Jumping translocations in multiple myeloma

Jumping translocations (JT) have been defined as nonreciprocal translocations involving a same donor chromosome arm or chromosome segment onto two or more recipient chromosomes in different cell lines in the same patient, leading to a mosaic karyotype. This definition has been expanded to also include extra copies of a same donor segment on different recipient chromosomes in a single clone. Six patients with multiple myeloma and JT involving chromosome arm 1q were identified among 37 patients presenting with chromosome 1 abnormalities. All six patients had an advanced disease and a short survival. The literature review allowed us to identify 24 additional patients with JT. Chromosomes 16 and 19 were the recipients in 11 (45.8%) and 6 (25%) of these 24 patients, respectively. Breakpoints on the recipient chromosomes were pericentromeric in 46.2% and telomeric in 40.4% of the breakpoints recorded. Since telomeres are made of (TTAGGG)n tandem DNA repeats that are also found in the pericentromeric heterochromatic regions (interstital telomeric sequences), it is presumed that jumping translocations arise through illegimate recombination between telomere repeat sequences and interstitial telomeric sequences.     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Conservative treatment in epithelial ovarian cancer: results of a multicentre study of the GCCLCC (Groupe des Chirurgiens de Centre de Lutte Contre le Cancer) and SFOG (Société Francaise d'Oncologie Gynécologique)

BACKGROUND: Results of conservative management of epithelial ovarian cancer (EOC) remain controversial in the literature. The aim of this study was to assess the clinical outcomes and fertility following fertility-sparing surgical management of EOC in a retrospective multicentre study. METHODS: A multicentre retrospective study was performed by members of two French groups. Six inclusion criteria were defined: (i) Histological review by the same pathologist; (ii) age < or =40 years; (iii) conservative management; (iv) complete peritoneal staging; (v) delivery of a platinum-based chemotherapy in stage > or = IC; and (vi) follow-up >1 year. RESULTS: Thirty-four patients fulfilled the inclusion criteria: 30 had stage IA disease; three had stage IC and one had stage IIA. Eleven patients had recurrence: 10 patients had invasive disease and one had borderline recurrence. Among 10 patients with invasive recurrence, initial stage and grade were: stage IA G1, n = 1; stage IA G2, n = 4; stage IA G3, n = 1; and stage> or = IC, n = 4. All patients with stage > IA had recurrence. Ten pregnancies were observed in nine patients. CONCLUSION: Conservative surgery for patients with EOC could be considered in young patients with stage IA G1 disease. This procedure should not be performed in patients with FIGO stage > IA.     

Language changes in schizophrenia: a limited replication

Similar changes in the spoken language of schizophrenic patients were demonstrated in two separate studies. Schizophrenic patients used less depth of clausal embedding and fewer reduced relative clauses; they uttered more semantically deviant sentences and were more dysfluent than either manic patients or control subjects. They appeared to demonstrate a language impairment characterized especially by reduced syntactic complexity. Four linguistic variables in a discriminant analysis produced an overall diagnostic confidence for schizophrenia in "grouped" subjects of 87 percent, replicating at 83 percent for "ungrouped" subjects from a separate study. These results demonstrate the stability of language changes in schizophrenia, together with acceptable levels of diagnostic sensitivity and specificity. Currently, the possible diagnostic utility of language analysis is constrained by its time-consuming nature. The issue of whether the language changes represent a specific (linguistic) or general cognitive impairment is being addressed in a second phase of the current study.     

Capsaicin and neurokinin A-induced bronchoconstriction in the anaesthetised guinea-pig: evidence for a direct action of menthol on isolated bronchial smooth muscle

1. For many years menthol has been used in the treatment of respiratory disorders although, a bronchodilator effect of menthol has yet to be described. Using the bronchoconstrictors capsaicin (acting via stimulating the release of neuropeptides from sensory afferents) and neurokinin A (NKA) we have raised airways resistance in the guinea-pig (GP) and studied the effect of menthol on both capsaicin and NKA-induced bronchoconstriction in vivo. In vitro the effect of menthol on acetylcholine (ACh) and KCl precontracted GP bronchi was also studied.
2. GP (n=13) were anaesthetized (urethane 1.5 g kg⁻¹, i.p.) and a bolus injection of capsaicin (7.5 μg ml⁻¹, i.v.) or infusion of NKA (1 μg min⁻¹, i.v.) was given either in the presence of air (0.81 min⁻¹) or air impregnated with menthol vapour (7.5 μg l⁻¹) freely breathed from a tracheal cannula via a T-piece. Airways resistance (R_aw) and ventilation were measured throughout. Bronchi of mean internal diameter (1029+73.6 μm; n=24) were removed from GP (n=16) and mounted in the Cambustion myograph. Bronchial rings were maximally precontracted with 80 mM KC1 or 2 mM ACh. Relaxation due to a cumulative dose of menthol (1–3000 μM) was measured.
3. Menthol produced a significant (P<0.05) 51.3% reversal of the capsaicin-induced increase in R_aw, and also inhibited the significant (P<0.05) reduction in minute ventilation (V_e) associated with the capsaicin-induced increased in R_aw. Menthol also caused a significant (P<0.05) 41% reversal of the NKA-induced increase in R_aw. The NKA-induced decrease in V_e was again significantly (P<0.05) reversed with menthol inhalation. Menthol caused a significant (P<0.001) dose-dependent relaxation of KCl and ACh precontracted bronchi.
4. We have shown that menthol attenuates both capsaicin and NKA-induced bronchoconstriction in vivo and relaxes KCl and ACh preconstricted bronchi in vitro. Menthol inhibition of NKA and capsaicin-induced bronchoconstriction could be, in part, explained by a direct action of menthol on bronchial smooth muscle.

