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Biomedical subjects

G Todd

Publications and source records attributed to G Todd.

At least 55 records · Page 3Linked to original sources

Hepatoerythropoietic porphyria precipitated by viral hepatitis.

Porphyria cutanea tarda (PCT), the condition resulting from a deficiency of hepatic uroporphyrinogen decarboxylase activity, is the commonest form of porphyria. Both acquired and familial form exist and are commonly associated in adults with liver disease and hepatic iron overload. The condition is extremely rare in children; most cases of childhood PCT are familial and some particularly severe cases have been shown to have a hepatoerythropoietic porphyria or homozygous uroporphyrinogen decarboxylase deficiency. A case is described of hepatoerythropoietic porphyria in which the disease was first precipitated at the age of two by a coincidental hepatitis A infection and improved as the hepatitis cleared. This paper reviews the evidence that viral hepatitis may precipitate overt PCT in children in a manner analogous to the precipitation of PCT in adults by alcohol associated liver disease.

Child, Preschool↗

Homozygous variegate porphyria: an evolving clinical syndrome.

Variegate porphyria is one of the most frequently encountered genetic conditions in South Africa. It is inherited as an autosomal dominant disease and in excess of 300 heterozygous cases have been studied by the Cape Town unit. Despite this, the homozygous condition has not previously been encountered in South Africa. We report two cases of homozygous variegate porphyria, one of whom represents the first South African case. We delineate a syndrome principally characterized by growth retardation, developmental delay, epileptic seizures, photosensitivity and an abnormal porphyrin excretion pattern. In addition we describe, in one case, two features not previously reported: skin disease in areas unexposed to light and a severe sensory neuropathy which may account at least in part for the hand deformities of this disorder.

Bone and Bones↗

Acute scleritis in porphyria cutanea tarda.

We examined three patients who had dermatologic and biochemical manifestations of porphyria cutanea tarda and localized thinning or excavation in the sun-exposed interpalpebral sclera, adjacent to the cornea. All three patients had signs of acute scleritis. The acute scleritis responded to oral indomethacin in one patient, but systemic corticosteroids were required to control the inflammation in the other two patients. Phlebotomy, protection from sunlight, and refraining from alcohol played an important part in the treatment of the patients.

Acute Disease↗

A ten-year experience with bacterial aortitis.

Twenty-one patients with bacterial aortitis were treated in four institutions over a 10-year period. Clues to the diagnosis were a pulsatile mass; fever; positive blood culture; CT scan revealing aortic nodularity, an aneurysm of irregular configuration, or air in the aortic wall; and angiography revealing a lobulated aneurysm. The most commonly identified organisms were Salmonella and Staphylococcus. Excision with in situ repair was performed in nine patients; 11 patients underwent extraanatomic bypass grafting with aortic ligation. In situ graft repair was performed when the infected aorta could be removed entirely or when the thoracic or suprarenal aorta was involved. Axillofemoral bypass grafting was used when infection was extensive. There were eight disease-related deaths. No graft infections were encountered in patients who survived.

Aged↗

The influence of preoperative total parenteral nutrition upon morbidity and mortality.

This study was done to examine the criteria for determining the adequacy of preoperative total parenteral nutrition (TPN). We hypothesized that an important criterion for adequate preoperative nutrition should be a contraction of the expanded extracellular fluid compartment known to occur in malnourished patients undergoing surgical treatment. Clinical evidence of this included a rise in the serum albumin level and weight loss. Fifty-nine patients requiring preoperative nutritional support for at least five days were admitted to the study. The patients were divided into three groups (group 1, group 2a and group 2b) based upon the response of the patients to TPN. Group 1 consisted of 23 patients who demonstrated a rise in serum albumin value, loss in body weight and diuresis after seven days of TPN. Group 2 was made up of 36 patients who failed to demonstrate a rise in the albumin level in response to nutritional support for one week. Of these patients, 20 underwent operation at the end of a week of nutritional support (group 2a) while 16 patients received four to six weeks of nutritional support preoperatively (group 2b). The complication rate in the three groups was 4.3 per cent for those in group 1; 45 per cent for those in group 2a and 12.5 per cent for those in group 2b (p less than 0.05), group 2a versus group 2b). The results of this study demonstrate a high mortality and morbidity in patients who fail to increase the serum albumin level after one week of TPN. The data suggest that a prolonged period of parenteral nutrition results in a substantial decrease in perioperative complications in this group of patients.

