An open-label extension trial of galantamine in patients with probable vascular dementia and mixed dementia

BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are the most common types of dementia worldwide. Galantamine, an acetylcholinesterase inhibitor and allosteric nicotinic modulator, has shown broad clinical benefits in patients with mild to moderate dementia due to AD, probable VaD, or AD with cerebrovascular disease (CVD)-so-called mixed dementia. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety profiles of galantamine 24 mg/d in patients with VaD or AD with CVD over the longer term (>6 months). METHODS: This was an open-label extension of a 6-month double-blind study of galantamine. Patients who had been randomized to receive galantamine 24 mg/d or placebo in the double-blind phase were eligible to continue open-label treatment with galantamine 24 mg/d for 6 months. The primary efficacy end point was change in cognition, based on scores on the 11-item Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog/11). Secondary measures included changes in functional ability (as measured on the Disability Assessment for Dementia [DAD]) and behavior (as measured on the Neuropsychiatric Inventory [NPI]). Safety and tolerability were also monitored. RESULTS: Four hundred fifty-nine patients (240 men, 219 women; mean [SE] age, 75.2 [0.33] years) entered the open-label phase. Of these patients, 195 (42.5%) had a diagnosis of probable VaD, and 238 (51.9%) had a diagnosis of AD with CVD; the remainder had an inconclusive diagnosis. At month 12 of the study, improvements from baseline (the start of the double-blind phase) in ADAS-cog/11 scores were observed in both the group that received placebo during the double-blind phase (placebo/galantamine group: -0.3 point; 95% CI, -1.64 to 1.06) and the group that received galantamine during the double-blind phase (galantamine/galantamine group: -0.9 point; 95% CI, -1.73 to 0.03). Improvement in functional ability was demonstrated by statistically significant mean (SE) changes from baseline in DAD score in both the placebo/galantamine group (-7.4 [1.68]; P < or = 0.001) and the galantamine/galantamine group (-3.6 [1.33]; P < or = 0.01). There was no significant change in mean (SE) NPI scores in either group (0.2 [0.98] and 0.1 [0.70], respectively). Galantamine treatment was well tolerated. CONCLUSIONS: In these patients with VaD and AD with CVD, galantamine treatment produced similar sustained benefits in terms of maintenance of or improvement in cognition (ADAS-cog/11), functional ability (DAD), and behavior (NPI) after 12 months.     

Endoprosthetic surface replacement of the head of the humerus

The concept of an endoprosthetic surface replacement of the humeral head differs from that of stemmed endoprostheses. It is the replacement of the destroyed joint surface with reconstruction of the normal anatomy and minimal bone resection. The aim of this prospective study was to evaluate the short-term results of a newly developed cup arthroplasty (Durom-Cup) for the humeral head. In a prospective study, 39 patients with 46 Durom-Cups were evaluated preoperatively and every 3 months postoperatively. The average follow-up was 15 +/- 9 months. The group included 28 shoulders with rheumatoid arthritis, 15 joints with osteoarthritis, and 3 humeral head necroses. The Constant-score and SAS-function score were used. The Constant-score increased from 20.25 +/- 9.06 points preoperatively to 46.62 +/- 14.05 at 3 months, to 48.11 +/- 14.49 at 6 months, and to 55.25 +/- 11.6 at 9 months postoperatively. The Constant-score stayed at this level during further follow-up and was 55.81 +/- 16.31 at 12 months postoperatively. The best results were seen in the group of humeral head necroses with a Constant-score of 71.0 +/- 12.2 compared to 54.66 +/- 13.89 in the group of osteoarthritis and 56.78 +/- 13.33 in patients with rheumatoid arthritis at 12 months postoperatively. The results with the Durom-Cup are encouraging so that cup arthroplasty seems to be a good alternative to stemmed prostheses. The main advantages of the humeral head resurfacing are the bone-preserving fixation and the relatively simple surgical technique.     

Prevention of recurrent bacterial urinary tract infections by intravesical instillation of hyaluronic acid.

OBJECTIVE: To evaluate the efficacy of vesical instillation of hyaluronic acid against recurrent urinary tract infections. METHODS: Twenty women with a history of recurrent urinary tract infections each received 9 intravesical instillations of hyaluronic acid over 6 months. Their status was assessed prospectively over 47.6 weeks and compared with a retrospective review of patient charts covering 36.2+/-6.2 weeks. RESULTS: The total numbers of urinary tract infections were 67 before and 10 after treatment (p<0.001). Thirteen patients (65%) were free of recurrences until the end of the study. One had a recurrence during treatment, and 6 (30%) during follow-up. The number of infections per year per patient was reduced from 4.99+/-0.92 to 0.56+/-0.82 (p<0.001). In women with recurrences, time to recurrence was 178.3+/-25.5 days, compared with 76.7+/-24.6 days before treatment (p<0.001). CONCLUSION: Intravesical instillation of hyaluronic acid is effective in preventing recurrent urinary tract infections.     

Five-year-survey of invasive aspergillosis in a paediatric cancer centre. Epidemiology, management and long-term survival.

