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Biomedical subjects

C Collin

Publications and source records attributed to C Collin.

At least 73 records · Page 4Linked to original sources

Increased adriamycin levels in hepatic implants of rabbit Vx-2 carcinoma from regional infusion.

Regional infusion chemotherapy for the treatment of primary or secondary hepatic cancer should allow delivery of a higher drug concentration to the tumor with decreased systemic exposure when compared with systemic therapy. Fifteen rabbits, each implanted with two hepatic Vx-2 tumors, were treated with infusion of Adriamycin (3 mg/kg and 7.5 muCi of [14C]Adriamycin) through the hepatic artery (n = 5), portal vein (n = 5), and a systemic vein (n = 5) at 20 mg/min. 99Tc-labeled macroaggregated albumin flow images documented specific hepatic perfusion in selected rabbits using this technique. Thirty min after infusion the animals were sacrificed, and multiple specimens of liver, tumor, and heart were taken for liquid scintillation counting and high-performance liquid chromatography. The 14C label remained associated with Adriamycin and metabolites. After systemic infusion 11.5 nmol/g of Adriamycin were found in tumor, and 32.4 nmol/g were found in liver. Infusion of Adriamycin through the hepatic artery produced drug levels of 34.3 nmol/g of tumor and 48.4 nmol/g of liver, while infusion through the portal vein produced drug levels of 6.5 nmol/g of tumor and 54.4 nmol/g of liver. The drug concentration in tumor was significantly higher after hepatic artery infusion compared with systemic (P less than 0.05) or portal vein (P less than 0.01) infusion. The tumor/liver ratio of [14C]Adriamycin tissue levels after hepatic artery infusion was greater than that measured after systemic vein treatment (no overlap of the 90% confidence intervals). Systemic infusion of Adriamycin produced a higher level of Adriamycin in the heart (13.6 nmol/g) than did hepatic artery (10.9 nmol/g) or portal vein (8.9 nmol/g) infusion. Hepatic artery infusion achieved the highest tumor Adriamycin level compared with systemic vein and portal vein infusion. The results suggest that these tumor implants are supplied primarily by the hepatic artery, that clearance of Adriamycin is efficient after regional infusion, and that systemic toxicity may be reduced using intraarterial infusion of Adriamycin for hepatic tumors.

Animals↗

Low-grade soft tissue sarcomas of the extremities. Analysis of risk factors for metastasis.

Of 130 patients with low-grade localized soft tissue sarcomas of the extremities treated at Memorial Hospital between 1968 and 1978, 18 (14%) developed metastases. The risk of metastasis could not be predicted by the clinical or pathologic size, tumor depth, proximal location, recurrence before presentation or subsequent to treatment at our institution, the type of surgical and adjuvant therapies, and the adequacy of surgical margins. The median age of patients with metastases was 10 years older than the other patients (57.5 years and 47.5 years, respectively). Of the more common sarcomas in this study, malignant peripheral nerve tumors and malignant fibrous histiocytomas had the highest prevalence of metastasis (27% (three of 11) and 17% (three of 18), respectively). Although patients with low-grade extremity sarcomas treated during the first 5 years of this review had an increased rate of metastasis, no other patient, tumor, or treatment variable examined significantly differed between the two time periods. Although grade alone is a good predictor of the risk of metastasis from soft tissue sarcomas of the extremity, 14% of patients in this series with low-grade histology developed metastases. Further review of larger numbers of these tumors should be undertaken in an effort to more definitively identify risk factors predictive of metastatic potential in low-grade sarcomas.

Age Factors↗

Sequential modification of membrane currents with classical conditioning.

