Clinical Assessment of Individualized Glycemic Goals in Patients With Type 2 Diabetes: Formulation of an Algorithm Based on a Survey Among Leading Worldwide Diabetologists.

OBJECTIVE: Observations over the past few years have demonstrated the need to adjust glycemic targets based on parameters pertaining to individual patient characteristics and comorbidities. However, the weight and value given to each parameter will clearly vary depending on the experience of the provider, the characteristics of the patient, and the specific clinical situation. RESEARCH DESIGN AND METHODS: To determine if there is current consensus on a global level with regard to identifying these parameters and their relative importance, we conducted a survey among 244 key worldwide opinion-leading diabetologists. Initially, the physicians were to rank the factors they take into consideration when setting their patients' glycemic target according to their relative importance. Subsequently, six clinical vignettes were presented, and the experts were requested to suggest an appropriate glycemic target. The survey results were used to formulate an algorithm according to which an estimate of the patient's glycemic target based on individualized parameters can be computed. Three additional clinical cases were submitted to a new set of experts for validation of the algorithm. RESULTS: A total of 151 (61.9%) experts responded to the survey. The parameters "life expectancy" and "risk of hypoglycemia from treatment" were considered to be the most important. "Resources" and "disease duration" ranked the lowest. An algorithm was constructed based on survey results. It was validated by presenting three new cases to 57 leading diabetologists who suggested glycemic targets that were similar to those calculated by the algorithm. CONCLUSIONS: The resultant suggested algorithm is an additional decision-making tool offered to the clinician to supplement clinical decision making when considering a glycemic target for the individual patient with diabetes.

Valproic acid-induced eosinophilic pleural effusion: a case report and review of the literature.

We present a case of eosinophilic pleural effusion due to valproic acid (VPA), a rare adverse event that has been reported previously. A 30-year-old male patient presented with respiratory symptoms and right-sided pleuritic pain, within days of initiation of VPA treatment for a generalized seizure. Chest radiography revealed a moderate-sized right-sided pleural effusion, which was an exudate with a pH of 7.54 and 48% eosinophils. Symptoms resolved soon after discontinuation of the drug, as did the effusion in a repeat radiograph 3 weeks later. The likelihood that VPA was the cause of the effusion is examined.

Conservative management of Achilles tendon wounds: results of a retrospective study.

Achilles tendon wounds are therapeutically challenging. The tendon`s functional importance, the paucity of soft tissue surrounding the ankle, and common patient comorbidities often limit surgical reconstructive procedure options. Depending on wound depth and overall patient health, secondary intention healing of these wounds can take many months. At the authors' wound care center, patients who are referred with recalcitrant, deep Achilles tendon wounds and who are able to visit the center two to three times per week are offered a protocol of topical hyperbaric oxygen (THBO) followed by low-level laser therapy (LLLT) and moisture-retentive dressings. A retrospective study was conducted to evaluate the outcomes of patients who received treatment for a deep Achilles tendon wound during the years 2004 through 2008. Patients who were seen but did not obtain care at the center were contacted via telephone. Of the 80 patients seen, 15 were referred for amputation, 52 obtained treatment elsewhere, and 13 received the THBO/LLLT protocol. Patient median age was 73 years (range 52-90 years) and most (85%) had diabetes mellitus. Average wound size was 90 cm2 (range 6.25-300 cm2) with an average duration of 11.7 months (range 2-60 months) before treatment. Complete re-epithelialization was achieved in 10 patients (77%) following a mean treatment time of 19 ± 10 weeks (range 5-42 weeks). Of those, seven remained ambulatory and ulcer-free at mean follow-up of 3.3 ± 1.8 years. Eight of the 52 patients (15%) who were not treated in the authors' center reported their ulcer was healed and 15 (29%) underwent amputation. Considering the severity of these wounds, the observed treatment outcomes are encouraging and may present a reasonable alternative for some patients with Achilles tendon wounds. Research is needed to clarify the role of these modalities in the conservative treatment of patients with Achilles tendon ulceration.

Low level laser irradiation stimulates mitochondrial membrane potential and disperses subnuclear promyelocytic leukemia protein.

