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Reversible exacerbation of parkinsonism during epirubicin-cyclophosphamide chemotherapy in a patient with PTEN hamartoma tumor syndrome and young-onset Parkinson's disease.

BACKGROUND: PTEN hamartoma tumor syndrome (PHTS), caused by germline loss-of-function variants in PTEN, typically manifests as macrocephaly, neurodevelopmental disorders, and cancer susceptibility. Parkinson's disease has not been recognized as part of its known neurological spectrum. METHODS: We describe the clinical course of a patient with a germline PTEN nonsense variant (p.Arg130Ter) who developed young-onset Parkinson's disease before being diagnosed with bilateral breast cancer. RESULTS: The patient developed asymmetric, levodopa-responsive parkinsonism at 35 years of age, with reduced bilateral striatal dopamine transporter uptake. During two cycles of epirubicin-cyclophosphamide chemotherapy, her previously well-controlled parkinsonism showed reproducible and severe exacerbations. Symptoms began several days after chemotherapy, reached their maximum severity approximately one week after treatment, and resolved completely within approximately two weeks without modification of her antiparkinsonian medications. No dehydration, electrolyte disturbance, infection, or exposure to dopamine-receptor antagonists was identified. The chemotherapy regimen was discontinued after the second episode because of the reproducible temporal association. CONCLUSIONS: This case demonstrates reproducible, fully reversible exacerbations of parkinsonism during epirubicin-cyclophosphamide chemotherapy in a patient with PHTS and young-onset Parkinson's disease. These episodes may reflect transient vulnerability of dopaminergic neurons to chemotherapy-related systemic stress, although the causal role of PTEN haploinsufficiency remains uncertain.

Humans↗

Pathogenesis of cardiotoxicity induced by anthracyclines.

Anthracyclines are potent anti-neoplastic drugs used in the treatment of solid and hematologic cancers. However, their use is limited by cumulative dose-related cardiotoxic adverse effects, which are progressive and irreversible from the first dose. Clinical trial data have shown that anthracycline cardiotoxicity is associated with slowly progressive deterioration of cardiac function, which continues for years after treatment cessation. Cardiac damage has been shown at cumulative doses as low as 200 mg/m2, well below levels currently assumed to induce injury. The widespread use of anthracyclines in childhood leukemia has resulted in an improved long-term prognosis; however, these patients are subsequently at high risk of developing long-term cardiac damage, with studies suggesting as many as 65% of survivors of childhood leukemia will develop cardiac abnormalities. Middle aged and elderly patients who are prone to cardiac disease may be more vulnerable to the cardiotoxic effects of anthracyclines. Therapies or strategies to prevent anthracycline-induced cardiotoxicity are essential; ideally, these should be initiated at the beginning of anthracycline therapy to reduce the possibility of cardiac damage and to ensure the optimal use of chemotherapy.

Anthracyclines↗

The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical study.

Glutathione (GSH) concentration is high in most tumour cells and this may be an important factor in resistance to chemotherapy. Previous in-vitro and animal experiments have shown a differential response of tumour versus normal cells to various cysteine delivery systems. More specifically, an in-vitro assay showed that at concentrations that induce GSH synthesis in normal human cells, a specially prepared whey protein concentrate, Immunocal, caused GSH depletion and inhibition of proliferation in human breast cancer cells. On the basis of this information five patients with metastatic carcinoma of the breast, one of the pancreas and one of the liver were fed 30 grams of this whey protein concentrate daily for six months. In six patients the blood lymphocyte GSH levels were substantially above normal at the outset, reflecting high tumour GSH levels. Two patients (#1, #3) exhibited signs of tumour regression, normalization of haemoglobin and peripheral lymphocyte counts and a sustained drop of lymphocyte GSH levels towards normal. Two patients (#2, #7) showed stabilisation of the tumour, increased haemoglobin levels. In three patients (#4, #5, #6,) the disease progressed with a trend toward higher lymphocyte GSH levels. These results indicate that whey protein concentrate might deplete tumour cells of GSH and render them more vulnerable to chemotherapy.

Adenocarcinoma↗

Antioxidants in food and chronic degenerative diseases.

