Actinomyces naeslundii displays variant fimP and fimA fimbrial subunit genes corresponding to different types of acidic proline-rich protein and beta-linked galactosamine binding specificity.

Actinomyces naeslundii genospecies 1 and 2 bind to acidic proline-rich proteins (APRPs) and statherin via type 1 fimbriae and to beta-linked galactosamine (GalNAcbeta) structures via type 2 fimbriae. In addition, A. naeslundii displays two types of binding specificity for both APRPs-statherin and GalNAcbeta, while Actinomyces odontolyticus binds to unknown structures. To study the molecular basis for these binding specificities, DNA fragments spanning the entire or central portions of fimP (type 1) and fimA (type 2) fimbrial subunit genes were amplified by PCR from strains of genospecies 1 and 2 and hybridized with DNA from two independent collections of oral Actinomyces isolates. Isolates of genospecies 1 and 2 and A. odontolyticus, but no other Actinomyces species, were positive for hybridization with fimP and fimA full-length probes irrespective of binding to APRPs and statherin, GalNAcbeta, or unknown structures. Isolates of genospecies 1 and 2, with deviating patterns of GalNAcbeta1-3Galalpha-O-ethyl-inhibitable coaggregation with Streptococcus oralis Ss34 and MPB1, were distinguished by a fimA central probe from genospecies 1 and 2, respectively. Furthermore, isolates of genospecies 1 and 2 displaying preferential binding to APRPs over statherin were positive with a fimP central probe, while a genospecies 2 strain with the opposite binding preference was not. The sequences of fimP and fimA central gene segments were highly conserved among isolates with the same, but diversified between those with a variant, binding specificity. In conclusion, A. naeslundii exhibits variant fimP and fimA genes corresponding to diverse APRP and GalNAcbeta specificities, respectively, while A. odontolyticus has a genetically related but distinct adhesin binding specificity.

Drug and alcohol use among injured motor vehicle drivers in Sweden: prevalence, driver, crash, and injury characteristics.

Injured motor vehicle drivers who were hospitalized (Umeå: n = 130) and fatally injured drivers who were autopsied (Umeå, Northern Sweden: n = 111; Gothenburg, Western Sweden: n = 136) from May 1991 through December 1993 were tested for alcohol and for both licit and illicit drugs. Nineteen percent of the Umeå-hospitalized drivers (UHDs), 26% of the Umeå fatally injured drivers (UFDs), and 21% of the Gothenburg fatally injured drivers (GFDs) tested positive for drugs and/or alcohol. Ten percent of the UHDs, 8% of the UFDs, and 6% of the GFDs tested positive for drugs. Almost 5% of the UHDs, had illicit drugs, and 6% had licit drugs. Only 3% of the GFDs and none of the UFDs had illicit drugs. Benzodiazepines, followed by opiates, tetrahydrocannabinol, and amphetamine were the most common drugs detected. Twelve percent of the UHDs, 24% of the UFDs, and 17% of the GFDs tested positive for alcohol. Two percent of the UHDs, 6% of the UFDs, and 2% of the GFDs had a combination of drugs and alcohol.

Oral treatment with RU 41.740 (Biostim) in patients with advanced colorectal cancer: influence on the blood lymphocyte population.

Twelve patients with advanced colorectal carcinoma received oral treatment with RU 41.740, an immunomodulatory drug obtained from Klebsiella pneumoniae. The patients received three courses of RU 41.740, each consisting of 8 mg daily for 7 consecutive days, with free intervals of 3 weeks. This treatment did not significantly change the distribution of various lymphocyte subsets in the blood or the NK activity of the lymphocytes. However, PHA reactivity of purified lymphocytes increased significantly and exhibited a 2-3-fold enhancement 3 weeks after the last course. Such an increase was not observed in lymphocyte preparations which were not depleted of monocytes. It is concluded that 41.740 may be immunopharmacologically active in man when administered by the oral route.

Two randomised phase II trials of intermittent intravenous versus subcutaneous alpha-2 interferon alone (trial 1) and in combination with 5-fluorouracil (trial 2) in advanced colorectal cancer.

