Treating Symptoms of Posttraumatic Stress in People with Dementia: Expert Consensus Using the Delphi Method.

OBJECTIVES: Posttraumatic stress disorder is frequently present in people with dementia, but the symptoms are difficult to recognize and suitable treatments are lacking. The aim of the present study was to investigate which trauma-focused treatments are applicable to these patients. METHODS: The Delphi method is a process which is used to reach consensus from a panel of experts. The study was conducted online and consisted of three rounds with statements about support for treatment, treatment, and implementation. RESULTS: There are several treatment options available, but it depends on the symptoms, and the severity of PTSD and dementia which treatment is most suitable. CONCLUSIONS: The outcomes offer some practical tips for health care workers, and they provide a fundamental base for future research. CLINICAL IMPLICATIONS: Clinicians should pay attention to the treatment of PTSD symptoms in people with dementia and it is necessary to examine the type and severity of both PTSD symptoms and dementia. Taking these factors into account, clinicians are able to focus on the best treatment option in order to improve the quality of life of these specific type of patients.

Performance validity in outpatients with multiple sclerosis and cognitive complaints.

BACKGROUND: Suboptimal performance during neuropsychological assessment renders cognitive test results invalid. However, suboptimal performance has rarely been investigated in multiple sclerosis (MS). OBJECTIVES: To investigate potential underlying mechanisms of suboptimal performance in MS. METHODS: Performance validity testing, neuropsychological assessments, neuroimaging, and questionnaires were analyzed in 99 MS outpatients with cognitive complaints. Based on performance validity testing patients were classified as valid or invalid performers, and based on neuropsychological test results as cognitively impaired or preserved. Group comparisons and correlational analyses were performed on demographics, patient-reported, and disease-related outcomes. RESULTS: Twenty percent displayed invalid performance. Invalid and valid performers did not differ regarding demographic, patient-reported, and disease-related outcomes. Disease severity of invalid and valid performers with cognitive impairment was comparable, but worse than cognitively preserved valid performers. Lower performance validity scores related to lower cognitive functioning, lower education, being male, and higher disability levels (p < 0.05). CONCLUSION: Suboptimal performance frequently occurs in patients with MS and cognitive complaints. In both clinical practice and in cognitive research, suboptimal performance should be considered in the interpretation of cognitive outcomes. Identification of factors that differentiate between suboptimal and optimal performers with cognitive impairment needs further exploration.

A new approach to simplify surgical colpotomy in laparoscopic hysterectomy.

New surgical techniques and technology have simplified laparoscopic hysterectomy and have enhanced the safety of this procedure. However, the surgical colpotomy step has not been addressed. This study evaluates the surgical colpotomy step in laparoscopic hysterectomy with respect to difficulty and duration. Furthermore, it proposes an alternative route that may simplify this step in laparoscopic hysterectomy. A structured interview, a prospective cohort study, and a problem analysis were performed regarding experienced difficulty and duration of surgical colpotomy in laparoscopic hysterectomy. Sixteen experts in minimally invasive gynecologic surgery from 12 hospitals participated in the structured interview using a 5-point Likert scale. The colpotomy in LH received the highest scores for complexity (2.8 ± 1.2), compared to AH and VH. Colpotomy in LH was estimated as more difficult than in AH (2.8 vs 1.4, p < .001). In the cohort study, 107 patients undergoing LH were included. Sixteen percent of the total procedure time was spent on colpotomy (SD 7.8 %). BMI was positively correlated with colpotomy time, even after correcting for longer operation time. No relation was found between colpotomy time and blood loss or uterine weight. The surgical colpotomy step in laparoscopic hysterectomy should be simplified as this study demonstrates that it is time consuming and is considered to be more difficult than in other hysterectomy procedures. A vaginal approach to the colpotomy is proposed to achieve this simplification.

PDK1 controls upstream PI3K expression and PIP3 generation.

The PI3K/PDK1/Akt signaling axis is centrally involved in cellular homeostasis and controls cell growth and proliferation. Due to its key function as regulator of cell survival and metabolism, the dysregulation of this pathway is manifested in several human pathologies including cancers and immunological diseases. Thus, current therapeutic strategies target the components of this signaling cascade. In recent years, numerous feedback loops have been identified that attenuate PI3K/PDK1/Akt-dependent signaling. Here, we report the identification of an additional level of feedback regulation that depends on the negative transcriptional control of phosphatidylinositol 3-kinase (PI3K) class IA subunits. Genetic deletion of 3-phosphoinositide-dependent protein kinase 1 (PDK1) or the pharmacological inhibition of its downstream effectors, that is, Akt and mammalian target of rapamycin (mTOR), relieves this suppression and leads to the upregulation of PI3K subunits, resulting in enhanced generation of phosphatidylinositol-3,4,5-trisphosphate (PIP3). Apparently, this transcriptional induction is mediated by the concerted action of different transcription factor families, including the transcription factors cAMP-responsive element-binding protein and forkhead box O. Collectively, we propose that PDK1 functions as a cellular sensor that balances basal PIP3 generation at levels sufficient for survival but below a threshold being harmful to the cell. Our study suggests that the efficiency of therapies targeting the aberrantly activated PI3K/PDK1/Akt pathway might be increased by the parallel blockade of feedback circuits.

