Biomedical subjects
Publications and source records attributed to K Nielsen.
During a period of ten years, 111 patients with cancer of the bladder were treated by total cystectomy. In 69 patients a preoperative radiation dose of 40 Gy was administered, 23 received 60 Gy and 19 received no radiation. The crude-survival was 50%. The postoperative mortality was low, 3.6%.
Fifty-eight consecutive patients diagnosed with prostatic cancer at transurethral resection in the period 1979-1983 were classified using histological grade according to Shelley, and using an unbiased estimate of mean nuclear volume. We find that both histological grade and mean nuclear volume appear to be significantly associated with survival. In eight of nine patients still alive after 89-130 months mean nuclear volume at diagnosis was in normal range and the histological grade showed a highly differentiated cancer in eight of the nine cases. These findings suggest highly differentiated cancer and normal range of mean nuclear volume may be important for long-term survival. In patients with advanced disease requiring endocrine treatment both histological grading and mean nuclear volume estimates failed to show any prognostic properties with regards to time to progression and time of survival. In patients not subjected to endocrine treatment histologic grade, but not mean nuclear volume, was found to be significantly associated with survival. Subtle changes in disease progression may be diagnosed early by repeated biopsies due to the accuracy and high reproducibility of mean nuclear volume measurements; however, a single estimate of mean nuclear volume has not been shown to offer advantage over histological grade with respect to prognostic properties.
Monoclonal antibodies (Mabs) to bovine immunoglobulin heavy chain of the four major isotypes gamma 1, gamma 2, alpha, mu and the light chains (combined kappa and lambda) were produced and found to cross-react in enzyme-linked immunoassay (ELISA) with immunoglobulins of some other animal species despite the discrete specificity associated with an antibody derived from a single clone. This cross-reactivity, particularly amongst ruminants, could be utilized in serological testing for the diagnosis of disease in these species. For example, Mabs produced against bovine immunoglobulin light chain cross-react with bison immunoglobulin light chain and were used successfully in serological testing as the secondary detection antibody in an indirect ELISA for the diagnosis of Brucella abortus in bison herds in north-western Canada.
The efficacy of urea synthesis as measured by functional hepatic nitrogen clearance (i.e., the relation of urea synthesis rate to blood alpha-amino nitrogen concentration) was studied before and after diet protein supplementation in six healthy subjects and five patients with stable cirrhosis (galactose elimination capacity about 60% of control). Daily protein intake was increased for 14 days by a protein-enriched liquid from (mean +/- S.D.) 1.01 +/- 0.32 g/kg body wt. to 1.62 +/- 0.31 g/kg body wt in the control subjects, and from 0.69 +/- 0.21 g/kg body wt. to 1.50 +/- 0.15 g/kg body wt. in the patients with cirrhosis. This increased the hepatic nitrogen clearance from 27 +/- 10 l/h to 39 +/- 15 l/h in the control subjects (p less than 0.05) and from 15 +/- 6 l/h to 21 +/- 7 l/h in the cirrhosis patients (p less than 0.05). There was no effect on the galactose elimination capacity in any group. Compared to the control subjects, the response in hepatic nitrogen clearance relative to the increase in protein intake was reduced by 60% in the patients. Basal glucagon was 75% higher in the patients and increased by 50% during high protein intake (p less than 0.05), but did not parallel the increase in hepatic nitrogen clearance, and it did not change in the control subjects. The study shows that an increase in protein intake selectively increases liver function with regard to disposal of amino nitrogen; the mechanism is qualitatively intact but quantitatively deficient in patients with cirrhosis of the liver, and does not seem to depend on glucagon.
Renal vein oxygen-saturation was measured in 56 patients with arterial hypertension and unilateral stenosis or occlusion of the renal artery. Oxygen-saturation in blood from the ischaemic kidney (84.4%, range 73-93%) was significantly higher than that from the 'normal' contralateral kidney (81.2%, range 70-90%, P less than 0.001). In only six patients, the ischaemic kidney revealed a venous oxygen-saturation below the contralateral value (mean difference ischaemic-normal kidney 3.2%, range -6 to 15%). The results indicate that the oxygen uptake in the chronic ischaemic kidney is more decreased than its blood flow. This is probably due to decreased filtration fraction and filtered sodium with subsequent reduction in absolute tubular re-absorption of sodium ions.
