Unilateral focal polymicrogyria in a patient with classical Aarskog-Scott syndrome due to a novel missense mutation in an evolutionary conserved RhoGEF domain of the faciogenital dysplasia gene FGD1

Faciogenital dysplasia or Aarskog-Scott syndrome (AAS) is an X-linked disorder characterized by craniofacial, skeletal, and urogenital malformations and short stature. Mutations in the only known causative gene FGD1 are found in about one-fifth of the cases with the clinical diagnosis of AAS. FGD1 is a guanine nucleotide exchange factor (GEF) that specifically activates the Rho GTPase Cdc42 via its RhoGEF domain. The Cdc42 pathway is involved in skeletal formation and multiple aspects of neuronal development. We describe a boy with typical AAS and, in addition, unilateral focal polymicrogyria (PMG), a feature hitherto unreported in AAS. Sequencing of the FGD1 gene in the index case and his mother revealed the presence of a novel mutation (1396A>G; M466V), located in the evolutionary conserved alpha-helix 4 of the RhoGEF domain. M466V was not found in healthy family members, in >300 healthy controls and AAS patients, and has not been reported in the literature or mutation databases to date, indicating that this novel missense mutation causes AAS, and possibly PMG. Brain cortex malformations such as PMG could be initiated by mutations in the evolutionary conserved RhoGEF domain of FGD1, by perturbing the signaling via Rho GTPases such as Cdc42 known to cause brain malformation.

A de novo 1.1-1.6 Mb subtelomeric deletion of chromosome 20q13.33 in a patient with learning difficulties but without obvious dysmorphic features

We report on a de novo submicroscopic deletion of 20q13.33 identified by subtelomeric fluorescence in situ hybridization (FISH) in a 4-year-old girl with learning difficulties, hyperlaxity and strabismus, but without obvious dysmorphic features. Further investigations by array-based comparative genomic hybridization (array-CGH) and FISH analysis allowed us to delineate the smallest reported subterminal deletion of chromosome 20q, spanning a 1.1-1.6 Mb with a breakpoint localized between BAC RP5-887L7 and RP11-261N11. The genes CHRNA4 and KCNQ2 implicated in autosomal dominant epilepsy are included in the deletion interval. Subterminal 20q deletions as found in the present patient have, to our knowledge, only been reported in three patients. We review the clinical and behavioral phenotype of such "pure" subterminal 20q deletions.

[Hypophyseal incidentaloma in a patient with autosomal dominant polycystic kidney disease]

The prevalence of incidentally discovered lesions within the pituitary (pituitary incidentalomas) is about 10%. The most common form of sellar mass are clinically nonfunctioning adenomas (less than 10 mm); functioning adenomas, however, are rare. Incidentally discovered pituitary microadenomas causing growth hormone hypersecretion are uncommon. In addition, the association of autosomal dominant polycystic kidney disease with acromegaly is exceptional and has not yet been reported to our knowledge.

[Irritation of the iliopsoas tendon after total hip arthroplasty]

Chronic irritation of the iliopsoas tendon is a rare cause of persistent pain after total joint replacement of the hip. In the majority of cases, pain results from a mechanical conflict between the iliopsoas tendon and the anterior edge of the acetabular cup after total hip arthroplasty. Pain can be reproduced by active flexion of the hip and by active raising of the straightened leg. In addition, painful leg raising against resistance and passive hyperextension are suggestive of an irritation of the iliopsoas tendon. Symptoms evolve from a mechanical irritation of the iliopsoas tendon and an oversized or retroverted acetabular cup, screws penetrating into the inner aspect of the ilium, or from bone cement protruding beyond the anterior acetabular rim. The diagnosis may be assumed on conventional radiographs and confirmed by CT scans. Fifteen patients with psoas irritation after total hip replacement are reported on. Eleven patients were treated surgically. The acetabular cup was revised and reoriented with more anteversion in six patients, isolated screws penetrating into the tendon were cut and leveled in three patients, and prominent bone cement in conflict with the tendon was resected once. A partial release of the iliopsoas tendon only was performed in another patient. Follow-up examination (range: 11-89 months) revealed that nine patients were free of pain and two patient had mild residual complaints. Psoas irritation in combination with total hip replacement can be prevented by a correct surgical technique, especially with proper selection of the cup size and insertion of the acetabular cup avoiding a rim position exceeding the level of the anterior acetabular rim.

Is the combination of morphine with ketamine better than morphine alone for postoperative intravenous patient-controlled analgesia?