Both preventive and chain breaking antioxidants have a role in the limitation of free radical damage. Some of these may be regarded as "classical", like vitamins E and C but others are more recently discovered, such as the flavonoids, widespread in plant tissues, and the muscle constituents anserine and carnosine. The major conditions in which the role of antioxidants is under intense investigation include coronary artery disease, cancer and diabetes. There are theoretical underpinnings for the efficacy of antioxidants in each of these, with the protection of low density lipoprotein (in respect of the first) being exceptionally persuasive. Much attention is now being focussed on the flavonoids, which are surprisingly pleiotropic in their effects. For one of them, quercetin, over a dozen seemingly independent biological effects can be listed, including the inhibition of low density lipoprotein oxidation. Flavonoids also inhibit peroxidation in foodstuffs, as opposed to tissues. There is much controversy over antioxidant supplementation policies, some authorities recommending a massive programme of supplementation for all ages and classes, others stressing the value of the traditional mixed diet. This matter is unlikely to be resolved soon, but in the meantime sensible supplementation policies should be continued for those most vulnerable, that is, babies and the aged.

Antioxidants↗

Use of preventive care by the working poor in the United States.

OBJECTIVE: Examine the association between poverty and preventive care use among older working adults. METHOD: Cross-sectional analysis of the pooled 1996, 1998 and 2000 waves of the Health and Retirement Study, a nationally representative sample of older community-dwelling adults, studying self-reported use of cervical, breast, and prostate cancer screening, as well as serum cholesterol screening and influenza vaccination. Adults with incomes within 200% of the federal poverty level were defined as poor. RESULTS: Among 10,088 older working adults, overall preventive care use ranged from 38% (influenza vaccination) to 76% (breast cancer screening). In unadjusted analyses, the working poor were significantly less likely to receive preventive care. After adjustment for insurance coverage, education, and other socio-demographic characteristics, the working poor remained significantly less likely to receive breast cancer (RR 0.92, 95% CI, 0.86-0.96), prostate cancer (RR 0.89, 95% CI, 0.81-0.97), and cholesterol screening (RR 0.91, 95% CI, 0.86-0.96) than the working non-poor, but were not significantly less likely to receive cervical cancer screening (RR 0.96, 95% CI, 0.90-1.01) or influenza vaccination (RR 0.92, 95% CI, 0.84-1.01). CONCLUSION: The older working poor are at modestly increased risk for not receiving preventive care.

Cost of Illness↗

Different effects of fractionated irradiation on potassium efflux and exocytotic amylase release.

Irradiation of head-neck cancer influences the salivary glands with dryness and discomfort for the patients as a consequence. In the present study we used in vitro secretory models and morphological characterization of rat parotid gland. Irradiation was given as a 5-day schedule with total doses from 20 Gy to 45 Gy. Electrolyte secretion (86Rb as indicator for potassium) caused by noradrenaline was decreased in correlation to irradiation dose delivered compared to controlateral control glands 10 days following irradiation. Noradrenaline stimulated exocytotic amylase release was not at all affected, and there were no signs of quantitative morphological alterations following irradiation compared to control glands. The results indicate that there are differences in radiation sensitivity for the two different secretory processes in the salivary glands; the structures regulating electrolyte and fluid secretion seem to be more vulnerable to irradiation than those regulating exocytosis.

Amylases↗

Pain-sensitive temperament: does it predict procedural distress and response to psychological treatment among children with cancer?

OBJECTIVE: To evaluate the relationship between pain sensitivity and children's distress during lumbar punctures (LPs), and whether pain sensitivity functions as a moderator of children's responses to a psychological intervention aimed at reducing LP distress. METHOD: Fifty-five children with acute lymphoblastic leukemia (ages 3 to 18) and their parents completed a questionnaire measure of pain sensitivity. Self-report, physiological, and observed measures of distress were collected during the study baseline LP. Children were then randomized into a psychological intervention or an attention control group. Postintervention and follow-up LPs were observed. RESULTS: Higher levels of pain sensitivity were associated with greater anxiety and pain, both prior to and during the LP. Preliminary analyses indicated that pain sensitivity moderated the effects of intervention on distress. Children who were more pain-sensitive and who received no intervention showed greater increases in LP distress over time. In contrast, children who were more pain-sensitive and who received intervention showed greater decreases in LP distress over time. CONCLUSIONS: A measurement of pain sensitivity may be useful in pediatric oncology settings for effectively targeting pain-vulnerable children for psychological intervention. Preliminary analyses indicate that an empirically-supported intervention for procedural distress is efficacious for those children who are most pain-sensitive.

