Finite element modelling of the surgical procedure for placement of a straight electrode array: Mechanical and clinical consequences.

A cochlear implant is an electronic device implanted into the cochlea to directly stimulate the auditory nerve. Such device is used in patients with severe-to-profound hearing loss. The cochlear implant surgery is safe, but involves some risks, such as infections, device malfunction or damage of the facial nerve and it can result on a poor hearing outcome, due to the destruction of any present residual hearing. Future improvements in cochlear implant surgery will necessarily involve the decrease of the intra-cochlear damage. Several implant related variables, such as materials, geometrical design, processor and surgical techniques can be optimized in order for the patients to partially recover their hearing capacities The straight electrode is a type of cochlear implant that many authors indicate as being the less traumatic. From the finite element analysis conducted in this work, the influence of the insertion speed, the friction coefficient between the cochlear wall and the electrode array, and several configurations of the cochlear implant tip were studied. The numerical simulations of the implantation showed the same pattern of the insertion force against insertion depth, thus indicating the different phases of the insertion. Results demonstrated that lower insertion speeds, friction coefficients and tip stiffness, led to a reduction on the contact pressures and insertion force. It is expected that these improved configurations will allow to preserve the residual hearing while reducing surgical complications.

The human otitis media with effusion: a numerical-based study.

Otitis media is a group of inflammatory diseases of the middle ear. Acute otitis media and otitis media with effusion (OME) are its two main types of manifestation. Otitis media is common in children and can result in structural alterations in the middle ear which will lead to hearing losses. This work studies the effects of an OME on the sound transmission from the external auditory meatus to the inner ear. The finite element method was applied on the present biomechanical study. The numerical model used in this work was built based on the geometrical information obtained from The visible ear project. The present work explains the mechanisms by which the presence of fluid in the middle ear affects hearing by calculating the magnitude, phase and reduction of the normalized umbo velocity and also the magnitude and phase of the normalized stapes velocity. A sound pressure level of 90 dB SPL was applied at the tympanic membrane. The harmonic analysis was performed with the auditory frequency varying from 100 Hz to 10 kHz. A decrease in the response of the normalized umbo and stapes velocity as the tympanic cavity was filled with fluid was obtained. The decrease was more accentuated at the umbo.

Intraocular pressure, ultrasonographic and echobiometric findings of juvenile Yacare caiman (Caiman yacare) eye.

OBJECTIVE: The aim was to determine the intraocular pressure (IOP), the ultrasonographic and echobiometric findings in the eyes of juvenile Yacare caiman (Caiman yacare). ANIMALS: Twenty-two healthy caimans from a breeding farm in Brazilian Pantanal. PROCEDURES: Intraocular pressure was measured under physical restraint and topical anesthesia by applanation tonometry. Five individual measurements of each eye were recorded by the same examiner. B-mode ultrasonography was performed with a 10-MHz linear transducer, and the anterior chamber depth, lens thickness, vitreous depth, and axial globe length were measured. Unpaired and paired t-tests were used to assess data. Pearson's test was used to assess correlations between IOP and ocular structures (P < 0.05). RESULTS: Mean ± SD IOP of the 44 eyes studied was 9.56 ± 2.69 mmHg, (range 5.4-15.6 mmHg). IOP did not differ significantly between right and left eyes or between genders (P > 0.05). Echobiometric measurements did not differ significantly between eyes and genders (P > 0.05). Intraocular structures measured in male and female subjects were, respectively, 2.61 ± 0.13 and 2.55 ± 0.18 mm for anterior chamber depth, 7.60 ± 0.17 and 7.54 ± 0.20 mm for lens thickness, 6.83 ± 0.20 and 6.90 ± 0.22 mm for vitreous chamber depth, and 17.55 ± 0.25 and 17.54 ± 0.29 mm for axial globe length. Correlations were not observed (P > 0.05). CONCLUSION: Reference values of tonometry and distances of intraocular structures of Yacare caiman were described. IOP did not correlate with echobiometric measurements in this crocodilian. The ultrasonographic appearance was similar to other domestic and wild species.

