Macrophage colony-stimulating factor (M-CSF) in plasma and CSF of patients with mild cognitive impairment and Alzheimer's disease.

Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that activates microglial cells, involved in phagocytosis of amyloid-beta (Abeta) in the brain. In the present study, we found in 50 patients with Alzheimer's disease (AD) significantly increased M-CSF plasma levels compared to 22 patients with mild cognitive impairment (MCI) and 35 age-matched healthy controls. In contrast, MCI patients showed significantly decreased M-CSF levels in cerebrospinal fluid (CSF) compared to AD patients and 20 patients with other non-inflammatory neurological disease (NIND). Analyzing the impact of Beta-amyloid 1-42 (Abeta 1-42), tau protein and M-CSF for differentiation between the groups we found that M-CSF, but not Abeta 1-42 and tau-protein is a significant parameter for distinction between MCI and NIND patients with 68.8% sensitivity and 75.0% specificity. M-CSF CSF levels < or = 357.8 pg/ml yielded 73.7% sensitivity and 75.0% specificity for diagnosing MCI patients in comparison with control subjects. In conclusion, our data indicate that M-CSF in CSF could be a putative biomarker for MCI.

[Premature immunosenescence: a pathogenetic factor in Alzheimer's disease?]. / Vorzeitige Immunalterung: ein pathogenetischer Faktor bei Alzheimer-Demenz?

While the familial form of Alzheimer's disease (AD) is known to be entirely inherited, the etiopathogenesis of the most common late-onset form of Alzheimer's disease still remains unresolved. Among various factors, aging seems to be one of the most prominent risk factors. Moreover, a large body of evidence points to the contribution of immunological alterations in AD. The involvement of inflammatory factors in the etiopathology has been widely discussed. Moreover, an impairment of certain immune responses in AD has been observed. Presumably, premature immunosenescence may lead to inadequate immune reactions. Against this background, the development of different immunotherapeutic strategies seems to be a promising challenge for future research.

Stage-dependent BDNF serum concentrations in Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive decline and loss of neurons in specific brain regions. Recent findings have suggested an involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of AD. BDNF is an endogenous protein involved in the maintenance of neuronal function, synaptic plasticity and structural integrity in the adult brain. To our knowledge, the present pilot study assessed for the first time BDNF serum and CSF concentrations in 30 patients with different stages of AD in comparison to 10 age-matched non-demendet controls. AD patients were divided in two groups according to their MMSE score: Group 1 (n = 15) in early stages with MMSE scores >or=21 (mean of 25.5) and Group 2 (n = 15) with more severe stages of dementia with MMSE scores <21 (mean of 13.3). As main results, we found in patients with early stages of probable AD significantly increased BDNF serum concentrations as compared to more severe stages of AD (p < 0.0001) and age-matched healthy controls (p = 0.028). BDNF serum values in all AD patients correlated significantly with MMSE scores (r = 0.486; p < 0.0001). Levels of BDNF were below the detection limit of the assay in unconcentrated CSF samples of AD patients and non-demendet controls.In summary, BDNF serum values are increased in early stages of Alzheimer's disease, which may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of beta-amyloid (Abeta). During the course of the disease, BDNF is decreasing, which correlates with the severity of dementia. The decrease of BDNF may constitute a lack of trophic support with an increase of Abeta accumulation and thus contribute to progressive degeneration of specific regions in the AD-affected brain. BDNF should be further evaluated as a candidate marker for clinical diagnosis and therapeutic monitoring in Alzheimer's disease.

The diagnostic value of examination of sternal marrow (continued from Vol. II, No. 2)

The first study on bone marrow in the Philippines is presentedThe total cell count and the differential bone marrow picture are discussed. The bone marrow cell count is about 100,000 per cm. for the normal Filipino adult. The total cell count includes nucleated red cells and all white cells. The relation between erythroblasts and white cells in adults is 10-20:100: in children it is higher, in the first year of life 30-40:10, then it slowly decreases with advance in ageThe bone marrow biopsy is indispensable for the diagnosis of all blood diseases. In pernicious anemia the diagnosis is based on the presence of megaloblasts in the bone marrow. The effect of liver therapy can be observed by the disappearance of the megaloblasts. All regenerative anemias are characterized by a severe erythropoetic activity of the bone marrow, and so the ratio of erythroblasts to white cells must be high. Post-infectious anemias are characterized by a shift to the left do not suggest splenectomy. The third possibility, the megakaryopenic purpura, is a clear contraindication for splenectomyIn infectious diseases such as septico-pyemias, pneumonias, etc. there are remarkable changes in the bone marrow. However,these changes are only of pathologic interest and we would not suggest sternal punctures in these cases because they do not help in the diagnosis. Similarly in Hogdkins disease there are no characteristic changes in the bone marrowBone marrow changes in malign new-growth are studied. There is sometimes a eosinophilia, but this is not constant. Both erythropoetic and hypoplastic responses of the bone marrow are observed. In old age the cell count and erythropoetic activity seem to be decreased. X-ray treatment of new-growth has a very important effect in the bone marrow, producing low cell counts and poor erythropoetic activity. (Summary)

