Intracardiac transplantation of a mixed population of bone marrow cells improves both regional systolic contractility and diastolic relaxation.

BACKGROUND: Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells. METHODS: Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically. RESULTS: All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype. CONCLUSIONS: Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction.     

Motor nerve conduction velocity distributions in man: results of a new computer-based collision technique

A new computer-based collision technique for direct measurement of the human motor nerve conduction velocity distribution is described. In contrast to previous collision techniques, the test muscle response is progressively cancelled to a null using an arrangement of proximal and distal stimuli which eliminates distortion of the test response caused by transient changes in nerve and muscle fibre conduction. The increased sensitivity of this new technique permits accurate measurement of the slowest 1% of alpha motor nerve fibres. We have used our modified collision technique to determine motor nerve conduction velocity distributions for the median nerve in 20 normal subjects aged between 19 and 59 (mean 35) years. 150% maximal stimulus intensities were used, with a controlled limb temperature of 35 degrees C. Group mean velocities (+/- S.D.) for the fastest (95%), mean (50%) and slowest (5% and 1%) motor fibres were 59.1 +/- 3.0, 56.9 +/- 2.9, 52.7 +/- 3.1 and 51.2 +/- 3.7 m/sec respectively. Data are also presented for the ulnar and peroneal nerves.     

Cisplatin-5-fluorouracil chemotherapy for advanced inoperable squamous carcinoma of the head and neck

Patients with locally advanced, inoperable squamous cell carcinoma of the head and neck were offered three courses of cisplatin and 96-h 5-fluorouracil (5-FU) infusion. Subsequent therapy included surgery when feasible, irradiation therapy, and a maintenance program of methotrexate (MTX)-5-FU. Thirty-three patients were evaluated prospectively. Seven patients underwent a single course of chemotherapy. Five patients underwent two courses of chemotherapy. Twenty-one patients underwent three courses of adjuvant chemotherapy. The overall response rate was 48% (16 of 33). Fifteen of 21 patients (76%) receiving three courses of chemotherapy evidenced a response; this included three complete responses (CRs) (9%). No responses were seen in patients receiving only one or two courses of chemotherapy. Among responding patients, the initial favorable response to chemotherapy was apparent after the first course of chemotherapy. Patients who failed to demonstrate any response after two courses of chemotherapy did not respond after a third course. A significant group of patients fail to respond and should be offered participation in other investigational protocols as they become available.     

Similar dose responsiveness of hepatic glycogenolysis and gluconeogenesis to glucagon in vivo

This study was undertaken to determine whether the dose-dependent effect of glucagon on gluconeogenesis parallels its effect on hepatic glycogenolysis in conscious overnight-fasted dogs. Endogenous insulin and glucagon secretion were inhibited by somatostatin (0.8 micrograms X kg-1 X min-1), and intraportal replacement infusions of insulin (213 +/- 28 microU X kg-1 X min-1) and glucagon (0.65 ng X kg-1 X min-1) were given to maintain basal hormone concentrations for 2 h (12 +/- 2 microU/ml and 108 +/- 23 pg/ml, respectively). The glucagon infusion was then increased 2-, 4-, 8-, or 12-fold for 3 h, whereas the rate of insulin infusion was left unchanged. Glucose production (GP) was determined with 3-[3H]glucose, and gluconeogenesis (GNG) was assessed with tracer (U-[14C]alanine conversion to [14C]glucose) and arteriovenous difference (hepatic fractional extraction of alanine, FEA) techniques. Increases in plasma glucagon of 53 +/- 8, 199 +/- 48, 402 +/- 28, and 697 +/- 149 pg/ml resulted in initial (15-30 min) increases in GP of 1.1 +/- 0.4 (N = 4), 4.9 +/- 0.5 (N = 4), 6.5 +/- 0.6 (N = 6), and 7.7 +/- 1.4 (N = 4) mg X kg-1 X min-1, respectively; increases in GNG (approximately 3 h) of 48 +/- 19, 151 +/- 50, 161 +/- 25, and 157 +/- 7%, respectively; and increases in FEA (3 h) of 0.14 +/- 0.07, 0.37 +/- 0.05, 0.42 +/- 0.04, and 0.40 +/- 0.17, respectively. In conclusion, GNG and glycogenolysis were similarly sensitive to stimulation by glucagon in vivo, and the dose-response curves were markedly parallel.     

