Increased augmentation index in patients with cystic fibrosis.

Increased large artery stiffness occurs in a range of inflammatory conditions indicating an ageing of the vasculature and additionally being an independent risk factor for cardiovascular events. We determined large artery parameters in adults with cystic fibrosis (CF). 50 clinically stable adult patients with CF (mean+/-sd age 28.0+/-8.2 yrs) and 26 controls matched for age, sex and body mass index were studied. Central aortic blood pressure, augmentation index (AIx) and aortic pulse wave velocity (PWV) were determined using applanation tonometry. Lung function, diabetic status and C-reactive protein (CRP) were also determined. Mean+/-sd AIx was greater in patients than controls, 8.5+/-11.1% and -1.8+/-13.1%, respectively (p<0.001), while PWV was similar. Although AIx was greatest in the sub-group with CF-related diabetes (CFRD), it was also increased in the non-CFRD sub-group when compared with controls. In patients, AIx was related to log(10) CRP (r = 0.33) and forced vital capacity (r = -0.34; both p<0.05), and CRP remained predictive in multiple regression. AIx is increased in adults with CF, in the presence of a normal blood pressure and independent of diabetic status. AIx was related to the systemic inflammatory status. These findings have implications for management and require further exploration so that cardiovascular health can be maintained.

A novel approach to central venous catheter thrombosis in a patient with cystic fibrosis.

Catheter directed thrombolysis has been described as a treatment for large pulmonary emboli resistant to systemic therapy [Kelly P, Carroll N, Grant C, Barrett C, Kocka V. Successful treatment of massive pulmonary embolism with prolonged catheter-directed thrombolysis. Heart Vessels 2006;21:124?6]. We now describe a case in which local catheter directed thrombolysis, via a peripherally inserted central catheter (PICC), was used to treat a large thrombus surrounding the tip of an indwelling central venous line that was causing superior vena cava obstruction (SVCO), in a patient with cystic fibrosis.

Predictive factors for the development of scoliosis in Duchenne muscular dystrophy.

OBJECTIVE: Scoliosis is a frequent complication (68-90%) of Duchenne muscular dystrophy (DMD). Prevention of limb deformities, rehabilitation in knee-ankle-foot-orthoses (KAFOs) and glucocorticoids prolong walking and standing, and might reduce scoliosis. We evaluated possible predictive factors for scoliosis development in a large DMD population. METHODS: Case notes of 123 DMD boys, > or = 17 years, followed at our centre between 1992 and 2002 were reviewed. Univariate analysis was used to relate two outcome measures (age at onset of scoliosis and severity at 17 years) with (i) glucocorticoids treatment; (ii) ages at (a) loss of independent ambulation, (b) rehabilitation into KAFOs, (c) loss of standing, (iii) forced vital capacity (FVC) (%) between 11 and 12 years and (iv) lower limb contractures. RESULTS: In total, 37/123 boys (30%) received intermittent prednisolone (0.75 mg/kg/day, 10 day/month) for a median 1-year (2 months-9 years), starting between 7.7 and 12.4 years (mean 9.5). About 96/123 (78%) were rehabilitated into KAFOs at 10.2+/-1.6 years. Age at loss of ambulation in KAFOs was 12.3+/-1.9 years and at loss of standing 12.8+/-2.1 years. About 95/123 (77%) boys developed scoliosis (Cobb angle >30 degrees ). Mean age+/-S.D. at scoliosis onset was 12.7+/-1.6 years. Forty-three boys (35%) had scoliosis surgery by 15+/-1.2 years. Later age at loss of ambulation (p<0.0001) and longer duration of prednisolone treatment (p=0.01) related to later scoliosis onset. Ages at loss of ambulation and standing were inversely related to scoliosis severity at 17 years (p<0.005). Hip asymmetry and %FVC at 11-12 years were directly related to scoliosis severity (p=0.02). CONCLUSIONS: Our data indicate a significant association between prolonged ambulation and a reduced risk of scoliosis development. Glucocorticoid administration, in our series, appear to be associated with a later onset of scoliosis, but did not alter the severity at 17 years, probably reflecting the shorter overall glucocorticoid exposure in this population.

