Biomedical subjects
Publications and source records attributed to T Alm.
Poly ICLC is an interferon (IFN) inducer and antiviral, antitumor, radioprotective, and immunoregulatory agent. We show that administration of poly ICLC to mice and rabbits also results in the presence of anti-IC antibodies in their serum.
The design and execution of the Cooperative Crohn's Disease Study in Sweden are described in this paper. A double-blind, double-dummy, crossover (2 X 4 mo) technique was used to compare the suppressive efficacy of metronidazole (0.4 g b.i.d.) and sulfasalazine (1.5 g b.i.d.). The number of randomized patients (78) presented approximately one-third of the available population. The Crohn's Disease Activity Index and the plasma level of orosomucoid were the main variables for clinical evaluation. Results were analyzed primarily in the first treatment period by ranking the clinical outcome of every patient according to a uniform and detailed scheme and applying Wilcoxon nonparametric statistics. The cross-over data only served as additional information. Thirty-six patients had had earlier and mostly positive experience with sulfasalazine. Repeated plasma drug analysis indicated good compliance. The blindness of the trial was tested and appeared satisfactory. The coordination of the trial proceeded as planned. A lack of full conformity in the electroimmunoassay of orosomucoid was taken care of satisfactorily.
Seventy-eight patients with active Crohn's disease participated in a randomized, double-blind, cross-over trial. The study comprised two 4-mo period. The purpose was to test the efficacy of metronidazole in comparison with that of sulfasalazine. As the main evaluation criteria the Crohn's Disease Activity Index and plasma levels of orosomucoid were chosen. In the first period no difference in efficacy as measured by Crohn's Disease Activity Index was found between the treatment groups. The reduction of the plasma orosomucoid level was significantly more pronounced in the metronidazole group. The hemoglobin concentration increased more in this group than in the sulfasalazine group, possibly due to a toxic effect of sulfasalazine. The erythrocyte sedimentation rate decreased similarly with both drugs. In 15 patients who had active disease throughout the first period, Crohn's Disease Activity Index decreased significantly in the second period for those who switched to metronidazole, but not for those who switched to sulfasalazine. After crossover, no apparent further change in Crohn's Disease Activity Index occurred in either of the treatment groups among patients who had responded favorably in the first period. The plasma concentration of orosomucoid increased significantly among the patients in the sulfasalazine group but not in the metronidazole group. It is therefore concluded that metronidazole is slightly more effective than sulfasalazine in the treatment of crohn's disease. It is worthwhile switching the drug regimen from sulfasalazine, when it fails, to metronidazole, but not from metronidazole to sulfasalazine.
Assays of in vitro biological properties associated with cellular transformation revealed differences in cultured skin cells within the heritable colon cancer syndromes with polyposis coli. Such evidence suggested that genetic heterogeneity, long assumed from in vivo differences in extracolonic lesions in these syndromes, could be detected in vitro. None of the properties studied nor any grouping of them made identification of a specific genotype possible.
It is proposed, based on in vitro studies on hereditary colorectal cancer syndromes (adenomatosis of the colon and rectum, ACR), that the presence/absence of specific abnormal culture phenotypes within and between such ACR kindreds will demonstrate the interaction of a modifying allele with its proposed major polyposis gene, influencing expression of this major gene, at least in vitro. Such in vitro evidence would suggest that the variability of clinical phenotype was due, at least in part, to such gene-gene interaction and this should be considered as well as the influence of enviornmental agents on the development of both pre-malignant lesions and clinical cancer in such cancer-prone families.
Cell culture studies on adenomatosis of the colon and rectum (ACR) suggested that the clinical phenotype, colonic adenomas which become malignant recognised as a single clinical entity, may not be entirely the result of a single dominant mutation. Of the dermal cultures containing both epithelioid and fibroblastic cells established from six affected subjects from six unrelated ACR families, four showed increased tetraploidy and two did not. Of similar cultures established from four affected subjects form families with ACR associated with sebaceous cysts in consecutive generations, three did and one did not have increased tetraploidy. Irrespective of the in vivo relationship of increased tetraploidy to colonic cancer, the cultures from seven ACR patients had populations of tetraploid cells, at least in vitro, with chromosome instability. Such a difference in expression of the ACR genotype in vitro suggested genetic heterogeneity within this clinically defined group.
