Recombinant human platelet-derived growth factor-BB (becaplermin) for healing chronic lower extremity diabetic ulcers: an open-label clinical evaluation of efficacy

Topically applied recombinant human platelet-derived growth factor-BB (becaplermin) is a new pharmacologically active therapy for chronic, neuropathic, lower extremity diabetic ulcers. In previous studies, becaplermin gel was administered once daily but dressings were changed twice daily. In the present study of 134 patients with diabetes mellitus and full thickness lower extremity ulcers, dressings were changed only once per day, simplifying the treatment regimen. Efficacy criteria included the percentage of patients achieving complete healing within the 20-week treatment period, the time to achieve complete healing, the rate of ulcer recurrence during the 6-month period following healing, and treatment compliance. Complete healing of ulcers was achieved in 57. 5% of patients, with a mean time to closure of 63 days and a recurrence rate of 21% at 6 months. Of the potential factors affecting ulcer healing, only drug compliance (p < 0.001), dressing compliance (p < 0.01), the presence of infection (p < 0.01), baseline ulcer area (p < 0.05), and baseline total wound evaluation score (p < 0.05) were significantly associated with healing. Results of this study further confirm the efficacy and safety of becaplermin gel for the treatment of lower extremity diabetic ulcers.     

Outcomes of outpatient breast cancer surgery at a private breast clinic

Advances in surgical and anesthetic techniques have allowed for outpatient treatment of breast cancer. We evaluated the feasibility, safety, efficacy, and surgical outcomes of outpatient surgery in 370 patients with breast cancer who underwent breast‐conserving surgery (BCS)/axillar lymph node (ALN) management. There were no deaths or severe intraoperative complications, but 41 complications were observed and disease recurrence occurred in 18 patients. The cumulative overall survival rate was 95.2%. Outpatient surgery was well tolerated, feasible, and safe in patients receiving BCS/ALN management.     

Young porcine endocrine pancreatic islets cultured in fibrin show improved resistance toward hydrogen peroxide

Aim: To study the protective effect of a fibrin scaffold toward embedded young porcine endocrine pancreatic islets from hydrogen peroxide within the context of islet encapsulation in transplantation. Methods: After isolation and in vitro maturation, groups of 200 young porcine islet equivalents (IEQ) were embedded in a 200 µL fibrin gel and exposed to 2 concentrations (10 and 100 µM) of hydrogen peroxide (H₂O₂) to investigate the ability of fibrin to protect islets against apoptotic stimuli. As a control, young porcine islets were seeded in tissue culture polystyrene (TCPS) well plates and exposed to the same H₂O₂ concentrations. Islet integrity, viability and function were then investigated. Results: Morphologically, the integrity of islets embedded in fibrin gels was better preserved compared with that of islets cultured in TCPS plates, when exposed to H₂O₂. Immunofluorescence staining showed that insulin and glucagon expression was higher in islets cultured in fibrin. Overall, H₂O₂ incubation led to decreased insulin and glucagon expression. A TUNEL assay revealed elevated numbers of apoptotic cells for islets cultured in TCPS plates when compared with those embedded in fibrin. Islets cultured in TCPS plates and exposed to H₂O₂ had diminished ability to secrete insulin in response to glucose stimulation, whereas islets embedded in fibrin maintained their glucose responsiveness. Insulin trapped in fibrin was extracted and quantified, revealing insulin in the extract. Conclusions/Interpretation: Fibrin has a protective effect on young porcine endocrine pancreatic islets exposed to hydrogen peroxide.     

Energy Expenditure and Caloric Balance After Burn: Increased Feeding Leads to Fat Rather Than Lean Mass Accretion

OBJECTIVE: Resting energy expenditure (REE) is commonly measured in critical illness to determine caloric "demands" and thus nutritive needs. SUMMARY BACKGROUND DATA: The purpose of this study was to 1) determine whether REE is associated with clinical outcomes and 2) determine whether an optimal caloric delivery rate based on REE exists to offset erosion of lean mass after burn. METHODS: From 1995 to 2001, REE was measured by indirect calorimetry in 250 survivors of 10 to 99%TBSA burns. Caloric intake and REE were correlated with muscle protein catabolism, length of stay, ventilator dependence, sepsis, and mortality. From 1998 to 2000, 42 patients (>60%TBSA burns) received continuous enteral nutrition at a spectrum of caloric balance between 1.0x REE kcal/d -1.8x REE kcal/d. Serial body composition was measured by dual energy x-ray absorptiometry. Lean mass, fat mass, morbidity, and mortality were determined. RESULTS: REE/predicted basal metabolic rate correlated directly with burn size, sepsis, ventilator dependence, and muscle protein catabolism (P <.05). Declining REE correlated with mortality (P <.05). 2) Erosion of lean body mass was not attenuated by increased caloric balance, however, fat mass increased with caloric supply (P <.05). CONCLUSION: In surviving burned patients, caloric delivery beyond 1.2 x REE results in increased fat mass without changes in lean body mass. Declining energy expenditure appears to be a harbinger of mortality in severely burned patients.     

Metabolic effects of growth hormone treatment: an early predictor of growth response?

Fourteen children receiving one year of recombinant human growth hormone (rhGH) treatment underwent measurement of serial changes in body composition (measured by skinfold thickness, bioelectrical impedance, and H2(18)O dilution), resting energy expenditure (REE, estimated by ventilated hood indirect calorimetry), and total free living daily energy expenditure (TEE, measured by the doubly labelled water technique). Mean height velocity increased from 4.9 to 8.6 cm/year after six months of treatment. Fat free mass (FFM) increased more during the first six weeks (24.4 g/day) than from six to 26 weeks of treatment (6.8 g/day); fat mass decreased by 7.2 g/day and 1.1 g/day respectively. The six week increase in REE (kJ/day) was maintained after six months of treatment, though expressed per kilogram FFM (kJ/kgFFM/day), returned to pretreatment values by three months. Height velocity increases at six months correlated with six week changes in fat mass measured by skinfold thickness and REE, though use of this relationship to predict growth response in individuals is limited by the wide 95% prediction intervals. No significant changes in growth, body composition, or energy expenditure were observed between six and 12 months of treatment, in either patients who had initially responded well to treatment or those who were poor initial responders to treatment and who had their dose of rhGH doubled after six months.     

