PERIPHERAL ARTERIOSCLEROSIS—Arterial Grafting Procedures—Indications and Results—Part II: Arteriosclerotic Arterial Occlusion

Arteriosclerotic thrombotic lesions involving the arteries to the lower extremities may be conveniently grouped into three categories. Lesions of the aorta-common-iliac level (Category I) appear to be most satisfactorily treated by thromboendarterectomy. Lesions in the femoral artery (Category II) are particularly amenable to bypass arterial grafts. Advanced lesions (Category III) involving both areas may be treated by one or the other method or a combination of both. Aortography is a necessary prerequisite in the selection of patients for operation and the determination of the method of surgical approach.     

On time dependency of frequency and distribution of chromatid aberrations induced by mutagens with delayed effects. An interpretation

This paper provides a theoretical analysis of pecularities of both the frequency and intrachromosomal distribution of chromatid aberrations observed in the first post-treatment mitosis and induced by clastogenic agents showing delayed effects (S-phase dependent clastogens), as functions of recovery time. The theoretical deductions are based on the following facts: (1) DNA is the target of clastogen action. Lesions induced by clastogens showing delayed effects (e.g. mono- and polyfunctional alkylating agents, ultraviolet light) give rise to aberrations only after interference with the process(es) associated with DNA replication. (2) DNA replication occurs asynchronously with respect to the local involvement in replication of different chromatin regions and according to a highly ordered pattern. (3) Lesions may be removed from DNA (or otherwise modified) by repair processes prior to replication. The removal of lesions from DNA is a time-dependent function.Several possibilities are analysed (i.e. random or non-random distribution of DNA lesions, uniform or locally differing capacities of pre-replicative repair of lesions, uniform or locally differing rates of DNA synthesis) and the frequencies and distribution patterns of chromosome structural changes, as expressed in form of aberration yield-time curves, have been discussed. The theory presented in this paper offers a simple interpretation both of variations of aberration frequency and aberration distribution in dependence on the cell's position within the cell cycle during induction of lesions.It is shown that the intrachromosomal aberration distribution is non-random even if random distribution of lesions and uniform repair rates between chromosome regions replicating at different time periods during S are assumed. Non-random aberration distributions are a necessary consequence of at least two factors: (a) the temporal replication pattern, and (b) the repair activities acting prior to replication. Random distribution of aberrations is only to be expected for the most simplified situation (random distribution of lesions along the DNA and equal transformation probabilities of a given kind of lesion into aberrations) when no loss of lesions prior to replication takes place (no pre-replicative repair) and cells treated with the mutagen during G1 are analysed.     

Traumatic, degenerative, and developmental lesions in wolves and coyotes from Saskatchewan.

A retrospective review was done of traumatic and osseous lesions in 241 wolves (Canis lupus) and 316 coyotes (Canis latrans) necropsied at the University of Saskatchewan between 1971 and 1990. Most lesions were the result of interspecific conflict. The most frequently occurring lesion in wolves was fracture of one or more bones, primarily ribs. Lesions were healed in most cases and appeared to be compatible with injuries caused by prey animals. One wolf, found dead, died as a result of thoracic trauma. Limb and skull fractures were less common. Fractures were uncommon in coyotes. The most frequent injuries in coyotes were related to gunshot wounds. Four coyotes had been killed but not eaten by wolves. One wolf had been killed and another attacked by wolves. Porcupine (Erethizon dorsatum) quills contributed to the death of a wolf and two coyotes. Degenerative joint disease, involving the spinal column and limb joints, was found in a few individuals of both species. A coyote had severe anomalies of the spinal column and a wolf had anomalous external genitalia.     

Lymphangioma. A long-term follow-up study.

