The Microalbuminuria Education Medication and Optimisation (MEMO) study: 4 years follow-up of multifactorial intervention in high-risk individuals with type 2 diabetes.

AIMS: The Microalbuminuria Education Medication and Optimisation (MEMO) study, revealed improved cardiovascular risk and glycaemic control with 18 months of intensive multifactorial intervention in high-risk people with type 2 diabetes, without any increase in severe hypoglycaemia. Our aim was to assess longer-term outcomes at 4-year follow-up in these participants. METHODS: Some 189 individuals with type 2 diabetes and microalbuminuria were recruited from a multi-ethnic population in Leicestershire, UK. The intervention group (n = 95) received multifactorial intervention with self-management education, and the control group (n = 94) received usual care. The primary outcome was change in HbA1c , and secondary outcomes were blood pressure (BP), cholesterol, microalbuminuria, estimated GFR, cardiovascular risk scores and major adverse cardiovascular events. RESULTS: Some 130 participants (68.7%), mean (sd) age 60.8 (10.4) years, duration of diabetes 11.5 (9.7) years, completed 4 years of follow-up. Mean change [95% confidence intervals (CI)] in HbA1c over 4 years was greater with intensive intervention compared with control (-3 mmol/mol, 95% CI -4.95,-1.11; -0.4%, 95% CI -0.67,-0.15; P = 0.002). Significant improvements over the 4 years were also seen in systolic BP (-7.3 mmHg, 95% CI -11.1, -3.5; P < 0.001), diastolic BP (-2.9 mmHg, 95% CI -5.4, -0.3; P = 0.026), cholesterol (-0.3 mmol/l, 95% CI -0.52,-0.12; P = 0.002), and 10-year coronary heart disease (-5.3, 95% CI -8.2,-2.3; P < 0.001) and stroke risk (-4.4, 95% CI -7.5, -1.3; P < 0.001). CONCLUSION: Multifactorial intervention with structured diabetes self-management education compared with usual diabetes care has benefits for cardio-metabolic risk factor profile. There was no increase in severe hypoglycaemia and cardiovascular mortality despite intensive glycaemic control, although the study was not powered to assess these outcomes.

Effects of the inverse alpha-agonist doxazosin in allergic rhinitis.

BACKGROUND: We examined the paradoxical hypothesis that the alpha-receptor inverse agonist doxazosin might produce beneficial effects in allergic rhinitis. OBJECTIVES: To evaluate single and chronic dosing effects of doxazosin on nasal airflow and symptoms in allergic rhinitis. METHODS: Fifteen patients randomized to receive 3-5 weeks of oral doxazosin 4 mg daily or placebo in crossover fashion. Measurements were taken at baseline and after first and last doses. RESULTS: There was a fall in peak nasal inspiratory flow (PNIF) between baseline vs. first dose of doxazosin: mean difference -19 L/min (95% CI -35 to -2) P = 0.03, with recovery between first and last doses: 21 L/min (95% CI 7-34) P = 0.006. Nasal visual analogue scale (VAS) and blockage scores were worse between baseline vs. first dose of doxazosin: mean difference VAS -10 mm (95% CI -18 to -2) P = 0.02, blockage -0.7 (95% CI -1.3 to -0.1) P = 0.02, with recovery between first and last doses: VAS 15 mm (95% CI 4-25) P = 0.009, blockage 1.1 (95% CI 0.5-1.6) P = 0.001. The oxymetazoline dose-response for PNIF was blunted after single vs chronic dosing with doxazosin: mean difference -17 L/min (95% CI -30 to -4) P = 0.01. Heart rate and diastolic blood pressure showed the same pattern. There was a significant difference between doxazosin and placebo for nasal blockage score and heart rate after single but not chronic dosing. CONCLUSIONS: There was a disconnect between single and chronic dosing effects of doxazosin for nasal symptoms, oxymetazoline response and cardiovascular outcomes, in turn suggesting alpha-1 receptor up-regulation.

The use of porcine factor VIII in the treatment of patients with acquired hemophilia: the United Kingdom experience.

