Well-defined Clinical Conditions Research Articles

Specific humoral response in cancer patients treated with a VEGF-specific active immunotherapy procedure within a compassionate use program

BackgroundCIGB-247 is a cancer therapeutic vaccine that uses as antigen a variant of human vascular endothelial growth factor (VEGF) mixed with the bacterially-derived adjuvant VSSP. CIGB-247 has been already evaluated in two phase I clinical trials (CENTAURO and CENTAURO-2), showing to be safe and immunogenic in advanced cancer patients selected under well-defined and controlled clinical conditions. Surviving patients were submitted to monthly re-immunizations and some of them showed objective clinical benefits. Based on these results, a compassionate use program (CUP) with CIGB-247 was initiated for patients that did not meet the strict entry criteria applied for the CENTAURO and CENTAURO-2 clinical trials, but could potentially benefit from the application of this cancer therapeutic vaccine.ResultsPolyclonal IgM, IgA and IgG antibodies specific for VEGF were detected by ELISA in serum samples from patients vaccinated with 400 μg of antigen combined with 200 μg of VSSP. Polyclonal antibody response showed no cross reactivity for other VEGF family member molecules like VEGF-C and VEGF-D. Serum from immunized individuals was able to block the binding of VEGF to its receptors VEGFR2 and VEGFR1. IgG fraction purified from immune sera shared the aforementioned characteristics and also inhibited the interaction between VEGF and the therapeutic recombinant antibody bevacizumab, an anti-angiogenic drug approved for the treatment of different tumors. No serious adverse events attributable to CIGB-247 have been documented yet in participants of the CIGB-247 CUP.The present paper is a first report of our findings concerning the humoral response and safety characteristics in treated CIGB-247 CUP cancer patients. The study has provided the unique opportunity of not only testing CIGB-247 in a broader clinical spectrum sample of Cuban cancer patients, but also within the context of the day-to-day clinical practice and treatment settings for these diseases in Cuban medical institutions.ConclusionsThe CIGB-247 CUP has demonstrated that immunization and follow-up of a variety of cancer patients, under day-to-day clinical practice conditions in several Cuban medical institutions, replicate our previous findings in clinical trials: CIGB-247 is safe and immunogenic.

Pathogen Profile of Patients with Sepsis in Internal Medicine, Dr. Hasan Sadikin General Hospital, Bandung 2013

Background : Sepsis is a continuous disease which begins with systemic inflammatory response syndrome (SIRS), seen in association with a large number of clinical conditions. These include infectious insults that produce SIRS, such as pancreatitis, ischemia, multiple traumas and tissue injury, hemorrhagic shock, immunemediated organ injury, and the exogenous administration of such putative mediators of the inflammatory process as tumor necrosis factor and other cytokines. A frequent complication of SIRS is the development of organ system dysfunction, including such well-defined clinical conditions as acute lung injury, shock, renal failure, and multiple organ dysfunction syndrome (MODS). Hence, this study was conducted to identify the pathogen profile that often causes sepsis. Methods : A retrospective study was performed to 152 medical records of patients diagnosed as sepsis from Internal Medicine Department Dr. Hasan Sadikin General Hospital from January 2013 to December 2013. The variables observed from the medical records were age, sex, comorbidity, main infection, culture sample, type of gram bacteria, resistant bacteria, and antibiotic susceptibility test. After data collection was completed, the data were analyzed using computer. The data were presented in percentage. Results : Sepsis in male was higher than female. Highest comorbid was chronic kidney disease (CKD). The main infection was health care acquired pneumonia (HCAP). Highest pathogen that caused sepsis was Escherichia coli and highest multidrug-resistant organism (MDRO) was extended spectrum beta-lactamase (ESBL) Escherichia coli. Conclusions : The most common pathogen that causes sepsis is Escherichia coli. [AMJ.2016;3(2):200–5] DOI: 10.15850/amj.v3n2.785

