Specific Clinical Form Research Articles

Brain network topological changes in inflammatory bowel disease: an exploratory study.

Although the aetio-pathogenesis of inflammatory bowel diseases (IBD) is not entirely clear, the interaction between genetic and adverse environmental factors may induce an intestinal dysbiosis, resulting in chronic inflammation having effects on the large-scale brain network. Here, we hypothesized inflammation-related changes in brain topology of IBD patients, regardless of the clinical form [ulcerative colitis (UC) or Crohn's disease (CD)]. To test this hypothesis, we analysed source-reconstructed magnetoencephalography (MEG) signals in 25 IBD patients (15 males, 10 females; mean age ± SD, 42.28 ± 13.15; mean education ± SD, 14.36 ± 3.58) and 28 healthy controls (HC) (16 males, 12 females; mean age ± SD, 45.18 ± 12.26; mean education ± SD, 16.25 ± 2.59), evaluating the brain topology. The betweenness centrality (BC) of the left hippocampus was higher in patients as compared with controls, in the gamma frequency band. It indicates how much a brain region is involved in the flow of information through the brain network. Furthermore, the comparison among UC, CD and HC showed statistically significant differences between UC and HC and between CD and HC, but not between the two clinical forms. Our results demonstrated that these topological changes were not dependent on the specific clinical form, but due to the inflammatory process itself. Broader future studies involving panels of inflammatory factors and metabolomic analyses on biological samples could help to monitor the brain involvement in IBD and to clarify the clinical impact.

Study of pattern of superficial dermatophytic infection in paediatric patients in tertiary health care centre

Background: It is difficult to ascertain reliably the overall incidence and prevalence of the various cutaneous infections in different parts of the world because studies of one region of the country may not be a true representation of the overall disease pattern of that country; furthermore, incidence and prevalence figures may only be representative of the population sampling, which may have associated risk factors for infection. Most of the studies done in this field are dealt with adults or with a specific clinical form of dermatophytosis. Only few surveys were performed in pediatric age group.Methods: It is an observational type of study. The present study was conducted in Department of Dermatology, Rajshree Medical & Research Institute, Bareilly, from 1st march 2021 to 28th February 2022.Results: Majority of the study population belonged to 11-15 years (48.7%) followed by 15-18 years (24.1%). The most commonly affected sites were Groin (47.2%) followed by trunk (29.9%), buttocks (29.1%), and upper limbs (24.0%). The predominant lesion type was Plaque (43.5%). The most common lesion feature found in most of the study group was discoloration (94.1%). The most common diagnosis was T. corporis (29.1%) followed by T. corporis + T. cruris (28.3%), T. cruris (22.4%).Conclusions: Total 237 patients of superficial dermatophytosis were included in the study, out of which mean age was 9.16±4.241 with female predominance (52.3%). Common presenting complaints were itching (95.3%), affected site was groin (47.2%) and annular plaque was predominant type of lesion. The most common made in our study was T. Cruris (47.2%).

Effects of Intra-Articular Autologous Adipose Micrograft for the Treatment of Osteoarthritis in Dogs: A Prospective, Randomized, Controlled Study.

