Primary breast lymphoma: outcome of 7 patients and a review of the literature

Primary breast lymphomas (PBL) are uncommon neoplasms. Seven PBL were diagnosed between March 1993 and October 2002. A lumpectomy (n = 4) or radical mastectomy (n = 3) was performed; 5 patients were in clinical stage (CS) II and 2 in CS IV; 6 patients received the CEOP regimen (cyclophosphamide, vincristine, epirubicin and prednisone) after surgery and 4 also had additional radiotherapy; 1 patient did not receive any treatment after local excision. Five patients (71%) achieved complete remission and 2 (29%) partial remission, with an overall response rate of 100%. All remitter patients are alive and well after a median follow-up of 75 months (range 10 - 121 months). Two patients in partial remission died of progressive disease. After a median follow-up of 99 months (range 84 - 111 months) for surviving patients, the 10 year overall and disease-free survival rates are both 71%, with 5 patients well and still free of disease. We conclude that the optimal sequence of full-dose anthracycline-containing regimens and radiation therapy should be the treatment of choice for patients with PBL.     

Mediators involved in decreasing peripheral vascular resistance with carbachol in the rat hind limb perfusion model

We examined the involvement of nitric oxide (NO) and/or endothelium-derived hyperpolarizing factor (EDHF) in decreasing peripheral vascular resistance in the rat hind limb perfusion model and analyzed the identity of EDHF in this model. The potency of carbachol (CCh) to produce relaxation was quantitatively similar to sodium nitroprusside (SNP). CCh-induced relaxation was abolished after endothelial denudation, but resistant to nitroarginine and indomethacin. The relaxation was inhibited by tetraethylammonium, ouabain, charybdotoxin plus apamin, and under depolarization. SNP-induced relaxation was accompanied by increased cGMP production, which was inhibited by ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-l-one). Although CCh produced a similar extent of relaxation to SNP, the cGMP level was 24 times lower than that with SNP. Low KCl produced a definite relaxation, which was inhibited by ouabain, but independent of NO, prostacyclin, and endothelium. 1-EBIO (1-ethyl-2-benzimidazolinone) as an activator of IK(Ca) channel also produced a concentration-dependent relaxation, which was inhibited by charybdotoxin, ouabain, and depolarization, but independent of NO and prostacyclin. Clotrimazole and 17-octadecynoic acid as inhibitors of P(450) monooxygenase inhibited the CCh-induced relaxation. Meanwhile, catalase at a concentration sufficient to inhibit H(2)O(2)-induced relaxation did not exert definite inhibition of the CCh-induced relaxation. These results suggest that CCh produces an endothelium-dependent, EDHF-dependent, and NO-cGMP-independent relaxation and that K(+) and metabolite(s) of P(450) monooxygenase possibly play an important role for this relaxation.     

Sarcoidosis (after cosmetic intervention)

The authors' report a case of a 26-year-old female. In 1996, and 1997 she underwent cosmetic lip augmentations (polymethyl methacrylate and silicone). After a six-year symptom free period sudden swelling of the lips developed and red-brown papules and subcutaneous nodules appeared in the scars of various body parts ( permanent make-up, tattoos, umbilical piercing). The clinical features, radiological signs and histology proved the diagnosis of systemic sarcoidosis. Systemic corticosteroid treatment was introduced. After 4 months of treatment the pulmonary and clinical symptoms showed regression. To be able to suspend the systemic treatment the silicone implant was removed.     

Update of the minimally invasive therapies for benign prostatic hyperplasia

PURPOSE OF REVIEW: The elevated impact benign prostatic hyperplasia has on patient quality of life has determined continuous research into the development of minimally invasive therapies aimed at restoring or preserving a good quality of life. The purpose of this review is to highlight recent developments in the field of minimally invasive treatment of benign prostatic hyperplasia, and to determine their possible impact on everyday clinical practice. RECENT FINDINGS: Recent publications have described some interesting new therapies and provided data concerning long-term follow up and cost-effectiveness that have been lacking up until now. The review mainly focuses on transurethral microwave thermotherapy, interstitial laser coagulation, transurethral laser ablation, laser prostatectomies (resection and enucleation), transurethral ethanol injection therapy, transurethral electrovaporization, and high-power (80-W) potassium titanyl phosphate laser vaporization. SUMMARY: Recent developments, new approaches and long-term reports of previously described minimally invasive therapies for the treatment of benign prostatic hyperplasia are presented. Cost-effectiveness studies were also carried out to complete the comparison with standard everyday procedures. Currently, transurethral microwave thermotherapy seems to offer the soundest basis for management of the condition, providing the longest term follow up and the largest numbers of studies completed to date. Among surgical alternatives, holmium laser enucleation has gained ground as an encouraging new approach, being similar to standard transurethral resection of the prostate, but reducing perioperative morbidity with the same long-term results. More randomized comparisons correctly conducted need to be undertaken before an accurate general picture is available for the urologist.     

