High-dose tamoxifen plus ifosfamide and anthracycline in a patient with angiosarcoma of the breast / Tamoxifen en dosis alta con ifosfamida y antraciclina en un paciente con angiosarcoma de mama

Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas ofthe breast.

Aunque el cáncer de mama, desafortunadamente, no es poco común en las mujeres, apenas 0.04% de los tumores malignos de mama son angiosarcomas primarios. La quimioterapia es el tratamiento de preferencia en los casos de angiosarcomas de mama. Sin embargo, no existen guías en relación con los protocolos o la quimioterapia óptima. En la actualidad, el pronóstico para los angiosarcomas de mama es pobre. Este informe del caso describe a una mujer de 24 años diagnosticada con angiosarcoma primario de mama. Inicialmente la paciente se negó a recibir tratamiento, pero volvió al hospital cuatro años más tarde con un hemoneumotórax. Fue tratada entonces con quimioterapia de rescate usando una combinación de alta dosis de tamoxifen con ifosfamida y epirrubicina (antraciclina). Llegó a responder parcialmente al tratamiento, pero falleció 16 meses después del inicio de la terapia. Se necesitan más investigaciones para elaborar nuevos quimioterápeuticos y protocolos que mejoren los resultados en los casos de mujeres diagnosticadas con angiosarcomas primarios de mama.

High-dose tamoxifen plus ifosfamide and anthracycline in a patient with angiosarcoma of the breast.

Although breast cancer is, unfortunately, not uncommon in women, a mere 0.04% of malignant breast tumours are primary angiosarcomas. Chemotherapy is advocated for treatment of breast angiosarcomas; however, no guidelines exist regarding optimal chemotherapeutics or protocols. Presently, the prognosis for breast angiosarcomas is poor. This case report describes a 24-year old woman diagnosed with primary breast angiosarcoma. She initially refused to receive treatment, but later returned to the hospital four years later with a haemopneumothorax. She was treated with rescue chemotherapy using a combination of high-dose tamoxifen plus ifosfamide and epirubicin (an anthracycline). She achieved a partial response, but died 16 months after therapy was initiated. More research is needed to devise novel chemotherapeutics and protocols to improve outcomes in women diagnosed with primary angiosarcomas of the breast.

Identification of the main generator source of longitudinal muscle contraction in the earthworm ventral nerve cord

The main generator source of a longitudinal muscle contraction was identified as an M (mechanical-stimulus-sensitive) circuit composed of a presynaptic M-1 neuron and a postsynaptic M-2 neuron in the ventral nerve cord of the earthworm, Amynthas hawayanus, by simultaneous intracellular response recording and Lucifer Yellow-CH injection with two microelectrodes. Five-peaked responses were evoked in both neurons by a mechanical, but not by an electrical, stimulus to the mechanoreceptor in the shaft of a seta at the opposite side of an epidermis-muscle-nerve-cord preparation. This response was correlated to 84 per cent of the amplitude, 73 per cent of the rising rate and 81 per cent of the duration of a longitudinal muscle contraction recorded by a mechano-electrical transducer after eliminating the other possible generator sources by partitioning the epidermis-muscle piece of this preparation. The pre- and postsynaptic relationship between these two neurons was determined by alternately stimulating and recording with two microelectrodes. Images of the Lucifer Yellow-CH-filled M-1 and M-2 neurons showed that both of them are composed of bundles of longitudinal processes situated on the side of the nerve cord opposite to stimulation. The M-1 neuron has an afferent process (A1) in the first nerve at the stimulated side of this preparation and the M-2 neuron has two efferent processes (E1 and E3) in the first and third nerves at the recording side where their effector muscle cell was identified by a third microelectrode.

Facilitation of the main generator source of earthworm muscle contraction by a peripheral neuron

A constant facilitation of responses evoked in the earthworm muscle contraction generator neurons by responses evoked in the neurons of its peripheral nervous system was demonstrated. It is based on the proposal that these two responses are bifurcations of an afferent response evoked by the same peripheral mechanical stimulus but converging again on this central neuron. A single-peaked generator response without facilitation was demonstrated by sectioning the afferent route of the peripheral facilitatory modulatory response, or conditioning response (CR). The multipeaked response could be restored by restimulating the sectioned modulatory neuron with an intracellular substitutive conditioning stimulus (SCS). These multi-peaked responses were proposed to be the result of reverberating the original single peaked unconditioned response (UR) through a parallel (P) neuronal circuit which receives the facilitation of the peripheral modulatory neuron. This peripheral modulatory neuron was named "Peri-Kästchen" (PK) neuron because it has about 20 peripheral processes distributed on the surface of a Kästchen of longitudinal muscle cells on the body wall of this preparation as revealed by the Lucifer Yellow-CH-filling method.