Pavlovian conditioning of the nudibranch mollusc Hermissenda crassicornis was previously shown to produce long-lasting reduction of two K+ currents measured across the Type B photoreceptor soma membrane (Alkon et al., 1982a; Alkon et al., 1985). Pavlovian conditioning of the rabbit was also shown to be followed by persistent K+ current reduction (Disterhoft et al., 1986). Here we report the first evidence that Ca2+ currents can also be modified by conditioning. The amplitude of the currents rather than their voltage-dependence remains reduced at least 1-2 d after conditioning (but not control procedures). Conditioning-induced changes of both K+ and Ca2+ currents increased as a function of training, the Ca2+ currents only changing substantially with greater than or equal to 250 trials. The later changes of the Ca2+ current may function to limit the magnitude of excitability increases due to associative learning.

Animals↗

Measuring everyday memory in elderly people: a preliminary study.

The effectiveness of a short test of everyday memory in discriminating memory ability of independently living and of partially dependent elderly people has been investigated. Results indicate that overall test performance is significantly different in the two groups but that not all individual items discriminate equally well. The test as a whole correlates well with a standard cognitive screening test but it also contains items for abilities not measured in the general test, notably visuo-spatial memory. In addition, it appears to provide a more sensitive measure of memory function when general cognitive decline is minimal.

Aged↗

The Barthel ADL Index: a reliability study.

The Barthel Index is a valid measure of disability. In this study we investigated the reliability of four different methods of obtaining the score in 25 patients: self-report, asking a trained nurse who had worked with the patient for at least one shift, and separate testing by two skilled observers within 72 hours of admission. Analysis of total (summed) scores revealed a close correlation between all four methods: a difference of 4/20 points was likely to reflect a genuine difference. In individual items, most disagreement was minor and involved the definition of middle grades. Asking an informed nurse or relative was as reliable as testing, and is quicker.

Activities of Daily Living↗

The Barthel ADL Index: a standard measure of physical disability?

There is no agreed single measure of physical disability for use either clinically or in research. It is argued that acceptance of a single standard measure of activities of daily living (ADL) might increase awareness of disability, improve clinical management of disabled patients, and might even increase acceptance of published research. The Barthel ADL Index is proposed as the standard index for clinical and research purposes. Its validity, reliability, sensitivity, and utility are discussed. The Barthel Index is as good as any other single simple index, and should be adopted as the standard against which future indices are compared. The temptation to use variations on the standard Barthel Index should be resisted.

Activities of Daily Living↗

Localized operable soft tissue sarcoma of the upper extremity. Presentation, management, and factors affecting local recurrence in 108 patients.

Radical ablative surgery for upper extremity sarcoma often results in significant loss of function. With the recent emphasis on limb preservation, function-sparing excision has been combined with adjuvant radiation and chemotherapy in an increasing number of patients. To assess the effect of changing management on local recurrence rates and identify factors governing local failure, the records of 108 patients with operable, nonmetastatic soft tissue sarcoma of the upper extremity, treated at the Memorial Sloan-Kettering Cancer Center between 1968 and 1978, were reviewed. Median follow-up care was 8.2 years. One third of the patients presented with locally recurrent tumors after initial treatment elsewhere. Over half of the lesions were above the elbow and 62% were high grade. Seventy-three patients (68%) had limb-sparing surgery (LSS), but margins were considered adequate in less than half. Local recurrence was directly related to the adequacy of the surgical margins and was significantly higher in the LSS patients (p = 0.008). Other factors associated with an increased risk of local failure included: presentation with local recurrence, superficial location, and invasion of vital structures (LSS only). Local failure varied significantly with histologic type and was highest in patients with embryonal rhabdomyosarcoma and angiosarcoma. When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of local failure: presentation with local recurrence, surgery by LSS, inadequate margins, angiosarcoma, and invasion of vital structures. These risk factors should be carefully weighed when selecting local treatment for patients with upper extremity soft tissue sarcomas.

Adolescent↗

Effects of alpha 2-adrenergic agonists and antagonists on photoreceptor membrane currents.