Simple SummaryOsteoarthritis (OA) is a very common musculoskeletal condition that affects dogs, as well as humans and other species, and causes pain, lameness, and disability. Since therapy is not always effective and is definitive only in some cases, OA is still a leading cause of euthanasia in dogs and a challenge for orthopedic surgeons. Recently, new therapeutic approaches, such as the use of autologous mesenchymal stem cells, have been developed. The purpose of this prospective, randomized, controlled, in vivo clinical study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs affected by spontaneous OA in comparison with a treatment with hyaluronic acid. Pain, lameness, the radiographic progression of OA, and synovial fluid inflammation were assessed. The results suggest that intra-articular injection of microfragmented autologous adipose tissue is safe, timesaving, cost-effective, minimally invasive, and can be easily done in one step. This treatment, compared with the hyaluronic acid treatment, showed better long-term pain control and an amelioration of synovial fluid quality, resulting in an improvement in joint function. This new treatment can be included among the effective therapies for OA. Additionally, the canine spontaneous OA model adopted in this study could play a key role in developing successful treatments for translational medicine.The purpose of this study was to estimate the safety, feasibility, and efficacy of the intra-articular treatment of autologous microfragmented adipose tissue in dogs with spontaneous osteoarthritis (OA) in comparison with hyaluronic acid (HA), the standard intra-articular treatment. Specifically, it clinically evaluated pain and lameness, the radiographic progression of osteoarthritis, and synovial fluid inflammation. This was a prospective, single-center, parallel-group, randomized, controlled, in vivo clinical study. Participants (n = 40) received either a single intra-articular injection of microfragmented adipose tissue or a single intra-articular injection of HA (1:1). Clinical outcomes were determined using a specialistic clinician assessment obtained by the completion of a specific clinical form based on the Vesseur modified lameness classification system, a pain evaluation using the Visual Analogue Scale (VAS), the measurement of the range of motion (ROM) of the affected joint, limb circumference, and the owners’ score evaluation using the Canine Brief Pain Inventory (CBPI) for up to 6 months after the time of injection. Patients underwent a radiographic examination to establish the degree of OA in the affected joint, and synovial fluid samples were collected to assess the biochemical environment of the joint and evaluate and quantify the cellular population and the presence of three specific inflammation biomarkers for up to 60 days. The results of this study suggest that microfragmented autologous adipose tissue is safe and can effectively relieve pain and improve function in dogs with spontaneous articular OA. This one-step procedure is simple, timesaving, cost-effective, minimally invasive, and eliminates the need for complex and time-intensive cell culture processing. Furthermore, the clinical evidence and cytological results suggest better long-term pain control, resulting in an improvement in joint function, compared to HA treatment. The canine spontaneous OA model could play a key role in developing successful treatments for human medicine.

Difficulties in diagnosis of chronic granulomatous disease in a 10-year-old child

Objective: to familiarize doctors with one of the rare variants of primary immunodeficiency – chronic granulomatous disease. The authors present a case of late diagnosis of chronic granulomatous disease in a 10-year-old child. The doctors missed the development of complications after BCG vaccination in the form of axillary lymphadenitis on the left (BCGitis), which led to the development of disseminated BCG infection, regarded as an infectious tuberculous process. The onset of chronic granulomatous disease occurred at the age of 10 months (paraproctitis complicated by an anal fistula). The assumption of the presence of immunodeficiency arose in connection with the recurrent course of pneumonia at the age of 4-5 years, but was regarded as a manifestation of a tuberculous infectious process. At the age of 8, during the protracted course of nonspecific polysegmental pneumonia, primary immunodeficiency without specific clinical form was diagnosed on the basis of the results of a comprehensive immunological examination. At the age of 10, chronic granulomatous disease was verified using a study of spontaneous and stimulated chemiluminescence of neutrophils and the results of a genetic study.

FEATURES OF PSYCHO-EMOTIONAL DISORDERS IN YOUNG PATIENTS SUFFERING FROM CHRONIC RADICULOPATHIES OF VERTEBROGENIC GENESIS

According to current notions, the development of neuropathic pain includes the mechanisms of peripheral and central sensitization, the emergence of a generator of pathologically enhanced excitation, pathological illogical system, on the basis of which a specific clinical form of pain is formed. The neuropathic nature of pain is observed in 30−40 % of the patients suffering from back pain. In order to study the psycho−emotional disorders in relation to the duration of chronic pain in young people suffering from the vertebrogenic lumbosacral radiculopathy, 97 people were examined. To estimate pain syndrome a visual−analog scale and DN4 questionnaire was used, for reactive and personal anxiety level we involved the Spielberger − Khanin test, the Beck's inventory was applied for the depression level, MFI−20 for objectification of asthenic manifestations was utilized. Complaints of the patients were divided into specific (nociceptive and neuropathic pain syndrome) and nonspecific. Non−specific complaints in the examined patients included disorders of the emotional sphere, which had the following structure: asthenic, anxiety, depressive and their combinations, as well as the presence of somatoform symptoms, which was confirmed by neuropsychological testing. In the analysis of the dependence of frequency and severity of emotional disorders on the duration of chronic pain, the patterns were found to increase the frequency of all emotional dysfunctions, reduce the severity of anxiety and increase depression with the same severity of asthenic ones. According to the results of this study, the following conclusions were made: the severity of anxiety disorders decreases with increasing duration of the disease, and the depressive disorders increase. The severity of asthenic syndrome did not differ significantly in this category of patients with any duration of chronic pain. Key words: chronic vertebrogenic lumbosacral radiculopathies, asthenic, anxious, depressive disorders, young patients.

