[Non-motor Symptoms Questionnaire and Scale for Parkinson's disease. Cross-cultural adaptation into the German language]. / Non-motor Symptoms Questionnaire und Scale für das idiopathische Parkinson-Syndrom. Interkulturell adaptierte Versionen in deutscher Sprache.

Idiopathic Parkinson's disease (PD) is a multisytem degenerative disorder. In addition to motor symptoms such as akinesia, rigidity and tremor, various non-motor symptoms occur, which are still insufficiently diagnosed. Moreover, the frequently used scales and scores do not adequately detect these non-motor symptoms. The Non-motor Symptoms Questionnaire (NMSQuest) is an established self-completed patient questionnaire with 30 qualitative questions covering all important non-motor symptoms of PD. The Non-motor Symptoms Scale (NMSScale) is a grade rating scale for estimating the frequency and severity of non-motor symptoms in PD. Since there are only original English versions of both questionnaires available, self-translated versions were frequently used or the questionnaires were not used at all in native German patients. We used international guidelines for cross-cultural adaptation of questionnaires to provide standard versions of both non-motor symptoms questionnaires in the German language.

Autosomal-dominant GTPCH1-deficient DRD: clinical characteristics and long-term outcome of 34 patients.

BACKGROUND: An autosomal dominantly inherited defect in the GCH1 gene that encodes guanosine triphosphate cyclohydrolase 1 (GTPCH1) is the most common cause of dopa-responsive dystonia (DRD). A classic phenotype of young-onset lower-limb dystonia, diurnal fluctuations and excellent response to levodopa has been well recognised in association with GCH1 mutations, and rare atypical presentations have been reported. However, a number of clinical issues remain unresolved including phenotypic variability, long-term response to levodopa and associated non-motor symptoms, and there are limited data on long-term follow-up of genetically proven cases. METHODS: A detailed clinical evaluation of 34 patients (19 women, 15 men), with confirmed mutations in the GCH1 gene, is presented. RESULTS AND CONCLUSIONS: The classic phenotype was most frequent (n = 23), with female predominance (F:M = 16:7), and early onset (mean 4.5 years) with involvement of legs. However, a surprisingly large number of patients developed craniocervical dystonia, with spasmodic dysphonia being the predominant symptom in two subjects. A subset of patients, mainly men, presented with either a young-onset (mean 6.8 years) mild DRD variant not requiring treatment (n = 4), or with an adult-onset (mean 37 years) Parkinson disease-like phenotype (n = 4). Two siblings were severely affected with early hypotonia and delay in motor development, associated with compound heterozygous GCH1 gene mutations. The study also describes a number of supplementary features including restless-legs-like symptoms, influence of female sex hormones, predominance of tremor or parkinsonism in adult-onset cases, initial reverse reaction to levodopa, recurrent episodes of depressive disorder and specific levodopa-resistant symptoms (writer's cramp, dysphonia, truncal dystonia). Levodopa was used effectively and safely in 20 pregnancies, and did not cause any fetal abnormalities.

Motor system inhibition in dopa-responsive dystonia and its modulation by treatment.

Dopa-responsive dystonia (DRD) causes dystonia-parkinsonism, which is abolished by levodopa. The authors assessed short intracortical inhibition and facilitation, silent period, blink reflex recovery cycle, and reciprocal inhibition in seven patients with DRD on and off treatment. Short intracortical inhibition and blink reflex recovery cycle were reduced, but increased with treatment. Silent period was normal on and off treatment. Third phase of reciprocal inhibition was reduced on and off treatment. A discrete pattern of motor inhibitory dysfunction occurs in DRD.

Familial dopa-responsive cervical dystonia.

The authors present four cases from two unrelated families with young-onset predominant cervical dystonia with a dramatic sustained response to levodopa. Onset age was 12 years (range 9 to 15). Additional symptoms included postural hand tremor and laryngeal dystonia. Genetic testing for GTP cyclohydrolase I, tyrosine hydroxylase, and sepiapterin reductase was negative. These cases may represent new forms of dopa-responsive dystonia. Levodopa is advisable in all patients with young-onset cervical dystonia.

