Pathogenesis of blood-filled cavities in estrogen-induced anterior pituitary tumors in male Sprague-Dawley rats. The formation of blood-filled cavities in developing tumors of the anterior pituitary of estrogen-treated male Sprague-Dawley rats was studied in a serial sacrifice experiment. Two treated and 2 control rats were killed at each of 15 time points ranging from 7-272 days after sc implantation of an estradiol-17 beta pellet. The pituitaries were examined using light and electron microscopy. Changes at 7-9 days after implantation included epithelial cell swelling and trabecular arrangement. At 11-13 days, epithelial cells were further enlarged. Arrangement of epithelial cells in islands and endothelial degeneration were first seen at this interval. Also, any sinusoids were distended, whereas some were compressed by swollen epithelial cells. At 16-81 days, scattered necrotic and immature epithelial cells were present, and cell size decreased. Endothelial degeneration and both distended as well as compressed sinusoids were more prominent at this time. Loss of basement membrane was first seen during this interval. At 114-133 days, small hemorrhagic areas partially lined by epithelium were first seen; sinusoidal compression, endothelial necrosis, and loss of basement membrane were more frequent, but there was less sinusoidal distention. Between 150 and 272 days, epithelial cells were increasingly pleomorphic and arranged in nodules, and there was an increase in number and size of the hemorrhagic areas. Sinusoidal compression, endothelial necrosis, and loss of basement membrane were abundant, whereas sinusoidal distention had almost disappeared at this interval. Local compression of sinusoids and perhaps compression of pituitary surface veins due to epithelial cell swelling, were thought to play a primary role in the development of ischemic endothelial damage leading to loss of endothelial lining and basement membrane, and eventually to the formation of blood-filled spaces partially lined by epithelial cells.


Histopathological effects in Poecilia reticulata (guppy) exposed to methyl mercury chloride. To evaluate the usefulness of histopathology in aquatic toxicity testing, studies were carried out on the small freshwater fish Poecilia reticulata (guppy) following aqueous methyl mercury chloride exposure. Fish were exposed to concentrations of 0, 1.0, 1.8, 3.2, 5.6, or 10 micrograms/L for 1 and 3 months. Histopathological changes included the occurrence of multiple granulomas in various tissues, in particular, the integument and orbit. These changes were accompanied by hyperplasia of monocytopoietic interrenal tissue, and hepatocellular change which was confirmed by morphometry. The latter findings were probably a result of monocyte "consumption" by granulomas, and hepatic synthesis of ("stress") proteins, respectively. The bile duct and, focally, the proximal intestine, showed hyperplasia of the epithelium. In the testis of sexually mature fish (3-month study), degeneration and necrosis of sperm occurred, with severe cases exhibiting Sertoli cell hypertrophy, interstitial inflammation, and absence of mature sperm. Epidermal mucous cells disappeared in the highest concentration used, and, after 3 months, clusters of undifferentiated basophilic cells were seen in the gas gland, which occasionally were suggestive of malignant growth. The changes in the kidney tubules were characterized by degeneration and necrosis of single cells which also showed mitotic figures. This is considered a result of the mitosis-disturbing activity of methyl mercury (MeHg). It is concluded that MeHg has effects on various target organs in guppies with the occurrence of granulomas as the most sensitive indicator, yielding a no-observed-effect concentration (NOEC) of 1.0 micrograms/L. In contrast to mammalian species, no morphologic evidence for neurotoxicity was found.


Rat urinary bladder hyperplasia induced by oral administration of carbonic anhydrase inhibitors. The carbonic anhydrase inhibitors, acetazolamide and MK-0927, were given by oral route to male Sprague-Dawley rats at 200 mg/kg/day and 25 mg/kg/day, respectively, for up to 4 weeks. Sequential necropsies were performed and urinary bladders were examined by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Similar urinary bladder changes were seen with both compounds. SEM evidenced slight multifocal urothelial changes consisting of cell swelling, dissociation, degeneration, and exfoliation after 3 and 5 days of treatment. After 2 and 4 weeks of treatment, elevated or leafy microridges on the luminal cell surfaces were seen together with foci of swollen cells. After a 2-month-recovery-period, the urothelial surfaces were normal. LM and TEM showed multifocal vacuolation of the urothelium associated with inflammation of the underlying lamina propria after 3 and 5 days of treatment. Cellular hypertrophy and hyperplasia of the transitional epithelium was seen after a 5-day treatment, persisted without increasing severity after 2 and 4 weeks of treatment, and totally regressed after the recovery period. It was concluded that, in the rat urinary bladder, oral administration of acetazolamide and MK-0927 induced early degeneration and inflammation followed by epithelial regeneration, resulting in a reversible hyperplasia of the transitional epithelium.


Evidence that chemical carcinogens interfere with specific regeneration-controlling mechanisms of urodeles. The present investigation was conducted in an attempt to understand the interrelationships between carcinogenesis and regeneration. The aim was to find out whether chemical carcinogens constitute a class of agents specifically interfering with the normal developmental process during amphibian limb regeneration. To achieve this, the potent chemical carcinogens N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and N-nitrosodimethylamine (DMN) were inserted at a position slightly proximal to the blastema of regenerating Triturus cristatus forelimbs. The results indicate that, sometimes, the two developmental parameters, growth rate and morphogenesis, were differently affected depending on the treated limb and the carcinogen used. The effect of DMN on regenerative growth rate was negligible, but morphogenesis was highly impaired. Similarly, MNNG-treated stumps displayed abnormal regenerates in both forelimbs, whereas growth rates were significantly affected only in the right forelimbs. The findings are discussed in the framework of the relevant hypotheses.


Quantitation of metastatic tumor burden from human colon tumor xenografts using radiolabelled monoclonal antibody 17-A fragments. In realistic models of human tumor xenograft metastasis, the metastatic foci arise in perivascular sites and rarely grow to sizes which are easily quantifiable by visual inspection. As an alternative approach, we have used monoclonal antibody (MAb) 17-1A F(ab')2 fragments labelled with radioiodine (125I) to study the differential accumulation of label in xenografts and metastatic tumor sites as well as in noninvolved tissues of NIH Swiss nude mice receiving HT-29 human colon tumor cells. Images of the whole-body distribution and sites of localization were determined using a pinhole-collimated Angergamma camera. Radioactivity was determined in tissue samples using a well scintillation system, and pharmacokinetics were assessed during the initial 72 h after injection of antibody fragments. The half-life of 125I-F(ab')2 fragments in the blood, 8.6 h, was similar in nontumor-bearing control and tumor-bearing mice. The half-life in subcutaneous tumor xenografts was 30.1 h. The tumor xenograft to tissue activity ratios per unit weight (radiolocalization indices) at 72 h were: blood 90, lung 65, pancreas 50, muscle 35, spleen 20, liver and mesenteric lymph node 10. All subcutaneous xenografts were successfully imaged, and images of 5 of 9 mice (55%) appeared to demonstrate the presence of metastatic tumor by differential and focal accumulation of MAb fragments after 48 or 72 h in the lung (2 cases) or abdominal cavity (3 cases). Necropsy and subsequent histological and biodistribution studies confirmed the presence of metastatic tumor in these sites and identified tumor in several additional sites. The smallest volume of metastatic tissue in liver or lung determined at necropsy which appeared to have been detected by imaging was about 20 mm3. Generally, for mice with metastatic tumors, the radioactivity per unit weight of metastatic tumor-bearing organs compared to tumor-free organs was 2- to 7-fold greater. The results indicate that a radiolocalization index of > or = 2 is generally necessary for metastatic tumor detection by imaging although this is influenced by the extent of anatomical location of the tumor. It was possible to predict the tissue distribution of the fragments from the planar image for the amounts of radioactivity (approximately 1 mCi/kg body weight) employed in this study. These results demonstrate the utility of this approach to quantitate the metastatic burden arising from human colon tumor xenografts in this experimental model.


Serum markers for primary and recurrent breast cancer: BCM-EIA, CAM 26 and CAM 29. Three sandwich enzyme immunoassays were used to evaluate serum from 93 women: 20 normal, 20 with benign breast disease, 22 with primary and 31 with recurrent breast cancer. Using the three assays, breast cancer mucin enzyme immunoassay (BCM-EIA) carcinoma-associated mucin antigen (CAM) 26 and CAM 29, both singly and in combination, we were unable to establish meaningful cut-offs to differentiate between patients with or without breast cancer. The sensitivity and specificity for BCM-EIA were 90% and 40%, for CAM 26, 89% and 42%, and for CAM 29, 91% and 66%, respectively. Serial serum specimens from 29 patients with recurrent breast cancer were assayed. At recurrence, an increase of 25% or more in marker level over the previous value was found in 24/29 (83%) BCM results, 14/29 (48%) CAM 26 results and 12/29 (41%) CAM 29 results. Prior to clinical detection of recurrence, stepwise increases in BCM and CAM 26 marker levels were seen up to 299 days prior to clinical detection of recurrence. We conclude that these markers may help in the early detection of recurrent breast cancer.


Detection of xenogeneic anti-idiotypic antibodies specific to murine monoclonal antibody 17-1A in patients with gastrointestinal cancer. Murine monoclonal antibody (MoAb) 17-1A, which reacts with an adenocarcinoma-associated antigen, has recently been utilized in a phase I clinical trial for patients with gastrointestinal tract cancers in Japan. In order to analyze anti-idiotypic (Id) antibodies to murine MoAb 17-1A in the sera of these cancer patients, we established a simple and specific assay. In a modified sandwich assay, normal mouse sera were utilized for neutralization of rat antimouse immunoglobulin (Ig) antibodies and reduction of their nonspecific effects. When the modified sandwich assay was applied to the sera of patients who had been treated with MoAb 17-1A, anti-Id antibodies were induced in 53% of 13 cancer patients with gastrointestinal cancers at 3-4 weeks after infusion of MoAb.


Clones of a spontaneously metastatic human lung carcinoma cell line differ in their in vitro and in vivo phenotypic characteristics. In order to isolate subpopulations of cells with differing metastatic capacity, a spontaneously metastatic human lung carcinoma cell line was cloned in vitro, using limiting dilution methods. The karyotypic profile, in vitro and in vivo growth as subcutaneous xenotransplants in athymic mice of 11 randomly selected clones were very similar. No consistent differences were seen in the adhesion to a variety of substrates or in the integrin profile of the few subunits examined. However, the in vivo metastatic capacities differed. Most of the isolated cell lines, in spontaneous metastasis assays, formed variable numbers of microscopically visible metastatic foci in only the lungs and lymph nodes of these animals. One of the 11 cell lines examined, TV9, was observed to form grossly visible metastases in the lungs as well as in the ovaries, pancreas and omental lymph nodes. Immunoprecipitation analyses detected a decrease in the expression of the previously described low-metastasis-associated H7 molecule within the high metastatic TV9. The low and high metastatic subpopulations thus isolated will provide a means to dissect the metastatic mechanisms of this human lung carcinoma cell line.