Adenocarcinoma arising in a retained esophageal remnant.

Fistulation between the trachea and an infected mucocele arising from an excluded retained esophageal segment is an interesting and unusual complication of esophageal bypass surgery. We present such a case in which there was also malignant transformation in the cyst wall, manifested by invasive adenocarcinoma and widespread high-grade glandular dysplasia.

Spontaneous migration of totally implanted venous catheter systems from subclavian into jugular veins.

Two cases of migration of totally implanted catheter systems are described. The complication is potentially life threatening.

Chemotherapy of advanced breast cancer: outcome and prognostic factors.

The outcome for 758 consecutive patients who had received one or more chemotherapy regimens for recurrent or metastatic breast cancer is presented. The response rate following first line treatment was 34%. Median duration of response was 7.8 months, median time to progression was 3.7 months and median survival was 7.9 months. The only factor predicting for response, of factors recorded at presentation and at initiation of chemotherapy, was the use of anthracycline based regimens, though this may reflect the patient selection policy. Initial disease free interval, presence of liver metastases and use of anthracyclines were significantly related to time to progression. Several factors related to survival following first chemotherapy, but anthracycline usage showed only a very weak correlation. One third of patients (249/758) received two or more chemotherapy regimens. The response rate (16%) and median time to progression (2.3 months) were significantly worse than for first line treatment. The outcome after third line chemotherapy was very similar to that observed following second line treatment. Achievement of an objective response with first line chemotherapy predicted for second response, but with insufficient power to be of use in selecting patients for subsequent chemotherapy. Time to progression following first line chemotherapy did not influence that after second line treatment.

Prednisolone improves the response to primary endocrine treatment for advanced breast cancer.

Two hundred and twenty patients with progressive advanced breast cancer were given primary endocrine treatment (PET) according to menstrual status. Pre-menopausal patients received ovarian irradiation (O) and post-menopausal tamoxifen 10 mg bd (T). Patients were randomised to receive either no additional treatment or prednisolone 5 mg bd (P). Similar results were observed in each menstrual subgroup. In 194 evaluable patients, the response to PET + P was 49% and to PET alone 30% (P less than 0.01). P increased the median duration of response from 9 to 14 months (P less than 0.002) and the median time to disease progression from 5 to 9 months (P less than 0.001). Response to P after O or T alone occurred in only 2/62 (3%). Median survival in patients randomised to receive P at the outset of PET was prolonged by 4 months (P less than 0.05). The addition of P significantly improves the response to O or T in the treatment of advanced breast cancer.

Small bowel transplantation in the rat. Effect of pretransplant blood transfusions and cyclosporine on host survival.

We investigated the effect of pretransplant conditioning as a way to reduce the need for the aggressive immunosuppressive therapy reportedly required in small bowel (SB) allograft recipients. LEW rats were conditioned with (1) a donor-specific blood transfusion (DST) on day -8 and a concurrent 5-day course of CsA (10 mg/kg/day); (2) a nonspecific blood transfusion and CsA; (3) CsA alone. A 10-cm segment of the host native bowel was then replaced with an equivalent segment of SB obtained from ACI rats. Postoperative treatment consisted of CsA at 2.5 mg/kg/day for 30 days. Rats conditioned with a nonspecific transfusion and CsA or with CsA alone survived for 14.1 +/- 5.8 and 18.3 +/- 5.7 days, respectively. In contrast, rats conditioned with DST and CsA survived for 60.3 +/- 36.2 days (P less than 0.001 vs. both controls). Biopsies taken from long-term survivors showed a normal bowel architecture. The function of the allografts was studied in a group of animals totally deprived of their native bowel and transplanted with a 30-cm segment of ACI SB. CsA-DST-treated recipients survived an average of 90 +/- 43 days and grew at a rate comparable to isografted animals. Treated allograft recipients had maltose absorption indistinguishable from isografted controls at all times tested. In contrast, maltose absorption was severely impaired in recipients rejecting their grafts. This study demonstrates that long-term survival of SB allograft recipients can be achieved with good functional results with low doses of CsA in recipients conditioned with DST and CsA.

