Long-term outcome and quality of life after nonaneurysmal subarachnoid hemorrhage

Purpose  

Nonaneurysmal subarachnoid hemorrhage (SAH) is an uncommon form of SAH. As nonaneurysmal SAH is often concentrated around the pons and midbrain, the term perimesencephalic SAH (pmSAH) is widely accepted to describe this entity, though there are patients with a more widespread distribution of subarachnoid blood (non-pmSAH). The outcome of pmSAH is commonly regarded as good, although often outcome is not analyzed using standardized tools of outcome measurement. In this study we focused on the patient’s quality of life after nonaneurysmal SAH.     

High Expression of Cathepsin D in Non-Hodgkin’s Lymphomas Negatively Impacts on Clinical Outcome

The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin’s Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as ‘low expressing’ (< 20% of tumor cells) or ‘highly expressing’ (≥ 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases; p = 0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases; p = 0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (~20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells (~70% at 5 year). This correlation was statistically significant (log-rank test, p = 0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs.     

Rapidly developing giant sized lupus vulgaris on the chest associated with bilateral scrofuloderma on the neck

Lupus vulgaris and scrofuloderma are the opposite poles of cutaneous tuberculosis. Lupus vulgaris of a giant size and scrofuloderma in the vicinity of this lesion were both present in a 70-year-old female patient. The purified protein derivative of tuberculin (PPD) skin test was strongly positive. In histopathological examination, granulomatous infiltration without caseation necrosis was seen in the dermis. The patient was treated with a four-drug therapy consisting of pyrazinamide (25 mg/kg), isoniazid (5 mg/kg), rifampin (10 mg/kg) and ethambutol (15 mg/kg) daily for 2 months, followed by dual therapy with isoniazid and rifampin for 6 months. Her cutaneous lesions significantly regressed after 4 months, leaving keloid scars.     

Plexiform neurofibroma of the tongue: a case report of a child

A three-year-old girl with a lingual plexiform neurofibroma treated by total excision is presented. Despite their occurrence in the head and neck region, neural sheath tumors are rarely encountered in the oral cavity. It is reported that 4-7% of patients affected by neurofibromatosis display oral manifestations. Neurofibromatosis is characterized by café-au-lait spots and cutaneous neurofibromas. Plexiform neurofibroma is said to be indicative of von Recklinghausen's disease (VRD) even though it may be the only manifestation of the disease. Generally, surgical resection represents the treatment of choice and the diagnosis can only be confirmed after histological examination. Affected patients need regular follow-up to detect malignant degeneration, an early recurrence or appearance of other manifestations of VRD.     

The frequency of auditory neuropathy detected by universal newborn hearing screening program

OBJECTIVE: Auditory neuropathy/auditory dyssynchrony (AN/AD) has become a well-accepted clinical entity. The combined use of oto-acoustic emissions (OAEs) and auditory brainstem response (ABR) testing in the universal newborn hearing screening (UNHS) has led to the easy recognition of this disorder. Although, we are now able to diagnose AN/AD reliably, little is known about its epidemiology, etiology, and especially the frequency of its occurrence. The primary goal of this study was to determine the frequency of AN/AD in the Western Anatolian region of Turkey. The secondary goal was to compare the detection rate of AN/AD before and after the implementation of the UNHS in the audiology department of Dokuz Eylul University Hospital. METHOD: Between 2005 and 2007, among the 23,786 newborns who were screened by automated click evoked oto-acoustic emissions (a-CEOAE) and automated auditory brainstem responses (a-ABRs), 2236 were referred to our department. All necessary audiological tests were performed for all the referred newborns. Among them, babies with deficient or abnormal ABR in combination with normal OAEs were considered as having AN/AD. These babies were evaluated with additional diagnostic audiological tests. Furthermore, comparison of the incidence of children diagnosed with AN/AD before and after the implementation of UNHS in our audiology department was also performed. RESULTS: Among the referred newborns, 65 had abnormal or deficient ABR test results. Ten of these 65 newborn babies (mean diagnostic age: 5.7 months) with hearing impairment showed electrophysiological test results that were consistent with AN/AD. The frequency of AN/AD in these 65 children with hearing loss was 15.38%. Moreover, the frequency of AN/AD within UNHS was found to be 0.044%. Seven of the 10 babies with AN/AD had hyperbilirubinemia as a risk factor, which is a high rate to be emphasized. On the other hand, the retrospective investigation of children diagnosed with AN/AD in the same audiology department between 1999 and 2005 (i.e. before the implementation of UNHS) revealed only 7 children, with an average diagnostic age of 34 months. CONCLUSION: After implementing the UNHS, the incidence of AN/AD in the audiology department increased from 1.16 to 4.13. Furthermore, the age of diagnosis of AN/AD decreased from 34 months to 5.7 months. This study shows that AN/AD, when screened, is a comparatively common disorder in the population of hearing-impaired infants. While newborn hearing screening provides early detection of babies with hearing loss, it also helps to differentiate AN/AD cases when the screening is performed with both a-ABR and automated oto-acoustic emission (a-OAE) tests. Thus, the routine combined use of a-ABR and a-OAE tests in UNHS programs, especially for the high-risk infants, can provide better detection of newborns with AN/AD. Furthermore, hyperbilirubinemia is merely an association and maybe etiologically linked.     