Neurological Signs and Symptoms of True Neurogenic Thoracic Outlet Syndrome

Thoracic outlet syndrome (TOS) is a well-known disorder, but many aspects of its pathology, including its definition, has been disputed. True neurogenic TOS (TN-TOS) is a rare but well-defined clinical condition. TN-TOS results from the compression of the C8/T1 roots (dominant for the T1 root) or the proximal lower trunk of the brachial plexus by a fibrous band. The band extends from the first rib to either the tip of an elongated C7 transverse process or a rudimentary cervical rib. The most common presenting symptoms of TN-TOS are insidious-onset atrophy and weakness of the intrinsic hand muscles, predominantly in the thenar eminence and radial digit flexors. Nerve conduction studies demonstrate pathognomonic findings: severely attenuated compound muscle action potential of the abductor pollicis brevis muscle, and usually, loss of the sensory nerve action potential of the medial antebrachial cutaneous nerve. Numbness and sensory loss are typically observed, mainly in the medial forearm, although they are usually mild, and may be absent in some patients. Severe pain or paresthesia proximal to the elbow is not observed. The classical concept of TOS underlie nonspecific neurogenic TOS. It has been primarily diagnosed using provocative maneuvers. However, there is controversy regarding its pathological conceptualization and existence, as objective evidence of the disease is still lacking.

Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

Discovery of most autosomal recessive disease genes has involved analysis of large, often consanguineous, multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of novel dominant causes of rare, genetically heterogenous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios 1,2. Here we analysed 4,125 families with diverse, rare, genetically heterogeneous developmental disorders and identified four novel autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (identifying probands with rare biallelic putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population, and (ii) the phenotypic similarity of patients with the same recessive candidate gene. This new paradigm promises to catalyse discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations, and those caused predominantly by compound heterozygous genotypes.

Comparative pharmacognostical and pharmaceutical evaluation of Vyaghri haritaki avaleha - an ayurvedic formulation

Kasa is well-defined clinical condition in Brihadtrayi, clearly correlate with cough and its pathophysiology exactly correlates with the mechanism of cough reflex in contemporary medical science. Everywhere, Paediatric Outdoor Patients Department (OPD) has more than half of the total patients having respiratory tract complaints. So, to treat the disease Kasa, Vyaghri Haritaki Avaleha (VHA) was taken from Bhaishajya Ratnavali. The present work was carried out to standardize the raw drugs and finished product-VHA with comparing API standards and previous research work done in same institute to conform its identity, quality and purity of the final product. The pharmacognostical work reveals that presence of Epidermis, Cork, Pericycle, Phloem etc. from Kantakari; Lignified fibre, Stone cells etc. of Haritaki; Aluerone grains, Prismatic crystals etc. of Shunthi observed microscopically. Organoleptic features of VHA made out of the crude drugs were within the standard range. The pH value of VHA was 4.5, Water soluble extract was 71.9 %w/w, Loss on drying was 30.41 %w/w, Reducing sugar was 27.92 %w/w and High Performance Thin Layer Chromatography (HPTLC) at 254nm and 366nm resulted into 2 and 5 spots respectively

AB1166 Henoch-schoenlein purpura: Clinical study of 340 patients

BackgroundMost Henoch-Schonlein Purpura (HSP) studies came from selected series and used different classification criteriaObjectivesOur aim was to assess the epidemiological, clinical features, treatment and prognosis in an unselected and well-defined...

Cytokine Profiles in Sepsis Have Limited Relevance for Stratifying Patients in the Emergency Department: A Prospective Observational Study

