Ubiquitinated neurites are associated with preamyloid and cerebral amyloid β deposits in patients with hereditary cerebral hemorrhage with amyloidosis Dutch type

Summary Here ditary cerebral hemorrhage with amyloidosis Dutch type (HCHWA-D) is characterized clinically by recurrent strokes and pathologically by deposition of amyloid (A) in cerebral vessel walls and, to a lesser extent, in the neuropil. Distinct from Alzheimer's disease, amyloid formation in HCHWA-D is not associated with neurofibrillary changes. Since a central issue in the pathophysiology of Alzheimer's disease and related conditions is the role of A in the neurodegencrative process, we investigated HCHWA-D brains for the presence of neuritic abnormalities using antibodies to ubiquitin and to phosphorylated neurofilaments. The study showed that amyloid deposits in the vessel walls and in the neuropil were surrounded by abnormal ubiquitinated neurites, suggesting that A deposition induces neuritic changes.Supported by the Italian Ministry of Health. Department of Social Services, and by N.I.H. Grants AG05891 and AG08721 (to B.F.)     

Lumbar disc herniation in teenagers

Summary We report 48 patients operated on for lumbar disc herniation in the second decade of life (aged 13–20 years) in our Neurosurgical Division. To analyze the clinical and diagnostic features and surgical outcome of the disease in teenagers and to point out any differences from adults, we made a detailed study of over 900 juvenile cases and compared them with 11000 adult cases reported in the literature. Low-back pain proved to be less frequent among youngsters both as a first symptom and at diagnosis, while sensorimotor deficits have the same frequency in the two age groups. Herniation occurs more often at L4–L5 and is more frequently median among teenagers. The long-term surgical results in children and adolescents are better than in adults.     

Laparoscopic management of urachal cysts in adulthood

PURPOSE: Managing persistent and symptomatic urachal anomalies requires wide surgical excision. Such intervention is recommended to prevent symptom recurrence and complications, most notably malignant degeneration. However, traditional open excision is associated with significant morbidity and prolonged convalescence. We report our experience with the laparoscopic excision of urachal remnants as a less morbid, minimally invasive surgical alternative. MATERIALS AND METHODS: Between October 1993 and December 1999, 4 patients with a mean age of 43.3 years who had a symptomatic urachal cyst underwent laparoscopic radical excision of the urachal remnant. Using 2, 10 mm. and 1 or 2, 5 mm. ports the urachus and medial umbilical ligaments were divided at the umbilicus cephalad to the cyst. The specimen, which included the urachus, cyst and medial umbilical ligaments, was then separated from the bladder dome with or without the bladder cuff and removed intact. We reviewed the perioperative records to assess morbidity, recovery and outcome. RESULTS: All 4 procedures were completed successfully. No intraoperative or postoperative complications were reported at a mean followup of 15 months (range 2 to 24). Mean operative time was 180 minutes (range 150 to 210) and average hospital stay was 2.75 days (range 1 to 4). Pathological evaluation confirmed a benign urachal remnant in each case. All patients resumed normal activity within 2 weeks. CONCLUSIONS: To minimize the morbidity of radical excision the laparoscopic management of benign urachal remnants in adulthood is efficacious and our preferred method of management.     

ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia.

PURPOSE: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. PATIENTS AND METHODS: Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. RESULTS: Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). CONCLUSION: Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.     

Antibacterial macrolides: a drug class with a complex pharmacological profile.

Macrolides are widely used antibacterial agents. Although generally well tolerated, they have a number of important additional pharmacological effects, which can sometimes result in significant adverse reactions. This review focuses on three of these side effects: the prokinetic action associated with stimulation of motilin receptors, the proarrhythmic effect due to prolongation of the QT interval of the electrocardiogram and the potential for drug interactions due to inhibition of drug metabolising enzymes. For macrolides that have obtained marketing authorisation in Italy, United Kingdom or United States of America, we also considered whether these actions are properly reported in the approved summaries of the product characteristics and tried to provide strategies to identify patients at risk of significant side effects when macrolides are administered.     

Densiron 68 heavy silicone oil in the management of inferior retinal detachment recurrence: analysis on functional and anatomical outcomes and complications

AIM: To assess the efficacy and safety of a heavy silicone oil (Densiron 68) in the management of inferior retinal detachment recurrence. METHODS: A retrospective non-comparative consecutive case series study. Forty-nine cases of complex inferior retinal detachment were treated using Densiron 68 heavy silicone oil (HSO) as the endotamponade. Our main purpose was anatomic reattachment following Densiron 68 removal. Functional outcomes, rate of recurrences, the presence of inflammatory complications and intraocular pressure alterations were evaluated. RESULTS: Forty-nine patients affected by complex retinal re-detachment were recruited. The mean follow-up was 7.6 (±1.5) mo. The mean best corrected visual acuity after Densiron 68 removal was 0.95 logMAR, standard error (SE: 0.068). Retinal reattachment was 61.2% after first surgery and 81.6% after second surgery. Nineteen cases (38.8%) had recurrences when intraocular heavy silicon oil was in situ, 26.3% (5 cases) of which involved the inferior retina. CONCLUSION: Densiron 68 ef?ciently fills the inferior retinal periphery and might lower the risk of inferior proliferative vitreoretinopathy development, in particular after a standard silicon oil tamponade that reduces the proliferative process in the upper quadrants of the retina.     