Persistent attenuation and enhancement of the earthworm main muscle contraction generator response induced by repeated stimulation of a peripheral neuron

Responses evoked in the earthworm, Amynthas hawayanus, main muscle contraction generator M-2 (postsynaptic mechanical-stimulus-sensitive) neuron by threshold mechanical stimuli in 2-s intertrial intervals (ITI) were used as the control or unconditioned responses (UR). Their attenuation induced by decreasing these intervals in non-associative conditioning and their enhancement induced by associating the unconditioned stimuli (US) to a train of short (0.1 s) hyperpolarizing electrical substitutive conditioning stimuli (SCS) in the Peri-Kästchen (PK) neuron were measured in four parameters, i.e., peak numbers (N) and amplitude (AMP )averaged from 120 responses, sum of these amplitudes (SAMP) and the highest peak amplitude (V) over a period of 4 min. Persistent attenuation similar to habituation was induced by decreasing the control ITI to 0.5 s and 2.0 s in non-associative conditioning within less than 4 min. Dishabituation was induced by randomly pairing one of these habituated US to an electrical stimulus in the PK neuron. All four parameters of the UR were enhanced by forward (SCS-US), but not backward (US-SCS), association of the US with 25, 100 and 250-Hz trains of SCS with 40-ms interstimulus intervals (ISI) for 4 min and persisted for another 4 min after turning off the SCS. The enhancement of these parameters was proportional to the SCS frequencies in the train. No UR was evoked by the SCS when the US was turned off after 4 min of classical conditioning.

Identification of the main generator source of longitudinal muscle contraction in the earthworm ventral nerve cord.

The main generator source of a longitudinal muscle contraction was identified as an M (mechanical-stimulus-sensitive) circuit composed of a presynaptic M-1 neuron and a postsynaptic M-2 neuron in the ventral nerve cord of the earthworm, Amynthas hawayanus, by simultaneous intracellular response recording and Lucifer Yellow-CH injection with two microelectrodes. Five-peaked responses were evoked in both neurons by a mechanical, but not by an electrical, stimulus to the mechanoreceptor in the shaft of a seta at the opposite side of an epidermis-muscle-nerve-cord preparation. This response was correlated to 84% of the amplitude, 73% of the rising rate and 81% of the duration of a longitudinal muscle contraction recorded by a mechanoelectrical transducer after eliminating the other possible generator sources by partitioning the epidermis-muscle piece of this preparation. The pre- and postsynaptic relationship between these two neurons was determined by alternately stimulating and recording with two microelectrodes. Images of the Lucifer Yellow-CH-filled M-1 and M-2 neurons showed that both of them are composed of bundles of longitudinal processes situated on the side of the nerve cord opposite to stimulation. The M-1 neuron has an afferent process (A1) in the first nerve at the stimulated side of this preparation and the M-2 neuron has two efferent processes (E1 and E3) in the first and third nerves at the recording side where their effector muscle cell was identified by a third microelectrode.

Facilitation of the main generator source of earthworm muscle contraction by a peripheral neuron.

A constant facilitation of responses evoked in the earthworm muscle contraction generator neurons by responses evoked in the neurons of its peripheral nervous system was demonstrated. It is based on the proposal that these two responses are bifurcations of an afferent response evoked by the same peripheral mechanical stimulus but converging again on this central neuron. A single-peaked generator response without facilitation was demonstrated by sectioning the afferent route of the peripheral facilitatory modulatory response, or conditioning response (CR). The multipeaked response could be restored by restimulating the sectioned modulatory neuron with an intracellular substitutive conditioning stimulus (SCS). These multipeaked responses were proposed to be the result of reverberating the original single peaked unconditioned response (UR) through a parallel (P) neuronal circuit which receives the facilitation of the peripheral modulatory neuron. This peripheral modulatory neuron was named "Peri-Kästchen" (PK) neuron because it has about 20 peripheral processes distributed on the surface of a Kästchen of longitudinal muscle cells on the body wall of this preparation as revealed by the Lucifer Yellow-CH-filling method.

Persistent attenuation and enhancement of the earthworm main muscle contraction generator response induced by repeated stimulation of a peripheral neuron.

