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PubMed1990

Left atrial dimensions in growth and development: normal limits for two-dimensional echocardiography.

Reference values for normal left atrial dimensions have been based primarily on blind M-mode measurements, with no reports based on two-dimensional echocardiography to provide a comprehensive analysis of the two-dimensional measurements from infancy to old age. This report analyzes the left atrial dimensions from two-dimensional echocardiographic studies in 268 normal healthy subjects to determine normal limits and relations among linear, area and volume measurements of the left atrium. The group mean values change with body size, fitting well to the exponential growth model (r = 0.78 to 0.92). The variance about the mean (which determines normal limits) is represented effectively by a quadratic function of body surface area (r = 0.84 to 0.99). The variables determined by this modeling simplify evaluation of normal limits for any body size at any desired level of confidence, and the data are useful reference standards for interpretation of two-dimensional echocardiograms.

Adult↗

PubMed1994

Outcome of percutaneous transluminal coronary angioplasty in subsets of unstable angina pectoris. A report of the 1985-1986 National Heart, Lung, and Blood Institute Percutaneous Transluminal Coronary Angioplasty Registry.

OBJECTIVES: The purpose of this study was to characterize the outcome of coronary angioplasty according to the various presentations of unstable angina pectoris. BACKGROUND: Although unstable angina is a mosaic of clinical manifestations, a comprehensive analysis of short- and long-term outcome of coronary angioplasty in subsets of unstable angina is not available. METHODS: Data from 15 clinical centers for the 857 patients with unstable angina in the 1985-1986 National Heart, Lung, and Blood Institute percutaneous transluminal coronary angioplasty registry were analyzed. Five-year follow-up was available in > 96.5%. Patients were first classified as those with (679 [79%]) or without (178 [21%]) rest angina. Patients were also allocated to five mutually exclusive categories of decreasing unstable angina severity: postinfarction angina, acute coronary insufficiency, plain rest angina, accelerating angina and new onset angina. RESULTS: The group with rest angina had more older patients (p < 0.01) and women (p < 0.001), and a greater proportion had a previous myocardial infarction (p < 0.001) and a left ventricular ejection fraction < or = 50% (p < 0.01) than did the group without rest angina. Angiographic characteristics were nearly the same, whereas procedural characteristics and outcome were the same for both categories. At 5-year follow-up, there was a higher crude mortality rate in patients with than without rest angina (p < 0.05). Resolution into five subsets yielded additional information. Women were more represented only in the acute coronary insufficiency and plain rest angina subsets (p < 0.001). Patients with angina after myocardial infarction had the second shortest history of angina (p < 0.001), the highest percent of smokers (p < 0.01) and, with those with acute coronary insufficiency, the highest incidence of congestive heart failure (p < 0.05) and an ejection fraction < or = 50% (p < 0.001). They had the highest percent of totally occluded arteries, coronary thrombus and collateral blood flow received but also the lowest rate of severe stenoses (p < 0.001 for all). Patients with new onset angina had the highest prevalence of single-vessel disease (p < 0.05), critical and complex stenoses (p < 0.001) and no coronary angioplasty-related deaths. The crude 5-year mortality rate was higher for both postinfarction and acute insufficiency groups (p < 0.05) than for the other subsets. After adjustments for risk factors, no significant differences in adverse event rates remained among the different unstable angina subgroups. CONCLUSIONS: Analysis of the diverse clinical presentations of unstable angina supports underlying pathogenetic differences. Coronary angioplasty is safe and effective in all subsets of unstable angina. Long-term survival is good in general but is related to the baseline status of left ventricular function.

Angina, Unstable↗

PubMed1992

Chemotherapy of advanced epithelial cancer--a critical review.

This article is a short version of a report which presents a comprehensive analysis of clinical trials and publications examining the value of cytotoxic chemotherapy in the treatment of advanced epithelial cancer. As a result of the analysis and the comments received from hundreds of oncologists in reply to a request for information, the following facts can be noted. Apart from lung cancer, in particular small-cell lung cancer, there is no direct evidence that chemotherapy prolongs survival in patients with advanced carcinoma. Except for ovarian cancer, available indirect evidence rather supports the absence of a positive effect. In treatment of lung cancer and ovarian cancer, the therapeutical benefit is at best rather small, and a less aggressive treatment seems to be at least as effective as the usual one. It is possible that certain sub-groups of patients benefit from the treatment, yet so far the available results do not allow a sufficiently precise definition of these groups. Many oncologists take it for granted that response to therapy prolongs survival, an opinion which is based on a fallacy and which is not supported by clinical studies. To date, it is unclear whether the treated patients, as a whole, benefit from chemotherapy as to their quality of life. For most cancer sites, urgently required types of studies such as randomized de-escalations of dose or comparisons of immediate versus deferred chemotherapy are still lacking. With few exceptions, there is no good scientific basis for the application of chemotherapy in symptom-free patients with advanced epithelial malignancy.

