Separate Disorders Research Articles

Percutaneous drilling for the treatment of secondary osteonecrosis of the knee

Osteonecrosis of the knee comprises two separate disorders, primary spontaneous osteonecrosis which is often a self-limiting condition and secondary osteonecrosis which is associated with risk factors and a poor prognosis. In a series of 61 knees (38 patients) we analysed secondary osteonecrosis of the knee treated by a new technique using multiple small percutaneous 3 mm drillings. Total knee replacement was avoided in 59 knees (97%) at a mean follow-up of 3 years (2 to 4). Of the 61 knees, 56 (92%) had a successful clinical outcome, defined as a Knee Society score greater than 80 points. The procedure was successful in all 24 knees with small lesions compared with 32 of 37 knees (86%) with large lesions. All the procedures were performed as day cases and there were no complications. This technique appears to have a low morbidity, relieves symptoms and delays more invasive surgery.

Asthma: Expanding the Medicine Chest

Vol. 114, No. 2 EnvironewsOpen AccessAsthma: Expanding the Medicine Chest Michael Szpir Michael Szpir Search for more papers by this author Published:1 February 2006https://doi.org/10.1289/ehp.114-a96bAboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit About 10% of the asthmatic population has a severe form of the disease that can require progressively higher doses of corticosteroid drugs to manage the symptoms. Now a new therapeutic approach, described in the December 2005 issue of Thorax, may help people whose severe asthma symptoms no longer respond to steroid treatments.Early research suggested that asthma was a so-called Th2 cytokine disorder involving certain white blood cells known as eosinophils. However, Stephen T. Holgate, a professor in the Infection, Inflammation, and Repair Division of Southampton General Hospital in the United Kingdom, and other researchers noticed that severe asthma was actually associated with neutrophils, another type of white blood cell that is associated with Th1 diseases such as rheumatoid arthritis and psoriasis. These diseases respond well to treatments that block the action of an immune system molecule called tumor necrosis factor–alpha (TNF-α). If severe asthma was truly a Th1 disease, Holgate hypothesized, it stood to reason that it too would respond to a TNF-α blocker.To test this idea, Holgate and his colleagues administered the drug etanercept (Enbrel®) to 17 subjects with severe asthma in a 12-week study. Etanercept is a soluble receptor that binds to TNF-α. Treatment was associated with significant improvements in asthma symptoms and lung function, and reduction of bronchial hyper-responsiveness (abnormal sensitivity to agents that narrow the airways) in the 15 patients who completed the regimen.Some research now suggests that asthma is not a single disease. “Mild and moderate forms of asthma may be disorders primarily characterized by a Th2-type immune response associated with allergen-specific IgE antibodies,” Holgate says. “In contrast, severe asthma, which is aggravated by viruses and air pollution, may be a separate Th1-type immune disorder that involves the excess production of TNF-α.” This could explain why the use of etanercept in previous studies of mild asthma produced no improvement in symptoms.Although the improvement in asthma symptoms and airway hyperresponsiveness are impressive, placebo-controlled studies are needed to assess the efficacy of anti-TNF-α therapy. According to Holgate, such studies are now under way in his and other laboratories, and the preliminary results look quite promising. “In twenty-seven years of asthma research, this is the biggest breakthrough that [our research group has] had,” he says.Asthma attacker?The drug etanercept binds to TNF-α to block its action on the immune system. The drug may be an effective treatment for severe asthma aggravated by factors that affect immunity, such as viruses and air pollution.FiguresReferencesRelatedDetails Vol. 114, No. 2 February 2006Metrics About Article Metrics Publication History Originally published1 February 2006Published in print1 February 2006 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.

Treatment of Eating Disorders in Children, Adolescents, and Young Adults

Treatment of Eating Disorders in Children, Adolescents, and Young Adults

Development of Multi-agency Referral Pathways for Attention-deficit Hyperactivity Disorder, Developmental Coordination Disorder and Autistic Spectrum Disorders: Reflections on the Process and Suggestions for New Ways of Working

This article summarizes the rationale for multi-agency working when assessing children and young people with suspected neurodevelopmental disorders such as attention-deficit hyperactivity disorder, developmental coordination disorder and autistic spectrum disorders. Details of referral pathways that have been drawn up for each separate disorder are given and the process through which multi-agency agreement was reached is described. Key features thought to be common to all three pathways are discussed and factors thought to have contributed to successful multi-agency working highlighted. The work is described in the context of existing national policy documents in the UK.

