Scanning electron microscopic study of degeneration and regeneration in the olfactory epithelium after axotomy

Summary The olfactory epithelium of the adult hamster (Mesocricetus auratus) was examined with the scanning electron microscope following olfactory nerve axotomy. Axotomy results in retrograde degeneration of mature olfactory neurons. Maximum degeneration was observed around day 4. During the degeneration period the epithelium consists primarily of supporting and basal cells. Microvillar columnar supporting cells were observed to have fine cellular processes extending from their lateral border to neighbouring cells. Supporting cells extended to the basal lamina where they terminated in foot-like processes of variable shapes (club, splay and hook). Basal cells which gave rise to new replacement olfactory neurons were observed near the basal lamina. They had a rough cellular surface covered with small granules and fine cellular extensions. Bowman's gland duct cells extended unbranched through the epithelium where they formed funnel duct openings covered with microvilli. During early recovery periods (5–30 days) the number of olfactory neurons in the lower epithelium region increased. We observed olfactory neurons with developing axon and dendritic processes. Specialized growth cone structures were seen at the tips. Olfactory neuron growth cones were elongated or club-shaped and had a ruffled membrane surface. Several thin filopodia extended from the growth cone and made contact with adjacent cells. At late recovery periods (35–120 days) there was a marked increase in the number of olfactory neurons within the middle and lower epithelium regions. Numerous dendritic processes extended to the epithelial surface and terminated in knob-like ciliated structures. Olfactory axons passed basally, forming small intra-epithelial bundles that penetrated the basal lamina then fasciculated into larger bundles within the lamina propria.This study provides detailed three-dimensional observations of the olfactory epithelium following neuron injury, and describes neural degenerative changes, replacement of olfactory neurons, development and maturation. In addition, we describe the structure and basal attachment of supporting cells and their glial-like relation with olfactory neurons.     

Optical Resolution of 1-Amino-2,3-Propanediol

The optical resolution of (R,S)-1-amino-2,3-propanediol was carried out in water with (S)(+)- and (R)(?)-2-(6-methoxy-2-naphthyl)propanoic acid according to Marckwald but using half the quantity of the optically active acid, the other half being constituted by hydrochloric acid.     

Trapeziometacarpal joint osteoarthritis: a retrospective study comparing arthrodesis to tendon interposition arthroplasty

Abstract Surgical management of trapeziometacarpal joint osteoarthritis (OA) is still controversial. The aim of this study was to evaluate and compare results of trapeziometacarpal arthrodesis and of tendon interposition arthroplasty. One hundred twenty-six patients suffering from trapeziometacarpal OA underwent surgery between 1996 and 2001. Of these patients, 62 (78 thumbs) treated with joint arthrodesis and 33 (41 thumbs) treated with tendon interposition arthroplasty with abductor pollicis longus (APL) have been evaluated at follow-up and therefore entered this study. Mean age was 53 years, while the mean follow-up was 36 months. Overall results were satisfactory in 84 patients with good pain improvement. Patients treated with arthrodesis showed better functional ability in bi-digital pinch and grip strength. First finger opposition motion, however, was better conserved in patients treated with interposition arthroplasty. Fusions had an 11.5% complication rate (9 thumbs) with nonunions, whereas 14.8% (6 thumbs) of patients treated with interposition arthroplasty developed 1 first metacarpal base collapse, resulting in 1 first ray length reduction. Despite complications, however, patients did not report unsatisfactory results and generally experienced marked pain reduction. This study shows that arthrodesis can be considered the treatment of choice in patients suffering from trapeziometacarpal OA at Eaton stage III or less, whatever the age and when a good pinch strength is needed.     

Fluorouracil-alone versus high-dose folinic acid and fluorouracil in advanced colorectal cancer: a randomized trial of the Italian Oncology Group for Clinical Research (GOIRC).

One hundred eighty-one patients with measurable recurrent or metastatic colorectal cancer, who had not received prior chemotherapy, were randomized in a prospective controlled trial to receive 5-fluorouracil (5FU), 13.5 mg/kg, for five days (arm A) or high-dose folinic acid [Cyanamid-Lederle, Italy] (FA), 200 mg/m2, for five days and 5FU, 400 mg/m2 for five days (arm B). The treatments were repeated every four weeks. One hundred fifty-five patients were evaluable for response. The two arms were balanced for all potential prognostic factors studied. The response rate (CR+PR) was 18% in the 5FU arm and 16% in the 5FU plus FA arm. Median duration of response was 56 weeks for 5FU alone and 42 weeks for the combination (p = 0.48). Median time to failure (TTF) was 20 weeks for arm A and 21 for arm B (p = 0.62). Median survival was 62 weeks on the 5FU arm and 53 weeks on the FA plus 5FU arm (p = 0.14). Dose intensity (DI) delivered was the same in both arms. Diarrhea and mucositis were the most frequent adverse reactions in arm B; 20% of the patients in arm A and 38% of those in arm B experienced diarrhea (p = 0.008). Mucositis occurred in 34% of patients in arm A and 42% in arm B (p = 0.04). In general nausea and vomiting were moderate. Hematological toxicity was more severe in patients treated with 5FU alone: 31% in arm A and 14% in arm B developed leukopenia (p = 0.015). In the combination arm one patient died due to gastrointestinal and hematological toxicity after the seventh cycle. This study indicates that, in advanced colorectal cancer, the combination of high-dose FA and 5FU is not superior to 5FU alone when utilized at standard high-dose intensity.     

