Squamous cell metaplasia of the bladder urothelium. A retrospective study of 36 patients.

In a retrospective study of 28 women and eight men with squamous cell metaplasia in different parts of the bladder, including the trigone, no histopathological differences were observed among the regions. All the five (female) patients with parakeratosis had a concomitant invasive bladder tumour. Thirty-eight% of all the patients had a simultaneous neoplastic tumour. The metaplastic lesions were investigated for keratin in 13 patients, and all were positive. In seven out of eight patients, the urothelium adjacent to the squamous cell metaplasia was also positive for keratin, indicating a direct transformation of the urothelium to squamous cell epithelium. The metaplastic cells were investigated for oestrogen receptors in five men and five women, and all were negative, suggesting no relationship between estrogens and squamous cell metaplasia of the bladder. Squamous cell metaplasia in the bladder is not considered a premalignant condition. However, metaplasia and neoplastic tumours are often associated with chronic tissue damage, and the presence of metaplasia may give a warning of conditions that can also cause cancer.     

Present status of boron neutron capture therapy.

The neutron capture reaction 10B(1n,4He)7Li produces two energetic particles, 4He2+ and 7Li3+ that are strongly cell toxic. Due to the short range of these nuclear fragments (5-9 microns) mainly those cells that have bound or internalized a 10B-containing substance are growth-inactivated. The most critical and difficult step in an efficient boron neutron capture therapy (BNCT) is the tumour targeting. It is today possible to synthesize a large number of boron compounds and conjugate them to tumour-seeking macromolecules, such as monoclonal antibodies or different polypeptides. The boron-containing substances presently considered for therapy are sulfhydryl boron hydride (BSH) and boron-phenylalanine, (BPA) for the treatment of gliomas and malignant melanomas respectively. Other boronated compounds considered are ligands for receptor-amplified tumour cells, antibodies for tumour cells with specific antigens and thioureas for treatment of melanotic melanomas. The required boron concentration is given by the relative dose due to neutron capture in 10B and that of the competing capture reactions in nitrogen and hydrogen. Capture in nitrogen produces protons with a range of about 10-11 microns and this gives a radiation dose to all cells in the neutron activated area. Calculations show that the local concentration of 10B near the critical radiation target, DNA, must be higher than 10 ppm (10 micrograms/g). Increased emphasis will be put on the development of combinations of treatments that fulfil the requirements for attacking the microscopic spread of the tumour.     

A multivariate study of protective effects of Zn and Cu against nephrotoxicity induced by cadmium metallothionein in rats.

Factorial experimental design was used to study the protective effects of Zn and Cu on cadmium-metallothionein(CdMT)-induced nephrotoxicity in male Wistar rats. In the factorial design two levels of Zn (0 and 25 mg/kg body weight), two levels of Cu (0 and 12.5 mg/kg), and two levels of CdMT (0.1 and 0.4 mg of Cd/kg) were used as varied factors. The factorial design was complemented with a center point with all three variables at an intermediate setting, i.e., Zn at 12.5 mg/kg, Cu at 6.25 mg/kg, and CdMT at 0.25 mg Cd/kg. Each of the nine combinations of settings was administered to one of nine groups with six rats in each. Zn and Cu were injected sc 24 hr prior to the injection of CdMT. The concentrations of protein and Ca in urine and Ca in renal cortex were used as effects. The relationship between the experimental design settings and the effects were modeled with multiple regression. The multiple regression analysis revealed that for the high dose of CdMT (i) the enhanced values of protein in urine caused by CdMT injection could be more efficiently reduced by Zn than by Cu, and (ii) excessive Ca in urine and renal cortex could be more efficiently reduced by Cu than by Zn. No significant synergism or antagonism between Cu and Zn was found. These models can be used to estimate the dose levels of Zn and Cu which will reduce the toxic effects of CdMT. The treatment of 20.4 mg/kg Zn, for example, will reduce the effects of 0.4 mg Cd/kg as CdMT on protein in urine, and 2.8 mg/kg Cu will reduce the Ca in urine to the levels of those caused by 0.25 mg Cd/kg (no Zn and Cu). Similarly, the effect of 0.4 mg Cd/kg on Ca level in renal cortex can be reduced to that of 0.28 mg Cd/kg as CdMT by 7.98 mg Cu/kg, which is three times as efficient as Zn. The obtained results might be of importance in understanding the mechanism of cadmium toxicity and the potential risk to the health of the population exposed to cadmium occupationally or environmentally.     