Pericardial effusion complicating breast cancer.

Thirty-five patients with metastatic breast cancer and pericardial effusions are described. They were treated with specific endocrine or chemotherapy. Twenty-two (63%) had presented in cardiac tamponade and were rapidly relieved by pericardiocentesis. Eighteen (82%) of these required no further local treatment, 2 obtained relief from a second aspiration and 2 needed additional treatment (intrapericardial bleomycin instillation and surgical pleuropericardial window). The median survival was 13.2 months. No patient relapsed again in the pericardium, suggesting that their prognosis was that of the underlying disease. Cardiac tamponade should be considered in any breathless patient with malignancy. In breast cancer, periocardiocentesis is lifesaving and systemic treatment can usefully prolong life.

Human pulmonary alveolar macrophages with smokers' inclusions: their relation to the cessation of cigarette smoking.

Bronchoalveolar lavage (BAL) was performed in 47 patients (24 smokers, 18 ex-smokers and 5 who never smoked). Cytocentrifuged preparations were stained with May-Grunwald-Giemsa (MGG) and differential counts of pulmonary alveolar macrophages (PAM) with smokers' inclusions were performed. The data supported an exponential reduction in this percentage and indicated that about 3 years elapsed before this percentage approximated to the values in patients who had never smoked. Electron microscopy was performed on eight BALs and the results supported those obtained by light microscopy.

Mitomycin C and vinblastine in the treatment of advanced breast cancer.

Forty-nine women with progressive metastatic breast cancer, extensively pretreated, received mitomycin C 12 mg/m2 and vinblastine 6 mg/m2 intravenously every 3 weeks. Eleven patients responded, giving a response frequency of 22%. Considering only the 40 patients evaluable after two or more courses of treatment, the response frequency is 27.5%. Responses occurred predominantly at soft tissue sites. Subjective toxicity was mild.

Mitoxantrone in advanced breast cancer--a phase II study with special attention to cardiotoxicity.

Thirty-four patients with advanced breast cancer, who had not received previous chemotherapy for metastatic disease, were treated with mitoxantrone 14 mg/m2 i.v. every 21 days. Eleven of 33 evaluable patients (33%) achieved a partial response; there were no complete responders. Before commencing mitoxantrone, and 3-monthly thereafter, radionuclide assessment of ventricular performance was obtained at rest and in response to stress. Ten patients showed a deterioration in ejection fraction, two of whom developed congestive cardiac failure. Dose-limiting toxicity was myelosuppression. Nausea and vomiting were generally mild and transient. Alopecia was minimal in most patients. Mitoxantrone is an active, well-tolerated new drug in the treatment of advanced breast cancer, but cardiotoxicity may occur in a proportion of patients. Further investigation is required to determine the precise nature, incidence and prognosis of cardiotoxicity encountered with mitoxantrone.

Norethisterone acetate in the treatment of advanced breast cancer.

One hundred and twenty-five patients with progressive advanced carcinoma of the breast were treated with norethisterone acetate 20 mg tds orally after prior hormonal treatment or chemotherapy. Ninety-nine patients are evaluable for response. Sixteen patients (16%) achieved a partial response (median duration 4.5 months), 26 (26%) had stable disease (median duration 3 months) and 57 (58%) developed progressive disease on treatment. Patients who responded to norethisterone acetate had more often responded to prior hormonal or ablative treatment (56% vs 25%) and had received less prior treatment than those who did not respond (p less than 0.05). There was no statistically significant correlation between response and age, menopausal status, disease-free interval, stage at diagnosis, or distribution of disease. Side effects led to cessation of therapy in nine patients (9%).