RESUMO
It has been reported that T helper 17 cells are involved in the pathogenesis of systemic lupus erythematosus, but there is no report on interleukin-17-targeted therapy. We report a case of a 62-year-old female who presented with psoriasis vulgaris and refractory lupus nephritis. Because her conditions were resistant to conventional treatment, and flow cytometry confirmed the proliferation of activated T helper 17 cells in peripheral blood, and examination of a renal biopsy tissue sample confirmed infiltration of numerous interleukin-17-positive lymphocytes to the renal interstitium, administration of the anti-interleukin-17A antibody secukinumab was initiated. After starting secukinumab the clinical and biological features were improved.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Interleucina-17/antagonistas & inibidores , Nefrite Lúpica/complicações , Psoríase/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Interleucina-17/sangue , Pessoa de Meia-IdadeRESUMO
Opioids, such as morphine and fentanyl, are widely used as effective analgesics for the treatment of acute and chronic pain. In addition, the opioid system has a key role in the rewarding effects of morphine, ethanol, cocaine and various other drugs. Although opioid sensitivity is well known to vary widely among individual subjects, several candidate genetic polymorphisms reported so far are not sufficient for fully understanding the wide range of interindividual differences in human opioid sensitivity. By conducting a multistage genome-wide association study (GWAS) in healthy subjects, we found that genetic polymorphisms within a linkage disequilibrium block that spans 2q33.3-2q34 were strongly associated with the requirements for postoperative opioid analgesics after painful cosmetic surgery. The C allele of the best candidate single-nucleotide polymorphism (SNP), rs2952768, was associated with more analgesic requirements, and consistent results were obtained in patients who underwent abdominal surgery. In addition, carriers of the C allele in this SNP exhibited less vulnerability to severe drug dependence in patients with methamphetamine dependence, alcohol dependence, and eating disorders and a lower 'Reward Dependence' score on a personality questionnaire in healthy subjects. Furthermore, the C/C genotype of this SNP was significantly associated with the elevated expression of a neighboring gene, CREB1. These results show that SNPs in this locus are the most potent genetic factors associated with human opioid sensitivity known to date, affecting both the efficacy of opioid analgesics and liability to severe substance dependence. Our findings provide valuable information for the personalized treatment of pain and drug dependence.
Assuntos
Analgésicos Opioides/administração & dosagem , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 2/genética , Metilases de Modificação do DNA/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/etiologia , Escalas de Graduação Psiquiátrica , Procedimentos de Cirurgia Plástica/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/genética , Adulto JovemRESUMO
Thoracic surgery poses a risk for complications in the respiratory system. In particular, for patients with bronchial asthma, we need to care for perioperative complications because it is well known that these patients frequently have respiratory complications after surgery, and they may have bronchial spasms during surgery. If we can get good control of their bronchial asthma, we can usually perform surgery for these patients without limitations. For safe postoperative care, it is desirable that these patients have stable asthma conditions that are well-controlled before surgery, as thoracic surgery requires intrabronchial intubation for anesthesia and sometimes bronchial resection. These stimulations to the bronchus do not provide for good conditions because of the risk of bronchial spasm. Therefore, we should use the same agents that are used to control bronchial asthma if it is already well controlled. If it is not, we have to administer a ß2 stimulator, aminophylline, or steroidal agents for good control. Isoflurane or sevoflurane are effective for the safe control of anesthesia during surgery, and we should use a ß2 stimulator, with or without inhalation, or steroidal agents after surgery. It is important to understand that we can perform thoracic surgery for asthma patients if we can provide perioperative control of bronchial asthma, although these patients still have severe risks.
Assuntos
Asma/complicações , Procedimentos Cirúrgicos Torácicos , Asma/terapia , Feminino , HumanosRESUMO
AIMS: The aim of this study was to isolate a thermotolerant micro-organism that produces polyhydroxyalkanoates (PHAs) composed of medium-chain-length (mcl) HA units from a biodiesel fuel (BDF) by-product as a carbon source. METHODS AND RESULTS: We successfully isolated a thermotolerant micro-organism, strain SG4502, capable to accumulate mcl-PHA from a BDF by-product as a carbon source at a cultivation temperature of 45°C. The strain could also produce mcl-PHA from acetate, octanoate and dodecanoate as sole carbon sources at cultivation temperatures up to 55°C. Taxonomic studies and 16S rRNA gene sequence analysis revealed that strain SG4502 was phylogenetically affiliated with species of the genus Pseudomonas. This study is the first report of PHA synthesis by a thermotolerant Pseudomonas. CONCLUSIONS: A novel thermotolerant bacterium capable to accumulate mcl-PHA from a BDF by-product was successfully isolated. SIGNIFICANCE AND IMPACT OF THE STUDY: A major issue regarding industrial production of microbial PHAs is their much higher production cost compared with conventional petrochemical-based plastic materials. Especially significant are the cost of a fermentative substrate and the running cost to maintain a temperature suitable for microbial growth. Thus, strain SG4502, isolated in this study, which assimilates BDF by-product and produces PHA at high temperature, would be very useful for practical application in industry.