[Problems of randomized studies in complementary medicine demonstrated in a study on mistletoe treatment of patients with breast cancer]. / Problematik randomisierter Studien in der Komplementärmedizin dargestellt am Beispiel der Misteltherapie bei Patientinnen mit Mammakarzinom.

BACKGROUND: Prospective randomized studies on mistletoe therapy repeatedly demonstrated that there is a basic problem in the matter of enrolling the appropriate number of patients within a reasonable amount of time. Most studies have to face this problem. However, recent experience suggests that this problem is more pronounced in the case of mistletoe treatment of cancer patients. OBJECTIVE: Possibility of recruitment and randomization of breast cancer patients for a mistletoe study. PATIENTS: During a period of 28 months every patient was registered who was admitted to the Gynecological Hospital of the University of Heidelberg because of suspected cancer. RESULTS: Out of 1,922 patients who were operated on for breast tumor, 521 first met the inclusion and exclusion criteria. 154 out of these 521 patients agreed to take part in the study. After availability of the final results on tumor staging and the therapy plan for conventional treatment, 80 out of the 154 women had to be excluded from the study. From the remaining 74 patients (48%), however, only 29 (39%) would have agreed to take part in a randomized mistletoe study. CONCLUSIONS: This confirms our suspicion that the difficulties of enrollment and randomization in the case of mistletoe studies exceed those of studies conducted in conventional oncology. The reasons for this dramatic effect and the possibility of alternative study designs are discussed.

Individualized homeopathic therapy for male infertility.

This prospective observational pilot study investigated the effect of individualized homeopathy on male infertility based on sperm count, hormone values and general health. Forty-five subfertile men were treated with single homeopathic remedies for an average of 10.3 months. The drugs were prescribed on the basis of the overall symptomatic situation. The variables 'sperm density', 'percentage of sperm with good progressive motility' and 'density of sperm with good propulsive motility' improved significantly, especially in cases of oligoasthenozoospermia. The general health of patients improved significantly. The following factors emerged as positive predictors of therapy success: alcohol consumption below 30 g/day, non-smoking, the presence of less than five dental amalgam fillings, no exposure to noxious substances at the workplace and no previous inflammatory genital diseases. The factors stress, age above 36, high coffee consumption and long duration of unwanted childlessness did not have a negative impact on therapy outcome in this study. The rate of improvement in sperm count through homeopathic therapy is comparable to the improvement achieved by conventional therapy, so that individualized-homeopathic treatment may be considered a useful alternative to conventional treatment of subfertile men. For further investigation, a randomised, therapy-controlled clinical study with parallel group design would be useful (homeopathic therapy vs conventional andrological therapy).

[Presenile dementia in polycystic lipomembranous osteodysplasia]. / Präsenile Demenz bei polyzystischer lipomembranöser Osteodysplasie.

We present a 36-year-old woman with a 3-year history of cognitive decline followed by development of a small stepped gait and urinary and fecal incontinence. Workup revealed multiple bone cysts documented by X-ray and idiopathic hyperprolactinoma. An MRI confirmed the CT finding of massive bilateral basal ganglia calcification. This is the first case of polycystic lipomembranous osteodysplasia described in Germany. We conclude that patients with presenile dementia, psychosis, or early-onset Parkinsonism associated with basal ganglia calcification should undergo X-rays of hand and feet to rule out polycystic lipomembranous osteodysplasia.

Individualized homeopathic therapy for male infertility

This prospective observational pilot study investidated the effect of individualized homeopathy on male infertility based on sperm count, hormone values and general health. Forty-five subfertile men... (AU)

Service-based survey of dystonia in munich.

We performed a service-based epidemiological study of dystonia in Munich, Germany. Due to favourable referral and treatment patterns in the Munich area, we could provide confident data from dystonia patients seeking botulinum toxin treatment. A total of 230 patients were ascertained, of whom 188 had primary dystonia. Point prevalence ratios were estimated to be 10.1 (95% confidence interval 8.4-11.9) per 100,000 for focal and 0.3 (0.0-0.6) for generalised primary dystonia. The most common focal primary dystonias were cervical dystonia with 5.4 (4.2-6.7) and essential blepharospasm with 3.1 (2.1-4.1) per 100,000 followed by laryngeal dystonia (spasmodic dysphonia) with 1.0 (0.4-1.5) per 100,000.