In a modified, double-blind controlled study, 163 prepubertal boys (aged 1.8-13.0 years) with bilateral and 94 (aged 1.5-13.1 years) with unilateral cryptorchidism were allocated to treatment with either human chorionic gonadotrophin (im), gonadotrophin releasing hormone (intranasally) or placebo (intranasally). In individuals with the bilateral condition treatment with human chorionic gonadotrophin resulted in complete descent of both testes in 23% of patients. Treatment with human chorionic gonadotrophin in unilateral cryptorchidism resulted in complete descent in 19% of patients; all results were significantly better than those obtained with gonadotrophin releasing hormone or placebo. Linear and logistic regression analysis of the results obtained by treatment of bilateral disease showed that all treatments were more successful the younger the age of the boys. The data indicated that bilateral and unilateral cryptorchidism respond differently to hormonal treatment. We suggest that human chorionic gonadotrophin should be the first choice of treatment for prepubertal boys older than one year.
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Two-dimensional (2D) 1H-NMR spectra of porcine-brain natriuretic peptide (pBNP) have been recorded at 300 MHz and 400 MHz. Peak assignments have been made and the combined information from chemical shifts, coupling constants, temperature coefficients and NOEs have been used to determine the conformational properties of pBNP in (C2H3)2SO. Overall the peptide appears to be flexible, with the possibility of some beta-type structure near the C terminus. Some of the assignments and deduced structural features in the current study differ from those in a recent report by Inooka et al. [Inooka, H., Kikuchi, T., Endo, S., Ishibashi, Y., Wakimasu, M. and Mizuta, E. (1990) Eur. J. Biochem. 193, 127-134] which may indicate the sensitivity of the structure of this peptide to differences in solution conditions.
A rapid, simple dot immunoperoxidase assay (DIPA) is described for visual detection and identification of bluetongue virus (BTV) antigens in samples of infected cell culture fluid. The assay was performed using nitrocellulose (NC) paper and 'dipsticks'. Dots of samples were adsorbed to the NC surface and the remaining non-specific binding sites were blocked with skim milk solution. BTV was detected with either of two murine monoclonal antibodies (4H4, 5G12) to the major group specific antigens of BTV, and the complex was reacted with a peroxidase conjugated anti-mouse immunoglobulin G (heavy- and light-chain specific). Positive reactions were easily visualized as brown spots after enzyme degradation of substrate containing H2O2 and diaminobenzidine (DAB). The DIPA was specific in detecting BTV in samples of cell culture fluid from baby hamster kidney (BHK-21) cells infected with U.S.A. isolates of the five BTV serotypes (2, 10, 11, 13 and 17) known to exist in the U.S.A., and South African isolates of 17 BTV serotypes (1-12, 14-16, 18 and 20), but not with two North American isolates of epizootic hemorrhagic disease of deer virus (EHDV) representing serotypes 1 and 2. Attempts to detect BTV directly in infected sheep blood cells and chick embryo tissue suspensions by DIPA were unsuccessful. Of 55 cell culture fluid samples examined from BHK-21 or Vero cell monolayers inoculated with 55 clinical specimens, propagated initially in embryonating chicken egg (ECE) 11 proved positive and 44 were negative by DIPA. The results were in complete agreement with the conventional ECE and tissue culture isolation systems. The DIPA appears to have potential application, especially as a 'dipstick' kit, for rapid and inexpensive laboratory diagnosis of bluetongue virus infection.
The combination of carboplatin and teniposide has been evaluated in a phase II trial including 47 previously untreated patients with extensive small cell lung cancer. Treatment was given at monthly intervals at a dose of 200 mg/m2 of carboplatin intravenously on day 1 and teniposide at a daily dose of 60 mg/m2 intravenously on days 1-5. Treatment response was complete in 4 (8.9%) and partial in 19 (42.2%) of 45 evaluable patients. The overall response rate was 51.1% (95% confidence interval 36%-66%). The median duration of response was 7.1 months (range 2.1-14.8) and the median survival was 6.7 months (0.3-22.2). Myelosuppression was the most prominent side-effect. Leukopenia (WHO grade 3-4) developed in 17 (37.8%) and thrombocytopenia (grade 3-4) in 5 (11.1%) of 45 patients evaluable for toxicity. 2 treatment-related deaths were registered. The present study shows that the combination of carboplatin and teniposide produces an acceptable response rate, but response duration and survival time are short.
A murine monoclonal antibody 105 made from spleen cells of a mouse immunized with a mixture of common Salmonella serotypes reacted specifically with salmonellae from the most frequently encountered O serogroups of A (O:2) to E (O:3), and with strains from the less common O serogroups that represent the subspecies I, II, IIIb, IV, V and VI. Specificity for Salmonella was demonstrated by the lack of reactivity of monoclonal antibody 105 with any of the 30 other different species of Gram-positive and Gram-negative bacteria tested including 16 species in the family of Enterobacteriaceae. Studies to elucidate its binding epitope have shown that it reacts with the three distal sugar residues joined through specific anomeric linkages as present only in the Salmonella lipopolysaccharide outer core, which explains its specificity for the Salmonella. The failure of monoclonal antibody 105 to react with a subspecies IIIa Salmonella suggested a different outer core structure in this strain of Salmonella and also that monoclonal antibodies to the outer core of Salmonella lipopolysaccharide should be useful in the molecular analysis of their diversity.