[Definition of asymptomatic biliary lithiasis]. Asymptomatic biliary lithiasis can be defined as biliary lithiasis having determined no complication and no episode of biliary pain. Biliary pain is a consequence of acute increase of pressure inside the biliary tract. The increased pressure is induced by a stone transiently obstructing the cystic duct or the Oddi sphincter. In most patients, the site of the pain is epigastric. The level of the pain is high. The duration of the episode of biliary pain is usually less than 5 hours. Abdominal pain having other characteristics, dyspepsia, and headache are not related to biliary lithiasis.


[Natural history of asymptomatic lithiasis]. The natural history of asymptomatic gallstones, according to the best published studies, indicates that seventy per cent of the patients remain symptom-free. Nonetheless there are no clinical or morphological findings which can predict the occurrence of symptoms on a individual basis.


[Management of asymptomatic lithiasis].

[Management of asymptomatic lithiasis]. A careful analysis of the series of patients with asymptomatic gallstones suggests that prophylactic cholecystectomy is not necessary. The purpose of this work was to try to detect subgroups of asymptomatic patients with factors predictive of symptoms or of severe complications such as acute cholecystitis, pancreatitis, or gallbladder carcinoma. Among local factors, neither the size, number or nature of gallstones, nor alterations of the walls or contractility of the gallbladder were predictive of symptoms or complications. Among general factors, neither the age or sex of patients nor associated diseases such as diabetes mellitus or recent organ transplantation were predictive of symptoms or complications. Only the few patients with a porcelain gallbladder were at high risk for gallbladder carcinoma requiring prophylactic cholecystectomy. In all other patients treatment of asymptomatic gallbladder stones is unnecessary as well as any surveillance.


[Results of the treatment with biliary dissolvents]. Cholesterol gallstones can be dissolved by chenodeoxycholic acid or by ursodeoxycholic acid administered orally. This treatment is subject to the following conditions: the gallbladder must be functioning; the gallstones must be radiolucent; the stones must not be too large; the main bile ducts must be patent; the cholelithiasis must be symptomatic but without severe complications. The two biliary acids are equally effective, but ursodeoxycholic acid is preferred to chenodeoxycholic acid because it is devoid of undesirable side-effects. The effectiveness of treatment varies from one published series to the other, but it primarily depends on the size of the gallstones: if they are less than 5 mm wide dissolution can be obtained in 70 to 80% of the cases. After the end of treatment the bile becomes lithogenic again, and a relapse is possible; after 5 years this relapse occurs in about 50% of the patients. The position occupied by biliary acids in the treatment of gallstones is modest, owing to the conditions of their use and to the advantages of surgery, and notably laparoscopic surgery. Biliary acids are usually given to elderly people or to subjects at high risk for anaesthesia or surgery. Attempts have been made to introduce another cholesterol dissolvant, methyl-tert-butyl-ester, directly into the gallbladder by the transcutaneous-transhepatic route. The gallstones were dissolved, but the invasiveness of this technique and the potential toxic effects of this particular drug are such that the indications for this treatment are extremely reduced.


[Results of extracorporeal lithotripsy in the treatment of cholelithiasis]. Treatment of gallstones with extracorporeal lithotripsy includes the stones fragmentation with shock-waves and the dissolution of fragments with bile acids. It is a well-tolerated treatment than can be performed on an out-patient basis. However, lithotripsy is an effective treatment only in highly selected patients (low calculous volume, radiolucent stones, functioning gallbladder). A satisfactory clearance rate is observed only in patients with solitary stones < or = 20 mm in diameter (70-80% at one year). The stone recurrence rate seems to be low in patients who had solitary stones.


[Oral dissolvents and extracorporeal lithotripsy: respective role and modalities of application]. Oral dissolution therapy can be proposed to patients with symptomatic gallstones, with stones less than 15 mm diameter, in any number, without calcification, within a functioning gallbladder (i.e. opacified by oral cholecystography). In particular, it may be useful in patients aged over 70, or with a high operative risk, or who refuse surgery or general anesthesia. Extracorporeal shock wave lithotripsy (followed by oral dissolution therapy) is also indicated in symptomatic gallstones, without calcification or slightly calcified in a functioning gallbladder, when stone size is between 8-10 and 30 mm and stone number lower than 3. After successful dissolution, recurrence is observed with an incidence of 5 to 10% per year during the first five years. In case of symptomatic recurrence, retreatment is indicated.


[Contact litholysis and contact lithotripsy of symptomatic biliary calculi]. Contact litholysis and lithotripsy are invasive methods of gallstone destruction, since the gallbladder must necessarily be approached by the transhepatic or transperitoneal routes or through Oddi's sphincter. Both methods expose to complications which may require a corrective operation. The risk of recurrence is the same as with extracorporeal lithotripsy. Unless proved otherwise by further clinical trials, in the future these experimental methods should be used in a very small number of patients.


[Cholecystectomy through laparotomy].

[Cholecystectomy through laparotomy]. Laparotomy cholecystectomy is the "gold standard operation". Its mortality is almost nil. Its morbidity dramatically decreased while digestive surgery was improving. Alternative therapies are to be compared to it. Indications of laparotomy cholecystectomy remain frequent today but will decrease promptly due to the functional and cosmetic benefits of coelioscopic cholecystectomy.


[Celioscopic cholecystectomy].

[Celioscopic cholecystectomy]. Laparoscopic cholecystectomy was born in 1987 and is now commonly performed, usually under general anaesthesia, and under the same technical conditions as conventional surgery. The operative procedure varies with the operators, but it is mandatory to evaluate the state of the bile duct by pre- or peroperative explorations. Compared with conventional surgery, the advantages of laparoscopic cholecystectomy are well known: the entire peritoneal cavity is explored; the lack of postoperative ileus makes it possible to resume normal feeding, and hence normal activity, after a short interruption; systemic and parietal complications are less frequent, but the biliary tract complication rate is higher, probably in relation to the operator's training. The indications were initially restrictive but now embrace the quasi-totality of gallstones, complicated or not, and in particular when the patient's general condition is fragile.


[Incidents, accidents and limits of cholecystectomy by celioscopy]. Series of coelioscopic cholecystectomy until 1991 has shown that morbidity rate of this procedure remains higher than conventional laparotomy. Complication are related to technical problems included: (a) biliary leak with a rate of 0.5%; (b) hemorrhage; and (c) digestive perforation. Contra-indication of this procedure are: cirrhosis, portal hypertension, bilio-biliary fistula and severe cholecystitis. Progress is expected with willing to open cholecystectomy; improvement of intervention, perioperative cholangiography and specific train of surgeons involved in the field of surgery.


[Training for celioscopic surgery].

[Training for celioscopic surgery]. All surgeons specialized in the digestive tract will have to use the laparoscopic approach in an unlimited number of operations. This has already been established in biliary tract surgery. Practising surgeons must learn to perform laparoscopic cholecystectomy by themselves, i.e. in a manner that is neither organized nor officially approved in France. Students in surgery benefit, as with other techniques, from team training. These two categories of surgeons should be able to receive a specific teaching in order to maintain the safety of biliary tract surgery at its high level of safety. To make sure that this is done, keeping national registers is strongly advised.


[Indications for classical surgery and celiosurgery. Evaluation]. Laparoscopic cholecystectomy is a novel technique resulting from the advances achieved in video-endoscopy. In the field of uncomplicated gallstones it has in a few years thoroughly altered the surgical indications, taking preference over conventional surgery and ousting extracorporeal lithotripsy. However, the risk of complications must be kept in mind, and the utmost care must be taken in training operators and in recording all cases and their complications. Nowadays, conventional cholecystectomy remains indicated when laparoscopy is contra-indicated, notably in cases with tight peritoneal adhesions precluding laparoscopy.


[Medico-economic strategy for biliary lithiasis]. The purpose of this study was to assess the relevance of a medico-economic evaluation of gallstones. In other words, would it be possible to define economic criteria that would permit to select the best therapeutic method whilst respecting medical ethics? The frequency of gallstones, the high consumption of goods and medical services they require and the important loss of productivity that ensues justify this approach. The medical literature and a number of experts have made it possible to evaluate the advantages and drawbacks of each therapeutic method by defining its indications according to criteria of effectiveness such as duration of survival, quality of life of asymptomatic patients, gallbladder clearance, etc. We have tried to find out whether the introduction of medico-economic criteria in this pathology was likely to modify the various therapeutic methods available at present. We give here three examples. The first one is that of asymptomatic gallstones where the introduction of a cost/effectiveness ratio let to the conclusion that abstention is better than surgical treatment. The second example is a comparison of costs between cholecystectomy and medical treatment in high risk patients; the result was that surgery is preferable at the age of 50 years and medical treatment from 70 years onward. Finally, a comparison between surgery and lithotrity including the cost/effectiveness ratio concluded in favour of surgery. However, ethical, methodological and conceptual problems taking into account the value of human life, the difficulty to evaluate the quality of life and exterior incitations make it necessary to moderate the practical applications of these results.


[Anti-cytoplasmic antibodies of polynucle or "ANCA". A new class of autoantibodies]. The specific antigens to antineutrophil cytoplasmic antibodies (ANCA) and their relations with renal diseases begin to be well-known. In patients with systemic vasculitis, two major antigens have been recognized: proteinase 3 and myoloperoxydase. These enzymes are located in the azurophilic granules of neutrophils and migrate to the surface of these cells when they are activated. Other antigens, such as elastase, lactoferrin, CAP57 and cathepsin G, have been identified, but they are less commonly encountered. The presence of ANCA is particularly frequent in Wegener's granulomatosis, microscopic periarteritis, crescentic necrotizing glomerulonephrites without immunoglobulin deposits; it is less frequent in periarteritis nodosa and in Churg-Strauss' syndrome. ANCA can now be considered as markers of vasculitis; they are related to disease activity and can be used to evaluate the effectiveness of treatments.


