Peripheral nociceptor sensitization mediates allodynia in patients with distal symmetric polyneuropathy.

Patients with painful neuropathy frequently complain of pain in response to normally non-painful brushing, namely dynamic mechanical allodynia. Despite many animal studies suggesting that allodynia arises when the spontaneous firing in damaged nociceptive afferents sensitise second-order nociceptive neurons to Aß-fibre input, no studies have sought to confirm this mechanism by investigating Aß-fibre sparing in human patients with allodynia. In this study we compared data from Aß-fibre-mediated nerve conduction studies and nociceptive-fibre-mediated laser-evoked potentials (LEPs) in 200 patients with distal symmetric polyneuropathy (114 with neuropathic pain, 86 without). Of the 114 patients with painful neuropathy studied, 44 suffered from allodynia. Whereas no statistical difference was found in nerve conduction study data between patients with and without allodynia, LEP amplitudes were larger in patients with allodynia than in those without (P < 0.01 by Mann-Whitney U test). The lack of difference in NCS data between patients with and without allodynia suggest that this type of pain, rather than arising through second-order nociceptive neuron sensitization to Aß-fibre input, might reflect a reduced mechanical threshold in sensitised intraepidermal nociceptive nerve terminals.

Mechanisms of pain in distal symmetric polyneuropathy: a combined clinical and neurophysiological study.

In patients with distal symmetric polyneuropathy we assessed non-nociceptive Abeta- and nociceptive Adelta-afferents to investigate their role in the development of neuropathic pain. We screened 2240 consecutive patients with sensory disturbances and collected 150 patients with distal symmetric polyneuropathy (68 with pain and 82 without). All patients underwent the Neuropathic Pain Symptom Inventory to rate ongoing, paroxysmal and provoked pains, a standard nerve conduction study (NCS) to assess Abeta-fibre function, and laser-evoked potentials (LEPs) to assess Adelta-fibre function. Patients with pain had the same age (P>0.50), but a longer delay since symptom onset than those without (P<0.01). Whereas the LEP amplitude was significantly lower in patients with pain than in those without (P<0.0001), NCS data did not differ between groups (P>0.50). LEPs were more severely affected in patients with ongoing pain than in those with provoked pain (P<0.0001). Our findings indicate that the impairment of Abeta-fibres has no role in the development of ongoing or provoked pain. In patients with ongoing pain the severe LEP suppression and the correlation between pain intensity and LEP attenuation may indicate that this type of pain reflects damage to nociceptive axons. The partially preserved LEPs in patients with provoked pain suggest that this type of pain is related to the abnormal activity arising from partially spared and sensitised nociceptive terminals. Because clinical and neurophysiological abnormalities followed similar patterns regardless of aetiology, pain should be classified and treated on mechanism-based grounds.

The management of hypertensive crises: a clinical review.

Hypertension is an exceedingly common disorder in Western societies; but, thanks to improved management of chronic hypertension, the number of patients who present with hypertensive crisis (HC) is less than 1%. However, critical elevation of blood pressure (BP) obliges to a proper and immediate management in order to prevent serious injury to organ target of hypertension (brain, heart, kidney and vessels). Moreover, the so called hypertensive emergencies (HE) and the hypertensive urgencies (HU) expect a several therapeutic approach. The HE warrant both prompt admission to an intensive care unit, where it is available a continuous monitoring of BP, and a prompt starting of a therapy with parenteral anti-hypertensive drugs. The treatment of HU can be managed choosing oral anti-hypertensive agents followed by a tight observation of the patient also in ambulatory system, lowering the BP more gradually over 12 to 24-48 hours. The present clinical review is aimed at reporting the current opinions on the management of HC, examining as well the drugs of largest use. Any drug that lowers BP precipitously should be avoided. Choice of the appropriate agent should be based on the underlying pathophysiological and clinical findings, on the mechanism of action, and on its potential side effects.

[Evaluation of the workload resulting from iatrogenic pathology in a medical ward in a regional hospital]. / Valutazione del carico di lavoro dovuto a patologia iatrogena in un Reparto di Medicina di un Ospedale Regionale.

