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Biomedical subjects

M Palazzo

Publications and source records attributed to M Palazzo.

13 recordsLinked to original sources

Caveolin-1 is expressed on multipotent cells of hair follicles and might be involved in their resistance to chemotherapy.

BACKGROUND: Caveolin-1 is the principal protein that composes caveolae, which are vesicular invaginations present on the plasma membrane of different cell types. Caveolae are involved in a variety of cellular functions including regulation of proliferation rate and resistance to chemotherapeutic drugs. Chemotherapy frequently induces alopecia which is reversible most probably due to the low proliferative rate of hair follicle stem cells and due to the expression of proteins which confer resistance. OBJECTIVES: Using a specific animal model and immunohistochemistry, we analysed the expression of both caveolin-1 and the cell proliferation marker beta-catenin, at different stages of the hair follicle cycle, both before and after doxorubicin (DXR) -induced alopecia. METHODS: Seven-week-old C57BL/6 mice were depilated in order to synchronize hair follicle cycle in the anagen phase. Chemotherapy with DXR 15 mg kg(-1) was used to induce alopecia. Control and treated mice were then sacrificed at precise time points and caveolin-1 expression in hairs at different stages of the cycle were analysed by immunohistochemistry. By double immunofluorescence, colocalization of caveolin-1 and cytokeratin-15 was confirmed in the bulge region. The state of proliferation of cells composing hair follicle was assessed by beta-catenin immunohistochemistry. RESULTS: Caveolin-1 was expressed by the cells of the bulge area, the multipotent compartment of the hair follicle, during all phases of growth (anagen), regression (catagen) and resting (telogen). During the anagen phases, nuclear beta-catenin labelling was not observed in bulge cells, but rather in the deeper portion of the follicle. Damaged hair follicles from DXR-treated mice presented bulge cells which still expressed caveolin-1, suggesting that this protein might play a role in their drug resistance. As expected, no beta-catenin nuclear staining was detectable in DXR-treated hair follicles, indicating the complete lack of proliferative processes. The differential localization of caveolin-1 and beta-catenin suggests that the mutually exclusive expression of these proteins is useful for correct hair regrowth, whether during the physiological cycle or after chemotherapy-induced alopecia. CONCLUSIONS: Expression of caveolin-1 within the multipotent cell compartment of the hair follicle can explain the resistance of bulge cells to many chemotherapeutics, suggested by the reversibility of chemotherapy-induced alopecia.

Alopecia↗

Effects of two different housing systems on behavior, physiology and milk yield of Comisana ewes.

Two groups of 20 early-lactating Comisana ewes were used in this study, and were allocated to either an indoor or outdoor daytime environment. The indoor environment was a 3mx12m straw bedded pen inside a pre-fabricated building. The outdoor environment was a 200m(2) paddock during daytime (09.00-19.00h) with ewes being moved to the shed, as described for the indoor treatment, at night. Behavior of ewes was recorded at 14 days interval from 09.00 to 19.00h. A phytohemagglutinin (PHA) skin test was performed at weeks 6, 11, 15 and 18 of the experiment to induce a non-specific delayed-type hypersensitivity in ewes. Jugular blood samples were taken at the beginning and at weeks 5, 10, 14 and 18 to determine endocrine and metabolic responses of animals to housing system and to changes in climatic conditions and stage of lactation. Ewe milk yield was recorded daily and individual milk samples were analyzed for milk composition, coagulating properties and somatic cell count (SCC) at 14 days interval. No differences were found between groups for endocrine and immune responses. Outdoor ewes had increased locomotor activities (P<0.01) and decreased idling (P<0.05) compared to indoor animals. The outdoor group had higher levels of blood creatinine (P<0.01) and inorganic phosphorus (P<0.05) as well as lower urea (P<0.01) and glucose (P<0.001) concentrations compared to the indoor group. Milk yield and composition were not changed by the housing system, though significant timextreatment interactions were found for milk constituents, with indoor-housed ewes having higher (P<0.05) milk protein, fat and lactose concentrations during the middle of the trial. Outdoor ewes had lower SCC (P<0.003) and pH (P<0.001) in their milk than indoor ewes, whereas renneting parameters were not different across treatments. Results suggest that ewe welfare and productivity were not substantially affected by the housing system. The provision of feeding rations that meet the greater energy demand for maintenance is required to sustain productivity in outdoor reared sheep.

Journal Article↗

Oxygen transport patterns in patients with sepsis syndrome or septic shock: influence of treatment and relationship to outcome.