[3 cases of polyarthritis treated with recombinant alfa interferon]. Bilateral symmetrical polyarthritis occurred in three patients (2 males and 1 female), with no previous history of inflammatory rheumatologic disease, given alpha-interferon for 1 1/2, 7, and 10 months as treatment of chronic non A-non B hepatitis, myelofibrosis, and thrombocytopenia with myeloproliferative disorder, respectively. Joint manifestations developed 1 1/2, 3, and 10 months after initiation of alpha-interferon in a dosage of 3.10(6) U three times a week, 4.5.10(6) U per day, and 8.10(6) U three times a week. Polyarthritis persisted following withdrawal of alpha-interferon in the two last patients of whom one had rheumatoid nodules and positive rheumatoid serology and the other had scleritis, exanthema, and negative rheumatoid serology. Erosive rheumatoid arthritis was diagnosed after 28 months and 12 months, respectively, in two patients who required systemic corticosteroids with antimalarials (1 case) or azathioprine after failure of methotrexate (one case). Follow-up in the third case (12 months) is too short to allow differentiation of systemic lupus erythematosus (ANA: 1/1500 H with anti-DNA antibodies 58 U/ml) and chronic autoimmune hepatitis. Reports of chronic inflammatory rheumatologic disease during alpha interferon therapy are exceedingly few in number. In the cases reported herein, alpha-interferon may have either triggered or revealed the joint disease. To prevent occurrence of this complication, exclusion from alpha-interferon therapy of patients with autoantibodies or a positive history for clinical evidence of immune dysfunction may be considered.


[Lumbar inter-apophyseal arthrosis and bone mineral content: prospective study versus controls with dual photonic absorptiometry and tomodensitometry]. Dual photon absorptiometry (DPA) is a non invasive and repeatable technique to measure vertebral bone mineral content (BMC). This method can be altered, in frontal incidence, by superposition of abnormal calcifications as calcified aorta or interapophyseal arthrosis. The authors studied nineteen females with lumbar apophyseal arthrosis compared with twenty one controls matched by age. Bone densitometry was performed by Am-Ba DPA and monoenergetic computerised tomodensitometry (CT) from L2 to L4. Arthrosis was studied by standard X ray radiographs and CT. Our results showed that inter-apophyseal arthrosis does increase BMC determined by DPA, especially when expressed as linear BMC (g/cm). The body mass index [weight (kg)/size (m2)] also increased these measures by DPA. CT results were, at the opposite, not influenced by osteo-arthrosis nor body mass index. Detailed analysis of DPA pictures allowed to recognize most of patients with osteo-arthrosis and to correct their results by using adjacent vertebral measures (L1) or abandoning pictures of unusual aspect. The authors mentionned necessity to match populations for age and body mass index and to include L1 in routine vertebral bone mineral content determination. By this way they supposed that osteo-arthrosis may not alter lumbar BMC measured with DPA technique.


[Aspects and role of spinal MRI in the assessment of solitary plasmacytoma and multiple myeloma. Apropos of 11 cases]. Spinal MRI was performed in 9 multiple myeloma and 2 solitary plasmacytoma, using sagittal, T 1-weighted (TR: 350-550 ms/TE: 15-26 ms) and T 2-weighted (TR: 2,000-2,500 ms/TE: 60-120 ms) sequences, with additional gadolinium injection in 3 cases. MRI features were the following: 1) round, patchy lesions with low T 1 signal highlighted by gadolinium and bright T 2 signal were present in 10 of the 11 patients: all osteolytic lesions seen on plain X-rays corresponded to such lesions and biopsy performed in 4 cases showed massive marrow replacement by plasma cells. 2) overall marrow signal was dramatically decreased in 3 patients (2 of whom had a high tumoral mass). 3) extra-dural compression was present in 4 cases. 4) 25 vertebral compression fractures (10 of whom with a "benign" appearance) and focal fat deposition were seen. 5) postradiation treatment examination seemed predictive of the outcome in the 2 solitary plasmacytomas. MRI proved to be more sensitive than plain X-rays or bone scintigraphy. Number and size of focal tumor-like lesions did not correlate with the low marrow signal appearance. Both correlated poorly with overall tumoral mass but diffuse abnormalities were associated with rapidly fatal outcome in three cases. These features might reflect qualitative rather than quantitative patterns of the disease (nodular or diffuse macroscopic marrow replacement). These findings are in agreement with those of the few previous studies. MRI is valuable for spinal cord damage assessment. It appears less accurate in benign versus malignant vertebral compression fracture determination than it does in bone metastasis. Its prognostic value is still questionable.


[Significance of inflammatory syndrome in the diagnosis of Horton's disease. Attempt at the application of Bayesian analysis]. This study was designed to investigate the value of biologic evidence of inflammation for the diagnosis of giant cell arteritis. Experienced physicians were asked to evaluate five pairs of medical records based on real cases. In each pair, one case lacked biologic evidence of inflammation. This study offered the opportunity to explore the feasibility of a simplified Bayes model. A blind evaluation obtained by showing the paired case-reports with similar evidence of inflammation in both cases of each pair to 14 specialty physicians yielded a likelihood of diagnosis of +/- 20%. Analysis of the 46 responses to the study demonstrated, despite wide variations, a significantly greater likelihood of diagnosis in the cases with evidence of inflammation. Nevertheless, 17% to 36% of physicians--according to the case-report--ascribed virtually no importance to the ESR. Most of the physicians considered temporal artery biopsy was warranted when the likelihood of diagnosis was greater than 25%. Emergency corticosteroid therapy while awaiting the histologic results was approved by most responders when the likelihood of diagnosis was greater than 65%. The "pre-test" likelihood, calculated assuming that sensitivity and specificity of the ESR are 0.99 and 0.50, respectively, ranged from 0.89 to 0.98 for the case-reports with no evidence of inflammation and from 0.16 to 0.59 for the case-reports with evidence of inflammation In theory, the figures for the two types of case-report should not differ by more than 20%. Use of a low value for specificity (0.05) would improve the fit of values in cases without evidence of inflammation but would increase discrepancies in the other cases.(ABSTRACT TRUNCATED AT 250 WORDS)


[Real effects of sport on the bone mass in women]. What is the role of physical training in the prevention of osteoporosis? The authors tried to answer the question, comparing the positive and negative effects of exercise on women bone mass before and after the menopause and proposed a way of management of bone loss in amenorrheic women athletes.


[Dermatopolymyositis induced by D-penicillamine in rheumatoid polyarthritis. Apropos of 1 case with review of the literature]. Treatment of rheumatoid arthritis (RA) with D-penicillamine (DP) is associated with development of dermatopolymyositis (DPM) in 0.2 to 1.2% of cases. A case of DPM which developed after four years DP therapy in a 58-year-old female with RA is reported. The favorable outcome after discontinuation of DP and administration of corticosteroids and the absence of recurrence or malignant disease after 4 years 9 months follow-up demonstrated the causal relationship between DP therapy and development of DPM. An analysis of 34 previously published cases of DP-induced DPM (DP/DPM) showed the following: development of DPM was not influenced by the dosage or duration of DP therapy; reported cases of DP/DPM were clinically identical with primary DPM but had a different outcome, with permanent recovery of DP/DPM occurring 1.5 to 6 months after withdrawal of DP; patients with DP/DPM had immune disorders, including antinuclear antibodies in 14 of 34 patients; the high prevalence of the B18, B35, DR4 haplotype in these patients denotes immunogenetic differences with primary DPM patients (B8-DR3) and DP-induced myasthenia (DR1).


[Lumbosacral pain revealing intramural rectal abscess. Apropos of 2 cases]. Intramural abscess of the rectum is an uncommon (7%) form of perianal abscess in which the suppuration moves upwards within the rectal wall. Diagnosis is usually readily established on the presence of prominent anorectal symptoms and on rectal examination findings. However, atypical cases occur occasionally. Two cases of intramural abscess with misleading presenting symptoms suggestive of rheumatologic disease are reported herein. Both patients had subacute lumbosacral pain suggestive of an inflammatory condition. In one patient, the correct diagnosis was established two years after onset of symptoms when the patient passed pus per rectum. In the other, endoscopic ultrasonography readily evidenced the abscess. Modern imaging techniques including endorectal ultrasonography, CT scan with enhancement and MRI are very helpful for the diagnosis of such difficult cases. Intramural rectal abscess should be added to the list of possible nonspinal visceral etiologies routinely looked for during the evaluation of patients with atypical lumbosacral pain.


[Tibial hyperostosis and Propionibacterium acnes]. In a 39-year-old patient with tibial productive osteitis, Propionibacterium acnes was identified in a surgical specimen of the bone lesion. Similar cases have been reported by others. The possibility that P. acnes may play in a pathogenic role in the SAPHO syndrome by causing inflammatory or infectious changes is discussed.


[Brucella osteomyelitis of the upper end of the humerus: contribution of magnetic resonance imaging]. The authors report a case of brucella osteomyelitis of the upper end of the humerus in a 77-year-old patient, presenting as a large swelling of the soft tissues of the shoulder, present for a year. The diagnosis was made by isolation of the organism and specific serology. The authors stress the value of magnetic resonance imaging, which provided confirmation of the diagnosis of osteomyelitis as well as an accurate topographic assessment.


[Inflammatory myalgic syndrome and muscular mitochondrial abnormalities: 4 cases]. Histologic and biochemical anomalies of muscle mitochondria were identified in four patients with predominantly rhizomelic myalgia clinically suggestive of an inflammatory disease but inconsistent biologic evidence of inflammation. This clinical pattern was initially suggestive of atypical polymyalgia rheumatica and could not be ascribed to any other disease. To explain this combination of anomalies, several hypotheses can be put forward, including coincidence, aging, and nonspecific mitochondrial anomalies resulting from immunologic or inflammatory disease. The speculation that these patients have an autonomous syndrome cannot be outruled but should be considered with caution. A therapeutic trial with coenzyme Q is under way.


[Infectious spondylodiscitis. Analysis of a series of 105 cases]. Among 105 cases of infectious spondylitis diagnosed and treated from 1971 through 1990, 23 were due to tuberculosis (TS) and 82 to other causes (NTS). The annual number of cases of NTS rose over the study period, partly because of an increase in iatrogenic spondylitis, whereas the number of TS cases fell. In both groups, mean age of patients was higher than in earlier studies. The leading causative agents in NTS were staphylococci, followed by streptococci, then Escherichia coli. Diagnosis of spondylitis was dependent on the imaging techniques used; among available methods, the most reliable was magnetic resonance imaging which improved diagnostic performance by detecting early, specific changes. Except in patients with positive blood cultures and in TS patients with Koch bacilli recovered from other visceral foci, bacteriologic diagnosis rested on studies of samples taken from the spinal infection site. Half the subjects underwent discovertebral needle biopsy, with a success rate of 47.5%, a figure comparable with those reported in other studies. In 30% of patients, bacteriologic documentation of the infection was not obtained and diagnosis rested on a set of clinical, biological, and radiological criteria.