At the Hospital for Sick Children 177 patients with lymphangioma, exclusive of those who had intra-abdominal lesions, were seen between 1927 and 1964. Forty-nine of these (aged 8 to 41 years) were available for follow-up examination. The results of treatment by surgical excision, aspiration, incision and drainage, and radiation are reported. No cases confirmed histologically as lymphangioma underwent spontaneous regression. Two histologically unconfirmed cases underwent partial regression. Four of the 11 who were left with lymphangioma tissue at operation never had significant recurrences. Therefore, this clinical study does not clarify the possible role of spontaneous regression in lymphangioma. Extensive surgery is the treatment of choice whenever feasible, but in unilocular or bilocular cystic lymphagnioma subsequent regression can be expected after palliative treatment (aspiration, or incision and drainage). Clinical and pathological criteria should be established for differentiation between lymphangioma and primary lymphedema. Lesions involving subepithelial, subdermal, and subcutaneous or internodal networks of lymphatics will produce lymphagioma; lesions of the collecting lymphatic trunks will result in lymphedema.     

The use of tumors in wild populations of fish to assess ecosystem health

Evidence has linked toxicants in aquatic systems with cancer in fish and population level effects on species. Thus some types of tumors may be useful monitors of ecosystem health, at least as affected by genotoxins and promoters. However, tumors caused by purely genetic mechanisms or by virus would not be good indicators. Only neoplasms which have chemicals as a portion of their etiology (either as initiators or promoters) would be useful in assessing ecosystem health. Lesions which may fit these criteria include liver neoplasms (both biliary and hepatic) and skin lesions in a variety of primarily benthic fishes, and neural lesions in various drum species and in butterfly fish species. Two studies purporting to demonstrate a lack of tumors in fish from polluted areas have been reexamined and found either to have insufficient data on vulnerable species or to actually support a tumor-pollution linkage. Thus certain lesions in vulnerable species or species groups may serve as a mechanism to assess one facet of ecosystem health.     

Environmental factors affecting tissue regeneration of the reef--building coral Montastraea annularis (Faviidae) at Los Roques National Park,Venezuela

In this study, the rates of tissue regeneration and recovery from injuries that emulated the bites of either butterfly or parrotfish on colonies of Montastraea annularis exposed to different sedimentation regimesp were determined. Two small reef patches were chosen close to key Dos Mosquises, north of the Venezuclan mainland. Sixteen colonies (8 treatments + a single replicate) were artificially damaged at each patch and their recovery was monitored for three months by photographic means. The lesions were inflicted using two different techniques: scratching the polyps with a hard-nylon brush to resemble parrotfish (Scaridae) damages (Lesions Type 1) or jetting out the tissue with a syringe to simulate butterflyfish (Chaetondontidae) bites (Lesions Type 2). The diameter of the wounds ranged from 5 (small lesion) to 8 cm (large lesions) and both kinds were inflicted on the top and bottom of the colonies, with a single replicate for each treatment. The main factors affecting the recovery of the colonies' surface were lesion features (type, position and size), turbidity and chiefly, the sedimentation rate. While lesion recovery was slow where sedimentation and resuspension rates were high, tissue regeneration was improved under low sedimentation and resuspension conditions. Moreover, lesions located at the bottom of colonies regenerated completely, whereas sediments frequently covered top lesions and limited their recovery. More than 60% of the colonies with small lesions recovered almost completely in less than 90 days, whereas those with larger injuries frequently showed extensions of their damage and increased mortality. Tissue-only lesions (LT2) regenerated two to three times faster than those involving both tissue and skeletal damage (LT1). Other variables not controlled in this study, such as diseases, encrusting organisms overgrowth and herbivory introduced further variability to the regeneration rates.     

Treatment of Basal Cell Carcinoma by Curettage and Electrosurgery

One hundred and forty-eight basal cell carcinomas were treated by curettage and electrosurgery. Twenty-six recurrent carcinomas were treated and 24 did not recur during a minimum two-year follow-up. Seventy-two newly diagnosed carcinomas were treated by the same method, and a two-year recurrence-free rate of 97.4% was obtained. About 50 new and recurrent lesions were treated in three patients in whom extensive cutaneous changes from actinic atrophy and previous therapy made the distinction between new and recurrent lesions difficult or impossible. This technique has a particular place in the management of multiple lesions. Patient acceptance is good. Lesions at some sites, e.g. on the nose, where closure of a wound is difficult, are better managed by this method than by surgical excision. Secondary infection is rare and the cosmetic results are excellent.     