Assuntos
Microbiologia Industrial , Poli-Hidroxialcanoatos/biossíntese , Pseudomonas/isolamento & purificação , Pseudomonas/metabolismo , Biocombustíveis , Carbono/metabolismo , DNA Bacteriano/genética , Temperatura Alta , Filogenia , Pseudomonas/genética , RNA Ribossômico 16S/genéticaRESUMO
A 77-year-old man complained general fatigue and fever. Preoperative echocardiography revealed vegetation of aortic valve, abnormal shunt flow from the sinus of Valsalva was detected in the right atrium and ventricle without perivalvular abscess cavity or aneurysm of the sinus of Valsalva. He diagnosed aortic valve endocarditis with aorto-right atrium and ventricle fistula. He received aortic valve replacement and patch closure at the sinus of Valsalva using the pericardium. Residural aortic-right atrium and ventricle shunt was not detected after the operation, the post operative course was uneventful without congestive heart failure nor signs of infection.
Assuntos
Endocardite/complicações , Fístula/complicações , Cardiopatias/complicações , Seio Aórtico , Fístula Vascular/complicações , Idoso , Endocardite/cirurgia , Fístula/cirurgia , Átrios do Coração , Cardiopatias/cirurgia , Ventrículos do Coração , Humanos , Masculino , Fístula Vascular/cirurgiaRESUMO
A 59-year-old man was admitted to our hospital because of angina pectoris and a large right coronary aneurysm. Two years previously, he underwent percutaneous coronary balloon angioplasty for a stenotic lesion in right coronary artery (RCA) #3. Angiography and computed tomography showed a large right coronary aneurysm. On-pump coronary artery bypass grafting (CABG), ligation of RCA proximal and distal to the aneurysm, resection of the aneurysm was performed successfully. Postoperative course was uneventful with satisfactory angiographic results.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Aneurisma Coronário/etiologia , Aneurisma Coronário/cirurgia , Infarto do Miocárdio/terapia , Aneurisma Coronário/diagnóstico , Ponte de Artéria Coronária , Diagnóstico por Imagem , Humanos , Ligadura , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
A 31-year-old man with systemic lupus erythematosus had received long term steroid therapy. He had no compliant, but magnetic resonance imaging showed aortic dissection and annulo-aortic ectasia. Echocardiogram showed severe aortic regurgitation. Therefore aortic root replacement was performed. A histological study of the aortic wall demonstrated myxomatous degeneration in the media. He recovered uneventfully, except for receiving continious hemodia filtration during 4 days after the operation
Assuntos
Aneurisma Aórtico/etiologia , Aneurisma Aórtico/cirurgia , Dissecção Aórtica/etiologia , Dissecção Aórtica/cirurgia , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Lúpus Eritematoso Sistêmico/complicações , Adulto , Dissecção Aórtica/diagnóstico , Aneurisma Aórtico/diagnóstico , Insuficiência da Valva Aórtica/diagnóstico , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/cirurgia , Diagnóstico por Imagem , Dilatação Patológica/diagnóstico , Dilatação Patológica/etiologia , Dilatação Patológica/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , MasculinoRESUMO
We report 3 cases of endovascular stent-grafting (ESG) for mycotic thoracic aortic aneurysm. The case 1 was a rupture of pseudoaneurysm of the descending aorta caused by mediastinitis due to perforation of esophageal ulcer. The patient underwent emergent ESG for temporary control of the rupture. He underwent esophagus reconstruction 5 month after ESG. The case 2 was admitted due to inflammatory reaction. She was diagnosed with mycotic descending aortic aneurysm and underwent elective ESG because of her old age. Her postoperative course was uneventful and no infection recurred. The case 3 underwent ESG for a ruptured mycotic descending aortic aneurysm. But 113 days after ESG, he underwent ESG again for a ruptured endoleak of the stentgraft. His blood culture demonstrated methillin-resistant Staphylococcus aureus (MRSA). He died of rupture to bronchus and esophagus at 18th day after ESG. We believe that ESG is useful in high risk patients for temporary management of the rupture.
