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Biomedical subjects

P Becker

Publications and source records attributed to P Becker.

At least 91 records · Page 5Linked to original sources

A bivalent immunoadhesin of the human interferon-gamma receptor is an effective inhibitor of IFN-gamma activity.

We describe here the bioengineering of a bivalent IFN-gamma-RFc immunoadhesin consisting of the extracellular domain of the human IFN-gamma receptor alpha chain (IFN-gamma-R) fused to a human IgG1 Fc region (encoding hinge, CH2 and CH3 domain) that was efficiently expressed as a covalently linked homodimer in insect cells and purified in a one-step purification procedure. The IFN-gamma-RFc fusion protein exerted a 3-fold higher ligand binding affinity in binding competition studies in vitro compared with the monovalent extracellular IFN-gamma-R domain. In addition, the in vitro antagonistic activity of IFN-gamma-RFc, as determined by inhibition of IFN-gamma-induced virus protection and HLA-DR expression, was more than 30-fold higher in comparison with the monovalent soluble receptor. The described IFN-gamma-R immunoadhesin is a potential therapeutic reagent to interfere with the disease-promoting activities of IFN-gamma in several autoimmune diseases.

Animals↗

[Papillary muscle rupture in myocardial infarction].

We report nine patients with acute mitral regurgitation secondary to post-infarction papillary rupture operated between 1980 and 1992. Seven cases had posterior papillary muscle rupture. All patients were in critical conditions with pulmonary edema at the moment of surgery. In eight cases, mitral valve replacement was performed (4 with mechanical prostheses) and in one, the valve was repaired with papillary muscle reimplantation. Six cases were also subjected to myocardial revascularization with sapheneous vein grafts. Two patients (22%) died during the postoperative period and 4 had postoperative complications. The seven survivors have been followed during 6 to 115 month. Of theses, one died six month after surgery due to congestive heart failure, three are in functional class I and the rest in functional class II. It is concluded that, although mitral valve replacement for papillary muscle rupture has a high operative mortality and morbidity, long term results are satisfactory.

Aged↗

[Retrograde cerebral perfusion during circulatory arrest with deep hypothermia. A new technique for brain protection in surgery of ascending aorta and aortic arch].

Between May 1993 and August 1994, 15 patients (10 men) with type A aortic dissection (9 acute) had a replacement of the ascending aorta and/or aortic arch with circulatory arrest with profound hypothermia and retrograde cerebral perfusion. Mean circulatory arrest time was 47.5 min (range 23 to 68 min). Three patients (20%) died in relation to postoperative bleeding. No patient had a new neurologic damage related to surgery. Ten patients were awake and oriented before 24 hours of the operation and another one before 48 hours; 4 patients required more than 48 hours to be completely awake and oriented. Two patients were operated on with a recent stroke. One of them recovered without sequelae before hospital discharge and the other one had a major regression of his brain damage. Two other patients had emergency surgery because of cardiac tamponade and cardiogenic shock. Both of them had a satisfactory recovery. Six patients presented azotemia but only 2 of them needed dialysis. There was no case of Q wave infarction nor congestive heart failure in the perioperative period. Follow-up was 100% completed (12 patients) with a mean of 9.8 months (range 5 to 18 months). One patient died on the 10th postoperative month because of a late infectious process. Eight patients are in functional class I and 3 in II. Ten of them are back to their usual activities'. Although retrograde cerebral perfusion is a new surgical technique, it seems to be a very valuable complement for brain protection in ascending aorta and/or aortic arch surgery with circulatory arrest with profound hypothermia.

Aged↗

Changes in cardiovascular risk profile during the cessation of smoking.

