Microarray analysis of healing rat Achilles tendon: evidence for glutamate signaling mechanisms and embryonic gene expression in healing tendon tissue.

Tendon healing is a complex process consisting of a large number of intricate pathways roughly divided into the phases of inflammation, proliferation, and remodeling. Although these processes have been extensively studied at a variety of levels in recent years, there is still much that remains unknown. This study used microarray analyses to investigate the process at a genetic level in healing rat Achilles tendon at 1, 7, and 21 days postinjury, roughly representing the inflammation, proliferation, and remodeling phases. An interesting temporal expression profile was demonstrated, identifying both known and novel genes and pathways involved in the progression of tendon healing. Both inflammatory response and pro-proliferative genes were shown to be significantly upregulated from 24 h postinjury through to 21 days. Day 7 showed the largest increase in genetic activity, particularly with the expression of collagens and other extracellular matrix genes. Interestingly, there was also evidence of central nervous system-like glutamate-based signaling machinery present in tendon cells, as has recently been shown in bone. This type of signaling mechanism has not previously been shown to exist in tendon. Another novel finding from these analyses is that there appears to be several genes upregulated during healing which have exclusively or primarily been characterized as key modulators of proliferation and patterning during embryonic development. This may suggest that similar pathways are employed in wound healing as in the tightly regulated progression of growth and development in the embryo. These results could be of use in designing novel gene-based therapies to increase the efficacy and efficiency of tendon healing.     

Impact of the black fly (Diptera: Simuliidae) control agent Bacillus thuringiensis var. israelensis on chironomids (Diptera: Chironomidae) and other nontarget insects: results of ten field trials.

Except for moderate mortality among filter-feeding chironomids, Rheotanytarsus spp., the results of 10 field trials with Bacillus thuringiensis var. israelensis (B.t.i.) indicated a wide margin of safety to the chironomid community and other stream nontarget insects. Mayflies, caddisflies and 2 other types of chironomids, i.e., tube-dwelling (Chironominae) and surface-dwelling, caseless larvae (mix of Chironominae, Diamesinae, Orthocladiinae, Tanypodinae), did not appear to be affected. The susceptibility of filter-feeding chironomids was considerably less than black flies; for example, 4 months of data collected during an operational black fly control program indicated a mean (+/- 95% CI) mortality among Rheotanytarsus larvae of 23 (15-32)% vs. 98 (97-99)% among black flies. Although clearly demonstrating the potential of adverse impact on filter-feeding chironomids in operational black fly programs, these trials also confirmed the narrow impact of B.t.i. on the overall stream insect community.     

The information needs of women newly diagnosed with breast cancer

Nurses can play a key role in patient education, including providing patients with useful and approrate information Rather than focusing on the process of education or information giving by nurses, this study places emphasis on the content of that information by taking the patients'perspective and asking the patients themselves what particular types of information are perceived as important at a specific point in time The aim of the study was to explore what particular types of information were important to women newly diagnosed with breast cancer, to enable nurses and other health care professionals to utilize their time as effectively as possible and provide a high-quality service to individuals in their care Women with breast cancer (a mean of 2 5 weeks from diagnosis) were interviewed and asked to compare items of information The items of information were presented m pairs and the women stated a preference for one item in that pan- Thirty-six pairs were presented in total The analysis involved the use of a Thurstone scaling model, which allowed rank ordermgs, or profiles of information needs, to be developed, reflecting the perceived importance of each item Information about the likelihood of cure, the spread of the disease and treatment options were perceived as the most important items of information at the tune of diagnosis Other information needs, in order of descending priority, included information about the risk to family, side-effects     

The effect of ionic strength on the kinetics of rigor development in skinned fast-twitch skeletal muscle fibres

 Recent atomic 3-D reconstructions of the acto-myosin interface suggest that electrostatic interactions are important in the initial phase of cross-bridge formation. Earlier biochemical studies had also given strong evidence for the ionic strength dependence of this step in the cross-bridge cycle. We have probed these interactions by altering the ionic strength (Γ/2) of the medium mainly with K⁺, imidazole⁺ and EGTA^2– to vary charge shielding. We examined the effect of ionic strength on the kinetics of rigor development at low Ca²⁺ (experimental temperature 18–22°C) in chemically skinned single fast-twitch fibres of mouse extensor digitorum longus (EDL) muscle. On average the delay before rigor onset was 10 times longer, the maximum rate of rigor tension development was 10 times slower, the steady-state rigor tension was 3 times lower and the in-phase stiffness was 2 times lower at high (230 mM) compared to low (60 mM) ionic strength. These results were modelled by calculating ATP depletion in the fibre due to diffusional loss of ATP and acto-myosin Mg.ATPase activity. The difference in delay before rigor onset at low and high ionic strength could be explained in our model by assuming a 15 times higher Mg.ATPase activity and a threefold increase in K _m in relaxing conditions at low ionic strength. Activation by Ca²⁺ induced at different time points before and during onset of rigor confirmed the calculated time course of ATP depletion. We have also investigated ionic strength effects on rigor development with the activated troponin/tropomyosin complex. ATP withdrawl at maximum activation by Ca²⁺ induced force transients which led into a ”high rigor” state. The peak forces of these force transients were very similar at low and high ionic strength. The subsequent decrease in tension was only 10% slower and steady-state ”high rigor” tension was reduced by only 27% at high compared to low ionic strength. Addition of 10 mM phosphate to lower cross-bridge attachment strongly suppressed the transient increases in force at high ionic strength and reduced the steady-state rigor tension by 17%. A qualitatively similar but smaller effect of phosphate was observed at low ionic strength where steady-state rigor force was reduced by 10%. The data presented in this study show a very strong effect of ionic strength on rigor development in relaxed fibres whereas the ionic strength dependence of rigor development after thin filament activation was much less. The data confirm the importance of electrostatic interactions in cross-bridge attachment and cross-bridge-attachment-induced activation of thin filaments. Received: 3 September 1997 / Received after revision and accepted: 12 December 1997     