Sixty-five patients with advanced colorectal cancer were randomised to one of two schedules of recombinant alpha-2 interferon (IFN). In the first study, 36 patients received single-agent IFN, either 50 X 10(6) U/m2 intravenously on 5 consecutive days every 4 weeks, or 20 X 10(6) U/m2 subcutaneously three times per week. No tumour responses were seen and toxicity was unacceptable. In the second study, 29 patients received IFN in two similar schedules, but the dose of IFN was reduced to 20 X 10(6) U/m2 per day in the intravenous arm and to 5 X 10(6) U/m2 per day in the subcutaneous arm. In addition these patients were administered intravenous 5-Fluorouracil (5-FU), 250-500 mg/m2 per day on the first 5 days of each 4-weekly cycle. Although the toxicity of this second study was tolerable, only one short-lived partial remission was observed. Alpha-2 interferon, alone or in combination with 5-FU, is ineffective in advanced colorectal cancer.

Selective venous sampling for localization of hyperfunctioning parathyroid glands.

Selective venous sampling with parathyroid hormone assay was used in 46 patients with primary hyperparathyroidism. All patients had previously been operated on in the neck region. In 80 per cent of the patients the method correctly located the position of the hyperfunctioning gland(s). No complications were observed. The method was found to be of great value when evaluating patients with persistent or recurrent hyperparathyroidism.

Early effects of preoperative irradiation upon the cell cycle composition in rectal adenocarcinomas. A flow-cytometric DNA investigation.

The DNA patterns were studied by means of flow cytometric analysis in 43 rectal adenocarcinomas. Ploidy level and cell cycle distribution were related to clinical stage and histopathology. The frequency of grossly aneuploid tumours and tumours with multiple aneuploid cell populations increased with more advanced clinical stages and with the degree of dedifferentiation. In 15 cases the DNA pattern was studied before and after preoperative irradiation. The ploidy level was not affected by irradiation. A pronounced increase in the proportion of G2 cells was found after irradiation. This G2 blockage was proportional to the amount of S-phase cells before irradiation. Since following irradiation the proportion of S-phase cells was low and the proportion of G1 cells unchanged, the existence of a high fraction of resting G1 tumour cells can be assumed.

Bladder and sexual function after surgery for rectal cancer.

Bladder function and sexual potency were studied before and after surgery for rectal carcinoma. Urinary voiding after postoperative removal of indwelling catheter was impaired in seven of 22 men, leading to prostatic surgery in four. Two years later, eight of 16 men reported disturbed voiding, but no significant changes were found in bladder capacity, residual volume, flow rate, or detrusor pressure. Sexual potency was reduced in five of ten men, in one with retrograde ejaculation; and three did not achieve erection. Objective postoperative bladder disturbance was surprisingly rare. Symptoms of denervation were more commonly attributable to sympathetic rather than parasympathetic lesions, possibly as a result of more energetic dissection in the anteroposterior plane than along the lateral pelvic walls. No patient had total autonomic denervation. Wide indications are advocated for prostatic resection in patients who have prostatic symptoms in association with surgery for rectal carcinoma.

Curative potential of EEA stapler in rectal carcinoma.

In a 5-year period (1980-1984), 96 patients were curatively treated for rectal carcinoma. Surgery consisted of local excision in 9 cases, resection with restoration of rectal continuity in 48 (the anastomosis EEA-stapled in 29 and hand-sewn in 19) and total rectal excision in 39 cases. These procedures were selected according to conventional principles, in non-randomized manner. Tumor stages were comparable in the groups with major surgery. After follow-up averaging 3 years, the crude survival rate was 76% in the EEA group, 53% after hand-sewn anastomosis and 69% after total rectal excision. Although the groups were not strictly comparable, the results showed that survival after low stapled anastomosis was not inferior to that after other treatment methods. Pelvic recurrence after stapling has so far appeared only in stage C cases. The study did not confirm recent alarming reports of high local recurrence risk after stapling. It supports the view that circular staplers permit preservation of sphincter without increased incidence of pelvic recurrence or compromised survival.

Colorectal carcinoma. A survey of 1345 cases 1950-1984.

A 35-year (1950-1984) experience of colorectal carcinoma is surveyed. Intendedly curative resection was performed in 941 (70%) of the 1345 patients, this proportion being constant throughout the study. The operative mortality was 4.6%, falling from 12% in the early 1950s to less than 1%. Five-year survival, calculated for 1066 patients seen in 1950-1979, was 35% overall and 49% after surgery with curative intent. Improved survival rates were mainly due to decline in operative mortality. In Dukes' stages A, B and C the respective 5-year rates were 83, 48 and 22%. Retention of the original Dukes' system is advocated. Further improvement in results probably cannot be achieved via surgical management. Intensive follow-up routines have not revealed significant numbers of curable recurrences, and adjuvant treatment has been disappointing. To improve the long-term prospects, earlier diagnosis seems to be essential. Screening for fecal occult blood may be valuable, but proof awaits the results of randomized clinical trials.

