Risk of hypoglycaemia with oral antidiabetic agents in patients with Type 2 diabetes.

In patients with Type 2 diabetes, the appropriate intensity of glucose control is determined by age, life expectancy, and the presence of concomitant disease. Geriatric patients are especially susceptible to hypoglycaemia and therefore particular care should be taken in this group characterized by polypharmacy, renal or hepatic dysfunction, cardiovascular multimorbidity and malnutrition. As hypoglycaemia is a significant cause of morbidity and mortality, treatment regimens for diabetes should minimize the occurrence of hypoglycaemic episodes and be tailored to the patient's individual needs. The pharmacological options for treating Type 2 diabetes have increased considerably and the risk of hypoglycaemia of the currently available drugs varies considerably. Metformin, thiazolidinediones, and acarbose, oral antidiabetic drugs that decrease insulin resistance or postprandial glucose absorption, are associated with a low risk of hypoglycaemia. These drugs can also be used effectively in various combination regimens; however, by improving insulin sensitivity, combinations of metformin and thiolidinediones with sulphonylureas or meglitinides may considerably increase the risk of hypoglycaemia. On account of its complex pharmacoprofile glibenclamide is a problematic substance carrying a high risk of hypoglycaemia. There are limited preliminary data indicating that, under routine conditions, glimepiride may be associated with a lower risk of hypoglycaemia than glibenclamide and is no more likely to cause hypoglycaemia than other shorter-acting agents such as gliclazide and glipizide. Nateglinide and repaglinide as short-acting insulin secretagogues may be associated with a reduced risk of hypoglycaemia compared with glibenclamide, in particular when dosed flexibly. Repaglinide might be beneficial in individuals with renal impairment.     

Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.     

Horizontal advancement flap for lateral dorsal nasal defects

BACKGROUND: Repairing dorsal nasal defects is a frequent challenge for dermatologic surgeons, mainly due to the high frequency of basal cell carcinomas on this site. Obvious scars, mismatched skin and distortion of the nasal contour are the surgical hazards that must be avoided in these cases. AIM: Our aim was to perform surgery involving a simple flap in order to repair medium to large defects on the dorsal side of the nose. METHODS: The dorsal horizontal advancement flap was studied in 12 patients, in order to evaluate the benefits and limits of this surgical procedure. RESULTS: The resulting scars on most of our patients were well-camouflaged among their natural skin lines, and there was neither distortion of the alar contour nor the nostril. CONCLUSIONS: This flap is easy to perform and, in selected cases, provides an outstanding alternative to second-intention healing, full-thickness skin grafts, transposition, rotation and pedicle flaps.     

Ketorolac during the induction phase of cyclosporin-A therapy.

PURPOSE: The aim of this study was to determine if the concomitant use of ketorolac 0.4% and cyclosporin-A improves patient comfort during the induction phase in treating chronic dry eye disease. METHODS: Patients (n = 52) with clinically diagnosed dry eye were randomized to receive either cyclosporin-A monotherapy twice-daily (BID) or a BID adjunctive regimen of ketorolac, followed by the instillation of cyclosporin-A 10 min later. Study visits were at baseline, week 2, and week 6. At each study visit, patients underwent an evaluation for corneal staining, Schirmer's scores, and tear break-up time tests. Patients were asked to rate ocular comfort on a 4-point scale and to complete the ocular surface disease index (OSDI). Changes from baseline readings were recorded at week-2 and week-6 visits, and final patient success on treatment regimen was evaluated at week 6. RESULTS: After 6 weeks, the mean ocular comfort score of adjunctive patients improved 2.55 +/- 0.95 points, versus 1.53 +/- 0.91 points for monotherapy (P = 0.309). The adjunctive regimen provided significantly greater corneal staining reductions versus monotherapy, mean reduction in staining of 1.74 +/- 0.9, versus 1.27 +/- 0.56 (P = 0.044). CONCLUSIONS: Concurrent ketorolac 0.4% use with cyclosporin-A significantly reduced corneal staining and increased comfort in the induction phase.     

p53 expression and disease outcome of breast cancer patients undergoing primary chemotherapy with anthracycline-containing regimens

Primary chemotherapy administered to breast cancer patientsis the best model to identify baseline features able to predictwhich patients may be most likely to benefit or not from a cytotoxicregimen. In the March issue of Annals of Oncology two papersevaluated the predictive role of immunohistochemical p53 expressionon     

Perspectives on Health Among Adult Users of Illicit Stimulant Drugs in Rural Ohio