Type B photoreceptors of the nudibranch mollusc Hermissenda crassicornis receive excitatory synaptic potentials (EPSPs) whose frequency is controlled by potential changes of a neighboring cell known as the S optic ganglion cell which is thought to be electrically coupled to the presynaptic source of these EPSPs, the E optic ganglion cell. The frequency of the EPSPs increases when a conditioned stimulus (light) is paired with an unconditioned stimulus (rotation) during acquisition of a Pavlovian conditioned response. The results of the present study are consistent with an adrenergic origin for these EPSPs. Noradrenergic agonists (greater than 100 microM), norepinephrine and clonidine, only slightly depolarize the type B cell but clearly prolong its depolarizing response to light. Serotonin, by contrast, causes hyperpolarization of the type B cell's resting potential as well as after a light step. Clonidine reduces voltage-dependent outward K+ currents (IA, an early current, ICa2+-K+, a late Ca2+-dependent current) that control the type B cell's excitability (and thus its light response and membrane potential). These effects of clonidine are reduced or blocked by the alpha 2-receptor antagonist, yohimbine (0.5 microM), but not the alpha 1-blocker, prazosin. The same yohimbine concentration also blocked depolarizing synaptic excitation of the type B cell in response to depolarization of a simultaneously impaled S optic ganglion cell. Histochemical techniques (both the glyoxylic acid method of de la Torre and Surgeon and the formaldehyde-induced fluorescence or Falck-Hillarp method) demonstrated the presence of a biogenic amine(s) within a single neuron in each optic ganglion as well as three or four cells within the vicinity of previously identified visual interneurons. No serotonergic neurons were found within the optic ganglion or in proximity to visual interneurons. A clonidine-like synaptic effect on type B cells, therefore, could amplify conditioning-specific changes of membrane currents by increasing type B depolarization and possibly, as well, by elevating intracellular second messengers.

Adrenergic alpha-Agonists↗

Localized extremity soft tissue sarcoma: an analysis of factors affecting survival.

The management of extremity soft tissue sarcoma is undergoing rapid change as new techniques of adjuvant treatment are developed. Critical assessment of these advances requires a fundamental understanding of the natural course of this disease. In an effort to define important prognostic factors, this review of 423 adults with localized extremity soft tissue sarcomas, treated at one institution (1968 to 1978), was undertaken. The effect of the following variables on survival was examined: patient factors, ie, age, sex, symptoms, and status at presentation; tumor factors, ie, site, size, depth, bone or neurovascular invasion, histogenesis, grade, and nodal status; and treatment factors, ie, biopsy technique, type of operation, surgical margins, adjuvant treatment, and subsequent local treatment failure. Patient factors with an adverse impact on survival included age greater than 53 and the presence of local symptoms. High tumor grade, positive regional nodes, histology other than liposarcoma, fibrosarcoma or malignant fibrohistiocytoma, invasion of vital structures, proximal site, deep location, and size greater than 10 cm were also poor prognosticators. Treatment factors correlating with optimal survival included limb sparing surgery, adequate margins, biopsy with delayed definitive resection, and absence of subsequent local failure. Patients treated by amputation had a greater proportion of risk factors than patients treated with limb-sparing surgery (LSS). When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of poor outcome: local symptoms, age greater than 53, high grade, proximal site, size greater than 10 cm, positive regional nodes, surgery by amputation, and inadequate margins. These factors are now to be evaluated in our prospective study based on 600 patients with soft tissue sarcoma of all sites admitted to our institution in the last 3 years. These factors should be considered as important stratifications in prospective trials.

Adolescent↗

Limb preservation and tumor control in the treatment of popliteal and antecubital soft tissue sarcomas.