[Rheumatoid metatarsals, original development of the first metatarsals]. Weight-bearing roentgenograms of 308 feet of rheumatoid arthritis patients were analyzed. Several angles were determined, including the metatarsus primus adductus angle (between the first and second metatarsals, > or = 10 degrees) and the forefoot spread angle (between the first and fifth metatarsals, > or = 30 degrees). Pes planus was diagnosed when the internal arch angle was equal to or greater than 130 degrees. Tarsal arthritis was defined as the presence of joint space narrowing. Varus of the first metatarsal was correlated with tarsal arthritis and pes planus but not with duration of the disease. Forefoot spread was correlated with duration of the disease and erosive metatarsal disease but not with involvement of the midfoot. These data demonstrate that orthopedic treatment should be initiated as soon as involvement of the first metatarsal is detected and should be directed at the hindfoot, midfoot, and first metatarsal whose deformations occur concomitantly.


[Value and limits of tomodensitometry applied to the diagnosis of sacroiliitis in young adults: study of 200 cases]. Diagnosis of sacroiliitis may be difficult to establish in patients under 25 years of age since growth is not yet completed and joint damage is often still minor. A prospective study of 200 subjects with a median age of 22 years was carried out to compare the value of CT scan and conventional radiology. The study population included 32 healthy subjects and 168 consecutive patients with presumptive spondylarthropathy including 36 with bilateral sacroiliitis and 8 with unilateral sacroiliitis. Conventional roentgenograms and CT scans were performed in every patient. Blind reading of roentgenograms and CT scans was carried out by two pairs of observers with differing experience. CT scan provided no additional information when reading was done by experienced observers: rates of mistaken and doubtful results were similar with both investigations (10%); specificity of both tests was comparable (90%) but sensitivity was significantly greater for CT scan (91.2%) than for conventional roentgenograms (71.6%), reflecting improved detection of roentgenographically occult sacroiliitis. Less experienced observers obtained better results with CT scans, illustrating the ease of interpretation of CT scan images. Analysis of false-positive CT scans revealed that normal variations and, above all, features due to as yet uncompleted growth were the main sources of mistakes. These mistakes cancelled the advantage of increased sensitivity of CT scan studies and explained why CT scan failed to improve diagnosis.


[Total prosthesis on a rheumatoid knee]. Results of 81 total knee replacements in 67 patients with rheumatoid arthritis were studied. Mean follow-up was three years. Pain was the main reason for knee replacement surgery; knee mobility was well preserved prior to surgery. Failure occurred in four patients, as the result of infection, due in three instances to skin necrosis. Arthrodesis of the knee proved necessary in these patients. The fourth patient developed delayed hematogenous infection which was treated by a change of prosthesis. At follow-up, 82% of patients reported no pain and 18% moderate pain. Mean passive flexion was 113 degrees +/- 17 degrees. HSS score was 83.6 +/- 1.3 and all the patients except for the four with prosthesis failure stated that they were satisfied on very satisfied. Mechanical results were satisfactory, with a mean mechanical femur-tibial angle of 180.4 degrees. A circling line was visible at follow-up in 40% of operated knees but was partial in every case. No reoperations for prosthesis loosening were required. These data show that total knee replacement is the only reliable and radical treatment of rheumatoid arthritis of the knee and should be performed as soon as fixed flessum or axial deviation develops.


[Rheumatic manifestations associated with human immunodeficiency virus infection (HIV)]. The number of subjects presenting articular manifestations associated with HIV-infection is constantly on increase due to the growing number of seropositive patients. The pathophysiological mechanism of this association is still unknown. A recent review of the literature has shown that spondyloarthritis are the most frequently observed articular manifestations in HIV-positive patients. Septic arthritis are rare but severe. The immunodepression due to HIV-infection makes it difficult to use immunosuppressors and renders local therapeutics preferable. The articular manifestations may allow to discover seropositivity that has not been diagnosed before. These data strongly suggest to include serological examination for HIV in the etiological screening for every articular manifestation of unknown origin, even if the patient presents no risk factors.


[Lupus chorea revealing. Study in magnetic resonance imaging. Success of plasma exchanges after resistance to pulsed cortisone]. Chorea as a manifestation of SLE is infrequent (1% of all cases of SLE). A new case is reported herein. The patient, a seventeen-year-old female, was admitted with a one-week history of choreic movements of the left half of the body and arthritis of both wrists. Biologic findings confirmed the diagnosis of SLE with presence of an antiprothrombinase circulating anticoagulant. Findings upon cerebral CT scan and magnetic resonance imaging were normal. Clinical symptoms worsened despite corticosteroids in a daily dosage of 1 mg/kg with three pulses of 800 mg methylprednisolone. High-dose neuroleptic therapy was given and three plasma exchanges were performed. A dramatic improvement in clinical symptoms and biological anomalies occurred and persisted during follow-up which now exceeds one year. The lack of MRI anomalies suggests that the pathogenesis of SLE-associated chorea involves functional neurone activation by immune complexes; the dramatic effectiveness of plasma exchanges may obviate the need for using immunosuppressant agents in patients who fail to respond to corticosteroids.


[A case of benign chondroblastoma of the iliac wing treated by extensive exeresis and reconstruction with methylmethacrylate]. Complete remission can be achieved by extensive surgical exeresis in patients with benign chondroblastoma of the iliac wing despite the reputation of these tumors for aggressive behavior. The case of a 28-year-old male treated with extensive surgery and acrylic cement reconstruction is reported. After seven years follow-up, the functional result is satisfactory and there is no evidence of local recurrence. Use of cement obviated the need for bone grafting. However, subsequent removal of the cement proved necessary because of skin intolerance. Data from a review of the literature confirmed that iliac chondroblastoma carries a poor prognosis, mainly because of the potential for mechanical complications. The cases of malignant transformation reported occurred after radiotherapy. In the authors' opinion, extensive surgical exeresis performed as early as possible is the treatment of choice.


[Peripheral erosive arthritis in pustulosis palmoplantaris. Apropos of 3 cases]. Three cases of pustulosis palmoplantaris with erosive arthritis are reported. There were two females (aged 53 and 59 years) and one male (aged 39 years). Skin lesions preceded joint lesions in every case (by 2 years, several weeks, and 1 year, respectively). Joints involved were one wrist in two patients and both hips in one patient. Inflammatory joint pain occurred concomitantly with an exacerbation of the skin disease. In two cases, an upper respiratory tract infection preceded the joint manifestations by a few days. Synovial fluid from affected joints was obtained in all three cases and found to be sterile. In the two patients who had histologic studies of skin lesion biopsy specimens, unilocular non-spongiform lesions suggestive of nonpsoriasic disease were found. Erythrocyte sedimentation rate and C-reactive protein levels were raised in every case. HLA groups were [A2, A19, B12, B27], [A2, A9, B12, B19, B27, Dr4, Dr6], and [A2, A19, B12, B13, Dr7, Dr8]. All three patients were given a nonsteroidal antiinflammatory agent. Despite this therapy, destruction of the wrist occurred in both females and bilateral hip destruction required bilateral total hip replacement in the male. The rapidity with which joint destruction occurred suggested infectious disease, especially due to a saprophytic organism. Virtually all previously reported pustulosis palmoplantaris patients with bone and joint manifestations had arthralgia or non-destructive arthritis in appendicular joints, whereas bone and joint destruction has been described in axial structures.


[Condensing myeloma. Apropos of 2 cases with bone histomorphometric study]. Two cases of myeloma with roentgenographic evidence of bone sclerosis confirmed by iliac histomorphometric measurements are reported. In one patient, increased resorption, major depression of osteoblast activity, initial intense myelofibrosis, and myeloid deposits were found. The other patient had both increased resorption and increased osteoblast activity with clinical manifestations suggestive of POEMS syndrome. These two cases are compared with 116 cases previously published in the occidental medical literature and with five histomorphometric studies demonstrating increased bone trabecula volume (BTV). Conventional histologic studies suggest several mechanisms as possible explanations for the occurrence of bone sclerosis, including increased modeling unit activity, isolated osteoblast activation, metamorphic neoosteogenesis in myelofibrosis foci, and, in exceptional cases, inhibition of resorption due to increased production of calcitonin. The diversity of bone modeling patterns evidenced by the seven histomorphometric studies reviewed in this article is striking. Bone modeling patterns provide only a snapshot of bone modeling units and may vary over time in a given patient. Reported cases are too few to allow conclusions but emphasize the need for performing further histomorphometric investigations.


[Otologic manifestations of the pain dysfunction syndrome of the stomatognathic system]. Phylogenesis, ontogenesis and anatomy explain the close relationship between temporo-mandibular joint and the middle ear and can therefore help understanding otologic symptoms such as: otalgia which often correspond to articular and muscular pain irradiation (coming from sterno-cleido-mastoid, lateral and medial pterygoid, deep layer of the masseter and temporal muscles); acouphens and ear block sensation that could be caused by a spasm extension of the manducatory (i.e. medial pterygoid) to levator and tympani tensors. These three muscles, which originate from the first branchial arch, have a proprioceptive sensitivity and share the same innervation. What is more tensor and levator veli exchange certain muscular fibers. Tensor tympani spasm can be held responsible both for a decrease or abolition of the Klockhoff's reflex, together with a decrease of the stapedian reflex, the latter due to tympani rigidity induced by a spasm of the tensor tympani.


[Occurrence of post-traumatic temporo-mandibular ankylosis. Trial of classification of anatomo-pathologic lesions]. According to the authors, who have an 18-year experience, the treatment of temporomandibular ankylosis in children consists in the resection of the ankylosis block and of the corresponding neck of the condyle, along with the preservation of the capsule and articular disk and a dynamic blockade with the mouth open until the mandibular condyle is completely reconstructed. After witnessing the constitution of ankylosis in a child who was initially examined 3 weeks after the trauma, we were able to carry out a thorough clinicopathological examination of the areas of tissue characterizing incipient ankylosis, both in the condylar cartilage and in the underlying bone. The initial stage produces the progressive emergence of the bony surfaces, which then bear no cartilage. This is osteogenesis as well as cartilage resorption, as evidenced by the presence of neoformed Haversian canals at that level. This is a formal argument in favor of a systematic dynamic blockade with the mouth open in all cases of fresh condylar surface and the menisceal surface of the joint is the best way to prevent ankylosis or malunion.