Nightmares: from anxiety symptom to sleep disorder

The DSM-IV-TR definition of nightmares-extremely frightening dreams from which the person wakes up directly-is unnecessarily narrow. Other emotions (anger, grief) have also been reported in nightmares, and direct awakening from a bad dream seems to be unrelated to increased distress. In addition, assessment of nightmares is problematic. Polysomnographic recordings have an ameliorating effect on nightmare frequency, retrospective measurements tend to underestimate nightmare frequency, and persons with frequent nightmares may feel reluctant to fill out (daily) prospective measurements. For studying nightmares, it is necessary to distinguish idiopathic nightmares from posttraumatic nightmares, which are part of a posttraumatic stress reaction or disorder that may result from experiencing a traumatic event. Both types of nightmares have been associated with an elevated level of periodic limb movements, although only posttraumatic nightmares seem to be related to more and longer nocturnal awakenings. Nightmares have also been repeatedly associated with the general level of psychopathology, or the so-called personality factor neuroticism. Nightmare distress, the impact on daily functioning caused by nightmares, may function as a mediating variable. Several studies in the last decades have shown that nightmares can be treated with several cognitive-behavioral techniques. The cognitive-restructuring technique imagery rehearsal therapy is the treatment of choice for nightmares, although a randomized controlled trial with an attention control-group has not yet been carried out. Nightmares are more than a symptom of a larger (anxiety) syndrome and need to be viewed from a sleep medicine perspective: nightmares are a highly prevalent and separate sleep disorder that can and should receive specific treatment.

Comorbidity of dyslexia, dyspraxia, attention deficit disorder (ADD), attention deficit hyperactive disorder (ADHD), obsessive compulsive disorder (OCD) and Tourette's syndrome in children: A prospective epidemiological study

Currently dyslexia, dyspraxia, attention deficit disorder, attention deficit hyperactive disorder, obsessive compulsive disorder and Tourette's syndrome of childhood are considered as being separate disorders. There is now evidence to suggest that, on the basis of comorbidity, they should be downgraded to symptoms that will appear in syndromes of developmental delay. To establish that a child diagnosed by a health practitioner or educational professional as having a single disorder in fact presents symptoms of other disorders in a pattern of comorbidity. A prospective epidemiological study of 100 children attending a specialist clinic. A clear pattern of comorbidity was demonstrated. Whilst not always quantifiable, no patient was found to have one condition in isolation and comorbidity rates were found at incidences of up to 95%, representing an increase on the expected prevalence in a general population of 160–2300%. The patterns of comorbidity occurred with such frequency that it would suggest that there could be an argument for the downgrading of these conditions from disorders per se to symptoms and that further investigation might suggest that the patterns of comorbidity may fit the criteria for a developmental delay syndrome.

Dopa-responsive dystonia and early-onset Parkinson's disease in a patient with GTP cyclohydrolase I deficiency?

We describe a patient with a combination of dystonic and parkinsonian signs. Paraclinical studies revealed a mutation in the GTP cyclohydrolase I gene (GCH1) and a decrease in [123I]-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane (123I-FP-CIT) binding ratios indicative of Parkinson's disease. We conclude that the patient probably suffers from a variant of dopa-responsive dystonia (DRD) or two separate movement disorders, normally considered to be differential diagnoses, DRD and early-onset Parkinson's disease with resulting difficulties concerning treatment and prognosis.