Data have been collected by questionnaire on 15 acute bleeding episodes in 12 patients with acquired hemophilia, treated with porcine factor VIII (FVIII). The median initial anti-human FVIII inhibitor level was 40 Bethesda Units (BU)/ml, whereas that against porcine was 1 BU/ml. The mean initial dose of porcine FVIII infused was 54 micrograms/kg, which resulted in a rise of 0.57 IU/mL in the FVIII concentration. Therapy was continued for a mean of 8.5 days, during which time the average number of infusions was 11. Clinical response was rated as good or excellent in 82% of recipients. Side effects were uncommon; only one patient experienced a severe reaction. Following therapy, no increase in antihuman antibody levels was noted; increased levels of antiporcine antibody was detected in only two patients. One patient bled on three further occasions and was successfully retreated with porcine FVIII. Porcine FVIII is a safe and clinically effective treatment for bleeding episodes in acquired hemophilia and should be considered as first-line therapy for patients with low antiporcine FVIII levels.

Elevated insulin-like growth factor (IGF) gene expression in sciatic nerves during IGF-supported nerve regeneration.

Nerve regeneration is augmented by neurotrophic activity, which has long been known to be increased in lesioned nerves. Of identified soluble nerve-derived neurotrophic factors, to date only insulin-like growth factors (IGFs) have been observed to increase the rate of axon regeneration in peripheral nerves. We report that IGF-I and IGF-II mRNA contents were significantly increased (P < 0.0005) distal to the site of crush in rat sciatic nerves, and decreased following axon regeneration. In transected nerves in which axon regeneration was prevented, IGF mRNAs remained elevated. IGF-I mRNAs per mg tissue were increased more in lesioned nerves than denervated muscles, whereas IGF-II mRNAs were increased more in denervated muscles than lesioned nerves. This suggested that IGF-I and IGF-II each play distinct regulatory roles during regeneration. These data bolster the hypothesis that increased IGF mRNA content in nerves supports the rate of nerve regeneration in mammals.

Osteolytic bone lesions in a patient with idiopathic myelofibrosis and bronchial carcinoma.

A 59 year old man with longstanding myelofibrosis and previous splenectomy was incidently found to have a large lytic lesion in his left femur which required operative fixation. He had undergone right upper lobectomy for squamous carcinoma of the bronchus five years earlier. Histological analysis of bone reamings showed no evidence of metastatic carcinoma. Osteosclerosis is frequently noted in patients with myelofibrosis but osteolytic lesions are uncommon and may be confused with metastatic malignancy.

A prospective randomised concurrent comparison of the COBE Spectra Version 4.7, COBE Spectra Version 6 (auto PBSC) and Haemonetics MCS+ cell separators for leucapheresis in patients with haematological and non-haematological malignancies.

A prospective study of the CD34+ cell collection efficiency of three cell separators was undertaken comparing the mononuclear cell, CD34+ cell and CFU-GM yield. Twenty patients were entered in the study, all had received mobilising chemotherapy and daily G-CSF (5 microg/kg subcutaneously). The first leucapheresis was performed when the peripheral blood absolute CD34+ cell count was > or = 20 cells/microl. All patients underwent two leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra Version 4.7 and then randomised to either the COBE Spectra Version 6 or Haemonetics MCS+ for the other leucapheresis. The target durations of the procedure on the COBE Spectra Version 4.7 and Version 6 were 180 min or two total blood volumes (TBV), and for the Haemonetics MCS+ was 20 cycles with four recirculations. All machines were operated on the 1997 software supplied by the respective manufacturers. The time taken for the procedure was significantly longer with both the Haemonetics MCS+ and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE Spectra versions processed significantly larger volumes of blood than the Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells were all significantly lower with the Haemonetics MCS+ compared with both COBE Spectra Versions, as were the yields per unit volume of blood processed. There was no significant difference in the reduction in the platelet count following leucapheresis with any of the machines.

Infective endocarditis as a complication of a permanent indwelling right atrial catheter in a patient with severe aplastic anaemia.

