The twisted structure of the Achilles tendon unraveled: A detailed quantitative and qualitative anatomical investigation.

The Achilles tendon (AT) consists of fibers originating from the soleus muscle (SOL), which lies deep, and the medial (GM) and lateral (GL) heads of the gastrocnemius muscle, which lie superficial. As the fibers descend toward the insertion of the AT, the individual subtendons twist around each other. The aim of this study was to investigate the twisted structure of the AT and its individual subtendons. Specimens of the AT, with preserved calcaneal bone and a fragment of the triceps surae muscle, were obtained from 53 fresh-frozen, male cadavers (n=106 lower limbs). The angle of torsion of each of the AT's subtendons was measured using a specially designed and 3D-printed tool. The mean distance between the most distal fibers of the triceps surae muscle and the superior border of the calcaneal bone was 60.77±14.15 mm. The largest component of the AT at the level of its insertion into the calcaneal bone is the subtendon from the GL (44.43%), followed by the subtendon from SOL (27.89%), and the subtendon from GM (27.68%). The fibers originating from the GM rotate on average 28.17±15.15°, while the fibers originating from the GL and SOL twist 135.98±33.58° and 128.58±29.63°, respectively. The torsion of superficial fibers (GM) comprising the AT is significantly lower than that of deeper fibers (GL and SOL). The cross-sectional area of the AT is smaller at the level of the musculo-tendinous junction than at the level of its insertion. This study illustrates the three types of the AT with differently twisting subtendons, as well as a generalized model of the AT. Types of AT torsion may potentially alter the biomechanical properties of the tendon, thus possibly influencing the pathophysiologic mechanisms leading to the development of various tendinopathies.

[Validation of a clinical prediction rule for the diagnosis of deep vein thrombosis of the lower limbs in primary care]. / Validation d'un score de prédiction clinique de la thrombose veineuse profonde des membres inférieurs spécifique à la médecine générale.

PURPOSE: Patients with suspected deep vein thrombosis (DVT) are often managed on an outpatient basis. The aim of the study was to validate a clinical prediction rule specifically for use in primary care to help physicians in their decision to start anticoagulant therapy while awaiting ultrasound examination. PATIENTS AND METHODS: Between September 2007 and October 2008, 194 general practitioners prospectively included patients with clinically suspected DVT without clinically suspected pulmonary embolism. All patients underwent a standardized clinical assessment in order to collect items included in the clinical prediction rule (personal history of venous thromboembolism +1, immobilization in previous month+1, estrogen contraceptive+2, active malignancy+3, swelling of the calf+1, the presence of an alternative diagnosis more likely than that of DVT-3. DVT unlikely if score<2, likely if score≥2). RESULTS: Among the 164 included patients, 56 (34%) had DVT of them 28 (17%) had a proximal DVT. Proportions of confirmed DVT were 29% in the unlikely group and 43% in the likely group against 26% and 63% respectively in the derivation study. CONCLUSIONS: This clinical prediction rule might not fulfill the required conditions to be considered as a usable help in the ambulatory management of DVT. Variations of the cut-off value could enhance its performance.

[Adaptation of computed tomography and roentgenography to bone density measurements]. / Adaptacja tomografii komputerowej i rentgenografii do pomiarów densytometrycznych tkanki kostnej.

The increasing interest in issues connected with osteoporosis has recently caused the development of many new diagnostic methods which allow the measurement of bone density. The DEXA method, performed by specialised densitometers, is one of the most developed and reliable methods. However, the high cost od densitometers and DEXA investigation prevent this method from becoming easily accessible for everyday diagnosis. The adaptation of computerised tomography and rentgenography to densitometric measurements could be one of the methods by which the problem of densitometric diagnosis accessibility could be solved. Both methods are usually applied in the imaging of human tissues, working on the basis of differences in tissue X-ray absorption. X-ray absorption and density are related by linear function in the energy range used in rentgenography and tomography; therefore, quantitative information concerning density should be easily received. The procedure adapting computerised tomography and rentgenography to quantitative measurements of bone density in the lumbar spine is outlined in this work. The quantitative information is obtained from digitalised tomographic and rentgenographic images through use of a personal computer. Both methods were tested using a set of phantoms imitating the lumbar spine and the surrounding tissues. The precision and accuracy of both methods were assessed and compared to the precision and accuracy of the DEXA method. The outlined results confirm the usefulness of the described method in diagnosis.