Body Fluid Compartments↗

Reaction of the leukocytes of melanoma patients and control donors, including pregnant women, with melanoma- and fetus-derived materials.

Using a one-stage capillary leukocyte migration inhibition assay, we examined peripheral blood leukocytes from 97 patients with malignant melanoma, 194 pregnant women, and 123 non-pregnant donors for their reactivity with materials from fetal and melanomatous tissues. As in previous studies, we found melanoma extracts selectively to inhibit melanoma patients' leukocytes. First-trimester fetal extracts also selectively inhibited melanoma patients' leukocytes, suggesting their cross-reactivity with melanoma-derived antigens. We could not localize the source of the inhibitory materials within the fetuses. We found no evidence that pregnant women were selectively immunized to fetal or melanoma extracts, regardless of their parity or the stage of their pregnancy.

Cell Migration Inhibition↗

Reinforcing and other behavioral effects of nicotine.

Published findings of intravenous nicotine self-injection indicate that the reinforcing properties of nicotine are weak when the drug is made available according to continuous reinforcement (CRF) or fixed-ratio (FR) schedules. CRF self-injection rates are generally only 2-3 times saline control levels and self-injection frequency is largely insensitive to changes in unit dose. In contrast, drugs of the psychomotor stimulant, opiate, and sedative-hypnotic classes, with similar pharmacokinetic parameters, maintain much higher self-injection rates and show systematic changes in rate with unit dose variations. Recent studies using interval and second-order schedules of nicotine presentation have been more successful in maintaining higher rates of self-administration behavior. Systematic dose-response functions have also been found under these conditions. Food-deprivation, species and strain differences, circadian rhythms, and duration of exposure to the drug also appear to be important variables in determining self-injection rate. Finally, the rapid development of tolerance to the effects of nicotine may account for changes in the pattern of self-administration within daily sessions and the differential sensitivity of those patterns to nicotine pretreatment.

Animals↗

A comparison of the macrophage electrophoretic mobility test and the leukocyte migration inhibition test in the detection of histocompatibility antigens on tumor cells.

Lymph node cells from mice sensitized by rejection of skin allografts were incubated in vitro with tumor cells carrying the sensitizing alloantigens. Products of the lymphocyte--antigen interaction released into the culture medium were simultaneously assessed by the macrophage electrophoretic mobility test and the leukocyte migration inhibition assay. Both macrophage slowing factor (MSF) and a factor which inhibited leukocyte migration (LIF) were produced. The release of both factors was detectable after comparable periods of incubation; their production was transient and ceased within 24 hours after it started.

Animals↗

In vitro reaction of cancer patients and others to Bacillus Calmette-Gueérin.

We examined the in vitro reaction of leukocytes from 71 cancer patients and 121 control donors (disease-free individuals or patients with non-malignant non-debilitating conditions) against Bacillus Calmette-Guérin using a one-stage capillary leukocyte migration assay. The proportion of reactive cancer patients and control donors increased with increasing BCG concentration, but the proportion of patients who reacted was less than that of control donors at all concentrations of BCG. As cancer stage advanced and the volume of clinically detectable tumor increased, the proportion of reactive patients decreased. There was a small age-related decline in reactivity in the control population. The results of simultaneous in vitro tests and Mantoux reactions were concurrent in a majority of normal individuals so tested.

Adolescent↗

Advantages of low dose steroid from the day after renal transplantation.

We have used a low dose of steroid (20 mg of prednisolone), commencing the day after transplantation, for 151 consecutive renal transplants in 141 patients. Five patients received grafts from living related donors, 146 received cadaver grafts. All patients received azathioprine for routine immunosuppression and the first 47 received a single dose of actinomycin C i.v. for treatment of rejection. No other immunosuppressive drugs were used. This treatment provided satisfactory immunosuppression as 109 of 151 grafts continue to function for periods of 3 months to 10 years and, of 42 grafts lost, only 17 failed from rejection. The cumulative survival of first cadaver grafts at 1 and 2 years in recipients of all ages (7 to 55 years) was 77.9 and 76.0%, respectively; in recipients 15 to 34 years old, 90.9 and 86.1%, respectively. Twenty-three patients died, no patient died from infection during the admission for transplantation, and infection played a part in the deaths of only four patients. The incidence of other complications was low; seven patients developed gastrointestinal complications, one died, four patients developed diabetes, all survived; only one patient developed avascular necrosis of bone.