Adaptation, Psychological↗

The health of the California region bordering Mexico.

Healthy Border (HB) 2010 is the health promotion and disease prevention agenda through the year 2010 of the United States-Mexico Border Health Commission (BHC). On the United States side, it draws from the Healthy People (HP) 2010 objectives, identifying those most important and relevant for the border. The BHC has harmonized the list of objectives from both countries into a set of 19 that will be monitored and addressed in a collaborative manner. HB provides a framework for describing the border region's health and comparing with others. For this report, available data were collected for the HB indicators for San Diego and Imperial counties, and for California. Data on Latino populations were considered a proxy for Mexican-Americans and people of Mexican origin in California, because more specific data are not available. Results are presented on the 14 indicators for which the data were most complete. Those of most concern include access to health care and tuberculosis in both counties, plus motor vehicle crash injury deaths and asthma hospitalizations in Imperial. These issues should be given priority attention. Conversely, the region's and Latinos' experience with breast cancer mortality and infant mortality is favorable. Recommendations include binational collaborations in assessing and improving the health of our border communities.

Accidents, Traffic↗

Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores.

BACKGROUND: Although iron deficiency occurs commonly in vulnerable groups of women of reproductive age, infants, and children, less is known about the iron nutriture of the elderly. OBJECTIVE: Our objective was to evaluate the iron status of a noninstitutionalized, elderly US population, with a particular focus on 2 concerns unique to the elderly: 1) potential confounding effects of chronic disease on iron measures and 2) increased occurrence of elevated iron stores. DESIGN: Multiple iron measures, including serum ferritin (SF), transferrin saturation, mean cell volume, and hemoglobin, were used to evaluate the prevalence of iron deficiency (ID), iron deficiency anemia (IDA), and other measures of iron nutriture in 1016 elderly white Americans aged 67-96 y from the Framingham Heart Study. "Diseased" subjects were defined as those with possible pathologically altered iron measures due to inflammation, infection, elevated liver enzymes, hereditary hemochromatosis, or cancer. The effect of altered iron status on various prevalence estimates was assessed. RESULTS: The elderly subjects had a low prevalence of ID (2.7%), IDA (1.2%), and depleted iron stores (3%; SF < 12 microg/L). In contrast, 12.9% had elevated iron stores (SF > 300 microg/L in men and SF > 200 microg/L in women), of which only 1% was attributable to chronic disease. The prevalence of ID, IDA, and depleted iron stores was unaffected by the presence of chronic disease. CONCLUSIONS: The Framingham Heart Study cohort is an iron-replete elderly population with a high prevalence of elevated iron stores in contrast with a low prevalence of iron deficiency, with insignificant effects of chronic disease on these iron status estimates. The likely liability in iron nutriture in free-living, elderly white Americans eating a Western diet is high iron stores, not iron deficiency.

Aged↗

Mortality, behavior and the effects of predators on the intertidal distribution of littorinid gastropods.