Issues of stage-by-stage approach to the external therapy of foot skin mycosis

Foot skin mycosis is one of the most topical problems in dermatovenerology due to the extreme prevalence of these diseases. Treatment of foot skin mycoses is the most important step in the prevention of onychomycosis. The tactics and a specific sequence of the external therapy depends on the specific clinical form of mycosis: acute inflammatory forms require the prescription of solutions and gels, subacute forms required creams, chronic forms require adhesive agents. Exudative form of the foot skin mycosis with vesiculation is an indication for the combination therapy.

A PCR System for Yersinia pseudotuberculosis Identification

Pseudotuberculosis is an acute infectious disease caused by Yersinia pseudotuberculosis. In the 1950 and 1960s, outbreaks of a new, previously unknown disease were registered in the Far East of Russia, called the “Far East scarletlike fever” (FESLF). FESLF is pseudotuberculosis, which has a specific clinical form. The disease is endemic to the Far Eastern, Siberian, and Northwestern regions of Eurasia. At present, there is only one system designed to detect Y. enterocolitis and Y. pseudotuberculosis for diagnostics by polymerase chain reaction. The disadvantage of this system is the lack of the possibility for the specific detection of Y. pseudotuberculosis. In this work, 35 strains of Y. pseudotuberculosis were characterized by the detection of the plasmid gene encoding the adhesin (yadA), MLST typing, and detection of the chromosomal gene of the Y. pseudotuberculosis—the cytotoxic necrotizing factor (cnfY). Detection of the yadA gene correlated with presence of the plasmid (pYV). The strains belonged to five MLST sequence types (STs), one of which, ST240, was described for the first time. All the studied strains of Y. pseudotuberculosis showed the presence of the cnfY gene. Additionally, the results of 68 previously described Y. pseudotuberculosis strains were analyzed. A total of 103 strains showed two allelic variants. Allele 1 was found in all strains isolated from patients with FESLF. The cnfY gene was not specifically associated with the presence of plasmids. The cnfY gene was absent in the Y. enterocolitica strains. Thus, the cnfY gene is a stable and specific marker of Y. pseudotuberculosis. On the basis of the obtained data, a PCR diagnostic system was developed for the detection and intraspecific differentiation of Y. pseudotuberculosis by determining the cytotoxic necrotizing factor gene in the biomaterial.

Regression of post-stroke aphasia and associated non-speech syndromes caused by a course of restorative treatment including intensive speech therapy

