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Biomedical subjects

G Lawrence

Publications and source records attributed to G Lawrence.

At least 91 records · Page 5Linked to original sources

Experimental pigbel: the production and pathology of necrotizing enteritis due to Clostridium welchii type C in the guinea-pig.

An animal model for pigbel in man was developed using guinea-pigs. Intragastric dosing with growing cultures of Clostridium welchii Type C only produced necrotic lesions if protease inhibitors were given as well. beta toxin, which is made by the Type C organism, causes the intestinal damage and is very easily destroyed by proteases. Protease inhibitors in soybean and aprotinin were effectively in inducing disease in animals on a normal diet, while inhibitors in sweet potato, which inhibit only trypsin, were only effective in animals on a low-protein diet. In experiments using intragastric dosing, and in those where cultures and toxic filtrates were injected directly into the jejunum, the animals could be protected with an excess of pancreatic enzymes or by active or passive immunization against beta toxin. The pathology off Type C necrotizing enteritis in guinea-pigs had the macroscopic and microscopic features of pigbel in man. These experiments suggested the basic importance of a low-protein diet and dietary trypsin inhibitors in the pathogenesis of pigbel in man.

Animals↗

Prevention of necrotising enteritis in Papua New Guinea by active immunisation.

Necrotising enteritis (pig-bel) caused by Clostridium welchii type C is a major cause of illness and death in the Highlands of Papua New Guinea. In a controlled trial of active immunisation with a clostridial toxoid prepared from type-C cultures the incidence of pig-bel in over 2500 immunised children within 24 months of immunisation was less than an eighth of that in a control group. Necrotising enteritis in Papua New Guinea is now a preventable disease.

Adolescent↗

Development, preparation and safety testing of a Clostridium welchii type C toxoid. I: preliminary observations in man in Papua New Guinea.

The reactogenicity and immunogenicity of various strengths of plain and adsorbed Cl. welchii type C toxoid have been evaluated in laboratory tests and in man in Papua New Guinea. The greater antigenicity and acceptable clinical reactivity of a vaccine containing 50 total combining power units per 0.5 mm of adsorbed toxoid resulted in its selection for further field studies.

Adult↗

The prevention of pig-bel in Papua New Guinea.

In many Highlands hospitals pig-bel is the commonest cause of death in children over 12 months of age. In a double blind controlled trial in Sina Sina we have shown that Clostridium welchii type C beta toxoid (beta toxoid) protects against pig-bel (p < 0.02). Of 2,538 children given beta toxoid, two developed pig-bel in the following two years. Seventeen of 2,532 control children vaccinated with tetanus toxoid developed pig-bel. We suggest that beta toxoid be given to Highlands children at two, four and six months of age. Boosters may be needed. Health services in the Highlands need to be improved so that this vaccine can be effectively delivered.

Adolescent↗

Photoradiation in the treatment of recurrent breast carcinoma.

Photoradiation, with the use of hematoporphyrin derivative (Hpd) activated by visible light in the red region of the spectrum, was an effective treatment for controlling local and regional chest wall recurrences of breast carcinoma. With sufficient time between iv injection of the drug and local activation with red light, cutaneous and subcutaneous masses were treated effectively without undue damage to overlying and adjacent skin. This high therapeutic ratio resulted from the ability to Hpd to accumulate and/or to be retained to a higher degree in malignant tissue than in many normal tissues. This technique can be used as a primary treatment or upon tumor recurrence following conventional modalities such as surgery, chemotherapy, and radiation therapy.

Breast Neoplasms↗

The medical management of enteritis necroticans (pigbel).

Pigbel is the commonest cause of death in children over 12 months of age at Goroka Hospital. The clinical features are described. The medical management of pigbel includes intravenous fluids, nasogastric suction, penicillin and chloramphenicol. The development of dehydration, anaemia, hyponatraemia, hypokalaemia and hypoalbuminaemia must be prevented. In severe pigbel prolonged starvation may result in malnutrition that impairs wound healing and increases mortality. Intravenous feeding is therefore desirable in some cases.

Acute Disease↗

The demonstration of in vivo misonidazole tumour toxicity using post radiation hypoxia.

The cytotoxic effect of the radiosensitizer misonidazole on hypoxic tumour cells in vivo has been studied. Using standard procedures of large single doses of X-ray (30 Gy) followed by 1.0 mg/g misonidazole, no significant cytotoxicity (measured by tumour regrowth) could be observed. In contrast, when utilizing post radiation hypoxia (3 h of 7% oxygen breathing) in conjunction with post radiation misonidazole, an increased amount of direct drug toxicity was demonstrated. The use of this acute hypoxia treatment may prove to be a useful tool for measuring various in vivo radiobiological responses.

Animals↗

Autosomal recessive inheritance of susceptibility to tinea imbricata.

Familial distribution of chronic tinea imbricata in an untreated Melanesian population was consistent with a genetic predisposition to this disease. The pattern suggested that susceptibility to chronic Trichophyton concentricum infection is recessively inherited and controlled by genes at a single autosomal locus. In married couples there was no concordance of the disease above that expected by chance and the observed segregation of tinea imbricata accorded well with that predicted by the genetic hypothesis.

Adolescent↗

Pathogenesis of enteritis necroticans in Papula New Guinea.

It is suggested that enteritis necroticans occurs in the people of the Highlands of Papua New Guinea because they have low levels of digestive proteases in the intestinal lumen. These low protease levels are the result of a low-protein diet and the presence of heat-stable trypsin inhibitors in sweet potatato, the dietary staple. Low proteolytic activity allows the B toxin of Clostridium welchii type C, which is extremely susceptible to proteolysis, to initiate the disease.

Adult↗

The effects of fast neutrons on inoperable carcinoma of the stomach.

Thirty-nine unselected patients suffering from inoperable, recurrent, or residual adenocarcinoma of the stomach were referred for palliation with fast neutrons from the Medical Research Council's cyclotron at Hammersmith Hospital. A full course of 1440 rads given in 12 treatments over 26 days was administered to the patients. Because of the relatively low energy (7-5 MeV) of the beam from this particular machine, it was not possible to deliver the full dose uniformly throughout the tumour except in extremely thin patients. Pain, dysphagia, vomiting, and bleeding were relieved in the majority of cases. The side effects were minimal and easily controlled. Palpable masses disappeared. Five patients required surgery after neutron therapy. All the incisions were made through irradioated tissue and all except one healed normally. Tumour was present outside the treated area, but the absence of any palpable mass within the treated area was a consistent finding. Radiologically, the stomachs remained abnormal and later changes included gross mucosal abnormality and shrinkage. Fourteen patients came to necropsy and in 10 no tumour was present macroscopocally. Tumour cells were seen in all except two cases but these were few, surrounded by dense fibrous tissue, and may not have been viable. The remaining stomach was abnormal with a thickened wall and destruction of mucosa. Three of the four cases in which macroscopic tumour was present received less than the standard dose because of the inadequate penetration of the beam. Excellent regression of tumors was achieved by the neutrons, but the stomachs did not recover from this satisfactorily. Gastrectomy four to six months after treatment is therefore suggested. This operation and other surgical procedures in other patients were successfully carried out. There is a need for higher energy neutrons to improve treatment and extend it to patients of thick-set build.

Adenocarcinoma↗