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PubMed1991

Stapes surgery in osteogenesis imperfecta: analysis of postoperative hearing loss.

The disappointing results in 12 of 58 stapedectomies, including 4 revision operations, performed on osteogenesis imperfecta patients were analyzed and compared with reports in the literature. It is concluded that the results described as disappointing were not always the product of the stapes operation. A progressive sensorineural hearing loss arising independently of the operation as a result of progression in the disease process of osteogenesis imperfecta appears to have a severe influence on the final hearing threshold.

Adolescent↗

PubMed1999

Prosthesis rejection in children with a unilateral congenital arm defect.

OBJECTIVE: To determine the rate of rejection for prosthetic use in children and to investigate reasons for this rejection. DESIGN: Cross-sectional study of a cohort of children. SETTING: Rehabilitation centre, St Maartenskliniek, Nijmegen, The Netherlands. SUBJECTS: Thirty-two children (0-18 years) with a unilateral congenital arm defect who visited the clinic between September 1991 and December 1996. METHODS: Parents of all children and 19 children (> or =6 years) completed a questionnaire. RESULTS: Eleven children (34%) rejected the prosthesis. A survival function shows that the rejection can be characterized by three periods: 0-40 months, 40-162 months and after 162 months. In the first and last period a high rate of rejection is seen, while in the second period a low rate exists. Fitting for the first time after 2 years of age seems to be related with higher rejection rate. Lack of functional gain with the prosthesis, as perceived by the subjects and the parents, is significantly associated with increased rejection rate. Increased rejection rate is associated with the parents' disappointment, insufficient involvement of the parents in treatment, and dissatisfaction pertaining to emotional and social guidance. CONCLUSIONS: Rejection seems to occur in two main periods: within 3.5 years after being provided with a prosthesis and after 13.5 years of prosthetic use, when most children experience puberty. Fitting before the age of 2 years seems to reduce rejection rate. Preventing the parents' disappointment about prosthetic benefits as well as providing them with sufficient involvement in treatment and adequate guidance are essential for optimal results of prosthetic rehabilitation.

Adolescent↗

PubMedDate not supplied

Preradiation chemotherapy with VM-26 and CCNU in patients with glioblastoma multiforme.

AIMS AND BACKGROUND: The objective of the study was to evaluate the efficacy of combined chemoradiation in patients with newly diagnosed glioblastoma multiforme. The main end points were time to progression and overall survival. METHODS: Thirty-one patients with glioblastoma multiforme underwent surgery whenever possible and then received intravenous VM26 (120 mg/m2) and oral CCNU (120 mg/m2) for three cycles followed by radiotherapy (60 Gy). RESULTS: Surgery consisted of a complete resection in 39% of patients, partial resection in 35% and a biopsy in 26%. Sixteen patients had clinical or radiological evidence of progression during or after chemotherapy. Hematologic toxicity was mild. Forty-five percent of patients received the scheduled dose of radiation. The outcome was disappointing, with a median time to progression of 18 weeks and median survival of 37.17 weeks. CONCLUSIONS: The survival of patients with glioblastoma multiforme remains disappointing. Multimodal therapy does not seem to modify the evolution of the tumor. Stratification according to prognostic factors might detect a potential benefit of other therapeutic approaches.

Administration, Oral↗

PubMed1995

Remote interpretation of microbiology specimens based on transmitted still images.

A pilot study was carried out to examine the feasibility of the remote interpretation of microbiology specimens, that is, micro-organisms grown on agar in Petri dishes. The objective of our study was to decide whether still images contained enough information for microbiology specialists to identify the microorganisms accurately. A representative sample of microbiology specimens grown on the most commonly used agar media was used. Still images were captured using a video camera and a PC-based system. The results from a pilot study with the first video camera were discouraging, the interpretations differing in five out of 22 specimens; results with a second video camera were also disappointing. Images were then captured on photographic film, at a considerably higher resolution than images captured by the digitizer board in the PC. Again, however, the results were disappointing. We conclude that interpretation of microbiology specimens based exclusively on visual information is problematical. Remote microbiology interpretation in the future will require images of higher information content (e.g., including three-dimensional information), and will probably require additional information as well, from other senses, such as smell.