Complete genomic sequence of a novel HLA-B allele, B*4456N.

A novel allele, HLA-B*4456N, was identified upon cloning and sequencing of genomic DNA.

Morphology of the rust fungus Puccinia boroniae revisited.

Puccinia boroniae Henns. is a rust fungus endemic to Australia, infecting various Boronia spp. This study describes and illustrates, using light and scanning electron microscopy, the telial stage, teliospore germination and basidiospore production of specimens collected from commercial Boronia plantations in Western Australia. Unusual formation of a single basidiospore per germinating teliospore, and the pycnial stage, observed on Boronia megastigma leaves, are reported for the first time for P. boroniae.

[Tropical diseases and imported disorders in 1763 patients seen at the Outpatient Clinic for Tropical Diseases, Academic Medical Center, Amsterdam (1996-1997)]. / Tropische ziekten en importaandoeningen bij 1763 patiënten op de polikliniek voor Tropische Ziekten van het Academisch Medisch Centrum, Amsterdam (1996-1997).

OBJECTIVE: To describe an analysis of the patients seen at the Outpatient Department (OPD) for Tropical Diseases in the Academic Medical Centre, Amsterdam, during 1996 and 1997. DESIGN: Descriptive cross-sectional study. METHOD: From our database of OPD-patients the following data were analysed: age, country of birth, travel destination and most frequent complaints at presentation. These were further analysed in relation to travel destination, diagnosis and need of admission. RESULTS: In 1996 and 1997 1763 patients visited the OPD. Abdominal complaints, fever, general malaise and skin diseases were the main problems. Abdominal complaints were more often acquired in Asia, fever in sub-Saharan Africa and skin problems in South America. General malaise was not related to a specific travel destination. Abdominal complaints, fever and general malaise were more often caused by parasites, and skin problems by bacteria. Plasmodia were the most frequently encountered microbial cause. Malaria was found in 1 out of every 3 Dutch, and 9 out of every 10 Ghanaian patients with fever from Africa. CONCLUSION: The analysis of the database yielded useful information regarding patients with import diseases in the Netherlands and with respect to travellers to tropical areas.

Travel-related morbidity in travelers with insulin-dependent diabetes mellitus.

BACKGROUND: To assess whether there are clinically significant problems in patients with insulin-dependent diabetes mellitus (IDDM) traveling to tropical countries regarding metabolic dysregulations, infectious complications and general health problems. METHODS: A retrospective, descriptive cohort study by telephone interview of all IDDM patients who had received pretravel health advice at our travel clinic during a 12 month period. Data were collected on IDDM related problems: hypo-/hyperglycemic dysregulation, infectious complications, practical difficulties, exploring risk factors, as well as on general health problems. RESULTS: Of the 19 respondents, 13 (68%) reported any metabolic dysregulation, including all but one respondents with Type 1 diabetes. Fifty-five percent of Type 1 diabetics reported to have dysregulated more often than in the preceding period at home. Critical dysregulations occurred in 2 of the 19 study patients. Only 4 out of 11 (36%) type 1 IDDM patients increased frequency of blood glucose monitoring while traveling. Three travelers reported a febrile illness which resulted in hyperglycemic dysregulation. Five study patients experienced difficulties in the adjustment of their insulin dosage to the unfamiliar circumstances of traveling in the tropics. CONCLUSIONS: Metabolic dysregulation was a clinically significant problem, thus IDDM travelers to tropical destinations probably run extra health risks. Fever, easily acquired in the tropics, appeared to be an additional, serious health problem for this study population. As the number of diabetic travelers will increase, more research on the importance of risk factors possibly leading to dysregulation is necessary.

Morphine, morphine-3-glucuronide, morphine-6-glucuronide, and 6-monoacetylmorphine determined by means of atmospheric pressure chemical ionization-mass spectrometry-liquid chromatography in body fluids of heroin victims.

