Early onset Alzheimer's disease in a South American pedigree from Argentina

We report the clinical, SPET, immunohistochemical and DNA features of an early-onset familial Alzheimer's disease (FAD) in an Argentine pedigree of South American indian ethnic background. Pedigree spans 5 generations comprising more than 110 biological relatives. Clinical data supported the diagnosis of early onset FAD (mean age at onset 38.9 years) in 10 family members, including 3 with pathological confirmation (mean age at death 48.5). The pattern of transmission suggested autosomal dominant inheritance. Prominent features were mood changes, early language impairment, myoclonus, seizures and cerebellar signs. SPET displayed bilateral frontal, temporo-parietal and cerebellar hypoperfusion in early stages and in an asymptomatic member at risk, suggesting that SPET may have predictive value in this family. Immunohistochemistry showed β amyloid deposits within neuritic plaques and vessel walls and no anti-PrP immunoreactivity. DNA analysis showed no abnormalities in the β amyloid precursor protein gene. The identification of additional genetic defects in well characterized independent FAD pedigrees will contribute to the understanding of the pathogenesis of Alzheimer's disease.     

Posterior Acromioclavicular Dislocation with Clavicular Fracture and Trapezius Entrapment

AbstractBackground: Posterior acromioclavicular dislocation is rare. Dislocation associated with fracture of the clavicle and simultaneous entrapment of the lateral end of the clavicle by trapezius muscle has not been reported. Posterior dislocation occurs frequently owing to forceful move of the scapula anteriorly and superiorly or from direct force applied to the lateral end of the clavicle and this may be associated with clavicular fracture. In acute dislocations, open reduction, internal joint stabilization and soft tissues reconstruction have been recommended.Case Study: Acute posterior dislocation occurred in a 32-year-old man. The lateral end of the clavicle was displaced posteriorly and inferiorly, and firmly entrapped in trapezius muscle. The clavicular fracture was undisplaced. The coracoclavicular ligaments were stretched but intact. Open reduction was secured with two smooth Kirschner wires. The disrupted soft tissues were repaired. The clavicular fracture was not explored. Shoulder movement started at 6 weeks. Wires were removed. 10 years later he had pain-free, unrestricted shoulder movement, and the radiographs showed wellreduced, essentially normal acromioclavicular joint.Conclusion: Open reduction, internal joint stabilization and soft tissue reconstruction will result in return and long lasting unrestricted pain-free function of the shoulder.     

Effect of calcium replacement on the hemodynamic changes associated with high dose interleukin-2 therapy.

Administration of high-dose IL-2 results in hemodynamic changes that are similar to those seen in septic shock. These include a decrease in systemic vascular resistance (SVR) with a resultant drop in mean arterial pressure (MAP). Hypocalcemia is seen in septic shock and with IL-2 administration. Calcium replacement in septic shock has been reported to result in hemodynamic improvement; we therefore administered calcium to patients receiving high dose IL-2 to correct ionized hypocalcemia. Five consecutive patients underwent invasive hemodynamic monitoring before and during IL-2 administration. Calcium chloride was administered to correct ionized hypocalcemia, and hemodynamic parameters were monitored before and after calcium administration. Ionized hypocalcemia was associated with an elevation in parathyroid hormone levels. There was no toxicity related to the administration of calcium. An improvement in the MAP and SVR was seen early and late (after a dose of IL-2 was held) in the IL-2 treatment cycle; there were minimal effects at other points. Because of the potential hemodynamic benefit of calcium replacement, we recommend that ionized hypocalcemia be corrected in patients receiving high-dose IL-2.     

Synthesis and properties of (D)- and (L)-lactide stereocopolymers using the system achiral Schiff's base/aluminium methoxide as initiator

The polymerization of lactides with various D /L enantiomeric compositions using achiral Schiff's base/aluminium methoxide as initiator (SALENAlOCH₃) in dichloromethane solution at 70°C is reported. The conversion was kept below 70% in order to limit transesterification reactions. The polymers obtained after precipitation show a narrow molecular weight distribution (ratio of weight- to number-average molecular weights M _w/M _n = 1,1–1,2) and an optical rotation higher than that expected from the optical purity of the starting monomers. The examination of the thermal properties reveals that whatever their enantiomeric composition all the prepared polymers are crystalline. This unusual behavior is explained by an end-chain propagation mechanism producing stereocopolymers with long enantiomeric sequences, i.e., increased isotacticity as substantiated by an examination of the microstructure of the polymers by means of ¹³C nuclear magnetic resonance. A stereocomplex formation was observed for stereocopolymers with optical purities below 40%.     