Effects of preoptic and hypothalamic lesions in female turkeys during a photoinduced reproductive cycle

Prolactin (Prl) is released by electrical stimulation in the turkey hypothalamus and preoptic area (POA). Possible trajectories for POA efferents to the median eminence (ME) were tested by placing lesions in the POA, the lateral hypothalamus (LHy), or the ventromedial nucleus of the hypothalamus (VMN) of reproductively quiescent turkey hens, then subjecting them to long photoperiods while monitoring their blood Prl levels and nesting activities. In addition, lesions were made in the VMN of a group of incubating hens to learn whether the lesions would cause the elevated Prl levels to fall or interfere with incubation behavior. Lesions in medial POA, LHy, or VMN prevented the onset of incubation and prevented the large rise in Prl associated with it. However, these lesions did not interfere with the initial, more gradual Prl rise caused by increasing daylengths. Lesions in LHy or VMN appeared to interfere with a pathway lying laterally from POA to ME. Electrical stimulation in medial POA, which caused an increase in circulating Prl, failed to do so in hens with LHy or VMN lesions. Lesions in the VMN of incubating hens caused them to leave the nest and suffer a large decline in Prl, both within 48 h. It is tentatively suggested that incubation behavior and its associated elevated Prl are prevented by the POA lesions and that lesions in LHy or VMN, which mimic POA lesion effects, interfere with POA efferents projecting to ME.     

Results of irradiation in cancer of the lip,tongue and ear

CANCER OF THE LIP: The primary lesion can be controlled by irradiation in approximately 80 per cent of cases. For lesions with metastases there is only about a 25 per cent chance of five-year arrest (irradiation of the primary lesion followed by excision of involved nodes). CANCER OF THE TONGUE: Lesions in the anterior two-thirds are controllable by irradiation in about 50 per cent of cases if the nodes are not involved; the salvage is only about 15 per cent if the nodes are involved (nodes treated surgically). Lesions in the posterior third of the tongue are seldom controlled in the author's experience. CANCER OF THE EAR (AURICLE): Five-year arrest of basal-cell lesions should be attained by irradiation in about 80 per cent of cases; of squamous-cell lesions in about 60 per cent. If the lesion is extensive, radiation does not offer a superior cosmetic result to operation and entails danger of late chondronecrosis. Therefore extensive lesions are probably best treated surgically. In either event, it appears probable that results of irradiation can be improved by the use of more adequate fields and greater fractionation.     

RESULTS OF IRRADIATION IN CANCER OF THE LIP,TONGUE AND EAR

Cancer of the lip: The primary lesion can be controlled by irradiation in approximately 80 per cent of cases. For lesions with metastases there is only about a 25 per cent chance of five-year arrest (irradiation of the primary lesion followed by excision of involved nodes).Cancer of the tongue: Lesions in the anterior two-thirds are controllable by irradiation in about 50 per cent of cases if the nodes are not involved; the salvage is only about 15 per cent if the nodes are involved (nodes treated surgically). Lesions in the posterior third of the tongue are seldom controlled in the author''s experience.Cancer of the ear (auricle): Five-year arrest of basal-cell lesions should be attained by irradiation in about 80 per cent of cases; of squamous-cell lesions in about 60 per cent. If the lesion is extensive, radiation does not offer a superior cosmetic result to operation and entails danger of late chondronecrosis. Therefore extensive lesions are probably best treated surgically. In either event, it appears probable that results of irradiation can be improved by the use of more adequate fields and greater fractionation.     

The effect of raphe nuclei lesions on the rat ovarian cycle

The effects of lesions of the median raphe or dorsal raphe nuclei on ovarian cycle were studied in rats. Lesions involving raphe nuclei decreased forebrain 5-HT and 5-hydroxyindole acid (5-HIAA) concentrations. Rats with lesions of the raphe showed prolonged estrous phase as well as an increase in both the eosinophilic index and karyopycnotic index of the vaginal smears. Histological examinations revealed that lesions of both the dorsal and median raphe produced marked increase in the number of maturing and mature follicles as well as an increase in corpora lutea. The increase in uterine weight was also observed. Present results indicate that lesions of the ascending 5-HT neurons stimulate ovulation and cause an increase in the estrogenic activity. Thus, the 5-HT neurons of the raphe nuclei seem to inhibit ovulation probably due to inhibiting of the hypothalamic releasing hormones.     