BACKGROUND: The addition of ketamine to morphine for patient-controlled analgesia (PCA) is supported by previous basic and clinical research, but has been challenged by subsequent negative studies. Important limitations of previous studies are the low number of patients analyzed, the use of morphine-ketamine combinations that may not the optimal, and that not all the relevant outcomes have been analyzed. In this study, we compared the combination of morphine and ketamine with morphine alone for postoperative PCA in large patient groups. We used a morphine-ketamine combination identified by an optimization procedure in our previous study. METHODS: After major elective orthopedic surgery, 352 patients received either PCA with morphine bolus 1.5 mg (Group M, n = 176) or a bolus of morphine plus ketamine 1.5 mg each (Group MK, n = 176) in a randomized, double-blind fashion. Unsatisfactory treatment was defined as the occurrence of either inadequate analgesia or unacceptable side effects. In addition, total consumption of PCA drugs, duration of PCA use, direct medical costs, and number of patients with chronic postoperative pain 3 and 6 mo after operation were recorded. RESULTS: The incidence of unsatisfactory treatment was 33.0% in Group M and 36.9% in Group MK (P = 0.50). No significant differences were found between the groups with respect to secondary end points. CONCLUSIONS: Small-dose ketamine combined with morphine for PCA provides no benefit to patients undergoing major orthopedic surgery and cannot be recommended for routine use.

Recurrent ischemic colitis in a patient with leiden factor V mutation and systemic lupus erythematous with antiphospholipid syndrome

Ischemic colitis results from insufficient blood supply to the large intestine and is often associated with hypercoagulable states. The condition comprises a wide range presenting with mild to fulminant forms. Diagnosis remains difficult because these patients may present with non-specific abdominal symptoms. We report a 51- year-old female patient with known Leiden factor V mutation as well as systemic lupus erythematous along with antiphospholipid syndrome suffering from recurrent ischemic colitis. At admission, the patient complained about abdominal pain, diarrhea and rectal bleeding lasting for 24 hours. Laboratory tests showed an increased C-reactive protein (29.5 mg/dl), while the performed abdominal CT-scan revealed only a dilatation of the descending colon along with a thickening of the bowel wall. Laparotomy was performed showing an ischemic colon and massive peritonitis. Histological examination proved the suspected ischemic colitis. Consecutively, an anti-coagulation therapy with coumarin and aspirin 100 was initiated. Up to the time point of a follow up examination no further ischemic events had occurred. This case illustrates well the non-specific clinical presentation of ischemic colitis. A high index of suspicion, recognition of risk factors and a history of non-specific abdominal symptoms should alert the clinicians to the possibility of ischemic disease. Early diagnosis and initiation of anticoagulation therapy or surgical intervention in case of peritonitis are the major goals of therapy.

[Psychophysiologic manifestations, psychological and somatic risk factors and the physician-patient relationship in patients with heart diseases]

In daily medicine we often see patients complaining about thoracic pain. There is little doubt about the etiology in the most cases, but several patients continue posing diagnostic problems. There are different pathophysiological views to understand the situation of those patients, and it is important to determine their mental and psychological conditions. For this purpose, the focus on transference and countertransference phenomena has to be stressed. With these elements it will be possible to determine the diagnostic and therapeutic approach to those patients to reassure them and to justify investigations.

Loss of pulp sensitivity and pain as the first symptoms of a Ewing's sarcoma in the right maxillary sinus and alveolar process: report of a case

This case report describes the diagnosis and treatment of a Ewing's sarcoma in the right maxillary sinus and alveolar bone of a 19-year-old female patient. The first clinical symptoms were a loss of sensitivity of the premolars and first molar in the right maxilla and acute pain located in the area of these teeth. Initially, the referring dentist had treated these findings as an acute apical periodontitis with root canal medication. Because swellings on the palatal and buccal aspects of the teeth occurred and could not be treated with incision and drainage, the dentist referred the patient. Cone-beam computed tomography revealed a proliferation of soft tissue in the right maxillary sinus, with a radiopaque material at the tip of the mesiobuccal root of the first molar and resorptive signs of the mesiobuccal and distobuccal roots of the first molar. The palatal cortical bone of the right alveolar process seemed to be intact. After explorative surgery with biopsies from the buccal, palatal, and sinus proliferation areas, the pathologist diagnosed the lesion as a Ewing's sarcoma. Treatment of the patient consisted of initial chemotherapy, hemimaxillectomy, and postsurgical chemoradiotherapy.

