Medical technology development: limiting regulation

The medical technology industry is one of the most innovative sectors of the US economy. The paper considers how the US federal government, in a variety of roles as promoter, protector and payer, is involved in every stage of the innovative process for medical technology. It discusses the influence of government policies on medical innovation     

The spinal muscular atrophy gene region at 5q13.1 has a paralogous chromosomal region at 6p21.3

We have examined acetaminophen (paracetamol) dosing for outpatient management of posttonsillectomy pain in children. Forty children, 5-15 years of age, undergoing tonsillectomy and their parents were randomly assigned to use a scheduled administration of acetaminophen in weight appropriate doses, 60 mg.kg-1.24h-1 orally, 90 mg.kg-1.24h-1 rectally, or to use acetaminophen 'as needed' according to present standards (control group). Postoperative pain was assessed by the child using the poker chip tool for the first three days after discharge. The prevalence of pain amongst all the children was high. The second day after discharge 22%-64% of the children in the study group and 36%-73% of the children in the control group rated severe pain. Recommended dose ranges of acetaminophen do not provide sufficient pain relief in children following tonsillectomy. Further studies are required to determine, whether higher doses of acetaminophen or analgesics with different analgesic properties will lead to improved analgesia in children following tonsillectomy.     

DNA damage induced by m-phenylenediamine and its derivative in the presence of copper ion

We have previously reported that long-term priming of human polymorphonuclear neutrophilic granulocytes (PMN) with interferon-gamma (IFN-gamma) increased the fMLP-stimulated calcium influx. We now show that also after short-term incubation with IFN-gamma, PMN calcium metabolism is modulated. Single adherent cells in three different calcium-containing buffers (high, normal, and low [Ca2+]) were stimulated with the bacterial peptide fMLP or the Ca-ATPase inhibitor thapsigargin (Tg) after about 5 min preincubation with IFN-gamma. The results of this protocol indicated that IFN-gamma increases both calcium influx and calcium sequestration. Store dependent Ca2+ influx, directly measured on readdition of calcium to Tg-treated cells incubated in EGTA buffer, was significantly enhanced in IFN-gamma-treated cells. This effect of IFN-gamma was enhanced by the tyrosine kinase inhibitor herbimycin A. Strikingly, in low extracellular calcium concentrations, IFN-gamma induced calcium transients in 20%-60% of the cells. The proportion of PMN responding with Ca2+ transients increased with decreasing extracellular calcium concentration. Average lagtime from addition of IFN-gamma to a response that could be measured was 7.3 sec, and average increase in [Ca2+] above the basal level was 790 nM. These IFN-gamma-induced transients could not be depressed by herbimycin A. Thus, IFN-gamma can increase capacitative calcium influx, induce calcium transients, and possibly affect calcium sequestration in human PMN.     

Continuous hyperfractionated accelerated radiotherapy with/without mitomycin C in head and neck cancer

PURPOSE: To evaluate the effect of mitomycin C to an accelerated hyperfractionated radiation therapy. The aim was to test a very short schedule with/without mitomycin C (MMC) with conventional fractionation in histologically verified squamous cell carcinoma of the head and neck region. METHODS AND MATERIALS: From October 1990 to December 1996, 188 patients entered the trial. Tumors originated in the oral cavity in 54, oropharynx in 82, larynx in 20, and hypopharynx in 32 cases, respectively. Patients' stages were predominantly T3 and T4 (158/188, 84%) and most patients had lymph node metastases (144/188, 77%) at diagnosis. Only 22 patients were female, 166 were male, the median age of patients was 57 years (range 34 to 76 years). Patients were randomized to one of the following three treatment options: conventional fractionation (CF) consisting of 70 Gy in 35 fractions over 7 weeks (65 patients) or continuous hyperfractionated accelerated radiation therapy (V-CHART; 62 patients) or continuous hyperfractionated accelerated radiation therapy with 20 mg/sqm MMC on day 5 (V-CHART + MMC; 61 patients). By the accelerated regimens, the total dose of 55.3 Gy was delivered within 17 consecutive days, by 33 fractions. On day 1, a single dose of 2.5 Gy was given, from day 2 to 17 a dose of 1.65 Gy was delivered twice: the interfraction interval was 6 hours or more. RESULTS: Mucositis was very intense after accelerated therapy, most patients experiencing a grade III/IV reaction. The mucosal reaction did not differ whether MMC was administered or not. Patients treated by accelerated fractionation experienced a confluent mucosal reaction 12-14 days following start of therapy and recovered (no reaction) within 6 weeks. The skin reaction was not considered different in the three treatment groups. Those patients treated with additional chemotherapy experienced a grade III/IV hematologic toxicity in 12/61 patients. Initial complete response (CR) was recorded in 43% following CF, 58% after V-CHART, and 67% after V-CHART + MMC, respectively (p < 0.05). Actuarial survival (Kaplan-Meier) was significantly improved in the combined treated patients. Local tumor control was 28%, 32%, and 56% following CF, V-CHART, and V-CHART + MMC, respectively (p < 0.05). CONCLUSION: We conclude that our continuous hyperfractionated accelerated radiation therapy regimen is equal to conventional fractionation, suggesting that by shortening the overall treatment time from 7 weeks to 17 days a reduction in dose from 70 Gy to 55.3 Gy is possible, with maintenance of local tumor control rates. The administration of MMC to the accelerated regimen is tolerable and improves the outcome for patients significantly.     