IntroductionMorbidity, mortality and social cost of sepsis are high. Previous studies have suggested that individual cytokines levels could be used as sepsis markers. Therefore, we assessed whether the multiplex technology could identify useful cytokine profiles in Emergency Department (ED) patients.MethodsED patients were included in a single tertiary-care center prospective study. Eligible patients were >18 years and met at least one of the following criteria: fever, suspected systemic infection, ≥2 systemic inflammatory response syndrome (SIRS) criteria, hypotension or shock. Multiplex cytokine measurements were performed on serum samples collected at inclusion. Associations between cytokine levels and sepsis were assessed using univariate and multivariate logistic regressions, principal component analysis (PCA) and agglomerative hierarchical clustering (AHC).ResultsAmong the 126 patients (71 men, 55 women; median age: 54 years [19–96 years]) included, 102 had SIRS (81%), 55 (44%) had severe sepsis and 10 (8%) had septic shock. Univariate analysis revealed weak associations between cytokine levels and sepsis. Multivariate analysis revealed independent association between sIL-2R (p = 0.01) and severe sepsis, as well as between sIL-2R (p = 0.04), IL-1β (p = 0.046), IL-8 (p = 0.02) and septic shock. However, neither PCA nor AHC distinguished profiles characteristic of sepsis.ConclusionsPrevious non-multiparametric studies might have reached inappropriate conclusions. Indeed, well-defined clinical conditions do not translate into particular cytokine profiles. Additional and larger trials are now required to validate the limited interest of expensive multiplex cytokine profiling for staging septic patients.

Disfunción de cuerdas vocales

Vocal cord dysfunction (VCD) is a well-defined clinical condition, which often goes unnoticed. The patients generally have a previous diagnosis of asthma, with a history of multiple visits to the emergency services and anti-asthmatic treatments without clinical results. We present the case of a 45-year old woman, nurse assistant, previously diagnosed of bronchial asthma, who consulted several times in the emergency service, and was treated with bronchodilators and corticosteroids with scarce clinical response. She was sent to Pneumology for study and diagnosed of VCD, with subsequent clinical improvement when initiating an adequate medical treatment. A review of the literature published up to date has been made.

Corpus Cavernosum Electromyography with Revised Methodology: An Explorative Study in Patients with Erectile Dysfunction and Men with Reported Normal Erectile Function

A lack of standardization of the recording techniques of corpus cavernosum electromyography (CC-EMG) and objective criteria to characterize the recorded signals (CC-potentials) are the main difficulties hindering the clinical application of this method. These difficulties have been recently overcome by revising the recording and interpretation methodology of CC-EMG AIM: To assess if CC-EMG performed with the revised methodology is discriminative for well-defined clinical conditions in patients with erectile dysfunction (ED). Based on blinded clinical diagnosis, ED patients were catalogued into five subgroups: severe penile fibrosis, cavernous arterial insufficiency (CAI), cardio-vascular comorbidity (CVCM) without proven CAI, post-radical retropubic prostatectomy (RRP), and psychogenic ED. With four electrodes placed on the penile shaft bilaterally, CC-EMG was recorded monopolarly for 30 minutes during flaccidity. After evaluation of the recordings by visual inspection, CC-potentials were analyzed using cross- and autocorrelation techniques. The parameters evaluated were amplitude, duration, dominant frequency (DF), and maximum cross-correlation coefficient (Rmax) of CC-potentials recorded from proximal and distal parts of the CC. Comparison of the values of parameters amplitude, duration, DF, and Rmax between patient and control groups. A total of 119 patients with ED and 43 men with reported normal erectile function were studied. Thirteen out of 14 patients with severe penile fibrosis did not show any distinguishable CC-potential. Patients with CAI had significantly decreased amplitude compared with the potent controls, as well as the patients with CVCM but without proven CAI. Significantly decreased amplitude and Rmax were detected in ED patients following RRP compared with the controls. Corpus cavernosum electromyography performed with the revised methodology is able to discriminate ED patients with conditions that are associated with cavernous smooth muscle degeneration and/or autonomic neuropathy from men with reported normal erectile function.

Evidence-based practices in mental health: Distant dream or emerging reality?