Patient satisfaction of primary care for musculoskeletal diseases: A comparison between Neural Therapy and conventional medicine

Background The main objective of this study was to assess and compare patient satisfaction with Neural Therapy (NT) and conventional medicine (COM) in primary care for musculoskeletal diseases. Methods A cross-sectional study in primary care for musculoskeletal disorders covering 77 conventional primary care providers and 18 physicians certified in NT with 241 and 164 patients respectively. Patients and physicians documented consultations and patients completed questionnaires at a one-month follow-up. Physicians documented duration and severity of symptoms, diagnosis, and procedures. The main outcomes in the evaluation of patients were: fulfillment of expectations, perceived treatment effects, and patient satisfaction. Results The most frequent diagnoses belonged to the group of dorsopathies (39% in COM, 46% in NT). We found significant differences between NT and COM with regard to patient evaluations. NT patients documented better fulfilment of treatment expectations and higher overall treatment satisfaction. More patients in NT reported positive side effects and less frequent negative effects than patients in COM. Also, significant differences between NT and COM patients were seen in the quality of the patient-physician interaction (relation and communication, medical care, information and support, continuity and cooperation, facilities availability, and accessibility), where NT patients showed higher satisfaction. Differences were also found with regard to the physicians' management of disease, with fewer work incapacity attestations issued and longer consultation times in NT. Conclusion Our findings show a significantly higher treatment and care-related patient satisfaction with primary care for musculoskeletal diseases provided by physicians practising Neural Therapy.

Patient satisfaction and side effects in primary care: An observational study comparing homeopathy and conventional medicine

Background This study is part of a nationwide evaluation of complementary medicine in Switzerland (Programme Evaluation of Complementary Medicine PEK) and was funded by the Swiss Federal Office of Public Health. The main objective of this study is to investigate patient satisfaction and perception of side effects in homeopathy compared with conventional care in a primary care setting. Methods We examined data from two cross-sectional studies conducted in 2002–2003. The first study was a physician questionnaire assessing structural characteristics of practices. The second study was conducted on four given days during a 12-month period in 2002/2003 using a physician and patient questionnaire at consultation and a patient questionnaire mailed to the patient one month later (including Europep questionnaire). The participating physicians were all trained and licensed in conventional medicine. An additional qualification was required for medical doctors providing homeopathy (membership in the Swiss association of homeopathic physicians SVHA). Results A total of 6778 adult patients received the questionnaire and 3126 responded (46.1%). Statistically significant differences were found with respect to health status (higher percentage of chronic and severe conditions in the homeopathic group), perception of side effects (higher percentage of reported side effects in the conventional group) and patient satisfaction (higher percentage of satisfied patients in the homeopathic group). Conclusion Overall patient satisfaction was significantly higher in homeopathic than in conventional care. Homeopathic treatments were perceived as a low-risk therapy with two to three times fewer side effects than conventional care

Transient apical ballooning syndrome--clinical characteristics, ballooning pattern, and long-term follow-up in a Swiss population

BACKGROUND: Transient apical ballooning syndrome (TABS) or Takotsubo cardiomyopathy mimics acute ST-elevation myocardial infarction, but is considered to have a good prognosis with only moderate elevation of myocardial enzymes and full recovery of left ventricular function. Although it is increasingly reported, its exact incidence, clinical presentation, and prognosis in non-Asian populations remain largely unknown. OBJECTIVE: To describe the clinical characteristics and long-term follow-up of patients who presented with TABS at our institution over a 3 year-period. METHODS: Patients were retrospectively retrieved from our local database. Patient charts were carefully reviewed and the diagnosis of TABS was based on the Mayo Clinic diagnostic criteria. Moreover, psychosocial stress or gastrointestinal disease was recorded. RESULTS: During the study period, 13,715 coronary angiographies were performed at our institution, including 2459 patients presenting with an acute coronary syndrome (ACS). Forty-one TABS were diagnosed, which represents an incidence of 1.7% of ACS-patients and 0.3% of all coronary angiographies performed, respectively. Mean age was 65 years, with 85% women. Clinical presentations included chest pain, dyspnoea, and cardiogenic shock. A preceding psychological or physical condition perceived as "stress" was reported in 61%. At a mean follow-up of 675+/-288 days, none of the patients died of cardiac causes, but two patients had a recurrence of symptoms. CONCLUSIONS: This is the largest cohort of TABS patients reported out of Europe so far. The good overall prognosis and low likelihood of recurrence were confirmed.

Pain relief in ventilated preterms during endotracheal suctioning: a randomized controlled trial

BACKGROUND: In Switzerland approximately 8% of infants are born prematurely. Some of them undergo mechanical ventilation including endotracheal suctioning (ETS). ETS is one of the most frequently performed interventions and is linked to stress and pain, but its treatment is controversial. In Switzerland there is a lack of standardisation in pain relief for ETS. AIMS: To test the hypothesis that an intermittent dose of morphine reduces pain during ETS and that subsequent multisensorial stimulation (MSS), as a non pharmacological comforting intervention, helps infants to recover from experienced pain. METHOD: A randomized placebo controlled trial in two tertiary neonatal intensive care units (NICU) with a sample of 30 mechanically ventilated preterm infants was conducted. Pain was measured by three pain assessment tools (Bernese Pain Scale for Neonates, Premature Infant Pain Profile and Visual Analogue Scale) RESULTS: Morphine did not lead to any pain relief from ETS as measured by three pain scales. Nor did the comforting intervention of MSS show any effect. Repeated-measure analysis of variance for the within and between groups comparison showed no statistical significance. CONCLUSIONS: The administration of morphine for pain relief in ventilated preterm neonates during ETS remains questionable and the use of MSS as a comforting intervention after painful stimulus cannot be recommended. The validity testing of the instruments for this patient population should undergo a systematic validation trajectory. Future research should focus on options among non pharmacological interventions for relieving pain during ETS.