The present study evaluated the intraindividual changes of serum lipids, blood pressure, adrenergic stimulation, and platelet reactivity in chronic smokers undergoing controlled smoking cessation assisted by nicotine chewing gum. One hundred twenty-one healthy smokers, who had smoked at least 20 cigarettes a day for at least 5 years, were included in the study. Serum lipids, blood pressure, catecholamine concentrations in serum and urine, platelet volume and platelet function in vitro were assessed during an initial phase of continued smoking, after stopping smoking during nicotine gum chewing, and after abstaining from both smoking and gum chewing. After a median of 11 weeks of chewing nicotine gum, 52 persons (43%) remained abstinent from smoking and chewing for at least 12 weeks. In these successful study participants, low-density lipoprotein (LDL)-cholesterol levels decreased significantly by a mean of 7.5 mg/dL (5.6%). High-density lipoprotein (HDL)-cholesterol increased by 5 to 6 mg/dL during the first weeks after ceasing to smoke, but levels at the end of study were only 2.1 mg/dL (3.4%) higher than baseline (nonsignificant difference). Triglyceride levels did not change during smoking cessation. While systolic blood pressure remained unchanged, diastolic blood pressure increased significantly by a mean of 3.5 mm Hg. For LDL-cholesterol, HDL-cholesterol, and systolic and diastolic blood pressure, there was an inverse correlation between the respective baseline values and the observed changes during the cessation of smoking. The urinary excretion of adrenaline and noradrenaline decreased upon quitting. The volume of platelets became significantly less during smoking cessation, but aggregation induced by adenosine diphosphate (ADP) and collagen and thromboxane synthesis in vitro remained uninfluenced. The platelet cyclic adenosine monophosphate (cAMP) response to stimulation of adenylate cyclase with prostaglandin E1 showed marked enhancement upon quitting. The changes observed intraindividually during smoking cessation largely correspond to the differences between smokers and nonsmokers described in epidemiologic studies. For serum lipids and blood pressure, a significant dependence of the changes on the respective values at baseline may indicate greater benefit for persons at higher risk. Decreased platelet volume and increased susceptibility of platelets to antiaggregatory prostaglandin E1 indicate a favorable influence of quitting on platelet reactivity.

Adult↗

Retroperitoneal laparoscopic nephrectomy and other procedures in the upper retroperitoneum using a balloon dissection technique.

This article describes a hydraulic balloon dissection technique. The retroperitoneum is developed via a small lumbodorsal incision between the edges of the musculus latissimus dorsi and musculus obliquus externus and then after visualization of its correct position the balloon catheter is filled with 500-1,200 ml of warm normal saline (according to patient size). The device consists of the finger of a surgeon's glove ligated around the end of a rigid bladder catheter. The balloon insufflation is maintained for 5 min to guarantee adequate hemostasis. Recently, we have replaced the balloon catheter by a balloon trocar sheath allowing direct endoscopic control of the hydraulic dissection. After retrieval of the balloon the CO2 insufflator is connected to the first trocar. All secondary trocars are placed under endoscopic control. The hydraulic dissection techniques also enable optimal creation of an effective pneumoperitoneum in children. Until now, we have used this technique for twelve procedures in the upper retroperitoneum including five nephrectomies, two nephroureterectomies, one tumor nephrectomy, one nephropexy, one renal cyst marsupialization and two renal biopsies. Up to now we have encountered no major complications. Three of the nephrectomized patients had undergone multiple previous abdominal surgical interventions. The retroperitoneal approach allows the surgeon to apply similar dissecting techniques as used in respective open procedures. It has become the routine approach for laparoscopic procedures in benign renal disease. This procedure can be performed even in cases with previous abdominal surgery.

Adult↗

[Pituitary tumors: clinical presentation and evaluation of transphenoidal surgical treatment].

The clinical manifestations and the surgical treatment results of 280 patients (179 female), undergoing a total of 319 operations at the Asenjo Institute of Neurosurgery were retrospectively analyzed. The surgical approach for the first operation was transphenoidal in 89.3% of patients and transcraneal in the rest. Tumors were non-secretory in 169 (60.4%) patients, prolactinomas in 75 (27.8%) and produced acromegalia in 29 (10.4%) and Cushing syndrome in 7 (2.5%) patients. There was extraselar extension in 42% of women and 71% of men. The surgical treatment of prolactinomas corrected endocrine alterations in 25 of 29 and visual alterations in 18 of 27 patients assessed. Surgical treatment of acromegalia improved endocrine alterations in 11 of 13 and visual alterations in 4 of 10 patients assessed. Treatment of non secretory tumors corrected visual alteratons in 38 of 64 patients assessed. The principal complication of transphenoidal surgery was transient diabetes insipidus in 6.8% of patients. Overall mortality was 2.3% for transphenoidal surgery and 5.6% for transcraneal surgery. It is concluded that transphenoidal surgery is effective for the management extraselar complications of pituitary tumors and endocrine management of selected cases.

