Subcortical angiopathic encephalopathy in a German kindred suggests an autosomal dominant disorder distinct from CADASIL.

A cerebral arteriopathy with subcortical infarcts and leukoencephalopathy is described with a pedigree suggestive for an autosomal dominant condition. In contrast to the vasculopathy designated with the acronym CADASIL, no deposits of granular osmiophilic material were detected in the vasculature and no point mutations in the NOTCH 3 gene were found. The disease occurred in a family living near Hamburg, Germany, and affected 11 women and 11 men over the last six generations. Onset of the disease was between the age of 12 and 50. Clinical symptoms included gait disturbances, dysarthria, sensomotoric deficits and a progressive dementia. Migraine-like complaints and epileptic seizures were observed in one case each. Cranial computer tomography and magnetic resonance imaging scans showed large confluent areas with decreased density in the white matter and small necroses in the brain stem, the basal ganglia and the white matter. A correlation with factors predisposing for vascular diseases could not be demonstrated. In five cases an autopsy was performed which disclosed an angiopathy affecting predominantly the penetrating arteries with consecutive lacunar infarcts, diffuse demyelination and rarefication of the subcortical white matter and degeneration of the pyramidal tracts. Histologically, the vessels showed concentric and excentric intimal proliferation, an elastosis and hyalinosis, splitting of the lamina elastica interna and a degeneration of the tunica muscularis. Electron microscopy revealed fragmentation and thickening of the basal lamina but electron-dense granules characteristic for CADASIL were not detected.

Randomized comparison of G-CSF + GM-CSF vs G-CSF alone for mobilization of peripheral blood stem cells: effects on hematopoietic recovery after high-dose chemotherapy.

Fifty patients with either lymphoid or selected solid tumor malignancies were apheresed an identical number of times for PBSC collection after being randomized to receive either G-CSF 10 microg/kg/day alone (arm I), or G-CSF at the same dose with GM-CSF 5 microg/kg/day (arm II). Growth factor(s) was/were given as the stem cell mobilizing agent for 5 days before the start of PBSC collection, and were continued throughout the 4 days of apheresis. Aspiration and cryopreservation of autologous bone marrow occurred on day 3 or 4 of growth factor(s). Thirty-one of 50 patients received one cycle only at time of evaluation, and 19 patients received two cycles of HDCT, each supported with PBSC with or without autologous bone marrow. No patients received growth factors post-autologous stem cell transplant, unless the absolute neutrophils count (ANC) failed to recover to > or = 100/microl by day +18 post-transplant. The median number of days to recovery of ANC to 100/microl, 500/microl and 1000/microl, and of platelet counts to 20000/microl, 50000/microl and 100000/microl after either cycle 1 or cycle 2 of HDCT and the number of febrile days and platelet and PRBC transfusion requirements was not significantly different between the two arms of the study. The duration of hospitalization was similar between study arms for cycle 1 of HDCT, but was 3.5 days less with arm II compared to arm I (P = 0.0248) for cycle 2 of HDCT. The bone marrow buffy coat and PBSC product mononuclear cell count (x 10(8)/kg) and CD34+ cell count (x 10(6)/kg) collected by each method of stem cell mobilization was not significantly different. There is questionable clinical benefit with PBSC products mobilized with the combination of G-CSF and GM-CSF vs G-CSF alone. Perhaps different dosages, schedules, or other growth factor combinations with G-CSF might enhance these differences.

Antifungal effects of yeast-derived rhu-GM-CSF in patients receiving high-dose chemotherapy given with or without autologous stem cell transplantation: a retrospective analysis.