     

The vasa vasorum and angioplasty

Interruption of flow in the vasa vasorum may lead to medial necrosis and aneurysm formation. The purpose of this study was to determine whether angioplasty produces significant alterations in the morphology or blood flow of the vasa vasorum of the dilated artery. The morphology of the canine vasa vasorum was studied before and after angioplasty; in a separate experiment vessel wall blood flow (VWBF) in canine carotid arteries was measured after angioplasty to determine whether physiologic regulation of the blood flow was disrupted by arterial dilation. No morphologic changes could be demonstrated in the vasa vasorum of the dilated artery; however, VWBF was increased by 1194 +/- 215% (mean +/- standard error, p less than 0.01) between 90 and 120 minutes after angioplasty. VWBF in the adjacent nondilated arterial segment was also increased (720 +/- 177% between 10-30 minutes, p less than 0.01) but returned toward normal after 60 minutes. Adenosine caused a "paradoxical" decrease in VWBF (p less than 0.05) of the dilated arterial segment while causing increased VWBF (p less than 0.05) in the thoracic aorta. Angioplasty appears to produce persistent hyperemia in the dilated arterial wall. A paradoxical response to adenosine suggests that vasa vasorum in the dilated arterial segment are maximally vasodilated. This may be due to mechanical disruption of vasomotor tone or to release of vasoactive substances.     

Clinical outcome after laparoscopic pure management of borderline ovarian tumors: results of a series of 34 patients.

BACKGROUND: The aim of this study was to assess clinical outcome after laparoscopic treatment of borderline ovarian tumor (BOT). PATIENTS AND METHODS: Thirty-four patients treated initially and/or for recurrent disease using a laparoscopic approach for BOT from 1984 to January 2002. RESULTS: Thirty-four patients underwent laparoscopic pure treatment (without conversion by laparotomy and/or reassessment surgery by laparotomy) for BOT. Conservative treatment was performed in 31 (91%) patients. Median follow-up time was 45 months (range 6-228). Six (17%) patients recurred (in the remaining ovary following conservative surgery in five patients and in the peritoneum in one patient). Two port-site metastases were observed. None of the patients had recurrent disease in the form of ovarian carcinoma. Nine spontaneous pregnancies were observed in six patients from a group of 15 patients desiring pregnancy. All patients are alive today and disease-free. CONCLUSION: These results seem to demonstrate that laparoscopic treatment can be safely performed in young patients with early stage BOT. Such a procedure is then feasible, but should be evaluated in patients with BOT and peritoneal implants.     

Prognostic factors for patients with advanced stage serous borderline tumours of the ovary.

BACKGROUND: The aim of this study was to determine the prognostic factors for patients with advanced stage, low malignant potential ovarian tumour (LMPOT). PATIENTS AND METHODS: A retrospective review of 80 patients with serous LMPOT and peritoneal implants treated at or referred to our institution was carried out. RESULTS: Sixty-five patients had non-invasive implants. Fifteen patients had invasive implants. Twenty-nine patients had stage II and 51 patients had stage III disease. Three patients died of evolutive invasive disease and four of complications of treatment. The only prognostic factor of progression to 'evolutive invasive disease' is the pathologic subtype of peritoneal implants. The 5-year rates of evolutive invasive disease in patients with non-invasive implants and invasive implants were 2% and 31%, respectively (P <0.002). CONCLUSIONS: In this series, the only prognostic factor for patients with advanced stage borderline tumour is the type of peritoneal implant. More patients died of the treatment's complications than of the disease itself. The patients' prognosis with non-invasive implants seems to be excellent, and conservative management could be discussed in younger patients.     

Longitudinal neurological follow-up of a group of HIV-seropositive and HIV-seronegative hemophiliacs: results from the hemophilia growth and development study

BACKGROUND: Boys and young men with hemophilia treated with factor infusions before 1985 had a substantial risk of acquiring the human immunodeficiency virus (HIV) and the acquired immunodeficiency syndrome. This study was designed to assess the effects of HIV and hemophilia per se on neurological function in a large cohort of subjects with hemophilia, and to investigate the relationships between neurological disease and death during follow-up. METHODS: Three hundred thirty-three boys and young men (207 HIV seropositive and 126 HIV seronegative) were evaluated longitudinally in a multicenter, multidisciplinary study. Neurological history and examination were conducted at baseline and annually for 4 years. The relationship between neurological variables, HIV serostatus, CD4+ cell counts, and vital status at the conclusion of the study was examined using logistic regression models. RESULTS: The risks of nonhemophilia-associated muscle atrophy, behavior change, and gait disturbance increased with time in immune compromised HIV-seropositive subjects compared with HIV seronegative or immunologically stable HIV-seropositive subjects. The risk of behavior change in immune compromised HIV-seropositive hemophiliacs, for example, rose to 60% by year 4 versus 10% to 17% for the other study groups. Forty-five subjects (13.5%), all of whom were HIV seropositive, died by year 4. Subjects who died had had increased risks of hyperreflexia, nonhemophilia-associated muscle atrophy, and behavior change. CONCLUSIONS: These results indicate that immune compromised, HIV-seropositive hemophiliacs have high rates of neurological abnormalities over time and that neurological abnormalities were common among subjects who later died. By contrast, immunologically stable HIV-seropositive subjects did not differ from the HIV-seronegative participants. Hemophilia per se was associated with progressive abnormalities of gait, coordination, and motor function.