Pharma clinics. How I treat...a diabetic patient with severe obesity

Obesity plays a crucial role in type 2 diabetes pathophysiology and a major weight loss markedly improves glycaemic control. The common failure of classical treatments leads to the use of more aggressive weight-reduction approaches, such as very-low-calorie diets (VLCDs), anti-obesity drugs or even bariatric surgery. VLCDs are very successful in the short-term but rather disappointing in the long-term. Anti-obesity compounds only induce a modest mean weight reduction, even if some patients appear to be better responders. Interestingly, serotoninergic agents increase insulin sensitivity and glycaemic control, independently of weight loss. Bariatric surgery provides the most impressive results. In well-selected subjects, gastroplasty (either vertical ring gastroplasty or adjustable silicone gastric banding) generally induces a considerable weight loss which results in a remarkable and sustained glycaemic control improvement and allows the reduction, or even the suppression, of any antidiabetic treatment. This ultimate solution should not be neglected after failure of medical approaches, provided that the indication is correct, the surgical procedure is performed in a specialized centre and the followup is well organized by a multidisciplinary team.     

Drug clinics. How I treat a cutaneous ulcer in outpatients

A case of angiolymphoid hyperplasia with eosinophilia arising on the face of a woman is reported. Histologically, the uniqueness of this case is the presence of multinucleated cells (MNCs), besides the conventional dermal changes. Electron microscopy showed that some of the apparent MNCs are clusters of endothelial cells forming immature vascular lumens with numerous microvilli, and the other MNCs displayed the recognized features of fibrohistiocytic or myofibroblastic cells. Immunohistochemically, some MNCs were positive for Ulex europaeus agglutinin and Factor VIII-related antigen. From these findings, some of the MNCs are histologically endothelial sprouts, and the others are fibrohistiocytic cells in the present case.     

Drug clinics. How I treat a patient with a low concentration of HDL cholesterol

The decision to treat an individual with low HDL cholesterol level depends on his overall cardiovascular risk profile and the therapeutic strategy is based upon the characteristics of the lipid profile (isolated abnormality, associated hypertriglyceridaemia or combined elevation of LDL cholesterol). The treatment must favour diet and exercise, before considering a possible pharmacological approach. Results are usually acceptable with better life habits and appropriate diet when low HDL cholesterol level is associated to hypertriglyceridaemia. From a pharmacological point of view, the best results are obtained with fibrates or nicotinic acid. However, results are often disappointing when low HDL cholesterol level is isolated.     

How I treat... trigeminal neuralgia in patients older than 60 years

Randomized controlled clinical study of Sulperazon (Sulbactam/Cefoperazon) was made in the surgical field. 35 cases were treated with Sulperazon and 32 cases with Ceftazidime. In the Sulperazon group (35 patients), the effective rate was 88.6% as compared with 90.6% of the patients in the Ceftazidime group (32 patients) (P > 0.05). The bacterial eradication rate was 86.2% in the Sulperazon group as compared with 88.5% in the Ceftazidime group. No significant difference was noted in both groups. In the Sulperazon group, side effects were not observed except nausea in one case.     

Drug clinics. How I treat various metabolic diseases treated by a drug intervention that targets the intestine]

Besides the classical dietary regimen, it is possible to use specific pharmacological approaches, targeted at the intestine, in order to treat some metabolic disorders. Three approaches will be described: anionic resins for treating hypercholesterolaemia, alpha-glucosidase inhibitors for treating diabetes mellitus and reactive hypoglycaemia, and intestinal lipase inhibitors for treating obesity. All these drugs are based on original concepts, but their clinical use is often limited by the occurrence of digestive side-effects. The latter may generally be reduced by progressive and individual titration of the dosage of each drug and/or by following an appropriate diet.     

