Biomarcadores de enfermedad de Alzheimer en deterioro cognitivo leve: experiencia en una clínica de memoria de Latinoamérica / Biomarkers of Alzheimer's disease in mild cognitive impairment: Experience in a memory clinic from Latin America

Objetivo: El objetivo de este estudio fue investigar el rol y pronóstico de los biomarcadores de enfermedad de Alzheimer en pacientes con diagnóstico clínico de deterioro cognitivo leve (DCL) en una clínica de memoria de Latinoamérica.MétodoOchenta y nueve pacientes con DCL, 43 con demencia tipo Alzheimer y 18 controles normales apareados por edad, sexo y escolaridad fueron estudiados con un extenso protocolo demográfico, neurológico y neuropsicológico en la clínica de memoria del Instituto FLENI de Buenos Aires. Todos completaron una RM cerebral, una PET con FDG, una PET con estudios amiloideo (PIB), genotipificación de APOE y estudio de Aβ1-42, tau and f-tau de líquido cefalorraquídeo. Basado en la presencia/ausencia de patología amiloidea y neurodegeneración los pacientes fueron categorizados como A+/A− y N+/N− respectivamente.ResultadosEn el estudio de líquido cefalorraquídeo el 18% de los controles, el 64% de los DCL y el 92% de las demencia tipo Alzheimer tenían patología amiloidea; y un 11% de los controles, el 6% de los DCL y el 8% de las DTA eran sospechosos de fisiopatología no Alzheimer. En el seguimiento a los 30 meses el 45% de los DCL con amiloide positivo y el 20% de los que presentaron amiloide negativo progresaron a demencia.ConclusionesEste estudio muestra el pronóstico de los DCL basado en los biomarcadores, y respalda su importancia en la toma de decisiones en la práctica diaria. (AU)

Objective: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America.MethodsWe studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aβ1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration.ResultsAmyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non–Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia.ConclusionsThis study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice. (AU)

Biomarkers of Alzheimer's disease in mild cognitive impairment: Experience in a memory clinic from Latin America. / Biomarcadores de enfermedad de Alzheimer en deterioro cognitivo leve: experiencia en una clínica de memoria de Latinoamérica.

OBJECTIVE: This study aimed to investigate the role and prognosis of Alzheimer disease biomarkers in patients with mild cognitive impairment (MCI) at a memory clinic in Latin America. METHODS: We studied 89 patients with MCI, 43 with Alzheimer-type dementia, and 18 healthy controls (matched for age, sex, and educational level) at our memory clinic (Instituto FLENI) in Buenos Aires, Argentina. Patients and controls underwent an extensive demographic, neurological, and neuropsychological assessment. All subjects underwent a brain MRI scan; FDG-PET scan; amyloid PET scan; apolipoprotein E genotyping; and cerebrospinal fluid concentrations of Aß1-42, tau, and phosphorylated tau. Patients were categorised as positive or negative for the presence of amyloid pathology and neurodegeneration. RESULTS: Amyloid pathology was observed in cerebrospinal fluid results in 18% of controls, 64% of patients with MCI, and 92% of patients with Alzheimer-type dementia. Suspected non-Alzheimer disease pathophysiology was found in 11% of controls, 6% of patients with MCI, and 8% of patients with Alzheimer-type dementia. At 30 months of follow-up, 45% of amyloid-positive patients with MCI and 20% of amyloid-negative patients with MCI showed progression to dementia. CONCLUSIONS: This study demonstrates biomarker-based MCI prognosis and supports its role in clinical decision-making in daily practice.

Collagen fibers in the rectus abdominis muscle of cadavers of different age.

PURPOSE: To assess collagen content and types in the rectus abdominis muscle of cadavers of different ages. METHODS: Forty fresh adult male cadavers within 24 h of death were obtained from an Institute of Legal Medicine and divided by age at death into Group 1 (mean age, 23.3 years; range, 18-30 years; n = 20) and Group 2 (mean age, 46.2 years; range, 31-60 years; n = 20). From each cadaver, samples of the rectus abdominis muscle measuring 1 cm(2) were collected 3 cm superiorly and 2 cm inferiorly to the umbilicus. Histological sections were prepared and stained with picrosirius red and Masson's trichrome stain for visualization of total collagen fibers, and immunohistochemical analysis was performed to distinguish types I, II, III, IV and V collagen. RESULTS: No significant differences in total collagen were found between groups by Masson's trichrome staining. However, picrosirius red staining revealed a significantly greater amount and higher concentration of total collagen and types I and III collagen in Group 1 than in Group 2 (P < 0.05). All but type II collagen were detected by immunohistochemistry in both groups. No significant difference in type IV collagen was found between groups. Type V collagen was detected by immunohistochemistry in both groups, but quantification was not possible due to background staining. CONCLUSION: The amounts of types I and III collagen in the rectus abdominis muscle were significantly smaller in older subjects.