Bacteria↗

PubMed2004

The role of social support in coping with daily pain among patients with rheumatoid arthritis.

Using a daily process methodology, the current study examined the role of social support in coping and pain severity among patients with rheumatoid arthritis (RA). Seventy-three adults with RA completed a structured record twice daily for one week on pain severity, pain coping, satisfaction with support and disappointment in support. Findings suggested that support influenced pain indirectly, by encouraging the use of specific coping strategies, as well as impacting coping effectiveness. Satisfaction with support was associated with adaptive and maladaptive coping, while disappointment was associated with maladaptive coping. Findings highlight the importance of close others in promoting adaptive coping strategies.

Adaptation, Psychological↗

PubMed2000

Family caregiving in dementia--an analysis of the caregiver's burden and the "breaking-point" when home care becomes inadequate.

The burden of caregivers of patients suffering from of Alzheimer type dementia (DAT) and vascular dementia (VD) was analysed at the critical time, the "breaking-point", when home care becomes insufficient and/or inadequate and the caregiver burden has probably reached its upper limit. Primary family caregivers of 39 DAT and 40 VD patients who were being considered for relocation into group-living units were studied. Total caregiving burden and different aspects of the burden: general strain, isolation, disappointment, and emotional involvement, were correlated with the patients' diagnoses, abilities, and symptoms. Closer kinship to the patient imposed a heavier burden. The caregiver's gender, social class, and previous institutionalization of the patient did not influence the caregiver burden. There was no significant correlation between the patients' ADL ability or cognition and the burden. A higher level of disappointment was found among the VD carers. Different symptomatology in patients of the two diagnostic groups was related to special aspects of the burden. Multiple regression analysis showed that the amount of caregiving time each week and impaired sense of own identity, misidentifications, clinical fluctuations, and nocturnal deterioration in the patients predicted the breaking-point.

Adult↗

PubMed2005

A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation.

Donor lymphocyte infusions (DLIs) induce potent graft versus tumor (GVT) effects for relapsed chronic myelogenous leukemia (CML) after allogeneic stem cell transplantation (SCT) but are disappointing for other diseases. Disease resistance can occur if donor T cells are not appropriately activated in vivo. Ex vivo T-cell activation might overcome disease-induced anergy and augment GVT activity. We performed a phase 1 trial of ex vivo-activated DLI (aDLI) for 18 patients with relapse after SCT. Activated donor T cells are produced through costimulation with anti-CD3- and anti-CD28-coated beads. Patients with aggressive malignancies received induction chemotherapy, and all patients received conventional DLI (median, 1.5 x 10(8) mononuclear cells/kg) followed 12 days later by aDLI. Activated DLI was dose escalated from 1 x 10(6) to 1 x 10(8) CD3+ cells per kilogram in 5 levels. Seven patients developed acute graft versus host disease (GVHD) (5 grade I-II, 2 grade III), and 4 developed chronic GVHD. Eight patients achieved complete remission, including 4 of 7 with acute lymphocytic leukemia (ALL), 2 of 4 with acute myelogenous leukemia (AML), 1 with chronic lymphocytic leukemia (CLL), and 1 of 2 with non-Hodgkin lymphoma (NHL). Four complete responders relapsed while 4 remain alive in remission a median 23 months after aDLI. Overall, 10 of 18 remain alive 11 to 53 months after aDLI. Adoptive transfer of costimulated activated allogeneic T cells is feasible, does not result in excessive GVHD, and may contribute to durable remissions in diseases where conventional DLI has been disappointing.

Adolescent↗

PubMed1998

Methodologic approaches to studying environmental factors in childhood cancer.