Bias↗

PubMed1994

The redox couple between glutathione and ascorbic acid: a chemical and physiological perspective.

This article provides a comprehensive analysis of the redox reaction between glutathione/glutathione disulfide and ascorbic acid/dehydroascorbic acid. It includes an historical perspective of the progression of the experiments, first begun more than 60 years ago and continuing today with heightened importance. Indeed, the antioxidant capacity of glutathione and ascorbic acid, whether singly or in combination, linked via the redox couple, is a subject of intense interest for studies by bench scientists and clinicians, particularly because a growing body of evidence suggests that free radicals may be involved in a variety of diseases. The authors begin with a detailed summary of "test tube" experiments (the chemical perspective) that have revealed the conditions that regulate the rate of the redox coupling between glutathione and dehydroascorbic acid and that promote or inhibit the decomposition of dehydroascorbic acid in ordinary, buffered aqueous media; results obtained in the authors' laboratory are used for illustration purposes and uniformity of presentation. The authors then proceed to a critical examination of the extent to which the redox couple between glutathione and ascorbic acid operates in a cell, using the often published antioxidant cascade (See Fig. 1) as the model for the analysis (the physiological perspective). The evidence for and the evidence against the presence of the enzyme dehydroascorbate reductase in animal cells is outlined in a balanced way in an attempt to make sense of this continuing controversy. Next, the authors carefully document the many studies showing that exogenous dehydroascorbic acid is transported into cells where it is reduced to ascorbic acid by glutathione. Finally, they probe the functional significance and efficiency of the redox couple in monolayer cultures of human retinal pigment epithelial (RPE) cells, as a prototypical cellular model. The authors include the results of new experiments showing that incubation of RPE cells with a nitroxide, TEMPOL, leads to the selective oxidation of intracellular ascorbic acid. This approach is desirable because it dissects the cascade at a specific site and permits measurements of the levels of ascorbic acid and glutathione in the cells before, during, and after oxidation. The results show that only partial regeneration of ascorbic acid is obtained when control conditions are restored. However, if either ascorbic acid or dehydroascorbic acid is added to the media during the recovery period following treatment of cells with TEMPOL, then full recovery of ascorbic acid is observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1994

Sequential cytogenetic alterations in hamster oral keratinocytes during DMBA-induced oral carcinogenesis.

Using the hamster cheek pouch oral cancer model, we have performed a comprehensive analysis of the cytogenetic changes in hamster oral keratinocytes during 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis. Tumour induction in the hamster cheek pouch required repeated application of the carcinogen for 14 weeks. We have found that this hamster oral cancer model to be suitable for cytogenetic studies. Unlike human oral cancers where chromosome breaks have been shown, this is only infrequently observed in DMBA-treated hamster oral keratinocytes. Of importance is the finding that at the beginning of the second week of DMBA treatment, there is a significant increase of karyotypes demonstrating tetraploid or near-tetraploidy. We propose that the significant increase in hamster oral keratinocytes exhibiting tetraploidy be further evaluated as a marker of premalignancy/malignancy.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1993

Diastolic dysfunction in post-cardiac surgical management.

Although an appropriate definition of primary diastolic failure is still not at hand, primary diastolic failure is a distinct pathophysiologic syndrome. It is due to an increased resistance to ventricular filling and results in an inappropriate upward shift of the diastolic P-V relationship, especially during exercise. This leads to exercise intolerance with symptoms of congestion. The causes are known, ie, impaired systolic relaxation, decreased diastolic compliance, and inappropriate tachycardia. Pathophysiologically impaired (incomplete or slowed) systolic relaxation must be distinguished from physiologic, compensatory prolonged contraction (delayed or retarded relaxation). Treatment of diastolic failure is feasible, but necessitates a clear understanding of the etiology, pathogenesis, and pathophysiology of the underlying cardiac disease. Optimal therapy will depend on the type of disease, on the phase during the pathophysiologic evolution of a given disease, and on the coexistence and relative contribution of various compensatory or decompensatory mechanisms. This often requires a comprehensive analysis of hemodynamics, for example, with echo-doppler, completed, whenever necessary, by catheterization.