Assuntos
Falso Aneurisma/cirurgia , Aneurisma Infectado/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular/métodos , Stents , Adulto , Idoso de 80 Anos ou mais , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
A 65-year-old man was admitted to the hospital because of effort chest pain, 8 years after he received coronary artery bypass grafting [CABG: left internal thoracic artery (LITA) to left anterior descending artery (LAD), saphenous vein graft (SVG) to first diagonal branch (D1) and SVG to postero-lateral branch (PL)]. Emergent coronary angiography revealed right coronary artery occlusion with well patent bypass grafts. Percutaneus coronary intervention (PCI) was performed successfully, but 9 hours later, ventricular septal perforation (VSP) was occurred. Swan-Ganz catheter revealed that pulmonary to systemic blood flow ratio (Qp/Qs) was 2.6. In spite of intensive medical care, his hemodynamics was gradually exacerbated. Subsequent intracavitary repair with equine pericardial patch, sutured using interrupted mattress sutures with felt pledgets, was performed. He had an uneventful recovery thereafter, extubated and weaned from an intra-aortic balloon pumping at the 1st day. He was discharged from hospital on the 27th postoperative day.
Assuntos
Infarto do Miocárdio/complicações , Ruptura do Septo Ventricular/etiologia , Ruptura do Septo Ventricular/cirurgia , Angina Pectoris/cirurgia , Angioplastia Coronária com Balão , Procedimentos Cirúrgicos Cardíacos , Ponte de Artéria Coronária , Humanos , Masculino , Infarto do Miocárdio/terapia , Fatores de Tempo , Resultado do TratamentoRESUMO
The synaptic localization of the N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) channel is a prerequisite for synaptic plasticity in the brain. We generated mutant mice carrying the carboxy-terminal truncated GluR epsilon2 subunit of the NMDA receptor channel. The mutant mice died neonatally and failed to form barrelette structures in the brainstem. The mutation greatly decreased the NMDA receptor-mediated component of hippocampal excitatory postsynaptic potentials and punctate immunofluorescent labelings of GluR epsilon2 protein in the neuropil regions, while GluR epsilon2 protein expression was comparable. Immunostaining of cultured cerebral neurons showed the reduced punctate staining of the truncated GluR epsilon2 protein at synapses. These results suggest that the carboxy-terminal region of the GluRepsilon2 subunit is important for efficient clustering and synaptic localization of the NMDA receptor channel.
Assuntos
Encéfalo/fisiologia , Hipocampo/fisiologia , Células Piramidais/fisiologia , Receptores de AMPA/fisiologia , Sinapses/fisiologia , Vias Aferentes/fisiologia , Animais , Células Cultivadas , Estimulação Elétrica , Biblioteca Genômica , Técnicas In Vitro , Substâncias Macromoleculares , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Knockout , Camundongos Mutantes Neurológicos , Fibras Nervosas/fisiologia , Plasticidade Neuronal , Reação em Cadeia da Polimerase , Deleção de Sequência , Células-Tronco , Transmissão Sináptica/fisiologia , TransfecçãoRESUMO
The large-scale copy-number variations (CNVs) in the human genome are associated with developmental disorders and susceptibility to diseases. More importantly, CNVs may represent a major genetic component of our phenotypic diversity. Following the development of methodologies and introduction of new research platforms, accumulation of the nature and pattern of CNVs from normal populations has progressed. The examination of relatively large numbers of specific ethnic groups has recently started. Although the results are not always consistent, it is likely that different human populations bear different CNVs, as is the case for single-nucleotide polymorphisms (SNPs) and insertion-deletion (indel) polymorphisms. We review recent publications about the nature of inter-population, especially inter-ethnic group, differences of CNVs.
Assuntos
Etnicidade/etnologia , Etnicidade/genética , Dosagem de Genes/genética , População/genética , Hibridização Genômica Comparativa , Simulação por Computador , Humanos , Análise de Sequência com Séries de OligonucleotídeosRESUMO
Chordoma is an uncommon primary bone tumor and the thoracic spine is the least common of all sites for a chordoma. It may recur despite slow-growing nature. Precise literature review will be performed and possible use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) for detection of both primary and recurrent diagnosis will be discussed. This article presents the case of a 73-year-old male patient who complained of back pain. Magnetic resonance (MR) imaging, computed tomography (CT) and FDG-PET demonstrated thoracic lesion and biopsy revealed chordoma. The patient was operated on and histological findings showed the tumor was chondroid chordoma. He suffered recurrence after 7 months by FDG-PET. He received 6,000 rads radiation therapy and is neurological free but, suffered backache 15 months after initial diagnosis. Only 12 cases including this case were reported precisely and this is the first report of FDG-PET for both initial and recurrent diagnosis of chordoma.