To analyze clinical and fMRI indicators related with the therapeutic effectiveness of complex restorative treatment including intensive speech therapy in various clinical forms and severity of the aphasia syndrome. The study included 40 right-handed patients with aphasia syndrome after the first hemispheric ischemic stroke. Patients were studied 3 month after disease onset. Patients were examined before and after rehabilitation treatment (4.7 weeks) including intensive speech therapy (15 hours of exercise per week). Evaluation of the effectiveness of treatment was carried out based on the dynamics of the results of neuropsychological, neurological and neuroimaging examinations of patients before and after treatment. The degree of recovery of speech and non-speech cognitive functions (based on the 10-point cognitive assessment, the dynamics of focal neurological deficit (NIHSS) and functional recovery of patients (Barthel index, modified Rankin scale) were assessed. Neuroimaging methods included structural MRI and two fMRI methods: fMRI resting state and fMRI equivalent of the evoked potentials of mismatch negativity (HP), using a sequence of standard and deviant sounds (Russian phonemes) to obtain the equivalent of HP. For statistical calculations, the program in Python version 3.6.0 was used. The maximum efficacy of restorative treatment (≥15% improvement in the scores of 10-point quantifying) was detected in 28 (70%) cases: 18 patients with initially severe and 10 patients with moderate aphasia, regardless of the clinical form of aphasia, and 11 patients with isolated sensory aphasia. Regression of speech and non-speech cognitive impairments in sensory aphasia was accompanied by a pronounced activation of intact speech homologues of the right hemisphere and the appearance of a small temporal and parietal region, which was small in volume and weak in intensity, similar in the localization to the norm. Regardless of the clinical form of aphasia, maximum therapeutic efficacy was accompanied by a reorganization of the speech neuronal rest network, which includes enhancement of both intra- and interhemispheric functional connectivity, with the predominance of amplification of the intra-hemispheric interactions of the posterior speech zones to the left while reducing their interhemispheric connectivity. Significant improvement in motor and sensory functions was detected in 9 (22%) patients with moderate contralateral spastic hemiparesis (p≤0.00) and did not correlate with the degree of regression of speech and non-speech focal cognitive impairments. A slight therapeutic effect was observed in 12 (30%) patients with mild to moderate speech and non-speech cognitive impairment. This effect was not correlated with a specific clinical form of aphasia. The maximum effectiveness of the 4.7 week restorative inpatient treatment, including intensive speech therapy (15 sessions per week), was obtained mainly with severe aphasia, and also with a specific clinical form - isolated sensory aphasia. According to the fMRI data, various compensatory reorganization of the neural speech network was detected, which probably reflects post stroke neuroplasticity associated with both the severity of aphasia and its specific clinical form.

Multimarker risk stratification approach at multiple sclerosis onset

Delay in the diagnosis of multiple sclerosis (MS) stems from the lack of specific clinical and analytical markers to assist in the early diagnosis and prediction of progressive course. We propose a decision-tree model that better defines early at onset MS patients and those with the progressive form by analysing a 12-biomarkers panel in serum and CSF samples of patients with MS, other neurological diseases (OND) and healthy contols. Thus, patients at onset of neurological disease were first classified by serum IL-7 levels <141pg/ml (OR=6.51, p<0.001). Combination of IL-7 and CXCL10 indicated risk for a specific MS clinical form, where IL-7<141 and CXCL10<570pg/ml were associated with the highest risk for PP-MS (OR=22, p=0.01). Unexpectedly, both PP-MS and RR-MS patients shared significantly decreased prototypical biomarkers of inflammation and tissue regeneration in CSF than OND suggesting a defective intrinsic immune response playing a role at the beginning of the disease.

Maxadilan-simile expression in Nyssomyia neivai, a sandfly vector in an endemic region of Brazil, and its immunogenicity in patients with American tegumentary leishmaniasis.

BACKGROUND Maxadilan (Max) is a salivary component in the sandfly Lutzomyia longipalpis (Lutz & Neiva 1912), a vector of visceral leishmaniasis. Max has a powerful vasodilatory effect and is a candidate vaccine that has been tested in experimental leishmaniasis. Nyssomyia neivai (Pinto 1926) is a vector of the pathogen responsible for American tegumentary leishmaniasis (ATL) in Brazil.OBJECTIVE We searched for Max expression in Ny. neivai and for antibodies against Max in ATL patients.METHODS cDNA and protein were extracted from the cephalic segment, including salivary glands, of Ny. neivai and analysed by polymerase chain reaction, DNA sequencing, and blotting assays. The results were compared with data obtained from Lu. longipalpis samples. We quantified antibodies against Max in serum samples from 41 patients with ATL (31 and 10 with the cutaneous and mucocutaneous forms, respectively) and 63 controls from the endemic northeastern region of São Paulo state, using enzyme-linked immunosorbent assay.FINDINGS Recognition of a Max-simile peptide by specific antibodies confirmed expression of a Max sequence in Ny. neivai (GenBank EF601123.1). Compared to controls, patients with ATL presented higher levels of antibodies against Max (p = 0.004); 24.4% of the patients with ATL and 3.2% of the controls presented anti-Max levels above the cutoff index (p = 0.014). The anti-Max levels were not associated with the specific clinical form of ATL, leishmanin skin test response, absence or presence of amastigotes in histopathologic exam, results of indirect immunofluorescence testing for leishmaniasis, or duration of cutaneous form disease.MAIN CONCLUSION High serum anti-Max levels did not protect patients against ATL, but confirmed previous natural exposure to Ny. neivai bites in this ATL endemic region.