[The discal system of the temporo-mandibular junction]. The discal apparatus represent the intra-articular part of the lateral pterygoid muscle tendon, which is differentiated in front of articular surfaces. It is involved in craniomandibular shock absorbing, joint proprioception, and also plays an important part in both condylar growth and morphogenesis. This is to emphasize the different roles of this apparatus, which should be religiously preserved, its lesions being, most of the time, irreversible and cause of TMJ disorders.


[Muscular insertions on the temporo-mandibular disk. Physiologic implications]. The aim of this work was to identify the elements of an anatomical consensus about the description of the direct and indirect muscular insertions on the temporomandibular meniscus. A classical dissection was performed on two joints and completed with a histological study. Fourteen joints were studied, after deep-freezing of fresh whole heads, with 3-millimeter thick macroscopic sections in the coronal, sagittal and axial planes and in a plane perpendicular to the axis of the condyle. The study of the specimens with a binocular magnifying glass was completed by oriented histological sections after fixation in 10% formaldehyde. The comparison of our findings with the studies published in the literature shows that the ideas are evolving towards an anatomical consensus about the reality of the direct and indirect insertion of the sole mandibular elevator muscles on the temporomandibular articular disk. The classical description of the dynamics of the meniscus must therefore be changed.


[Complications of temporo-mandibular arthroscopy. Report of 100 arthroscopies]. TMJ arthroscopy is a little invasive and of poor morbidity procedure of both investigation and treatment of temporomandibular pathology. A highly equipped operating room (double instrumentation) together with fine skill and proper knowledge of arthroscopic joint anatomy can easily prevent the rare complications described (articular, vascular, neurologic and otologic).


[Reconstruction of the mouth floor with nasolabial flap after cancer resection. Report of 81 cases]. The authors report functional results in a series of 81 patients with carcinoma of the floor of the mouth treated by surgical resection and reconstruction by nasolabial flap. The study confirms the literature concerning advantages and limits of such a flap. With regards to others techniques of reconstruction, nasolabial flap is still perfectly usefull in reconstruction of T2 T3 carcinomas of the floor of the mouth.


[Dentascan in dental implantation].

[Dentascan in dental implantation]. The software called dentascan utilizes the data acquired during a conventional CT examination to reconstruct accurate images with a 1/1 scale, both of sections taken at right angles to the axis of curvature of the bony relief of the maxillary or mandibular arch and of sections taken parallel to this axis. This means of investigation proves to be practical and useful for assessment before implantation.


[Skin aplasia of the vertex. Report of a familial form]. The authors report about a familial case of skin aplasia of the vertex cranii, of which they present a form that required emergent surgical repair with a favorable outcome. The investigation allowed tracing two relatives with minor forms expressed as alopecia of the vertex. Skin aplasia of the vertex cranii is an exceptional condition, which consists in the congenital absence of cutaneous, bony and/or dural tissue in the cranium. The various etiopathogenetic, clinical, diagnostic, evolutive and therapeutic aspects are reviewed.


[Our experience with surgical treatment of posterior epistaxis. Report of 16 cases]. Management of intractable posterior epistaxis remains a challenge to the otolaryngologist. When anterior and posterior packing techniques fail to control the hemorrhage, a surgical technique designed to interrupt the blood supply to the posterior parts of the nose is indicated. The common procedures employ ligation of the external carotid artery, of the maxillary artery and its terminal branch the sphenopalatine artery. Those procedures performed on 16 patients are clearly described and the indications for each one are established. Immediate control of bleeding was accomplished in 14 of 16 patients. Two patients had postoperatively recurrent but less severe epistaxis.


[Microscopic innervation and vascularization of the tongue. General study]. Our study deals with 23 prenatal human tongues, and a comparative study was carried out on one neonatal tongue and a few human and animal postnatal tongues. Sagittal and coronal sections were stained with various techniques. After the 7th week, the development of the nerves and their relationships with the neighboring structures can be observed. There are very few capillaries making up the superficial vascular network under the epithelium. The vessels whose walls are beginning to develop include the future red blood cells with their basophilic nuclei. During the whole process of evolution, there is a tight correlation between the collagen fibers and the neighboring structures. The innervation and vascularization--the latter with changes in the vascular walls--progressively increase. A short time before birth, the nerve fibers include their characteristic components, except for the Schmidt-Lantermann fissures. A considerable innervation advances towards the papillae, and anterior and posterior nerve networks enter the papillae, whose connective tissue includes groups of corpuscles on serial sections.


[Decision strategy in orthognathic surgery. Part 2: The esthetic choice in orthognathic surgery--practical applications]. Even if the functional factors are the most important in the decision, we have always to remember the need of our patient concerning aesthetic improvement. At this moment, the traditional approach based upon morphologic cephalometric analysis (which are frequently discordant) must be substituted by an aesthetic approach. The goal is to obtain a realistic 3D-imaging of the face as it will be after surgery. But it cannot really be achieved yet and we are obliged to work on lateral X-ray cephalograms. The most important at this stage of the decision is not to make a static aesthetic evaluation. It is on the contrary to perform a prospective simulation of the new profile line, as accurate as possible, based upon statistical correlations between soft- and hard-tissues changes. Even if there are some technical problems, even if the results are not currently good enough, the aesthetic prospective analysis allows validation or modulation of the initial functional surgical indication. We can compare for instance the aesthetic results of different amounts of displacements in bimaxillary surgery. Meanwhile, it is sure that the result depends also on the precision of the surgical procedure and on the good functional re-equilibration which is essential for the stability.


[Post-traumatic enophthalmos. Pathogenic, diagnostic and therapeutic approaches]. Post-traumatic enophthalmos has a complex pathogenesis, resulting from injuries to the bony walls of the orbit or to the intraorbital contents. Computed tomography allows specifying this pathogenesis by locating displaced bone, fat leakage or muscle incarceration, as well as calculating the volumes of the orbit and of the soft tissues. This assessment guides surgery (most often bone grafts), but correction remains limited by scar retraction, especially around the orbit. The prognosis of enophthalmos mainly depends on a general initial treatment after the trauma.


[Enophthalmos of the enucleated eye].

[Enophthalmos of the enucleated eye]. Even when it is corrected by an ocular prosthesis, enucleation often causes enophthalmos. After studying the integrality of the walls of the orbits with CT, the presence and position of the intraorbital implant must be controlled and the enophthalmos treated by compensating for the residual volume loss of the orbital content (bone or biomaterials) and, sometimes, filling up the upper palpebral space (dermal graft, galea flaps or biomaterials). The retraction of palpebral scars limits the possibilities of correction.


[Cutaneous melanoma of the cervicofacial region. Personal experiences]. The malignant melanomas are expansive tumors of neoplastic melanocytes. In the present study, five cases of patients are reported which have been hospitalized in E.N.T. department of our hospital during the last four years with skin melanomas of the head and neck. We note our opinions on diagnosis and treatment of these malignant tumors.


[Inverted papilloma of the nose. Apropos of a case associating polyps and an inverted papilloma of the nose]. In this article is presented a case report of a 59 years old woman with a medical history of recurrent nasal polyps (from 20 years ago). This woman presented an inverted papilloma in the middle meatus of the lateral wall of the nasal cavity simultaneously with the nasal polyps, and she was faced with surgical intranasal removal. The patient, two years later, presented again nasal polyps, but without any indication of the recurrence of the inverted papilloma. It is noticed the value of the local surgical removal of the inverted papilloma in patients who do not present extensive tumors.


[Orofacial dyskinesia. A current pathology]. Bucco-facial dyskinesia is particularly frequent in aged persons, for whom the condition is a definite handicap because of its social and, sometimes, functional impact. The etiology of these abnormal movements is variable. On one hand, many treatments can be incriminated, especially neuroleptics, and on the other hand, there also are frequent spontaneous dyskinesias, movements for which the risk factors are described. The physiopathology remains open to discussion and research, but we already know that the regulation of the nigro-striated pathway plays a role in it, as well, maybe, as toxic (free radicals) and immunological factors. Various therapies are described, but the outcome for such dyskinesias is often unfavorable, at least in elderly subjects, hence the merits of prevention. The latter is based on the prescription of as few neuroleptic drugs as possible, on the use of possibly protective substances, and finally on the suppression on the triggering elements that some local factors may form.


Inadvertent intracranial placement of a Foley catheter. A rare iatrogenic complication of severe frontomaxillary trauma. Severe comminuted fractures of the facial bones involving the cranial base are often accompanied by heavy bleeding into the nasopharynx. This presents considerable problems in primary care both for the anesthesiologist and the surgeon. Such bleeding can be controlled by Bellocq tamponade or using a Foley inflatable catheter. Skull base fractures may involve the risk of the catheter inadvertently penetrating into the brain. The authors describe a case in which a misguided Foley catheter, which was blindly inserted through the nose in an attempt to tampon the nasopharynx, resulted in fatal cerebral damage.


[Biopsy of the salivary glands. The importance and technic of biopsy of the sublingual gland on its anterio-lateral side]. A new method of taking a sublingual gland sample is suggested by the authors in the fore pole. They emphasize on this straightforward operating act and on the amount of tissue removed. The aim of the removal could be etiologic within the framework of the Gougerot-Sjögren's syndrome, diagnostic in the sarcoidosis and rheumatoid arthritis, prognostic in the graft versus host disease.


[Adenomatoid odontogenic tumor].

[Adenomatoid odontogenic tumor]. Adenomatoid odontogenic tumor is observed most frequently in male patients aged between 10 and 20 years. Occurring usually in the anterior part of the upper jaw, its discovery is often fortuitous during routine radiological examinations, which show a well defined clear zone 1 to 3 cm in diameter. Treatment by curettage results in healing by secondary bone cicatrization. A case is reported and epidemiological, clinical, diagnostic, therapeutic and prognostic features reviewed.


[The use of cryotherapy in oral pathology. Our experience in 36 cases]. Cryotherapy is a simple to use, weakly invasive technique provoking only moderate complications in the treatment of certain mucosal lesions of the buccal cavity. Indications of choice for this type of treatment are angioma and papilloma. Long term follow up of patients treated for reactive keratosis or epithelioma in situ is at present insufficient to establish precise indications.


[The brevity of the acquisition period of phonemes. Arguments for the early treatment of maxillo-palatal clefts]. Very early, the new-born no more listen the phonemes which are not used around him. In the same way, he does not listen the phonemes impossible to pronounce by himself, because he is not concerned. He does not engrave then. Consequently, we must give him, quickly, complete anatomical means of pronunciation, and train him by early intensive imitation-interchange mechanism. For those two reasons, we propose to complete immediately the early surgical reparation of the soft palate by a thin obturating plate and by an early orthophonic parental guidance.