Attitudes of Swiss veterinarians towards pain and analgesia in dogs and cats.

A survey was performed to evaluate the use of perioperative analgesia in dogs and cats by veterinary practitioners. Questions were grouped in seven sections recording personal data, education in veterinary analgesia, general ideology regarding treatment of perioperative pain, personal experience, assessment, and use of main analgesics to treat perioperative pain. A total of 258 received forms were analyzed. Based on 5 questions, 88 % showed excellent motivation to use perioperative pain therapy. The main reason declared for the use of analgesics was to relieve the patient from pain (64.1 %). Most veterinarians reported to routinely administer analgesics before (71 - 96 %) or after (2 - 23 %) surgery. The most used analgesics were non-steroidal anti-inflammatory drugs (carprofen, meloxicam) and opioids (butorphanol, buprenorphine). Animals were routinely evaluated for pain after recovery. Only 43.8 % of veterinarians declared to use loco-regional anaesthesia. Swiss veterinarians appear to recognize well the need for perioperative pain treatment. However, weakness was shown in evaluating pain severity, distinguishing between opioid classes, and using loco-regional anaesthesia.

En 2010 un questionnaire sur le thème de l'analgésie péri-opératoire chez le chien et le chat, divisé en sept chapitres, a été envoyé à 1000 vétérinaires suisses. Outre les données personnelles et les informations relatives aux formations suivies en matière de traitement de la douleur, on s'est intéressé aux conceptions personnelles quant à la lutte contre la douleur, aux expériences faites dans cette lutte ainsi qu'à l'utilisation des principaux analgésiques. Au total, ce sont 258 questionnaires qui ont été analysés. Chez 88 % des personnes, la motivation à utiliser des analgésiques lors d'opérations était élevée. La raison principale de cette utilisation était la réduction des douleurs (64.1 %). La plupart des vétérinaires déclaraient administrer des antalgiques avant (71 ­ 96 %) ou après (2 ­ 23 %) l'intervention. Il s'agissait principalement d'anti-inflammatoires non stéroïdiens (Carprofène, Meloxicam) et d'opioïdes (Butorphanol, Buprénorphine). Après guérison, 97 % des animaux étaient contrôlés de façon routinière par les vétérinaires quant aux douleurs. 43.8 % des vétérinaires utilisaient des techniques d'anesthésie locorégionales. En Suisse, la profession vétérinaire a reconnu la nécessité d'une antalgie péri-opératoire. Toutefois les différences d'intensité douloureuse prévisibles selon les opérations de même que les différences entre les diverses classes d'opioïdes sont estimées différemment de ce qu'on prévoyait. Les techniques d'anesthésie locorégionales sont relativement peu utilisées.

The influence of the mechanical behaviour of the middle ear ligaments: a finite element analysis.

The interest in computer modelling of biomechanical systems, mainly by using the finite element method (FEM), has been increasing, in particular for analysis of the mechanical behaviour of the human ear. In this work, a finite element model of the middle ear was developed to study the dynamic structural response to harmonic vibrations for distinct sound pressure levels applied on the eardrum. The model includes different ligaments and muscle tendons with elastic and hyperelastic behaviour for these supportive structures. Additionally, the nonlinear behaviour of the ligaments and muscle tendons was investigated, as they are the connection between ossicles by contact formulation. Harmonic responses of the umbo and stapes footplate displacements, between 100 Hz and 10 kHz, were obtained and compared with previously published work. The stress state of ligaments (superior, lateral, and anterior of malleus and superior and posterior of incus) was analysed, with the focus on balance of the supportive structures of the middle ear, as ligaments make the link between the ossicular chain and the walls of the tympanic cavity. The results obtained in this work highlight the importance of using hyperelastic models to simulate the mechanical behaviour for the ligaments and tendons.

Pre-zygotic factors best explain reproductive isolation between the hybridizing species of brittle-stars Acrocnida brachiata and A. spatulispina (Echinodermata: Ophiuroidea).