[Complementary medicine and patient contentedness - a survey]. / Komplementärmedizinische Therapien und Patientenzufriedenheit - eine Befragungsstudie.

BACKGROUND: Increasing popularity and concomitant application of complementary and conventional methods by patients and doctors in Germany. INTENTION: To examine attitudes and patient contentedness. METHOD: Open, retrospective, postal survey in 1,582 female patients treated with complementary methods between 1991 and 1996, using a structured trilateral questionnaire. RESULTS: Of 1,582 mailed questionnaires 808 (51%) were evaluable. About 50% of the patients in the survey felt that the results of their complementary treatment were 'very successful' (22%) or 'rather successful' (24%). 80% of the patients were 'very' oder 'rather satisfied' with the complementary treatment. This positive assessment was also found in patients without treatment success. 50% indicated a significant change in health behavior, more than two thirds indicated a change in life-style attitude. More than 90% of the patients would be ready to pay for part of their treatment. Half of the surveyed women used natural remedies without knowledge of their family doctor. Because of a low response rate of 50%, there is the possibility of selection bias which makes a cautious interpretation of these results necessary. CONCLUSION: Because of the approaches and methods applied, complementary medicine is particularly suited to induce patient treatment satisfaction. Further studies are necessary to verify positive long-term health effects of complementary interventions and treatment.

Psychosocial characteristics of infertile couples: a study by the 'Heidelberg Fertility Consultation Service'.

BACKGROUND: The aim of the study was to identify differences in psychological characteristics between couples with fertility disorders, especially idiopathic infertility, and a representative sample. MATERIAL AND METHODS: A total of 564 couples was examined using psychological questionnaires pertaining to sociodemographic factors, motives for wanting a child, dimensions of life satisfaction and couple relationships, physical and psychic complaints, and a personality inventory. RESULTS: Specific to our sample was the high educational level of the couples, and the large number with idiopathic infertility (27% of all diagnoses). There were no remarkable differences in psychological variables between the infertile couples and a representative sample, except that the infertile women showed higher scores on the depression and anxiety scales. Couples with idiopathic infertility showed no remarkable differences in the questionnaire variables compared with couples with other medical diagnoses of infertility. CONCLUSIONS: A typical psychological profile for infertile couples could not be identified using standardized psychometric rating methods. This may be an effect of the specific characteristics of our sample. For some couples, the infertility crisis can be seen as a cumulative trauma, which indicates that these couples have a marked need for infertility counselling.

Nitromusk compounds in women with gynecological and endocrine dysfunction.

Musk xylene (MX), musk ketone (MK), musk ambrette, musk moskene, and musk tibetene are synthetic fragrances. Between 1994 and 1996 these five nitromusk compounds (NMCs) were tested in the blood of 152 women who consulted the Endocrinological Department of the University Hospital of Obstetrics and Gynecology, Heidelberg, Germany, because of gynecological problems. The testing was conducted by gas chromotography with mass-specific detector and mass spectrometry in a retrospective cross-sectional study. MX was detected in 95% and MK in 85% of the blood samples (>20 ng per liter whole blood). The median concentration of MX was 65.5 ng/L and the maximum level of MX was 1183 ng/L; the corresponding values for MK were respectively 55.5 and 518 ng/L. The other three NMCs were found in only a few patients or not at all. Significant associations between MX and MK concentrations were found in blood and different clinical parameters of the endocrine system. MX and MK may act centrally as a disrupter of the (supra-) hypothalamic-ovarian axis, which may result in a mild ovarian insufficiency. On the basis of our data, a reproductive toxicity and an endocrine effect of NMCs in women cannot be ruled out. Further experimental and clinical studies should be conducted.

[The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study]. / Die wirksamkeit des komplexmittels Phyto-Hypophyson L bei weiblicher, hormonell bedingter sterilität.