Current trends in psychological research on children with high-functioning autism and Asperger disorder

This review explores current trends in the literature during 2004 on psychological studies of children with high-functioning autism and Asperger syndrome. Studies are reviewed that examine diagnostic dilemmas and methodological concerns, cognitive and social deficits, and interventions. There is considerable debate over the distinction between high-functioning autism and Asperger syndrome, but few studies find support for separate disorders. Most studies reviewed combine high-functioning autism and Asperger syndrome into an autism spectrum disorder group or study only one diagnostic group, either high-functioning autism or Asperger syndrome. Research into cognitive processes (specifically mentalizing) and social understanding (nonliteral language) continue to dominate research efforts. Current studies suggest specific weaknesses in many areas of nonliteral language, such as humor, irony, and teasing. Studies rely heavily on current theoretical explanations for deficits, namely the central coherence, social inference, and executive function theories, and varying levels of support were found for all three theories. Intervention and outcome studies lag behind experimental and theoretical studies, but two studies employed scientifically rigorous intervention designs with promising results. Children with high-functioning autism and Asperger syndrome have a great deal of potential with respect to long-term developmental outcomes, and yet they continue to be understudied and under-served in current intervention programs. Future studies are needed in developmental processes and outcomes in this population, and in the development of effective treatment strategies that have undergone scientifically rigorous testing.

Irritable bowel syndrome and inflammatory bowel disease: interrelated diseases?

In the past inflammatory bowel disease (IBD), celiac disease and irritable bowel syndrome (IBS) were regarded as completely separate disorders. Now, with the description of inflammation, albeit low-grade, in IBS, and of symptom overlap between IBS and celiac disease, this contention has come under question. Is there true overlap between these disorders? Despite the limitations of available data one cannot but be struck by some areas of apparent convergence: IBD and celiac disease in remission, lymphocytic colitis and microscopic inflammation in IBS, in general, and, especially, in the post-infectious IBS category. The convergence between latent celiac disease and sub-clinical IBD, on the one hand, and IBS, on the other, appears, based on available evidence, to be somewhat spurious and may largely relate to misdiagnosis, a phenomenon which may also explain the apparent evolution of IBS into IBD in some studies. Similarities between IBS and lymphocytic colitis are more striking and less readily dismissed; as for IBS, well documented instances of progression of lymphocytic colitis to full-blown IBD are infrequent, suggesting a true separation between this disorder and classical IBD. Do IBS and lymphocytic colitis represent different responses to similar triggers? Will some of the 'inflamed' IBS subgroup be reclassified as part of the spectrum of lymphocytic colitis in the future? Will inflammation emerge as a common underlying factor in the pathogenesis of IBS? The answer to these and many questions must await further study of this fascinating area.

Avoidant personality disorder and social phobia: distinct enough to be separate disorders?

Existing evidence from anxiety disorder research indicates that social phobics (SP) with avoidant personality disorder (AVPD) experience more anxiety and show more impairment than patients with SP alone. The purpose of this study was to examine whether in patients diagnosed with AVPD, the co-occurrence of SP adds to its severity. We hypothesized that the addition of SP will not add to the severity of AVPD alone. Two groups of patients (AVPD=224; AVPD/SP=101) were compared at baseline and 2 years later on multiple demographic and clinical variables. Patients with AVPD and an additional diagnosis of SP differed little from patients with AVPD alone. These findings suggest that AVPD and SP may be alternative conceptualizations of the same disorder.

Endorsement frequencies and factor structure of DSM-III-R and DSM-IV Generalized Anxiety Disorder symptoms in women: implications for future research, classification, clinical practice and comorbidity

We investigated dimensions of liability to Generalized Anxiety Disorder (GAD) and whether evidence exists for distinct pathological versus normal clusters in the population. Structured interviews were administered to a general population sample of 2,163 female twins in a cross-sectional design. Endorsement rates were estimated using full information maximum likelihood factor analyses of the DSM-III-R and DSM-IV GAD symptoms, which provides appropriate treatment of the stem-probe structure of the clinical interview. Endorsement rates were highest for symptoms retained in DSM-IV. For both DSM-III-R and DSM-IV, a two-factor model fit the data better than a single-factor model. There was no evidence for non-normality in the liability to GAD. For DSM-III-R, autonomic symptoms loaded on a factor with panic disorder, while fatiguability, difficulty concentrating and hypervigilance loaded on a factor with major depression. For DSM-IV, all items loaded on one factor, and muscle tension also loaded on a second. Major depression, panic, phobias and alcohol dependence diagnoses also loaded on the first factor. Future research involving structured interviews should take into account the stem-and-probe format and focus on common factors rather than separate disorders; GAD is not a unidimensional construct and pathological anxiety may differ only quantitatively from normal anxiety.