Mycobacterium avium-related epizootic in free-ranging lesser flamingos in Kenya

An epizootic in free-ranging lesser flamingos (Phoeniconaias minor) in Kenya resulted in more than 18,500 deaths from August through mid-November 1993. Disease was concentrated along the shores of Rift Valley Lakes Bogoria and Nakuru (Kenya) and did not involve any of the other avian or mammalian species frequenting the lakes. Coincidental to the outbreak was a bloom of algae on Lake Bogoria, toxins from which were first suspected to be causative. Discrete necrotic and granulomatous lesions were often noted in spleen and liver, and Mycobacterium avium serovar I was isolated from both organs. Escherichia coli and Pseudomonas aeruginosa also were often recovered in pure culture from liver. Gross and histopathological evaluation of the cases disclosed signs of acute sepsis and also chronic, potentially life-threatening lesions of mycobacteriosis, primarily involving the spleen and liver. Lesions typical for algae toxicosis were not seen in any birds. Deaths were attributed to septicemia complicated in those affected, by mycobacteriosis.     

Evidence for centers in the central nervous system that regulate fat mobilization in dogs

Infusions of 2-deoxyglucose (2-DG) into intact, adrenalectomized, and adrenalectomized-hypophysectomized dogs caused increases in plasma free fatty acid (FFA) levels which could be reversed by infusing hexamethonium, or prevented by epidural anesthesia or destruction of the thoracic spinal cord. Similar infusions of 2-DG were given to adrenalectomized dogs after transection of the spinal cord. Lesions between C 4 and T 7 prevented the increase in FFA while lesions at T 8 or C 2-3 did not. These results indicate that inhibition of glucose metabolism by 2-DG causes an increase in plasma FFA by a pathway involving the sympathetic nervous system and that there are centers regulating this activity in the cervical portion of the spinal cord.     

Avipox sp. in a colony of gray-crowned rosy finches (Leucosticte tephrocotis)

Members of a wild-caught colony of 16 gray-crowned rosy finches (Leucosticte tephrocotis) were presented with dermal and mucosal lesions, anorexia, emaciation, lethargy, and sudden death. Lesions included dermatitis, conjunctivitis, and glossitis. Skin scrapings from and bacterial culture of dermal lesions yielded Staphylococcus aureus and Candida albicans. Necropsy and histologic examination revealed characteristic epidermal and mucosal pox lesions, with the presence of characteristic Bollinger body intracellular inclusions. Electron microscopy (EM) provided confirmation of pox virus infection. This epornitic resulted in the death or euthanasia of 12 birds (75% morbidity and associated mortality) and was brought to conclusion through culling of affected birds. The source of infection remains unknown, although multiple modes of introduction exist. Similar epornitics may be prevented through indoor, species-specific housing, and quarantine. Vaccination and antiparasitic treatment may reduce the risk of disease spread.     

Influence of template strandedness on in vitro replication of mutagen-damaged DNA

We analyzed the ability of DNA polymerases to bypass damage on single- and double-stranded templates. In vitro DNA synthesis was studied on UV-irradiated and polyaromatic hydrocarbon reacted (benzo[a]pyrenediol epoxide and oxiranylpyrene) double-stranded templates by a protocol involving initiation on a uniquely nicked circular double-stranded template. The template was prepared by treating single-stranded (+)M13mp2 circular strands with mutagen and then hybridizing with restricted M13 RFmp2, followed by isolation of the nicked RFII forms. The protocol permits either (+), (-), or both strands to carry lesions. We found that the rules for termination and bypass of lesions previously observed with single-stranded DNA templates also hold for double-stranded templates. Termination of synthesis occurs primarily one nucleotide 3' to the lesion in the template strand. Bypass of UV-induced lesions can be followed in a series of three partial reactions in the presence of Mn2+ and dGMP, which relax the specificity of nucleotide insertion and 3'----5' exonuclease activity, respectively. There is no evidence for greater permissivity of bypass in double-as opposed to single-stranded templates. As with single-stranded templates, purines and preferentially deoxyadenosine (dA) are inserted opposite lesions. Lesions in the nontemplate strand elicit neither termination nor pausing. The addition of Rec A protein resulted in a measurable increase of bypass in this system.     