Upper gastrointestinal bleeding as a complication in end stage renal disease patients. The commonest pathological findings in the upper gastrointestinal tract have been verified by studying 320 autopsies as related to chronic renal failure through the 20-year span. In our series of 99 patients having been hospitalized within the period of 1989 to 1990, lesions of upper gastrointestinal tract were summarized that might be responsible for bleeding in the course of the dialysis and after renal transplantation. In accordance with literature sources, the investigated group showed gastric and duodenal mucosal lesions to be the most frequent sources of hemorrhages. For both the early diagnosis and therapy all patients have to be examined prior to the initiation of a regular maintenance dialysis. Gastroscopy is also indicated in all patients without any exception. Subsequent conservative treatment should be performed in an intensive and accurate way. While unsuccessful, the surgery is indicated. Authors referred to indicatory criteria based on surgical management of gastroduodenal ulcer. Both the early diagnosis and indication to surgery were stated to be of crucial importance for patient's destiny when the conservative treatment has failed. The present study should contribute to a closer collaboration of nephrologists, gastroenterologists and surgeons in order to prevent such serious complications that are represented by gastrointestinal bleeding in patients with chronic renal failure.


The changing pattern in peptic ulcer surgery. The authors analyse the methods of treatment for the peptic ulcer disease (PUD) in two 5-year periods (group A 1979-1983, group B 1985-1989). From these groups patients with perforated gastroduodenal ulcer were excluded. In the first period 206 operations were carried out using nearly exclusively classical partial gastrectomies of both types (94 per cent). The second period involves 94 operations, where the most frequent type of operations was the proximal gastric vagotomy (40.4 per cent), and vagotomy with anthrectomy in the Roux-en-Y modification (26.6 per cent). The number of operations for a complicated PUD has increased from 43.2 per cent to 53.2 per cent, the ratio between the duodenal and gastric ulcer has changed from 3:1 to 2:1. The mortality was 5.3 and 4.7 per cent respectively, the morbidity 14.5 and 13.8 per cent respectively. The authors confirmed their accordance with the world-wide trend of diminution of the proportion of surgically treated PUD and a shift in the pattern of surgical methods towards the non-resective and more physiological procedures.


Surgical treatment of cardiospasm and megaoesophagus. Long-term results of operative treatment of cardiospasm and megaoesophagus in 111 patients are presented. There were 67 women and 44 men treated, age 4 to 65. The authors have for several years used their own, in this Department developed method of operation for cardiospasm, which joins Heller's operation with the reconstruction of the cardia to prevent reflux. In very advanced stages of the disease as megaoesophagus they use an original surgical procedure, which consists in connecting the thoracic segment of the oesophagus with the prepyloric part of the stomach by means of a pedicle jejunal graft. Clinical follow-up supported by x-ray examination and endoscopy has shown very good results of such treatment.


Complicated duodenal ulcer, vagotomy or distal resection--own experience. An analysis of clinical material through 10-year-period (1980-1989) is presented. There were 708 gastric operations performed for gastroduodenal ulcer disease. Most frequently distal gastric resections (585) were used, 233 in B. I. and 352 in B II. modification. Selective proximal vagotomy (SPV) was less frequently used (only 116 cases). Authors think there is no reason for a general use of SPV for each form of duodenal ulcer because of very serious competition with the H2 blockers. A different individual proved choice of the method as well as an appropriate subtle operating technique is considered to be essential.


Pathogenesis of carcinoma in operated stomach--an animal model. An experimental study on rats was performed to observe pathogenetic factors causing cancerogenesis in operated stomach. In sets I and II without exogenous carcinogen exposition 450 rats were operated upon by a different methods. In groups I it was B II gastrectomy, B II with Braun's anastomosis, B II in Roux en Y modification, B I and B I with jejunal interposition. In group II non-resective methods were tested: gastroenterostomy, gastroenterostomy with Braun's anastomosis, gastroenterostomy in Roux en Y modification, and vagotomy with pyloroplasty. In the group III 147 rats with different gastric operations were submitted to oral nitrate and nitrate with ascorbic acid exposition. The results confirmed significant pathogenetic influence of enterogastric reflux on cancerogenesis in the operated stomach. Ascorbic acid added to the exogenous cancerogen leads to a suppression of development of gastric cancer in rats.


[Fibroplastic dust and cardio-respiratory functions]. Repeated measurements of dust concentrations and work loads were made at the workplaces in iron foundries (interval 10 years) and processing of asbestos (dusts 27 years and work load 8 years). The work load was mild to moderate, rarely heavy (energy output 2.0 to 5.7 MJ in the shift) with a mean heart rate 94-106. The incidence of occupational diseases was stabilized in the foundries, increased in the asset processing plants (mostly lung cancer). Two thirds of the workers were smokers, in spite of that the workers in the foundries had their mean flow-volume curve almost identical with the standards. Their age conditioned diminution was faster especially for FEF50 and 25 and accompanied with a bigger rise of FRC and RV. Exercise testing demonstrated the same fitness as in normal population (2.7 +/- 0.7 l/min). As far as asbestos processing is concerned, a diminution of dust concentrations below the limits was found. Despite of this, an increase in lung cancer incidence was observed probably as a consequence of high dust concentrations in the past and smoking habits (2/3 of workers). The flow-volume curves were obviously smaller than the normals. With the rising of exposure to asbestos and with the advancing age (more close correlation), the deterioration of respiratory parameters (measured during 6-7 years) was two times faster. The correlations were more close for women then for men. In the man group, this deterioration was greater in the last measurements. The results of ergometer testing up to anaerobic threshold were identical with those found in normal population.


On the relationship between theoretical presumptions asbestos genotoxicity and the practical monitoring of exposed workers. From the genotoxic viewpoint, there exists a sufficient evidence for asbestos carcinogenicity to human population and animals. Asbestos is a solid cancer promoter (cocarcinogen) of non-mutagenic character having epigenetic effects (15, 16). No data have been published on its mutagenic activity in "in vivo" conditions in man. The only results are those of our pilot study carried out in the period of 1981-1983, which cast doubts on the official view of non-mutagenic character of asbestos--at least under occupational conditions of its processing (34, 36, 37). The study presented here represents ten years' efforts made in the biological (cytogenetic) monitoring of persons occupationally exposed to asbestos in a factory for its processing (occupational risk). Simultaneously, a preliminary answer is given to the question whether the Osinek factory (situated in a housing area) is or is not dangerous for inhabitants of the town of Kostelec nad Orlicí, namely for their genetic apparatus (environmental risk). Using the method of chromosome aberrations analysis in peripheral blood lymphocytes, a total of 431 subjects (245 males and 186 females) were examined in the period of 1981 to 1988. Of these, 111 persons were from control workplaces (from Osinek or--starting from 1984--from other plants in Kostelec nad Orlicí; in addition to that 14 pensioners without any occupational exposure were examined). The average age of workers exposed to asbestos risk was 42.7 years, in the controls it was 43.9 years, in pensioners exposed to asbestos earlier 63.5 years and in those never exposed to asbestos 66.5 years. The average number of years spent at Osinek factory amounted to 21.5 years. About one third of employees were found to suffer from allergies (first of all those of air passages) and one sixth from chronic ailments of the upper air passages (Staphylococcus aureus, Haemophilus influenzae and Streptococcus beta-haemolyticus were diagnosed most frequently). A third part of workers from high-risk workshops are smokers, only a fourth of the controls. About 40% of workers regularly consume alcoholic drinks. The average morbidity rate at Osinek in 1981 to 1988 was 6.3% (in workers as high as 9%), which is about 2% higher as compared with mean values obtained in the district of Rychnov nad Knĕznou and East-Bohemian region. Within the nine-year period (1981-1989), 21 occupational diseases were diagnosed, while in the previous 24 years there were 24 cases of an occupational disease. Earlier they were mainly asbestoses (87%), in the last period mainly cancer diseases coinciding with asbestosis (81%).(ABSTRACT TRUNCATED AT 400 WORDS)


Scleroplasty in progressive myopia--selection of materials. Scleroplastic surgery is known to encounter the pathogenetical agent when the progressive myopia develops. In the first part, the implemented surgical approaches as well as up-to-date surgical techniques are presented. The experimental part is reserved for the selection of material which is necessary to perform scleroplasties. Both the allogenic and xenogenic grafts have been studied for histocompatibility on 20 rabbits. Following materials were used: 2 types of collagenic sponge, native and deproteinated human sclera, modified dura mater as well as both the native and devitalized sclera from rabbits. The best results were obtained with allogenic sclera, deproteinated xenogenic sclera and collagenic sponge. The application of other materials is discussed.


Communication with patients as a problem in undergraduate medical education. The work is based on the following concepts: communication with patients ceases being a matter of experience learning only (the trial and error method) and should become a part of systematic training; it should not be included only into continuous education of graduated physicians but must be gradually introduced into undergraduate education as well; it is not an optional activity which may but may not be performed by physicians, but it is a specific component of their clinical competence. Today attempts to instruct medical students in communication with patients and their relatives are being made at many medical schools all over the world. Reports on such instruction are, however, scattered in various journals or in internal publications published by universities, faculties and clinics. Thus they are not available very easily. If there exist some survey works, they are mostly conceived on the national level. The objective of the study presented here is to show a comparatively comprehensive survey dealing with the medical student instruction on the international level, analyze trends in development and identify problems that have not been solved so far. The work consists of five chapters. The first one gives a short survey of current concepts in communication with patients reaching beyond the traditional training in taking medical history. Among others, the following factors are included here: explanation of both diagnostical and therapeutical methods to the patient, informing the patient about results obtained from the examination, telling him or her general conclusions and recommendations, informing patients of social associations of the disease, developing in the patients those attitudes which support their cooperation with physicians and the patient's will to live, ability to treat serious and terminal patients properly, ability to treat patients' relatives and communicate with other members of a medical team. The second chapter shows current attempts to train the medical student-patient communication in Czechoslovakia, especially at Charles University. Third chapter describes how medical students in the former USSR were instructed, especially at medical schools in Moscow. This kind of information is still difficult to be had for people from abroad. The fourth chapter is the most important. Current attempts to train medical students in communication with patients in Europe, North and South America, Asia, Africa and Australia are described there. Reference frames in which the instruction takes place (medical, educational, psychological frames) are studied.(ABSTRACT TRUNCATED AT 400 WORDS)


Increased breathing gas density enhances cardiac workload. The effect of increased breathing gas density on the left ventricular pressure (LVP), cardiac contractility (dP/dt), heart rate (HR), intrapleural pressure (P(ip)) and respiratory frequency (RF) was evaluated in pentobarbital-anaesthetized rats (n = 8) and cats (n = 6). Catheters were placed in the left cardiac ventricle via the right carotid artery to measure the LVP, in the oesophagus for indirect measurements of P(ip) and RF, and into the aorta from the right femoral artery for arterial pressure measurements. The RF fell significantly within the first 30 s and had reached a stable value 2 min after gas shift in both rats and cats. Concomitant with the RF fall, the depth of inspiration and intrapleural pressure differences in both rats and cats increased. The acid-base balance remained at control levels in both animal groups. LVP and dP/dt started to increase during the first half-minute, and reached their maximum values 2-5 min after the introduction of normoxic sulphur hexafluoride. A linear relationship between the enhanced dP/dt and the P(ip) increase was found. The HR remained unchanged in both cats and rats. These findings indicate that the breathing gas density might influence the cardiac contractility found during hyperbaric exposure, and that a gas density of five times that of air at 1 bar does not influence the diffusion of O2 and CO2 in the lung. The O2 consumption of the heart in cats and rats was calculated to rise by 25% and 30% respectively in the dense breathing gas atmosphere.