OBJECTIVES: 1) To estimate the burden to diagnose and treat iatrogenic disorders out of all the activities of a referral hospital's medical ward. 2) To investigate about the main causes making the iatrogenic disorders arouse. DESIGN AND SUBJECTS: The entire series of iatrogenic disorder bearing patients (in- and out-), treated in the Institute of Medical Pathology of Ancona throughout a period of two years, were studied retrospectively. The low therapeutic index treatments (i.e. antiproliferative drugs, therapies under emergency, surgical amputations) were ruled out. The data to address the objectives were gathered. RESULTS AND CONCLUSIONS: 1) Highly probable iatrogenic disorders were diagnosed in 84/1620 patients (5.2%). 2) For this task 108/2763 medical performances were carried out (3.9%); 3) iatrogenic disorders were Slight in 20 (24%), Moderate in 44 (52%) and Severe in 20 (24%) patients. 4) Some facilitaters (poor monitoring of adverse drug reactions, primary disease incorrect treatment, poor accuracy of primary disease diagnosis, incoordination among therapists) were detected in 32, 25, 14, and 7%. 5) The most commonly occurring facilitaters were detected more frequently in Severe rather than Non Severe iatrogenic disorder bearing patients. 6) Severe iatrogenic disorders and the serious consequences of them, such as death and permanent serious harm, occur more often, when there are combinations of facilitaters; 7) Costs were minor in 69% and major in 31%.

Paraneoplastic syndromes in 68 cases of resectable non-small cell lung carcinoma: can they help in early detection?

The aim of this study was to assess the importance of paraneoplastic syndromes as an early sign of non-small cell lung cancer (NSCLC). A procedure for searching paraneoplastic syndromes, based on 40 years of reports in the literature, was established and the prevalence of paraneoplastic syndromes estimated in 68 patients with resectable NSCLC. Stages I and II were considered eligible for surgery straight away. Patients in Stage IIIA underwent surgery if partially or completely responsive to three courses of neo-adjuvant chemotherapy. Paraneoplastic syndromes were assessed and confirmed in nine patients (13%). Motor-sensory neuropathy, arthritis and arthralgias to the knees, periarthritis to the shoulder, hypertrophic osteopathy, clubbing, pruritus were observed. Only three patients with painful osteoarthropathies were diagnosed with NSCLC by tracing their paraneoplastic syndrome, whereas most of them (36/68) were diagnosed incidentally through a chest radiograph taken for tumour-unrelated symptoms. A careful research of paraneoplastic syndromes in high risk patients may guide the doctor to a resectable NSCLC diagnosis. Recent onset arthritis and arthralgias, which cannot be explained otherwise, should be considered to be early clues of lung cancer.

[Diagnosis of fever of unknown origin: use of Bayes theorem]. / La diagnosi di febbre di origine oscura: applicazione del teorema di Bayes.

Sophisticated tests and time are needed to establish the diagnosis of fever of unknown origin (FUO). Bayes theorem can guide the clinician to early probabilistic diagnosis. The authors had estimated the a priori probabilities in a previous study yet. In this paper the diagnostic probabilities of four clinical signs (arthralgias, myalgias, splenomegaly, multiple micro-lymphoadenopathies) and the probabilities of abnormalities of some routine laboratory tests (neutrophils count, lymphocytes count, platelets count, hemoglobin, lactic-dehydrogenase, C3 and C4 complement subunits and fibrinogen plasma concentrations, erythrocyte sedimentation rate) and of the positive bacterial cultures, were estimated in the main groups of FUO disease (indefinite, aspecific bacteria infections, non-bacterial or specific bacteria infections, neoplasias, connective tissue diseases, miscellaneous group). The data suggest that the a priori probability is not affected by the clinical signs. Arthralgias increase the probability of connective tissue diseases. Normal erythrocyte sedimentation rate and plasma fibrinogen concentrations increase the probability of paraneoplastic and indefinite fever. Thrombocytosis increases the probability of paraneoplastic fever. Over 1200 U/l serum lactic-dehydrogenase serum concentrations guide to non-bacterial or specific bacteria infectious diseases and to malignancies. Neutrophilia decreases the probability of indefinite diagnosis, even though it is not specific. The heterogeneity of the miscellaneous group makes the interpretations of the data very hard.

Combined malignant hemangiopericytoma and deep venous thrombosis. A case report.

Malignancies, antiproliferative drug treatment, cancer-related conditions like immobilization, perioperative status and radiotherapy are risk factors for hypercoagulability. Setting aside mass or invasion-related venous thrombosis, the differential diagnosis regarding the etiopathogenesis (paraneoplastic syndrome or antiproliferative treatment) is usually problematic. The authors report a case of combined malignant hemangiopericytoma and recurrent deep venous thrombosis in the right inferior limb. Through a literature review, the following issues are discussed: 1) the criteria for cyto-histopathologic assessment; 2) the involvement of pericytes both in coagulation and platelet aggregation; 3) the importance of discriminating true paraneoplastic syndromes from other tumor-related clinical manifestations; 4) the response to external radiotherapy of malignant hemangiopericytoma as limited disease; 5) the poor results of doxorubicin-ifosfamide polychemotherapy and dacarbazine monochemotherapy in metastatic disease. Although doxorubicin-ifosfamide treatment was in progress in the reported case, the authors conclude that the recurrent deep venous thrombosis is likely to be paraneoplastic, even if such a diagnosis has not been previously reported in the literature.