Improving tension decrease in components separation technique.

PURPOSE: The purpose of this study is to evaluate the tension at the aponeurotic edges after the undermining of the anterior rectus sheath associated with the classic components separation in cadavers. METHODS: Twenty fresh adult cadavers were placed supine and an incision in the anterior rectus sheath was done, thus exposing the posterior sheath. The two levels to be studied were marked 3 cm above and 2 cm below the umbilicus. An analogical dynamometer was used to measure the traction values, consecutively during four stages as follows: initial stage, no aponeurotic undermining; Stage 1, separation of the anterior rectus sheaths; Stage 2, after Stage 1 the external oblique aponeurosis were incised along the semilunaris and the external oblique muscles were undermined; Stage 3, after Stage 2 rectus muscles were completely separated from their posterior sheaths. Statistical analysis was done by Friedman's analysis of variance (p < 0.05). RESULTS: There was a progressive and significant decrease in tension along the stages (Friedman's analysis of variance, p < 0.001). Traction indexes were higher in the initial stage and became gradually lower along the other stages. CONCLUSION: The undermining of the anterior rectus sheaths helps to decrease tension during the components separation technique. LEVEL OF EVIDENCE: Level V, experimental study.

A pragmatic way to treat abdominal deformities based on skin and subcutaneous excess.

An objective classification for abdominoplasty based on subcutaneous and skin deformities is described. Type 0 patients are those who present excess fat with very little excess skin or without surplus skin, on which liposuction is indicated. Types I, II, and III are patients that demonstrate various degrees of excess skin and three basic patterns of skin resection are described. Type I patients present mild excess skin with a high umbilicus. Type II patients are those with mild excess skin and a well-positioned umbilicus, as well as patients with moderate excess skin. Type III patients present severely excessive skin. One hundred and eleven patients with abdominal deformity were reviewed and the incidence of each deformity was determined on this population. This study presents a practical classification that permits the plastic surgeon to critically evaluate which is the best option to correct abdominal deformities considering specific skin and subcutaneous deformities.

An aesthetic classification of the abdomen based on the myoaponeurotic layer.

An objective classification for abdominoplasty based on myoaponeurotic deformities is described. Types A, B, C, and D correspond to different myoaponeurotic deformities. Patients with type A display rectus diastasis secondary to pregnancy, and plication of the anterior rectus sheath is indicated. Patients with type B present with laxity of the lateral and inferior areas of the abdominal wall after approximation of the anterior rectus sheaths. An L-shaped plication of the external oblique aponeurosis is performed in addition to the correction of rectus diastasis. Patients with type C are those whose rectus muscles are laterally inserted on the costal margins. Release and undermining of the rectus muscles from their posterior sheath and advancement of these muscles, attached to the anterior sheath, is the procedure of choice in these cases. Patients with type D display a poor waistline definition; external oblique muscle rotation associated with plication of the anterior rectus sheath is the procedure used to correct this deformity. Eighty-eight patients who underwent abdominoplasty were reviewed, and the incidence of each deformity was determined on this population. This study presents a practical classification that permits the plastic surgeon to critically evaluate which is the best option to correct abdominal deformities considering specific areas of myoaponeurotic weakness.

Advancement of the external oblique muscle flap to improve the waistline: a study in cadavers.

Waist definition is an important goal of abdominoplasty. The purpose of this report is to study the effect of advancement and rotation of the external oblique muscles in the waistline. Twenty cadavers were dissected. Two parameters were analyzed: measurement of the waist circumference and the width of overlapped skin flaps of the abdomen in the midline. Three stages of dissection were compared: (1) initial stage, in which the myoaponeurotic structure of the anterior abdominal wall was intact; (2) stage 1, after advancement of the rectus muscles and its anterior aponeurosis toward the midline; and (3) stage 2, after advancement and rotation of the external oblique muscle. A significant statistical difference was found when waist circumference measured before dissection was compared with values obtained after the procedure. When the width of the overlapped skin flaps was compared during the different stages of dissection, a significant statistical difference was observed after each stage (paired t test). Therefore, the approximation of the rectus muscles alone improves the waistline, and when associated with external oblique muscle flap advancement and rotation, the cosmetic result in this area is even better. In conclusion, the procedure described decreases waist circumference and improves the frontal view of the waist.