Cotard's Syndrome Triggered by Fear in a Patient with Intellectual Disability: Causal or Casual Link?

Cotard's syndrome is a neuropsychiatric disease characterized by a variety of nihilistic delusions, commonly associated with several psychotic and major affective disorders, and neurological diseases, including stroke, dementia, and mental retardation. A 39-year-old male with mental retardation developed Cotard's syndrome, following an important episode of fear. During admission to our neurological unit, the patient underwent an accurate assessment, including neuroradiological, clinical, and neuropsychological examinations. At the psychiatric evaluation, he presented nihilistic delusions, in which he negated the existence of his body parts and the existence of his family members. The neuropsychological assessment ruled out other possible causes of misidentification, including the post-traumatic stress disorder. Thus, since also organic causes of Cotard's syndrome were excluded, the correlation between fear and the syndrome has been postulated and the patient opportunely treated, using a multidisciplinary approach. Our case suggests that in predisposed individuals negative emotions, including fear, may lead to delusional syndromes.     

Fractional CO₂ vaginal laser for the genitourinary syndrome of menopause in breast cancer survivors

Adjuvant chemotherapy and endocrine therapy can induce early iatrogenic menopause or worsen pre-existing menopausal symptoms in breast cancer survivors (BCS). The second most frequent menopausal symptom after hot flushes is the genitourinary syndrome (GSM). Since hormone replacement therapy is contraindicated in BCS, vaginal laser might represent a new nonhormonal option for GSM. This study aims at evaluating the effectiveness of the fractional CO₂ vaginal laser for GSM in BCS compared with healthy women. This is a retrospective study on 135 postmenopausal women (45 BCS and 90 healthy women) who underwent fractional CO₂ laser for GSM. Objective (VHI and VVHI) and subjective outcomes (VAS for dyspareunia and vaginal dryness and a pain questionnaire) were evaluated at baseline visit and at every follow-up visit. Subjective and objective parameters improved significantly in both groups after laser therapy. The improvement was progressive and long-lasting up to 12 months after the end of the treatment. No severe adverse events were observed during the treatment. Fractional CO₂ vaginal laser induces a significant and long-lasting improvement on GSM symptoms in BCS. However, this improvement is slower than in healthy women undergoing the same treatment. Laser therapy turns out to be safe and well-tolerated.     

Management of respiratory complications and rehabilitation in individuals with muscular dystrophies: 1st Consensus Conference report from UILDM - Italian Muscular Dystrophy Association (Milan,January 25-26, 2019)

Respiratory complications are common in the patient with muscular dystrophy. The periodic clinical and instrumental respiratory evaluation is extremely important. Despite the presence in the literature of updated guidelines, patient associations often report lack of knowledge of these pathologies, particularly in peripheral hospitals. The purpose of this work, inspired by the Italian Muscular Dystrophy Association (UILDM) is to improve management of respiratory problems necessary for the management of these patients complex. To this end, the main items that the specialist can meet in the follow-up of these pathologies have been analyzed and discussed, among which the respiratory basal evaluation, the criteria of adaptation to non-invasive ventilation, management of bronchial secretions, situations of respiratory emergency, indications for tracheostomy and the subject of advance directives of treatment (DAT).Key words: respiratory failure, muscular dystrophy, cough efficacy, spirometry, polygraphy, non-invasive ventilation, arterial blood gases, cough machine, invasive ventilation, tracheostomy, mechanical ventilation     

Joint line position in revision total knee arthroplasty: the role of posterior femoral off-set stems

BackgroundElevation of the joint line frequently occurs in revision total knee arthroplasty (RTKA) because of a wider flexion space than extension space. One solution to balance this flexion-extension space involves the introduction of couplers between the stem and femoral components, and the use of posteriorly offset femoral stems that we hypothesized would improve gap balancing and facilitate joint line restoration.MethodsWe retrospectively reviewed a selected series of 43 RTKA. Postoperative joint line height was subtracted from intended height using postoperative lateral radiographs. The value was negative if the joint line position was lowered, and positive if raised.ResultsForty knees were followed for a mean of 3.5 years. Mean postoperative joint line position change from intended position was 1.5 mm (range ? 2.5–7.5 mm). In 28 knees (70%), the joint line position was restored to within ± 2 mm of the intended position; in eight knees (20%), from 2–4 mm; and in four knees (10%), > 4 mm. Joint line position was raised in 32 knees (80%) and lowered in eight (20%). In the offset stem knees, the intended joint line position was 0.9 mm (range ? 1.2–3.4 mm) as compared with 3.2 mm (range ? 2.5–7.5 mm) for the straight stem knees.ConclusionsA coupler system between the femoral stem and femoral component restored the joint line in 70% of cases. The posterior offset stem provided increased posterior condylar offset, addressed the wider flexion space, provided better positioning of the stem, and restored the joint line.Level of evidenceTherapeutic Study Level IV