The two brittle-stars Acrocnida brachiata (Montagu 1804) and A. spatulispina (Stöhr and Muths in J Mar Biol Assoc, 2009) exhibit strong spatial segregation along the coast of Brittany (France), the first being subtidally distributed relative to the other intertidal species. Despite a very high degree of mitochondrial DNA divergence, previous preliminary results hinted at the potential for hybridization to occur. Therefore, we specifically aim to determine local levels of hybridization between these two species and to investigate the relative roles of pre- and post- zygotic isolation processes acting to decrease local hybridization patterns. Mitochondrial DNA, allozymes and the Internal Transcribed Spacer 2 region of the ribosomal DNA were all used on 529 brittle-stars sampled locally in June and September 2005, among six stations in Douarnenez Bay, a site situated at the tip of Brittany. Only 2.6% of all samples analyzed were identified as potential hybrids. However, these were twice more frequent in June, just after the reproductive period, than in September after selective mortality acted to reduce the proportions of hybrids. In addition to the abrupt bathymetric segregation between the two species, spawning asynchrony also clearly restricts hybridization to low levels, which shows the importance of pre-zygotic mechanisms in maintaining reproductive isolation. Moreover, both limited hybridization events and adult mortalities following reproduction tend to generate local genetic differentiation at the intra-species level. On the contrary, the genetic structure is homogenized by migration of juveniles or adults and hybrids mortalities over the summer period.

Implante de cartilagem auricular autóloga no reparo de desvio de pênis de bovinos / Implantation of the autologous auricular cartilagem in the repair of penile deviation in cattle

Dezoito novilhos de diferentes raças, com idade de 18-24 meses foram submetidos a remoção do ligamento apical para ocasionar desvio de pênis. Decorridos 60 dias os animais foram colocados em presença de fêmeas em estro, sendo verificado desvio ventral e lateral direito do pênis, com incapacitade de cópula. Os animais foram submetidos ao transplante autólgo de um segmento da cartilagem do pavilhão auricular, sobre a túnica albugínea, substituindo o ligamento apical do pênis removido. Os bovinos quando em presença de fêmeas em estro não apresentaram desvio de pênis e alteração do comportamento sexual. Notou-se a presença de poucas células mononucleares, polimorfonucleares e células gigantes e formação de tecido conjuntivo fibroso, ocasionando aderências resistentes e capacidade de sustentar a extremidade livre do pênis. O método cirúrgico mostrou-se eficiente para corrigir desvios ventral e lateral de pênis de bovinos.

Eighteen 18 to 24-month-old mixed breed bullocks were submitted to removal of the apical ligament of the penis to induce penile deviation. After 60 days from the surgery the steers were put together with cows in heat. A ventral and right lateral penis deviation leading to incapacity to copulate was observed. The bullocks were then submitted to an autolgous transplant of a cartilage segment from the ear pinna placed on top of the tunica albuginea, replacing the penile ligament apical tha had been removed. The implanted material was well tolerated; histologically with only infiltration few mononuclear cells, polymorpho nucleated cells and giant cells, and fibrosis, which caused strong adherence and provided ability to sustain the free penile extremity. The bullocks that were cows in heat did not show any degree of penile deviation nor any change in sexual behavior. The surgical method described here was shown to be satisfactory as to be indicated for correction of ventral and right lateral penile deviation in bullocks.

Anthropometric, bone age, and bone mineral density changes after a family-based treatment for obese children.

Our objective was to identify anthropometric, bone age, and bone mineral density (BMD) changes after a family-based treatment program for obese children. We conducted a longitudinal prospective study of 50 obese children (body mass index percentage [BMI%] > or =120%) aged 9.12 +/- 1.72 years (range 6-13) at baseline. A family-based treatment program, based on inadequate feeding style with progressive modification, aerobic physical exercise increase, active parental involvement, and the use of behavioural strategies (contracting, self-monitoring, social reinforcement), was developed during a 12-month period. Anthropometric data, lumbar spine (L2-L4) BMD by dual-energy X-ray absorptiometry, bone age (BA), bone age to chronological age ratio (BA/CA), and predicted adult height (PAH) were determined at baseline and 12 months. The statistical method used was analysis of variance and the paired Student t-test. Mean BMI standard deviation score (SDS) loss was -0.61 +/- 0.76 and BMI% loss was -5.17 +/- 9.73%. Height SDS significantly decreased, BA/CA ratio also decreased significantly, and PAH change was not significant. Lumbar spine BMD SDS and BMD% did not significantly change. A family-based treatment program was effective in obese children by reducing by 5% the BMI in 1 year and increasing the activity level. Treatment reduced growth velocity and delayed bone maturation rate without affecting PAH, reflecting a situation of previous early maturation. The treatment did not modify gaining bone mass.