OBJECTIVE AND DESIGN: In a prospective, randomized, placebo-controlled, double-blind study, the effects of Phyto Hypophyson L (Steierl-Pharma GmbH, Herrsching, Germany), an Agnus castus-containing homeopathic preparation, were investigated in 67 women with fertility disorders. PATIENTS AND METHODS: 37 women with oligomenorrhea and 30 women with amenorrhea received 50 drops of Phyto Hypophyson L or placebo 3 times a day over 3 months or 3 cycles. OUTCOME MEASURE AND RESULTS: The outcome measure being spontaneous menstruation, improved concentration of progesterone in the luteal phase, shortening of the cycle, earlier ovulation, and pregnancy was achieved in 38 out of 67 women. It was achieved more often from women with oligomenorrhea in the Phyto Hypophyson L group compared to the placebo group (82 versus 45%, p = 0.021). However, there was no significant effect when viewing the whole group. The baby take-home rate during the therapy and 6 months after the end of the therapy showed a ratio of 6 : 2 (18.7 : 6.4%). This result was not significant. Furthermore, in the oligomenorrhea verum group we observed a significant increase of progesterone during the luteal phase compared to the oligomenorrhea placebo group. Only very few undesirable drug effects were observed. CONCLUSION: In women with sterility and oligomenorrhea, a treatment with Phyto Hypophyson L can be recommended over a period of 3-6 months.

Long-term exposure to wood-preserving chemicals containing pentachlorophenol and lindane is related to neurobehavioral performance in women.

BACKGROUND: The adverse neurobehavioral effects of long-term low exposure to wood-preserving chemicals (WPC) containing solvents, pentachlorophenol (PCP) and gamma-hexachlorocyclohexane (gamma-HCH; lindane), and other neurotoxicants were investigated in a neuropsychological group study. METHODS: Out of a population of 2,000 women visiting the outpatient practice of a gynecological department, a sample of 15 women aged 31-56 (mean 43) with long-term exposure to WPC verified by self-report, biological monitoring, and environmental samples was investigated. Fifteen controls aged 42 (31-56) years were drawn from the same population and pair-wise matched with respect to sex, age, education, and estimated intelligence. RESULTS: For the exposed group, mean PCP serum level was 43.6 micrograms/l and mean gamma-HCH blood level was 0.085 microgram/l. Mean duration of exposure was 10 (5-17) years. Intellectual functioning, attention, memory, and visuo-motor performance were examined, suggesting significant group differences in visual short-term memory (Benton Test; d = 1.5, P = .005), verbal memory (paired associate learning and Peterson paradigm; d = 4.3 and 1.6, P < .001), and an incidental learning task (d = 2.3; P = .001). Frequent subjective complaints as assessed by questionnaire were attenuated motivation (d = 1.7; P = .001), increased fatigue (d = 1.6; P = .001), distractibility (d = 1.0; P = .003), and depressed mood (d = 1.9; P = .004). PCP blood level was significantly associated with paired-associate learning, Benton Test, and reading/naming speed. CONCLUSIONS: Long-term low-dose exposure to WPC in the domestic environment could be related to subjective complaints (attention, mood, and motivation) and to subtle alterations of neurobehavioral performance (e.g., working memory) in women.

Chlorinated hydrocarbons in infertile women.

This study was conducted to investigate the hypothesis that chlorinated hydrocarbons (CHC) may affect fertility in women. In 489 infertile women, CHC levels were measured in whole blood. Different anamnestic and clinical parameters were obtained or investigated in order to detect possible associations to CHC concentrations. CHC levels were correlated to the women's age, body mass index, and nationality. Especially in women with uterine fibroids, endometriosis, miscarriages, persistent infertility, and hormonal disturbances, elevated concentrations of chlorinated hydrocarbons with long half-lives were observed. Chlorinated hydrocarbons may play a role in female infertility and may be an underlying factor in certain gynecological conditions.

Pentachlorophenol exposure in women with gynecological and endocrine dysfunction.