Little is known about environmental causes of childhood cancer. This is probably due to the relative rarity of cancer in children. In the United States, cancer incidence in adults is over 20 times greater than cancer incidence in children. The situation is compounded by the fact that two groups of cancers, leukemias and brain and spinal tumors, account for half of all childhood cancers. The rarity of childhood cancer renders the conduct of most cohort studies infeasible. The majority of studies assessing potential environmental risk factors for childhood cancers have been case-control studies, which are highly efficient for studying rare diseases. Case-control studies of childhood cancers have been greatly facilitated by using cooperative clinical trial groups for case identification. The national studies that have emerged utilize random-digit telephone dialing and telephone interviewing as feasible and economic means of identifying and interviewing controls. Other approaches such as descriptive epidemiology, ecologic studies, and studies of cancer clusters have proven to be disappointing in elucidating environmental causes of childhood cancer. Descriptive and ecologic studies provide no information on specific exposures of study subjects; rather, they use population levels as surrogates for individual exposure. Studies of cancer clusters have also proven to be disappointing. Although there are numerous difficulties in conducting research on the causes of childhood cancer, these difficulties can be remedied by using carefully designed and conducted studies. It should be remembered that the epidemiologic approach is probably the most likely research venue for uncovering environmental causes of childhood cancer.

Case-Control Studies↗

PubMed2003

Repetition compulsion and self-psychology: towards a reconciliation.

The concept of repetition compulsion, which has never been fully acknowledged by Kohut and his followers, is re-evaluated in this article within the context of self-psychology. In line with the underlying principles of defensive contact-shunning on the one hand, and non-traumatic empathic failure on the other hand, the repetition can be seen as the twofold expression both of the wish for a new benign relationship and of the dread of traumatic, repeated disappointment. Therefore, early non-traumatic disappointments are initiated by the patient, and role-responded to by significant others. This way, the risk of disillusionment of full-blown expectations is avoided. The repetition compulsion, then, is a complex mechanism: preventive in one part, it protects the vulnerable self from potentially traumatising experiences; thus, it is operated in response to the danger signal of emotional cravings, once the latter are experienced as getting out of hand. Providing novel experiences, in its other part, it can lead to opening the road for change; such curative impact relies on lengthy working through in a safe, empathic, holding environment.

Compulsive Behavior↗

PubMed2001

New therapies and vaccines for meningococcal disease.

Meningococcal disease (MCD) is an important cause of morbidity and mortality. The pathophysiology consists of a complex interaction of bacterial and host factors, triggered by the release of endotoxin which initiates the inflammatory cascade, resulting in multi-organ failure, coagulopathy, capillary leak, metabolic derangement and eventually death. Prompt recognition and aggressive management are essential in reducing mortality. Over the past decade, there has been intense research into novel therapies and vaccines, with largely disappointing results. Therapies have been broadly divided into anti-endotoxin and anti-TNF-alpha therapies, treatment aimed at correcting coagulopathy and at blood purification and anti-inflammatory cytokine therapy. The reasons for the disappointing results in the search for new therapeutic strategies are difficult to identify. The disordered physiology in MCD results from a complex interaction of several mediators; therefore attempts to correct this by altering just one step represents a gross oversimplification of the process. In addition, the experimental model of endotoxaemia, which is often used, is a poor representation of an acutely ill patient with rapidly progressive shock. There have been several small or poorly designed trials, which have failed to reach definite conclusions. In order to yield conclusive results any future trials must be multicentre, randomised, controlled trials, but these are expensive and, in practice, difficult to conduct. The BPI trial (vide infra) was a significant step forward in this regard and demonstrated the ability to organise a large multicentred trial which can act as a template for future trials. Although the results were not significant there was an overall trend towards improved outcome in the treatment arm. Whilst the development of effective therapies and vaccines are awaited, the priorities at present must be the prompt recognition and aggressive management of disease.

Animals↗

PubMed1988

Precocious ego development and obsessive compulsive neurosis.

Precocious ego development is frequently mentioned in psychoanalytic theory as an important determinant of obsessive-compulsive neurosis. Writers such as Anna Freud suggest that an imbalance in the development of ego over drive may lead to obsessional neurosis. However, further examination of the psychoanalytic literature reveals that the nature of this supposed link is not clear. Explanations couched in economic language or in terms of an early hypersensitivity to stimulation are open to theoretical criticism or are unsatisfying. The author suggests that we focus on the effect of precocious ego development on developing object relations. It is suggested that precocity may lead to early disappointment in parental objects. The inter-relationships of disappointment with early identifications, premature sense of autonomy and anal problems are discussed. A case of an obsessive-compulsive adolescent girl is presented to illustrate the role of precocious ego development and superior intelligence in the formation of the symptoms.

