A cross-country review of strategies of the German development cooperation to strengthen human resources

Background  

Recent years have seen growing awareness of the importance of human resources for health in health systems and with it an intensifying of the international and national policies in place to steer a response. This paper looks at how governments and donors in five countries – Cameroon, Indonesia, Malawi, Rwanda and Tanzania – have translated such policies into action. More detailed information with regard to initiatives of German development cooperation brings additional depth to the range and entry doors of human resources for health initiatives from the perspective of donor cooperation.     

When should home mechanical ventilation be started in patients with different neuromuscular disorders?

BACKGROUND AND OBJECTIVES: Current international consensus guidelines identify a number of indicators for the establishment of home mechanical ventilation (HMV) for patients with neuromuscular diseases but do not address the possible clinical differences between each of the underlying disorders. This study assessed the differences in the physiological parameters of patients with neuromuscular disease commenced on HMV for the treatment of symptomatic chronic hypercapnic respiratory failure. METHODS: Patients commenced on HMV for the treatment of symptomatic chronic hypercapnic respiratory failure over a 9-year period were studied. Physiological parameters at the time of referral for HMV, impact of HMV and survival were analysed. RESULTS: The study recruited 66 patients with neuromuscular disease. Thirty-one patients had rapidly progressive disease: amyotrophic lateral sclerosis (ALS, n = 19), Duchenne muscular dystrophy (DMD, n = 12) and 35 patients had slowly progressive disease. Mean FVC at HMV onset was 40.3 +/- 17.5% predicted in all patients, but was >50% predicted in eight patients (12%). ALS patients were more hypercapnic (P = 0.03) and more hypoxaemic (P < 0.001), but had better FEV(1) at HMV onset, compared with DMD patients (P = 0.005). Maximal inspiratory mouth occlusion pressure (PImax) was 3.0 +/- 1.6 kPa in all patients, but values were lower compared with international consensus guidelines (5.88 kPa). Median survival in DMD, slowly progressive diseases and ALS was 132, 82 and 16 months, respectively (P < 0.001). CONCLUSIONS: Blood gases and lung function parameters vary substantially between patients with differing underlying neuromuscular disorders when commenced on HMV for the treatment of symptomatic chronic hypercapnic respiratory failure. In contrast, PImax is equally reduced in all patients and more severely reduced compared with consensus guidelines. The specific underlying neuromuscular disease has a major impact on outcome. Specific selection criteria are needed for the use of HMV in the different diseases that comprise neuromuscular disorders.     

Prognostic value of mouth occlusion pressure in patients with chronic ventilatory failure

BACKGROUND: Mouth occlusion pressure measurement is widely used for assessment of respiratory muscle function, particularly in patients with respiratory failure. However, its predictive value for long-term survival remains largely unexplored. METHODS: In 464 patients with chronic hypercapnic respiratory failure (CHRF) due to various underlying disorders and receiving non-invasive ventilation (NIV), maximal inspiratory mouth pressure (PI(max)), mouth occlusion pressure at 100 ms during quiet breathing (P(0.1)) and the ratio P(0.1)/PI(max) were assessed prior to and after treatment including NIV. Baseline data and changes at follow-up were used to evaluate their predictive value for long-term survival. RESULTS: Overall, median (quartiles) P(0.1) was 177.0 (109.2;287.0) %pred, PI(max) 35.0 (24.0;47.0) %pred, and P(0.1)/PI(max) 564.0 (275.7;1082.3) %pred. In multivariate analyses, P(0.1) was related to airflow obstruction, lung hyperinflation, haemoglobin (Hb) and leukocytes, and PI(max) to airflow obstruction and hyperinflation (p<0.05 each). All-cause mortality during follow-up (median 31.6 months) was 31.5%. Survival was associated with age, body-mass index (BMI), lung function, leukocytes, Hb, PI(max), P(0.1) and P(0.1)/PI(max) (p<0.01 each, univariate). Among these multivariate Cox regression identified age, BMI, FEV(1), leukocytes and P(0.1)/PI(max) as independent predictors (p<0.05 each). Furthermore, the decrease of P(0.1)/PI(max) at follow-up was associated with improved survival in patients with high baseline P(0.1)/PI(max) (>50th or 75th percentile; p<0.05). CONCLUSIONS: In patients with CHRF and current NIV therapy, P(0.1)/PI(max) was an independent predictor of long-term survival, in addition to previously established risk factors. Moreover, a decrease in P(0.1)/PI(max) after treatment including NIV was associated with an improved survival in patients with high baseline P(0.1)/PI(max) values.     

Is alpha-synuclein pathology a target for treatment of neurodegenerative disorders?