Therapeutic plasma exchange for the treatment of thrombotic thrombocytopenic purpura: a retrospective multicenter study.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare disease that is fatal if it is not treated. Therapeutic plasma exchange (TPE) has resulted in excellent remission and survival rates in TTP patients. MATERIAL AND METHODS: We describe our experience with 52 TTP patients treated with TPE during the past eight years (65% of the patients were females; patient median age=34 years, range: 17-73). TPE was carried out 1-1.5 times plasma volume. Fresh frozen plasma (FFP) or cryosupernatant plasma (CSP) was used as the replacement fluid. TPE was performed daily until normalization of serum LDH and recovery of the platelet count to >150 x 10(9)/dL; TPE was then slowly tapered. Clinical, laboratory data, the number of TPE, other given therapy modalities, treatment outcomes and survival rate were evaluated retrospectively. RESULTS: Overall response (OR) and complete response (CR) rates were 77% and 60%, respectively. Response was excellent in 82.8% of the patients with primary TTP among whom 74.2% were CR. Additionally, there were statistical differences in terms of CR rate between patients with primary TTP and secondary TTP (74.2% vs. 29.4%; p=0.005). OR and CR rates were 79% and 57.9% in patients on TPE alone and 75.8% and 60.6% in patients on TPE+prednisolone, respectively (p=1 and p=0.8). Additionally, there were no statistical differences in terms of OR and CR rates between patients on TPE with FFP and CSP (p=0.25 and p=0.16, respectively). The presence of fever and the number of TPE were statistically important factors influencing the probability of response in multivariate logistic regression analysis (p<0.01 and p<0.01, respectively). Additionally, in multivariate Cox's regression analysis, the probability of survival was higher in patients who were responsive to treatment compared to patients who were unresponsive (p<0.001). CONCLUSION: TPE is an effective treatment for primary TTP; however, it may be used as adjunctive therapy for secondary TTP until it is under control. The addition of steroids to TPE had no advantage compared to TPE alone. CSP as replacement fluid is not superior compared to FFP. Fever appears to be a bad prognostic indicator. Therefore, prolonged treatment with TPE may be needed in patients with fever.     

Furosemide rescues hypercalciuria in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis model

Aim

Perturbed calcium homeostasis limits life expectancy in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC). This rare disease occurs by loss-of-function mutations in CLDN16 or CLDN19 genes, causing impaired paracellular reabsorption of divalent cations along the cortical thick ascending limb (cTAL). Only partial compensation takes place in the ensuing late distal convoluted tubule, connecting tubule, and collecting duct, where the luminal transient receptor potential channel V5 (TRPV5), as well as basolateral plasma membrane calcium ATPase (PMCA) and sodium-potassium exchanger (NCX1) mediate transcellular Ca²⁺ reabsorption. The loop diuretic furosemide induces compensatory activation in these distal segments. Normally, furosemide enhances urinary calcium excretion via inhibition of the aforementioned cTAL. As Ca²⁺ reabsorption in the cTAL is already severely impaired in FHHNC patients, furosemide may alleviate hypercalciuria in this disease by activation of the distal transcellular Ca²⁺ transport proteins.

Methods

Cldn16-deficient mice (Cldn16^−/−) served as a FHHNC model. Wild-type (WT) and Cldn16^−/− mice were treated with furosemide (7 days of 40 mg/kg bw) or vehicle. We assessed renal electrolyte handling (metabolic cages) and key divalent transport proteins.

Results

Cldn16^−/− mice show higher Ca²⁺ excretion than WT and compensatory stimulation of Cldn2, TRPV5, and NCX1 at baseline. Furosemide reduced hypercalciuria in Cldn16^−/− mice and enhanced TRPV5 and PMCA levels in Cldn16^−/− but not in WT mice.

Conclusions

Furosemide significantly reduces hypercalciuria, likely via upregulation of luminal and basolateral Ca²⁺ transport systems in the distal nephron and collecting duct in this model for FHHNC.