[The treatment of stroke in internal medicine wards or in an intensive care unit?]. / Trattamento dell'ictus cerebrale in Reparti di Medicina Interna o in Unità di Terapia Intensiva?

The mortality and complication rates have been studied in a series of 92 patients with stroke, who have been treated in a general medicine ward in central Italy. The data have been compared and discussed in relationship with analogous parameters reported about some series from north-European stroke units (SU) and general medicine wards (RMG). The mortality rates have been 11% over the first 7 days and 18% over the first 30 days. In a series of patients from northern Europe these parameters have been 12 and 19%. In severe prognosis patients the complication rate has been 83%, whereas in the series from northern Europe it has been estimated 97%. The infectious diseases have been complicating stroke in 21% of the patients. This rate is as high as in SU's, but lower than in RMG (49%). In the over 65 patients the mean hospital stay has been 19 days versus 24 in the SU. The percentage of the patients dismissed home has been higher than in the SU and in the RMG. Taking into consideration only the above-mentioned short term parameters and the acute phase management, the SU do not apparently have any advantage in comparison to the general medicine ward in central Italy which has been considered for this study.

[Low-grade fever of protracted course. Retrospective study of 30 cases and reflections for a low-cost management]. / Febbre di basso grado a decorso protratto. Studio retrospettivo di 30 casi e riflessioni per una gestione a basso costo.

The objects of this paper were the following: 1) to establish in a group of persistent (over four weeks) low grade fever (LGF) patients the percentage of cases in which a definite diagnosis could not be made; 2) where a definite diagnosis could be made, to describe the most commonly occurring diseases; 3) to follow up the uncertain diagnosis cases for at least two years. Thirty cases of persistent LGF were retrospectively studied. They did not include drug hyper-dysthermia and temporary and/or metabolic vasomotor reactions. The data suggest that: 1) two thirds of persistent LGF are likely not to be definitely diagnosed; 2) some certain diagnoses were: dental granulomas, mycobacteria infections, thyroiditis, factitious fever, rheumatic polymyalgia, Hodgkin's lymphoma and pulmonary thromboembolism; 3) in 14/19 undiagnosed cases the fever subsided permanently, without any treatment, within one year, whereas it persisted in 5/19, but no deterioration of the overall clinical status was observed; 4) although some of the undiagnosed cases were examined elsewhere, a certain diagnosis was never achieved in spite of their undergoing sophisticated and expensive clinical, laboratory and X-ray tests. Therefore it is concluded that: 1) persistent LGF should be managed more conservatively than fever of unknown origin so as to preserve resources; 2) some diseases should be included in the differential diagnoses from the beginning of the initial clinical work up; 3) undiagnosed LGF fever either subsides and returns to normal within one year or the fever persists, but no deterioration of the clinical and performance status is likely to occur.

[Fever of unknown origin. Comparison of the diagnostic spectrum of 53 cases in a medical ward in an Italian hospital with those of other 9 countries]. / Febbre di origine ignota. Confronto tra lo spettro diagnostico di 53 casi di un Reparto di Medicina di un ospedale italiano con quello di altri nove Paesi.

In the Institute of Medical Pathology of Ancona University, 53 cases of fever of unknown origin (FUO) were reviewed. In 44 cases (83%) the diagnosis was certainly stated. The diagnostic spectrum of the diagnosed cases was: 31 infectious (58%), 3 neoplastic (6%), 8 autoimmune (15%), 2 miscellaneous diseases (4%). Nine cases (17%) were undiagnosed. The mortality rate of the diagnosed cases was 16% within 16 months. The diagnostic spectrum, compared with the FUO series from nine countries, is unlike because of a higher rate of infectious diseases and a lower rate of neoplastic diseases. The methods, successfully used to achieve the final diagnosis were: laboratory tests, including bacteriologic studies, in 39%, evaluation of the clinical course and follow-up in 25%, imaging scan tests, including radionuclide, ultrasound, magnetic resonance, computed tomography, in 23%, and anatomopathological studies in 13%. A three years' follow-up was successfully carried out in 7 out of the 9 undiagnosed patients: 5 were healed without any treatment, 1 healed through a course of non steroid anti-inflammatory drugs and only one died because of the FUO carrying disease. None was persistently sick. The data are discussed through a comparison with the series of FUO bearing patients from other 9 countries.