Morphine, morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), and 6-monoacetylmorphine (6-MAM) were isolated from body fluids using solid-phase extraction and determined by means of atmospheric pressure chemical ionization-mass spectrometry-liquid chromatography (APCI-LC-MS) in selected ion monitoring mode. The following ions were monitored: m/z 286 for morphine; m/z 286 and 462 for M3G and M6G; m/z 211, 268, and 328 for 6-MAM; and m/z 289 for morphine-d3 (internal standard). The recoveries ranged from 82 to 89% The limits of detection were as follows: 0.1 ng/mL (morphine), 0.5 ng/mL (6-MAM), and 1 ng/mL (M3G and M6G). The analytes were determined in samples taken from 21 heroin-overdose victims. Twenty-one blood samples, 11 cerebrospinal fluid (CSF) samples, 12 vitreous humor (VH) samples, and 6 urine samples were investigated. Blood concentrations (ng/mL) of morphine ranged from 8 to 1539, of M3G from 111 to 941, of M6G from 32 to 332, and of 6-MAM from 0 to 73. The levels of morphine were correlated with glucuronide values and with 6-MAM. The concentrations of morphine, M3G, and M6G in CSF were, as a rule, lower than in blood and lower in VH than in CSF. The concentrations of morphine and molar ratios of M6G-morphine in blood and CSF were correlated. Low ratios of M3G-morphine and M6G-morphine in blood of heroin-overdose victims indicated short survival time after drug intake.

Recombinant follicle-stimulating hormone (follitropin beta, Puregon) yields higher pregnancy rates in in vitro fertilization than urinary gonadotropins.

OBJECTIVE: To assess ongoing pregnancy rates (PRs) in IVF after treatment with recombinant FSH (follitropin beta, Puregon; NV Organon, Oss, The Netherlands) as compared with urinary gonadotropins. DESIGN: A combined analysis of three prospective, multicenter, randomized, comparative trials. SETTING: Twenty-five IVF centers in 13 countries. PATIENT(S): Six hundred ninety-seven infertile women receiving recombinant FSH and 463 women receiving hMG or urinary FSH and undergoing one cycle of controlled ovarian hyperstimulation and IVF-ET. INTERVENTION(S): A center-based and study-based analysis weighing the treatment differences in individual centers and studies, respectively. MAIN OUTCOME MEASURES(S): Pregnancy rate at least 12 weeks after ET per started cycle. RESULTS(S): In the center-based analysis, the ongoing PR was 22.9% for recombinant FSH and 17.9% for urinary gonadotropins. The 5.0% treatment difference (95% confidence interval [CI], 0.2% to 9.7%) was significant. When the results of the cryoprogram were included, the treatment difference increased to 6.4% (95% CI, 1.4% to 11.3%). Also in the study-based analysis, significantly higher PRs were seen after follitropin beta treatment. CONCLUSION(S): Follitropin beta (Puregon) used for controlled ovarian hyperstimulation in IVF yields significantly higher PRs compared with urinary gonadotropins.

Cryopreservation: the practicalities of evaluation.

An attempt was made to integrate data from cryopreserved embryos with those from fresh embryos to obtain a realistic assessment of the role of cryopreservation in assisted reproductive treatment. Principles were applied to previously published data from a large prospective randomized multicentre study comprising recombinant and urinary follicle stimulating hormone in in-vitro fertilization.

Determination of morphine and its 3- and 6-glucuronides, codeine, codeine-glucuronide and 6-monoacetylmorphine in body fluids by liquid chromatography atmospheric pressure chemical ionization mass spectrometry.

A selective assay of morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), morphine, codeine, codeine-6-glucuronide (C6G) and 6-monoacetylmorphine (6-MAM) based on liquid chromatography atmospheric pressure chemical ionization mass spectrometry (LC-APCI-MS) is described. The drugs were extracted from serum, autopsy blood, urine, cerebrospinal fluid or vitreous humor using C18 solid-phase extraction cartridges and subjected to LC-APCI-MS analysis. The separation was performed on an ODS column in acetonitrile-50 mM ammonium formate buffer, pH 3.0 (5:95), using a flow-rate gradient from 0.6 to 1.1 ml/min (total analysis time was 17 min). The quantitative analysis was done using deuterated analogues of each compound. Selected-ion monitoring detection was applied: m/z 286 (for morphine, M3G-aglycone and M6G-aglycone), 289 (for morphine-d3, M3G-d3-aglycone and M6G-d3-aglycone), 300 (for codeine and C6G-aglycone), 303 (for C6G-d3-aglycone), 306 (for codeine-d6), 328 (for 6-MAM), 334 (for 6-MAM-d6), 462 (for M3G and M6G), 465 (for M3G-d3 and M6G-d3), 476 (for C6G) and 479 (for C6G-d3). The limits of quantitation were: 1 microg/l for morphine, 2 microg/l for 6-MAM, 5 microg/l for M3G, M6G and codeine and 200 microg/I for C6G. The recovery ranged from 85 to 98% for each analyte. The method appeared very selective and may be used for the routine determination of opiates in body fluids of heroin abusers and patients treated with opiates.