Cardiac Output, Low↗

PubMed1992

Relationships between quantitative histological measurements and noninvasive assessments of bone mass.

We performed a comprehensive analysis of the relationships between histologic indices in the iliac crest (cancellous bone volume, trabecular structural indices, cortical width, and core width) and bone density in the spine, hip, and wrist in 81 patients with various metabolic bone diseases including osteoporosis, osteomalacia, hyperparathyroidism, and Paget's disease. In the whole group, all of the histologic indices correlated significantly with bone mineral density (BMD) of the spine and the three regions of the hip (r = 0.28-0.73), with the exception of cortical width which correlated with the hip but not the spine (r = 0.21). There was no relationship between the histologic variables and either the distal or proximal radius. When the osteoporotic subgroup was considered separately, the relationships between BMD and both cancellous bone volume and the structural indices (trabecular number, separation, and thickness) were lost. In contrast, cortical width correlated more strongly with both spine and hip BMD. The relationship between core width and the spine was lost but persisted in the hip region. In female osteoporotic patients alone, only cortical width remained significantly correlated with spine or hip BMD. We conclude that the relationships between bone densities in the axial and peripheral regions and histomorphometric variables in iliac crest are not constant. In addition, cancellous bone volume and the trabecular structural indices relate well to noninvasive axial BMD measurements only in a heterogenous group with a large variance in both parameters. In the more homogeneous group with osteoporosis, cortical width appears to be a more powerful predictor of BMD at the important sites of osteoporotic fracture.

Bone Density↗

PubMed2026

Antibody-drug conjugates against multidrug-resistant cancers: Biomarker-guided patient selection, payload engineering, linker chemistry, and bystander effects.

Antibody-drug conjugates (ADCs) are one of the most significant advancements in modern cancer therapeutics. Combining the target selectivity of monoclonal antibodies with the cytotoxic potential of payloads, ADCs effectively kill cancer cells and offer hope to patients with even refractory cancer types. Beyond simply increasing the number of therapeutic options available for cancer patients, ADCs have become a powerful frontline agent in overcoming multidrug resistance (MDR). As one of the most challenging obstacles to effective cancer care, MDR is mediated by ATP-binding cassette (ABC) transporter-mediated drug efflux, target-based mutations, and dysregulated apoptosis. The clinical success of ADCs specifically engineered to overcome MDR, including in heterogeneous tumors and cancer cells that exhibit bypass signaling, is well established. This is especially evident with trastuzumab deruxtecan (T-DXd) in HER2-low, HER2-positive, and HER2-mutant cancers; sacituzumab govitecan (SG) in TROP2-expressing triple-negative breast cancer (TNBC) and urothelial carcinoma; and enfortumab vedotin in Nectin-4-positive bladder cancer. By overcoming MDR, ADCs have enabled more effective treatment algorithms across multiple malignancies. Most importantly, the clinical application of ADCs has become inextricably linked to cancer genomics. HER2 testing has evolved from a two-tiered system to a continuous spectrum including HER2-ultralow, HER2-low, HER2-positive, and ERBB2-mutant categories. Each of these categories exhibits different eligibility guidelines for ADC patient selection. As cancer cells continue to evolve and develop resistance to even ADCs through mutations and variants, researchers and clinicians have used pharmacogenomics to predict ADC response and resistance. To define the genomic architecture of ADC-resistant tumor subpopulations, single-cell transcriptomic studies and liquid biopsy approaches are being used to enable real-time examination of the tumor genome during ADC therapy, thereby optimizing treatment and circumventing resistance driven by emerging mutations and variants. This review provides a comprehensive analysis of the molecular structure of ADCs, the pharmacological principles underlying their potent cytotoxic activity against MDR cancer cells, the genomic and transcriptomic biomarkers that guide ADC patient selection, and the emerging resistance mechanisms that will shape the next generation of promising ADC development.

Humans↗

PubMed2025

One thousand SARS-CoV-2 antibody structures reveal convergent binding and near-universal immune escape.