Responses evoked in the earthworm, Amynthas hawayanus, main muscle contraction generator M-2 (postsynaptic mechanical-stimulus-sensitive) neuron by threshold mechanical stimuli in 2-s intertrial intervals (ITI) were used as the control or unconditioned responses (UR). Their attenuation induced by decreasing these intervals in non-associative conditioning and their enhancement induced by associating the unconditioned stimuli (US) to a train of short (0.1 s) hyperpolarizing electrical substitutive conditioning stimuli (SCS) in the Peri-Kästchen (PK) neuron were measured in four parameters, i.e., peak numbers (N) and amplitude (AMP) averaged from 120 responses, sum of these amplitudes (sigma AMP) and the highest peak amplitude (V) over a period of 4 min. Persistent attenuation similar to habituation was induced by decreasing the control ITI to 0.5 s and 2.0 s in non-associative conditioning within less than 4 min. Dishabituation was induced by randomly pairing one of these habituated US to an electrical stimulus in the PK neuron. All four parameters of the UR were enhanced by forward (SCS-US), but not backward (US-SCS), association of the US with 25, 100 and 250-Hz trains of SCS with 40-ms interstimulus intervals (ISI) for 4 min and persisted for another 4 min after turning off the SCS. The enhancement of these parameters was proportional to the SCS frequencies in the train. No UR was evoked by the SCS when the US was turned off after 4 min of classical conditioning.

An analysis of fetal hemoglobin variation in sickle cell disease: the relative contributions of the X-linked factor, beta-globin haplotypes, alpha-globin gene number, gender, and age.

Five factors have been shown to influence the 20-fold variation of fetal hemoglobin (Hb F) levels in sickle cell anemia (SS): age, sex, the alpha-globin gene number, beta-globin haplotypes, and an X-linked locus that regulates the production of Hb F-containing erythrocytes (F cells), ie, the F-cell production (FCP) locus. To determine the relative importance of these factors, we studied 257 Jamaican SS subjects from a Cohort group identified by newborn screening and from a Sib Pair study. Linear regression analyses showed that each variable, when analyzed alone, had a significant association with Hb F levels (P < .05). Multiple regression analysis, including all variables, showed that the FCP locus is the strongest predictor, accounting for 40% of Hb F variation. beta-Globin haplotypes, alpha-globin genes, and age accounted for less than 10% of the variation. The association between the beta-globin haplotypes and Hb F levels becomes apparent if the influence of the FCP locus is removed by analyzing only individuals with the same FCP phenotype. Thus, the FCP locus is the most important factor identified to date in determining Hb F levels. The variation within each FCP phenotype is modulated by factors associated with the three common beta-globin haplotypes and other as yet unidentified factor(s).

An analysis of fetal hemoglobin variation in sickle cell disease: the relative contributions of the x-linked factor, á-Globin haplotypes, O-globin gene number, gender, and age

Five factors have been shown to influence the 20-fold variation of fetal hemoglobin (Hb F) levels in sickle cell anemia (SS): age, sex, the O-globin gene number, á-globin haplotypes, and an X-linked locus that regulates the production of Hb F-containing erythrocytes (F cells), i.e., the F-cell production (FCP) locus. To determine the relative importance of these factors, we studied 257 Jamaican SS subjects from a cohort group identified by newborn screening and from a sib pair study. Linear regression analyses showed that each variable, when analyzed alone, had a significant association with Hb F levels (P < 0.05). Multiple regression analysis, including all variables, showed that the FCP locus is the strongest predictor, accounting for 40 percent of Hb F variation. á-Globin haplotypes, O-globin genes, and age accounted for less than 10 percent of the variation. The association between the á-globin haplotypes and Hb F levels becomes apparent if the influence of the FCP locus is removed by analyzing only individuals with the same FCP phenotype. Thus, the FCP locus is the most important factor identified to date in determining Hb F levels. The variation within each FCP phenotype is modulated by factors associated with the three common á-globin haplotypes and other as yet unidentified factor(s).(AU)

Identification of efferent-stimulus-responding neurons in the earthwoem 3rd segmental nerve by Lucifer yellow-ch backfilling

The objective of the present study was to identifify the mechanism for the decreased efferent reflex response recorded extracellulary from an earthworm 3rd segmental nerve after the nerve had been cut. Four neurons which showed a correlated decrease in their efferent responses were identified in the ventral nerve cord by the broken-microelectrode-backfilling method using Lucifer Yellow-CH. The long processes of these neurons extended into the 3 rd nerve trunk.Thus teses neurons may neurons mayrepresent an efferent link in the this complicated reflex are

Identification of efferent-stimulus-responding neurons in the earthworm 3rd segmental nerve by lucifer yellow-CH backfilling.

The objective of the present study was to identify the mechanism for the decreased efferent reflex response recorded extracellularly from an earthworm 3rd segmental nerve after the nerve had been cut. Four neurons which showed a correlated decrease in their efferent responses were identified in the ventral nerve cord by the broken-microelectrode-backfilling method using Lucifer Yellow-CH. The long processes of these neurons extended into the 3rd nerve trunk. Thus, these neurons may represent an efferent link in this complicated reflex arc.

Decremental propagation of reflex spikes along giant axons of the earthworm Amynthas hawayanus.