Nylon versus polydioxanone in the correction of rectus diastasis.

Nylon and polydioxanone are two sutures commonly used to correct rectus diastasis. Polydioxanone, as an absorbable suture, has the advantage of not being palpable in thin patients. Because several forces act against the plication, an absorbable suture would not be efficient in these cases. In this study, two groups of 10 patients each were studied. These patients underwent abdominoplasty and correction of rectus diastasis. In the control group, 2-0 nylon was used to plicate the anterior aponeurosis and 0-polydioxanone was used in the experimental group. The tension of the abdominal wall was measured with a dynamometer in both groups. The width of rectus diastasis was measured 3 cm above and 2 cm below the umbilicus, using a computed tomography (CT) scan before the operation and 3 weeks and 6 months after surgery. The width of rectus diastasis was measured intraoperatively at the same levels. The data were analyzed by Student's t test. Both groups had similar abdominal wall tension on both levels. The diastasis recti was completely corrected at both levels, as confirmed by the 3-week postoperative CT scan and the 6-month CT scan. At the superior level, the width of the rectus diastasis on the preoperative CT scan (2.6 +/- 0.7 cm) was similar to the values obtained intraoperatively (2.7 +/- 0.6 cm), showing no significant statistical difference. At the inferior level, the largest difference between the preoperative CT scan and the intraoperative finding was 0.3 cm. In conclusion, the correction of rectus diastasis with 2-0 nylon and 0-polydioxanone was achieved and maintained after 6 months. CT scans are an accurate method for studying rectus diastasis and other muscles of the abdominal wall.

The role of plastic surgery in congenital cutis laxa: a 10-year follow-up.

The clinical features and the plastic surgery management of a 23-year-old woman with cutis laxa are presented. Two rhytidectomies were performed in this patient within 1 year. The first was associated with a SMAS flap; the second employed a prehairline incision. The evolution of the aging facial appearance 10 years after the last face lift was evaluated and compared with the preoperative situation. Repeated face lifts seem to be an interesting way to manage patients with cutis laxa. Unlike patients with other disorders of the connective tissue, those with cutis laxa have no vascular fragility and heal well. The role of plastic surgery and the clinical features and timing for operation are reviewed and discussed.

Abdominal wall closure after selective aponeurotic incision and undermining.

The tension required to pull the anterior and the posterior rectus sheaths toward the midline was studied in 20 fresh cadavers at two levels: 3 cm above and 2 cm below the umbilicus. The quotient of the force used to mobilize the aponeurotic site to the midline and its resulting displacement was called the traction index. These indices were compared in three situations: (1) prior to any aponeurotic undermining, (2) after the incision of the anterior rectus sheath and the undermining of the rectus muscle from its posterior sheath, and (3) after additionally releasing and undermining the external oblique muscle. A significant decrease in aponeurotic resistance was observed after each dissection. The anterior sheath showed higher resistance to traction compared with the posterior sheath on both levels. No statistical difference was noted in the comparison of the values of the aponeurosis above and below the umbilicus. These results suggest that these procedures are effective in assisting in the closure of abdominal wall defects because these maneuvers decrease substantially the tension required for advancement of the aponeurotic edges.

Should diastasis recti be corrected?

The plication of the anterior rectus sheath is a procedure that is performed by most surgeons during abdominoplasty. A main concern is whether the correction of recti diastasis is really effective and if it is stable. In order to verify the position of the rectus muscle, a CT-scan was used in 14 patients who underwent abdominoplasty with rectus plication to compare the preoperative situation of these muscles with their position 3 weeks and 6 months postoperatively. None of these patients had had previous abdominal surgery. The recti diastasis was corrected with a two-layer 2-0 Nylon suture. A dynamometer was used to measure the resistance force of the anterior aponeurosis of the rectus. In all cases the CT data shows that correction of the diastasis was achieved completely after 6 months.

Effect of melphalan administration on the activity of natural killer and natural cytotoxic spleen cells of normal and tumor-bearing mice.

The effect of melphalan (L-PAM; L-phenylalanine mustard) administration on natural killer (NK) and natural cytotoxic (NC) activities of spleen cells from normal noninoculated BALB/c mice and mice bearing large MOPC-315 plasmacytoma tumors was investigated. Injection of L-PAM (7.5 or 15.0 mg/kg) had no effect on NK and NC activities of spleen cells from normal mice whereas stimulation by PHA was markedly suppressed. NK activity was markedly suppressed in spleens of tumor-bearing mice whereas NC activity was not affected. Therapy with L-PAM of tumor-bearing mice led to transient recovery of NK activity which was possibly related to the effect of L-PAM on macrophage suppressive activity on NK cells. It is concluded that NK and NC cell activities and the response to PHA stimulation are selectively affected by L-PAM administration.