Systemic fungal infections (SFI) in patients receiving high-dose chemotherapy (HDC) are a frequent cause of morbidity and mortality. Preclinical studies have reported augmented antifungal activity of monocytes, macrophage cells, and neutrophils exposed to certain colony-stimulating factors (CSF), including GM-CSF. We conducted a retrospective descriptive epidemiologic study to examine the characteristics of 145 consecutive patients receiving HDC administered with or without autologous stem cell transplantation (ASCT) and who subsequently received either GM-CSF and G-CSF, G-CSF alone, GM-CSF +/- IL-3 or no CSF. The analysis of this patient population sought to define the incidence of SFI and its relationship to therapy with monocyte/macrophage-stimulating (MMS group) cytokines (GM-CSF and G-CSF; GM-CSF +/- IL-3) or to cytokines which do not result in monocyte/macrophage stimulation (NMMS group, G-CSF alone or no CSF). Risk factors for the development of SFI were balanced between the MMS (n = 70) and NMMS (n = 75) groups. Two patients (2.9%) in the MMS and nine patients (12%) in the NMMS groups developed SFI. The risk ratio for developing SFI in the NMMS group compared to the MMS group was 4.20 (P = 0.023). This relationship was confounded, however, by the diagnosis of hematologic tumor or solid tumor (RR = 3.15, P = 0.082). SFI was the primary cause or major contributing factor in five of the 10 total deaths in our study population. Four SFI-related deaths occurred in the NMMS group and one SFI-related death occurred in the MMS group. Our data suggest a protective role for GM-CSF, IL-3 or other MMS cytokines in preventing SFI in patients receiving HDC. This should be further investigated as a potential complementary approach to conventional strategies in antifungal prophylaxis for patients receiving HDC.

The Demers atrial catheter: experience with a single-lumen silicone catheter as short- and long-term access for hemodialysis.

The Demers catheter is a silicone atrial catheter with a dacron cuff used as short- and long-term access for hemodialysis. It was implanted in 316 patients between January 1, 1987 through May 31, 1991. Data on these implantations were retrospectively analyzed and are reported here. Follow-up and analysis was possible in 404 of 417 Demers catheter implantations. The mean age of patients in this study was 61 years. For short-term use (< 91 days) 153 catheters were implanted in 135 patients, for long-term use (> 90 days) 251 catheters in 181 patients. The median life span of all 404 catheters was 87 days. The median life span for long-term use was 150 days (2-1302) per catheter and 220 days (92-1717) per patient. Catheter malfunction (arterial blood flow < 200 ml) was encountered every 876 days in the running time of the catheter. Twenty percent (n = 80) of the catheters were explanted because of complications. These included 42 cases of catheter malfunction and 22 cases of infection.

Randomized study of growth factors post-peripheral-blood stem-cell transplant: neutrophil recovery is improved with modest clinical benefit.

PURPOSE: To evaluate the clinical value of growth factors (GFs) with peripheral-blood stem cells (PBSC) collected following mobilization with GFs, we randomized patients to receive or not to receive GFs following transplant. PATIENTS AND METHODS: Thirty-seven patients were apheresed after receiving the combination of granulocyte colony-stimulating factor (G-CSF) with granulocyte-macrophage colony-stimulating factor (GM-CSF) at doses of 10 micrograms/kg/d and 5 micrograms/kg/d, respectively, for 6 days before apheresis and during a median of 4 days of collections. One day after the infusion of autologous marrow and PBSC, patients were randomly assigned to receive no GFs or a combination of G-CSF (7.5 micrograms/kg/d) and GM-CSF (2.5 micrograms/kg/d), both as a 2-hour intravenous (i.v.) infusion twice per day until the neutrophil count was greater than 1,500/microL. RESULTS: The median days to recovery to an absolute neutrophil count (ANC) of 100/microL (9 v 11.5, P = .0005), 500/microL (10 v 16, P = .0004), or 1,000/microL (12 v 21, P = .0008) was shortened with the use of GFs, post-PBSC infusion. In addition, the duration of hospitalization was shorter (19 v 21 days, P = .0112) in the arm receiving GFs post-PBSC infusion. There was no significant difference between the two study arms in the duration of fever, documented septic episodes, or RBC or platelet transfusion requirements. CONCLUSION: Despite faster neutrophil recovery and shortened duration of hospitalization with GFs administered after PBSC transplantation, the measured clinical variables of febrile days, septic episodes, and transfusion requirements were similar between the study arms. The use of GFs post-PBSC transfusion is associated with a modest clinical benefit.