First results of a clinical pilot study on intraarterial chemotherapy with haemofiltration of locally advanced gastrointestinal cancers.

Intra-arterial chemotherapy combined with haemofiltration enables the administration of drugs to confined neoplastic tissue while limiting the systemic drug exposure. During the procedure, the cytotoxic drugs are injected into the arterial supply of the tumour and the venous blood coming from the tumour bed is pumped out and filtered trough haemofiltration unit in order to extract the cytotoxic drug not fixed on the tumour. The patients selected for such treatment failed previous intravenous chemotherapy. Thirteen patients underwent intra-arterial chemotherapy injections combined with haemofiltration procedures: 8 unresectable liver metastases from colorectal cancer and 5 pelvic recurrences from rectal cancer. Fluorouracil, mitomycin C and doxorubicin were infused. One out of thirteen patients presented a complete regression of his liver metastases, 5/13 presented a partial regression, 2/13 patients did not show any significant modification of the size of their lesions and were classified as stable disease, 5/13 patients showed a progression of their neoplastic disease. No nephrotoxicity or major gastrointestinal side effects were observed. Intra-arterial chemotherapy combined with haemofiltration procedure is a therapeutic modality that could be considered in patients with locally advanced cancer who failed previous first line intravenous chemotherapy.

Adjuvant treatment in gastric cancer. Possibilities to take or to leave it.

The primary mode of management of gastric carcinoma is surgical resection with 5-year survival rate following curative resection of about 30 to 40%. This article reviews the results of randomized clinical trials including adjuvant chemotherapy, radiation treatment and chemoimmunotherapy after curative surgical resection. Randomized trials done to date largely do not support the use of adjuvant chemotherapy in resected gastric cancer. Mitomycin C or FAM association have demonstrated the best efficiency with increase of median survival in treated patients. Mitomycin C demonstrated a significant advantage by reduction of the incidence of hematogenous metastases. Encouraging perspectives come from the association between chemotherapy and biochemical modulators.

[Cholestatic hepatitis and amoxicillin-clavulanic acid combination. Personnel case report and literature review]. / Hépatite cholostatique et association amoxicilline-acide clavulanique. Observation personnelle et revue de la littérature.

The association amoxicillin-clavulanic acid is a widely used medication. Only about 15 cases of cholestatic hepatitis were reported in Belgium between 1990 and 1993; about 100 cases have been reported to the pharmaceutical company. This effect is severe but reversible. The injury is probably idiosyncratic or immunologically based. Age, sex and treatment duration are as many agents of risk. The diagnosis is undertaken on basis of clinical examination, chronological study, biological evolution and histology.

Duodenal diverticula--diagnosis and management of complicated forms: report of two clinical cases and review of the literature.

Duodenal diverticula are frequent, they are present in 22% of the cases at autopsy. However, radiological assessment demonstrates duodenal diverticula in 1 to 5% of the patients only. Perforation, the main complication, is very rare. Preoperative diagnosis is exceptional. In a 69-year patient admitted for diffuse abdominal pain, a computerized abdominal tomography, completed by opacification of the gastroduodenal transit allowed diagnosis. In the second case, diagnosis was made peroperatively. Based on these two observations, the authors review the elements of diagnosis and management in complicated duodenal diverticula.

Determination of leucovorin and 5-fluorouracil in plasma by high-performance liquid chromatography.

A method was developed for the determination of (6R)- and (6S)-leucovorin and 5-fluorouracil in plasma. As leucovorin diastereoisomers cannot be separated on a classical reversed-phase column, it was necessary to use a chiral stationary phase. The method presented is based on the same principle as the method described by Wainer and Stiffin [J. Chromatogr., 424 (1988) 158], i.e., coupling of a bovine serum albumin phase to an achiral stationary phase. Before the chromatography, the drug was isolated from the plasma matrix by solid-phase extraction. For 5-fluorouracil, chromatography was performed on a classical RP-18 column after extraction from the plasma by liquid-liquid extraction. Both methods were validated and applied to the analysis of patients' samples.

Colonoscopic snare polypectomy: analysis of 1485 resections comparing two types of current.

