Toronto valve (TSPV) at 5 to 6 years.

The early hemodynamic benefits of stentless aortic valves have been well documented. The issue of long-term functional integrity remains unanswered. We report the clinical results of a multicenter registry with prospective data on 621 patients monitored for 7.1 years. Patient data were collected and analyzed at St Jude Medical Inc, St Paul, Minnesota. In all, 66% of patients were male; the average age was 65.9 years +/-11.0 years, with 39% older than 70 years. Native aortic valves were bicuspid in 40.6%, 91.5% were calcified and 65.7% stenotic. Most valves implanted (83.1%) were sizes 25, 27, or 29 mm. Concomitant coronary bypass was performed in 42% of patients. Total follow-up time for the 621 patients was 1,944.5 valve years (mean 3.1 years per patient). At 5 years, 86.1% (n = 137) and at 6 years 80.4% (n = 51) were in New York Heart Association class I, and 78% had no or trivial atrial insufficiency. The average mean systolic gradient for all valves at 6 years was 4.0 mm Hg, and the peak gradient was 8.6 mm Hg. The effective orifice area varied from 1.4 cm2 (23-mm valve) to 2.7 cm2 (29-mm valve). The decrease in left ventricular mass index was significant and sustained. Actuarial survival at 6 years was 84.2%, and freedom from cardiac-related deaths was 90.1%. Freedom from valve-related deaths was 95.7%, and freedom from prosthetic endocarditis was 98.6%. There were no instances of primary tissue valve failure during follow-up, with 97.2% freedom from reoperation. The early hemodynamic benefits of the TSPV are well maintained during more than 6 years of follow-up, without evident valvular dysfunction. Longer follow-up time is required to validate durability, but there is increasing evidence for well-maintained structural and functional integrity.

Actuarial Analysis↗
PubMed1981

Contractile mechanics and interaction of the right and left ventricles.

The heart and lungs, together with hemoglobin, provide for the transport of oxygen from the atmosphere to the metabolizing tissue. The oxygenation of blood and the circulation of oxygenated blood are precisely synchronized so that the heart and lungs constitute an integrated cardiopulmonary unit. The functional integration of the heart and lungs is fostered by their anatomic arrangement and mechanical interaction. The cardiopulmonary unit consists of the right and left ventricles (two in-series pumps composed of cardiac muscle), which are mechanically coupled by the lungs. The factors that control cardiac muscle shortening (fiber length, afterload and myocardial contractile state) also regulate the pumping behavior of each ventricle. Because the ventricles are aligned in series a perturbation in the mechanical events of one ventricle will influence the behavior of the other ventricle. The interventricular septum and pericardium further promote the mechanical interplay between ventricles. Intrathoracic pressure (the pressure that surrounds the cardiopulmonary unit) creates an additional interaction between the ventricles as well as the heart and lungs.

Acute Disease↗
PubMed1998

Anastomotic integrity and function: role of the colonic J-pouch.

Since the colonic J-pouch with a colo-anal anastomosis was first introduced in 1986, many reports have shown the superiority of this design as compared to a "straight" colo-anal anastomosis. These advantages have been demonstrated in retrospective, prospective, and prospectively randomized reports. Furthermore, these attributes are realized for at least 12 and possibly more than 24 months after surgery.

Anal Canal↗