Byline: Nimesh. Desai In the contemporary scientific environment, practice draws heavily upon evidence. This is particularly so in case of medicine, which has a strong scientific tradition, although the tradition of paternalistic decision-making by experienced senior clinicians has been no less strong. In the traditional model of practice of medicine (including mental health), the science base or the evidence was expected to yield to the wise and considered, even if intuitive, opinion of the treating clinician. This traditional model has been in transformation during the twentieth century, in a variety of ways, and from many directions and forces. Systematic efforts of 'research to practice' and expert or consensus guidelines, and clinical practice guidelines (CPGs), have been attempts at translating scientific evidence to clinical practice. The more recent and influential movement of evidence-based medicine (EBM) and evidence-based practice (EBP) takes a decisive position against the traditional model of practice, wherein the individual opinion or wisdom of a clinician is expected to yield to, or at least consider significantly, the available current scientific evidence. Indeed, it moves beyond this reversal to incorporate the principle of medical practice and healthcare being patient-centred, i.e. in terms of individualizing the evidence and encouraging personal choices. It has been said that 'EBM assumes that patient preferences, expressed as informed choices, always outweigh the scientific evidence'![1] The four fundamental principles of EBM have been outlined as (i) use the best available scientific evidence, (ii) individualize the evidence, (iii) incorporate patient preferences, and (iv) expand clinical expertise. The traditional model did not and does not equip the clinicians with adequate expertise to be able to follow these principles and the need to expand the clinical expertise to a wide variety of skills required has also been emphasized.[1] EBM is about the use of the four fundamental principles to individual treatment decisions in each case. EBPs refer to the forms of healthcare interventions, and the capacity to provide interventions that have been shown to be effective. In other words, EBP is about the extent to which individual practitioners, teams and departments/hospitals, follow and practice the principles of EBM. Further, evidence-based healthcare (EBHC) is about the optimal availability of national/ provincial healthcare systems and thus refers to macro policy decisions for creating healthcare systems which are governed by the principles of EBM. The application of the four fundamental principles are required to guide the decision-making at various levels by individual clinicians/teams in each case for EBM, by departments/institutions as a standard practice for EBP, and by health systems of state or country for EBHC. In a short time, the movement has found wide acceptance and stability in medicine and healthcare. The Institute of Medicine's report[2] gives the summative description of EBP as 'the integration of their research evidence, with clinical expertise and patient values', which is far too basic to be refuted or not be recognized as the way forward. The potential for application of this movement in the field of mental health, especially in developing countries, is worth examining. Is it a distant dream or an emerging reality? The principle of using the best available scientific evidence is not entirely new to the field of mental health. Parallel to, and sometimes independently ahead of medicine, the field of mental health has generated and documented 'evidence' through controlled studies, including the gold standard evidence of randomized controlled trials (RCTs). Such studies have been possible only with well-defined clinical conditions, and not for a wide variety of mental health problems. In the hierarchy of 'evidence' in EBM, below the gold standard of RCTs, in that order, are quasi-experimental studies, open clinical trials, systematic observations and unsystematic observa-tions. …

Defibrillation threshold testing: Is it really necessary at the time of implantable cardioverter-defibrillator insertion?

The purpose of this study was to (1) determine how often implantable cardioverter-defibrillator (ICD) system modifications were needed to obtain an adequate safety margin for defibrillation, (2) identify how often and for what indications defibrillation threshold (DFT) testing was not performed, and (3) identify factors predicting the need for modification. Ventricular fibrillation (VF) typically is induced at the time of ICD insertion. Although DFT testing often is minimized, a safety margin of 10 J has been utilized as a standard of care. However, current devices offer technology such as biphasic waveforms and high outputs, and the need for testing has been questioned. We reviewed the records of the last 1,139 patients undergoing initial ICD placement, generator replacement, or revision. Seventy-one patients (6.2%) were identified as having an unacceptably high DFT (<10 J safety margin) requiring intervention, and some required >1 modification. Use of a high-output device alone was not enough to obtain an adequate DFT in 48% (34/71) of patients who required modifications (3% of the total population). No arrhythmia inductions were performed in 54 patients (4.7%) because of well-defined clinical conditions. Patients who required system modification had a lower ejection fraction, were younger, were less likely to have coronary artery disease, were more likely to be undergoing upgrade/generator replacement, and were more likely to be taking amiodarone. Long-term mortality was not different between the group of patients who required modification compared with those who did not (17% vs 20%, P = NS). Routine VF induction and documentation of effective defibrillation still remains a reasonable part of ICD placement because an inadequate safety margin may occur in >6% of patients. The incidence of patients who were inappropriate for testing based on well-defined clinical conditions is small (<5%) in this unselected large series. Although some clinical features may predict the need for system modification, additional studies are needed to better define "acceptable efficacy" of ICDs in preventing sudden death prior to altering these standards in selected patients.

