An atypical case of mononeuritis multiplex in primary Sjogren's syndrome

We present an atypical case of peripheral nervous system (PNS) involvement in Sjogren's syndrome in a 63 year-old woman. Symptoms of an entrapment neuropathy were the first manifestation of the systemic disease and they were subsequently coupled to those of a mononeuritis multiplex. Clinical and laboratory signs for the diagnosis of Sjogren's syndrome became subsequently overt. The mononeuritis multiplex remained clinically limited to the upper limbs and characterized by unusually severe motor symptoms which progressed up to the development of a final complete deplegia. By contrast, sensory symptoms at the upper limbs remained mild over the entire course of the disease and the lower limbs revealed a subclinical sensory-motor damage only during the late stage.     

The structure of Schwann cells in unmyelinated fibres. A qualitative and quantitative electron microscope study

The structure, size and distribution of many cytoplasmic components of Schwann cells associated with unmyelinated axons in lizard thoracic spinal roots were analysed under the electron microscope. The percentages of Schwann cell cytoplasmic area occupied by the following cytoplasmic components were determined: mitochondria, Golgi apparatus, granular endoplasmic reticulum, multivesicular bodies, smooth endoplasmic reticulum, lipofuscin granules, peroxisome-like bodies, autophagic vacuoles, dense bodies and lipid droplets. A linear correlation was found between the sectional areas of the mitochondria and granular endoplasmic reticulum of the Schwann cell and both length of Schwann cell plasma membrane profile and size of the related axoplasm. The structure of Schwann cells associated with unmyelinated axons and that of Schwann cells associated with myelinated axons were compared in the same species and in the same region of the peripheral nervous system using the same fixative and the same preparation technique. Some differences were detected in the organization of the granular endoplasmic reticulum, in the presence of cilia and in the percentages of cytoplasm occupied by various components. The hypothesis that Schwann cell mitochondria and granular endoplasmic reticulum are involved in the production and storage of proteins for the plasma membrane of this cell as well as the hypothesis that these organelles are involved in the production and storage of protein metabolites which are subsequently transferred to the related axons seem applicable not only to Schwann cells associated with myelinated axons (Pannese et al., in press), but also to those associated with unmyelinated ones.     

Chronic morphine affects working memory during treatment and withdrawal in rats: possible residual long-term impairment

An eight-arm radial maze was used to investigate a possible short-term (during the development of tolerance and dependence) and long-term (6, 9 and 12 months after treatment) effect on working memory, in young rats, which drank morphine (0.5mg/ml) for 1 month, or to which the drug was administered by i.p. injection (at weekly increasing doses of 20, 50, 100, 200mg/kg). Tail flick test and cortically derived electroencephalographic (EEG) recordings were also carried out in the same rats to determine any modifications in analgesia and in total EEG mean power spectra during treatment and withdrawal. Complete tolerance to morphine analgesia developed during the period of drug treatment. Chronic morphine significantly impaired radial maze performance in the working memory components of the task during both treatment and early withdrawal, but only in the i.p. group. Six and 9 months after morphine treatment, both the oral and i.p. group showed a significant impairment of radial maze performance. The mean power spectra were altered during treatment but returned to baseline values during abstinence, except for the first day. These findings suggest the possibility of morphine-induced premature ageing, which is more evident in i.p. treated animals. The mechanism by which morphine treatment produces residual long-term learning impairment requires further elucidation.     

Reduced platelet glutamate uptake in Parkinson's disease

Summary. Defects in mitochondrial enzymes have been found not only in substantia nigra, but also in platelets from Parkinson's Disease (PD) patients, suggesting a systemic impairment of energy metabolism. Since platelets present an energy-dependent glutamate uptake similar to that described in central nervous system, glutamate uptake was determined in platelets from 34 PD patients and 21 age-related normal controls, as Na⁺-dependent [³H]glutamate influx; glutamate level was also analyzed by reverse-phase HPLC. A 50% reduction of glutamate uptake (p < 0.001) was observed in idiopathic PD patients, respect to controls and secondary parkinsonian syndromes. The decrease correlated with the severity of PD, measured by the UPDRS (r = −0.54; P < 0.05). Glutamate level was increased in platelets of PD patients, but was not correlated to the uptake decrease. Both phoenomena may be explained by the modifications of mitochondrial enzymes described in platelets, which could be used as a peripheral model of glutamatergic function in PD. Received October 7, 1998; accepted January 7, 1999     

The complexity of cancer survivorship: a case for personalized medicine. Report of the 2014 Grandangolo conference

This article reviews the Grandangolo conference on cancer survivorship and highlights the major findings. These include the improvement in survivorship, and the emergence of survivorship related syndromes, such as new neoplasms, cardiomyopathy, neutorpathy fatigue and memory loss. Emotional disorders may include the Lazarus’ Syndrome and the post-traumatic stress disorder. An open question is whether we should have specialists of survivorship or primary care physicians or oncologists could fulfill this role.     