Incomplete cryptic speciation between intertidal and subtidal morphs of Acrocnida brachiata (Echinodermata: Ophiuroidea) in the Northeast Atlantic.

The brittle-star Acrocnida brachiata (Montagu) lives in sandy-bottom habitat of both intertidal and subtidal zones along the coasts of the northwestern Europe. An allozyme frequency-based survey (five enzyme loci) was combined with a mitochondrial (mt) COI haplotype analysis (598-bp sequences) on 17 populations to trace back past colonization pathways from the actual population structure of the species. Both genetic markers display a sharp genetic break between intertidal (clade I) and subtidal populations (clade S). This break corresponds to an allele frequency inversion at three enzyme loci (Hk, Pgm and Pgi) and a deep divergence of about 20% in mtCOI sequences between most of the intertidal populations and other samples. The geographic distribution of clade I seems to be more restricted than clade S as it is absent from the intertidal of the eastern English Channel and North Sea and may be replaced by clade S in south Brittany. Applying previously published rates of mutation, divergence between the two clades is estimated to pre-date 5 million years ago and may be due to allopatric speciation processes at the Mio-Pliocene transition. The occurrence of putative hybrids in a few localities, however, suggests incomplete cryptic speciation with secondary contact zones. The relative importance of colonization history vs. habitat specialization are discussed in the light of neutral evolution as tested from mtCOI gene sequences. While differential selection seems to have contributed little to the separation of the lineages, it may have played a role in the emergence of adaptive polymorphisms in the hybrid zone. Furthermore, congruent spatial patterns of differentiation were observed in both clades suggesting a recent increase in population size. These findings are in agreement with a recent expansion of the populations during or after the formation of the English Channel, from a southern refuge for the subtidal clade whereas the intertidal clade may have persisted further north. As previously suspected for a species with a very short pelagic larval phase, contemporary gene flow between distant or adjacent populations appears to be extremely reduced or even absent.

Comparative phylogeography of two coastal polychaete tubeworms in the Northeast Atlantic supports shared history and vicariant events.

The historic processes which have led to the present-day patterns of genetic structure in the marine coastal fauna of the Northeast Atlantic are still poorly understood. While tectonic uplifts and changes in sea level may have caused large-scale vicariance, warmer conditions during glacial maxima may have allowed pockets of diversity to persist to a much wider extent than in the Northwestern Atlantic. The large-scale geographic distribution of deeply divergent lineages of the coastal polychaete tubeworms Pectinaria koreni (two clades) and Owenia fusiformis (three clades) were compared using a fragment of the mitochondrial cytochrome oxidase I gene (mtCOI). All lineages were present along the biogeographic transition zone on the north coast of Brittany (France) and we found evidence pointing towards congruence in the timing of cladogenic events between Pectinaria sp. (P. auricoma/P. belgica and P. koreni) and Owenia sp., suggesting a shared history of vicariant events. More conserved 16SrRNA sequences obtained from four species of Pectinariidae together with mtCOI sequences of P. koreni seem consistent with an initial establishment of pectinariids in the north, and a southward colonization of the Northeast Atlantic. Phylogeographic patterns in O. fusiformis were also consistent with a north/south pattern of lineage splitting and congruent levels of divergence were detected between lineages of both species. We observed signatures of both persistence in small northern glacial refugia, and of northwards range expansion from regions situated closer to the Mediterranean. However, whether the recolonization of the Northeast Atlantic by both species actually reflects separate interglacial periods is unclear with regards to the lack of molecular clock calibration in coastal polychaete species.