Evolutionary genomics of Staphylococcus aureus: insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic.

An emerging theme in medical microbiology is that extensive variation exists in gene content among strains of many pathogenic bacterial species. However, this topic has not been investigated on a genome scale with strains recovered from patients with well-defined clinical conditions. Staphylococcus aureus is a major human pathogen and also causes economically important infections in cows and sheep. A DNA microarray representing >90% of the S. aureus genome was used to characterize genomic diversity, evolutionary relationships, and virulence gene distribution among 36 strains of divergent clonal lineages, including methicillin-resistant strains and organisms causing toxic shock syndrome. Genetic variation in S. aureus is very extensive, with approximately 22% of the genome comprised of dispensable genetic material. Eighteen large regions of difference were identified, and 10 of these regions have genes that encode putative virulence factors or proteins mediating antibiotic resistance. We find that lateral gene transfer has played a fundamental role in the evolution of S. aureus. The mec gene has been horizontally transferred into distinct S. aureus chromosomal backgrounds at least five times, demonstrating that methicillin-resistant strains have evolved multiple independent times, rather than from a single ancestral strain. This finding resolves a long-standing controversy in S. aureus research. The epidemic of toxic shock syndrome that occurred in the 1970s was caused by a change in the host environment, rather than rapid geographic dissemination of a new hypervirulent strain. DNA microarray analysis of large samples of clinically characterized strains provides broad insights into evolution, pathogenesis, and disease emergence.

Carotidinia como forma de presentación de hemicránea paroxística

Paroxysmal hemicrania is a well-defined clinical condition about which many articles have been published. Attempts have been made to explain the response of this illness to indomethacin, suggesting its possible cervical origin. In some patients it is set off by stimulation of certain trigger zones situated in this region. The exceptional radiation of the pain seen in our patient clearly supports this theory. A 34 year old man with a past history of a similar but briefer episode 5 years previously presented to us. He complained of repeated episodes of stabbing pain with no obvious cause. The pain started at the base of the neck and radiated along the right carotid vessels to the cheek, base of the nose and ipsilateral eye. This was accompanied by injection of the conjunctivae, tears, nasal congestion and nasal discharge. Each episode lasted 15 to 30 minutes and was repeated 20 to 25 times a day without any particular relation to the time of day. The neurological examination, MR and angio-MR were normal. Before being seen by us he had been treated with prednisone and verpamil without effect. Indomethacin at a dose of 100 mg/day controlled the problem completely. We report a case of paroxysmal hemicrania with a spontaneous description of pain starting at the base of the neck and radiating along the carotid vessels. We consider this clinical description to be of interest since it supports the theories of a cervicogenic origin of this type of headache.

Human T-cell lymphotropic virus types I and II infections in patients with leukaemia/lymphoma and in subjects with sexually transmitted diseases in Nigeria.

Serological assays that distinguish antibodies to human T-cell lymphotropic virus types I (HTLV-I) and type II (HTLV-II), and polymerase chain reaction (PCR) tests were used to investigate association of these two human retroviruses with several well-defined clinical conditions in Nigeria. We compared the frequency of HTLV-I and HTLV-II infections among patients with lymphopholiferative disorders (n=65), individuals with various sexually transmitted diseases (n=40), patients with genitals candidiasis (n=25) and apparently healthy individuals (n=60). Serological analysis of blood samples from all four groups showed that 10 of the 190 (5.3%) individuals tested were confirmed positive for the presence of antibodies to HTLV-I(6) or HTLV-II(4). Using the PCR technique, specific HTLV-I or HTLV-II sequences were amplified from the genomic DNA of 4 of 6 HTLV-I seropositive and 3 of the 4 HTLV-II seropositive individuals respectively. However, sequences of both viruses were amplified from the genomic DNAs of the remaining 3 seropositive individuals. Since one of the 5 sets of primer pairs [SK110(II)/SK111(II)], which is used for specific identification of HTLV-II did not amplify the target sequence from the genomic DNAs of any of the 4 HTLV-II confirmed seropositive individuals in this study, it suggested sequence diversity of these viruses in Nigeria. The virus-infected individuals identified in this study were one (1.5%) of the 65 patients with leukaemia/lymphoma (HTLV-I), 6 of 40 (15.0%) individuals (HTLV-I = 1 , HTLV-II = 3, HTLV-I/II = 2) with sexually transmitted diseases (STD), one of 25(4.0%) subjects with genital candidiasis for HTLV-I and 2 of 60 (33.3%) healthy individuals (one for HTLV-I and one for HTLV-I/II). There was a significant difference (P < 0.025) between the prevalence of HTLV-I/II infections among patients with lymphoma/leukaemia and those who attended STD clinic in Ibadan, Nigeria. This study also suggests that while HTLV-I and HTLV-II may be important sexually transmitted viruses, they may not be specific aetiological agents of the common lymphoproliferative disorders in Nigeria.