Affinity chromatographic identification and quantitation of blood group A-active oligosaccharides in human milk and feces of breast-fed infants

The finding of large quantities of blood group A-active oligosaccharides in the feces of a blood group A breast-fed infant motivated a search for the origin of these compounds. Using an affinity chromatographic technique, the nature of A-active oligosaccharides in human milk is demonstrated. The amounts of A-active tetrasaccharide (A-tetra) and the Lewis b-active lacto-N-difucohexaose I (LND-I) varied between 19-375 mg/L for A-tetra and 14-710 mg/L for LND-I. Using the same technique, the amounts of A-tetra and LND-I in milk samples from five women of different blood groups were compared with those in the feces of their breast-fed infants. The A-tetra was present only in feces from infants of blood group A or AB mothers and the amount per 24 h corresponded roughly to that in a I-L portion of milk. One of the milk samples was also analyzed for the presence of larger A-active oligosaccharides (A-pentasaccharide, A-hexasaccharide, and A-heptasaccharide). Their amounts were much less as compared to the amounts present in feces. These results indicate that milk is a possible source for the smallest A-tetrasaccharide found in the feces of breast-fed infants, while the larger A-active oligosaccharides might be the result of an intestinal metabolic modification.     

Prostaglandins and CGRP release from cardiac sensory nerves

Summary (1) The possible influence of Prostaglandins (PG) E₁ and I₂ as well as ischaemia, ouabain and bradykinin on the outflow of calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity (LI) from the guinea-pig heart was studied in vitro. (2) Exposure to PGE₁ (10^–5 M), but not PGI₂ (10^–5 M), induced an increased outflow, suggesting release of CGRP-LI. PGE₁ simultaneously increased the contractile force and heart rate while no effects were observed on perfusate volume or outflow of NPY-LI. PGI₂ had no effect on contractile parameters or coronary flow. In separate experiments on capsaicin-pretreated animals, the stimulatory effects of PGE₁ on heart rate and contractile force remained unchanged while no increased CGRP-LI outflow was detectable. (3) Ouabain, bradykinin and reperfusion after total stop-flow ischaemia was associated with an indomethacin-resistant increase in perfusate levels of CGRP-LI but not of NPY-LI. While ouabain markedly increased the contractile force, exposure to bradykinin or ischaemia did not induce any clear-cut changes in contractile force or heart rate. (4) Capsaicin-exposure evoked a markedly increased outflow of CGRP-LI but not of NPY-LI in combination with an increase in heart rate and a decrease in contractile force. Repeated administration of capsaicin induced tachyphylaxis. The stimulatory effects of capsaicin on CGRP-LI outflow and heart rate, but not the negative inotropic effect, did not occur in capsaicin-pretreated animals. (5) It is concluded that PGE₁, but not PGI₂, can activate cardiac capsaicin-sensitive fibres as revealed by increased outflow of CGRP-LI. The cardiostimulatory effects induced by PGE₁ are not related to CGRP release, however. A possible prostaglandin link in the CGRP-LI released by ouabain, bradykinin or ischaemia seems unlikely. Send offprint requests to: A. Franco-Cereceda at the above address     

Parastomal hernia in relation to site of the abdominal stoma

Parastomal hernia is a common late complication of enterostomy, especially colostomy, and sometimes requires surgical treatment. A possible contributory factor, location of the stoma in relation to the rectus abdominis muscle, was studied by examination of 130 patients with permanent intestinal stoma. The bowel had been brought out through the rectus abdominis muscle in 107 patients and lateral to it in 23 patients. The respective prevalence of parastomal hernia in these groups was 2.8 per cent and 21.6 per cent. The highly significant difference indicates that enterostomy should be constructed through the rectus abdominis muscle, not lateral to it.     

Human spumaretrovirus antibody reactivity in multiple sclerosis

The role of human spumaretrovirus (HSRV) infections in the pathogenesis of multiple sclerosis (MS) was investigated with recombinant HSRV env-specific enzyme-linked immunosorbent assay. The presence of HSRV antibodies was determined in pairs of serum and cerebrospinal fluid (CSF) samples from 60 MS patients. In 7 of these patients serial serum and CSF samples were obtained in relation to the clinical activity of the disease during a period of 2 years. No increased antibody reactivity was demonstrable in the MS population compared with 14 aseptic meningitis patients, 50 blood donors and 16 healthy controls. Slightly elevated levels of antibodies were demonstrable in serum and/or CSF in 4 MS patients but also in 1 patient with aseptic meningitis, 1 blood donor and 1 child. No marked serum or CSF HSRV antibody fluctuation was observed in the MS patients followed longitudinally. Thus, this study does not support the involvement of HSRV in the pathogenesis of MS.