On malnutrition in childhood in the Philippines: IV. Malnutrition and iron deficiency anemia

Sixty-nine cases of malnutrition in 1956, admitted to the Department of Pediatrics of the Philippine General Hospital, have been examined for iron-deficiency anemia. There is, however, no relation between the anemia, malnutrition, impairment of increase in weight and growth, and dysproteinemia in the observed cases. The frequency of iron deficiency anemia is due to the fact that diets poor in protein are, likewise, poor in iron. However, protein deficiency may also play an important role in the development or iron deficiency anemia. Therefore, the newest progress in the knowledge of protein malnutrition, the imbalance of amino acids in certain proteins and the importance of canning of food, especially milk, are discussed as factors contributing to iron deficiency anemia. Iron deficiency, if present in malnutrition, aggravates the prognosis of malnutrition considerably. (Summary and Conclusion)

On malnutrition in childhood in the Philippines III. pathological findings in malnutrition in the Philippines

The histologic changes in different organs of 32 Filipino infants who died in a state of severe malnutrition were studied. Changes in the intestines, liver and pancreas which have already been described were confirmed. A significant finding was that hemorrhage had occurred in some organs in a total of 29 (91%) of the cases. The frequency distribution of hemorrhages in various organs is as follows: adrenals (medulla) - 26 (81%); bone marrow - 16 (50%); kidneys - 13 (41%); lungs - 13 (41%); liver - 7 (22%); pituitary gland - 5 (16%); heart muscle, thymus, and lymph nodes - 2 cases each (6%); and testes - 1 (3%). The brain was not studied in most of these casesThese findings are interpreted to indicate a general hemorrhagic tendency among cases of severe malnutrition in Filipino infants; furthermore, massive hemorrhages in the adrenal medulla is apparently the cause of death in a high percentage of these cases. The underlying mechanism of this hemorrhagic tendency has yet to be clarifiedHyperemia found in different organs suggests impairment of cardiac function which cannot be detected by electrocardiography as the entire heart muscle seems to be involved. Histologically evident infections seem to play only a minor role in malnutrition; however, complete bacteriologic study of malnutrition cases is strongly indicated. Degenerative changes in the kidney with discharge of a hyaline material into the tubules was observed in about one-half of the cases. (Summary and Conclusions)

On plasma phosphatase levels in pregnancy in the Philippines

During pregnancy, the alkaline plasma phosphatase should increase. In the Philippines, in spite of a definite tendency to increasing values with the progress of pregnancy, the observed levels are still below normal due to the abnormally low initial values. Low plasma phosphatase levels may have an effect on the ossification processes of the fetus. As consequence of the low phosphatase levels of the mothers, newborn infants have a very low plasma phosphatase level. The low levels are most probably due to unbalanced diet of the mother, if we like to avoid the term "malnutrition". We found likewise low levels in pregnant women and in some adult of both sexes. Low plasma phosphatase levels seem to be the rule in Filipinos of any age. (Summary and Conclusion)

Lymphosarcoma cell leukemia (Leukosarcoma sternberg)

A case of lymphosarcoma cell leukemia in a 52-year-old male is presented. The diagnosis was established by the presence of lymphosarcoma cells in the peripheral blood and in the bone marrow intra vitam. Anatomic and histologic findings, microphotograms of different organ sections and of the blood and bone marrow are presented. (Summary and Conclusion)

Is there pernicious anemia in the tropics

Two cases of pernicious anemia are described, both occuring in elderly Filipinos. Symptomatology , differential diagnosis, and blood and bone marrow findings are discussed. As both cases show macrocytosis, hyperchromia, megalocytosis and megaloblastosis marked anisocytosis, leucopenia, granulocytopenia, "shift to the right" of the neutrophiles and hypersegmentation of the segmented cells; as there is absence of free hydrochloric acid in both cases; as the therapeutic test in both is positive; and finally as the anemia is "idiopathic" in the sense that any secondary anemia can be ruled out, the cases fulfill all requirements for the diagnosis of pernicious anemia. (Summary and Conclusion)

Iron deficiency in the Philippines

Iron deficiency is very widespread in the first years of life in the Philippines. Plasma iron determinations show that the iron levels are much lower than those found in the Western countries. The clinical importance of iron deficiency is discussed. The low iron level in the plasma is, in the overwhelming majority of the cases, a part of malnutrition due to multiple deficiencies. (Summary and Conclusions)

On athyrosis (creatinism in the Philippines)

A case of creatinism (athyrosis) at the age of 14 months is discussed, especially the radiologic findings. it is more than probable that the metabolic deficiency started during intrauterine life, in spite of the normal thyroid function of the mother. This is the first case with a series of characteristic bone changes described so far in the Philippines. (Summary and Conclusions)

Infectious mononucleosis

A brief history, symptomatology, diagnosis, prognosis, and treatment of infectious mononucleosis is given; and the six cases we observed for a short space of time are reported. A case of infecious lymphocytosis is also reported, to show its distinguishing characteristics from infectious mononucleosis which it closely resembles. (Summary)