The significance of DNA distribution pattern in rectal carcinoma. A preliminary study.

The DNA distribution pattern was determined retrospectively in 25 rectal carcinomas and the possible correlation to clinical outcome evaluated. The DNA content in individual cells was measured according to a cytophotometric method based on light transmission measurement of Feulgen-stained nuclei. Tumor cells with DNA content exceeding an upper limit, i.e., the 90 percentile of the control cells, were considered to be nondiploid (aneuploid). Virtually all long-term survivors had less than 50 per cent of the tumor cells exceeding the upper diploid level, whereas those developing only a local recurrence had 50 to 70 per cent. Patients with disseminated disease and short survival time had all of their tumor cells exceeding the upper diploid level. There was a highly significant correlation between Dukes' stage and aneuploidy and probably a significant correlation between histologic grading and aneuploidy. The clinical significance of these results lies in the fact that DNA can be measured in biopsy specimens. It might thus be possible to "tailor" the operation according to the future clinical course to be expected. It could be hypothetically argued that patients with a DNA profile heralding disseminated disease and short life expectancy should have surgery that preserves quality of life, whereas those tending to develop a local recurrence should have more aggressive surgery. It may also be possible to define groups of patients thought to prosper from a more intense postoperative surveillance. The scientific basis for these suggestions is still lacking, and further studies on a prospective basis are currently in progress.

Flow-cytometric DNA analysis as a means for early detection of malignancy in patients with chronic ulcerative colitis.

A new approach to the problem of monitoring patients with chronic ulcerative colitis is presented and discussed in connection with a case report. When annual colonoscopies are performed, biopsies are taken for histopathological examination and DNA measurements are made using flow-cytometric techniques (FCM). Using the latter approach, gross chromosomal aberrations indicating malignant transformation in a cell population may be detected. In a 46 year old man with a long history of ulcerative colitis, an area with slight mucosal dysplasia at light microscopy was accompanied by two aneuploid cells lines - that is, colonic mucosa cells with an abnormal amount of DNA in the nuclei. An operation one year later revealed a 5 X 2 mm large adenocarcinoma in the corresponding area of the colon. We suggest that flow-cytometric techniques can be used as a complement to already practised methods for monitoring the colorectal mucosa in colitic patients for the early detection of malignancy.

Villous dysplasia. An ominous histologic sign in colitic patients.

Preoperative biopsies and colectomy specimens from 40 patients with long-standing ulcerative colitis (of whom 20 had adenocarcinoma at colectomy) were searched for the presence of villous adenomatous changes with or without cellular dysplasia. Villous adenomatous changes were found in available preoperative punch biopsies in nearly 70 per cent of the patients with carcinoma, but in none of the preoperative punch biopsies from the 20 patients without cancer. Only three of the preoperative biopsies from patients with carcinoma showed severe dysplasia, and also one of the 20 colitic patients without carcinoma. The mucosal tip in villous adenomatous changes was usually covered by columnar epithelium without dysplasia. In preoperative punch biopsies from patients with long-standing ulcerative colitis, the presence of structures compatible with villous adenoma--even those without cellular dysplasia--should be considered an ominous histologic sign and, thus, an indication for panproctocolectomy.

High dose rDNA human alpha 2 interferon therapy in patients with advanced colorectal adenocarcinoma: a phase II study.

Eighteen patients with advanced and inoperable colorectal adenocarcinomas were treated with high doses of alpha 2 Interferon (Schering-Plough Corporation). The patients were randomized to receive either subcutaneous injections of 20 X 10(6) I.U./m2 three times weekly for 3 months, or pulsed treatments of 50 X 10(6) I.U./m2 daily, given intravenously, for 5 consecutive days every 4 weeks. No objective tumour regression was seen in any patient. The side effects were considerable.

Treatment of patients with disseminated colorectal cancer with recombinant human alpha 2-interferon. Studies on the immune system.