Endoscopy‐negative reflux disease: part of the spectrum of non‐steroidal anti‐inflammatory drug or a separate disorder? Implications for treatment

Endoscopy‐negative reflux disease: part of the spectrum of non‐steroidal anti‐inflammatory drug or a separate disorder? Implications for treatment

HER2 or Not HER2: That Is the Question

It is becoming increasingly apparent that the longappreciated clinical heterogeneity in breast cancer arises in large part from intrinsic biologic heterogeneity within the tumor. In other words, there is more than one type of breast cancer. Different tumor types are not merely arbitrarily defined subsets, but rather different diseases. Underlying this revised taxonomy are different identifiable growth factors and receptors, reflecting the different molecular and cellular features of these distinct tumor types. Hormone receptor–positive and –negative breast cancer and human epidermal growth factor receptor 2 (HER2) –positive and –negative breast cancer are as different from one another as pneumococcal and staphylococcal pneumonia or acute myeloid leukemia and acute lymphoblastic leukemia. The preliminary but provocative results from the preoperative treatment of HER2-positive breast cancer using chemotherapy with or without trastuzumab, reported in this issue by Buzdar et al, provide the opportunity to reflect on the challenges clinicians and clinical researchers face in acknowledging and responding to the biologic heterogeneity of breast cancer. In particular, these findings have led us to imagine a time, probably not far from now, when different breast cancers are treated along distinctive pathways that target their intrinsic biologic features. At a minimum, it is likely that treatment will vary depending on hormone receptor expression and HER2 expression and that other novel molecular targets will be identified in years to come. The dilemma that will confront clinically oriented thinking is that many recent lessons regarding optimal breast cancer therapy have been derived from treating patients without prior selection of tumors based on biology. It is not clear how such lessons will apply to biologically defined classes of breast tumors. The trial from the M.D. Anderson Cancer Center randomly assigned women with HER2-positive, operable breast cancer to either preoperative chemotherapy alone or to chemotherapy and trastuzumab. There was a substantial improvement in pathologic complete response (pCR) rate with trastuzumab-based therapy. The chosen end point of pCR has been widely used in preoperative treatment trials because of the reproducibility of the measurement and because it may be a surrogate for long-term treatment outcomes. It is not all that surprising that trastuzumab improved pCR because randomized trials in the metastatic setting have demonstrated that trastuzumab-based treatment substantially increases response rate, progression-free survival, and overall survival for patients with HER2positive breast cancer compared with chemotherapy alone. It is critical to articulate what the M.D. Anderson data do not tell us about a standard approach to breast cancer therapy. The study, with approximately 20 patients per arm, is too small to demonstrate with confidence the safety of preoperative trastuzumab administered with or without anthracycline-based chemotherapy. In particular, the study cannot exclude the possibility of clinically important risks of heart failure. The study was not designed to demonstrate, nor did it report, whether trastuzumab would improve long-term results, such as recurrence-free or overall survival, and we await the data from the many randomized trials in the adjuvant setting to define such benefits. The study does not suggest that trastuzumab-based treatment facilitates breast-conserving surgery; the rates of mastectomy were the same in each treatment arm, at approximately 55%, based on the high clinical response rate. For all these reasons, the use of preoperative trastuzumab remains an investigational approach for HER2overexpressing, early-stage breast cancer. Notwithstanding these limitations, this small trial confirms previous reports of preoperative trastuzumab-based treatment in early-stage breast cancer. Moreover, the M.D. Anderson data suggest that it may not be too soon to begin to anticipate the era when HER2-positive breast cancer (20% to 25% of all cases) is treated as a separate disorder, and then to assess the implications for how we will care for the remaining three quarters of breast cancer patients. Consider first the impact of winnowing the HER2positive breast cancer cases out of the pool of unselected tumors. HER2 overexpression is widely appreciated to have JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 16 JUNE 1 2005

Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2

The inherited osteolysis syndromes are a heterogeneous group of skeletal disorders whose classification is still uncertain. Three osteolysis syndromes show autosomal recessive inheritance and multicentric involvement: Torg syndrome (OMIM 259600), Winchester syndrome (OMIM 277950) and Nodulosis-Arthropathy-Osteolysis syndrome (NAO; OMIM 605156). The 2001 Nosology of the International Skeletal Dysplasia Society (Hall CM, Am J Med Genet 2002: 113: 65) classifies NAO as a variant of Torg syndrome, while Winchester syndrome is considered as a separate disorder. Recently, mutations in the matrix metalloproteinase 2 (MMP2) gene were identified in affected individuals with a clinical diagnosis of NAO in two Arab families. We report a homozygous missense mutation (E404K) in the active site of MMP2 in a 21-year-old woman with a severe form of osteolysis best compatible with a diagnosis of Winchester syndrome. The clinical and molecular findings suggest that Torg, NAO and Winchester syndromes are allelic disorders that form a clinical spectrum.

Commentary on Chan S & Levy V (2004) Postnatal depression: a qualitative study of the experiences of a group of Hong Kong Chinese women. Journal of Clinical Nursing 13, 120–123

Commentary on Chan S &amp; Levy V (2004) Postnatal depression: a qualitative study of the experiences of a group of Hong Kong Chinese women. <i>Journal of Clinical Nursing</i> 13, 120–123

An attitude of ego psychology towards development and mental disorders of adolescents

Period of adolescence is specific because a very rapid development is going but there is also a period when serious mental disorders begin – schizophrenia, depression, personality disorders, etc. Although many psychological theories study the reasons of psychopathology manifestation in adolescence, yet psychodynamic paradigm which emphasizes a meaning of internal processes towards personality functioning may help to answer a question what are the underlying reasons which encourage the beginning of one or another dysfunction. One of the reasons may be a disturbance of Ego functioning. Hartmann (1964) asserts that Ego is responsible for an adaptation and mental health, its development is very rapid during adolescence (Blos, 1962), so two questions are analysed in this article: normal Ego development and disturbances of Ego functioning during adolescence. We are trying to answer these questions both reviewing classical attitude towards Ego development during adolescence (with reference of S. Freud, A. Freud, H. Hartmann, E. Erikson, P. Blos works) and analyzing empirical researches of late years. P. Blos (1962) gives nearly the most consistent attitude towards developmental processes running during adolescence. By his opinion, the process of individuation-separation repeats itself during adolescence, i.e. adolescent seeks to separate from his/her parents and to create his/her own feeling of identity. Oscillation of regress and progress is typical characteristic of Ego development, but psychopathology shows off when regress of Ego towards early developmental fixations is very pronounced and subsequent development comes to a dead lock (Blos, 1967).Current researches of adolescents’ Ego can be divided into three big groups: normal Ego development is investigated on J. Loevinger’s (1977) Ego development theory basis, where she distinguishes several separates stages of Ego development based on both the theoretical concepts of psychodynamic paradigm and ideas of other psychology trends (for example, humanistic psychology). The second group of researches analyses the development of identity feeling during adolescence based on theory of E. Erikson. Results of researches demonstrate that development of identity feeling goes on both during early adolescence and after adolescence is over and different aspects of identity feeling develop during different developmental periods. The third group of researches includes Ego function researches of separate mental disorders cases. Probably mostly investigatable are adolescents with borderline personality and behavioural disorders. It is established that disturbance of Ego functions is unequal in cases of different mental disorders, besides disturbance of Ego functions is related to disturbance of identity feeling, for example there is a very close relation between disturbance of identity feeling and disturbance of thought processes. If psychodynamic paradigm gives us some insights about the significance of Ego on mental disorders manifestation during adolescence but still there is a lack of empirical researches which might more clearly define development of separate Ego functions during adolescence, relation between Ego and identity feeling, the disturbance of Ego functioning in cases of mental disorders, etc.