Response of diastolic blood pressure to long-term sodium restriction is posture related. Eighty-five subjects, aged 31-55 years, suffering from uncomplicated essential hypertension and receiving no regular medication were randomized to sodium restriction and control groups. Systolic (SBP) and diastolic (DBP) blood pressure were measured during an orthostatic test at baseline and after 6 months sodium restriction. The mean daily sodium excretion of 43 treated subjects decreased from 193 +/- 91 mmol to 95 +/- 70 mmol (p less than 0.001). Treated patients were divided on the basis of their mean overall out-patient clinic (OC) DBP decrease in the sitting position during the 6 months (monthly measurements) into sodium-sensitive (DBP decrease greater than 10 mmHg, n = 17), indeterminate (DBP decrease 5-10 mmHg, n = 18) and sodium-resistant (DBP decrease less than 5 mmHg, n = 8) subgroups. At 6 months the level of DBP in the supine position was lower than at baseline in both sensitive and resistant subgroups, whereas in the standing position a lower DBP than at baseline was seen only in the sodium-sensitive subgroup. The magnitude of the subsequent OC DBP decrease was significantly associated with a high baseline seated OC DBP (p less than 0.001) and a high, for baseline OC DBP adjusted orthostatic DBP increase (p = 0.014). Our data suggest that posture should be included in the concept of sodium sensitivity and that an orthostatic test is useful in the prediction of seated and standing DBP decrease produced by moderate, long-term sodium restriction.


A microtitre assay system for glucocorticoid receptors: decreased receptor concentration in myocardial infarction. A major difficulty in determination of glucocorticoid receptor sites is the very complicated assay procedure. Therefore, we describe a microtitre assay system for glucocorticoid receptors which is a whole-cell competitive binding radioassay using [3H]-dexamethasone as radioligand. This modification of a previously described protocol simplifies and reduces laboratory work and allows assay reproducibility to be controlled more reliably. Thus enabled to perform the test on multiple blood samples in parallel, we investigated cardiac infarction patients over a 12-day period to test if glucocorticoid receptor binding is altered in this 'stressful' disease. On the first day of the disease, glucocorticoid receptor capacity was significantly decreased without alteration of the receptor-ligand affinity, whereas on days 4 and 12 the number of receptor sites was normal again. This result fits well into the general observation of stress-induced down-regulation of immune responses.


Both the polysaccharide and lipid A parts of endotoxins are needed for the inhibitory effects of endotoxins on cellular LDL uptake. We previously reported that endotoxins inhibit low-density lipoprotein (LDL) uptake and degradation in Hep G2 cells. In the present study, we tried to elucidate which part(s) of the endotoxin molecules contribute(s) to the inhibitory effect of endotoxins on LDL uptake and degradation. The results show that the endotoxin isolated from Salmonella minnesota Re595 (Re mutant), which lacks polysaccharide, had no effect on the uptake and degradation of 125I-labelled LDL in Hep G2 cells. This mutant form also decreased the inhibitory effects of endotoxins which have complete polysaccharides on cellular LDL uptake and degradation. However, the polysaccharide part of endotoxins by itself had no effect on LDL catabolism by the cells. This suggests that both the polysaccharide and the lipid A parts of endotoxins are needed for the inhibitory effects of endotoxins on LDL uptake and degradation.


Enhanced urinary excretion of albumin in congestive heart failure: effect of ACE-inhibition. Urinary excretion of albumin and beta 2-microglobulin were measured in 13 patients with congestive heart failure, NYHA class II-IV, before and after captopril treatment for 4 weeks, and in 13 healthy control subjects. The urinary excretion of albumin was enhanced in heart failure patients compared to control subjects (12.0 micrograms min-1 vs 2.8 micrograms min-1; medians, p less than 0.01), whereas beta 2-microglobulin excretion was normal. No significant change in urinary excretion of albumin was observed after captopril. Using Spearmann's test the urinary excretion of albumin was correlated to the NYHA class (Px = 0.681, p less than 0.05, plasma renin (Px = 0.886, p less than 0.01) and plasma angiotensin II (Px = 0.5840, p less than 0.05). Correlations with atrial natriuretic peptide (rho = 0.412, p = 0.153) and aldosterone (Px = 0.487, p = 0.106) did not reach significance. By multiple linear regression analysis only plasma renin activity was correlated to albumin excretion. In conclusion, patients with congestive heart failure had an increased urinary excretion of albumin. It is suggested that the enhanced transglomerular passage of albumin in congestive heart failure is partly due to an increased intra-renal angiotensin II generation, but elevated plasma level of atrial natriuretic peptide and increased renal venous pressure may also be important pathogenetic factors.


CA 125 serum levels in patients with non-neoplastic liver diseases. A clinical and laboratory study. CA 125 is a tumour marker usually used in the monitoring of ovarian carcinoma patients. This study was performed to evaluate the behaviour of CA 125 in 159 patients with benign diffuse hepatic diseases who underwent thorough clinical and laboratory evaluation. Abnormal serum levels of CA 125 were found in 40.3% of the 159 patients, 70.6% of the 85 cirrhotics and 5.4% of the 74 non-cirrhotics. There was a correlation between CA 125 and numerous biochemical parameters characteristic of liver diseases, the liver failure tests being the most relevant. Ascites was a determining factor of serum CA 125 levels (98.4% of the ascites patients and only 4.1% of the non-ascitic patients had abnormal levels), and CA 125 had excellent sensitivity, specificity, efficiency, predictive values and likelihood ratios to detect ascites. In the absence of ascites, liver dysfunction played a small but significant role in the increase of CA 125. In liver disease patients with ascites the threshold required to obtain only 10% of abnormal values was more than 50-fold the basal level. These findings invalidate CA 125 as a tumour marker in these patients.


Alteration of erythrocyte glutathione, cysteine and glutathione synthetase in alcoholic and non-alcoholic cirrhosis. Glutathione (GSH) and cysteine were determined in the plasma and the erythrocytes of alcoholic and non-alcoholic cirrhotics as fluorescent monobromobimane derivatives by high-performance liquid chromatography (HPLC). Cirrhotic patients displayed a significant decrease of plasma GSH, as well as of plasma cysteine, that was related to the degree of liver disease but not to the nutritional conditions. On the contrary, erythrocyte cysteine was found to increase significantly in all cirrhotics, particularly in alcoholics, regardless of the severity of disease. In an attempt to find a possible explanation of these alterations, the GSH synthesizing enzymes, gamma-glutamylcysteine synthetase (GC-s) and GSH synthetase (GSH-s) activities were determined in the erythrocytes. GSH-s activity was significantly lower in cirrhotic patients, whereas GC-s activity did not differ in the three groups.


Long-term supplementation with n-3 fatty acids, I: Effect on blood lipids, haemostasis and blood pressure. The effect of dietary supplementation with 4 g of n-3 polyunsaturated fatty acids (PUFA) daily for 9 months on blood pressure, plasma lipids and lipoproteins, platelet function, coagulation and fibrinolysis was studied in 24 healthy volunteers. Each variable was determined before, after 6 weeks and 9 months of supplementation with n-3 PUFA, and 3 months after the supplementation period had ended. Systolic and diastolic blood pressure declined after intake of n-3 PUFAs. Plasma triglycerides were reduced, and there was a trend towards an increase in HDL-cholesterol after 9 months of supplementation, while total cholesterol, LDL-cholesterol and apolipoproteins A1 and B were unaltered. The bleeding time was increased, and plasma levels of von Willebrand factor decreased after 9 months supplementation with n-3 PUFA. Fibrinogen levels increased, while fibrinolysis was reduced after 9 months supplementation with n-3 PUFA. Overall, no clear benefit on lipid pattern and haemostasis was achieved with respect to development of coronary heart disease.


Long-term supplementation with n-3 fatty acids, II: Effect on neutrophil and monocyte chemotaxis. The effect of a daily supplement with 4 g of n-3 polyunsaturated fatty acids (PUFA) for 9 months to 24 healthy volunteers on neutrophil and monocyte chemotaxis was studied using the under-agarose technique. Autologous serum and n-formyl-methionyl-leucyl-phenylalanine were used as chemoattractants. The effect after 9 months of supplementation with n-3 PUFA was also compared to results after short-term supplementation with n-3 PUFA for 6 weeks. Monocyte chemotaxis was reduced after 9 months of supplementation with n-3 PUFA to the same extent as after 6 weeks supplement. Neutrophil-directed migration towards chemoattractants was reduced after 9 months on fish oil, and this decrease was significantly greater than the decrease obtained after 6 weeks of supplementation. The spontaneous migration of neutrophils was significantly attenuated after 9 months compared to baseline and to 6 weeks. These findings lend support to a role for n-3 PUFA in the management of chronic inflammatory and atherosclerotic vascular diseases.