Predators can affect the vertical distribution of mobile intertidal invertebrates in two ways: they can (1) cause greater mortality of prey at certain intertidal levels, and (2) induce prey to seek safer intertidal areas. In this study, we investigate whether low-intertidal and subtidal predators affect the intertidal distribution of two congeneric species of small herbivorous gastropods of northeastern Pacific shores, Littorina sitkana Philippi 1846, and L. scutulata Gould 1849. In particular, we tested the hypothesis that predators affect the distribution of these snails by inducing them to seek higher and safer intertidal areas. On a wave-sheltered shore in Barkley Sound, British Columbia, L. sitkana and L. scutulata were both killed by predatory crabs (e.g., Cancer productus) more frequently when tethered near the lower limit of their intertidal distribution ( approximately 1 m) than when tethered where they were most common ( approximately 2.5 m), suggesting that high mortality rates are partly responsible for the lower-limit of these snails' intertidal distribution. However, two field mark-recapture experiments indicated that the snails' behavioral response to predation risk also influences their distribution. In the first experiment, snails from the 2.5-m level (low risk) transplanted to the 1.0-m level (high risk) displayed a strong and consistent tendency to move shoreward, especially L. sitkana, some traveling 10-15 m in 2-3 days to regain their original level. These shoreward movements were especially precise in the northern part of the study area, where predation rates on tethered snails were greatest. Furthermore, larger more vulnerable snails were more strongly oriented shoreward than smaller individuals, indicating that antipredator behavior might also contribute to intertidal size gradients in these species. In the second mark-recapture experiment, we manipulated predation risk using small cages and found that snails exposed to the odors of C. productus crabs foraging on conspecific and heterospecific snails displayed more precise (L. sitkana and L. scutulata) and longer (L. sitkana) shoreward movements than snails held in control conditions. These results provide the first experimental evidence that antipredator behavior may contribute to the intertidal distribution patterns of littorinids.

Journal Article↗

Is the WHI relevant to HRT started in the perimenopause?

The Women's Health Initiative (WHI) hormone replacement therapy (HRT) estrogen plus progestin (E+P) and estrogen-only arms are part of a large NIH-sponsored randomized controlled trial (RCT). Both arms were terminated prematurely after 5 and 8 yr, respectively. The E+P arm showed non-statistically significant increased incidences of cardiovascular events and breast cancer, whereas the E-only arm did not. Both arms showed an increased rate of thromboembolic events and stroke. Both arms showed protection against fractures and with protection against colon cancer only in the E+P arm. These results have been widely generalized as indicating a negative risk/benefit ratio for HRT in menopausal women. The WHI results are at odds with results of large epidemiological studies that showed protection against cardiovascular disease. Although the latter data are, in part, confounded by a "healthy user bias," much of the inconsistency may be explained by the fact that women in the latter studies initiated HRT at the menopausal transition, whereas the WHI trial was conducted in older women (mean age 63.3), who were, on average, approx 12 yr postmenopausal. In addition, older trials included women on either unopposed estrogen therapy (ERT) or cyclic HRT regimens. Whatever other forces may have been at work, observational and experimental evidence supports the conclusion that estrogen's atheropreventive effects predominate early, in the absence of vulnerable plaque to be ruptured or thrombotic episodes propagated by narrowed lumens and intravascular turbulence. On the contrary, age-related adverse effects of HRT may prevail once complex atheromas and luminal narrowing/irregularity are established. It is known that prevalence of subclinical "at-risk" atherosclerotic lesions increases in women during the first 5-10 yr after menopause. Furthermore, animal and clinical evidence supports the use of lower doses of estrogen than were employed in the WHI in older/longer postmenopausal women.

Arteriosclerosis↗

Assessing the effects of endocrine disruptors in the National Children's Study.

Children are uniquely vulnerable to toxic chemicals in the environment. Among the environmental toxicants to which children are at risk of exposure are endocrine disruptors (EDs)--chemicals that have the capacity to interfere with hormonal signaling systems. EDs may alter feedback loops in the brain, pituitary, gonads, thyroid, and other components of the endocrine system. They can affect development. Effects of EDs have been described in wildlife populations, in animals exposed experimentally, and to a more limited extent in humans. Mechanisms of action of EDs are increasingly being elucidated, and genetic polymorphisms that convey differential susceptibility to EDs are beginning to be explored. It is hypothesized that in utero and early childhood exposures to EDs may be responsible, at least in part, for decreases in semen quality; increasing incidence of congenital malformations of the reproductive organs, such as hypospadias; increasing incidence of testicular cancer; and acceleration of onset of puberty in females. The National Children's Study (NCS) will provide a unique opportunity to test the validity of these hypotheses in the context of a large prospective multi-year epidemiologic investigation. It will be essential in the NCS to assess exposures to a range of putative natural and synthetic EDs, to assess outcomes possibly due to ED exposure, to examine the potential interplay between EDs and genetic polymorphisms, and to seek links between ED exposures in early life and endocrine, reproductive, neurobehavioral, and other outcomes throughout the life span.