Anemia of aging: the role of chronic inflammation and cancer

Aging is associated with increased incidence and prevalence of anemia, leading to a number of adverse health outcomes. These include death, functional dependence, increased risk of therapeutic complications, falls, and dementia. In approximately 30% of cases, anemia in older individuals is due to either relative or absolute erythropoietin (EPO) deficiency. Absolute EPO deficiency may be primary or secondary to declining renal function. Relative EPO deficiency is due to an age-related pro-inflammatory status that reduces the sensitivity of erythropoietic precursors to EPO. Despite this condition of EPO deficiency, the management of anemia of aging with erythropoiesis-stimulating agents (ESAs) is controversial, unless the anemia is due to renal insufficiency. The main concern related to this treatment arises from eight studies of ESAs in cancer, suggesting that ESAs may reduce patient survival in addition to increasing the risk of deep vein thrombosis. The results of these studies contrast with a host of other trials showing the safety of ESAs. The discrepancy may be explained in part by the fact that, in the trials suggesting a detrimental effect of ESAs, the goal was to obtain hemoglobin (Hb) levels higher than 12 g/dL. Because of this concern, correction of anemia in elderly individuals with relative EPO insufficiency should not be attempted outside clinical trials.     

Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus

Summary Diabetic autonomic dysfunction is associated with a high risk of mortality which makes its early identification clinically important. The aim of our study was to compare the detection of autonomic dysfunction provided by classical laboratory autonomic function tests with that obtained through computer assessment of the spontaneous sensitivity of the baroreceptor-heart rate reflex (BRS) by time domain and frequency domain techniques. In 20 normotensive diabetic patients (mean age ± SD 41.9 ± 8.1 years) with no evidence of autonomic dysfunction on laboratory autonomic testing (D0) blood pressure (BP) and ECG were continuously monitored over 15 min in the supine position. BRS was assessed as the slope of the regression line between spontaneous increases or reductions in systolic BP and linearly related lengthening or shortening in RR interval over sequences of at least 4 consecutive beats (sequence method), or as the squared ratio between RR interval and systolic BP spectral powers around 0.1 Hz. We compared the results with those of 32 age-matched normotensive diabetic patients with abnormal autonomic function tests (D1) and with those of 24 healthy age-matched control subjects with normal autonomic function tests (C). Compared to C, BRS was markedly less in D1 when assessed by both the slope of the two types of sequences (data pooled) and by the spectral method (–71.3 % and –60.2 % respectively, both p < 0.01). However, BRS was consistently although somewhat less markedly reduced in D0, the reduction being clearly evident for all the estimates (–57.0 % and –43.5 %, both p < 0.01). The effects were more evident than those obtained by the simple quantification of the RR interval variability. These data suggest that time and frequency domain estimates of spontaneous BRS allow earlier detection of diabetic autonomic dysfunction than classical laboratory autonomic tests. The estimates can be obtained by short non-invasive recording of the BP and RR interval signals in the supine patient, i. e. under conditions suitable for routine outpatient evaluation. [Diabetologia (1997) 40: 1470–1475] Received: 30 April 1997 and in revised form: 31 July 1997     

Decreased platelet glutamate uptake in patients with amyotrophic lateral sclerosis

Decreased glutamate uptake and a loss of the astrocytic glutamate transporter EAAT2 (GLT-1) have been shown in spinal cord and motor cortex of patients with ALS. Because platelets express the three major glutamate transporter subtypes, including GLT-1, and possess a high-affinity glutamate uptake, the authors investigated glutamate uptake in platelets from patients with ALS and controls. A 43% reduction of high-affinity glutamate uptake rate (p < 0.0001) was observed in patients with ALS compared with normal controls and chronic neurologic disorder patients, suggesting a systemic impairment of glutamate uptake in ALS.     

Skeletal muscle glycogenosis type II: Biochemical and electron microscopic investigations of one case

Summary A 7 year-old boy suffering since early infancy from muscular weakness with diffuse hypotrophy and hypotonia is described. There was a remarkable intellectual retardation, but not hepato or cardiomegaly.A muscle biopsy revealed large quantities of glycogen stored inside the muscular fibres; electron-microscopic investigations indicated that glycogen was lying free between the myofilaments and was also stored in membrane-bound vescicles, possibly lysosomes. Biochemical studies showed the absence of acid maltase in muscular tissue.The case has been considered as a mild form of glycogenosis type II (Pompe's disease) without visceral involvement and with survival into adult life.The possibility that a peculiar metabolic pattern could be present in this form of glycogenosis is discussed along with other existing hypotheses seeking to explain the relative mildness of the disease in spite of the huge accumulation of glycogen.

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Zusammenfassung Es wird ein 7jähriger Knabe beschrieben, welcher seit früher Kindheit eine Muskelschwäche mit diffuser Hypotrophie und Hypotonie aufwies. Psychischer Entwicklungsrückstand, aber keine Hepato- oder Kardiomegalie.Eine Muskelbiopsie zeigte große Mengen von Glykogen innerhalb der Muskelfasern. Die elektronenoptische Untersuchung zeigte, daß das Glykogen sowohl frei zwischen den Myofilamenten als auch in membranumgebenen Vesikeln, möglicherweise Lyosomen gespeichert war. Es konnte biochemisch das Fehlen der sauren Maltase im Muskelgewebe gezeigt werden. Es wurde angenommen, daß es sich um eine milde Form der Glykogenose vom Typus II (Pompe) handelt ohne viscerale Beteiligung und mit Überleben bis in das Erwachsenenalter. Es wurde die Möglichkeit diskutiert, daß im vorliegenden Fall eine besondere Form der Stoffwechselstörung vorlag, welche den relativ milden Verlauf der Erkrankung trotz der hochgradigen Glykogenspeicherung erklären könnte.