Endocarditis is a recognized complication of both temporary and permanent indwelling right atrial catheters. Endocardial damage by the catheter may result in non-bacterial thrombotic endocarditis. Sterile vegetations composed of platelets and fibrin may become infected, either by direct spread of bacteria along the catheter, or following an episode of bacteraemia. Bacteria in infected vegetations may be protected from phagocytosis by a 'roof' of fibrin. Echocardiography is a valuable non-invasive method of diagnosis and may be used to monitor the resolution of vegetations and valve function. The right atrial catheter produces reflections which must be distinguished from cardiac abnormalities. We report a case of infective endocarditis in a patient with severe aplastic anaemia and a permanent indwelling right atrial catheter which was managed conservatively.

Use of porcine factor VIII in the treatment of patients with acquired hemophilia.

Data have been collected from 47 centers in Europe and North America on the treatment with porcine factor VIII concentrate of 74 acute bleeding episodes in 65 patients with acquired hemophilia. The median initial anti-human factor VIII auto-antibody inhibitor level was 38 Bethesda unit (BU)/mL (range 1.2 to 1,024) whereas that against porcine was 1 BU/mL (range 0 to 15). The mean initial dose of porcine factor VIII infused was 84 IU/kg, which increased the plasma factor VIII:C activity by 0.85 IU/mL. Therapy was continued for a mean of 8.5 days during which time the average number of infusions was 11. Objective clinical responses were rated as good or excellent in 78% of recipients. Side effects were uncommon; only one patient experienced a severe anaphylactic reaction necessitating the discontinuation of porcine FVIII therapy. After therapy, no increase in the median level of anti-human FVIII or anti-porcine antibody was noted in the group as a whole, although 13 patients showed individual increases in either anti-human or anti-porcine antibody levels or both of more than 10 BU/mL. Of the 7 patients who subsequently rebled, 5 were successfully re-treated and 2 did not respond to further porcine factor VIII treatment. Porcine factor VIII is safe and clinically effective treatment for bleeding episodes associated with acquired hemophilia and should be considered as first-line therapy for patients whose acquired anti-factor VIII:C antibody cross-reacts with porcine factor VIII:C at low levels.

Soluble transferrin receptor: a discriminating assay for iron deficiency.

The distinction between iron deficiency anaemia (IDA) and the anaemia that accompanies infection, inflammation or malignancy, commonly termed the anaemia of chronic disease (ACD), is often difficult, as the conventional laboratory indices of iron status are often influenced by acute phase responses. In recent years, the soluble transferrin receptor (sTfR) has been introduced as a sensitive, early and highly quantitative new marker of iron depletion, increasing in proportion to tissue iron deficit. Unlike conventional laboratory tests, the sTfR is not an acute phase reactant and remains normal in patients with chronic disease. In this study TfR concentrations were compared with the gold standard of iron stores, bone marrow iron. The sTfR concentration was shown to be the most efficient test in predicting bone marrow iron stores in 20 patients with ACD (75% efficiency) and in 18 patients with rheumatoid arthritis (RA) (94% efficiency). Measurement of sTfR may be a useful addition in the differential diagnosis of ACD and IDA.

Prospective randomised concurrent comparison of the COBE spectra version 4.7, COBE spectra version 6 (Auto PBSCtrade mark), and haemonetics MCS+ cell separators for leucapheresis in patients with haematological and non haematological malignancies.

A prospective study of three cell separators was undertaken to compare the mononuclear cell, CD34+ cell and CFU-GM yield. Twenty patients were entered in the study; all had received chemotherapy and daily G-CSF (5 microg/kg subcutaneously) up to and including the first day of leucapheresis. The first leucapheresis was performed on the first day the peripheral blood absolute CD34+ cell count was > or =20 cells/microl. All patients underwent two leucaphereses on consecutive days. The patients were randomised to undergo either the first or second leucapheresis using the COBE Spectra Version 4.7 and then randomised to either the COBE Spectra Version 6 or Haemonetics MCS+ for the other leucapheresis. The target durations of the procedure on the COBE Spectra Version 4.7 and Version 6 were 180 minutes or 2 total blood volumes (TBV), and for the Haemonetics MCS+ was 20 cycles with four recirculations. All machines were operated on the 1997 software supplied by the respective manufacturers. The time taken for the procedure was significantly longer with both the Haemonetics MCS+ and the COBE Spectra Version 6 than the COBE Spectra Version 4.7. Both COBE Spectra versions processed significantly larger volumes of blood than the Haemonetics MCS+. The absolute yield of mononuclear cells, CFU-GM and CD34+ cells were all significantly lower with the Haemonetics MCS+ compared with both COBE Spectra versions, as were the yields per unit volume of blood processed. The product volume was significantly higher with the COBE Spectra Version 4.7 compared to the other two machines. There was no significant difference in the reduction in the platelet count following leucapheresis with any of the machines. The COBE Spectra Version 6 is particularly useful for patients with potentially poor peripheral venous access because of its increased interface stability.