The complications related to 1485 colonic snare polypectomies were analyzed according to the type of current which was used for resection. From January 1982 to August 1986 (period 1), blended current was used in 758 snare polypectomies, while continuous coagulation current was applied in 727 polypectomies from September 1986 to October 1989 (period 2). The incidence of complications observed in the entire series was low, consisting of 0.26% perforations and 0.9% major hemorrhages. There were no deaths in this series. Twelve of 14 hemorrhages occurred after resection of polyps larger than 1 cm. Although the incidence of complications was not statistically different in the two groups, there was a significant difference in the timing of hemorrhages. All of the major hemorrhages were immediate (eight) when the blended current was used, but delayed (six; from 2 to 8 days after polyp resection), when pure coagulation current was applied.

Modulation by estrogen of the incidence of diethylnitrosamine-induced gamma-glutamyltranspeptidase-positive foci in rat liver.

We measured the number and size of foci of altered hepatocytes induced after 8 weeks by diethylnitrosamine (DENA) in the liver of rats pretreated with 17 beta-estradiol (E2), 1 or 24 h prior to the administration of the carcinogen. The average size of the lesions was the same in the E2 pretreated and unpretreated animals. The number of gamma-glutamyltranspeptidase (GGT)-positive foci per cm3 of liver increased from 364 +/- 57 in unpretreated animals to 1149 +/- 186 in animals receiving E2 24 h before DENA; it raised to 3779 +/- 280 when the hormone was injected 1 h before the carcinogen, i.e. about 25% of the number of foci scored in rats receiving the carcinogen 24 h after partial hepatectomy. The hypothesis is proposed that 1-h pretreatment with E2 increases hepatocyte susceptibility towards DENA action by enhancing the accessibility of the genome to the carcinogen.

Modulation by indomethacin of diethylnitrosamine-induced early changes in c-myc and c-ras expression and late incidence of preneoplastic lesions in rat liver.

We measured the levels of c-myc and c-ras expression before and after diethylnitrosamine (DENA) treatment in the liver of rats previously submitted to partial hepatectomy (PH), in the presence or absence of indomethacin (IMC), given at a dose that reduced by 75% the incidence of preneoplastic foci of altered hepatocytes scored 8 weeks after application of the carcinogen. The time-course evolution of c-myc response to PH was similar in IMC-treated and untreated rats (with a peak at 3-8 h at least as high in IMC-treated animals as in the hepatectomized reference group), whereas the overall c-ras response was significantly reduced by the IMC treatment, resulting in much lower c-ras expression at 18-24 h posthepatectomy. Treatment with DENA 24 h after PH did not significantly modify c-ras expression compared to partially hepatectomized controls. In contrast, DENA treatment resulted in a marked transient increase in c-myc expression that was at least as pronounced, if not the same, in the IMC-treated animals. These results leave open the possibility that increased c-myc expression under DENA influence might play a role in foci induction but exclude that this might be sufficient. They are consistent with a role for c-ras expression in determining the susceptibility of hepatocytes towards the carcinogenic action of DENA.

Modulation by indomethacin or prostaglandin E2 of the incidence of diethylnitrosamine-induced gamma-glutamyltranspeptidase-positive foci in rat liver.

We investigated the effect of a pretreatment with indomethacin (IMC, ip 3.6 mg/kg body weight (bw)) or dimethylprostaglandin E2 (PGE2, ip 10 micrograms/kg bw) on the incidence and development of gamma-glutamyltranspeptidase (GGT)-positive foci of altered hepatocytes, scored 8 or 14 weeks after ip injection of diethylnitrosamine (DENA, 50 mg/kg bw) to rats submitted to two-thirds hepatectomy (PH) or sham operation (Sh). IMC reduced by about 4 times the incidence of DENA-induced GGT-positive foci per cm3 of liver tissue in sham-operated as well as in two-thirds hepatectomized rats, compared to the respective unpretreated controls. In contrast, PGE2 pretreatment increased the incidence of DENA-induced foci in both groups, this effect, in terms of absolute numbers of foci, being additive to that of PH alone. IMC pretreatment resulted in foci with lower average size in the Sh but not in the PH animals, whereas with PGE2 pretreatment the mean volume of the foci was increased in the two groups of rats. At the dose used, IMC did not modify the proliferative response of hepatocytes to PH, and PGE2 did not stimulate proliferation in the sham-operated animals. Altogether, these results indicate that: 1, the incidence of DENA-induced foci can be negatively modulated by interfering with the prostaglandins pathway through a mechanism that does not involve an action either on proliferative activity or on any other process that would be specific to the post-hepatectomy regenerative state; 2, positive modulation of the incidence of DENA-induced foci does not necessarily require stimulation of proliferation.