Adolescent↗

Melanoma risk and residence in sunny areas. EORTC Melanoma Co-operative Group. European Organization for Research and Treatment of Cancer.

Melanoma risk among subjects from Germany, France and Belgium who had lived for 1 year or more in sunny climates was examined in a one-to-one unmatched case-control study conducted among white subjects 20 years old or more. A total of 412 consecutive patients with melanoma diagnosed from 1 January 1991 onwards, were derived from hospital registers; 445 controls were randomly chosen in the same municipality as the cases. After adjustment for host characteristics, melanoma risk associated with residence in a sunny area was 2.7 (95% CI: 1.4-5.2), increasing to 4.7 (95% CI: 1.4-13.5) if subjects sought a suntan when residing in sunny climates, and to 4.3 (95% CI: 1.7-11.1) if subjects arrived before the age of 10 years in the sunny area. Residence in sunny areas and recreational sun exposure seemed to combine their effects on melanoma risk. Increase in melanoma risk conveyed by deliberate sun exposure during adulthood was highest among subjects who had lived in sunny areas as a child or adolescent and lowest among subjects who had never resided in sunny areas. Our results support conclusions from migrant studies that indicated that childhood is a critical period of either vulnerability to solar radiation or more frequent exposures to melanoma risk factors. They also suggest that moderate sun exposure of an adult who was heavily sun exposed in childhood is associated with a higher melanoma risk than that of high sun exposure of an adult who was sun protected in childhood.

Adult↗

Low activities of glutathione-related enzymes as factors in the genesis of urinary bladder cancer.

A comparative study of reduced glutathione (GSH) concentrations and activities of GSH related-enzymes in urinary bladder transitional epithelium (UBTE), urinary bladder nontransitional tissue (UBNT), and liver of the rabbit, was carried out to investigate the reasons for the susceptibility of UBTE towards peroxidase-mediated chemical carcinogenesis. Cooxidative activation of chemical carcinogens by prostaglandin H synthase occurs at high levels in UBTE and minimally in UBNT. Other peroxidases are also likely to activate carcinogenic xenobiotics in the urinary bladder. GSH concentrations in UBTE and UBNT were low compared to that in the liver. gamma-Glutamyl transpeptidase activities were much lower in UBTE and in UBNT than those in the liver. Activities of selenium-dependent and selenium-independent glutathione peroxidases were very low in UBTE and UBNT. Cytosolic glutathione S-transferase activity towards 1,2-epoxy-(4-nitrophenoxy)propane was very low in UBTE. Microsomal glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene was much lower in UBTE than in the liver. We propose that the low GSH concentration and diminished activities of glutathione peroxidases, gamma-glutamyl transpeptidase, and certain isozymes of glutathione S-transferase could be responsible for the vulnerability of UBTE towards chemical carcinogenesis.

Animals↗

Improving end of life care: an information systems approach to reducing medical errors.

Chronic and terminally ill patients are disproportionately affected by medical errors. In addition, the elderly suffer more preventable adverse events than younger patients. Targeting system wide "error-reducing" reforms to vulnerable populations can significantly reduce the incidence and prevalence of human error in medical practice. Recent developments in health informatics, particularly the application of artificial intelligence (AI) techniques such as data mining, neural networks, and case-based reasoning (CBR), presents tremendous opportunities for mitigating error in disease diagnosis and patient management. Additionally, the ubiquity of the Internet creates the possibility of an almost ideal network for the dissemination of medical information. We explore the capacity and limitations of web-based palliative information systems (IS) to transform the delivery of care, streamline processes and improve the efficiency and appropriateness of medical treatment. As a result, medical error(s) that occur with patients dealing with severe, chronic illness and the frail elderly can be reduced.The palliative model grew out of the need for pain relief and comfort measures for patients diagnosed with cancer. Applied definitions of palliative care extend this convention, but there is no widely accepted definition. This research will discuss the development life cycle of two palliative information systems: the CONFER QOLP management information system (MIS), currently used by a community-based palliative care program in Brooklyn, New York, and the CAREN case-based reasoning prototype. CONFER is a web platform based on the idea of "eCare". CONFER uses XML (extensible mark-up language), a W3C-endorced standard mark up to define systems data. The second system, CAREN, is a CBR prototype designed for palliative care patients in the cancer trajectory. CBR is a technique, which tries to exploit the similarities of two situations and match decision-making to the best-known precedent cases. The prototype uses the opensource CASPIAN shell developed by the University of Aberystwyth, Wales and is available by anonymous FTP. We will discuss and analyze the preliminary results we have obtained using this CBR tool. Our research suggests that automated information systems can be used to improve the quality of care at the end of life and disseminate expert level 'know how' to palliative care clinicians. We will present how our CBR prototype can be successfully deployed, capable of securely transferring information using a Secure File Transfer Protocol (SFTP) and using a JAVA CBR engine.