Acantholytic variant of squamous-cell carcinoma of the breast

Three cases of acantholytic squamous-cell carcinoma of the breast are reported. They all had histological features resembling those of angiosarcoma or adenocarcinoma. They were not angiosarcoma, since in all three cases areas of squamous differentiation were present; in addition, the neoplastic cells were negative when stained for factor VIII, but were positive with anti-epidermal keratin. The glandular pattern exhibited, especially in Case 2, was difficult to differentiate from that of an ordinary carcinoma. However, the presence of dyskeratotic cells within the lumina, and the absence of alcian blue/periodic acid-Schiff positive material, and epithelial membrane antigen staining, were evidence against the diagnosis of adenocarcinoma. The patients died 5, 6, and 16 months after the diagnosis. Tumors with these histological features may have a very aggressive clinical course.     

The role of the chest X-ray in the evaluation of chronic severe heart failure: things are not always as they appear

The chest x-ray has become a standard clinical test to aid in the evaluation of patients with chronic severe heart failure. To evaluate just how useful this tool is in the routine assessment of pulmonary venous hypertension secondary to heart failure, we compared the radiologist's interpretation of the chest x-ray with hemodynamic data obtained from right heart catheterization in a group of patients undergoing protocol evaluation of an experimental treatment for heart failure. Of 23 patients with pulmonary venous hypertension (pulmonary capillary wedge pressure greater than 20 mmHg) and a complete data base, only 11 had chest x-rays showing evidence of pulmonary venous congestion or interstitial or alveolar edema. The sensitivity of the chest x-ray in selecting patients with a pulmonary capillary wedge pressure over 20 mmHg in this setting was only 48%. In other studies, where the radiologist was aware that his or her reading was being compared to hemodynamic assessments, the sensitivity of the chest film has approached 85%. We feel our analysis more closely parallels routine clinical practice. Clinicians should be aware that the chest x-ray may not be a very sensitive tool for the assessment of pulmonary hemodynamics in patients with severe heart failure.     

Modulation of X-ray-induced damage recognition and repair in ageing human peripheral blood mononuclear cells by an interleukin-6-type cytokine

We have investigated the effects of an interleukin (IL)-6-type cytokine on the DNA-binding activity of ku and on unscheduled DNA repair in X-ray-treated peripheral blood mononuclear cells (PBMC) from human subjects of different ages. The cytokine used, called K-7/D-6, is an IL-6 variant with increased in vivo and in vitro biological activity compared to the wild type molecule. Ku is the DNA-binding component of the DNA-dependent protein kinase (DNA-PK). It binds the ends of various types of DNA discontinuity and is involved in the repair of DNA breaks caused by V(D)J recombination, isotype switching, physiological oxidation reactions, ionizing radiation and some chemotherapeutic drugs. The ku-dependent repair process, called non-homologous end joining, is the main DNA double strand break repair mechanism in irradiated mammalian cells. Results show that K-7/D-6 significantly increases DNA-binding activity of ku in irradiated PBMC from young but not from elderly subjects. However, K-7/D-6 is able to induce unscheduled DNA repair in irradiated PBMC from both young and elderly subjects. These effects of K-7/D-6 are relevant to the mechanisms of the cellular response to DNA damage.     

The nociceptin/orphanin FQ/NOP receptor system as a target for treatment of alcohol abuse: a review of recent work in alcohol-preferring rats

The intracerebroventricular administration of the 17 amino acid peptide nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the NOP receptor (previously referred to as ORL-1 or OP4 receptor), reduces voluntary 10% ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. Studies aimed at the pharmacological characterization of the receptor, which mediates the effect, have shown that the C-terminal 13 amino acid sequence is crucial for activity and that the selective NOP receptor antagonist [Nphe(1)]N/OFQ(1-13)NH(2) blocks the effect of N/OFQ on ethanol drinking. In place conditioning studies, N/OFQ abolishes the conditioned place preference (CPP) induced by ethanol in msP rats, or by morphine in nonselected Wistar rats; these findings suggest that N/OFQ is able to abolish the rewarding properties of ethanol and morphine. Moreover, N/OFQ inhibits reinstatement of alcohol-seeking behavior induced to electric footshock stress, as well as reinstatement of alcohol-seeking behavior induced by ethanol-paired cues. Together, these findings suggest that N/OFQ and its receptor may represent an interesting target for pharmacological treatment of alcohol abuse.