Immune reactivity of the tumor-resistant X/Gf mouse.

Parameters of immune reactivity of the tumor-resistant X/Gf mouse have been studied. X/Gf mice show better survival than do control strains following i.p. inoculation with graded doses of YAC lymphoma cells. The natural killer cell activity of X/Gf mice was higher than that of control mice, and this elevated NK activity was inherited by (C57BL/6 X X/Gf)F1 mice. Differences in NK activity of fresh spleen cells from X/Gf, C57BL/6, and (C57BL/6 X X/Gf)F1 mice were not reflected in their ability to lyse in vitro-derived, cloned, transformed cell lines from X/Gf or C57BL/6 mice in an 8 h 51Cr assay; however, the X/Gf-derived malignant cells were more sensitive to lysis than the C57BL/6-derived cells. In order to test whether X/Gf mice demonstrated any exceptional ability to recognize and destroy altered autologous cells, experiments were performed with TNP-modified syngeneic cells. While X/Gf and B10.A effector cells appeared to respond with similar magnitude, hapten-modified X/Gf cells were stronger stimulator cells and more sensitive targets than control strain cells. The ability of X/Gf mice to reject H-2 compatible and incompatible skin grafts is normal, as judged by a comparison of the rejection times with control strains. Allogeneic mixed lymphocyte reactivity, T-cell-mediated lympholysis, delayed-type hypersensitivity reactions, and in vivo phagocytosis of inert particles are of comparable magnitude in X/Gf and control strain mice.

In vitro induction of malignant transformation and in vivo resistance to tumor growth in the X/Gf mouse.

Inbred X/Gf mice are reported to have a very low incidence of spontaneous and induced tumors. Experiments were performed to determine whether the cells of the X/Gf mouse are themselves resistant to in vitro oncogenesis or the organism as a whole is surveyed by a homeostatic mechanism that prevents the expression of potential neoplasia. Cultures of X/Gf or C57BL/6J embryonic fibroblasts were exposed to the chemical carcinogens 7,12-dimethylbenz[a]anthracene and benzo[a]pyrene to test whether the cells of the X/Gf mouse are themselves resistant to oncogenesis. The chemical carcinogens caused transformation of both X/Gf and C57BL/6 fibroblasts into cells that demonstrated altered growth patterns in liquid culture and grew in a clonal fashion in soft agar. Cloned transformed cells were shown to be malignant and resulted in the growth of sarcomas in vivo. X/Gf mice were decidedly more resistant than were C57BL/6 mice to their respective clones of transformed cells. The resistance to neoplastic growth demonstrated by the X/Gf mice was inherited by (C57BL/6J X X/Gf)F1 mice that were resistant to the growth of X/Gf-transformed and C57BL/6-transformed cells at cell doses at which the parental X/Gf mice had survived but at which the C57BL/6 had succumbed to progressively growing tumors. It has thus been established that the tumor resistance of the X/Gf mice is not based on the resistance of isolated cells from these animals to malignant transformation, but rather is attributable to an in vivo homeostatic mechanism that prevents tumor growth.

In vitro induction of cell-mediated immunity to murine leukemia cells. III. Effect of methanol extraction residue fraction of BCG on the generation of cytotoxic lymphocytes against leukemia.

Effects of the methanol extraction residue (MER) fraction of tubercle bacilli (BCG) on the generation of cytotoxic lymphoid cells were studied in vitro with the use of unidirectional mixed lymphocyte-tumor cell cultures. These cultures consisted of splenocytes of lymph node cells from normal donor C57BL/6, BALB/c, and strain A mice and mitomycin C-inactivated leukemia cells of both syngeneic and allogeneic origin. Addition of small amounts of MER (0.2-5 microgram/ml) to the cultures potentiated appreciably the elicitation of cytotoxic reactivity (as measured by the 51Cr-release assay) of the sensitized cells, whereas higher quantities (10-40 microgram/ml) had a strong suppressive effect. MER also induced some cytotoxic capacity in normal murine and human lymphoid cells not exposed to specific tumor cell stimulation. The stimulatory and suppressive effects were noted only when MER was present during the initial 24-48 hours of the 6-day culture. With the nylon wool fractionation technique, it was apparent that MER affected primarily the nonadherent cell population. MER could also prevent the generation of nonspecific suppressor cells by splenocytes maintained for 3-6 days in tissue culture.