Administration, Oral↗

Donor pretreatment: rat heart allograft survival and measurement of passenger leukocyte depletion with indium-111.

The present experiment was designed to study the relationship between rat heart allograft survival and passenger leukocyte depletion in donor-pretreated animals. Untreated Lewis rats served as recipients of cardiac allografts from treated Fischer rats. Passenger leukocyte depletion was assayed with indium-111 oxine-labeled leukocytes (predominantly lymphocytes) which were infused into donor rats 6 hr before treatment with cyclophosphamide, antilymphocyte globulin (ALG), sublethal total body irradiation, or in vitro perfusion-preservation of the isolated beating heart. In vivo pretreatment of the donor with cyclophosphamide resulted in a significant prolongation of heart allograft survival but effected no reduction in graft-labeled lymphocytes. In vitro perfusion-preservation of the donor heart, for 1 to 2 hr, led to a 50 to 60% reduction in graft-labeled lymphocytes but failed to significantly prolong the survival of the heart allografts. Both ALG and sublethal total body irradiation donor pretreatments resulted in significant prolongation of heart allograft survival and a 20 to 25% labeled passenger lymphocyte depletion. This study demonstrates that there is no direct correlation between allograft survival and the degree of mobile passenger lymphocyte depletion, suggesting that the efficacy of leukocytotoxic donor pretreatment methods may depend in part on alternative mechanisms.

Animals↗

Biochemical aspects of neutrophil chemotaxis.

Solutions of crude casein contain a chemotactic peptide with a molecular weight of 2 200 daltons. As in the case of other cytotaxins, this compound displays hydrophobic properties. Partially purified casein cytotaxin stimulated the disproportionate oxidation of glucose-1-carbon, from which we infer that hexose monophosphate shunt activity is increased in cells exposed to cytotaxin. No evidence could be found to support the suggestion that cytotaxin stimulation leads to activation of latent cellular esterases.

Animals↗

Indirect leukocyte migration assay in patients with malignant melanoma.

Leukocytes from 72 melanoma patients and 75 control donors were examined in a two-stage (indirect) leukocyte migration assay, using formalin-fixed melanoma cells (FMC) and control, normal or non-melanoma tumour cells (FCC) as the source of antigen. Inhibitory supernatants were produced significantly more often by cultures of melanoma leukocytes and FMC than by melanoma leukocytes and FCC or control leukocytes and FMC or FCC. Reactive leukocytes were most frequently derived from stage II patients (65%), followed by stage I patients with tumour present (58%), stage III patients (29%) and stage I patients without detectable tumour (20%). The likelihood that a melanoma patient's leukocytes would react increased progressively with the number of different FMC preparations tested. A similar, though less steep increase in reactivity was seen with control donor leukocytes and different FMC preparations. No significant increase in reaction frequency was seen with melanoma or control leukocytes exposed to increasing numbers of different FCC preparations. Significant discrimination between melanoma patients' and control donors' leukocytes was achieved with FMC from both primary and metastatic tumours. Concordance of positivity or negativity was seen in 60% of concurrent one-stage and two-stage leukocyte migration assays.

Adult↗

Selective lymphoid irradiation. I. An approach to transplantation.

The kinetics, distribution, and radiobiologic effects of palladium (Pd)-109-hematoporphyrin were determined in the rat. In addition, we studied the effect on rat heart allograft survival of Pd-109-hematoporphyrin, with and without antilymphocyte serum (ALS). A single sublethal dose of Pd-109-hematoporphyrin (up to 36 muCi/kg) resulted in the following: predominant concentration in lymphoid tissue and proximal bone marrow, complete central and proximal bone marrow ablation with preservation of distal bone marrow, massive depletion of lymphocytes from lymph nodes and spleen, an 80% reduction in peripheral blood lymphocytes which was completed by the addition of ALS, full recovery of lymphoid tissue and blood cellularity within 60 days of administration of radionuclide, and a 100% animal survival rate. This method of selective lymphoid irradiation (SLI) prolongs indefinitely Fisher cardiac allografts in Lewis recipients and significantly prolongs cardiac allograft survival across major histocompatibility barries (ACI to Lewis or to Fisher). Specific tolerance to donor strains was demonstrated by the acceptance of Fisher skin by Lewis recipients carrying 150-day-old Fisher hearts. Third party (ACI) skin allografts were rapidly rejected by the same animals. Further studies of SLI in larger animals are required to determine the optimal safe dose of SLI in man.

Animals↗