[The usefulness of plasmapheresis in a case of nephrotic syndrome in Berger's disease]. / Utilità della plasmaferesi in un caso di sindrome nefrosica in corso di malattia di Berger.

Berger's disease, or IgA mesangial nephropathy, is a frequent form of focal and/or segmental proliferative glomerulonephritis that occasionally may present as nephrotic syndrome. The authors reports a clinical case of a young woman come to their observation with a severe clinical picture characterized by asthenia, anasarca, serious no selective proteinuria, microscopic hematuria, blood hypotension from mesangial proliferative glomerulonephritis IgA. Because of the null response to traditional therapy the patient was submitted to plasmapheresis "cascade model", or double filtration, a certainly experimental treatment for this disease, and a remission of the nephrotic syndrome was obtained as confirmed by follow-up at three, six months and one year. Since at present times the therapy is supportive only and no therapeutic maneuvers have been found to be consistently effective in the Berger's disease, plasma exchange plus immunodepressive therapy seems to be useful particularly in the rare patients with rapidly progressive glomerulonephritis. Further and more extensive studies and a fair follow-up are necessary to prove our results.

Relationship between prothrombin activation fragment F1 + 2 and serum cholesterol.

Plasma levels of fibrinogen, factor VIIc and prothrombin fragment F1 + 2, a marker of thrombin generation in vivo, were studied in 68 subjects with serum total cholesterol (TC) levels between 135 and 349 mg/dl but without clinical evidence of cardiovascular disease and other atherosclerotic risk factors. F1 + 2 plasma levels were directly correlated with TC (p < 0.0004), low-density lipoprotein cholesterol (LDL-C; p < 0.0018) and factor VIIc (p < 0.024). Thirty-five subjects with TC greater than 249 mg/dl (median value of the whole group) showed higher levels of F1 + 2 (p < 0.0001) and fibrinogen (p < 0.0015) than those with TC lower than 249 mg/dl. In subjects with TC > 249 mg/dl and F1 + 2 > 1.2 nM (median value of the whole group), a cholesterol-lowering drug (simvastatin) was able to reduce F1 + 2 (p < 0.009) as well as TC and LDL-C. This study shows a relationship between serum cholesterol and the rate of thrombin generation supporting the hypothesis that a hypercoagulable state may occur in hypercholesterolemic subjects before the onset of clinical evidence of atherosclerotic cardiovascular disease.

Signal-averaged electrocardiography and echocardiography in the evaluation of myocardial involvement in progressive systemic sclerosis.

To assess the myocardial involvement in progressive systemic sclerosis we evaluated the presence of late potentials by signal-averaged electrocardiography (signal-averaged ECG) and the left ventricular function by M-mode, two dimensional and Doppler echocardiography. Fifteen outpatients, 7 with diffuse progressive systemic sclerosis and 8 with CREST syndrome variant, without clinical or electrocardiographic evidence of cardiac disease were studied and compared with 18 normal subjects. Late potentials occurred in 5 out of 15 progressive systemic sclerosis patients (33%) with a significant difference versus controls (P < 0.05) and were present only in the patients with diffuse progressive systemic sclerosis (P < or = 0.001 vs. controls). All progressive systemic sclerosis patients showed a normal left ventricular systolic function. Abnormal left ventricular filling was found in 9 progressive systemic sclerosis patients (5 with diffuse progressive systemic sclerosis and 4 with CREST). A more severe impairment of the mean values of diastolic function indexes was found in diffuse progressive systemic sclerosis than in CREST. In all diffuse progressive systemic sclerosis patients at least one method showed altered results, whereas half the CREST patients showed no pathological findings with both techniques. These results confirm a lower myocardial involvement in the CREST syndrome than in diffuse progressive systemic sclerosis and consequently this is probably related to a better prognosis.

[A case of non-Hodgkin T-cell lymphoma with predominantly cutaneous manifestations]. / Su di un caso di linfoma non-Hodgkin a cellule T con manifestazioni prevalentemente cutanee.