Neurolepsia prolongada com decanoato de haloperidol no tratamento de dermatite psicogênica em um cão doméstico (Canis familiaris, 1758) / Long-term Neurolepsy with Haloperidol Decanoate in the Treatment of Psychogenic Dermatitis in a Domestic Dog (Canis Familiaris, 1758) / Neurolepsia de largo plazo con decanoato de haloperidol en el tratamiento de dermatitis psicogénica en un perro (canis familiaris 1758)

Relata-se o tratamento de um caso de dermatite psicogênica em um cão Rottweiler macho, com idade de 13 meses, pesando 42 kg. O paciente apresentava graves lesões dermatológicas devidas a auto-mutilação por lambedura, em ambas as regiões metatarsianas, e a anamnese indicava que o distúrbio psíquico tivesse origem no estresse provocado por uma mudança ambiental. Prescreveu-se tratamento com um neuroléptico de ação prolongada, o decanoato de haloperidol, com dose calculada por meio de extrapolação alométrica interespecífica, usando-se como modelo a dose total humana de 100 mg/70 kg. A dose total calculada para o cão de 42 kg foi de 70 mg, sendo administrada semanalmente, durante seis semanas. Já na segunda semana a recuperação era satisfatória, sendo que a cura completa foi obtida no 28º dia de tratamento. Mantido em observação por um período de seis meses, o paciente não apresentou quaisquer sinais de recidiva. Os resultados indicam que a droga apresenta excelentes perspectivas para o tratamento desta dermatopatia canina, e que o método de extrapolação alométrica interespecífica é plenamente eficiente no estabelecimento de protocolos posológicos individualizados.

ABSTRACT: This paper reports the results of the treatment of a 13 month-old male Rottweiler dog, weighing 42 kg, affected by psychogenic dermatitis. The patient presented serious cutaneous lesions due to self-licking, affecting both metatarsal areas. Anamnesis indicated that the psychic disturbance was caused by stress provoked by an environmental change. It was prescribed haloperidol decanoate, a long-acting neuroleptic, with dose calculated by interspecifi c allometric scaling, using as model the human total dose of 100 mg/70 kg. The total dose calculated for the 42 kg dog was 70 mg, and it was administered weekly for six weeks. Clinical recovery was already satisfactory in the second week, and complete cure was obtained in the 28th day of treatment. The patient was monitored by a six months period and did not present any relapsing signs. The results indicate that the drug presents excellent perspectives for the treatment of this canine skin disease, and that the method of interespecifi c allometric scaling is effi cient in the establishment of individualized therapeutic protocols.KEY WORDS: psychogenic dermatitis, neuroleptic, haloperidol decanoate, allometric scaling, dog

RESUMEN: Relata-se el tratamiento de un caso de dermatitis psicogénica en un perro Rottweiler macho, con edad de 13 meses y peso de 42 kg. El paciente presentaba graves lesiones dermatológicas debidas a auto-mutilación por lamedura, en ambas las regiones metatarsianas, y la anamnesia indicaba que la enfermedad tuviese origen en el estrés provocado por un cambio ambiental. Se prescribió tratamiento con un agente neuroléptico de acción prolongada, el decanoato de haloperidol, con dosis calculada por extrapolación alométrica interespecífi ca, se usando como modelo la dosis total humana de 100 mg/70 kg. La dosis total calculada para el perro de 42 kg fue de 70 mg, sendo administrada semanalmente, durante seis semanas. La recuperación clínica ya era satisfactoria en la segunda semana, y la cura completa se obtuvo en el vigésimo octavo día de tratamiento. El paciente fue supervisado por un periodo de seis meses y no presentó ninguna señal de retorno de la enfermedad. Los resultados indican que la droga presenta perspectivas excelentes para el tratamiento de esta enfermedad en perros, y que el método de extrapolación alométrica descascarar es en el establecimiento de protocolos terapéuticos individualizados.