Regulatory affairs and biotechnology in Europe II.

This paper describes the EEC regulatory requirements for the preparation and execution of a community concertation "High Tech" procedure and compares this "High Tech" procedure with the Multi-State procedure. According to a decision of the European Commission enforced in July 1987, medicinal products, derived from high technology methods have been grouped in two categories: A. and B. Category A. concerns biotechnology products made by R-DNA techniques and by manipulation of mammalian cells. Category B. comprises all other products made by high technology. Before applying for an EEC marketing licence (e.g. submission for registration) one must ascertain whether a product is most appropriate in Category A. or B. and one should contact a licencing authority at an early stage to discuss the planned submission. Various procedures for submission have to be followed: 1. for the so-called "High Tech" products and especially products derived from biotechnology with therapeutic applications (Category A.), it is mandatory that one of the Member States accepts the submission. 2. The "High Tech" procedure is derived from the so-called "2-country" (Multi-State) procedure, in which for the latter procedure a marketing licence in one of the Member States (except Portugal) is required before application in other Member States. The Multi-State and "High Tech" (other products: Category B.) procedures are optional. When the procedures are started, all Member States concerned are involved in evaluation of full or abbreviated dossiers through mediation of the European Commission represented by the CPMP (Committee for Proprietary Medicinal Products), Brussels, Belgium. No application for a marketing licence of Category A. products is allowed without mediation of the CPMP. For Category B. products the applicant may opt for a national submission in one or more of the Member States without using the "High Tech" procedure. However, after consultation with the competent authority in one of the Member States, a "High Tech" procedure for Category B. products might still be advisable, but the applicant is not required to follow this procedure. Both the "High Tech" and the Multi-State procedure are currently executed by the mediation of a rapporteur, who liaises with the applicant from the start of the "High Tech" procedure. Ideally, the applicant should contact a licencing authority some 6 to 9 months before an application is planned: to ensure that the near future submission is acceptable. The institution of a rapporteur (appointed by the licencing authority in the country from where the procedure has recently been established) is introduced for the Multi-State procedure.(ABSTRACT TRUNCATED AT 400 WORDS)     

Exertional myopathy in translocated river otters from New York.

Lesions consistent with exertional myopathy (EM) were documented postmortem in four North American river otters (Lutra canadensis) during translocation for a population restoration project. Clinical signs in these otters included depression, anorexia and shock. Gross lesions in one otter included locally extensive linear, pale areas within the subscapularis, rectus abdominis, quadriceps, and dorsal laryngeal muscles. Microscopic lesions were characterized by acute to subacute myofiber necrosis of varying severity, and occurred in a variety of skeletal muscles as well as cardiac muscle in one otter. Based on these observations, we conducted a retrospective review of records of otters which experienced similar capture, transfer, and holding protocols between 1995 and 1997, but with a successful outcome (n = 69). Significant elevations in serum aspartate aminotransferase (AST) and creatine kinase (CK) were observed in 19 (28%) of the otters, but may have been higher due to delayed sample collection from some otters. However, none of the otters with elevated enzymes exhibited clinical signs suggestive of EM. These findings indicate that river otters may develop EM when translocated, but many cases may be mild or clinically inapparent.     