CONTEXT: Although the nonmedical use of stimulant drugs such as cocaine and methamphetamine is increasingly common in many rural areas of the United States, little is known about the health beliefs of people who use these drugs. PURPOSE: This research describes illicit stimulant drug users' views on health and health-related concepts that may affect their utilization of health care services. METHODS: A respondent-driven sampling plan was used to recruit 249 not-in-treatment, nonmedical stimulant drug users who were residing in 3 rural counties in west central Ohio. A structured questionnaire administered by trained interviewers was used to collect information on a range of topics, including current drug use, self-reported health status, perceived need for substance abuse treatment, and beliefs about health and health services. FINDINGS: Participants reported using a wide variety of drugs nonmedically, some by injection. Alcohol and marijuana were the most commonly used drugs in the 30 days prior to the interview. Powder cocaine was used by 72.3% of the sample, crack by 68.3%, and methamphetamine by 29.7%. Fair or poor health status was reported by 41.3% of the participants. Only 20.9% of the sample felt they needed drug abuse treatment. Less than one third of the sample reported that they would feel comfortable talking to a physician about their drug use, and 65.1% said they preferred taking care of their problems without getting professional help. CONCLUSIONS: Stimulant drug users in rural Ohio are involved with a range of substances and hold health beliefs that may impede health services utilization.     

Pick’s disease with Pick bodies combined with progressive supranuclear palsy without tuft‐shaped astrocytes: A clinical,neuroradiologic and pathological study of an autopsied case

We report clinical, neuroradiologic features, and neuropathologic findings of a 76‐year‐old man with coexistent Pick’s disease and progressive supranuclear palsy. The patient presented with loss of recent memory, abnormal behavior and change in personality at the age of 60. The symptoms were progressive. Three years later, repetitive or compulsive behavior became prominent. About 9 years after onset, he had difficulty moving and became bed‐ridden because of a fracture of his left leg. His condition gradually deteriorated and he developed mutism and became vegetative. The patient died from pneumonia 16 years after the onset of symptoms. Serial MRI scans showed progressive cortex atrophy, especially in the bilateral frontal and temporal lobes. Macroscopic inspection showed severe atrophy of the whole brain, including cerebrum, brainstem and cerebellum. Microscopic observations showed extensive superficial spongiosis and severe neuronal loss with gliosis in the second and third cortical layers in the frontal, temporal and parietal cortex. There were Pick cells and argyrophilic Pick bodies, which were tau‐ and ubiquitin‐positive in neurons of layers II–III of the above‐mentioned cortex. Numerous argyrophilic Pick bodies were observed in the hippocampus, especially in the dentate fascia. In addition, moderate to severe loss of neurons was found with gliosis and a lot of Gallyas/tau‐positive globus neurofibrillary tangles in the caudate nucleus, globus pallidus, thalamus, substantia nigra, locus coeruleus and dentate nucleus. Numerous thorned‐astrocytes and coiled bodies but no‐tuft shaped astrocytes were noted in the basal ganglion, brainstem and cerebellar white matter. In conclusion, these histopathological features were compatible with classical Pick’s disease and coexistence with progressive supranuclear palsy without tuft‐shaped astrocytes.     

Fetal growth patterns in fetuses of women with pregestational diabetes mellitus.

OBJECTIVE: To assess the effect of glucose control on the rate of growth of fetuses in women with pregestational diabetes mellitus (Types 1 and 2). METHODS: All pregestational diabetic women booked at Mater Mothers' Hospital, Brisbane, Australia, between 1 January 1994 and 31 December 2002, were included. Pregnancies with congenital fetal anomalies, multiple pregnancies, and pregnancies terminated prior to 20 weeks' gestation were excluded. Dating scans were performed before 14 weeks' gestation and serial scans were performed at 18, 24, 28, 32 and 36 weeks. Fetal parameters, including biparietal diameter, femur length and abdominal circumference, were recorded. The daily growth rates for biparietal diameter, femur length, and fetal abdominal area were calculated and compared with those in a low-risk (non-diabetic) population. The growth rates in fetuses of women with satisfactory diabetic control (HbA1c < 6.5%) and unsatisfactory control (HbA1c > or = 6.5%) in the three trimesters were compared. RESULTS: A total of 174 diabetic pregnancies were included and a total of 997 ultrasound scans were performed. The growth rates for fetuses of mothers with diabetes mellitus were significantly higher than for those in the low-risk population. The z-scores for biparietal diameter, femur length, and fetal abdominal area were 0.18, 0.59 and 1.44, respectively. Fetuses of diabetic mothers with high HbA1c in the first trimester had significantly greater fetal abdominal area growth rate than those with normal HbA1c (fetal abdominal area z-score of 1.7 vs. 0.75, P = 0.009). Although the fetal abdominal area z-scores in fetuses of diabetic mothers with high HbA1c in the second or third trimesters were also higher than those with normal HbA1c levels, the differences did not reach statistical significance. Maternal obesity did not influence the fetal growth rate. CONCLUSION: The rate of growth of fetuses of diabetic mothers differs from that of the normal population. Growth acceleration persists until the late third trimester. Moreover, periconceptional glucose control appears to have a significant effect on accelerated growth of the fetal abdominal area.