Metastatic papillary carcinoma of thyroid in a patient undergoing allogeneic BMT for CML.

A 30-year-old woman underwent HLA-compatible bone marrow transplant for chronic myeloid leukaemia. Her post-transplant course was complicated by disseminated aspergillus and CMV infections resulting in death 65 d post transplant. At post-mortem, multiple pulmonary metastases of papillary carcinoma of the thyroid were found with a small (< 8 mm) primary carcinoma in the thyroid. It is suggested that the progression of this tumour was related to the patient's immunocompromised state.

Evaluation and eligibility of HLA-identical sibling donors for stem cell/bone marrow donation.

Overall, the number of allogeneic transplants performed world-wide has not increased dramatically over the past 5 years. However, the proportion of allogeneic transplants undertaken using peripheral blood progenitor cells (PBPCs) has risen significantly. Currently, as part of an ethically approved trial, potential donors are seen, assessed and consented by physicians not caring directly for the recipients. Thirty-five potential sibling donors were seen and assessed for their willingness and fitness to donate for 28 patients. One donor opted to give bone marrow and the rest selected PBPC donation. Seven of these donors were found to have concurrent medical conditions. Due to poor venous access, one donor was advised to donate bone marrow and two others donated bone marrow due to an underlying condition. Four others were deemed unfit for donation. Donation of stem cells from bone marrow or peripheral blood is not a risk-free procedure; careful preassessment and counselling is mandatory especially when the age of prospective patients and therefore donors is increasing.

Infusion pump adverse events: experience from medical device reports.

Infusion pumps are used in the hospital setting, nursing home, and increasingly, in the home. Medical Device Reports to the Food and Drug Administration of adverse events during the use of infusion pumps for a 10-year period are described. Examples of cases reported to the Food and Drug Administration are provided. The problems reported by medical facilities (hospitals, medical centers, hospital pharmacies, or nursing homes) are compared with those that occur in the home or reported by home health care agencies. Overall, there were no differences in the types of adverse events reported by medical facilities when compared with reports from home health care agencies. However, there were differences in the location of use of some of the infusion pumps studied, which could reflect the trend toward home care over the past decade.

Selective vasopressin, angiotensin II, or dual receptor blockade with developing congestive heart failure.

With developing congestive heart failure (CHF), activation of the vasopressin V(1a) and angiotensin II type 1 (AT(1)) receptors can occur. In the present study, we examined the direct effects of V(1a) receptor blockade (V(1a) block), selective AT(1) receptor blockade (AT(1) block), and dual V(1a)/AT(1) receptor blockade (dual block) with respect to left ventricular (LV) function and contractility during the progression of CHF. LV and myocyte functions were examined in pigs with pacing CHF (rapid pacing, 240 beats/min, 3 weeks, n = 10), pacing CHF with concomitant V(1a) block (SR49059, 60 mg/kg, n = 8), pacing CHF with concomitant AT(1) block (irbesartan, 30 mg/kg, n = 7), or pacing CHF with dual block (n = 7). LV end-diastolic dimension and peak wall stress were reduced in all receptor blockade groups compared with CHF values. However, LV fractional shortening was increased only in the dual block group compared with CHF values (29 +/- 3 versus 21 +/- 2, P <.05). Basal LV myocyte percent shortening increased in the dual block group compared with CHF values (3.44 +/- 0.23 versus 2.88 +/- 0.11, P <. 05). Although V(1a) or AT(1) block reduced LV loading conditions, only dual block resulted in improved LV and myocyte shortening.