H-coil repetitive transcranial magnetic stimulation for pain relief in patients with diabetic neuropathy.

BACKGROUND: Painful neuropathy is associated with plasticity changes in the nervous system. Standard repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique used to study changes in cortical excitability and to inhibit pain perception. Deep rTMS is a newer development that allows direct activation of deeper neuronal populations, by a unique coil design termed the H-coil. This study was designed to assess whether deep rTMS applied over the motor cortical lower-limb representation relieves pain in patients with diabetic neuropathy. METHODS: Patients were randomly assigned to receive daily real or sham H-coil rTMS for 5 consecutive days. After a 5-week washout period, they crossed over to the alternative treatment for additional 5 days (according to a crossover study design). Outcome measures were changes in the visual analogue scale (VAS) for pain and in area and threshold of RIII nociceptive flexion reflex (RIII reflex). RESULTS: Of the 25 patients randomized, 23 completed the study. After real rTMS, the VAS scores decreased significantly (p=0.01), and so did RIII reflex area (p<0.01), while no significant effects in these variables were induced by the sham rTMS treatment. The rTMS-induced changes in the outcome measures disappeared about 3 weeks after stimulation. All patients tolerated stimulation well. CONCLUSIONS: Deep H-coil rTMS provides pain relief in patients with diabetic neuropathy. This innovative technique can induce a therapeutic effect on brain areas that otherwise remain difficult to target. rTMS may produce its analgesic effects, inducing motor cortex plasticity and activating descending inhibitory pain control systems.

Deep transcranial magnetic stimulation as a treatment for psychiatric disorders: a comprehensive review.

Deep transcranial magnetic stimulation (TMS) is a technique of neuromodulation and neurostimulation based on the principle of electromagnetic induction of an electric field in the brain. The coil (H-coil) used in deep TMS is able to modulate cortical excitability up to a maximum depth of 6 cm and is therefore able not only to modulate the activity of the cerebral cortex but also the activity of deeper neural circuits. Deep TMS is largely used for the treatment of drug-resistant major depressive disorder (MDD) and is being tested to treat a very wide range of neurological, psychiatric and medical conditions. The aim of this review is to illustrate the biophysical principles of deep TMS, to explain the pathophysiological basis for its utilization in each psychiatric disorder (major depression, autism, bipolar depression, auditory hallucinations, negative symptoms of schizophrenia), to summarize the results presented thus far in the international scientific literature regarding the use of deep TMS in psychiatry, its side effects and its effects on cognitive functions.

Clinical patterns of Fusarium infections in immunocompromised patients.

Fusarium is an ubiquitous fungus commonly found in soil and on plants. Human infection usually occurs as a result of inoculation of the organism through the body surface, thus causing skin infection, onychomycosis, keratitis, endophthalmitis and arthritis. Dissemination may occur in subjects with underlying immunodeficiency. Among immunocompromised hosts, Fusarium sp. is an emerging pathogen in neutropenic patients. To our knowledge, since 1973, when the first disseminated fusariosis in a child with acute leukemia was reported, about 80 new cases have been reported, mainly occurring in patients with haematologic malignancies. Specific portals of entry are not well understood, nevertheless the respiratory tract, colonised gastrointestinal tract, onychomycosis, disrupted skin barrier and central venous catheter have been reported as entry sites of deep seated Fusarium infections. Fever, positive blood cultures, severe myalgias, disseminated ecthyma gangrenosum-like skin lesions, ocular symptoms and multiple-organ-system involvement are distinctive features in most cases of disseminated fusariosis. The prognosis is very poor with death generally following despite antifungal therapy, unless an increase in the white blood cell count occurs. All available antifungal drugs show a low activity against the various species of Fusarium. Nevertheless, amphotericin B seems to have the highest in vitro activity and, even if it does not appear to be effective in persistently neutropenic patients, it should be currently considered to be the treatment of choice.

Fungemia in patients with leukemia.

A nine-year retrospective study on fungemia in patients with leukemia was conducted. A total of 79 episodes of fungemia in 77 patients with leukemia were documented. Candida parapsilosis fungemia was associated more frequently with the presence of a central venous line and to the use of parenteral nutrition than the other fungal species (p = 0.00026 and p = 0.01, respectively). The same fungus was isolated from both blood and surveillance cultures in 95% of Candida albicans and in 89% of Candida tropicalis fungemia (p < 0.01 and p = 0.02, respectively). The neutropenia and fungus colonization that resulted was associated significantly with the presence of invasive disease (p = 0.0024 and p = 0.0028, respectively). Conversely, central venous catheterization and parenteral nutrition appeared to be associated with episodes without deep tissue invasion (p = 0.000037 and p = 0.001, respectively). Invasive mycosis due to the fungus isolated from blood was documented in 51 patients with a mortality rate of 69%, whereas in 20 patients without invasive mycosis, mortality rate was 21% (p = 0.000059). In patients with fungemia, related or unrelated to the presence of a central venous catheter, mortality was 24% and 64%, respectively (p = 0.00042). Mortality was highest with C. tropicalis (p = 0.0017) and lowest with C. parapsilosis (p = 0.057). Severe neutropenia (polymorphonuclears < 100/mmc) appeared associated with a higher mortality rate (p = 0.012), whereas the recovery of neutropenia was related adversely to a fatal outcome (p < 0.01). With antifungal therapy, there was no statistically significant difference whether antifungal therapy was given or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Piperacillin plus amikacin vs. piperacillin plus amikacin plus teicoplanin for empirical treatment of febrile episodes in neutropenic patients receiving quinolone prophylaxis.