Recombinant follicle stimulating hormone (rFSH; Puregon) in assisted reproduction: more oocytes, more pregnancies. Results from five comparative studies.

The clinical assessment of recombinant follicle stimulating hormone (rFSH; Puregon) in assisted reproduction technologies such as in-vitro fertilization (IVF) has probably been the most extensive clinical trial programme ever performed for the evaluation of a new fertility drug. It started with a pilot study to evaluate the potential of rFSH to stimulate the ovaries in the absence of luteinizing hormone (LH) using various gonadotrophin-releasing hormone (GnRH) agonists. After it became clear that FSH-induced steroidogenesis was not jeopardized even after severe pituitary suppression, comparisons between rFSH and urinary FSH or human menopausal gonadotrophins were made using different GnRH agonists or no agonists at all. In addition, the effects of the route of administration (s.c. or i.m.) were assessed. The study with the strongest statistical power to truly assess clinically relevant differences between rFSH and urinary FSH included approximately 1000 patient cycles. It indicated that after rFSH treatment, significantly more oocytes were retrieved, more embryos obtained and, as a result, more pregnancies achieved when the results of the cryoprogramme were included.

A prospective, randomized, assessor-blind, multicentre study comparing recombinant and urinary follicle stimulating hormone (Puregon versus Metrodin) in in-vitro fertilization.

Urinary follicle stimulating hormone (FSH) is being used for the treatment of human infertility. Recently, FSH manufactured by means of recombinant DNA technology with a much higher purity (> 99%) has become available. A prospective, randomized, assessor-blind, multicentre (n = 18) study was conducted in infertile women undergoing in-vitro fertilization comparing recombinant FSH (Org 32489, Puregon) and urinary FSH (Metrodin). Eligible subjects were randomized (recombinant versus urinary FSH = 3:2) and pretreated with buserelin for pituitary suppression. FSH was given until three or more follicles with a diameter of at least 17 mm were seen. After oocyte retrieval, fertilization routines were applied according to local procedures. No more than three embryos were replaced. In all, 585 subjects received recombinant FSH and 396 urinary FSH. Significantly more oocytes were retrieved after recombinant FSH treatment (mean adjusted for centre 10.84 versus 8.95, P < 0.0001). Ongoing pregnancy rates per attempt and transfer in the recombinant FSH group were 22.17 and 25.97% respectively, and in the urinary FSH group, 18.22 and 22.02% respectively (not significant). Ongoing pregnancy rates including pregnancies resulting from frozen-thawed embryo cycles were 25.7% for recombinant and 20.4% for urinary FSH (P = 0.05). Compared to urinary FSH, the total dose of FSH was significantly lower with recombinant FSH (2138 versus 2385 IU, P < 0.0001) in a significantly shorter treatment period (10.7 versus 11.3 days, P < 0.0001). No clinically relevant differences between recombinant and urinary FSH were seen with respect to safety variables. It is concluded that recombinant FSH (Puregon) is more effective than urinary FSH in inducing multifollicular development and achieving an ongoing pregnancy.

[Imported malaria: epidemiological, clinical and therapeutic data of 74 patients during 1 year in the Academic Medical Center, Amsterdam]. / Importmalaria: epidemiologische, klinische en therapeutische gegevens van 74 patiënten gedurende 1 jaar in het Academisch Medisch Centrum, Amsterdam.

OBJECTIVE: To gain insight into the changes concerning diagnosis and treatment of malaria since 1984. DESIGN: Retrospective. SETTING: University Medical Centre, Amsterdam. METHOD: From October 1991 to October 1992, 74 patients with malaria were diagnosed and treated. Country of origin, plasmodium strain involved, country of infection, interval between return to the Netherlands and onset of symptoms, prophylaxis and therapy, were recorded in every case. RESULTS: Of these patients 46 (62%) were of European origin; 28 were born in endemic malarial areas. Plasmodium falciparum was diagnosed in 49 of the 74 patients; 88% of these infections were acquired in subsaharan Africa, mainly West Africa. In falciparum malaria, the first symptoms were noticed I-30 days after returning home. P. vivax infections occurred up to 2 years after return. Five of the 49 patients developed severe complications; 2 died. Twenty-six (53%) of the 49 patients had not taken any chemoprophylaxis. The patients with falciparum malaria were treated with sulfadoxine-pyrimethamine or halofantrine, often combined with quinine; the cure rate was 90%. CONCLUSION: Quinine remains the mainstay in the treatment of complicated falciparum malaria, but is also often used in the initial treatment of uncomplicated malaria. Compliance in malaria prophylaxis still remains a problem.