Assuntos
Cordoma/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Vértebras Torácicas/diagnóstico por imagem , Idoso , Dor nas Costas/etiologia , Biópsia , Cordoma/patologia , Cordoma/terapia , Diagnóstico Diferencial , Erros de Diagnóstico/prevenção & controle , Humanos , Imageamento por Ressonância Magnética , Masculino , Recidiva Local de Neoplasia/radioterapia , Procedimentos Neurocirúrgicos , Valor Preditivo dos Testes , Neoplasias da Coluna Vertebral/patologia , Neoplasias da Coluna Vertebral/terapia , Vértebras Torácicas/patologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
The role of bone marrow (BM)-derived cells in the process of pancreatic islet regeneration remains unclear. The purpose of this study was to determine the role of BM cells in the repair process or regeneration of pancreatic islets in mice using chimeric green fluorescent protein (GFP) expressing BM cells. BM-infused chimeric mice were made diabetic by streptozotocin (STZ) injection or 60% partial pancreatectomy. GFP-positive cells within the islets and pancreas were studied immunohistologically. STZ treatment induced a 10-fold increase in PCNA-positive cells within the islets on day 7 posttreatment. GFP-positive cells increased in number within the islets as well as in the pancreatic parenchyma immediately after STZ injection. The partial pancreatectomy induced 2- to 3-fold increases on day 7 to 28 posttreatment. GFP-positive cells increased in number in pancreatic parenchyma but not within the islets. BM traffic to the pancreas significantly increased in the 2 models inducing islet regeneration. In both models, GFP-positive cells were not positive for antibodies against insulin, glucagon, or somatostatin, but were positive for markers of macrophages or fibroblasts, suggesting their involvement in the initiation of islet regeneration.
Assuntos
Células da Medula Óssea/fisiologia , Transplante de Medula Óssea , Ilhotas Pancreáticas/fisiologia , Regeneração/efeitos dos fármacos , Estreptozocina/farmacologia , Animais , Genes Reporter , Insulina/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Pancreatectomia , Antígeno Nuclear de Célula em Proliferação/análiseRESUMO
Autologous blood transfusion (ABT) is rarely employed in patients with end-stage renal disease (ESRD); these patients are usually anemic. Since 1998, we have attempted ABT for ESRD patients undergoing living-related kidney transplantation. Among 20 patients enrolled in this study the preoperative hemoglobin and hematocrit levels were 10.0 +/- 1.2 mg/dL (range, 8.1-11.7) and 30.0 +/- 3.7% (range, 24.7-34.3), respectively. Blood volume collected on each occasion was 235.7 +/- 57.7 mL (range, 200-400), and the number of blood collections was 2.45 +/- 0.9 (range, 1-4). Total collected volume was 567.5 +/- 157.5 mL (range, 400-800). Symptomatic hypotension was seen in two patients, but vital signs recovered spontaneously. No other problems related to blood collection were observed. Allogeneic transfusion was need in only one patient (5%). ABT was safe and efficacious in ESRD patients scheduled for living-related kidney transplantation.
Assuntos
Transfusão de Sangue Autóloga , Transplante de Rim/fisiologia , Adolescente , Adulto , Anemia/etiologia , Família , Feminino , Hematócrito , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Diálise RenalRESUMO
We report a patient with Marfan syndrome who received successful 7 consecutive operations during 11 years. She underwent descending aortic replacement for chronic type B dissection at the age of 24. Mitral valve replacement (MVR) was performed for mitral regurgitation (MR) at the age of 30, and abdominal aortic replacement was done for persistent dissection at the age of 31, aortic root and arch replacement was done at the age of 34. The 9 months later, she received re-MVR for dysfunction of bioprosthesis and tricuspid valve anuloplasty (TAP) for tricuspid regurgitation (TR). But severe paravalvuler leakage of mitral valve necessitated direct closure of detachment. Thoracoabdominal replacement was performed for rupture of persistent dissection at the age of 35. She was discharged on the 54th day after the 7th surgery.
Assuntos
Síndrome de Marfan/cirurgia , Adulto , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Aneurisma Aórtico/cirurgia , Feminino , Humanos , Insuficiência da Valva Mitral/cirurgia , Reoperação , Valva Tricúspide/cirurgiaRESUMO
A 74-year-old man had pustulant bilateral arthritis complicated with sepsis and disseminated intravascular coagulation (DIC). Microbiologic study of blood sample showed Streptococcus and methicillin resistant Staphylococcus aureus (MRSA). He was complicated with postulant diskitis since then. Medical treatment for DIC and administration of antibiotics were performed. Preoperative echocardiography revealed massive aortic regurgitation and vegetation of aortic valve, moderate pulmonary regurgitation and vegetation of pulmonary valve, massive mitral regurgitation, massive tricuspid regurgitation. He was diagnosed as infective quadruple valve endocarditis. He received aortic valve replacement, pulmonary valve replacement, mitral valve repair and tricuspid valve repair. Postoperative echocardiography showed satisfactory function of bioprosthesis. Postoperative course was uneventful.