A prospective, randomized trial was initiated to evaluate the efficacy of two antibiotic regimens, differing in the agent included with activity against gram-positive bacteria, for the empirical treatment of febrile episodes in neutropenic patients with hematologic malignancies (group 1, piperacillin plus amikacin; group 2, piperacillin plus amikacin plus teicoplanin). After 72 hours of therapy, patients in group 1 who were still febrile were administered teicoplanin and those in group 2 were administered amphotericin B. A total of 158 evaluable episodes were observed within 8 months. The success rate was 50.6% in group 1 and 60% in group 2. The response rate among patients who did not respond to the original regimen increased to 86.7% with the addition of teicoplanin (group 1) and to 90% with the addition of amphotericin B (group 2). There were 86 unexplained febrile episodes and 56 documented episodes of bacteremia (34 caused by gram-positive organisms). Our results indicate that teicoplanin is safe, well tolerated, and effective for the treatment of documented episodes of gram-positive bacteremia and as an empirical agent. The inclusion of teicoplanin in the initial empirical regimen appears unnecessary if a combination of antibiotics active against gram-positive organisms is used, unless infections are due to oxacillin-resistant staphylococci.

Typologies of family reaction to pediatric malignancies.

The psychologic adaptation of children with malignancies is influenced by the strategies that both the relatives and the other members of the family employ as a reaction towards the disease and the therapeutic progress. Our experience in the Department of Hematology of the University "La Sapienza": by carefully observing the communication styles, the distribution of roles, and the modification of the family organization up to the eventual adaptation to the disease, we have been able to identify various reaction typologies of the family, and also to evaluate their frequency and their varying functionality with time. A thorough analysis of these modalities of reaction may allow prompt recognition of problems related with psychologic and social adaptation of both the pediatric patient and his family, and may allow the adoption of pertinent strategies of intervention, in order to guarantee a better compliance throughout the whole therapy.

Single daily dose ceftriaxone plus amikacin treatment of febrile episodes in neutropenic patients attending day hospital for hematologic malignancies.

Once-a-day ceftriaxone and amikacin was administered in case of fever to 46 neutropenic patients attending day hospital for hematologic malignancies. All patients were admitted to a short-term ward for infective complications, but were discharged in the event of prompt disappearance of fever and of clinical signs of infection continuing their therapy either by daily reporting to the hospital, or at home. Response to the initial empiric therapy was obtained in 37 cases (76%). Twenty-four patients who promptly responded to therapy completed their treatment on an outpatient basis, their mean number of days of hospitalization being reduced to 4.6 versus a mean of 9.6 days in the overall patient population being considered. Since the outpatient treatment accounted for 21% of the antibiotic therapy administered, the above treatment may result in cost containment and better quality of life for patients, provided that these data are confirmed by prospective randomized studies.

Spontaneous pneumothorax complicating pulmonary mycetoma in patients with acute leukemia.

Pneumothorax caused by the rupture of a mycetoma into the pleural space is rarely reported in patients undergoing intensive cytotoxic therapy for hematologic malignancies. We reviewed 46 episodes of mycetoma that developed in 43 patients undergoing antineoplastic therapy; six (13%) of these episodes were further complicated by the occurrence of pneumothorax that developed after bone marrow recovery with return to normal granulocyte count. Etiologic agents included Aspergillus fumigatus, Aspergillus fumigatus plus Blastoschizomyces capitatus, and Mucor (one case each). No pathogen was detected in the remaining three cases of pneumothorax. Four of the six patients died (7, 10, 27, and 50 days after the onset of pneumothorax). Two of the six patients with pneumothorax died of massive hemoptysis, whereas only one of the 40 patients who did not develop pneumothorax died of hemoptysis. This suggests that both pneumothorax and hemoptysis may represent the clinical expression of a more destructive course of invasive fungal diseases.

Catheter-related right-sided endocarditis in bone marrow transplant recipients.