Supplementary prognostic factors should be added to the TNM classification for oral squamous cell carcinomas in order to optimize its clinical value. We have recently published two prognostically valuable malignancy grading systems based on histopathology and immunohistology of the most invasive cells in oral squamous cell carcinomas (OSCCs). However, a major problem with classifications based on histologic features is frequent lack of interobserver agreement which limits the clinical value of subjective histologic classifications. Thirty-eight file cases of OSCCs were therefore graded by three pathologists according to criteria of the histologic malignancy grading system which includes 5 morphologic features, each graded from 1 to 4. Agreement was calculated by kappa statistics, which showed that interobserver agreement was not optimal, but significantly better than by chance alone. We also studied the reproducibility of grading of immunohistologic membrane expression of a tumor-associated marker (blood group antigen H), and found a similar level of agreement. We conclude that the clinical value of our grading systems will increase by improving reproducibility.
A more objective and reproducible grading system is needed in order to give better prognostic indicators and thereby offer improved treatment to oral cancer patients. Recently, simple objective stereological techniques for cellular estimates have emerged, of which the estimate of mean nuclear volume has shown a correlation with prognosis for various cancers. We have therefore measured the mean nuclear volume in 44 invasive buccal mucosal squamous cell carcinomas and related it to the survival of patients. The mean nuclear volume did not correlate with prognosis for these patients (p = 0.25). However, the nuclear polymorphism, which is subjective even though it is based on well-described criteria in a histopathological grading system, correlated significantly with prognosis (p = 0.03). These findings indicate that the traditional histopathological evaluation of nuclear polymorphism includes valuable prognostic information.
Cleavage of host defense proteins from reproductive secretions was investigated as a potential virulence mechanism for Tritrichomonas foetus extracellular proteinases. Three categories of susceptibility to digestion were found among the defense proteins tested. Cleavage of fibrinogen, fibronectin, and albumin occurred rapidly with more than 50% of these digested within 30 min. Lactoferrin, immunoglobulin G1, and immunoglobulin G2 were more than 50% digested after 4 h. Transferrin, immunoglobulin M, and immunoglobulin A were the most resistant to the Tritrichomonas foetus extracellular proteinases, since 50% or more of the parent molecule remained after 24 h. The responsible proteinases were classified as cysteine (thiol) proteinases because cleavage was inhibited by the cysteine proteinase specific inhibitor, trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane and not by the serine proteinase specific inhibitor, phenylmethylsulfonyl fluoride. In addition, alpha 2-macroglobulin, but not alpha 1-antitrypsin, inhibits the action of the proteinases. The ratio of this naturally occurring inhibitor to the quantity of proteinases released may determine whether the above substrates are cleaved in vivo. Since these substrates are implicated in iron acquisition, cell adherence, and acquired immunity, Tritrichomonas foetus proteinases are likely to play a role in host-parasite interactions.
A case is presented of tubulo-villous adenoma in the vagina of a 43-year-old woman. The possible origin of this rare condition is discussed and the need for careful follow-up is emphasized.
During the 2-year period 1985-86 a total of 1,876 patients were admitted to our hospital after milder head trauma including cerebral concussion. Two hundred and eighty four patients who had a skull X-ray were not selected from guidelines. In 1,592 patients without a skull X-ray, signs of an intracranial complication developed in six cases and were verified by CT. In the 284 patients with skull X-ray a fracture was demonstrated in 25, and of these 25 patients only one patient disclosed a cerebral contusion. In the 259 patients with skull X-ray, but without demonstration of fracture, there were subsequently seen one subdural haematoma and one cerebral contusion. The incidence of intracranial complications in patients without and with skull X-ray with or without fracture does not differ significantly. In these circumstances we do not find any justification for routine skull X-ray after milder head trauma.
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The DNA content was investigated by means of flow cytometry in frozen tumor specimens from 33 patients with uterine endometrial carcinoma. The association was tested between ploidy and S-phase fraction on one hand and clinico-pathological parameters on the other. Aneuploidy appeared in 15 (45%) of the patients, and the average S-phase fraction was 0.18 (0.04-0.34). There was a highly significant correlation between DNA-Index (DI) and histologic differentiation (p = 0.01) and a less significant correlation between DI and estrogen receptor content (p = 0.04). DNA ploidy measured by flow cytometry is a highly reproducible parameter that in addition to routine histopathological examination may provide useful information. Further studies are needed to establish the prognostic importance of the flow cytometric parameters.