Adolescent↗

PubMed2005

Epoetin alfa: basic biology and clinical utility in cancer patients.

Anemia in cancer patients undergoing treatment is common and can cause debilitating symptoms such as fatigue and reduced exercise tolerance. The introduction of recombinant human erythropoietin represents a potential improvement in the treatment of this condition. Clinical studies in patients with solid tumors and nonmyeloid hematologic malignancies have convincingly shown an improvement in mean hemoglobin concentration, a reduction in transfusion requirement along with an improvement in quality of life scores, although an effect on survival is less clear. In myeloid disorders such as myelodysplasia, response to single-agent recombinant human erythropoietin is disappointing but significant synergism with granulocyte colony stimulating factor has been demonstrated and different dosing regimens may also improve response. Unfortunately, a significant proportion of patients remain refractory to treatment. Efforts have been made to identify treatable causes of erythropoietin refractoriness, such as functional iron deficiency, and concomitant intravenous iron supplementation does appear to improve response rates. The search for pretreatment factors that predict response has been largely disappointing, although a promising model for myelodysplasia has been developed that awaits large-scale evaluation. Recombinant human erythropoietin is well tolerated, although there were concerns in the late 1990s due to a rising incidence of pure red cell aplasia in chronic renal failure patients treated with subcutaneous Eprex (Ortho Biologics) in Europe. Since potentially contributory manufacturing processes have been identified and corrected, the incidence of this complication has been falling.

Anemia↗

PubMed2001

Optimising outcomes in acute pancreatitis.

Acute pancreatitis is a common cause for presentation to emergency departments. Common causes in Western societies include biliary pancreatitis and alcohol (the latter in the setting of chronic pancreatitis). Acute pancreatitis also follows endoscopic retrograde pancreatography in 5 to 10% of patients, a group that could potentially benefit from prophylactic treatment. Although episodes of pancreatitis usually run a relatively benign course, up to 20% of patients have more severe disease, and this group has significant morbidity and mortality. Therefore, attempts have been made to identify, at or soon after presentation, those patients likely to have a poor outcome and to channel resources to this group. The mainstay of treatment is aggressive support and monitoring of those patients likely to have a poor outcome. Pharmacotherapy for acute pancreatitis (both prophylactic and in the acute setting) has been generally disappointing. Efforts initially focused on protease inhibitors, of which gabexate shows some promise as a prophylactic agent. Agents that suppress pancreatic secretion have produced disappointing results in human studies. Infection of pancreatic necrosis is associated with high mortality and requires surgical intervention. In view of the seriousness of infected necrosis, the use of prophylactic antibacterials such as carbapenems and quinolones has been advocated in the setting of pancreatic necrosis. Similarly, data are accumulating to support the use of prophylactic antifungal therapy. Recently, it has become apparent that the intense inflammatory response associated with acute pancreatitis is responsible for much of the local and systemic damage. With this realisation, future efforts in pharmacotherapy are likely to focus on suppression or antagonism of pro-inflammatory cytokines and other inflammatory mediators. Similarly, animal studies have demonstrated the importance of oxidative stress in acute pancreatitis, although to date there is a paucity of information regarding the efficacy of antioxidants. Although the clinical course for most patients with acute pancreatitis is mild, severe acute pancreatitis continues to be a clinical challenge, requiring a multidisciplinary approach of physician, intensivist and surgeon.

APACHE↗

PubMed2004

Maintenance of remission in Crohn's disease: current and emerging therapeutic options.