OBJECTIVE: To investigate the relationship between oxygen transport patterns and outcome in patients with sepsis syndrome or septic shock managed according to two different treatment regimens. DESIGN: Retrospective study of a subgroup of patients with sepsis syndrome or septic shock taken from a randomized, prospective, controlled trial. SETTING: General intensive care units in a teaching and a district general hospital. PATIENTS: Seventy-eight patients classified according to predetermined criteria as having sepsis syndrome or septic shock were drawn retrospectively from a larger study group of 109 consecutive patients considered to be at risk for developing multiple organ failure. INTERVENTIONS: All patients received volume expansion to an optimal pulmonary artery occlusion pressure. If the therapeutic goals (cardiac index of > 4.5 L/min/m2, oxygen delivery [DO2] of > 600 mL/min/m2, and oxygen consumption [VO2] of > 170 mL/min/m2) were not achieved with fluids alone, patients were randomized to either a control group or a treatment group. In the treatment group, dobutamine (5 to 200 micrograms/kg/min) was administered to increase cardiac index and DO2 until all three goals were simultaneously achieved. In the control group, dobutamine was administered only if the cardiac index was < 2.8 L/min/m2. In both groups, norepinephrine was infused to maintain mean arterial pressure at 80 mm Hg. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, oxygen transport, and lactate measurements were made at the time of admission to the study, at the time of optimal volume administration, at 1, 2, 4, 8, 12, 16, 20, and 24 hrs, then every 6 hrs for the next 24 hrs, and at least every 8 hrs thereafter. The time at which all therapeutic goals were first achieved simultaneously or the time of maximal DO2 was identified and termed "tmax." Survivors from both the control and treatment groups significantly (p < .001) increased cardiac index and DO2 in response to maximal resuscitation, and despite an associated decrease in oxygen extraction (p < .01), there was a significant (p < .01) increase in VO2. In nonsurvivors from both groups, despite significant increases in cardiac index (p < .05) and DO2 (p < .01) at tmax, oxygen extraction decreased (p < .01) and VO2 remained unchanged. DO2 and VO2 were significantly lower (p < .05) at tmax in nonsurvivors than in survivors from both groups. Persistently high lactate concentrations were characteristic of nonsurvivors. CONCLUSIONS: Survivors of sepsis syndrome or septic shock are characterized by an ability to increase both DO2 and VO2. In contrast, nonsurvivors typically have reduced cardiac reserve, they fail to increase VO2 following resuscitation, and when delivery is enhanced with aggressive inotropic support, oxygen extraction falls. These patterns of response were similar in both treatment and control groups, although the magnitude of the changes was exaggerated in the treatment group. These observations may help to explain the findings by some investigators that treatment aimed at achieving survivor values of cardiac index, DO2, and VO2 fails to improve outcome when instituted following admission to intensive care.

Adrenergic alpha-Agonists↗

Elevation of systemic oxygen delivery in the treatment of critically ill patients.

BACKGROUND: Elevation of systemic oxygen delivery and consumption has been associated with an improved outcome in critically ill patients. We conducted a randomized trial to determine whether boosting oxygen delivery by infusing the inotropic agent dobutamine would improve the outcome in a diverse group of such patients. METHODS: On the basis of previously published recommendations, we established the following goals: a cardiac index above 4.5 liters per minute per square meter of body-surface area, oxygen delivery above 600 ml per minute per square meter, and oxygen consumption above 170 ml per minute per square meter. If these goals were not achieved with volume expansion alone, patients were randomly assigned to a treatment or control group. The treatment group received intravenous dobutamine (5 to 200 micrograms per kilogram of body weight per minute) until all three goals had been achieved. Dobutamine was administered to the control group only if the cardiac index was below 2.8 liters per minute per square meter. RESULTS: A total of 109 patients were studied. In nine patients the therapeutic goals were achieved with volume expansion alone; all nine patients survived to leave the hospital. Fifty patients were randomly assigned to the treatment group, and 50 to the control group. During treatment, there were no differences between the two groups in mean arterial pressure or oxygen consumption, despite a significantly higher cardiac index and level of oxygen delivery in the treatment group (P < 0.05). Although the predicted risk of death during hospitalization was 34 percent for both groups, the in-hospital mortality was lower in the control group (34 percent) than in the treatment group (54 percent) (P = 0.04; 95 percent confidence interval, 0.9 to 39.1 percent). CONCLUSIONS: The use of dobutamine to boost the cardiac index and systemic oxygen delivery failed to improve the outcome in this heterogeneous group of critically ill patients. Contrary to what might have been expected, our results suggest that in some cases aggressive efforts to increase oxygen consumption may have been detrimental.

Adult↗

An impaled neck. Management of difficult airway access.

We describe the management of a patient impaled through the lower submandibular area by the top spike of some iron railings which immobilised his jaw and blocked access to the trachea. The Fire Brigade used specialised equipment to cut out a section of the railings so that the patient could be transported to hospital. Awake fibreoptic intubation was used to gain access to the patient's airway before induction of anaesthesia.

Adult↗

Logistic regression analysis of fixed patient factors for postoperative sickness: a model for risk assessment.

One hundred and forty-seven patients undergoing minor orthopaedic surgery were studied prospectively by logistic regression analysis to determine the association of independent fixed patient factors with the incidence of postoperative sickness (nausea, retching or vomiting). Gender, history of previous postoperative sickness, postoperative opioids and interaction between gender and previous history of sickness were significant independent factors for postoperative sickness; history of motion sickness was weakly associated. The probability of postoperative sickness in the first 24 h after surgery may be estimated from the equation: logit postoperative sickness = -5.03+2.24(postoperative opioids) +3.97 (previous sickness history) +2.4 (gender) +0.78 (motion sickness) -3.2 (gender x previous sickness history). (Log likelihood ratio test for 5 degrees of freedom for the coefficients, chi-square = 53.5 (P < 0.001).) It is suggested that the calculated probability for sickness may be a useful addition for balancing patient treatment groups and allowing between-study comparisons.

Adolescent↗