A recent 3-month implantation study indicated that a new porous ceramic material might be suitable as a bone substitute in regions exposed mainly to compressive forces. The porous ceramics were implanted into the medial condyle of the tibia of sheep. In the present study the implants were left for 10 months in three animals, and 12 months in two. In the two animals with 12 months' observation, the plate which had been used to stabilize the implant was removed at 10 months. The implants and the adjacent bone tissue were studied macroscopically, radiographically and by microradiography and transmitted light microscopy. All the implants were bound to the adjacent bone by ingrowth of bony tissue. The depth of the bony invasion was slightly greater than that observed at 3 months, being maximally 3-4 mm. Some signs of ossification were still seen within the pores. The bony bridges between the implants and the surrounding bone were particularly well developed in regions of maximal stress. This was interpreted as a sign of active adaption of the bone formation to the actual stress to which the shearing surfaces were exposed. It is concluded that the properties of the porous ceramic implants justify a clinical trial in man.
An investigation of the prevalence of hereditary adenomatosis of the colon and rectum (ACR) in Sweden was started in 1959. Up to the end of 1972, 97 families were traced and 80 of them were more fully investigated. In 56 of the latter families there were at least 2 affected members; in the other 24, only one. In all, 340 affected individuals were found, 150 of whom were operated upon with the aim of cure. Of the operated patients 82 had presented with symptoms, the propositi group, while 68 affected individuals were detected during the family investigations and underwent prophylactic operations, the call-up group. A comparison was made between the two groups of the primary and long-term results after operation. Major surgery with total proctocolectomy and ileostomy (PCI) or colectomy with ileorectal anastomosis (IRA) was performed in 135 cases, 67 propositi and 68 call-up patients; minor surgery with segmental resection (SR) in 15 propositi. The propositi group is presented in detail in this paper, the call-up group in a following paper. In the propositi group there were 3 surgical deaths (3.7%). At the time of operation 48 patients (58.5%), had already developed cancer. Up to the end of the period of observation 16 of them died from metastases, 2 of other malignancies, and 3 of nonmalignant disease.
During the investigation, started in 1959, of Swedish families with hereditary adenomatosis of the colon and rectum (ACR), 68 affected, but symptom-free, individuals were detected and referred for surgical treatment. In all of them major surgery was performed, total proctocolectomy and ileostomy (PCI) in 10 cases, colectomy with ileorectal anastomosis (IRA) in 58. The surgical mortality was 4.4%. Six patients had cancer at the time of operation, and another 2 patients were operated on for colonic cancer many years prior to the diagnosis of ACR. One of those 8 patients died from metastases. Primary malignant kidney tumour was responsible for the only additional late death in this group. In a preceding paper the primary and long-term results after surgery in a group of patients who presented with symptoms, the propositi group, were reported in detail. In this group cancer was found in 48 patients, 16 of whom died from metastases. The most suitable time for operation, and the choice of operative method are discussed. The need for future supervision of affected families is stressed, and the arrangement of follow-up is outlined.
Hereditary adenomatosis of the colon and rectum (ACR) invariably leads to malignant transformation unless the patients undergo prophylactic operations. The serum level of carcinoembryonic antigen (CEA) was determined in 130 individuals belonging to different ACR-families. Fifty-six of them were operated upon with colectomy, 27 affected individuals were still not operated on, and 47 were unaffected first degree relatives. Around 20 percent of the patients in each of these groups had moderately raised CEA serum levels compared to unrelated healthy subjects. Since the serum values were low or only moderately raised and occurred in all groups, the determination of serum levels cannot be generally used to indicate malignant transformation of adenomas. However, assays of the tissue CEA content in six histologically verified adenomas showed values similar to those of overt colonic carcinomas. This opens up stimulating possibilities of investigating the CEA activity in serum and tissues of chosen individuals with ACR.
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