Understanding antibody recognition and adaptation to viral evolution is central to vaccine and therapeutic development. Over 1,100 SARS-CoV-2 antibody structures have been resolved, marking the largest structural biology effort for a single pathogen. We present a comprehensive analysis of this landmark dataset to investigate the principles of antibody recognition and immune escape. Human immunoglobulins and camelid single-chain antibodies dominate, collectively mapping 99% of the receptor-binding domain. Despite remarkable sequence and conformational diversity, antibodies exhibit convergence in their paratope structures, revealing evolutionary constraints in epitope selection. Analyses reveal near-universal immune escape of antibodies, including all clinical monoclonals, by advanced variants such as KP3.1.1. On average, over one-third of antibody epitope residues are mutated. These findings support pervasive immune escape, underscoring the need to effectively leverage multi-epitope-targeting strategies to achieve durable immunity. To support community accessibility, we developed an interactive web server for visualization and analysis of antibody-antigen complexes and mutational data.

SARS-CoV-2↗

PubMed2026

Comprehensive identification of carboxylic acids by using bromine isotope-based chemical isotope labelling and structure-guided molecular network.

Carboxylic acids (CAs) are important contributors to the flavor quality of sauce-flavor Chinese Baijiu, yet their comprehensive analysis remains challenging due to poor ionization efficiency, weak chromatographic retention, and limited annotation capability. Herein, we developed a workflow for the high-coverage discovery and annotation of CAs in Baijiu by coupling chemical isotope labeling-liquid chromatography-mass spectrometry with a structure-guided molecular network strategy (SGMNS). A bromine-containing derivatization reagent, 1-(3-aminopropyl)-3-bromoquinolin-1-ium bromide (APBQ), was designed and synthesized to exploit the natural isotope distribution of bromine and characteristic MS/MS fragmentation behavior. Following APBQ derivatization, the target CAs showed superior chromatographic retention and favorable analytical performance. Based on isotopic peak pairing in MS1 and diagnostic fragment validation in MS2, 372 potential CA derivatives were discovered from pooled Baijiu samples and 355 of them were validated by diagnostic fragments in MS2 spectra. To address the scarcity of derivatized spectral libraries, SGMNS was employed for annotation using a background network constructed from APBQ-labeled candidates derived from the Expanded Chinese Baijiu Compound Database. The developed method was further applied to profile Baijiu samples, revealing pronounced differences in CA composition across the seven fermentation rounds. Notably, rounds 3 to 5 exhibited the largest numbers of differential CAs. This study provided an effective analytical strategy for large-scale CA profiling, offering new insight into the chemical basis of flavor formation during multi-round fermentation of sauce-flavor Baijiu.

Isotope Labeling↗

PubMed2026

Clinical and endocrine correlates of genetic etiologies in severe hypospadias: Study from 34 patients.

OBJECTIVE: Hypospadias is a prevalent congenital anomaly (0.3%-1.0%); however, severe hypospadias (defined as proximal cases with the meatus at the penoscrotal junction, scrotum, or perineum) is a rare and clinically challenging entity with a multifactorial etiology. This study aimed to characterize the interrelationships among the clinical, endocrine, and genetic profiles in children with severe hypospadias. MATERIALS AND METHODS: We conducted a comprehensive analysis of 34 male patients with severe hypospadias. Preoperative hormone levels were measured using two methods: chemiluminescent immunoassay for luteinizing hormone and follicle-stimulating hormone, and liquid chromatography-tandem mass spectrometry for testosterone (T), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), 17α-hydroxyprogesterone (17α-OHP), and other steroids. Genetic analysis was conducted via whole exome sequencing. RESULTS: The diagnostic yield of clinically relevant genetic variants (including pathogenic and likely pathogenic, and variants of uncertain significance) in our cohort was 41.2% (14/34) of patients. Patients carrying these variants exhibited a more complex phenotypic profile compared to non-carriers, including a significantly higher rate of patients with ≥3 associated malformations and a greater prevalence of cryptorchidism. Furthermore, the group with clinically relevant variants showed selective elevations in adrenal-derived precursors, specifically 17α-OHP and DHEA. Correlation analysis revealed significant positive associations of both 17α-OHP levels and the T/DHT ratio with the number of associated malformations. CONCLUSION: This study reveals significant genetic heterogeneity in patients with severe hypospadias. Those carrying genetic variants was associated with more severe clinical phenotypes, while certain endocrine variations, including the elevation of adrenal-derived hormones, were also observed in this cohort.

Humans↗

PubMed2024

Identification of a Proteomic Signature for Predicting Immunotherapy Response in Patients With Metastatic Non-Small Cell Lung Cancer.