Exposure to wood preservatives containing pentachlorophenol (PCP) was detected in 65 women who consulted the Endocrinological Department of the University Hospital of Obstetrics and Gynecology, Heidelberg, Germany, because of gynecological problems. Blood PCP levels ranged from 20.7 to 133 microg per liter of serum. One hundred and six women with similar clinical conditions, corresponding age and body weight, no PCP exposure in history, and PCP levels below 20 microg per liter of serum served as control group. Significant associations were found between serum PCP concentrations, age, and different parameters of the endocrine system. PCP may act centrally on a hypothalamic or suprahypothalamic level which may result in mild ovarian and adrenal insufficiency. PCP may, therefore, play a role in the increasing infertility problem.

Chlorinated hydrocarbons in women with repeated miscarriages.

This study was conducted to investigate a possible etiological role of chlorinated hydrocarbons in the pathogenesis of repeated miscarriages. The blood levels of chlorinated hydrocarbons [CHCs: pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, the dichlorodiphenyltrichloroethane (DDT) group, polychlorinated biphenyls] were determined in 89 women with repeated miscarriages, who were referred to the University Hospital of Obstetrics and Gynecology of Heidelberg for investigations between 1989 and 1993, and compared to a previously investigated reference population. In more than 20% of the women, at least one of the CHC levels exceeded the reference range. CHC levels did not differ significantly between women with primary or secondary and early or late miscarriages; neither did they differ between women with hormonal or immunological disorders as causes of repeated miscarriages or women with idiopathic repeated miscarriages. No significant associations were detected between CHC levels and further conceptions or the outcome of further pregnancies. As significant associations were found between increasing CHC blood concentrations and immunological and hormonal changes, CHCs may have an impact on the pregnancy course in certain cases.

Heavy metals and fertility.

Heavy metals have been identified as factors affecting human fertility. This study was designed to investigate whether the urinary heavy metal excretion is associated with different factors of infertility. The urinary heavy metal excretion was determined in 501 infertile women after oral administration of the chelating agent 2,3-dimercaptopropane-1-sulfonic acid (DMPS). Furthermore, the influence of trace element and vitamin administration on metal excretion was investigated. Significant correlations were found between different heavy metals and clinical parameters (age, body mass index, nationality) as well as gynecological conditions (uterine fibroids, miscarriages, hormonal disorders). Diagnosis and reduction of an increased heavy metal body load improved the spontaneous conception chances of infertile women. The DMPS test was a useful and complementary diagnostic method. Adequate treatment provides successful alternatives to conventional hormonal therapy.

Impact of heavy metals on hormonal and immunological factors in women with repeated miscarriages.

In 111 women with repeated miscarriages, the urinary excretion of heavy metals was determined in a challenge test with the chelating agent 2,3-dimercaptopropane-1-sulphonic acid in addition to hormonal, chromosomal, immunological and uterine investigations. The heavy metal excretion was correlated to different immunological (natural killer cells, T cell subpopulations) and hormonal (progesterone, oestradiol, prolactin, thyroid stimulating hormone) parameters. We conclude that heavy metals seem to have a negative impact on ovarian as well as on pituitary function. The heavy metal-induced immunological changes may interfere with the physiological adaptation of the immune system to the state of pregnancy with the result of a miscarriage. The observed heavy metal-induced hormonal and immunological changes may be important factors in the pathogenesis of repeated miscarriages.

Activated autologous blood therapy in recurrent spontaneous abortion--results of a pilot study.

This study was undertaken to investigate the influence of activated autologous blood therapy on immunological parameters and on the clinical outcome in patients with recurrent spontaneous abortion. In a prospective trial, 36 women with recurrent spontaneous abortion were treated with intramuscular reinjections of extracorporally haemolysed and ultraviolet irradiated autologous blood. A comprehensive immunological investigation revealed significant changes in lymphocyte subpopulations, plasma complement levels, mitogen stimulation and immunoglobulin levels during the treatment period. No side-effects were reported by the patients. From June 1994 to November 1995, 22 intrauterine and one extrauterine pregnancies occurred, resulting in 19 (86%) live births, two (9%) spontaneous abortions and one (4%) artificial abortion compared with a 64% live birth rate in the historical control group. We conclude that activated autologous blood therapy has detectable effects on the immune system, and seems to be promising for further investigation concerning the treatment of idiopathic recurrent spontaneous abortion.