Alpha-synuclein is the main constituent of intra-neuronal Lewy bodies, which are characteristic of Parkinson's disease, but aggregates are also found as axonal inclusions. Alpha-synuclein pathology is found together with beta-amyloid plaques and neurofibrillary tangles in Alzheimer's disease and other neurodegenerative disorders. In spite of the fact that the biological function of this synaptic protein is not known so far, there is an increasing body of evidence indicating an interaction with amyloid peptides, but also with tau-hyperphosphorylation. A high proportion of alpha-synuclein purified from Lewy bodies is phosphorylated on Ser129. There are still different opinions about the toxicity of the alpha-synuclein aggregates. Alpha-synuclein seems to influence different intracellular signaling pathways which are in direct relation to defense mechanisms against reactive oxygen species or apoptosis. It is obvious that overproduction of alpha-synuclein, but also different mutations, are inducing the formation of aggregates. Because of the possible link to neurodegeneration, different attempts have been made to counteract alpha-synuclein aggregation. An interesting approach is utilizing beta-synuclein, a biological factor, with an aminoacid sequence closely resembling that of alpha-synuclein. Proof of concept studies indicated that overexpression of beta-synuclein is able to counteract alpha-synuclein aggregation in a transgenic animal model, while also ameliorating functional deficits. As an alternative approach, the use of low molecular beta-synuclein N-terminal peptide derivatives has been considered. Several of these structures displayed clear neuroprotective activities in tissue culture models of neurodegeneration, including beta-amyloid toxicity. Therefore it has been speculated that these compounds might have a broad therapeutic efficacy in different neurodegenerative disorders. A proof of concept study in hAPP-transgenic animals resulted in a highly significant decrease in beta-amyloid plaque load, an increase in soluble beta-amyloid peptides and a decrease in insoluble forms. There was also significant improvement of cognitive deficits in this APP transgenic mouse model following intranasal but also peripheral treatment with three of these compounds. From this study it is concluded that the observed effects of the peptides derived from beta-synuclein N-terminus are depending on both, a direct interaction with aggregation of proteins, but also with stimulation of anti-apoptotic and anti-oxidative intracellular signaling pathways.     

Effects of Cerebrolysin on amyloid-beta deposition in a transgenic model of Alzheimer's disease

We investigated the potential mechanisms through which Cerebrolysin, a neuroprotective noothropic agent, might affect Alzheimer's disease pathology. Transgenic (tg) mice expressing mutant human (h) amyloid precursor protein 751 (APP751) cDNA under the Thy-1 promoter (mThy1-hAPP751) were treated for four weeks with this compound and analyzed by confocal microscopy to asses its effects on amyloid plaque formation and neurodegeneration. In this model, amyloid plaques in the brain are found much earlier (beginning at 3 months) than in other tg models. Quantitative computer-aided analysis with anti-amyloid-beta protein (A beta) antibodies, revealed that Cerebrolysin significantly reduced the amyloid burden in the frontal cortex of 5-month-old mice. Furthermore, Cerebrolysin treatment reduced the levels of A beta(1-42). This was accompanied by amelioration of the synaptic alterations in the frontal cortex of mThy1-hAPP751 tg mice. In conclusion, the present study supports the possibility that Cerebrolysin might have neuroprotective effects by decreasing the production of A beta(1-42) and reducing amyloid deposition.     

High-grade metachronous osteosarcoma. A case report over a 23-year period

This is a case report on the remarkable 23-year course of a metachronous osteogenic sarcoma in a 31-year-old man. Histology invariably showed the features of a high-grade osteogenic sarcoma with predominantly chondroblastic cells. During the observed period the patient developed nine osseous metastases. The quiescent clinical course of some metastases was in sharp contrast to the histological pattern. The patient finally died from symptoms of increasing cervical spinal cord compression without ever developing lung metastases.     

Arterial blood supply of the maxillary sinus.

Knowledge of the arterial supply of the maxillary sinus region is essential for surgical treatment in this area (e.g., implantation of grafting materials, repair of injuries, sinus floor elevation). The goal of this study was to describe the arterial architecture of the maxillary sinus region in respect to sinus lift procedures. In 18 unfixed human cadavers, the arterial vessels of the head were injected with a mixture of latex and barium sulfate. Afterward, the arteries entering the maxilla were prepared. The number and calibers as well as anastomoses were carefully documented. In addition, we measured the distance between the alveolar ridge and the lower main branches. The arterial supply of the maxilla originated from the posterior superior alveolar artery as well as from the infraorbital artery. In all specimens we found an intraosseous anastomosis between these two vessels. The oral mucosa in the area of interest is supplied by the posterior superior alveolar artery and the infraorbital artery, and an extraosseous anastomosis was found in 44% of our cases. The two anastomoses build up a double arterial arcade, supplying the lateral wall of the antrum and parts of the alveolar process.