Molecular analysis and associated pathology of beak and feather disease virus isolated in Italy from young Congo African grey parrots (Psittacus erithacus) with an “atypical peracute form” of the disease

This study is the first report on the genetic and pathogenic characterization of beak and feather disease virus (BFDV) occurring in Italy. Twenty BFDV strains isolated in Italy from juvenile Congo African grey parrots (Psittacus erithacus) were investigated. Seventeen strains showed an “atypical peracute form” (aPF) of the disease, and three a chronic form (CF). The birds with aPF had been weaned, were independent as far as food and protection were concerned and apparently were without lesions. The gene coding for the putative coat protein was amplified in all isolates while the BFDV genome was sequenced completely in 10 samples, eight of them belonging to aPF affected birds and two from CF of the disease. All full genomes clustered into the J strain of BFDV, where two new subtypes were identified. Recombination analyses showed evidence of genetic exchanges in two BFDV genomes. In addition, a correlation between viral isolate and origin of the breeding material was shown, while an association between the genetic features of the virus and the clinical form was not observed. Histologically, apoptosis was detected frequently in aPF samples and sporadically in CF samples. Interestingly, BFDV antigens were detected in the nuclei and cytoplasm of such apoptotic cells. The data presented here support the hypothesis that, in the absence of a defined BFDV genetic variant accountable for a specific clinical form of psittacine beak and feather disease, differences in the apoptotic rate between aPF and CF are strictly host related.

Acute Disseminated Encephalomyelitis Without Optic Neuritis Followed by Optic Neuritis in a Child Due to the Sudden Cessation of Steroid Therapy

Acute disseminated encephalitis (ADEM) is an autoimmune demyelinating disorder of the central nervous system that usually occurs in children after viral infection or vaccination. It is not uncommon for ADEM to be accompanied by optic neuritis. However, ADEM followed by optic neuritis is a rare. We report the case of a 6-year-old girl who initially presented with ADEM (without optic neuritis) due to a live measles, mumps, and rubella vaccine and was treated with intravenous high-dose corticosteroids. After steroid therapy, she recovered neurologically and was not prescribed any medication, including an oral steroid taper, for use after discharge. Three weeks later, she developed unilateral optic neuritis and was again treated with steroid therapy. This is a rare case of ADEM without optic neuritis in a child, followed by optic neuritis due to the sudden cessation of steroid therapy. Further studies and follow-ups are needed to determine whether ADEM followed by optic neuritis can be considered a specific clinical form of this disorder.

Acute-on-chronic liver failure: current concepts on definition, pathogenesis, clinical manifestations and potential therapeutic interventions

In recent years, acute-on-chronic liver failure has been recognized as a specific clinical form of liver failure associated with cirrhosis. The syndrome refers to an acute deterioration of liver function and subsequently of other end organs over a period of weeks following a precipitating event in a patient with previously well- or reasonably well-compensated cirrhosis. These precipitating events include either an indirect (e.g., variceal hemorrhage, sepsis) or a direct (e.g., drug-induced) hepatotoxic factor. The short-term mortality for this condition is more than 50%. At present, considerable efforts are ongoing to better characterize the syndrome, to gain further insight into its pathophysiology and to optimize therapy. This article aims to highlight the current concepts of these various aspects.

