Biomedical subjects
Publications and source records attributed to M Martin.
We report a 3 month old boy with tetraploidy, found in peripheral blood and skin fibroblast cultures, with severely delayed growth and neurodevelopment, and with a cleft lip; these findings have not been described before. This report brings to seven the total number of liveborn infants with a 92,XXYY karyotype.
In 1980, second-look laparotomy was introduced simultaneously into the treatment regimen for ovarian carcinoma at the two main referral centers of northern Spain. First-line chemotherapy after initial surgery was, however, different at both hospitals. At one of them (Bilbao), a combination involving the use of cisplatin was employed (cyclophosphamide 600 mg/m2, Adriamycin 45 mg/m2, and cisplatin 80 mg/m2 i.v. on day 1), whereas the patients of the other hospital were treated mainly with single-agent chemotherapy (melphalan 0.2 mg/kg p.o. on days 1-5) and never with a cisplatin combination as first-line therapy in any case. In all, 92 patients (42 stage I, 14 stage II, 33 stage III, and 3 stage IV) could be treated during the study period with optimal surgery (complete tumor excision or largest residual tumor less than 2 cm in diameter). This was followed by adjuvant chemotherapy for 12-18 months in all cases, except for 18 patients with a stage Ia borderline or G1 tumor. The latter were merely kept under observation until their second-look laparotomy after 1 year of negative follow-up. All of the 74 patients who received adjuvant chemotherapy, of whom 36 with cisplatin and 38 without, were clinically disease free after at least twelve courses of treatment and had a second-look laparotomy performed. This was positive in 33.3% of the cases after cisplatin-containing therapy and in 26.3% of the cases after cisplatin-free therapy. This difference is not statistically significant. The mean follow-up period after negative second-look was 34 months. The long-term results of both patient groups were comparable as far as rate of positive second-look laparotomies and survival rate, overall and stage for stage are concerned. The use of cisplatin did not result in any significant therapeutic improvement. It was uniformly bad tolerated by the patients and carried higher cost, since all patients had to be hospitalized for treatment.
1. Conditions were examined under which estimates of drug clearance made from a single measurement of plasma concentration effectively represented multiple-sample estimates of clearance for quinidine, valproic acid, unbound valproic acid, and lorazepam. When plasma concentrations were measured at various post-dose times, both individual and mean values of single-sample clearance estimates, CL, corresponded closely to multiple-sample clearance estimates. Best post-dose sampling times were: quinidine, 8 h; valproic acid, 24 h; and lorazepam, 24 h. 2. Single-sample clearance estimates, CL, were calculated for seven drugs employed as probes of human hepatic drug-metabolizing enzymes. Valproic acid was used to probe microsomal and peroxisomal beta-oxidase activity; antipyrine, phenytoin, quinidine, carbamazepine, and theophylline were used as probes of hepatic mixed-function oxidases (MFO), and lorazepam as a probe for UDP-glucuronosyltransferase activity. 3. A clearance index (CI, namely probe CL for smokers divided by probe CL for non-smokers) was calculated for each probe. The effect of cigarette smoking (and presumably polycyclic aromatic hydrocarbon exposure) on all probe CL values was consolidated and plotted as the logarithm of the CI to produce a handprint of drug metabolizing enzyme activity for cigarette smokers. 4. Only theophylline CL was significantly faster among smokers than non-smokers (P less than 0.01). 5. We conclude that the use of multiple probes of MFO activity when given in a single-dose, single-sample protocol for structuring handprints represents a minimally invasive and useful approach to characterize xenobiotic-mediated effects on hepatic MFO.
Twenty-eight patients receiving their first cycle of carboplatin treatment (300-400 mg/m2) entered a prospective study in which the natural course and intensity of postchemotherapy emesis was evaluated. Twenty-five patients (89%) experienced nausea at some time after carboplatin treatment and twenty-three patients (82%) vomited. The median number of emetic episodes was 13.5. In the 23 patients who experienced vomiting, the mean period of latency of vomiting (time from start of carboplatin administration to onset of vomiting) was 6.25 h. The period of maximum incidence of vomiting was between 8 and 12 h (71% of patients with vomiting). Between 6 and 14 h after the start of carboplatin treatment, more than 50% of patients were continuously vomiting. Vomiting declined significantly after 24 h. According to these data, carboplatin is a severely emetic drug. Prospective antiemetic trials are necessary in order to obtain antiemetic schedules which are able to increase the tolerance to carboplatin treatment.