Immunotherapy has improved survival rates in patients with cancer, but identifying those who will respond to treatment remains a challenge. Advances in proteomic technologies have enabled the identification and quantification of nearly all expressed proteins in a single experiment. Integrating mass spectrometry with high-throughput technologies has facilitated comprehensive analysis of the plasma proteome in cancer, facilitating early diagnosis and personalized treatment. In this context, our study aimed to investigate the predictive and prognostic value of plasma proteome analysis using the SWATH-MS (Sequential Window Acquisition of All Theoretical Mass Spectra) strategy in newly diagnosed patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab therapy. We enrolled 64 newly diagnosed patients with advanced NSCLC treated with pembrolizumab. Blood samples were collected from all patients before and during therapy. A total of 171 blood samples were analyzed using the SWATH-MS strategy. Plasma protein expression in metastatic NSCLC patients prior to receiving pembrolizumab was analyzed. A first cohort (discovery cohort) was employed to identify a proteomic signature predicting immunotherapy response. Thus, 324 differentially expressed proteins between responder and non-responder patients were identified. In addition, we developed a predictive model and found a combination of seven proteins, including ATG9A, DCDC2, HPS5, FIL1L, LZTL1, PGTA, and SPTN2, with stronger predictive value than PD-L1 expression alone. Additionally, survival analyses showed an association between the levels of ATG9A, DCDC2, SPTN2 and HPS5 with progression-free survival (PFS) and/or overall survival (OS). Our findings highlight the potential of proteomic technologies to detect predictive biomarkers in blood samples from NSCLC patients, emphasizing the correlation between immunotherapy response and the idenfied protein set.

Humans↗

PubMed2025

Structural diversity and evolutionary constraints of oxidative phosphorylation.

The oxidative phosphorylation (OxPhos) system is central to metabolism. The more than 90 structural subunits are encoded by different chromosome categories (autosomal, X, and mtDNA). The system is envisioned as an invariant structure between cells and individuals. However, a comprehensive analysis of the 1,000 Genomes Project data reveals unexpected genetic intra-individual variability resulting from the heterozygosity of diploid autosomal genes, while diversity at the population level is generated by variability in mtDNA. We characterized the different levels of structural constriction at evolutionary and population levels for all OxPhos protein residues. To support this analysis, we developed ConScore, a conservation-based predictor of variant impact within OxPhos proteins (area under the receiver operating characteristic curve [ROC-AUC] = 0.97; area under the precision-recall curve [PR-AUC] = 0.94). Notably, for the nuclear-encoded subunits, we found mechanisms limiting individual variability as allelic imbalance or homozygosity bias. Integrating structural, functional, and genetic data, we highlight the significance of each OxPhos protein position, expanding insights into its role in speciation and disease.

Oxidative Phosphorylation↗

PubMed1994

Vagaries of the lavage white blood cell count in evaluating abdominal stab wounds.

BACKGROUND: The clinical value of an elevated white blood cell (WBC) count on a diagnostic peritoneal lavage (DPL) performed in an asymptomatic patient with a penetrating abdominal stab wound is controversial. METHODS: We performed a comprehensive analysis of asymptomatic patients (no signs of peritonitis) with stab wounds who underwent an exploratory laparotomy based solely on a WBC count > 500/mm3 in the effluent of an open DPL. RESULTS: Twenty-eight patients, 25 with injury to the gastrointestinal (GI) tract and 3 with injury to the liver, obtained true-positive results from DPL. Their mean WBC count in lavage effluent obtained at a mean of 7.6 hours after the stab wound was 3,380/mm3 and their mean serum WBC count, obtained at the same time, was 12,324/mm3. Fifteen patients had false-positive results from DPL. They were lavaged at a mean of 7.2 hours after the stab wound, and had a mean lavage WBC count of 1,228/mm3 and a mean serum WBC count of 9,084/mm3. CONCLUSIONS: Patients lavaged at a mean 6 to 7 hours after an abdominal stab wound will have a significant incidence of false-positive studies based on an elevated WBC count alone. Lavage WBC counts > 3,000/mm3, particularly when associated with a serum WBC count > 11,000, are likely to be true positives and to indicate injury to the GI tract.

Abdominal Injuries↗

PubMed1990

Using FACS vs. communication scores to measure spontaneous facial expression of emotion in brain-damaged patients: a reply to Mammucari et al. (1988).