Perfil epidemiológico dos pacientes com hanseníase no extremo sul de Santa Catarina, no período de 2001 a 2007

Leprosy is one of the oldest diseases of humanity and persists as a serious public health problem. Brazil has the highest incidence and second highest prevalence. In the Americas, it accounts for 93% of the cases, according to World Health Organization data from 2008. The objective of this study was to ascertain the profile of leprosy patients in the municipalities of the Association of Municipalities of the Carboniferous Region (AMREC), over the period from January 1, 2001, to December 31, 2007. This was a retrospective cross-sectional study carried out in the AMREC region in Santa Catarina, Brazil. The sample was of census type, in which all the patients notified were analyzed. 54 patients were analyzed, among whom 57% were female and 42.6% were male. The most prevalent age group was from 30 to 39 years old (31.5%) and 79.6% had white skin color. The occupation was unknown in 51 cases, as was bacilloscopy in 98%. The tuberculoid and Virchowian forms each presented a frequency of 27.8%. The coefficient of detection observed in the municipalities ranged from low to very high. Neither multibacillary nor paucibacillary forms predominated in the analysis, nor any specific clinical form. Nevertheless, it is known that cases are being diagnosed late because of the low percentage of indeterminate cases, with predominance among females. Added to this, the information on the notification forms is sparse, which makes it impossible to show the realities of the study population.

Significance of Clinical Signs in Diagnosing Each Variant of Periapical Pathology: A Random Population Study in 1000 Patients

Objectives: To find out the accurate prevalence of periapical pathology and to see the significance of the clinical signs in diagnosing each variant of periapical pathology. Methods: A study of 1000 patients chosen consecutively, who visited the department of oral radiology, for intraoral periapical radiographs. The clinical data of all the variants of periapical pathology were registered in a specific clinical form followed by intraoral periapical radiographs of the same site All the data were entered into Microsoft Excel and analyzed using Chi-square test setting a value of p < 0.05 for the prevalence and distribution of periapical pathology and Z-test setting a value of p < 0.05 to see the significance of the clinical signs in diagnosing each variant of periapical pathology. Results: A total of 584 radiographs were diagnosed with periapical pathology- Periapical rarefying osteitis was present in almost every second radiograph (4127%) and the less common were periapical cysts and infected periapical cysts (6.3% each). No sex predilection in distribution of periapical pathology (p = 0415) and the majority of the patients (36.30%) belonged to 25 to 36 years age group (p = 0.000). Mandibular molars (512%) were the most common and mandibular canines (0.51 %) were the least common sites to involve with periapical pathology (p=0-000). Overall significance of the clinical signs in diagnosing each variant of periapical pathology was observed (p = 0-000). Conclusion: Our results suggested high prevalence rate of periapical pathology. This study also elaborated all the clinical signs of periapical pathology and their statistical significance in diagnosing each variant of periapical pathology.

Prise en charge thérapeutique des pubalgies de l’adulte sportif

Groin pain is a very complex pathology in sports. We described our experience in therapeutic management of male athletes in each specific clinical form of groin pain and for each step of treatment and rehabilitation.

Clinical significance of anti-Ro/SSA-52 kDa antibodies--a retrospective monocentric study

Two types of anti-Ro/SSA antibodies have been described, anti-SSA-52 kDa (aSSA52) and anti-SSA-60 kDa (aSSA60), each specific to different antigens. However, conflicting data exist concerning the involvement of the aSSA52 in autoimmune diseases (ADs). We therefore determined the clinical significance of these antibodies in patients displaying aSSA52, but not aSSA60. The 2005-08 retrospective monocentric study: all patients positive for aSSA60 and/or aSSA52 antibodies were investigated. Among 297 patients, 82 were aSSA52 positive and aSSA60 negative. There were 21 males and 61 females. Forty-eight (58.5%) patients met our criteria for an AD. Two groups were distinguished according to the association (Group 1) or not (Group 2) of the aSSA52 with other autoantibodies. In Group 1, 33 out of 34 patients suffered from an AD. The two most common being SLE and SSc. The prevalence of AD was lower in Group 2 (15 out of 48, 31.3%, P = 0.001). aSSA52 levels were similar in patients with or without AD. The existence of aSSA52 in association with other antibodies did not predict the presence of AD. There was no evidence to suggest that aSSA52 antibodies were associated with a specific clinical form of SLE or SSc. In the absence of other autoantibodies, aSSA52 was less associated with the presence of an AD. A positive aSSA52 test is of low diagnostic value for AD. Nevertheless, a longitudinal prospective follow-up study would determine whether or not persistence of these autoantibodies was of use in diagnosing AD.