Characterization of Lawsonia intracellularis gen. nov., sp. nov., the obligately intracellular bacterium of porcine proliferative enteropathy.

A novel obligately intracellular bacterium, ileal symbiont intracellularis, which was obtained from the intestines of pigs with proliferative enteropathy disease, was grown in pure cocultures with tissue cultures of rat cells. An examination of the 16S ribosomal DNA gene sequence revealed that the isolates which we obtained are members of the delta subdivision of the Proteobacteria and that the sequences of these organisms exhibit a level of similarly of 91% with the sequence of Desulfovibrio desulfuricans ATCC 27774. These isolates were homogeneous and differed in cellular morphology, acid fastness, phenotype, electrophoretic protein profile, and habitat from Desulfovibrio species. On the basis of the results of an integrated study of the phenotype and genotype of a consistent morphological entity found in particular porcine cells and associated with a well-defined clinical condition, we concluded that these bacteria belong to a previously undescribed genus and species, for which we propose the name Lawsonia intracellularis gen. nov., sp. nov. A species-specific recombinant DNA probe was cloned previously, and this probe was used to identify the bacterium in tissue culture cells and in the ileal epithelia of pigs with proliferative enteropathy disease. Coculture of the organism with a rat enterocyte cell line allowed us to designate strain NCTC 12656 the type strain and to describe the new genus and species. The organism which we cultured is pathogenic for pigs and causes proliferative enteropathy lesions in their ilea and colons, and Koch's postulates were fulfilled for this organism.

Etiology and pathogenesis of the prune belly syndrome

The congenital triad of abdominal muscle deficiency, severe urinary tract abnormality, and cryptorchidism forms a rare but well-defined clinical condition popularly known as the prune syndrome (PBS) [1–10]. The term prune belly is descriptive of the characteristic wizened, dried-plum appearance in the newborn and young infant (Fig. 1). The peculiar and, in classical cases, pathognomonic aspect of the thin, transparent, redundant abdominal skin, which is loose rather than stretched, nestling to the wobbly intestines at birth, becomes less marked with advancing age. With age, the wrinkles flatten out as the subcutaneous fat and intraabdominal content increase, expanding further the flaring and floppy flanks and the paunch. In addition to the therapeutic challenge presented by the PBS, its etiology and pathogenesis have been controversial. Earlier studies suggested a mesenchymal developmental arrest during the 6th to 7th week of gestation leading to coordinated defects of dependent structures [11, 12]. Recently, an old hypothesis has been resurrected and extended [13–15]. It explains the morphologic characteristics of the PBS as sequelae of an intrauterine distension of the abdomen, usually by enlargement of the bladder due to an obstruction of the proximal urethra [16–19]. Operative removal of the obstructing tissue such as an valve would under these circumstances be a logical measure in the affected newborn or infant. Our personal experience with 14 patients with PBS and a critical analysis of the literature do not support the hypothesis of a secondary pathogenetic sequence arising from a primary obstructive uropathy. PBS and the urethral obstruction malformation complex [14] are different conditions, which can be separated by clinical, radiographic, endoscopic, and histologic evaluation. This distinction determines the choice of the most effective form of therapy.