FK506 is a potent immunosuppressive agent which is undergoing clinical testing in liver, kidney, heart, and bone marrow transplantation. It has been shown to effectively prevent and reverse ongoing rejection in these models. From the outset, FK506 was used with low-dose steroids to treat 110 primary liver, 30 heart, and 66 kidney graft recipients. FK506 was also used in the setting of complications related to CsA or to ongoing chronic or acute rejection. One hundred seventy-three liver, 21 kidney, 10 heart, and 11 bone marrow recipients were converted to FK506 and low-dose steroids, from a combination of CsA, steroids, and/or Aza. A randomized, prospective trial comparing FK506 with CsA in primary liver transplantation has verified the lower incidence of rejection and greater ease in treating rejection episodes, with fewer adverse effects. In summary, FK506 has proven to be an effective baseline immunosuppressive agent, as well as a dose-adjustable agent for the treatment of rejection.
The therapeutic regimen used consisted of an ultrahigh streptokinase dosage scheme with an infusion rate of 1.5 million units per hour over a period of 6 hours. Where no immediate clearance occurred or where residual stenoses persisted, a catheter dilation (PTA) was subsequently carried out. Favorable results were achieved in the group of up to 6 week old femoral occlusions with 2 or 3 calf arteries open and an occlusion length below 15 cm. Iliac occlusions responded well to lytic treatment if a 3 month history was not exceeded.
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Thermostimulated current spectroscopy has been applied to the investigation of molecular mobility in human calcified tissue. A comparative study of extracts at various stages of demineralization is presented. The response of an organic-mineral complex interphase has been identified.
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Diagnostic subxiphoid pericardiotomy (SP) is presently advocated for the diagnosis of occult cardiac injuries in patients with stable vital signs with juxta-cardiac-penetrating chest wounds. This approach, however, results in a reported 80% negative pericardial exploration rate. To investigate the reliability of bedside two-dimension echocardiography (2-D echo) in predicting cardiac injury as compared to SP, a prospective study was undertaken of patients with stable vital signs who were admitted with penetrating chest wounds that were located within the space bounded by the manubrium, nipples, and subcostal line. Initial evaluation of the patients with bedside 2-D echo was found to have a 96% accuracy, 97% specificity, and 90% sensitivity in predicting cardiac injury. The only false-negative findings were in a patient who consented to SP 18 hours after bedside 2-D echo was performed. The reliability of bedside 2-D echo compared to SP was not significantly different according to the kappa measure of reliability. These data suggest that bedside 2-D echo is an expeditious and reliable method to diagnose occult cardiac injuries during the initial assessment of a patient with stable vital signs who had penetrating chest trauma. This approach may allow for the selective use of SP on patients with positive bedside 2-D echo and could eliminate unnecessary surgical procedures.
Applications of science and technology in the (re)habilitation of children and young adults can have dramatic, positive influences on their lives. Prosthetics, orthotics, mobility, postural support and seating, communication and education are responsibilities of the rehabilitation engineer. A holistic approach in meeting individual needs for technology is essential. The concerted rehabilitation engineering programme at The Hugh MacMillan Rehabilitation Centre supports service programmes with relevant research and development work.
The effects of a zinc-deficient diet (1.5 mg/kg) on nitrogen balance in rats, fed ad libitum during 30 days, was tested. Three nitrogen balances, each of 5 days, were done on the 4th, 15th and 25th days. A pair-fed group, with a supplemented diet at 80 mg/kg of zinc, was used as control. No significant differences (P less than or equal to 0.05) in any nitrogen balances for True Digestibility, Operative Biological Value and body weight were found. Nevertheless a trend was observed in all studied variables, indicating that the proteins of the control diet were better utilized than those of the zinc-deficient ones. The variation of the Biological Value of the proteins in the zinc-deficient group along the experimental period was similar to the control group.