Release of macromolecular markers (enzymes) from liposomes treated with antibody and complement: An attempt at correlation with electron microscopic observations

Antibody-complement dependent damage to liposomal model membranes has been previously investigated by measuring the release of low molecular weight markers such as glucose. To determine whether larger solutes are also released under these conditions, experiments have been performed using immunologically sensitive liposomes that contained not only trapped glucose, but also enzymes (hexokinase, glucose-6-phosphate dehydrogenase, β-galactosidase) as macromolecular markers. The largest of these enzymes (β-galactosidase) has dimensions which closely approximate the diameter of the lesions detected by negative staining in natural membranes after immune lysis. Liposomes prepared with lecithin, and either actively sensitized with globoside or passively sensitized with alkali-treated lipopolysaccharide, released the enzymes in parallel with glucose upon incubation with the appropriate antiserum and native guinea pig serum as source of complement. Immune damage to sphingomyelin liposomes was characterized by a significantly lower loss of the enzymes in comparison to the percentage of glucose released; a comparable response was manifested by liposomes prepared from sheep erythrocyte lipids. Electron microscopic examination of negatively stained lecithin liposomes, which had released the macromolecular markers, failed to reveal the characteristics lesions; these findings are consistent with evidence obtained by other laboratories suggesting that the lesions may not correspond to functional holes. Lesions were, however, consistently observed in liposome preparations that had been treated with the polyene antibiotics, filipin; this antibiotic causes appreciable loss of both glucose and enzymes from either lecithin or sphingomyelin liposomes.     

Striatal Damage and Oxidative Stress Induced by the Mitochondrial Toxin Malonate Are Reduced in Clorgyline-Treated Rats and MAO-A Deficient Mice

Intrastriatal administration of the succinate dehydrogenase (SDH) inhibitor malonate produces neuronal injury by a "secondary excitotoxic" mechanism involving the generation of reactive oxygen species (ROS). Recent evidence indicates dopamine may contribute to malonate-induced striatal neurodegeneration; infusion of malonate causes a pronounced increase in extracellular dopamine and dopamine deafferentation attenuates malonate toxicity. Inhibition of the catabolic enzyme monoamine oxidase (MAO) also attenuates striatal lesions induced by malonate. In addition to forming 3,4-dihydroxyphenylacetic acid, metabolism of dopamine by MAO generates H2O2, suggesting that dopamine metabolism may be a source of ROS in malonate toxicity. There are two isoforms of MAO, MAO-A and MAO-B. In this study, we have investigated the role of each isozyme in malonate-induced striatal injury using both pharmacological and genetic approaches. In rats treated with either of the specific MAO-A or -B inhibitors, clorgyline or deprenyl, respectively, malonate lesion volumes were reduced by 30% compared to controls. In knock-out mice lacking the MAO-A isoform, malonate-induced lesions were reduced by 50% and protein carbonyls, an index ROS formation, were reduced by 11%, compared to wild-type animals. In contrast, mice deficient in MAO-B showed highly variable susceptibility to malonate toxicity precluding us from determining the precise role of MAO-B in this form of brain damage. These findings indicate that normal levels of MAO-A participate in expression of malonate toxicity by a mechanism involving oxidative stress.     

Brown spot disease of citrus caused by Phaeoisariopsis sp.

Brown spot disease of Citrus spp. was shown to be caused by Phaeoisariopsis sp. It severely affects all varieties of sweet orange, tangerine, grapefruit, lime and rough lemon, smooth lemon being relatively resistant. Fruits and leaves are much more susceptible than stems on which symptoms are rare. On the young fruit circular, slightly sunken, brown necrotic lesions are often associated with a surrounding ring of raised epicarp, giving the fruit a blistered appearance. Lesions on older fruits are usually flat and brown and surrounded by yellow haloes. Premature abscission, especially of young fruits, is common. Leaf symptoms start as greenish yellow patches and a fully formed leaf spot consists of light brown or greyish centre which is surrounded by a dark brown margin bordered by a yellow halo. Generalised foliar chlorosis, caused by coalescence of several lesions, culminates in premature defoliation. During wet weather, centres of both fruit and foliar lesions sporulate and become black. Stem lesions, dark brown and mostly occurring as extensions of petiole lesions, may coalesce causing stem die-back or resulting in the formation of corky internodal lesions. In artificial culture, the fungus sporulated only on media containing an extract of citrus leaf or fruit peel. The characteristics of the fungus mostly based on examination of structures formed on naturally infected parts of the plant, are described. This is probably the first report of a Phaeoisariopsis sp. on citrus.