There is a wealth of experiences concerning cancer and leukemia induced in human populations by radiation. The contribution of the nuclear industry to the radiation exposure of the general population is small, but there is the risk of catastrophic accidents causing a large number of deaths. The authors describe the case of a 48 year old black man accidentally exposed to the effects of radiations during the nuclear disaster of Chernobyl in 1986. The patient showed, many years later, a predominantly cutaneous high-grade T cell lymphoma, which was refractory to traditional treatments but sensitive to high doses of a recombinant interferon. Unluckily the patient died, six months later, because of autoinfection overwhelming. The goal of the authors is again to ask to reflect on the risk of the use of nuclear power and to debate the possible choice of the still experimental treatments.

[Calcium antagonists in the therapy of arterial hypertension in the aged]. / Trattamento con calcio-antagonisti dell'ipertensione arteriosa nell'anziano.

A large number of epidemiologic and interventional studies go to show that acute cerebral and cardiac events and chronic organ injury are significantly less frequent in treated compared to untreated elderly hypertensives. These observations clearly show that hypertension in the elderly must be treated. As to water-electrolyte metabolism, activity of the renin-angiotensin-aldosterone axis as well as volemia are reduced in the elderly while extravascular liquid compartment and activity of the natriuretic atrial factor are both increased. In addition, there is reduction of the baroceptor reflexes accompanied by vasoconstriction and hypertrophy of the smooth muscles associated with increased intracellular calcium ion content. These pathophysiologic conditions appear to supply the rationale for the preference accorded to calcium channel blockers compared to other drugs usually employed in the management of younger hypertensives. Moreover, second generation dihydropyridines, thanks to their liposolubility and ties with calcium channel subunits, show rapid onset and long action that allows for a single daily dose and lowers the incidence of side effects. A large number of interventional trials employing calcium channel blockers have demonstrated the efficacy of these drugs for reducing arterial hypertension. However, these trials concern young hypertensives whereas there is a lack of similar studies in elderly subjects, were clinical trials are few and involve limited numbers of subjects. Results of multicentre studies, at present in progress, will permit to assess the efficacy and incidence of side effects of second generation calcium channel blockers in hypertension of the elderly.

[The efficacy of i.v. immunoglobulins at high doses in a case of thrombocytopenia with an immune pathogenesis in chronic lymphocytic leukemia]. / Efficacia delle immunoglobuline e.v. ad alte dosi in un caso di piastrinopenia a patogenesi immunitaria in corso di leucemia linfatica cronica.

The authors report a case of chronic lymphocytic leukemia with thrombocytopenia caused by antiplatelet antibodies. The customary treatments of this condition having proved ineffective, therapy with large I.V. doses of Ig (0.4 g/kg body weight daily for five consecutive days) was started, which is believed to increase platelet count although the mechanism of this action is not yet fully understood. Interesting changes in laboratory parameters were observed, especially those concerning electroimmunophoresis and immunofixation and these might be useful for a better understanding of the various hypotheses that have been put forward to account for the mechanism(s) of action possibly at work. Treatment proved effective wherefore the authors hope that further studies will be carried out in order to increase our knowledge of the modulation and regulation of the immune response, a primary element in the management of these disorders which is at present only experimental.

[Amebic liver abscess: clinical and therapeutic considerations]. / Ascesso amebico epatico. Considerazioni cliniche e terapeutiche.

The authors report the case of a young adult with an amebic liver abscess. The primary infection localized in the gut occurred during a vacation in Africa. This disorder is fairly uncommon in western countries which is why the authors considered it worthwhile to draw practitioners' attention to it, stressing that it should be taken into account in differential diagnosis of fever of unknown origin in young adults who have travelled to regions where amebiasis is endemic. In addition, the diagnostic procedures used and especially the treatment applied are briefly set out. Medical therapy is almost always successful but if significant improvement is not achieved within a reasonable lapse of time and if complications are suspected, all possible therapeutic measures, including surgery, must be applied.

[Isolation of rotavirus from the feces of subjects (children and adults) from various hospitals in Rome]. / Isolamento di rotavirus nelle feci di soggetti (bambini ed adulti) ricoverati in vari ospedali di Roma.

Enteric infections in childhood are estimated to be a primary cause of illness and death in the third world and Rotaviruses play a very important role in acute nonbacterial diarrheal enterocolitis. The Authors analyse the latest results of the direct investigation of the virus in the feces by ELISA method. The improvements in diagnostic techniques and the new knowledges about Rotaviruses and their pathogenic power acquired during the last decade have made it easier to know the consequences of Rotavirus infections particularly in the poorest countries, with very bad sanitary conditions. Much attention has therefore been paid to the study of dietetics and immunoprophylaxis in order to find the most suitable cure. At present only some vaccines of animal origin are available that many Authors consider to be harmless, and that, might hopefully be employed in the third world countries.