The constant-velocity conduction of an action potential evoked by stimulating the isolated nerve cord of the earthworm Amynthas hawayanus differs from the propagation of a reflex spike evoked by stimulating the epithelium of an epithelio-muscular-nerve-cord (EMNC) preparation and recorded between pairs of microelectrodes spaced every 10 segments along either giant axon. The reflex spike is decremental and lasts for no more than 20 segments before it eventually disappears. Secondary and tertiary spikes sometimes arise even before the disappearance of the primary spike, and disappear after propagating for a short distance. This decremental propagation is tentatively attributed to the summation of excitatory postsynaptic potentials from the synaptic impingings of afferent interneurons in a polysynaptic reflex arc.

Decremental propagation of reflex spikes along giant axons of the earthworm amynthas hawayanus

the constant-velocity conduction of an action potential evoked by stimulating the isolated nerve cord of the earthworm Amynthas hawayanus differs from the propagation of a reflex spilke evoked by stimulating the epithelium of an epithelio-muscular-nerve-cord (EMNC) preparation and recorded between pairs of microelectrodes spaced every 10 segments along either giant axon. The refloex spike is decrmental and lasts for no more than 20 segments before it eventually disappears. Secondary and tertiary spikes sometimes arise even before the disapperance of the primary spike, and disappear after propating for a short distance. This decremental propagation is tentatively attributed to the summation of excitatory postsynaptic potentials from the synaptic impingngs of afferent interneurons in a polysynaptic reflex arc

Identification of the two cell groups in the longitudinal muscle layer of the earthworm Amynthas hawayanus by a single microelectrode with lucifer yellow-CH.

Previous electrophysiological studies have suggested the presence of two types of muscular cells in the longitudinal muscle of A. hawayanus. However, a definite classification of such cells as muscles has been hindered by lack of morphological evidence. This study identified these cells electrophysiologically and morphologically by using the same intracellular microelectrode to record cell activity and inject Lucifer Yellow-CH. Electrophysiological measurements clearly differentiated the two groups of cells. One group did not respond to nerve stimulation but was spontaneously active, whereas the other responded to nerve stimulation with endplate potentials and did not discharge spontaneously. Morphological examination revealed two very similar types of longitudinal muscle cells. These results clearly show that, although morphologically similar, there are two distinct groups of muscle cells in the longitudinal muscle layer of the earthworm.

A rhythmically discharging neuron in the earthworm ventral cord nerve as identified by lucifer yellow-CH injection.

In the process of mapping the ganglionic neurons in the earthworm ventral nerve cord by simultaneous recording and Lucifer Yellow-CH injection or by backfilling, a rhythmically discharging neuron with a continuous train of 100 cps over the entire recording period was encountered at the dorsal side of the cord near the base of the 2nd-3rd nerves, with its axon extending toward the 2nd-3rd contralateral nerves. It could not be determined whether branches of this axon entered these contralateral nerves. The rhythmic discharge could not be recorded extracellularly from the nerves or from the cord by suction or hook electrodes, nor did the cell respond to either intra- or extracellular stimulation through the recording and injection microelectrode. Although contralateral neurons have been described in histological works, this neuron may not be identifiable one of them until its relationship with other neurons becomes clear.

Lucifer yellow-CH identification of a primary neuron connecting the first segmental nerve to the three giant axons in the nerve cord of the earthworm Amynthas hawayanus.

This is the first step in the identification of a primary or first-order neuron connecting terminal organs, such as receptors or muscle, to interneurons, such as giant axons. The preparation employed here was a single segment of the ventral nerve cord between the 30th and the 40th segment, with a single first segmental nerve connected. A small drop of 7% Lucifer Yellow-CH was placed at the cut end of the first nerve in the absence of detergent or electric current. A structured complex could be seen in the cord anterior to the first nerve after one or two min backfilling. Several long processes extend from this structure to the contralateral side of the nerve cord and terminate in button-like structures near the medial giant axon and the contralateral lateral giant axon. The afferent or efferent function of this neural complex remains to be determined.

Responses to electrical and mechanical stimuli of the epithelium in earthworm giant axons identified by lucifer yellow-CH dye.

The present study shows a correlation between the evoked response and the cell where the response was recorded. The cells in question are the three giant axons, one median giant fiber (MGF) and two lateral giant fibers (LGF), and the responses were evoked by electrical and mechanical stimuli applied to the epithelial surface of an isolated neuromuscular preparation from the earthworm, Amynthas hawayanus. Extra- and intracellular responses were recorded from the ventral nerve cord and from the three giant axons. Lucifer Yellow-CH was injected into the axon simultaneously while recording intracellularly with a Dagan 8,500 high impedance bridge system. The action potentials thus evoked were conducted antero-posteriorly and postero-anteriorly in both types of giant axons. Different latencies were found between the electrically and the mechanically evoked responses and between the responses recorded from the MGF and from the LGF. These differences may be attributed to different neuronal circuits conveying these responses to both giant axons.