BACKGROUND AND OBJECTIVES: Low level laser irradiation (LLLI) is used to promote wound healing. Molecularly it is known to stimulate mitochondrial membrane potential (MMP), cytokine secretion, and cell proliferation. This study was designed to determine the influence of LLLI on the kinetics of MMP stimulation and decay, specific cytokine gene expression, and subcellular localization of promyelocytic leukemia (PML) protein on HaCaT human keratinocytes. STUDY DESIGN/MATERIAL AND METHODS: The cells were irradiated by a 780 nm titanium-sapphire (Ti-Sa) laser with 2 J/cm(2) energy density. MMP was monitored with Mitotracker, a mitochondrial voltage-sensitive fluorescent dye. Cytokine gene expression was carried out using semi-quantitative-reverse transcription polymerase chain reaction. Subcellular localization of PML protein, a cell-cycle checkpoint protein, was determined using immunofluorescent staining. RESULTS: The fluorescence intensity of MMP was increased immediately after the end of LLLI by 148 +/- 6% over control (P<0.001). Subsequently it decayed, reaching 51 +/- 14% of the control level (P < 0.01) within 200 minutes. This decay was characterized by an exponential curve (R = 0.96) with a lifetime of 79 +/- 36 minutes (P < 0.05). Following irradiation, the expression of interleukin-1alpha, interleukin-6, and keratinocyte growth factor (KGF) genes were transiently upregulated; but the expression of the proinflammatory gene interleukin-1beta, was suppressed. The subnuclear distribution of PML was altered from discrete domains to its dispersed form within less than 1 hour after LLLI. CONCLUSIONS: These changes reflect a biostimulative boost that causes a shift of the cell from a quiescent to an activated stage in the cell cycle heralding proliferation and suppression of inflammation. Further characterization of MMP kinetics may provide a quantitative basis for assessment of the effect of LLLI in the clinical setting.

Agranulocytosis associated with initiation of famotidine therapy.

OBJECTIVE: To report a case of agranulocytosis associated with initiation of famotidine. CASE SUMMARY: An 87-year-old white man was admitted to the internal medicine department of an acute care hospital because of fever and agranulocytosis (granulocyte count 0). Eight days prior to admission, famotidine therapy had been initiated. Famotidine was discontinued and granulocyte-macrophage colony stimulating factor was administered, with concomitant recovery of the granulocyte count and subsequent development of a leukemoid reaction. DISCUSSION: According to the Naranjo probability scale, famotidine was the probable cause of agranulocytosis. This is a rare adverse effect of this medication; only a few other cases have been reported. CONCLUSIONS: Although agranulocytosis is a rare adverse effect of famotidine, the pharmacist and physician should be aware of this potentially fatal event. If any patient treated with famotidine develops fever, the clinician should consider, among other things, performing a white blood cell count.

Effects of the superoxide dismutase-mimetic compound tempol on endothelial dysfunction in streptozotocin-induced diabetic rats.

Evidence exists to support the beneficial effects of superoxide dismutase on endothelial dysfunction induced by hyperglycemia in vitro. In vivo, however, studies of the effects of native superoxide dismutase preparations on the vascular complications accompanying diabetes are limited, and their therapeutic application potential has so far been disappointing. The objective of this study was to evaluate, for the first time in vivo, the effects of long-term administration of tempol, a stable superoxide dismutase-mimic compound, on diabetes-induced endothelial dysfunction in rats. Diabetes was induced by streptozotocin and rats were monitored for 8 weeks with or without treatment with tempol (100 mg/kg, s.c., b.i.d). Diabetic rats showed increased vascular levels of superoxide, which was accompanied by increased levels of the oxidative stress markers malondialdehyde and 8-epi-prostaglandin F(2alpha). In addition, the vasorelaxant as well as the cGMP-producing effects of acetylcholine and glyceryl trinitrate were reduced in diabetic rats. Treatment with tempol abolished not only the differences in the vascular content of superoxide, malondialdehyde and 8-epi-prostaglandin F(2alpha), but also the differences in the relaxation and cGMP responses of aortic rings to both acetylcholine and glyceryl trinitrate between control and diabetic rats. These results support the involvement of reactive oxygen species in mediation of hyperglycemia-induced endothelial dysfunction in vivo, and provide the rationale for potential utilization of stable superoxide dismutase-mimic nitroxides for the prevention of the vascular complications accompanying diabetes.

Effects of the SOD mimic nitroxide 3-carbamoyl-PROXYL on oxidative stress markers and endothelial dysfunction in streptozotocin-induced diabetic rats.

OBJECTIVE: To evaluate the effects of 3-carbamoyl-PROXYL (CP), a stable superoxide dismutase (SOD) mimic compound, on oxidative stress markers and endothelial dysfunction in diabetic rats. ANIMALS AND METHODS: Rats were made diabetic by a single vein injection of streptozotocin (65 mg/kg) and diabetes was verified by the existence of excessive hyperglycemia a week after the treatment. Control and diabetic rats received vehicle or drug for eight weeks, after which the vascular tissue was examined for relaxation and oxidative stress markers. RESULTS: Diabetic rats showed increased vascular levels of superoxide that were accompanied by increased tissue levels of the oxidative stress markers malondialdehyde (MDA) and 8-iso-prostaglandin F2alpha (8-ISO). The vasorelaxant as well as the cyclic guanosine 5'-monophosphate (cGMP)-producing effects of acetylcholine (ACh) and nitroglycerine were reduced in diabetic rats. Treatment of diabetic rats with CP (50 mg/kg intraperitoneally, bid) abolished not only the differences in superoxide, MDA and 8-ISO levels, but also the differences in the relaxation and cGMP responses of vascular tissue between control and diabetic rats to both ACh and nitroglycerine. CONCLUSIONS: These results support the involvement of reactive oxygen species in mediation of diabetes-induced endothelial dysfunction in vivo, and provide the rationale for the potential use of SOD mimics in the treatment of diabetes.