Radio-immunoassay of atrial natriuretic peptide (ANP) and characterization of ANP immunoreactivity in human plasma and atrial tissue. A sensitive radio-immunoassay (RIA) was developed to determine the occurrence of atrial natriuretic peptide (ANP) in plasma and atrial extracts from patients undergoing open heart surgery. The immunoreactive ANP (irANP) was characterized by high-pressure liquid chromatography coupled with RIA. The plasma irANP response to releasing stimuli during the operation was determined in simultaneously sampled venous and arterial blood, in order to evaluate any differences. The antiserum recognized the intact ring-structure of alpha-humanANP (alpha-hANP) and its propeptide gamma-hANP, as well as beta-hANP, an anti-parallel dimer of alpha-hANP. Less bioactive N-or C-terminal fragments of alpha-hANP, or an N-terminal fragment of the propeptide, gamma-hANP 1-67, did not cross-react with the antiserum. Sep Pak C18-extraction of plasma resulted in an 80% recovery of synthetic alpha-hANP. The assay had a sensitivity of 1.9 pmol l-1, well below the venous plasma concentrations of irANP found in healthy volunteers (7.4 +/- 1.3 pmol l-1, mean +/- SEM, n = 19), and the local standard was identical to an international standard of alpha-hANP. In atrial extracts three major peaks of irANP were identified as alpha-, beta- and gamma-hANP, with gamma-hANP as the most abundant form. In plasma alpha-hANP dominated, but in two cases high plasma levels of beta-hANP were seen, reflecting the high atrial content in these patients. In peripheral arterial blood, irANP was on an average 56% +/- 20% (p less than 0.01, n = 18) higher than in venous blood; this was associated with more distinct arterial irANP responses to releasing stimuli during the operation.


Calcium clamp technique: suppression of serum intact PTH by induced hypercalcaemia in normal man and primary hyperparathyroidism. The aim of the study was to investigate the interrelation between induced hypercalcaemia and serum intact parathyroid hormone (S-PTH(1-84)) in normal man and in patients with primary hyperparathyroidism (PHPT) by measuring blood ionized calcium (B-Ca++) and S-PTH(1-84) before and during a controlled calcium infusion. Guided by frequent measurements of B-Ca++, we adjusted the calcium infusion rate continuously, thereby keeping B-Ca++ in a steady state at a pre-determined level approximately 0.25 mmol l-1 above baseline values. This calcium clamp technique (CCT) applied to 14 normal volunteers for 120 min established a standardized reference for parathyroid suppression and the renal physiological PTH response. The reproducibility of the method and the results obtained by the CCT were satisfactorily assessed in six of the 14 normal subjects. In normal subjects B-Ca++ was raised from 1.25 +/- 0.3 mmol l-1 (mean +/- SD) to 1.49 +/- 0.02 mmol l-1 suppressing S-PTH(1-84) to 264 +/- 9.9% of pre-infusion levels. We applied the CCT to 10 patients with PHPT for 120 min raising B-Ca++ from 1.41 +/- 0.09 mmol l-1 to 1.69 +/- 0.08 mmol l-1, thereby suppressing S-PTH(1-84) to 47.9 +/- 16.3% of pre-infusion levels. The renal handling of calcium and phosphate during CCT demonstrates the biological effects of suppressed activity of PTH on the renal tubules showing increments in the maximal tubular phosphate reabsorption in relation to the glomerular filtration rate (TmP/GFR) and decreased tubular reabsorption fraction of calcium. The described CCT is a safe and reliable dynamic test.(ABSTRACT TRUNCATED AT 250 WORDS)


Cardiac systolic time intervals and thyroid hormone levels during treatment of hypothyroidism. This study was undertaken to compare results of modern serum thyroid hormone assays with cardiac systolic time intervals (STI) during thyroxine treatment in hypothyroid patients. The patients were assessed clinically (Billewicz index) and the STI and serum thyrotropin (TSH), total and free thyroxine (T4) and total and free triiodothyronine (T3) were determined in 16 hypothyroid women (Group I) treated with 50 micrograms increments of thyroxine, and in 13 women who had a history of thyroid carcinoma and high-dose thyroxine replacement therapy and had elevated thyroid hormone concentrations (Group II). The STI of 24 matched healthy female controls were used for reference of STI. The pre-ejection period (PEP) index and the PEP/LVET ratio (left ventricular ejection period) were greater in untreated overtly and mildly hypothyroid patients (p less than 0.05) than in the controls. During stable thyroxine therapy [mean daily dosage for Group I 137.5 (7.3) micrograms and for Group II 220 (61) micrograms] the PEP correlated with serum free T4 (FT4), as measured by a two-step method (SpectriaR) (r = -0.55, p less than 0.01, n = 29) and total T4 (r = -0.51, p less than 0.05, n = 29), but not with TSH, T3, FT3 or FT4 measured by an analogue method Amerlex-M(R). The TRH test was not valuable in follow-up because of the strong correlation between basal TSH and stimulated TSH values (r = 0.95). In conclusion, STI are useful for assessment of the thyroid state in untreated hypothyroid patients. Serum TSH becomes normal in the same time as STI and is the best for follow-up. If serum TSH is low and the patient is on stable thyroxine therapy, we recommend serum FT4 for monitoring thyroxine replacement. Two-step FT4 assays had the best correlation with STI, which has significance in patients with non-thyroidal illness.


Levels of calprotectin (leukocyte L1 protein) during apheresis. The plasma concentration of calprotectin was measured before, during and after apheresis in patients with Guillain-Barré Syndrome (GBS), Waldenstrøm's syndrome or hypercholesterolaemia and in healthy donors of platelets. Increased calprotectin levels were found after plasma exchange in the Waldenstrøm's syndrome patients, probably caused by release of the protein from activated leukocytes. The decreased calprotectin values observed in the other patients, may be due to plasma dilution. Unexpectedly, the GBS patients were found to have high initial calprotectin levels in plasma but not in cerebrospinal fluid. In donors, normal and unchanged calprotectin concentrations were found throughout.


What causes impaired glucose tolerance to deteriorate or normalize? Twenty-five middle-aged subjects with impaired glucose tolerance (IGT) were analysed 5 years later, showing normal glucose tolerance in 28% and persistent glucose deterioration in 72%. Body mass index (strongly) and 2-h glucose levels were clinically useful predictors, in the newly detected IGT-subjects, of persistent glucose deterioration (IGT or NIDDM) 5 years later. The frequency of hypertension was 36% in the newly-detected IGT subjects. Five years later this frequency increased to 54% in the persistently hyperglycaemic group, and decreased to none in the normalized group. Predictors of hypertension at the follow-up were baseline blood pressure and parts of the hyperinsulinaemic syndrome, such as serum triglyceride at baseline, BMI and 2-h glucose at the follow-up. Microalbuminuria (greater than 20 mg day-1) was not found at the 5-years follow-up, either if the subjects then had NIDDM, IGT or normal glucose tolerance. ECG abnormalities (ST segment and T wave changes) were two-fold more prevalent in the group with IGT or NIDDM than in the normalized group at the follow-up. Predictors were baseline BMI and incremental BMI. In conclusion, obesity and high 2-h glucose in newly-detected IGT-subjects seemed to predict the persistence of IGT 5 years later. Hypertension, but not microalbuminuria, was frequent when glucose deterioration persisted.


Measurement of CA 125 by an automated microparticle enzyme immunoassay; comparison with a manual enzyme immunoassay. The technical characteristics and the clinical usefulness of a new automated microparticle enzyme immunoassay (Abbott IMxR CA 125) for cancer antigen 125 (CA 125) in serum were investigated. The microparticle enzyme immunoassay (MEIA) had a high degree of practicability and a short turn-around-time. The imprecision (2.5-6.4%), detectability (less than 1 kU l-1), and carryover (less than 0.01%) of the analysis were low and the recovery of CA 125 after dilution with serum from ovarian cancer patients was good. The antigen was measured in samples from 72 ovarian cancer patients by the MEIA and a well documented manual enzyme immunoassay (Abbott CA 125 EIA). The correlation between the CA 125 MEIA and EIA results was non-linear. CA 125 EIA values below 39 kU l-1 (95% CI: 36-42) gave higher MEIA results and EIA values above this level resulted in lower MEIA values. The marker was measured before second-look laparotomy of 57 ovarian cancer patients. Using different cut-off levels, the clinical information of CA 125 MEIA measurements was equivalent to that obtained by EIA. The relationship between the CA 125 EIA values and the corresponding MEIA results was complex and the clinician may have difficulties in interpreting the MEIA CA 125 results until the calibration has been approximated to that of EIA. Alternatively, clinical investigations should be performed to establish an upper reference limit of MEIA CA 125 values.


Apolipoprotein(a) in insulin-dependent diabetic patients with and without diabetic nephropathy. Insulin-dependent diabetic patients with diabetic nephropathy have a highly increased morbidity and mortality from cardiovascular diseases. To determine whether altered levels of apolipoprotein(a) (apo(a)), the glycoprotein of the potentially atherogenic lipoprotein(a) (Lp(a)), contribute to the increased risk of ischaemic heart disease, apo(a) was determined in 50 insulin-dependent diabetic patients with diabetic nephropathy (group 1), in 50 insulin-dependent diabetic patients with microalbuminuria (group 2), in 50 insulin-dependent diabetic patients with normoalbuminuria (group 3), and in 50 healthy subjects (group 4). The groups were matched with regard to sex, age and body mass index. The diabetic groups were also matched with regard to diabetes duration. The level of apo(a) was approximately the same in the four groups, being: 122 (x/ divided by 4.2) U l-1, 63 (x/ divided by 4.4) U l-1, 128 (x/ divided by 3.5) U l-1 and 126 (x/ divided by 3.7) U l-1 (geometric mean (x/ divided by antilog SD)) in group 1, 2, 3 and 4, respectively. 1 U l-1 apo(a) approximates 0.7 mg l-1 Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of nicotinic acid on glucose tolerance and glucose incorporation into adipose tissue in hypertriglyceridaemia. Nicotinic acid 4 g daily was given to 28 weight-stable hypertriglyceridaemic patients. The aim was to study its effects on serum lipoprotein lipid levels, intravenous glucose tolerance (k-values) and glucose incorporation into subcutaneous adipose tissue (GLIAT) in vitro. The investigations were performed prior to the nicotinic acid therapy, after 6 weeks, and 6 months of drug treatment. Fasting blood glucose levels increased by 13%, whereas k-values fell by 26% after the nicotinic acid treatment. Decrease in k-values was predicted from the initial k-values (R2-value = 0.76). GLIAT increased by 76%, while in the subgroup of eight patients, treated for 6 months with nicotinic acid, GLIAT increased by 331%. The changes in k-values and GLIAT were not significantly interrelated. Serum triglyceride levels were strongly decreased. The most likely explanation for the decrease in intravenous glucose tolerance is that nicotinic acid stimulates glucose output from the liver and that this effect outweighs the stimulating effects of the drug on glucose utilization in extrahepatic tissues. The latter is reflected by the increased uptake of glucose in adipose tissue. A stimulated GLIAT, reflecting formation of alpha-glycerophosphate in adipose tissue, might contribute to the reduction of serum triglyceride levels induced by nicotinic acid, since alpha-glycerophosphate is the acceptor of fatty acids assumed to be liberated from circulating triglycerides by lipoprotein lipase.