Development of a screening tool predicting the transition from acute to chronic low back pain for patients in a GP setting: protocol of a multinational prospective cohort study

BACKGROUND: Low back pain (LBP) is by far the most prevalent and costly musculoskeletal problem in our society today. Following the recommendations of the Multinational Musculoskeletal Inception Cohort Study (MMICS) Statement, our study aims to define outcome assessment tools for patients with acute LBP and the time point at which chronic LBP becomes manifest and to identify patient characteristics which increase the risk of chronicity. METHODS: Patients with acute LBP will be recruited from clinics of general practitioners (GPs) in New Zealand (NZ) and Switzerland (CH). They will be assessed by postal survey at baseline and at 3, 6, 12 weeks and 6 months follow-up. Primary outcome will be disability as measured by the Oswestry Disability Index (ODI); key secondary endpoints will be general health as measured by the acute SF-12 and pain as measured on the Visual Analogue Scale (VAS). A subgroup analysis of different assessment instruments and baseline characteristics will be performed using multiple linear regression models. This study aims to examine: 1. Which biomedical, psychological, social, and occupational outcome assessment tools are identifiers for the transition from acute to chronic LBP and at which time point this transition becomes manifest. 2. Which psychosocial and occupational baseline characteristics like work status and period of work absenteeism influence the course from acute to chronic LBP. 3. Differences in outcome assessment tools and baseline characteristics of patients in NZ compared with CH. DISCUSSION: This study will develop a screening tool for patients with acute LBP to be used in GP clinics to access the risk of developing chronic LBP. In addition, biomedical, psychological, social, and occupational patient characteristics which influence the course from acute to chronic LBP will be identified. Furthermore, an appropriate time point for follow-ups will be given to detect this transition. The generalizability of our findings will be enhanced by the international perspective of this study. TRIAL REGISTRATION: [Clinical Trial Registration Number, ACTRN12608000520336].

Differences across health care systems in outcome and cost-utility of surgical and conservative treatment of chronic low back pain: a study protocol

BACKGROUND: There is little evidence on differences across health care systems in choice and outcome of the treatment of chronic low back pain (CLBP) with spinal surgery and conservative treatment as the main options. At least six randomised controlled trials comparing these two options have been performed; they show conflicting results without clear-cut evidence for superior effectiveness of any of the evaluated interventions and could not address whether treatment effect varied across patient subgroups. Cost-utility analyses display inconsistent results when comparing surgical and conservative treatment of CLBP. Due to its higher feasibility, we chose to conduct a prospective observational cohort study. METHODS: This study aims to examine if1. Differences across health care systems result in different treatment outcomes of surgical and conservative treatment of CLBP2. Patient characteristics (work-related, psychological factors, etc.) and co-interventions (physiotherapy, cognitive behavioural therapy, return-to-work programs, etc.) modify the outcome of treatment for CLBP3. Cost-utility in terms of quality-adjusted life years differs between surgical and conservative treatment of CLBP.This study will recruit 1000 patients from orthopaedic spine units, rehabilitation centres, and pain clinics in Switzerland and New Zealand. Effectiveness will be measured by the Oswestry Disability Index (ODI) at baseline and after six months. The change in ODI will be the primary endpoint of this study.Multiple linear regression models will be used, with the change in ODI from baseline to six months as the dependent variable and the type of health care system, type of treatment, patient characteristics, and co-interventions as independent variables. Interactions will be incorporated between type of treatment and different co-interventions and patient characteristics. Cost-utility will be measured with an index based on EQol-5D in combination with cost data. CONCLUSION: This study will provide evidence if differences across health care systems in the outcome of treatment of CLBP exist. It will classify patients with CLBP into different clinical subgroups and help to identify specific target groups who might benefit from specific surgical or conservative interventions. Furthermore, cost-utility differences will be identified for different groups of patients with CLBP. Main results of this study should be replicated in future studies on CLBP.

[A 56-year-old patient with Gaucher's disease sustaining a pathologic subcapital fracture of the humerus]

We present a case of a pathologic humerus fracture in a patient with the initial diagnosis of Gaucher's disease, which is the most frequent form of lipidosis transmitted as an autosomal recessive trait. It often results in orthopaedic complications with pain, osteonecrosis, fractures and joint infractions. If there is cause for suspicion, beta-glucocerebrosidase in white blood cells should be measured because of the important consequences for treatment. Therapy with a modified enzyme is effective in managing the disease.