How I evaluate...diabetic nephropathy. First part: micro- and macroalbuminuria

Diabetic nephropathy (DN) appears in about 30% of patients with type 1 diabetes (D1) and 15 to 60% of patients with type 2 diabetes (D2). It is preceded by microalbuminuria. Microalbuminuria is defined as an albumin excretion rate between 30 and 300 mg/24 h (on a 24-hour urine collection) or between 20 and 200 micrograms/min (on an overnight collection) in at least two out of three consecutive collections made within a 6-month period. Alternative screening techniques use either dipstick (Micral-Test II) or the albumin to creatinine ratio on an early morning urine sample (30-300 mg/g creatinine). Once persistent microalbuminuria is confirmed, 80% of type 1 diabetic patients and 20 to 50% of type 2 diabetic patients will progress to DN. In D2, microalbuminuria also represents a powerful predictor of early mortality from cardiovascular disease. Macroalbuminuria (AER > 300 mg/24 h, corresponding to a total protein excretion > 500 mg/24 h) will eventually lead to a end-stage renal insufficiency within 10 to 20 years. In D2, numerous patients will die from cardiovascular disease before reaching end-stage renal failure. Angiotensin-converting enzyme inhibitors can slow down the evolution toward DN when prescribed when microalbuminuria appears. Screening for microalbuminuria should therefore be a part of the annual clinical assessment in every diabetic patient.     

How I examine...diabetic nephropathy. Second part: assessment of glomerular filtration

This study was conducted to determine the uptake of dihydroergotamine (DHE) into the brain after intravenous and intranasal administration in rats. Eight anesthetized rats received either an intravenous (i.v.) or two successive intranasal (i.n.) doses of tritium labeled dihydroergotamine (3H-DHE) with 14C-inulin as a non-BBB (blood-brain barrier) permeable marker. Radioactivity concentrations in plasma were determined at designated times within 30 min postdose, and in blood and seven brain regions (olfactory bulb, frontal cortex, parietal cortex, occipital cortex, cerebellum, mid-brain areas, and brain stem) at 30 min. The plasma-to-brain permeability*area product (PeA) following an i.v. dose was calculated based on the 30-min brain tissue concentration and the area under the plasma concentration-time curve (AUC0-30 min, i.v.) assuming unidirectional transport from plasma to brain. Direct transport from nasal cavity to brain was assessed based on the amount of radioactivity in brain determined experimentally and predicted based on plasma AUC0-30 min, i.n. and PeA obtained from i.v. data. Following an i.v. dose, DHE distributed into the brain with a brain-to-plasma concentration ratio of approximately 5% at 30 min postdose. The PeA value of DHE ranged from 8.6 x 10(-4) to 37.5 x 10(-4) mL min(-1) g(-1) in different brain regions. Following i.n. doses the experimentally determined concentration in olfactory bulb was approximately 51 times, and in other regions three to seven times, greater than predicted values based only on PeA and plasma AUC, suggesting a direct transport pathway from the nasal cavity to the brain. As a result, the brain tissue concentrations at 30 min were similar to (0.31-1.04 times) those following an i.v. dose except for the olfactory bulb, in which the concentration was approximately four times greater than that following an i.v. dose. In conclusion, 3H-DHE penetrated the BBB following intravenous administration. Following i.n. doses, 3H-DHE was able to enter the brain directly from the nasal cavity, with the olfactory bulb being a part of the direct passage from nasal cavity to brain.     

How not to do research: or How I escaped alive from a social service agency.

Relates a personal experience of being in charge of a research project in a social service agency. Problems encountered included lack of office space and equipment, hiring of assistants, and conflicting views of project personnel. (0 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of shock on pain reactivity: I. Whether hypo- or hyperalgesia is observed on how pain reactivity is tested.

Prior research has shown that exposure to shock can induce a decrease in pain reactivity (hypoalgesia). The present experiments show that, at the same time points that subjects are less responsive to radiant heat applied to the tail (the tail-flick test), tailshock elicits enhanced motor reactivity and vocalization. This enhanced responsiveness, or hyperalgesia, is observed with both magnitude (Experiment 1) and threshold (Experiment 2) measures and decays within 32 min (Experiment 2). Experiment 3 shows that the hyperalgesia decays irrespective of whether or not subjects remain in the shock context, which suggests that the loss of hyperalgesia does not reflect extinction of the context–shock association. Neither removing subjects from the shock context (Experiment 4) nor the presentation of a postshock distractor (Experiment 5) affected the hyperalgesia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)