bluuebunny/crossref_metadata_2025 huggingface dataset:
Rosiglitazone inhibits the insulin‐mediated increase in PAI‐1 secretion in human abdominal subcutaneous adipocytes
Authors: Harte A. L. , McTernan P. G. , McTernan C. L. , Smith S. A. , Barnett A. H. , Kumar S.
Published: August 2003

Objective:  The aim of this study was to investigate the effect of insulin and an insulin‐sensitizing agent, rosiglitazone (RSG), on the production of plasminogen‐activator inhibitor‐1 (PAI‐1) in isolated subcutaneous abdominal adipocytes. Human tissue‐type plasminogen activator (t‐PA) was also measured to assess changes in overall thrombotic risk.

Methods:  The mean depot‐specific expression of PAI‐1 and t‐PA mRNA (n = 42) in subcutaneous abdominal (n = 21), omental (n = 10) and thigh (n = 11) adipose tissue depots was examined. Furthermore, subcutaneous adipocytes were treated with insulin, RSG and insulin in combination with RSG (10−8 m) for 48 h. Conditioned media were collected and enzyme‐linked immunosorbent assays performed for PAI‐1 and t‐PA (n = 12) antigen. PAI‐1 and t‐PA mRNA levels were also assessed.

Results:  PAI‐1 mRNA levels were significantly higher in subcutaneous and omental abdominal tissue than in thigh fat (p = 0.037 and p = 0.014). No change in t‐PA mRNA expression between the adipose tissue depots was observed. Insulin stimulated PAI‐1 protein secretion in a concentration‐dependent manner in adipocytes (control: 68.3 ± 1.2  ng/ml (s.e.m.); 10 nm insulin: 73.7 ± 3.8 ng/ml↑; 100 nm insulin: 86.8 ± 4.1 ng/ml↑**; 1000 nm insulin: 102.0 ± 4.8  ng/ml↑***; **p < 0.01, ***p < 0.001). In contrast, insulin + RSG (10−8 m) reduced PAI‐1 production relative to insulin alone (***p < 0.001), whilst RSG alone reduced PAI‐1 protein secretion in a concentration‐dependent manner (RSG at 10−10 m: 50.4 ± 2.87 ng/ml↓***; RSG at 10−5 m: 30.3 ± 2.0 ng/ml↓***; p < 0.001). No difference was observed between control and treatments for t‐PA secretion (range 7–11 ng/ml).

Conclusions:  Insulin stimulated PAI‐1 secretion, whilst RSG reduced both PAI‐1 secretion alone and in combination with insulin. These data suggest that adipose tissue may contribute significantly to the elevated circulating PAI‐1 in obesity. Therefore, RSG's effects on PAI‐1 production in adipose tissue may contribute to the fall in circulating PAI‐1 levels observed in patients receiving RSG therapy.
Humalog® Mix50™ before carbohydrate‐rich meals in type 2 diabetes mellitus
Authors: Roach P. , Arora V. , Campaigne B. N. , Mattoo V. , Rangwala S. ,   The India Mix25/Mix50 Study Group
Published: August 2003

Aim:  To compare pre‐meal injection of Humalog® Mix50™ (Mix50) and Humalog® Mix25™ (Humalog® Mix75/25™ in the US; Mix25) with respect to 2 h postprandial (2 h pp) blood glucose (BG) control after a carbohydrate‐rich breakfast in patients with type 2 diabetes.

Research Design and Methods:  One hundred and sixteen patients were enrolled in a 16‐week crossover trial and received two treatment regimens in a randomized crossover fashion: (i) Mix50 before breakfast and Mix25 before the evening meal (Mix50/Mix25) and (ii) Mix25 before both breakfast and the evening meal (Mix25 twice daily). Insulin doses were adjusted according to stated glycaemic targets. After 6 and 8 weeks of treatment, the patient's usual morning insulin dose was administered, followed immediately by a test breakfast representative of the patient's usual breakfast meal. Fasting and 2 h pp BG concentrations were measured at the time of the test meal. Haemoglobin A1c (A1C) was measured, and information regarding hypoglycaemia (symptoms) was collected at the end of each treatment period.

Results:  Insulin doses were similar between treatments (morning = 31–33 U, evening = 26–28 U) at endpoint. Following the test breakfast, the 2 h pp BG was lower (10.9 ± 0.3 mmol/l vs. 12.4 ± 0.3 mmol/l, p = 0.0012) and the 2 h pp BG excursion was smaller (1.4 ± 0.28 mmol/l vs. 3.5 ± 0.28 mmol/l, p < 0.001) during treatment with Mix50/Mix25 than during treatment with Mix25 twice daily. There was no difference between the treatments with respect to fasting BG (Mix50/Mix25, 9.5 ± 0.3 mmol/l vs. Mix25 twice daily, 8.9 ± 0.3 mmol/l; p = NS), A1C (8.14% ± 1.14% vs. 8.14% ± 1.07%; p = NS) or the incidence of self‐reported hypoglycaemia (34% vs. 23%; p = NS).

Conclusions:  Compared with treatment with Mix25 twice daily, treatment with Mix50 before breakfast and Mix25 before the evening meal resulted in better pp glycaemic control following a carbohydrate‐rich meal, and similar fasting BG, A1C and incidence of hypoglycaemia in patients with type 2 diabetes.
Effects of cyclo (his–pro) plus zinc on glucose metabolism in genetically diabetic obese mice
Authors: Hwang I. K. , Go V. L. W. , Harris D. M. , Yip I. , Kang K. W. , Song M. K.
Published: August 2003

Aims:  The specific objective of this study was to determine acute and long‐term effects of cyclo (his–pro) (CHP) plus zinc and l‐histidine (CZH) treatment on glucose metabolism in genetically obese (ob/ob), type 2 diabetic mice.