Adolescent↗

Engraftment of normal murine marrow into nonmyeloablated host mice.

When 200 x 10(6) male BALB/c cells are given by tail vein injection to female nonmyeloablated hosts in one injection, a relatively low engraftment percentage is seen, but when the same total number of cells is given over five injections (separated by 24 hours), the observed engraftment is much higher. A further increase in engraftment appears to occur when the same number of cells is given in 10 injections separated by at least 24 hours. These data suggest that somewhere between 5 and 10% of marrow niches are available at intervals of 24 or more hours and that the keys to high levels of engraftment are the cell cycle status of the engrafting stem cell and the schedule of engraftment.

Animals↗

[Reactivity of internal mammary artery and saphenous vein used in human myocardial revascularization: studies with endogenous vasoconstrictors and vasodilators].

Biopsies of human internal mammary artery and saphenous vein were examined to ascertain the functional integrity of these vessels employed in myocardial revascularization. Studies were performed in vascular rings derived from 28 patients without previous consideration of age, sex, underlying additional pathology or drug treatments previous to and during surgery. Isometric muscle contraction of the circular muscle layer was monitored. Endothelin-1 (ET) is equipotent as a vasoconstrictor in arteries and veins, with a potency at least 10 to 100-fold that of noradrenaline (NA) or serotonin (5-HT). The potency of ET, NA or 5-HT is unaltered by mechanical removal of the endothelial cell layer. Arterial rings precontracted with NA relaxed in a concentration-dependent fashion in the presence of acetylcholine and sodium nitroprusside. Whereas the potency of nitroprusside was unaltered by removal of the endothelium, the efficacy of acetylcholine was greatly reduced. Saphenous vein rings were refractory to acetylcholine but not nitroprusside. Results open new perspectives to explain the larger patency of internal mammary artery grafts as compared to that of saphenous vein grafts in human myocardial revascularization.

Endothelium, Vascular↗

Botulinum A chemodenervation: a new modality in cerebral palsied hands.

Botulinum A chemodenervation of the Adductor Pollicis muscle for the treatment of the thumb-in-palm deformity in cerebral palsied hands is presented as a new therapeutic option. Early results of a clinical trial in five hemiparetic Cerebral Palsied (C.P.) children are assessed using a prospective nontrialist-biased study design based on an independent panel assessment of pre- and post-intervention photographic and videotaped records of hand function and appearance, in combination with grip dynamometry and goniometry. All cases are shown to improve in terms of both function and appearance with results approaching statistical significance (p = 0.06) when assessed by the Wilcoxon's matched-pairs signed rank test, despite the small study group. The modality is shown to be simple, safe and effective over the period reported (229 days). The benefit is sustained beyond the period of muscle paresis and ongoing long term follow-up will document the need for, and timing of, reinjection.

Botulinum Toxins↗

The prevalence of diabetes mellitus and impaired glucose tolerance in a group of urban South African blacks.

The prevalence of diabetes mellitus and impaired glucose tolerance (IGT) was determined in 479 urbanised South African blacks (141 men and 338 women) of Zulu descent selected by cluster sampling in a suburb of Durban. All subjects underwent a modified glucose tolerance test whereby fasting and 2-hour post-glucose (75 g) plasma glucose levels were measured. On the basis of the revised World Health Organisation criteria, the overall prevalence of diabetes was 4.2% and of IGT 6.9%; the age- and sex-adjusted prevalences were 5.3% and 7.7% respectively. Diabetes mellitus was more common in women (5.2% v. 2.3%), while the reverse was true of IGT (5.5% v. 11.5%). The mean age-adjusted body mass indices (BMIs) of diabetic (31.3 +/- 1.9) and IGT (29.7 +/- 1.9) subjects were significantly higher than those of the group with normal glucose tolerance (28 +/- 0.5). Female subjects with all types of glucose tolerance had significantly higher mean BMIs than men. There was a significant correlation between BMI and both fasting glucose (r = 0.16; P = 0.0039) and 2-hour plasma levels (r = 0.15; P = 0.0065) in the women, while in men only the fasting levels showed such a relationship (r = 0.21; P = 0.01719).