Relaxation Therapy and Compliance in the Treatment of Adolescent Headache

SYNOPSIS
Few controlled studies have examined the effectiveness of relaxation therapy for the treatment of adolescent headaches. In this study, ten chronic headache sufferers (migraine or muscle contraction), ranging in age from 12 to 17 years (M = 13.5 SD = 1.3), were sequentially assigned to either a relaxation therapy or waiting-list control group. Following treatment, subjects in the treatment group demonstrated significantly lower Headache Index scores than subjects in the control group (U = 0, p £ .004). Group differences in Headache Free Days, Peak Headache Rating, and Medication Index scores were not significant; differences in Medication Index scores approached significance at U = 3, p £ .03. Objective compliance to treatment data indicated subjects overreported their actual practice time, on average, by 70%. Results and implications for future research are discussed.     

Clinical and demographic factors associated with DSM-IV melancholic depression.

BACKGROUND: The purpose of this paper is to use demographic and clinical data from a large diverse group of outpatients diagnosed with non-psychotic major depression to investigate the validity of the DSM-IV concept of melancholic depression. METHODS: Baseline clinical and demographic data were collected on 1500 outpatients (1456 of whom melancholia could be determined) with non-psychotic major depressive disorder (MDD) participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Depressive symptom severity was assessed by clinical telephone interview using the 17-item Hamilton Rating Scale for Depression (HRS-D17) and the 30-item Inventory of Depressive Symptomatology (IDS-C30). The types and degrees of concurrent psychiatric symptoms were measured using a self report, the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items relevant to each diagnostic category endorsed by study participants. RESULTS: Adjusting for severity of depression (as measured by the total HRS-D17 scores), no differences were found in the rate of melancholic depression by race, marital status, education, employment status, family history of depression, primary care versus specialty care, monthly income, and degree of psychiatric and medical co-morbidity. Melancholic depression was significantly more likely in men than women. Melancholic depression after adjustment for severity was associated with a slightly younger age at study entry, as well as with greater illness severity, and slightly shorter duration of current episode. Hispanic ethnicity was associated with lower melancholic depression rates at the .06 level of significance. CONCLUSIONS: Among outpatients with MDD, melancholic features were less likely in Hispanic patients, but more likely in slightly younger patients and in men. Melancholic features were also related to a slightly shorter current episode. These findings are consistent with the notion that external socio-demographic factors do not play an important role in the pathophysiology of melancholic depression.     

Cross sectional investigation of the effects of inhaled corticosteroids on bone density and bone metabolism in patients with asthma

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several decades. The possibility of confounding by age, menopausal status, physical activity and, especially, past oral steroid use has not been excluded in most studies. The present study was designed to assess the magnitude of any reduction in bone mineral density in relation to inhaled steroid use after adjusting for these factors. METHODS: Bone mineral density (BMD), vertebral fractures, and markers of bone metabolism (serum osteocalcin, procollagen peptide I, bone-specific alkaline phosphatase, and urinary deoxypyridinoline cross links) were measured in 81 patients with asthma age 20-40 years; 34 patients (19 men) who had never had inhaled or systemic steroids and 47 (19 men) who had taken inhaled steroids for at least five years with limited exposure to systemic steroids in the past. Data relating to past medication use, physical activity, smoking, and other confounding factors were collected by questionnaire. The relation between inhaled steroid dose and duration and BMD was assessed by linear regression analysis, accounting for potential confounders including weight, exercise, and oral steroid use. RESULTS: The 47 patients taking an inhaled steroid had a mean current dose of 620 micrograms/day (range 100-3000 micrograms), a mean duration of use of 7.8 years, and had had a mean of 0.85 courses of prednisolone in the past. There was no significant difference in mean BMD values between those who were and those who were not on inhaled steroids in men or women. However, on multivariate analysis, cumulative inhaled steroid dose was associated with a reduction in posterior-anterior (P-A) and lateral lumbar spine bone mineral density in women, equivalent to a 0.11 standard deviation reduction in bone density per 1000 micrograms/day inhaled steroid per year after adjustment for potential confounding factors (95% CI for P-A spine 0.01 to 0.22; for lateral spine 0.02 to 0.21). Previous oral steroid use was not an important confounding factor in these patients. Inhaled steroid use was not related to BMD at the wrist or hip in women or at any skeletal site in men. Women taking an inhaled steroid had lower levels of serum osteocalcin than those not taking them, although this was not dose related. Inhaled steroid use was not associated with differences in other markers of bone metabolism in men or women or with the presence of vertebral fractures. CONCLUSIONS: Although an effect of confounding factors cannot be excluded entirely in a cross sectional study, our findings are in keeping with an effect of inhaled steroid therapy in reducing bone density in the spine in women and provide an estimate of the magnitude of this effect.