The influence of recombinant human alpha 2-interferon (alpha 2-IFN) therapy on various aspects of the immune system was studied in 18 patients with disseminated colorectal cancer. The IFN was given as continuous (20 X 10(6) units/m2 three times weekly) or intermittent (50 X 10(6) units/m2 daily for 5 consecutive days every 4 weeks) treatment. Natural killer (NK) cell activity increased during continuous treatment and in the patients receiving repeated cycles of IFN, all cycles seemed to be associated with an elevation of NK activity. Prior to treatment, addition of IFN to the assay in vitro induced an enhancement of NK activity, whereas during treatment, IFN in vitro did not cause any further enhancement of NK activity. The proportions of total T cells, suppressor T cells and helper T cells, as measured by Leu 1, Leu 2a and Leu 3a monoclonal antibodies, were not altered to any major extent during treatment. This was found to be the case also for the number of cells detected by monoclonal antibodies against NK cells (Leu 7). The phagocytic activity of granulocytes was not altered during IFN therapy, whereas the capacity of these cells to reduce nitroblue tetrazolium (NBT) increased after the first injection of IFN. The in vivo influence of high doses of highly purified recombinant alpha 2-IFN on NK cells and granulocytes seems to be similar to that of partially purified natural IFN-alpha.

EEA stapler for mid-rectum carcinoma. Review of recent literature and own initial experience.

Over a three-year period, 1980-82, 79 per cent of our patients with rectal cancer were treated with the intention of cure, and sphincter-saving procedures were performed in 62 per cent of these cases. This report concerns 21 patients with mid-rectum cancer operated on with low anterior resection and extraperitoneal EEA-stapled anastomosis. Nine patients had Dukes' stage A tumors, seven had stage B, and five had stage C tumors. An 86-year-old woman died in the sixth postoperative week, and a 74-year-old man died after 20 months with a probable recurrence. Nineteen patients are currently alive 4 to 40 months post-operatively, with no overt signs of recurrence. We cannot confirm recent alarming reports on a significant incidence of early local recurrence. Routine Gastrografin enemas were performed and offered very little in terms of clinical guidance. Significant anastomotic leakage occurred in four patients, although without clinical symptoms or the need for fecal diversion. Despite initially intact anastomoses in 13 patients, pelvic sepsis with late dehiscence developed in three, all of whom required fecal diversion. The clinical leak rate was thus 3 of 21, 14 per cent, and the total incidence of leakage 7 of 21, 33 per cent. We performed routine colostomy on the first three patients but, in retrospect, believe this was unneccessary. Only one of the 19 survivors still has a colostomy, due to a benign anastomotic stricture. We consider anterior resection of mid-rectum carcinoma with EEA-stapled anastomosis a highly feasible procedure, the curative potential of which, however, can be established only by long-term follow-up studies.

Effects of intraluminal pressure on regional blood flow in obstructed and unobstructed small intestines in the rat.

Small bowel circulation in the rat was studied with the microsphere technique before and after 10 minutes of elevated intraintestinal pressure. A distal small bowel loop consisting of 10 vascular arcades was used. The specimens were inflated with nitrogen gas. Regional blood flow in both obstructed and unobstructed small bowels was significantly diminished by an intraintestinal pressure of 40 mm Hg. A pressure of 20 mm Hg impaired circulation only in the obstructed small intestine, whereas the unobstructed intestine did not show a similar decrease. These findings suggest that moderate intraluminal pressures can imply a potential hazard to the vulnerable capillary bed of an obstructed intestine. Hence, it is suggested that intraoperative decompression should be performed to avoid this postoperative threat to bowel viability.

The histological classification of early gastric cancer (micro-invasive carcinoma of the stomach).

During a 3.5-year period, January 1976 to June 1979, eleven cases of micro-invasive carcinoma of the stomach (early gastric cancer) were detected in 45 gastrectomy specimens having a pre-operative diagnosis of gastric carcinoma. The histological types found in the surgical specimens were highly differentiated (1), moderately differentiated (4), poorly differentiated (3) adenocarcinomas, one specimen had undifferentiated carcinoma, and in the remaining two cases mixed types were found. Multiple lesions were present in five specimens. In ten of the eleven specimens, focal cystic dilatation of the deeper part of the gastric glands were found in areas overlapped by micro-invasive carcinoma and/or in areas overlapped by mucosa showing chronic inflammation. The frequency of cystic dilatation of the gastric gland was much lower in specimens from patients with gastric or duodenal peptic ulcers. Thus, focal cystic dilatation present in negative gastric biopsies should be reported, thereby alerting the referring physician as to the possibility of a gastric malignancy.