Pressão Intra-ocular em Cães com Catarata / Intra-ocular Pressure in Dogs with Cataract / Presión intraocular en perros con catarata

A catarata é reconhecida como qualquer opacificação da lente e seu tratamento é cirúrgico. A pressão intra-ocular é dada pelo equilíbrio entre a entrada e saída de humor aquoso nas câmaras anterior e posterior do olho. Este artigo traz uma revisão a respeito das implicações da catarata e de seu tratamento cirúrgico sobre a pressão intra-ocular, bem como discute os métodos indicados para controle e manutenção da pressão intra-ocular em cães.

ABSTRACT: Cataract is a disease recognized as any lens opacifi cation and its treatment is surgical. The intra-ocular pressure is given by the balance between the entrance and the exit of aqueous humor in the anterior and posterior chambers of the eye. This article presents a review about the implications of cataract and its surgical treatment on the intra-ocular pressure, as well as it discuss the indicated methods for control and maintenance of the intra-ocular pressure in dogs.

RESUMEN: La catarata es una enfermedad reconocida como cualquier opacidad del cristalino, y su tratamiento es quirúrgico. La presión intraocular es debida al equilibrio entre la entrada y la salida del humor acuoso en las cámaras anterior y posterior del ojo. Este artículo presenta una revisión a respecto de las implicaciones de la catarata y de su tratamiento quirúrgico sobre la presión intraocular, así como discute los métodos para control y manutención de la presión intraocular en perros.

Sharp genetic break between Atlantic and English Channel populations of the polychaete Pectinaria koreni, along the North coast of France.

This study uses enzymatic and mitochondrial genes to infer the relative importance of historical processes and contemporary hydrodynamic features on the observed patterns of genetic structure in subdivided populations of Pectinaria koreni (Polychaeta: Pectinariidae) along the coasts of Brittany and the English Channel. Nucleotide sequence variation of a 603-bp fragment of the mtDNA cytochrome oxidase subunit I gene revealed a surprisingly deep phylogeographic break of about 16% divergence separating the Brittany and Channel populations, which coincides with a biogeographic boundary along the western coast of Brittany. Deep sequence divergence with fixed haplotype differences and the inversion of allele frequencies at two enzyme loci suggests the occurrence of potential cryptic or sibling species of P. koreni. The two clades showed opposite features. Channel populations exhibited bimodal match-mismatch curves due to two highly divergent haplotypes occurring at high frequencies and no overall heterozygote deficiencies at enzyme loci, suggesting respectively, a historic secondary contact between two differentiated populations followed by contemporary panmixia. On the contrary, Brittany populations displayed unimodal curves with low nucleotide diversity and highly significant heterozygote deficiencies, probably reminiscent of a recent population expansion and recolonisation of Brittany with contemporary admixture of divergent populations.

Byte structure variable length coding (BS-VLC): a new specific algorithm applied in the compression of trajectories generated by molecular dynamics

Molecular dynamics is a well-known technique very much used in the study of biomolecular systems. The trajectory files produced by molecular dynamics simulations are extensive, and the classical lossless algorithms give poor efficiencies in their compression. In this work, a new specific algorithm, named byte structure variable length coding (BS-VLC), is introduced. Trajectory files, obtained by molecular dynamics applied to trypsin and a trypsin:pancreatic trypsin inhibitor complex, were compressed using four classical lossless algorithms (Huffman, adaptive Huffman, LZW, and LZ77) as well as the BS-VLC algorithm. The results obtained show that BS-VLC nearly triplicates the compression efficiency of the best classical lossless algorithm, preserving a near lossless behavior. Compression efficiencies close to 50% can be obtained with a high degree of precision, and the maximum efficiency possible (75%), within this algorithm, can be performed with good precision.

IIB osteosarcoma. Current management, local control, and survival statistics--São Paulo, Brazil.