Brown–Vialetto–Van Laere syndrome; variability in age at onset and disease progression highlighting the phenotypic overlap with Fazio-Londe disease

We report four siblings showing features of a pontobulbar palsy, a mixed spinal and upper motor neuropathy and variable deafness. The observation of affected males and females born to consanguineous first cousin parents suggests autosomal recessive inheritance. Two children presented in the first 16 months of life with stridor and died of respiratory failure by the age of 2 years. Hearing loss was not apparent in these infants. In contrast, 2 further siblings developed a bulbar palsy in their sixth year followed by the onset of deafness and features of an anterior horn neuropathy with corticospinal tract involvement. They exhibited a relatively slow but relentless decline over a period of several years. These cases highlight the phenotypic overlap of Brown–Vialetto–Van Laere syndrome with Fazio–Londe disease. Rather than representing two separate disorders, our findings suggest the possibility of a single disease entity which may usefully be considered a form of juvenile amyotrophic lateral sclerosis.

Lack of depression effect on platelet activation in patients with heart failure

P-selectin is a marker of platelet activation. Previous studies have reported elevated P-selectin in patients with congestive heart failure (CHF) and depression as separate disorders. We examined if comorbid depression had an effect on platelet activation in CHF patients. Soluble (s)P-selectin was measured in 108 CHF patients; 24 with comorbid depression. There were no significant differences in age, cardiac parameters or (s)P-selectin levels between CHF-only patients and patients with comorbid depression. Our data show no group differences in P-selectin values, which suggests that comorbid depression has no additive effect on platelet activation in CHF patient.

The clinical necessity for assessing Attention Deficit/Hyperactivity Disorder (AD/HD) symptoms in children with high-functioning Pervasive Developmental Disorder (PDD)

Although the DSM-IV diagnostic criteria for Attention Deficit/Hyperactivity Disorder (AD/HD) exclude Pervasive Developmental Disorder (PDD), some clinicians find that the two disorders can be comorbid and, in fact, make a dual diagnosis. Nevertheless, few empirical studies have investigated the clinical necessity for this practice. In the first of our two studies, children with high-functioning PDD were selected from among 520 outpatients. Of these, children also meeting the DSM-IV criteria for AD/HD were identified through a psychologist's observation, the completion of the ADHD-Rating Scale by parents and/or teachers, and a child psychiatrist's examination. We then examined the impact of PDD subtype and age on the co-occurrence rate. Study 2 analyzed comorbidity in two cases taken from Study 1. Of the 53 subjects in Study 1, 36 children also met the DSM-IV criteria for AD/HD. The co-occurrence rate for Asperger's Disorder (AS)/Pervasive Developmental Disorder, Not Otherwise Specified (PDDNOS) (85%) was significantly higher than for Autistic Disorder (57.6 %), and AD/HD symptoms were more common in younger children. Study 2 demonstrated the existence of comorbidity of PDD and AD/HD as separate disorders. We conclude not only that AD/HD symptoms occur frequently in children with PDD, but also that in some cases a dual diagnosis is essential to the implementation of effective treatment.

Posttraumatic stress disorder and depression following trauma: understanding comorbidity.

Posttraumatic stress disorder (PTSD) and major depression occur frequently following traumatic exposure, both as separate disorders and concurrently. This raises the question of whether PTSD and depression are separate disorders in the aftermath of trauma or part of a single general traumatic stress construct. This study aimed to explore the relationships among PTSD, depression, and comorbid PTSD/depression following traumatic injury. A group of 363 injury survivors was assessed just prior to discharge from hospital and 3 and 12 months postinjury. Canonical correlations were used to examine the relationship between PTSD and depression symptom severity and a set of predictor variables. Multinomial logistic regression was used to identify whether the diagnostic categories of PTSD, depression, and comorbid PTSD/depression were associated with different groups of predictors. The majority of psychopathology in the aftermath of trauma was best conceptualized as a general traumatic stress factor, suggesting that when PTSD and depression occur together, they reflect a shared vulnerability with similar predictive variables. However, there was also evidence that in a minority of cases at 3 months, depression occurs independently from PTSD and was predicted by a different combination of variables. While PTSD and comorbid PTSD/depression are indistinguishable, the findings support the existence of depression as a separate construct in the acute, but not the chronic, aftermath of trauma.