Dr. Fanous and Colleagues Reply

Back to table of contents Previous article Next article Letters to the EditorFull AccessDr. Fanous and Colleagues ReplyAYMAN H. FANOUS M.D.,EDWIN J. van den OORD Ph.D.BRIEN P. RILEY Ph.D.STEVEN H. AGGEN Ph.D.MICHAEL C. NEALE Ph.D.KENNETH S. KENDLER M.D.,F. ANTHONY O’NEILL M.D.,DERMOT WALSH M.B., F.R.C.P.I.,AYMAN H. FANOUS M.D.Search for more papers by this author,EDWIN J. van den OORD Ph.D.Search for more papers by this authorBRIEN P. RILEY Ph.D.Search for more papers by this authorSTEVEN H. AGGEN Ph.D.Search for more papers by this authorMICHAEL C. NEALE Ph.D.Search for more papers by this authorKENNETH S. KENDLER M.D.Search for more papers by this author,F. ANTHONY O’NEILL M.D.Search for more papers by this author,DERMOT WALSH M.B., F.R.C.P.I.Search for more papers by this author,Published Online:1 May 2006https://doi.org/10.1176/ajp.2006.163.5.941AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To The Editor: We read with interest the letter submitted by Drs. Doi and Usui regarding our article. Several points are made in their letter. First of all, the authors state that our main finding, that subjects inheriting the high-risk haplotype in DTNBP1 had higher levels of negative symptoms than expected by chance, “was derived from the observation that the high-risk haplotype frequency was higher in the subjects in the upper 40th percentile for the negative symptom factor.” Actually, our results were not derived from analyses of the frequency of the high-risk haplotype in the various clinical subgroups, although frequencies were provided in our table. Rather, we employed the Transmission-Disequilibrium Test (1) . This is a popular family-based association method that tests for excess transmission of alleles (or haplotypes) from heterozygotic parents to affected offspring. This transmission information, moreover, is not present in allele frequencies, which are derived from examining the entire group as a whole. In our experience, employing case-control methods, which are based on allele frequencies, in our group of 270 high-density schizophrenia families is less powerful than family-based tests such as the Transmission-Disequilibrium Test. Second, they state that the “frequency of the high-risk haplotype was higher in the upper 20%–40% subgroup for the negative symptom factor than in the upper 0%–20% subgroup.” Actually, the two groups that we tested were 1) the upper 0%–20% subgroup and 2) the 0%–40% subgroup. Therefore, the former was a subset of the latter group, comprising approximately half of it. Although we saw no preferential transmission to the 0%–20% group, we interpreted this as being due to insufficient power to detect association, which was recovered when we broadened our definition of affection to additionally include subjects in the upper 21%–40%. We believe that the interpretation of Drs. Doi and Usui, i.e., that these results suggest a protective effect of the DTNBP1 high-risk haplotype, would therefore not follow. As an additional check, we went back to analyze the 21%–40% group. We found that the ratio of observed-to-expected transmissions was basically the same as that in the 0%–20% group. Our interpretation of the results is that the DTNBP1 high-risk haplotype preferentially increases risk for a more or less specific clinical form of illness, namely, one that is associated with higher levels of negative symptoms. It is not clear to us that this has implications for a protective effect of the DTNBP1 genotype on the illness. A protective effect requires that one or more haplotypes be less likely to be transmitted to affected offspring than would be expected by chance. In the case of DTNBP1 , if the high-risk haplotype were truly protective against negative symptoms, then it should be transmitted to all groups defined by high levels of negative symptoms (i.e., 0%–20%, 0%–40%, and 21%–40%) less— not more—as we observed, than would be expected by chance. In furthering their argument, Drs. Doi and Usui adduce results indicating that the neuregulin 1 high-risk haplotype was associated with nondeficit (not deficit) schizophrenia (Bakker et al. in previous letter). We believe that these data can just as well be interpreted in a similar way as our data and that these haplotypes increase the risk of a more or less specific form of illness. We have previously called genes containing such haplotypes “modifier-susceptibility genes” (2) . Finally, we would like to thank Drs. Doi and Usui for their interest in our article and hope that we have provided some clarity on the topic. Washington, D.C.Richmond, Va.Belfast, U.K.Dublin, IrelandReprints are not available; however, Letters to the Editor can be downloaded at http://ajp.psychiatryonline.org.