Crohn's disease is a chronic inflammatory bowel disorder with a relapsing and remitting course. Once remission is achieved, the main aim of the management of Crohn's disease is maintenance of that remission. Significant advances have been made into understanding the aetiology and pathogenesis of inflammatory bowel disease. With these advances in understanding come increasing numbers of new agents and therapies, aimed both at active disease and the subsequent maintenance of remission in Crohn's disease. Current therapeutic strategies in maintaining remission in Crohn's disease include 5-aminosalicylates (e.g. sulfasalazine, mesalazine), thiopurines (e.g. azathioprine, 6-mercaptopurine [mercaptopurine]), methotrexate and infliximab. The 5-aminosalicylates appear to have efficacy limited to either surgically induced remission and/or limited small bowel Crohn's disease. The immunomodulators now have an established role in Crohn's maintenance. Azathioprine and 6-mercaptopurine are effective in chronic active disease and corticosteroid-dependent Crohn's disease. Methotrexate has similar indications, although it appears to be an alternative in patients who are intolerant of, or resistant to, the thiopurines. The most recent breakthrough has been in the field of biological therapy for maintenance of remission in Crohn's disease. Treatment of patients with the anti-tumour necrosis factor (TNF)-alpha antibody infliximab has been shown already to be effective in inducing remission. Recent studies have now confirmed a role for infliximab in delaying relapse and maintaining remission in patients responsive to infliximab induction therapy. However, results with soluble TNF alpha receptors have been disappointing. A number of other biological and nonbiological agents have shown potential, though trials of the 'newer' biological agents have thus far been disappointing, in the maintenance of remission in Crohn's disease. The evidence for theses agents is currently limited, in many cases to treating active disease; however, these data are discussed in this article in order to provide an overview of future potential therapies. The aim of this review is to provide clinicians with an insight into current and emerging therapeutic agents for the maintenance of remission of Crohn's disease.

Adjuvants, Immunologic↗

PubMed2004

Is there a future for neural transplantation?

Traditionally neural transplantation has had as its central tenet the replacement of missing neurons that have been lost because of neurodegenerative processes, as exemplified by diseases such as Parkinson disease (PD). However, the effectiveness and widespread application of this approach clinically has been limited, primarily because of the poor donor supply of human fetal neural tissue and the incomplete neurobiological understanding of the circuit reconstruction required to normalize function in these diseases. So, in PD the progress from promising neural transplantation in animal models to proof-of-principle, open-labeled clinical transplants, to randomized, placebo-controlled studies of neural transplantation has not been straightforward. The emergence of previously undescribed adverse effects and lack of significant functional advantage in recent clinical studies has been disappointing and has served to cast a new, and perhaps more realistic, perspective on this treatment approach. In fact, there have been calls by some involved in neural transplantation to return to the drawing board before pressing on with further clinical trials, and the return to basic experimentation. This therefore precipitates the question - is there a future for neural transplantation? It is important to remember that there are a number of possible explanations for the disappointing results from the recent clinical trials in PD, ranging from the mode of transplantation to patient selection. Nevertheless, almost irrespective of these reasons for the current trial results, there have always been significant practical and ethical problems with using human fetal tissue, and so a number of alternative cell sources have been investigated. These alternative sources include stem cells, which are attractive for cell-based therapies because of their potential ease of isolation, propagation and manipulation, and their ability in some cases to migrate to areas of pathology and differentiate into specific and appropriate cell types. Furthermore, the availability of stem cells derived from non-embryonic sources (e.g. adult stem cells derived from the sub-ventricular zone) has removed some of the ethical limitations associated with the use of embryonic human tissue. These potentially beneficial aspects of stem cells means that there is a future for neural transplantation as a means of treating patients with a range of neurological disorders, although whether this will ever translate into a truly effective, widely available therapy remains unknown.

Animals↗

PubMed1997

FDG PET in head and neck cancer.