Artificial Intelligence↗

Oncogenes-antioncogenes and virus therapy of cancer.

Viruses can render services to mankind. 1. Retroviruses pinpoint and transduce cellular oncogenes. 2. Retroviral vectors can introduce antioncogenes (the RB gene) into malignant cells thus rendering the recipient cells nonmalignant. 3. Oncolytic viruses lyse tumor cells. 4. Parvoviruses replicate only in dividing cells and exert lysis and antioncogene effect in tumor cells without affecting resting normal cells. 5. Myxo- and paramyxoviruses (and other viruses) upgrade the immunogenicity of cell surface antigens thus eliciting rejection type host immunity against these cells which is operational against not virus-infected cells of the same type (post-oncolytic antitumor immunity). 6. Viruses or virally infected cells (including tumor cells) induce the production of lymphokines and cytokines (interferons, interleukins and tumor necrosis factor) and activate NK cells and specific immune T cells cytotoxic to virus-infected cells (including tumor cells). 7. Measles virus may activate suppressor cells and both directly (by infecting lymphoma cells) and indirectly (by inducing molecular mediators of suppressor mononuclear cells inhibitory to the growth of neoplastic lymphoid and hematopoietic cells) induce remissions of lympho- and hematopoietic malignancies. 8. Retroviral vectors deliver genes into tumor cells for encoding new surface antigens that render the tumor cells highly antigenic and more vulnerable to rejection type immune reactions of the host. Examples illustrate each statement. Immunotherapy of tumors with active tumor-specific immunization after the induction of suppressor cells by fetal antigens and the elimination of the proliferating suppressor clones by cyclophosphamide will again be proposed.

DNA Transposable Elements↗

The Human Genome Project and eugenic concerns.

The U.S. Human Genome project is the largest scientific project funded by the federal government since the Apollo Moon Project. The overall effect from this project should be of great benefit to humankind because it will provide a better understanding both of single gene defects and multifactorial or familial diseases such as diabetes, arteriosclerosis, and cancer. At first this will lead to more exact ways of screening and diagnosing genetic disease, and later it will lead, in many if not most instances, to specific genetic cures. However, in the past, in both the U.S. and German eugenic movements genetic information has been misused. Hopefully, by remembering and understanding the past injustices and inhumanity of negative eugenics, further misuse of scientific information can be avoided.

Ethical Theory↗

Radiation-induced brachial plexopathy: neurological follow-up in 161 recurrence-free breast cancer patients.

PURPOSE: The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients, treated according to the Danish Breast Cancer Cooperative Group protocols. METHODS AND MATERIALS: One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months (13-99 months). After total mastectomy and axillary node sampling, high-risk patients were randomized to adjuvant therapy. One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks. In addition, 82 of these patients received cytotoxic therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and 46 received tamoxifen. RESULTS: Five percent and 9% of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy, respectively. Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy (p = 0.04) and in younger patients (p = 0.04). The clinical manifestations were paraesthesia (100%), hypaesthesia (74%), weakness (58%), decreased muscle stretch reflexes (47%), and pain (47%). CONCLUSION: The brachial plexus is more vulnerable to large fraction size. Fractions of 2 Gy or less are advisable. Cytotoxic therapy adds to the damaging effect of radiotherapy. Peripheral nerves in younger patients seems more vulnerable. Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus.

Adult↗