Rheological characterisation of dextran-concanavalin A mixtures as a basis for a self-regulated drug delivery device.

The rheological characterisation of glucose sensitive mixtures containing dextran and concanavalin A (con A) with and without glucose, was undertaken using oscillatory rheometry at 20 and 37 degrees C so that comparative data could be gathered in the linear viscoelastic (LVE) range. Measurements for a series of mixtures showed that complex viscosity is a function not only of the con A concentration but of the content and molecular weight of the dextran used. The extent of liquefaction on addition of glucose also depended on these factors. The tan delta profiles confirmed the change from semi-solid towards fluid behaviour. This occurs when glucose effects dismantling of the three-dimensional structure of the dextran-con A system by competitive binding to the glucose receptors in the protein. For the mixtures studied, the changes occurred between contents of 0 and 1% (w/w) glucose at 20 and 37 degrees C and form a useful basis for the formulation of a self-regulating delivery device for the control of hyper-and hypoglycaemia in diabetes.     

Human immunodeficiency virus-related connective tissue diseases: a Zimbabwean perspective

Our clinical experience with patients in Zimbabwe suggests that an arthropathy may be a feature of HIV disease. This takes two forms: the first is a reactive arthropathy usually affecting the large, lower limb joints with no other clinical features of a connective tissue disease. The second form is seen in association with features of complete or incomplete Reiter's syndrome with involvement of large and small peripheral joints (having an asymmetric distribution). Although this arthropathy may been seen in association with HIV positive asymptomatic disease and often is the reason for first presentation at hospital, the majority of our patients have clinical features of persistent generalized lymphadenopathy, plus or minus features of constitutional illness (such as fever, weight loss, and diarrhea). A small percentage of our patients have arthropathy in association with secondary systemic infection. Other locomotor conditions have been observed, although their numbers are too small to determine whether or not they truly are related to HIV disease. In Zimbabwe there is no association between the development of HIV-associated arthropathy and the presence of HLA-B27.     

Maternal Position at Midwife‐Attended Birth and Perineal Trauma: Is There an Association?

ABSTRACT: Background: Most women will sustain some degree of trauma to the genital tract after vaginal birth. This study aimed to examine the association between maternal position at birth and perineal outcome in women who had a midwife‐attended, spontaneous vaginal birth and an uncomplicated pregnancy at term. Methods: Data from 3,756 births in a major public tertiary teaching hospital were eligible for analysis. The need for sutures in perineal trauma was evaluated and compared for each major factor studied (maternal age, first vaginal delivery, induction of labor, not occipitoanterior, use of regional anesthesia, deflexed head and newborn birthweight >3,500 g). Birth positions were compared against each other. Subgroup analysis determined whether birth positions mattered more or less in each of the major factors studied. The chi‐square test was used to compare categorical variables. Results: Most women (65.9%) gave birth in the semi‐recumbent position. Of the 1,679 women (44.5%) who required perineal suturing, semi‐recumbent position was associated with the need for perineal sutures, whereas all‐fours was associated with reduced need for sutures; these associations were more marked in first vaginal births and newborn birth weight over 3,500 g. When regional anesthesia was used, semi‐recumbent position was associated with a need for suturing, and lateral position associated with a reduced need for suturing. The four major factors significantly related to perineal trauma included first vaginal birth, use of regional anesthesia, deflexed head, and newborn weight more than 3,500 g. Conclusions: Women should be given the choice to give birth in whatever position they find comfortable. Maternity practitioners have a responsibility to inform women of the likelihood of perineal trauma in the preferred birth position. Ongoing audit of all clinicians attending births is encouraged to further determine effects of maternal birth position and perineal trauma, to investigate women's perception of comfortable positioning at birth, and to measure changes to midwifery practice resulting from this study.