In our extensive experience with FDG PET imaging in head and neck cancer, we have found the technique to be of high accuracy but of limited usefulness. This seeming paradox arises from several causes. Competing techniques such as CT, MR imaging, and even clinical examination already have good accuracy. In addition, high-resolution studies such as CT and MR imaging provide information required for treatment planning that is unavailable from FDG PET images. The high cost of FDG PET militates against its use in this setting, in which only a small marginal gain can be expected. In the special problem areas in which FDG PET might be expected to offer unique advantages, such as screening for second primary lesions, searching for unknown primary lesions, or differentiating benign salivary rumors from malignant lesions, the results of FDG PET have been disappointedly poor. Of these special problem areas, only the question of accuracy in finding occult primary lesions appears unresolved and in need of further study. The single application in which FDG PET appears to be advantageous is the posttherapy setting. In this setting, the technique is definitely superior to alternative methods of determining tumor recurrence and differentiating posttherapy sequelae such as radiation necrosis from tumor recurrence. We believe that considerable opportunity remains for further research on the use of FDG PET in head and neck cancer. Other agents such as 11C-methionine for example, might improve the diagnostic accuracy of FDG PET in some of the problem areas that we have identified, such as the early postirradiation period. We currently have such a study under way. Also, because FDG PET offers a unique way to measure tumor metabolism, further investigation of the use of FDG PET tracers to evaluate various biologic parameters such as proliferation rates or tumor hypoxia are needed. Such studies could provide a noninvasive technique to identify which fractionation schemes or combinations of therapy might be useful for individual patients. A final caveat is in order. Although our findings of the usefulness (and lack thereof) of FDG PET in head and neck cancer may be disappointing to many, these results should not be generalized to other applications of FDG PET in oncology. Each tumor type and setting presents its own specific problems, and in some instances FDG PET offers unique advantages over other imaging techniques. A good example is the setting of primary lung cancer, in which FDG PET appears clearly superior to all other methods of pretherapy screening [19-20].

Adult↗

PubMed2005

Who is still using expanded polytetrafluoroethylene?

BACKGROUND: Expanded polytetrafluoroethylene (ePTFE) is a permanent, solid implant that has been used for facial soft tissue augmentation. The implants are generally used in the lower third of the face for filling lips, nasolabial folds, and deeper facial lines. Many physicians have noted complications with this use. OBJECTIVE: To determine physician satisfaction trends for ePTFE. METHODS. A physician satisfaction survey was sent out in February 2000. Information regarding perceived patient and physician satisfaction regarding favored sites for the use of augmentation with ePTFE, the quantity used, and revision rates was assessed. A second survey was mailed in July 2003 to the same physicians to gain information regarding long-term satisfaction with ePTFE. RESULTS: The results from the first survey revealed that 10 of 12 physicians perceived that their patients were satisfied with ePTFE implants in all locations with the exception of the lips. There was a wide variation in the number of cases of ePTFE performed per year among the different physicians. Reported revision rates varied from less than 1 to 100% in the lips. The majority of the physicians found that removal of the implant was easy. The results from the second survey in 2003 revealed that 100% of the physicians were disappointed with these products. Physicians' assessments of their patients' satisfaction revealed that one-third were mildly disappointed and two-thirds were satisfied. Revision rates in all cases were increased between the first and second survey. A subjective patient satisfaction survey was not done during either of these time periods. CONCLUSIONS: New procedures are often quickly embraced by both physicians and patients. It is crucial that we reevaluate and report long-term experience and satisfaction. Although this informal survey has limitations, it appears that some physicians are less satisfied with ePTFE as a soft tissue implant. Larger studies including objective measurements delineating the degree of improvement and subjective patient satisfaction would be welcomed.

Cosmetic Techniques↗

PubMed1978

Our surprising inability to predict the outcomes of psychological treatments--with special reference to treatments for drug abuse.

Our ability to predict the outcome of psychological treatments, particularly for drug dependence, is examined by (1) new data on a VA sample, (2) a review of studies predicting the outcome of drug abuse treatment, and (3) a review of predicting the outcome of psychotherapy for other types of patients. For (1), the direct predictions of 13 staff members' ratings of the outcome of treatment correlated .27 with the outcome. Although staff predictions improved when grosser predictions were examined, the results are disappointing given the level of discrimination required and the modest levels of prediction attained. For (2), prediction success with drug abuse patients in other studies were also disappointing and the bases for predictions often did not hold up on crossvalidation. For (3), direct predictions in the Penn Psychotherapy Study were similar to the VA sample in level of success. Other studies produced insignificant or similarly low levels of prediction success. In our discussion we suggest that rather than relying mainly upon pretreatment status for prediction, two promising areas should be examined in future studies: (1) the patient's early response to the treatment and to the therapist, (2) the patient's environment posttreatment that should be altered to consolidate and perpetuate the gains made during treatment. In conclusion, it is true that we are surprisingly unable to predict the outcomes of psychological treatments beyond a very modest level.

Adult↗