Adolescent↗

Effects of single and repeated doses of theophylline on aspects of performance, electrophysiology and subjective assessments in healthy human subjects.

The effects of both single and repeated doses of theophylline were evaluated on a battery of nine performance tests, the EEG, the EMG and on subjective assessments of mood and side-effects. The subjects were 20 healthy adults who participated in both phases of this randomized, double-blind, placebo controlled, crossover study. The single dose of 400 mg and the repeated doses of 300 mg b.d. for 4 weeks were intended to attain therapeutic serum concentrations. The Sternberg Additive Factors Method for assessing information processing revealed enhanced performance in both phases of this study, while the Horizontal Addition Test showed improved performance in the single dose phase only. The remaining seven performance tests failed to show significant differences between theophylline and placebo. Single doses of theophylline did not significantly alter mood, but marked adverse effects were encountered in the repeated dose phase, possibly related to unpleasant side-effects. Both EEG and EMG findings indicative of stimulation were associated with a single dose of theophylline, but substantial tolerance developed during 4 weeks of therapy. These findings demonstrate CNS stimulation by both single and repeated doses of theophylline with the occurrence of adverse side-effects during repeated administrations.

Adult↗

CD10 antigen density in childhood common acute lymphoblastic leukaemia: comparisons of race and sex.

During the 25 month period from July 1989 until August 1991, 58 children with FAB defined acute lymphoblastic leukaemia (ALL) were referred for immunophenotypic analysis. Of these, 42 children with a common/pre-B phenotype (CD19/CD10-positive) were studied specifically to assess CD10 antigen density. A pattern of segregation was found between males and females and between black and white children. Black males, who are the worst prognostic group, had the lowest CD10 density, while white females, known to constitute the best prognostic group, had significantly higher CD10 antigen density than the other groups. Black females and white males occupied intermediate positions with respect to CD10 antigen density. A two way analysis of variance showed that although sex had contributed significantly to this variation (p = 0.0038), the contribution of race was marginal (p = 0.0530). It is hypothesized that low CD10 antigen density patterns in males and in Blacks could be causally related to poor prognosis.

Black People↗

The empty sella: results of treatment in 76 successive cases and high frequency of endocrine and neurological disturbances.

OBJECTIVE: We assessed the frequency of endocrine or neurological disturbances and the results of surgery in patients with empty sella, diagnosed with cisternography and/or computerized tomography scanning. DESIGN AND PATIENTS: Analysis of hospital records of 76 successive patients (73 primary, three secondary empty sella) from a single institution. MEASUREMENTS: Clinical and neuro-ophthalmological evaluation. Serum PRL, GH, TSH, LH, FSH, T4, T3 by radioimmunoassay. Diagnosis of empty sella with cisternography and/or computerized tomography scanning (n = 69), or discovered at surgery (n = 7). RESULTS: Patients with empty sella had: headache (69.7%), visual disturbances (34.2%), cerebrospinal fluid rhinorrhoea (11.8%), endocrine disturbances (51.4%, including hyperprolactinaemia, acromegaly, Cushing's syndrome). A pituitary tumour was discovered in two patients, in seven other ones it was suspected but not found at surgery. Transsphenoidal packing of empty sellas was done in 56 cases, with 7.1% post-operative complications. With surgery there was improvement of headache in 71%, of visual disturbances in 46%. Cerebrospinal fluid rhinorrhoea (discovered at surgery in four other patients) was not resolved by the first operation in six out of 13 patients. In 20 patients without surgery, headache improved in 64.6%. CONCLUSIONS: The empty sella is frequently associated with a variety of neurological and endocrine disturbances, which is contrary to conventional belief. Cerebrospinal fluid rhinorrhoea is not a rare complication and it may be difficult to treat. Some cases of empty sella may be due to partial pituitary apoplexy. Autoimmunity may have existed in other cases. Surgery may be useful in many patients, but a judicious selection is needed because it entails complications and non-operated patients may improve spontaneously.