[Polyps with an invasive degenerated focus]. / Polypes à foyer dégénéré invasif.

Advances in technology of flexible endoscopes have greatly changed the management of patients with adenomatous polyps of the colon and rectum. Some controversy still exists concerning the best treatment for invasive polyps. For some authors, invasive polyps need radical operation, while others think that unless cancer goes beyond the bounds of a removed polyp, endoscopic resection is an adequate procedure. We designed a study of 65 patients presenting an invasive carcinoma arising in adenomatous polyps and who underwent a colorectal resection thereafter, in order to determine which endoscopic and histological features correlated best with a curative treatment by polypectomy. When the group of "non-curative polypectomies", (carcinoma in the surgical specimen: 34 patients) was compared to the group of "curative polypectomies" (carcinoma in the surgical specimen: 31 patients), there was no significant difference in the number of pedunculated or sessile polyps but a polyp's size exceeding 30 mm was significantly more frequent in the group of "non-curative polypectomies" (P less than 0.005) as well as a tubulo-villous or villous histological type (P less than 0.001) and presence of vascular neoplastic invasion (P less than 0.01). In conclusion, a surgical resection after endoscopic polypectomy of a polyp containing an invasive carcinoma is necessary for a polyp's size exceeding 30 mm, for a villous or tubulo-villous type and in the presence of vascular neoplastic invasion in the pathological analysis of the removed polyp.

Modulation of rat pancreatic muscarinic cholinergic receptors by caerulein.

To evaluate the modulation of pancreatic muscarinic receptors in two states of pancreatic growth, hypertrophy and hyperplasia, caerulein, a cholecystokinin analog, (1 microgram/kg) was administered thrice daily for 2 and 4 days to adult rats. After 2 days of treatment, pancreatic hypertrophy was well established as evidenced by increases in pancreatic weight, cellular mass and protein content. Using an increase in DNA content as an index of hyperplasia, we demonstrated that pancreatic hyperplasia occurred only after 4 days of caerulein treatment. Caerulein increased the concentration of muscarinic receptors per DNA in pancreatic homogenate by 57% over control value after 2 days of treatment without modification of the receptor affinity for the ligand QNB. This increase involved mainly receptors in the low affinity state for carbamylcholine and their concentration returned to control levels after 4 days of treatment. The functional capacity of the acini was significantly increased after 2 days of caerulein as amylase release (U/mg DNA) was significantly increased but the sensitivity of these acini to carbamylcholine was significantly decreased. After 4 days of caerulein, the functional capacity has returned towards control values but the sensitivity to carbamylcholine remained decreased. The increase in muscarinic receptor concentration could be ascribed to a general increase in cellular proteins, as part of the hypertrophic effect of caerulein. This specific effect would also explain the increased functional secretory capacity of the caerulein-treated acini but the decreased sensitivity to carbamylcholine probably resulted in changes at a postreceptor loci since the affinities of the muscarinic receptors for carbamylcholine remained unaffected.

Muscarinic cholinergic receptors in pancreatic acinar carcinoma of rat.

The active enantiomer of tritiated quinuclidinyl benzilate (3H(-)QNB) was used as a ligand to evaluate the muscarinic receptors. The 3H(-)QNB binding characteristics of muscarinic cholinergic receptors obtained from normal and neoplastic tissues were studied to determine changes in receptor properties during neoplastic transformation. Saturable and stereospecific binding sites for 3H(-)QNB are present in homogenates of rat pancreatic adenocarcinoma. The proportions of high- and low-affinity agonist binding sites are similar for neoplastic and normal tissues. The density of muscarinic receptors is higher in neoplastic (200 femtomoles/mg protein) than in normal pancreatic homogenates (80 femtomoles/mg protein). The muscarinic binding sites of the neoplastic and fetal pancreas show similar KD values which are higher than those observed for normal pancreas.

Evaluation of ammonium chloride as a urinary acidifier in the cat.