Rainfall and birthweight distribution in rural Tanzania.

PIP: This paper explores the possibility of using different techniques of time-series analysis lagged regression analysis for the study of the complicated interaction between ecological, socioeconomic and nutritional variables. The data discussed originate from a rural area in Tanzania, where life is subject to a marked seasonal variation, dependent on a bi-modal rainfall pattern. The unreliability of rainfall is characteristic: both drought and excessive rainfall are frequent occurrences. Seasonal variationns in birthweights over a 10-year period (1972-81) are here compared with the local rainfall pattern. Data on birthweight for this period show that birthweight was highest at the end of the dry season, fell rapidly during the 1st 1/2 of the rainy season, rose again during the later part of the rainy season, and fell to its lowest value just after the rans. It is argued that there are good reasons to attribute these variations to changes in labor output, food consumption, and health status, all of which are related to the seasonal cycle. Mean birthweight fell by about 60g. in the course of the rainy season. Lagged regression analysis reveals a negative impact of rainfall on birthweight after 3 months. Deviations from average rainfall show a positive correlation with birthweight after 4 months, but only in the months when rainfall is critical for food crop production. The interactions of these contrary effects are held responsible for the observed sudden fluctuations in mean birthweight.^ieng

Drug prescribing pattern of a psychiatric university hospital in Germany.

1. The drug treatment of 1,263 psychiatric patients (= 96% of all in-patients admitted during a period of 2 years) was analyzed by means of case histories. During hospitalization 7.4% of all patients were treated completely drug-free; 12.5% received no psychoactive drugs. 2. The patients were hospitalized for 50 days on the average, and received psychoactive drugs on 43 days. During the total treatment period, they were prescribed an average of 4.3 (median 3.8) different drugs; of these, 2.7 (median 2.3) were various psychoactive drugs. Neuroleptics were the most frequently used drugs; they were prescribed at least once during treatment for 62% of all patients. Antidepressants were prescribed for almost 30% of the patients. 3. For the neuroleptics prescriptions decreased with patient's age; they increased for the antidepressants. Antiparkinsonian agents were prescribed to 51% of neuroleptic-treated patients under 45 years of age, and to 26% of these patients over 45. 4. Neuroleptics were prescribed more frequently in male patients, antidepressants in female patients. 5. Among the individual prescriptions, perazine was the most favoured of the neuroleptics, and amitriptyline of the antidepressants. Clozapine was prescribed for the longest period among all psychotropic agents except lithium salts. Antiparkinsonian agents were used for shorter periods than the neuroleptics administered simultaneously. One-fifth of the patients were given analgesics for brief periods. 6. Medication pattern is related to specific nosology. 95% of schizophrenic patients received neuroleptics for at least an average of 41 days; every second patient in this group received antiparkinsonian agents. 90% of unipolar depressed patients were given antidepressants; during one course of treatment at least 2 different antipressant drugs were prescribed for 32% of these patients. 43% of unipolar depressed patients received neuroleptics for an average of 33 days. Lithium salts were administered for an average of 45 days to 43% of the patients with affective disorders. 7. Treatment surveys of this kind supplement the collection of data on adverse drug reactions by drug monitoring systems. The relationship between the side effects of drugs and the prescription pattern of individual drugs allows one to determine the incidence rates of drug side effects.

Synthesis of renin substrate by rat liver.

The present study attempts to determine if the isolated rat liver is capable of synthesizing renin substrate from 14C-labelled amino acids added in the perfusate. The renin substrate is characterized via reaction with renin, forming a substance that is subsequently identified as proangiotensin. Extensive evaluation of the reaction product is carried out by using molecular-sieve chromatography, countercurrent distribution, reactivity with converting enzyme, radioimmunological technique and bioassay. The results demonstrate that isolated rat liver perfused with artificial salt solution is capable of synthesizing a protein that reacts with renin to form a radioactive substance indistinguishable from proangiotensin.