Experiments were carried out in the intact functioning rat kidney to study the effect of lithium on both the renal transport of alpha-ketoglutarate (alpha-KG) along the nephron by micropuncture techniques and the renal uptake and peritubular transport of alpha-KG by measuring the renal blood flow, the urinary flow and the rate of renal alpha-KG delivery, filtration, reabsorption or secretion and excretion. At endogenous plasma alpha-KG concentration, 2.3 mM plasma lithium caused an increase in the fractional excretion of alpha-KG, whereas 4.6 mM plasma lithium led to a net secretion of alpha-KG. The micropuncture data indicate that this secretion occurred between the late proximal and the distal tubule, i.e., in the pars recta and/or in the loop of Henle. When plasma alpha-KG concentration was elevated, the two doses of lithium used inhibited the reabsorption of alpha-KG both in the proximal tubule and in the pars recta and/or the loop of Henle. Renal arteriovenous measurements reveal that, at low plasma alpha-KG concentrations, lithium caused a significant decrease in both the renal uptake of alpha-KG and the peritubular transport of this organic anion. These results suggest that the alpha-KG secreted in the pars recta and/or the loop of Henle was synthesized within the renal cells of the latter segments and not transported from the blood to the tubular lumen. At higher plasma alpha-KG concentrations, both the peritubular transport and the renal reabsorption were reduced by lithium.
The present study deals with long-term results in patients in whom deep venous occlusions were removed by fibrinolytic treatment. For this an ultrahigh streptokinase regimen was used. The average follow-up period was 18.9 +/- 6.7 months. The number of patients investigated was 27. In the group of femoral veins formerly cleared by fibrinolysis 2 of 21 (9.5%) were recorded as reoccluded. An unexpected removal of a femoral thrombosis still in existence immediately after fibrinolytic therapy was seen in one patient and evaluated as a late lytic event. In the group of iliac vein thrombosis cleared by fibrinolytic treatment no reocclusions occurred. In conclusion it can be said that the reocclusion-tendency of veins cleared by fibrinolysis is relatively low. This finding constitutes a special incentive for fibrinolytic treatment of deep vein thrombosis.
This study was performed on an experimental porcine model of acute local gamma irradiation to simulate accidents which occurred among humans. It enabled us to determine the development and the physiopathological characteristics of the fibrous tissue which developed in skeletal muscle. In the first month after irradiation, the strong inflammatory reaction which initiated the radiation induced fibrosis was characterized by edema as visualized on MRI imaging and X rays computed tomography and by acute phase reactant proteins changes, associated with elevations of local and general temperatures in irradiated animals. At the margin of the irradiated tissue myofibroblasts isolated among collagen bundles or grouped in nodullary reinforcements, are seen associated with intense capillary neogenesis. Several months after irradiation normal skeletal muscle was replaced by atrophic fibrosis delimited by an inflammatory perifibrotic tissue. The muscular fibrosis was characterized by a high density of myofibroblasts and by an inflammatory distribution pattern of collagen types I, III, IV, laminin, fibronectin and fibrinogen as visualized by immunohistochemical methods. Biochemical results showed an increase in collagen content and synthesis in fibrotic tissue whereas the cells in the perifibrotic zone synthesized more non collagenous proteins as compared with the normal muscle. The contributions of granulation tissue, cellular mediators and inhibition of muscular regeneration in the persistence of the invasive character of the muscular radiation induced fibrosis are discussed.
A 5-year retrospective review of 3,503 diagnostic peritoneal lavage (DPL) patients was conducted, identifying 48 (13%) blunt trauma patients who had a DPL WBC count greater than or equal to 500/mm3. The mean DPL WBC count was 1,646 +/- 2,275. Twenty (42%) of these patients were observed and discharged without subsequent operation or morbidity. Laparotomy was performed on 28 (58%) patients; 17 (61%) had a negative lap, 11 (39%) had intra-abdominal injuries requiring surgical repair or drainage (54% solid organ, 27% hollow viscus, 18% diaphragmatic). There were no significant differences between the three subgroups with regards to age, injury severity, time interval between injury and DPL, or mean DPL WBC count (p greater than 0.05). The negative-lap and no-lap groups had a significantly larger number of females; one presented with PID. The positive predictive value (PPV) of an isolated lavage WBC count of greater than or equal to 500/mm3 for intra-abdominal injury was 23% (11/48). The PPVs for DPLs performed less than and greater than or equal to 3 hours or those recalculated using WBC values higher than 500/mm3 were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
Non transformed epithelial hepatic cells (established cell line and adult rat hepatocytes) treated by liver tumor promoters, phenobarbital and biliverdin, for 24 and 48 h showed a fragmentation and loss of F-actin and a depolymerisation of microtubules. This pattern closely resembles that of transformed cells which were not susceptible to the action of promoters. In liver preneoplastic nodules obtained from rats submitted to an initiation-promotion process, actin almost completely disappeared with the concomitant appearance of a characteristic enzymatic pattern rich in GGT and GST-P. Therefore, cytoskeleton of hepatic cells is a target for tumor promoters and could play a role in promotion mechanism.