Iron deficiency anemia in Bataan province

Iron deficiency anemia is rampant in the Philippines, especially in the province of Bataan, due to lack of sufficient iron intake with the food. The diet of all the cases examined was deficient in iron; hence the finding of hypochromia in majority of the casesThe best method of eradicating iron-deficiency anemia is the administration of inorganic iron salts with the daily food. The daily intake of iron ought to be around 12 milligram for adult males and 25 to 50 per cent more for females. As there is some iron in the food, not the whole amount has to be administered. At any rate, even the whole amount, administered as ferrous sulfate would not change the taste of table, salt, to which it ought to be addedAlthough protein deficiency may also cause anemia, protein deficiency does not seem to be important in the Philippines. Protein deficiency causes macrocytic anemia, which may be hypochromic if there is simultaneous iron deficiency anemia; hyperchromic, if there is none. All in all, only four cases had marked macrocytosis. In these cases, protein deficiency may be considered a possibility. If the blood proteins had been determined, and if hypoproteinemia had been found, the evidence of protein deficiency would have been clearThe problem of macrocytic anemia in the Philippines will be discussed in a separate paper. I hope to receive soon the equipment for determining iron and copper levels in the blood serum. Then the early stage of iron-deficiency anemia, characterized by low serum iron, level, will be diagnosed before symptoms of anemia appearFor the time being, it could be accepted as evident that iron deficiency anemia is very widespread in the Philippines. Iron deficiency causes decreased resistance, and decreased resistance is followed by secondary infections. In order to improve health conditions, besides beriberi, even iron deficiency anemia has to be eliminated. Iron deficiency anemia seems to be even more frequent than beriberi as 80 per cent of all children below the age of five years and of all pregnant women are suffering from iron deficiency, while beri-beri in these age groups is definitely less frequent. The prevention has been discussed. (Summary and Conclusion)

On the classical type of chronic familial hemolytic anemia in the Philippines

It has been claimed that the classical or Minkowski-Chauffard type of chronic familial hemolytic anemia does not exist among Filipinos. This type is presented in this paper in a father and a daughter. Both recovered completely after splenectomy. Spherocytosis, increased fragility of the red cells and the typical histological findings in the spleen as the most important differential diagnostic features, are discussed. The differential diagnosis of the Stransky-Regala-type and malaria are likewise discussed. (Summary and Conclusions)

On cancer in childhood in the Philippines

Statistics on cancer is childhood, as observed at the Philippine General Hospital, are offered. The most important forms of cancer in childhood, including leukemia, are discussed; and some diagnostic hints are givenThe report deals with 50 cases of different malignant newgrowths, and including 45 cases of leukemia in childhood. (Summary and conclusions)

Agnogenic lymphoid metaplasia of the spleen

A condition of lymphoid metaplasia of the spleen, accompanied by symptoms of hypersplenism arising from an unknown stimulus, is reported. As far as is known, this is the first reported case. The value of splenic and bone marrow puncture in diagnosing splenomegalies of obscure nature is pointed outAnother case was observed as early as the Japanese occupation. But as the chart was destroyed by fire, all reports were lost.(Summary)

Noma in the Philippines

Noma, or stomatitis gangrenosa, cancrum oris, is not yet rare in the Philippines, as it has become in America and Europe. Forty-two cases of noma are describedNoma is a secondary disease due to bad general condition brought about by diseases such as ileocolitis, measles, tuberculosis, sometimes pertussis and bronchopneumoniaThe mortality of noma is excessively high. It is probable that noma occurs in connection with deficiency diseasesIt is a disease of the preschool age in the PhilippinesThe treatment must be a treatment of the primary diseaseImprovement of nutrition and public welfare will put an end to the disease in the near future.(Summary)

On tuberculosis of the bones in the Philippines

A case of tuberculosis of the bones was described in a girl not yet three years old. While the findings in the right hand (first metacarpal bone) and first phalanx of the index finger are characteristic, there are changes characterized by massive periostitis of the right humerus and left ulna which as far as we know have not yet bee described in the literature. (Summary and conclusions)

The efficacy of oral electrolyte fluid in the therapy of diarrhea

The administration of an oral electrolyte solution for the provision of maintenance fluid requirement in comparable to strict intravenous fluid therapy in the management of children with acute diarrhea. This efficacy is established on definite clinical and chemical criteria set forth for this studyOral electrolyte solution has the added advantage of being more convenient to administer as it requires less nursing care, and more applicable in remote areas where facilities and equipments for intravenous therapy may be scarce, if not absent. (Summary and conclusion)

On a peculiar type of achondroplasia (osteochondrodysplasia congenita)

A newborn female with all the manifestations of osteochondrodystrophy and with post mortem findings is presented. The case is characterized by extremely short and bowed shafts of all long bones, like those observed on Moqruio-Brailsfords diseases. Symptoms and radiologic and histologic changes are described. This case seems to be the first of this kind with observation of already well developed bony and cartilaginous changes in the newborn. There is, however, no history of familial incidence in our case. (Summary and Conclusions)