Neonatal stroke: Clinical characteristics and cerebral blood flow velocity measurements

The clinical courses of 8 term infants with focal cerebral infarction or neonatal stroke were studied to determine whether such infants can be identified by current markers of perinatal distress, and whether changes in cerebral blood flow velocity (CBFV) occur during the acute phase of the disease. CBFV was measured from the middle cerebral artery (MCA) and anterior cerebral artery (ACA) utilizing duplex Doppler. Seven of the 8 patients required no resuscitation in the delivery room; 1 infant required brief bag and mask ventilation. No infant had evidence of severe fetal acidemia (i.e., cord pH <7). All 8 infants were initially admitted to the newborn nursery. Infants were identified on the basis of abnormal clinical findings observed during the first 48 hours: seizures (n = 6) and hypotonia and apnea (n = 2). Serum electrolytes, calcium, magnesium, and glucose levels were normal, and the sepsis evaluation including a spinal tap was sterile in all patients. Neuroimaging revealed nonhemorrhagic left focal MCA infarction (n = 6) and right focal MCA infarction (n = 2). Duplex Doppler demonstrated transient ipsilateral decreases in CBFV as compared to the contralateral unaffected side at clinical presentation in 4 infants. In 2 of these infants the decrease in CBFV involved both the MCA and ACA, and in 2 infants, only the MCA vessels. These side-to-side differences were not present at subsequent CBFV measurements. The data indicate that infants who develop neonatal stroke cannot be distinguished from infants who do not develop the lesion by current markers of perinatal distress. Because neonatal stroke frequently occurs as an unanticipated event, prevention may not be possible.     

Some considerations about the procedure of informed consent in patients prepared for electroconvulsive treatment

Electroconvulsive therapy (ECT) as a medical procedure of higher risk as well as a therapy evoking certain controversies requires strict obedience to the conditions of acquiring the patient's informed consent to the offered method of treatment. To acquire the patient's consent it is necessary to inform him/her about the different aspects of electroconvulsive therapy. The paper stresses that in the case of ECT therapy, the spoken information given to the patient seems insufficient. It is necessary to work out a Polish questionnaire for acquiring the patient's consent to electroconvulsive therapy and to apply it in all psychiatric institutions that carry out ECT procedures.     

Acute vagus nerve stimulation does not suppress spike and wave discharges in genetic absence epilepsy rats from Strasbourg

We evaluated the efficacy of vagus nerve stimulation (VNS) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a validated model for absence epilepsy. In the first experiment, we investigated whether VNS applied at seizure onset can interrupt spike and wave discharges (SWD). In the second experiment, we investigated whether SWD are suppressed or shortened in duration when VNS is applied several hours per day. Both control and VNS groups underwent EEG and VNS electrode implantation. For the first experiment, a randomized crossover design was used. Stimuli (amplitude: 3 V; frequency: 30 Hz; pulse duration: 500 micros) were given when an SWD occurred on the EEG. The experiment was repeated the next day. In the second experiment, treated animals were stimulated (amplitude: 1.5 mA; frequency: 30 Hz; pulse duration: 500 micros; on/off time cycle: 30 s / 5 min) for 3h per day, during five consecutive days. In the first experiment, the duration of the SWD was increased on day 1, (P < 0.05). There was no difference in SWD duration on Day 2. In the second experiment, no significant differences could be found in number, duration and EEG frequency of SWD. VNS applied at the onset of an SWD can prolong the duration of SWD in GAERS. As a 5-day stimulation protocol had no effect, long-term VNS might be necessary to affect SWD.     

Neurostimulation for refractory epilepsy

Neurostimulation is an emerging treatment for refractory epilepsy. To date the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond to such a treatment and may guide the search for optimal stimulation parameters and finally improve clinical efficacy. In the past ten years some progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in patients and animals undergoing vagus nerve stimulation (VNS). Interesting results have been found in VNS-treated patients that underwent evoked potential measurements, cerebrospinal fluid investigation, neuropsychological testing and PET, SPECT and fMRI testing. Desynchronisation of abnormal synchronous epileptic activity is one of the hypotheses on the mode of action that might primarily be responsible for an anti-seizure effect. There is however increasing evidence from research and clinical observation that VNS might establish a true and long-term anti-epileptic effect. It has been shown that VNS influences neurotransmission in the brain and provokes long-term changes in cerebral blood flow in areas crucial for epileptogenesis such as the thalamus and medial temporal lobe structures. Deep brain stimulation (DBS) for epilepsy has regained interest. Central nervous system structures known to play a key role in the epileptogenic network such as the thalamus and subthalamic nucleus have been targeted. Another approach is to target the ictal onset zone such as the medial temporal lobe. At Ghent University Hospital 10 patients have been treated with long-term amygdalohippocampal DBS. Several hypotheses have been raised for the mechanism of action of DBS for refractory seizures. Seizure reduction may be due to a microlesion caused by electrode insertion or by provoking a reversible functional lesion due to the effect of electrical current on hyperexcitable tissue. Neurophysiological techniques such as evoked potentials monitoring and intraoperative single unit potential recordings may guide correct electrode placement, individual DBS titration and elucidation of the mechanims of action of DBS for epilepsy.