Review of: Gene expression profiling identifies molecular subtypes of inflammatory breast cancer

Citation of original article:F. Bertucci, P. Finetti, J. Rougemont, E. Charafe-Jauffret, N. Cervera, C. Tarpin,et al. Gene expression profiling identifies molecular subtypes of inflammatory breast cancer.Cancer Research2005;65(6): 2170–8.Abstract of the original articleBreast cancer is a heterogeneous disease. Comprehensive gene expression profiles obtained using DNA microarrays have revealed previously indistinguishable subtypes of non-inflammatory breast cancer (NIBC) related to different features of mammary epithelial biology and significantly associated with survival. Inflammatory breast cancer (IBC) is a rare, particular, and aggressive form of disease. Here we have investigated whether the five molecular subtypes described for NIBC (luminal A and B, basal, ERBB2 overexpressing, and normal breast-like) were also present in IBC. We monitored the RNA expression of approximately 8,000 genes in 83 breast tissue samples including 37 IBC, 44 NIBC, and 2 normal breast samples. Hierarchical clustering identified the five subtypes of breast cancer in both NIBC and IBC samples. These subtypes were highly similar to those defined in previous studies and associated with similar histoclinical features. The robustness of this classification was confirmed by the use of both alternative gene set and analysis method, and the results were corroborated at the protein level. Furthermore, we show that the differences in gene expression between NIBC and IBC and between IBC with and without pathologic complete response that we have recently reported persist in each subtype. Our results show that the expression signatures defining molecular subtypes of NIBC are also present in IBC. Obtained using different patient series and different microarray platforms, they reinforce confidence in the expression-based molecular taxonomy but also give evidence for its universality in breast cancer, independently of a specific clinical form.

Gene Expression Profiling Identifies Molecular Subtypes of Inflammatory Breast Cancer

Breast cancer is a heterogeneous disease. Comprehensive gene expression profiles obtained using DNA microarrays have revealed previously indistinguishable subtypes of noninflammatory breast cancer (NIBC) related to different features of mammary epithelial biology and significantly associated with survival. Inflammatory breast cancer (IBC) is a rare, particular, and aggressive form of disease. Here we have investigated whether the five molecular subtypes described for NIBC (luminal A and B, basal, ERBB2 overexpressing, and normal breast-like) were also present in IBC. We monitored the RNA expression of approximately 8,000 genes in 83 breast tissue samples including 37 IBC, 44 NIBC, and 2 normal breast samples. Hierarchical clustering identified the five subtypes of breast cancer in both NIBC and IBC samples. These subtypes were highly similar to those defined in previous studies and associated with similar histoclinical features. The robustness of this classification was confirmed by the use of both alternative gene set and analysis method, and the results were corroborated at the protein level. Furthermore, we show that the differences in gene expression between NIBC and IBC and between IBC with and without pathologic complete response that we have recently reported persist in each subtype. Our results show that the expression signatures defining molecular subtypes of NIBC are also present in IBC. Obtained using different patient series and different microarray platforms, they reinforce confidence in the expression-based molecular taxonomy but also give evidence for its universality in breast cancer, independently of a specific clinical form.