Assuntos
Endocardite/cirurgia , Doenças das Valvas Cardíacas/cirurgia , Valvas Cardíacas/cirurgia , Idoso , Endocardite/microbiologia , Doenças das Valvas Cardíacas/microbiologia , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Resistência a Meticilina , Índice de Gravidade de Doença , Infecções Estafilocócicas , Infecções Estreptocócicas , Resultado do TratamentoRESUMO
BACKGROUND: The levels of corneal donation are insufficient to meet the demand for corneal transplantation in Japan. To overcome this problem, we started to routinely mention the possibility of corneal donation to the families of patients who died in our hospital's Urology Department in February 2008. In this study, we evaluated the effectiveness of this approach. METHODS: We retrospectively reviewed the medical records of the patients who died in the Department of Urology, St. Marianna University School of Medicine Hospital, and analyzed the patients' characteristics and information about corneal donation. RESULTS: In total, 211 patients died in our department between February 2008 and March 2017, and 155 patients were medically suitable corneal donors. We mentioned the possibility of corneal donation to 129 (83.2%) families, and 29 (18.7%) families agreed. Three families subsequently withdrew their consent. Finally, 26 (16.8%) of the families that were approached about corneal donation by urologists agreed to donate their relatives' corneas. Another 2 families voluntarily offered to donate their relatives' corneas. Thus, 28 (18.1%) of 155 medically suitable donors donated their corneas for transplantation. Twenty-six (92.8%) donors were 60 years or older and all donors were affected with malignant genitourinary tumors. Fifty-four (96.4%) corneas were successfully transplanted into recipients. CONCLUSIONS: Even elderly patients who die of solid carcinoma can be an important source of corneal donors. In this study, we showed that routine referral by urologists increased corneal donation. If this approach were adopted by other departments, it might further increase the number of corneal donations.
Assuntos
Transplante de Córnea , Encaminhamento e Consulta , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/métodos , Transplantes/provisão & distribuição , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Urológicas/mortalidade , UrologistasRESUMO
Water scarcity is rapidly increasing in many regions. In a novel, multi-model assessment, we examine how human interventions (HI: land use and land cover change, man-made reservoirs and human water use) affected monthly river water availability and water scarcity over the period 1971-2010. Here we show that HI drastically change the critical dimensions of water scarcity, aggravating water scarcity for 8.8% (7.4-16.5%) of the global population but alleviating it for another 8.3% (6.4-15.8%). Positive impacts of HI mostly occur upstream, whereas HI aggravate water scarcity downstream; HI cause water scarcity to travel downstream. Attribution of water scarcity changes to HI components is complex and varies among the hydrological models. Seasonal variation in impacts and dominant HI components is also substantial. A thorough consideration of the spatially and temporally varying interactions among HI components and of uncertainties is therefore crucial for the success of water scarcity adaptation by HI.
RESUMO
Primary epidermal keratinocytes obtained from 25 patients with xeroderma pigmentosum (XP) (nine with XP-A, one with XP-C, two with XP-D, five with XP-E, and eight with XP-variant) exhibited less UV-induced unscheduled DNA synthesis (UDS) than did those from 34 normal subjects. Levels of UDS depended greatly on the type of XP; i.e., 3-17% of the control in XP-A, 14% in XP-C, 33-53% in XP-D, 38-77% in XP-E and 58-98% in XP-variant. The extent of UDS in epidermal keratinocytes was almost the same as that in dermal fibroblasts in XP-C, D, and E, but in three out of eight of the XP-variant the level of UDS in epidermal keratinocytes was significantly lower than that in normal subjects. Clinically, three out of nine XP-A patients developed skin neoplasms before 20 years of age. Both patients with XP-D developed skin neoplasms around 40 years of age. In the five XP-E patients, two developed multiple basal cell epithelioma on sun-exposed areas during the forth decade, and one of them also developed squamous cell carcinoma at the age of 50. Four out of the eight patients with the XP-variant developed various skin neoplasms during their 20s and 30s. These results suggest that a defect in UV-induced UDS in epidermal keratinocytes of XP patients is responsible for skin carcinogenesis and the extent to which this defect occurs tends to relate to the age of onset of skin neoplasms.