Adolescent↗

HIV-1 infection among heterosexual attenders at a sexually transmitted diseases clinic in Durban.

In a study of 2,682 selected attenders at a sexually transmitted diseases (STD) clinic for blacks in Durban, antibodies to human immunodeficiency virus type 1 (HIV-1) were detected in 63 (2.4%)--30 of 937 women (3.2%) and 33 of 1,745 men (1.9%). Women aged 15-19 years (P = 0.002) were at greater risk of HIV-1 infection than women of other age groups. Among men, HIV-1 seropositivity was associated with genital ulcer disease (GUD) (P = 0.007) and donovanosis (granuloma inguinale) (P = 0.02). Among seropositive men with donovanosis the probability of HIV-1 infection increased as the duration of lesions increased. When HIV-1 seropositive women were compared with a subgroup of 73 seronegative women with GUD, inflammatory cytological changes were associated with antibodies to HIV-1 (P = 0.02). Among women overall, HIV-1 seropositivity was associated with previous syphilis (P = 0.03). In men herpes zoster (P = 0.04) and in women lymphadenopathy (P = 0.002) accounted for HIV-1 seropositivity in patients with medical complaints. HIV-1 seropositivity in men with gonorrhoea and genital warts was less than in men without gonorrhoea (P = 0.001) and genital warts (P = 0.03). These results support the causal hypothesis of HIV transmission whereby mucosal discontinuity acts as a portal of entry for the virus. GUD and cervical inflammation secondary to STDs in seronegative subjects may facilitate HIV transmission. The relative risk of various STDs are probably dependent upon the duration of epithelial damage and exposure to HIV-1.

Adolescent↗

The intrasession repeatability of pattern electroretinograms and the effects of digital filtering.

Transient pattern electroretinograms were recorded in 12 normal young volunteers with the use of 12' and 30' checkerboard stimuli and 1 c/deg and 2.5 c/deg vertical gratings. The intrasession repeatability of pattern electroretinograms was determined by employing alternative statistics to the frequently used correlation coefficients. Comparisons were made with the repeatability of cone electroretinograms elicited by ganzfeld stimulation. The coefficient of repeatability was substantially lower (better) for pattern electroretinogram b-wave implicit times than for a-wave implicit times and b-wave amplitudes, the latter having high coefficients of repeatability. Cone electroretinograms had better repeatability with respect to all three parameters. Digital filtering using a bandpass of 1-40 Hz was applied to the original pattern electroretinograms recorded with a bandpass of 1-250 Hz. Although peak definition was generally enhanced, repeatability did not show marked improvement. Differences between broadband analogue-filtered pattern electroretinograms and the same responses with high-frequency noise removed by digital filtering need to be taken into account. The coefficient of repeatability statistic appears to facilitate the assessment of pattern electroretinograms and permits the comparison of the repeatability of both implicit time and amplitude parameters irrespective of absolute values. The implications of the relatively poor repeatability of pattern electroretinogram b-wave amplitudes for clinical applications need to be considered.

Adult↗

Rapid inhalation induction with isoflurane in humidified carrier gas.

This study was designed to determine if rapid inhalation induction of anaesthesia (RII) with 5% isoflurane (4.5 MAC equivalent) in oxygen offers any advantage in terms of complication rate, speed of induction and patient acceptance in comparison with a previously described technique of RII using 2% isoflurane in nitrous oxide and oxygen. Forty ASA I and II unpremedicated patients were allocated randomly to receive RII with either 5% isoflurane in oxygen or 2% isoflurane and nitrous oxide in oxygen. The carrier gas was humidified in order to limit airway irritation associated with the use of isoflurane for inhalation induction. In this study the observed difference in mean induction time (7 s) between the two groups was neither clinically nor statistically significant. The groups were similar also with regard to complication rate and patient acceptance.

Adolescent↗