Soft tissue sarcomas of the antecubital and popliteal space often involve the neurovascular bundle and are prone to recurrence after surgical resection. Amputation has frequently been performed for control of these tumors. A multimodality treatment program consisting of limb-sparing resection, tumor-bed radiation using temporary iridium 192 implants, and adjuvant chemotherapy for high-grade lesions, has yielded satisfactory preservation of limb function and no local tumor recurrence in ten patients after a median follow-up time of 5 years. Eight of the ten patients are still alive, five of whom beyond 5 years; six of the eight survivors had high-grade tumors. These results are superior to those of 14 patients with similar tumors treated earlier by surgery alone: seven by amputation and seven by soft part resection; four of the latter resulted in local recurrence and all of the seven who had high-grade sarcoma died of disease. Multimodality treatment including limb-sparing resection merits consideration in the management of antecubital and popliteal soft tissue sarcomas.

Adolescent↗

Localized, operable soft tissue sarcoma of the lower extremity.

Recent developments in adjuvant treatment of soft tissue sarcomas of the extremities have altered the surgical approach to this disease. To assess the effects of changing management on local recurrence rates and to examine factors governing local failure, we reviewed the records of 315 adults with operable, nonmetastatic soft tissue sarcoma of the lower extremity who were treated at one institution over a ten-year period. The median follow-up was 8.2 years. One third of our patients presented with locally recurrent tumors after initial treatment elsewhere. Sixty-six percent of the lesions were above the knee, and 60% were high grade. Two thirds of the patients underwent limb-sparing surgery (LSS), which in the latter half of the study period outnumbered amputations by four to one. Local recurrence was directly related to the adequacy of the surgical margins. Adjuvant radiotherapy and chemotherapy did not significantly decrease local recurrence in patients who underwent LSS, although favorable trends were observed. A significantly increased risk of local failure was associated with age greater than 53 years, presentation with local recurrence, high tumor grade, deep location, positive nodes, and less than adequate surgical margins. Local failure also varied significantly with histologic type and was highest in patients with embryonal rhabdomyosarcoma and neurofibrosarcoma. Improved local control, particularly in patients with high-grade tumors, was observed in the latter half of the study period despite the increased use of LSS. When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of local failure: age greater than 53 years, presentation with local recurrence, high grade, less than adequate margins, embryonal rhabdomyosarcoma, and neurofibrosarcoma. The key to local control of sarcomas of the extremities is resection of the tumor with adequate margins. The role of adjuvant treatment, particularly following LSS, is still being evaluated. The risk factor profile should be considered when selecting a treatment program for patients with lower extremity sarcomas.

Adolescent↗

Within-subject variability of the percentage of morphologically abnormal spermatozoa among fertile men: biological and measurement components.

Two groups of men were studied to determine how much an individual's spermatozoal morphology varies and which part of the variability is due to biological and to measurement variation. A first group of ten subjects each provided five ejaculates; the other group of four subjects each provided one ejaculate, from each of which five smears were prepared, and evaluated twice. The slides were examined in random order and blindly by the same experienced technician. The total within-subject variability of the percentage of abnormal forms was large (SD = 8.8%), as was the component of this variability due to biologic fluctuation (SD = 5.8%). The distribution of the various abnormalities also varied greatly from one ejaculate to another. The results indicate that more work is needed to determine why biological variation exists, and that several ejaculates (three if possible, two at minimum) are needed for an accurate evaluation of spermatozoal morphology, whereas the examination of greater than 100 spermatozoa/ejaculate is not advantageous.

Fertility↗

Headache and school absence.

The amount of time missed from school in two small town school populations was estimated by measuring absence from school and attendance at sickbay, and stated causes were analysed. School absence related to headache (expressed as percentage of pupil days missed out of possible pupil days, during two 12 week periods) in children aged 5 to 14 years, was 0.05%. This represented approximately 1% of all school absence, and was recorded (usually only once) in 3.7% of children. The duration of absence was one day or less on 85% of occasions. This low absence rate was in contrast with the high prevalence of headache reported by children aged 9 to 14 of between 76 and 94% according to age and sex. Attendance at school sick bay because of headache was recorded in 3.6% of children aged 5 to 19 (only 0.5% then left school early because of headache) in one 12 week period. It is concluded that although headache prevalence is high in the age groups studied, it is not a prominent cause of time missed from school.

Absenteeism↗