     

Detection of scrapie-associated fibrils (SAF) and SAF proteins from scrapie-affected sheep

Scrapie-associated fibrils (SAF) were detected by negative-stain electron microscopy in the brains (by two different isolation procedures) and spleens of sheep naturally and experimentally infected with scrapie. Although the numbers of SAF varied from case to case, the yield of SAF from brains of naturally affected sheep was lower than that from experimentally affected sheep. SAF-specific, protease-resistant proteins (PrPs) were detected by silver staining and western blot analysis in most samples of brain from experimentally affected sheep. PrPs, however, could be detected in only a limited number of natural cases of sheep scrapie because of the lower yields of SAF. PrPs from sheep SAF appear biochemically and antigenically similar to PrPs from other species infected with unconventional agents. This study further establishes the unique association of SAF and PrPs with natural or experimentally induced scrapie in its natural host.     

The adult and a new late adult forms of neuronal ceroid lipofuscinosis

Summary Three cases of the late adult form of neuronal ceroid lipofuscinosis (NCL) are reported. Two of these are siblings with a late clinical onset at ages 26 and 44 years. The third case, sporadic, has the oldest reported age for the onset of NCL, at 63 years and may be regarded as the first example of the presenile form of NCL. The clinical, morphological, histochemical, ultrastructural and genetic features of these three cases are discussed. The literature of the clinicopathological NCL cases with an onset at age of 25 and older is reviewed. The clinical and morphological differences between the late adult form and the presenile form of NCL as well as the difficulties in making the diagnosis are discussed.Supported by NIH Grant NS23717     

Spectrum of morphological appearance of amyloid deposits in Alzheimer's disease

Summary Immunocytochemical staining with monoclonal antibodies to the -protein on tissue sections which have been pretreated with formic acid is not only a very specific but also a highly sensitive method for the detection of amyloid deposits in the brains of Alzheimer's disease victims. We report here a spectrum of morphological appearance of the brain amyloid deposits which are one of the main histopathological correlates of this disorder. Deposits of the -protein are not only found in the well-known lesions [congophilic angiopathy and senile (neuritic) plaques] but are also seen under various morphological forms for which the word plaques does not appear an appropriate term: amyloid fibrils are found as large areas of diffuse infiltration of the neuropil, as ribbon-like infiltration in the subpial layer of the cerebral cortex, as granular deposits in the white matter, as diffuse deposits in the molecular layer of the cerebellum and the basal ganglia and as star-shaped deposits in the cerebellar Purkinje cell layer. The morphology of these deposits seems to depend on the cyto-and fibroarchitectonics of the brain region in which they are found, on the amount of amyloid deposited, and also on the type of staining technique used. It is only under specific circumstances that the deposition of amyloid in the neuropil is accompanied by the formation of paired helical filaments in nerve cell processes and their parent perikarya. In conclusion, our studies suggest that the extent of brain amyloidosis in Alzheimer's disease is much wider than so far appreciated.Supported in part by grants 5-AGO-4220-05 and 5-HD-22634-02 from the National Institutes of Heath