The epidemiology, management, and long-term survival of invasive aspergillosis was assessed in a prospective, 5-year observational study in 346 unselected paediatric cancer patients receiving dose-intensive chemotherapy for newly diagnosed or recurrent malignancies. Invasive aspergillosis occurred exclusively in the context of haematological malignancies, where it accounted for an incidence of 6.8% (n = 13 of 189). The lung was the primary site in 12 cases, and dissemination was present in three of those. Prior to diagnosis, the overwhelming majority of patients had been profoundly neutropenic for at least 14 days (n = 11 of 13) and were receiving systemic antifungal agents (n = 10 of 13). Clinical signs and symptoms were nonspecific but always included fever. All 11 patients who were diagnosed and treated during lifetime for a minimum of 10 days responded to either medical or combined medical and surgical treatment, and seven were cured (64%). Nevertheless, the overall long-term survival was merely 31% after a median follow-up of 5.68 years after diagnosis. Apart from refractory or recurrent cancer, the main obstacles to successful outcome were failure to diagnose IA during lifetime and bleeding complications in patients with established diagnosis. The frequency of invasive aspergillosis of greater than 15% in paediatric patients with acute myeloblastic leukaemia and recurrent leukaemias warrants the systematic investigation of preventive strategies in these highly vulnerable subgroups.     

PIXE analysis in different stages of psoriatic skin

Elemental distribution in psoriatic skin varies with the functional state of the keratinocytes, e.g., electrolytes influence cell metabolism and cell proliferation, and trace elements play a crucial role in a great number of enzymes. Elemental distribution in pinpoint lesions, old plaques, and uninvolved skin of 5 psoriatic patients and 4 healthy controls was studied by means of PIXE (proton-induced x-ray emission) analysis. This technique allows the simultaneous detection of elements with an atomic number greater than or equal to 14 along the epidermis and dermis in freeze-dried skin biopsies. Trace elements such as Fe, Cu, and Zn were determined down to a level of 1 ppm. In comparison with uninvolved skin, concentrations of P and K were elevated in psoriatic epidermis. In addition, increased levels of K were correlated with the stage of the psoriatic lesion. Zinc concentrations were significantly elevated in pinpoint lesions. The Zn concentration profiles within the epidermis and upper dermis showed high correlation to the P concentration profiles. Iron levels were decreased in old psoriatic plaques, whereas Cu concentrations varied considerably. In comparison to the controls, Cl concentrations were markedly decreased in the dermis of involved and uninvolved psoriatic skin, whereas epidermal Cl levels were unaffected. As high K levels prevent the Ca-induced differentiation of keratinocytes, high K levels may be the cause of the high cell differentiation in psoriatic skin. Elevated DNA- and RNA-polymerases might be the cause of elevated Zn levels in pinpoint lesions.     

Rate and time distribution of relapses in multibacillary leprosy

Of the 47,068 patients registered in the Polambakkam Leprosy Center between 1955 and 1982, we selected 1886 cases having shown bacteriological positivity at any time during this period, whatever their classifications at registration, and subsequently found bacteriologically negative. After an average follow-up period of 10 years, 243 relapses were observed, giving a crude relapse rate of 12.8 per person-years of observation and a cumulative probability of relapse of 18.9%. Relapse rates were found to be dependent on regularity during smear-positive and -negative periods; a regularity greater than 75% in the smear-positive period proved to be particularly important. The results show no evidence that relapses occurring after 3 years of negativity could be reinfections, and that the relapse rate was still affected by regularity 7 years after negativation. The median delay of relapses was found to be 4.4 years and was not affected by the regularity of treatment.     

Studies of brain stem function in infants with apnea syndrome using acoustically evoked brain stem potentials and heart rate variability

Twenty-four infants aged between 6 days and 7 months and 2 infants (16 m and 3 y) were subjects of combined brain-stem auditory evoked potential and heart rate variability measurements. Ten infants had a sleep apnea syndrome and one a Near miss sudden infant death syndrome; thirteen infants formed the control group. Seventeen of the twenty-six infants had normal, age-depended brain stem potentials. All infants of the apnea syndrome-group, which had no therapy, had increased I to V interpeak latencies outside of the one-sigma level, the six infants treated with aminophylline were within the normal range. Heart rate variability measurements revealed the following mean +/- standard deviation of the control group: 4.5% +/- 1.5%; of the apnea syndrome-group without therapy: 5.4% +/- 2.0%.     

Erbliche Ursachen und Risikofaktoren der Alzheimer-Krankheit

Der Gro?teil der F?lle von Alzheimer-Krankheit (AK) hat eine multifaktorielle ?tiologie. Das bedeutet, bisher nicht genauer bekannte Umwelteinflüsse und genetische Faktoren spielen bei der Entwicklung der Krankheit eine wesentliche Rolle. Von seiten der Genetik unterscheidet man bei der AK gegenw?rtig genetische Risikofaktroren und Mutationen. Der einzige bisher gesicherte genetische Risikofaktor ist das Allel ɛ4 des Gens für Apolipoprotein E auf Chromosom 19. Dieses Allel erh?ht die Wahrscheinlichkeit, an der AK zu erkranken, ist jedoch weder eine notwendige noch eine hinreichende Bedingung. Neben den h?ufigen Formen mit multifaktorieller ?tiologie kommen seltene Varianten der Krankheit vor, die nach Mendelschen Regeln vererbt werden. Bisher sind 3 Gene bekannt, die bei diesen seltenen, in der Regel früh auftretenden und autosomal dominant vererbten Formen mutiert sein k?nnen. Am h?ufigsten findet sich bei den autosomal-dominanten F?llen eine Mutation im Gen pr?senilin 1 auf Chromosom 14, seltener liegen Mutationen im Gen pr?senilin 2 auf Chromosom 1 und im Gen des Amyloid- Vorl?uferproteins auf Chromosom 21 vor. In diesem Beitrag geben wir eine übersicht über gegenw?rtige Befunde zur Genetik der AK und diskutieren die Bedeutung dieses Wissens für Patienten und deren Verwandte.