Bone marrow transplant recipients are at increased risk of severe central venous catheter-related septicemias that may be complicated by endocardial infection. In view of this, we prospectively evaluated 141 consecutive patients receiving allogeneic or autologous bone marrow infusion. Seven (5%) of 141 patients developed eight episodes of a clinical syndrome compatible with catheter-related right-sided infective endocarditis; this diagnosis was confirmed at autopsy in two patients who died. Staphylococcus epidermidis was the most frequent isolate (four cases). Other offending pathogens were, in one case each, Enterococcus faecalis, Corynebacterium jeikeium, Pseudomonas alcaligenes, and Achromobacter xylosoxidans plus Candida species. Three- to 7-week courses of antibacterial therapy were associated with a favorable outcome in six of the seven cases. Infective endocarditis may be a complication of the use of central venous catheters and should be actively sought in septicemic bone marrow transplant recipients.

Ceftriaxone and amikacin as single daily dose in the empiric therapy for febrile episodes in neutropenic patients.

One hundred thirty-three febrile episodes in 115 neutropenic patients with hematologic malignancies were empirically treated with ceftriaxone and amikacin in a single daily dose. An indwelling central venous catheter (CVC) was present in 44 cases. Septicemia was documented in 18 (41%) patients with CVC (13 gram-positive, 5 gram-negative and 1 fungus) and in 30 (34%) patients without CVC (19 gram-positive, 10 gram-negative and 2 fungi). Coagulase-negative staphylococcus was observed in 10 out of 19 blood isolates in the presence of a CVC and in 6 out of 31 blood isolates in patients without CVC. Empiric therapy was successful in 56.4% of cases. Improvement after the addition of vancomycin or teicoplanin was observed in 38.6% of cases with a CVC and in 13.5% of those without (p less than 0.02). Only two patients died from gram negative septicemia, and the substitution of ceftriaxone with another beta-lactam was necessary in only 6% of the cases. Empiric therapy with single daily-dose ceftriaxone and amikacin appears to be effective in febrile neutropenic patients; our data, however, show the high incidence of Staphylococcus epidermidis septicemia and the frequent need to add an anti-gram-positive drug in patients with an indwelling CVC.

Pefloxacin in the treatment of gram-negative infections in patients with hematologic diseases.

Quinolones are active against gram-negative strains. They are commonly used for selective intestinal decontamination in patients with hematologic malignancies and prolonged neutropenia due to chemotherapy. In our open study we used pefloxacin, a new fluoroquinolone, for the treatment of fifteen documented gram-negative infections in hematologic patients. Thirteen patients were mildly neutropenic, and in nine cases they received oral treatment as non-hospitalized patients. Cure was achieved in fourteen cases, with microbiological eradication of the offending pathogen.

Aspergillus colonization of the nose and pulmonary aspergillosis in neutropenic patients: a retrospective study.

Fungal infections are definitely increasing in neutropenic patients with hematologic malignancies. In view of a previous report on a likely correlation between nose cultures positive for Aspergillus spp. and pulmonary aspergillosis, a retrospective study on 306 consecutive neutropenic patients was performed. Twenty-six patients had one or more nose cultures positive for Aspergillus: thirteen of them developed pulmonary aspergillosis. On the other hand, only twenty out of the remaining 280 patients with negative nose cultures developed this fungal pneumonia (p less than 0.00001). Even if negative results do not obviously exclude the possibility of invasive aspergillosis, nose cultures positive for Aspergillus might prove helpful in predicting this fungal infection in febrile neutropenic patients.

Treatment of febrile episodes in neutropenic leukemic patients with the antibiotic combinations piperacillin or ceftazidime plus amikacin: results of a randomized study.

Seventy-six consecutive neutropenic patients with hematologic malignancies, admitted to the "Department of Hematology" of Rome between March and September 1986, were randomly assigned to receive either piperacillin (300 mg/kg in four divided doses) or ceftazidime (100 mg/kg in four divided doses) plus amikacin (15 mg/kg in two divided doses) whenever they developed a febrile episode (temperature greater than 38 degrees C thrice over 12 hours, not related to drugs or transfusions, or else temperature greater than 38.5 degrees C). After 72 hours of antibiotic therapy, in case of persistent fever, piperacillin or ceftazidime was added to the ceftazidime + amikacin or piperacillin + amikacin combination, respectively. The antibiotic treatment was, however, modified according to in vitro susceptibility if a positive culture was present. Success without regimen modification was observed in both antibiotic combinations in 52.6% of cases. Considering the empiric cross of antibiotics, the response rate reached 78%. Neither toxicity nor side effects were observed in the reported groups. Considering blood isolates, we observed a greater incidence of gram-positive organisms compared with gram-negatives (28 cases vs 5 cases, 84.7% vs 15.3% respectively). Fungal infections were documented in four cases, two in each group. Even though no statistical difference was found between the two groups as far as patients not responding to the first antibiotic combination are concerned, piperacillin seems to have had more efficacy (twelve patients responding to the addition of piperacillin vs seven patients responding to the addition of ceftazidime). Piperacillin + amikacin seems to be as effective as ceftazidime + amikacin in the empirical therapy of febrile episodes in neutropenic patients.