Twenty-four cats were fed a dry commercial cat food once daily for 2 weeks and then ad libitum for 2 weeks. Urine pH was measured 4 times daily the last 3 days of each feeding period. Subsequently, the cats were allotted to 2 equal groups and fed ad libitum an experimental, dry ration with or without 1.5% ammonium chloride for 11 months. During this period, urine pH was measured at 1, 3, 6, and 9 weeks, then monthly through 29 weeks, and then every 6 weeks for the duration of the study. When the cats were fed ad libitum, urine pH remained constant throughout the day, regardless of ration. In cats fed once daily, urine pH increased to 7.6 by 2 hours after feeding and remained between 6.6 and 7.6 for 9 hours. Urine pH remained constant throughout the study when cats were fed the experimental ration with or without 1.5% ammonium chloride, but was significantly different (P less than 0.01) between the 2 groups, 5.9 +/- 0.3 (n = 1,035) and 7.0 +/- 0.5 (n = 616), respectively. Ammonium chloride consumption had no effect on food and water consumption or body weight. It was concluded that ammonium chloride was an effective urinary acidifier for a prolonged time, maintained urine pH below 6.6, and did not decrease food intake when given at a concentration of 1.5% of the diet.

Urinary acidification in the prevention and treatment of feline struvite urolithiasis.

Two groups of 12 cats were fed ad libitum an experimental dry expanded ration high in magnesium (0.37%, dry matter basis) and similar to most commercial dry cat foods in all other nutrients. The diet of one of the groups contained 1.5% ammonium chloride, which was added to the diet before processing. Urethral obstruction developed twice in 7 of the 12 cats fed the ration without ammonium chloride. Of the 5 remaining cats in that group, 2 had calculi in the urinary bladder and urethra at necropsy. In contrast, only 2 of the 12 cats fed the ration containing ammonium chloride had urethral blockage once; neither cat had another blockage. Both cats had been catheterized twice as paired controls before urethral obstruction. One of these 2 cats died from a urinary tract infection apparently introduced through the indwelling catheter, and at necropsy there were 2 small calculi in the urethra. At the end of the study, only 1 other cat fed the ammonium chloride diet had a calculus in the urinary bladder at necropsy; this cat had not had a urethral obstruction throughout the study. After each cat had 2 urethral blockages, its diet was changed. Four cats were fed the ration containing ammonium chloride and 3, a dry, commercial ration. Of the 4 cats fed the diet containing ammonium chloride, none developed another urethral obstruction within 6 months, and at necropsy, no calculi were in the urinary bladder or urethra. Two of the 3 cats fed the commercial ration experienced urethral blockage within 3 months. These 2 cats were then fed the diet containing ammonium chloride.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparison between muscarinic receptor occupancy, adenylate cyclase inhibition, and inotropic response in human heart.

Binding to muscarinic receptors was compared with adenylate cyclase inhibition in membranes derived from human heart auricles, and with inhibition of the contraction of auricular muscle fibers. In the absence of GTP, agonists recognized two classes of receptors both of which bound antagonists with the same affinity. In the presence of GTP, both classes of receptors for agonists were converted into a single low affinity state. Carbachol and oxotremorine inhibited adenylate cyclase activity by 43%, pilocarpine being less efficient (-28%). The 3 agonists exerted similar inhibitory effects on the inotropic response, in 7 out of 9 preparations of electrically- and norepinephrine-stimulated fibers. Dose-effect curves suggested that spareness (or an amplification mechanism) was implicated in the occupancy of low affinity binding sites by carbachol and oxotremorine (but not by the partial agonist pilocarpine) and the resulting inhibition of both adenylate cyclase activity and contractile force.

The human heart beta-adrenergic receptors. I. Heterogeneity of the binding sites: presence of 50% beta 1- and 50% beta 2-adrenergic receptors.

Beta-adrenergic receptors were characterized in a particulate fraction of human auricles obtained from patients operated upon for coronary insufficiency or valvular disease. [125I] Hydroxybenzylpindolol binding was evaluated in terms of kinetics; KD and Bmax values; and inhibition of binding in the presence of 10 microM GTP and of increasing concentrations of four nonselective agonists giving a Hill coefficient of 1 (isoproterenol, salbutamol, fenoterol, and epinephrine), of two nonselective antagonists giving a Hill coefficient of 1 (pindolol and propranolol), and of a series of selective drugs giving a Hill coefficient of 0.60-0.72 that included three beta 1-selective antagonists (practolol, metoprolol, and atenolol) and two beta 2- selective agonists (procaterol and zinterol). KD values for all drugs were compatible with the coexistence in membranes from human auricles of beta 1- and beta 2-adrenergic receptors, the relative proportions of receptors of each subclass being approximately the same.