Structure-activity relationships of alkylxanthines: alkyl chain elongation at the N1- or N7-position decreases cardiotonic activity in the isolated guinea pig heart

Relationships between the alkyl substitutions (C1-C6) and cardiac inotropic activities of xanthine derivatives were studied in isolated guinea pig heart muscles. Most of the alkylxanthines exhibited positive inotropic activity on the left atrium, which was increased with an elongation of alkyl chain at the N3-position but decreased by substitution of a long alkyl group at the N1- or N7-position of the xanthine skeleton. Although positive inotropic activity in the right ventricular papillary muscle was also increased by longer alkyl groups at the N3-position, the inotropic activity became negative with an increment in alkyl chain length at the N1- or N7-position. The positive inotropic activity of alkylxanthines was correlated with their inhibitory activity on the phosphodiesterase (PDE) III isoenzyme. Adenosine A1 antagonism and PDE IV inhibitory activity were also partly associated with the inotropic activity because H-89, an inhibitor of cyclic AMP-dependent protein kinase, diminished the positive inotropic action and potentiated the negative inotropic action. These results indicate that the positive inotropic activity of alkylxanthines becomes weak with elongation of alkyl chains at the N1- and N7-positions; In particular, xanthines having two long alkyl chains show a negative inotropic activity on the right ventricular papillary muscle, an effect that could not be elucidated from their cyclic AMP-dependent action.     

Diarrhea in young children associated with Escherichia coli non-O157 organisms that produce Shiga-like toxin

The aim of this study was to evaluate the way in which short-term protection declines and is eventually lost in preconditioning and to determine the efficacy of a second preconditioning at various reperfusion intervals. Male rabbits were divided into six groups. Forty-five minutes (sustained) ischemia followed by 120 minutes reperfusion was applied 60, 65, 70, 75, and 80 minutes after a 5 minute preconditioning (groups A, B, C, D, and E) and in a control group (F) after no preconditioning. The infarct to risk ratio (I/R) was 38.3 +/- 3.5% in group A, 46.0 +/- 7.8% in B, 61.6 +/- 9.7% in C, 68.1 +/- 4.2% in D, 64.5 +/- 7.8% in E, and 61.0 +/- 7.7% in F. Group A had a smaller I/R compared with groups C, D, E, and F (p < 0.05). In another series, groups G, H, and I were exposed to two 5-minute preconditioning stimuli, separated, respectively, by 45, 60, and 75 minutes of reperfusion; 10 minutes after the last preconditioning, the animals were exposed to 45-minutes ischemia and 120 minutes reperfusion. Groups A and D (with the smaller and higher I/R ratio) were also incorporated into this protocol in order to compare the effect of the additional preconditioning with the single one. The I/R ratio was 25.4 +/- 8.5% in group G, 22.8 +/- 7.0% in group H, and 14.7 +/- 4.0% in group I (p = NS). Group D showed a higher I/R compared with groups G, A, and H (p < 0.01), and group I had a smaller I/R compared with groups A (p < 0.01) and D (p < 0.001). Cardioprotection after a first preconditioning declines gradually and is eventually lost. An additional preconditioning is always effective, and the longer the interval from the first preconditioning, the more potent is the effect.     

Multiple coronary artery aneurysm

Co-Cinobufotalin Oral Liquor (CCOL) was studied for its ability to inhibit hepatitis B virus DNA replication, HBsAg and HBeAg expression in a HBV-transfected cell line (2.2.15 cell). The result showed that ID50 (the drug concentration that inhibits HBsAg or HBeAg secretion by 50%) was 0.08 mg/ml and 0.07 mg/ml on HBsAg and HBeAg respectively. CD50 (the drug concentration that reduces cell growth by 50%) was 2.5 mg/ml. TI (therapeutic index) was 31.3 and 35.7 respectively. The present data suggest that CCOL could exert a potent antiviral activity against HBV in vitro. Southern blot showed that CCOL inhibited HBV-DNA repication in a dose-dependent manner.