Ninety-two patients with IIB osteosarcoma of the extremities were treated with intraarterial (IA) cisplatinum (CDDP) followed by surgery [amputation (61.6%) or resection with endoprosthesis (38.4%)]. Postoperative chemotherapy alternating adriamycin and CDDP was used. The total three-year survival was 62.1%, and the disease-free survival was 41.1%. The pathologic evaluation of the degree of tumor necrosis in response to the IA CDDP showed that in 53.2%, the necrosis was over 90%. The multivariate analysis of prognostic factors has shown that the highest survival was among females with tumors smaller than 15 cm. Patients with lesions equal to or larger than 15 cm were three times as likely to die of the disease. A second, more aggressive study is now underway, in which high dose methotrexate (HDMTX) is preoperatively combined with adriamycin and CDDP. Following operation, ifosfamide is added to the cases with a smaller degree of tumor necrosis, while the other group of patients will continue with HDMTX, in addition to CDDP and adriamycin (these last two drugs are used in both arms). Until now, complete remission has been achieved in 82% and 86%, respectively, with a follow-up examination varying from four to 26 months (average, 14 months). This is of extreme importance, because the majority of the authors' patients have tumors at initial evaluation larger than 10 cm in diameter.

Increased survival, limb preservation, and prognostic factors for osteosarcoma.

Preoperative intraarterial (IA) cisplatin (CDP) was administered to 92 patients with nonmetastatic osteosarcoma. The ages of the patients ranged from 4 to 28 years. Sixty-four patients (70%) received 2 or 3 preoperative courses and 28 (30%) received 4 or more. Sixty-two specimens were available for pathologic examination to assess the degree of tumor necrosis. More than 90% tumor destruction was observed in 16 of 42 patients (38%) who received 1 to 3 preoperative courses as opposed to 17 of 20 (85%) who received 4 or more courses. Patients who received 4 or more courses had a 2-fold probability of achieving more than 90% tumor necrosis, and 68% underwent conservative surgery. Of those who received 3 or less courses, 23% underwent conservative surgery. Postoperatively, patients were treated with intravenous (IV) CDP alternating with doxorubicin (ADR) (Adriamycin, Adria Laboratories, Columbus, OH). Pulmonary metastases developed in 36 patients, bone metastases in 2, and local recurrence in 6. Two patients died of cardiac failure without evidence of disease. Thus, 46 patients (50%) were continuously free of disease 18 to 78 months after diagnosis. Univariate and multivariate analyses showed that male sex, low grade preoperative chemotherapy-induced necrosis, and nonosteoblastic histologic condition were prognostic factors predictive of recurrence, while male sex and large tumor size were prognostic factors predictive of death. These results are comparable with those reported by other centers and are superior to our previous experiences that yielded survival rates of 5% to 10%. A substantial number of patients also had the opportunity to achieve tumor removal with conservative surgery.

Treatment of disseminated malignant melanoma with high-dose oral BCG.

Thirty patients with unresectable disseminated melanoma (Stage IV) were treated with Bacillus Calmette-Guerin (BCG) (Moreau strain--Rio de Janeiro) by mouth, with weekly doses ranging between 200 mg and 28,000 mg. Five patients died in the first two months of treatment. Of the remaining 25 patients, two (8%) showed complete regression, and one (4%) partial regression. Seven patients (28%) had stabilization of the disease for a six-month period, and 15 (60%) had progression of the disease. Complete and partial regressions were seen only in patients with extravisceral (subcutaneous) metastases, and were associated with a longer survival time. Regression of the subcutaneous metastatic nodules was always accompanied by the following local phenomena: increased temperature; local inflammation; softening, pain and pruritus at the nodule site; and a gradual decrease in size. At the site of the tumor mass, a hypochromic halo appeared. This halo remained permanently and was pathognomonic of the metastatic nodule rejection. When the halo was fully established, the inflammatory infiltrate was minimal and the malignant cells disappeared. If the area contained hairs, they underwent complete albinization. Serial biopsies of the nodules undergoing inflammatory changes and decreased consistency exhibited an intense cellular infiltration of lymphocytes, macrophages, and plasma cells around the malignant cells. This sometimes simulated lymphoid follicle formation involving the melanoma cells associated with necrosis in a centripetal way. Some patients with visceral metastases (particularly pulmonary) had an unexpectedly long survival, apparently associated with interruption of the growth rate of the masses. Eleven out of 20 deaths were due to cerebral metastases. When cerebral disease was diagnosed, BCG was discontinued and the administration of corticoids was usually associated with a disappearance of the inflammatory signs at the nodule sites, but with progression of the disease. Toxicity was minimal.