Neurofibromatosis type 1: brain stem tumours

We describe the clinical and imaging findings of brain stem tumours in patients with neurofibromatosis type 1 (NF1). The NF1 patients imaged between January 1984 and January 1996 were reviewed and 25 patients were identified with a brain stem tumour. Clinical, radiographical and pathological results were obtained by review of records and images. Brain stem tumour identification occurred much later than the clinical diagnosis of NF1. Medullary enlargement was most frequent (68 %), followed by pontine (52 %) and midbrain enlargement (44 %). Patients were further subdivided into those with diffuse (12 patients) and those with focal (13 patients) tumours. Treatment for hydrocephalus was required in 67 % of the first group and only 15 % of the second group. Surgery was performed in four patients and revealed fibrillary astrocytomas, one of which progressed to an anaplastic astrocytoma. In 40 % of patients both brain stem and optic pathway tumours were present. The biological behaviour of brain stem tumours in NF1 is unknown. Diffuse tumours in the patients with NF1 appear to have a much more favourable prognosis than patients with similar tumours without neurofibromatosis type 1. Received: 21 November 1996 Accepted: 22 December 1996     

A modified technique of delayed primary closure using a povidone iodine wick: Influence on wound healing in an experimental model

We report a modified technique of delayed primary wound closure using a wound wick. A rodent model was used to determine its influence on healing. After loose primary closure of two paravertebral incisions on the dorsum of male rats, a 10 cm length of ribbon gauze, soaked in either saline or 1% povidone-iodine, was inserted into the right sided wound. Wicks were soaked daily with the same solution until removal on the third post-operative day. The inclusion of a wick soaked in saline had an early transient effect on healing. A more prolonged impairment of healing was demonstrated in povidone-iodine wicked wounds and their respective controls. These data suggest that povidone-iodine impaired healing not only in the wicked wound, but also inhibited healing in the adjacent unwicked wound which was not directly exposed to the antiseptic. The observed delay in healing in povidone-iodine wicked wounds must however be balanced against its beneficial effect on wound infection rates. We suggest that further evaluation of this method of closure in contaminated wounds is warranted.     

Human neural transplantation

Great advances in neurobiology have resulted from 100 years of neural transplantation research. In the last 20 years, there has been a focus on using neural transplantation to repair the damaged central nervous system (CNS) utilising experimental animal models of various human neurodegenerative disease and CNS injury. Since 1985, there has been a rapid proliferation of adrenal medullary autograft transplantation to the caudate nucleus of humans with Parkinson's disease. However, this operation proved to be unsuccessful and was associated with unacceptable morbidity. Implantation of human fetal mesencephalon into patients with severe parkinsonism has supplanted the adrenal operation and has produced promising results, with some patients reported to improve markedly and some evidence of graft survival noted on positron emission tomography (PET). Host tissue recovery appears to be an important mechanism for this clinical improvement. The optimal technique is to use three to four fetuses from induced abortions of 6.5 to 8 weeks gestation, with multiple stereotactic implants into the putamen and caudate nucleus. Many biological questions still remain and the community remains troubled by the ethical problems of using fetal tissue obtained from abortions. This procedure is still experimental and should be restricted to a few centres with excellence in cell and molecular biology. A multicentre study is needed to more carefully evaluate CNS transplantation. Cloned neural precursor cells or immortalized embryonic cell lines genetically modified to manufacture selected growth factors or neurotransmitters may offer an alternative to the use of human fetal tissue. Much more experimental animal research is necessary before transplantation can be used to treat other CNS maladies.     

Ninety-Six Five-Year Survivors After Liver Resection for Metastatic Colorectal Cancer

Background: Studies have consistently confirmed the benefit of liver resection for metastatic colorectal cancer. Few reports, however, have a long enough followup or sufficient 5-year survivors to study the clinical course of patients beyond 5 years.

Study Design: From July 1985 through December 1991, 456 patients underwent liver resection for colorectal metastases. Ninety-six actual 5-year survivors (21%) were identified and their clinical course retrospectively reviewed.

Results: Five-year survivors (n = 96) were more likely to have a Duke’s B primary colorectal carcinoma, fewer than four metastatic lesions, unilobar disease, and a negative histologic margin when compared with patients not surviving 5 years (n = 298). Forty-four (46%) of the 96 five-year survivors had a recurrence after hepatectomy. Of these 44, 19 (43%) were rendered disease free after further treatment. Overall, 71 of the 96 five-year survivors were free of disease at last followup. The actuarial 10-year survival of this group was 78%.

Conclusions: Patients that are disease free 5 years after liver resection are likely to have been cured by liver resection. Patients should be aggressively followed for recurrence because of the potential for further treatment and longterm survival.     

Recurrent Ectopic Pregnancy Following Repeat Sterilization

EDITORIAL COMMENT: We accepted this case for publication not only because of its rare anecdotal interest but to remind readers that sterilization can fail even when performed competently. That this occurred twice in the same patient is extraordinary.