Antibiotic resistance: a local hospital or community problem.
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Biomedical subjects
Publications and source records attributed to C Stephens.
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It has frequently been suggested that there may normally be small quantities of heparin in human blood, but amounts so small that their direct demonstration is not possible by available methods [1-4]. In this communication, we provide direct electrophoretic visualization that heparin or a closely related substance, is present in normal human plasma. After isolating glycosaminoglycans (GAGs) from 2-3 mls of plasma, a modification of the discontinuous high voltage electrophoretic method developed by Cappelletti et al. was used to successfully separate and identify the GAGs present in six normal adults (4 men and 2 women). In each case, in addition to chondroitin-4-SO4, chondroitin-6-SO4, and heparan-SO4, we were able to show the presence of a band which corresponds to that of heparin.
Qualitative and quantitative methods were used to determine changes in glycosaminoglycans (GAGs) in the spleen and plasma during initial stages of experimental amyloidosis and acute inflammation. GAG deposition in the spleen during the early stages of amyloidosis consists of a 16-fold heparin and heparan sulfate increase. Though splenic weights do increase during protracted inflammation only minor changes arise in splenic GAGs in the absence of amyloid deposition. An overall increase in plasma GAGs, consisting of a 4.5-fold chondroitin-4-sulphate increase, occurred at the time of GAG deposition in the tissues (spleen, liver) and probably accounts for the minor GAG changes seen in the spleen during inflammation. The time course of splenic heparin/heparan sulfate increase during amyloid deposition coincides with the histochemical changes previously described. Plasma GAG changes follow a pattern similar to that of acute phase protein reactants. The results suggest that GAG metabolism, in particular heparin/heparan sulfate, are intimately involved in the process of AA amyloidogenesis.
An activity that stimulates glycosaminoglycan and proteoglycan synthesis by confluent connective tissue cells in culture ("matrigenin" activity) has been partially purified from bovine bone. This activity is expressed on fibroblastic cells from several types of connective tissues, including synovium, and on cartilage tissue, but not on cells of unrelated origin. For synovial fibroblastic cells, matrigenin activity stimulated both hyaluronic acid and proteoglycan synthesis. The major proteoglycan whose synthesis was stimulated, contained primarily chondroitin-6-sulfate chains and eluted in the range of 400-600 Kdaltons. It is suggested that matrigenin activity in bone matrix has the potential to modulate remodelling (repair) in bone and in the synovial and cartilagenous regions abutting on bone.
Fifty-eight infants with congenital diaphragmatic hernia presenting within the first 6 hours of life, who underwent surgical repair, were analysed prospectively in order to produce a reliable index of severity of disease that would reliably predict eventual outcome. All were treated with paralysis hyperventilation and intravenous (IV) isoproterenol for the first 48 hours. There were 30 survivors and 28 deaths in this series (mortality 48%). Using arterial PCO2 values measured 2 hours after surgical repair and correlating them with an index of mechanical ventilation (mean airway pressure and respiratory rate), we have been able to clearly define two groups of diaphragmatic hernia based on their response to IPPV. The first group, with CO2 retention and severe preductal shunting, was unresponsive to hyperventilation with high rates and pressures; the mortality was 90%. The second group responded well to hyperventilation and demonstrated reversable ductal shunting only. Survival in this group was 97%. Only four patients out of 58 exhibited the "honeymoon period," with a period of stability followed by severe ductal shunting. Arterial CO2 accurately reflects the degree of lung development in this disease and separates those patients with severe pulmonary hypoplasia, where the outcome is invariably fatal, from those with a well-developed contralateral lung where there is excellent potential for survival.
Between 1955 and 1980 there were 14 patients treated at The Hospital for Sick Children with hemangiomas of the liver. Eight were seen at birth and 13 within the first 6 wk of life. The presenting clinical feature was that of massive hepatomegaly. Two children who had presented in the neonatal period were found to have had cardiac failure. Six patients were anemic and required blood transfusions. Before 1976 all patients who did not have cutaneous hemangiomas underwent laparotomy. Since 1976 only one laparotomy was done, the remaining 5 patients all having been treated symptomatically without operation. All the tumors involuted in the first year of life. Follow-up ranged from 1 to 20 yr and all are living and without symptoms. We recommend no active treatment if complications are absent. Steroids and radiotherapy are not used. If anemia and/or cardiac failure supervene, appropriate nonoperative management is necessary. Surgical treatment is indicated only if medical management fails or for rupture of the lesion.
A late complication of the Martin repair for total colonic aganglionosis is described. Pouch malfunction resulted in stasis and ulceration, excessive blood and protein loss, and bacterial overgrowth of the small intestine. The severity and nature of the lesion was identified by colonoscopy.
Three complete rations containing 15.8% of the dry matter as crude protein were compared to a 14.5% crude protein basal ration (dry matter basis) through eight Holstein cows in a replicated 4 times 4 Latin square design. The high protein rations contained supplemental nitrogen totally from soybean meal, urea, or Starea, the latter two providing 16 and 22% of total ration nitrogen, respectively. Concentrations were mixed with wilted alfalfa-bromegrass silage and complete rations fed ad libitum. Data were collected during the last week of each 28 days. Ration had no effect on milk yield, composition of fat or protein, or apparent digestibility of dry matter, crude protein, or acid detergent fiber. Weight gains and dry matter intake were greatest with the soybean meal ration. Intake of the low protein ration was depressed. There were no significant differences between the high protein rations for efficiency of nitrogen utilization.
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Work on metalloprotein export in bacteria, and protein import into chloroplasts, has converged in the recognition of a novel membrane translocation system with two fascinating properties: it is driven energetically by the transmembrane pH gradient, and it is capable of translocating folded proteins.
Local hyperthermia combined with intralesional cisplatin chemotherapy is a logical and potentially effective therapeutic approach for localized cancers. A trial using outbred animals with spontaneously occurring tumours was initiated to evaluate the toxicity and efficacy of this approach. Treatment consisted of injection of a colloidal suspension of cisplatin into the tumour prior to hyperthermia once a week for 4 weeks. Immediately after intratumoral injection of a mixture of cisplatin and collagen, thermotherapy was given. The goal temperature was 42 +/- 1 degrees C for 30 min. Ten animals (nine dogs and one cat) with soft tissue neoplasms were treated with one to four hyperthermia and cisplatin sessions for a total of 30 treatment sessions. Complete responses occurred in 4/10 cases (one carcinoma, two sarcomas, one melanoma). One dog with haemangiopericytoma had partial response. The lack of systemic toxicity and the minimal local normal tissue reactions indicate that the treatments were well tolerated. These data provide preliminary evidence that a combination of local hyperthermia and intratumoral cisplatin chemotherapy is a safe and effective method for the treatment of selected localized neoplasms.