No evidence of ATP1A2 involvement in 12 multiplex Italian families with benign familial infantile seizures

A missense mutation in the gene encoding the alpha(2) subunit of the Na(+),K(+) ATPase pump (ATP1A2) was found in a family with both familial hemiplegic migraine (FHM) and Benign Familial Infantile Seizures (BFIC). As it is still unclear whether ATP1A2 is responsible for pure BFIC syndromes, we checked mutations of the ATP1A2 gene in probands of 12 Italian multiplex families with pure BFIC, who were negative for mutations in the SCN2A gene. We screened the ATP1A2 gene by denaturing high performance liquid chromatography (D-HPLC) and direct sequencing of DNA fragments showing an aberrant elution pattern. We found one exonic variant and five intronic variants, none leading to significant amino acid changes or causing a modification of the physiological mRNA maturation. The ATP1A2 gene does not appear to be involved in the ethiopathogenesis of pure BFIC syndromes, at least in the explored Italian multiplex families. It could be either responsible of a minority of cases, or of complex syndromes where BFIC and FHM co-occur.     

Sodium enoxaparin treatment of sensorineural hearing loss: an immune-mediated response?

The authors propose the existence of a new entity of autoimmune sensorineural hearing loss on the basis of diagnostic study and treatment experience with a series of 30 patients. Immunological mechanisms play an important role in the pathogenesis and natural course of various inner-ear diseases. Patients may present clinically with symptoms resembling Ménière's disease or even with sudden deafness. Currently, no widely used standard protocol for treatment of this autoimmune sensorineural hearing loss exists. Prompted by such observations, we implemented a protocol using a particular kind of heparin--sodium enoxaparin--with a low molecular weight. Patients were randomly assigned to two groups; to those in the first group, enoxaparin was administered subcutaneously at a dose of 2,000 IU twice daily for 10 days; the patients in the second group were treated with placebo. At the beginning and at the end of the therapy period, the patients were evaluated by instrumental examinations. Specifically excluded were patients with abnormal known coagulation. On discharge, all patients treated with enoxaparin presented both a subjective and objective decrease in symptoms. No patient experienced side effects from this treatment. The results indicate that administration of sodium enoxaparin abates sensorineural hearing loss in patients with autoimmune diseases. The clinical response to therapy can confirm diagnosis.     

Mitochondrial succinate is instrumental for HIF1alpha nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions

The genes encoding succinate dehydrogenase (SDH) subunits B, C and D, act as tumour suppressors in neuro-endocrine tissues. Tumour formation has been associated with succinate accumulation. In paraganglioma cells, two forms of SDHA (type I, II) were found which might preclude significant succinate accumulation in the case of a mutation in either form. In fibroblasts only SDHA type I is found. In these cells, SDHA type I mutation leads to SDH deficiency, succinate accumulation and hypoxia-inducible factor 1alpha(HIF1alpha) nuclear translocation. HIF1alpha nuclear translocation was not observed in ATPase-deficient fibroblasts with increased superoxide production and was found to be independent of cellular iron availability in SDHA-mutant cells. This suggests that neither superoxides nor iron were causative of HIF1alpha nuclear translocation. Conversely, alpha-ketoglutarate (alpha-KG) inhibits this nuclear translocation. Therefore, the pseudo-hypoxia pathway in SDH-deficient cells depends on the HIF1alphaprolyl hydroxylase product/substrate (succinate/alpha-KG) equilibrium. In SDH deficiency, organic acids thus appear instrumental in the HIF1alpha-dependent cascade suggesting a direct link between SDH and tumourigenesis.