Buck and Duffy (1980) and Borod et al. (1985) found evidence of deficits in spontaneous expressiveness in right brain-damaged (RBD) patients relative to LBD patients and controls. Using FACS, Mammucari et al. (1988) failed to replicate this result and questioned our methods and findings. This paper replies (a) that Mammucari et al. (1988)'s review of our work is selective and misleading; (b) that there are aspects of their study that can account for their null results, including the insufficient sensitivity of FACS for the measurement of spontaneous expressiveness; and (c) that the results of Mammucari et al. (1988) regarding "aversive eye movements" to a negative film in LBD and control, but not RBD, patients are in fact compatible with our findings. This paper also suggests a general strategy for the objective and comprehensive analysis of spontaneous emotional expressiveness.

Brain Damage, Chronic↗

PubMed1989

Interplay of hydrophobic and electrostatic interactions in biopolymer chromatography. Effect of salts on the retention of proteins.

The effect of salt on the retention behavior of proteins in electrostatic and hydrophobic interaction chromatography is described by a three-parameter equation, log k' = A - B log ms + Cms, where k' is the retention factor and ms is the molality of the salt in the eluent. Parameter B, termed the electrostatic interaction parameter, depends on the characteristic charge of the protein and the salt counterion and governs the change of retention with the salt concentration in ion-exchange chromatography. According to the model the magnitude of the hydrophobic interaction parameter C is determined by the hydrophobic contact area upon protein binding at the stationary phase surface and the properties of the salt as measured by its molal surface tension increment. Retention data measured at different salt concentrations in the eluent on a variety of ion exchangers can be fitted to the above equation which yields U-shaped plots of log k' against log ms. The limiting slopes of the appropriate plots at sufficiently low and high salt concentrations can be used to evaluate the electrostatic and hydrophobic interaction parameters, respectively. The approach, which is based on a combination of established treatments of electrostatic and hydrophobic interactions offers a convenient framework for analyzing retention data in biopolymer high-performance liquid chromatography and for the characterization of stationary phases. Furthermore, it may facilitate some characterization of protein molecules on the basis of their retention behavior as a function of the concentration and nature of the salt in the eluent. In the treatment of electrostatic interactions use is made of the counterion condensation theory that is believed to make possible a more comprehensive analysis than the traditional stoichiometric ion-exchange model which assumes binding of the proteins by coulombic interactions at discrete sites. The treatment of hydrophobic interactions is based on an adaptation of the solvophobic theory which predicts that the hydrophobic portion of the free energy of binding is proportional to the hydrophobic contact area and the microthermodynamic surface tension of the aqueous salt solution. Despite its simplicity the theory was successful in explaining the observed effect of the nature and concentration of salt in the eluent, the pH and the effect of the density of fixed charges at the surface of the stationary phase in the absence of specific salt effects.

Biopolymers↗

PubMed1995

Curative treatment for pancreatic neoplasms. Radical resection.

The available data suggest that lymph node involvement is an important prognostic factor in patients with carcinoma of the head of the pancreas. Lymph node metastases occur in as many as 50% of the cases of even the smallest pancreatic cancers now being diagnosed and resected (i.e., those < 2 cm in diameter). There is some evidence, especially from clinical experience in Japan, that wider lymphatic dissections (i.e., wider than those commonly done with the standard Whipple resection) may prolong survival. Unfortunately, many of the available data around the world are retrospective and are not randomized between the standard and the radical operation. Moreover, the pathologic material has not been staged uniformly according to accepted criteria. Thus the various series are not comparable. Comparisons between series require standardization with respect to stage of disease, pathologic classification, and treatment protocols. Before any modification of the standard pancreaticoduodenectomy is adopted, an appropriately designed study should be performed to test its efficacy. This study would also require a more comprehensive analysis of the pathologic material than is commonly performed today in the United States and Europe.

Humans↗

PubMed1989

Patellofemoral instability in total knee arthroplasty.

Patellofemoral instability following total knee arthroplasty remains one of the major complications requiring operative intervention. In spite of recent advances in technique and instrumentation, the rate of this complication remains disturbingly high. A comprehensive analysis of cause reveals malalignment of any of the components to be potentially responsible, particularly valgus or internal rotation malalignment of either femoral or tibial component, as well as lateral displacement of the patellar component. Underresection of the patella or oversizing the femoral component may also contribute to excessive lateral retinacular tightness. When confronted with patellofemoral instability, the surgeon must first look for and correct the cause. Component malalignment requires component revision. Extensor mechanism imbalance requires either proximal or distal realignment. Lateral release alone invites recurrence of the problem.

Arthroplasty↗