Methods:  Acute effects of 0.3 mg of CHP plus 10 mg of zinc and 0.5 mg of l‐histidine/kg body weight (BW) on fed blood glucose concentrations and 3‐h average of above fasting blood glucose concentrations (TAFGCs), an index of oral glucose tolerance test, in lean and ob/ob mice were determined. To evaluate long‐term effects of CZH on TAFGCs, lean and ob/ob mice were treated with drinking water containing increasing doses of CHP (0, 0.5, 1.0 or 1.5 mg/l) plus 10 mg zinc and 0.5 mg of l‐histidine/l for 3 weeks. During the treatment period, fed blood glucose concentrations, BW and food and water intake were determined. At the end of the treatment, fasting blood glucose concentrations, TAFGC and fed plasma insulin concentrations were determined.

Results:  Blood glucose concentrations significantly decreased when CZH was administered acutely via gastric gavage in food‐deprived ob/ob mice. Similarly, 1.0 mg/l CHP treatment of mice with fixed amounts of 10 mg zinc and 0.5 mg l‐histidine/l was optimal to decrease fed blood glucose and plasma insulin concentrations during a 3‐week treatment period in ob/ob mice. TAFGC values in these mice also improved most significantly with the same combination of CHP, zinc and l‐histidine used to test for fed blood glucose and plasma insulin levels. Fasting blood glucose concentrations and BW gains also decreased in ob/ob mice treated with 1.0 mg of CHP/l plus the same amount of zinc and l‐histidine used in the above experiments. No effects of CZH treatment in lean mice were observed.

Conclusions:  CZH is effective in decreasing blood glucose concentrations in genetically obese (ob/ob), type 2 diabetic mice. These data support our working hypothesis that CZH may be an important anti‐hyperglycaemic agent.
Effects of dietary supplementation with isoflavones from red clover on ambulatory blood pressure and endothelial function in postmenopausal type 2 diabetes
Authors: Howes J. B. , Tran D. , Brillante D. , Howes L. G.
Published: August 2003

Objective:  The aim of this study was to determine whether dietary supplementation with isoflavones from red clover affected ambulatory blood pressure and forearm vascular endothelial function in postmenopausal type 2 diabetic women.

Design:  Sixteen postmenopausal type 2 diabetics treated with diet or oral hypoglycaemic therapy completed a randomized double‐blind crossover trial of dietary supplementation with isoflavones from red clover (approximately 50 mg/day) for 4 weeks compared to placebo. Twenty‐four‐hour ambulatory blood pressure recordings and forearm vascular responses to acetylcholine, nitroprusside and L‐nitromonomethylarginine (L‐NMMA) were measured at the end of each treatment period.

Results:  Mean daytime systolic and diastolic blood pressures were significantly lower during isoflavone therapy compared to placebo (−8.0 ± 3.4 and −4.3 ± 1.9 mmHg respectively, p < 0.05). The increase in forearm vascular resistance following L‐NMMA was significantly greater during isoflavone supplementation (20.9 ± 6.5) than placebo (3.7 ± 2.9 arbitrary units, p < 0.05), suggesting an improvement in basal endothelial function. Plasma lipoproteins, glycated haemoglobin and forearm vascular responses to acetylcholine and nitroprusside did not differ significantly between isoflavone and placebo therapy.

Conclusion:  Isoflavone supplementation from red clover may favourably influence blood pressure and endothelial function in postmenopausal type 2 diabetic women.
Lipoprotein risk factors for cardiovascular disease in patients with type 2 diabetes mellitus treated with oral antihyperglycaemic agents
Authors: Chu J. W. , Abbasi F. , McLaughlin T. L. , Lamendola C. , Schaaf P. , Carlson T. H. , Leary E. T. , Reaven G. M.
Published: August 2003

Aims:  To compare lipoprotein risk factors for cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (DM) treated with a sulphonylurea (SU) compound only, metformin (MET) only, or combined SU + MET.

Methods:  The study population consisted of 62 patients with type 2 DM, whose antihyperglycaemic treatment program had been stable for at least 3 months, divided into three groups: 26 patients in the SU group, 17 patients in the MET group and 19 patients in the SU + MET group. None of the patients were taking lipid‐lowering drugs. Fasting venous blood samples were taken to measure concentrations of glucose, total cholesterol, triglycerides (TG), high‐density lipoprotein‐cholesterol (HDL‐C), low‐density lipoprotein‐cholesterol (LDL‐C) and remnant lipoprotein‐cholesterol (RLP‐C) as well as for determination of LDL particle diameter.

Results:  The three groups were similar in terms of age, gender, body mass index and fasting plasma glucose concentrations. Total cholesterol concentrations were significantly lower (p < 0.05 for trend) in those treated with SU + MET as compared with the other two groups. However, there were no significant differences between the three groups in their plasma concentrations of TG, LDL‐C, HDL‐C or RLP‐C; furthermore, the proportion of individuals within each treatment group with small LDL particle diameter was also not different.

Conclusions:  The lipoprotein profile of patients with type 2 DM, matched for level of fasting hyperglycaemia, was similar irrespective of treatment with SU alone, MET alone or SU + MET. Thus, we could not identify any changes in lipoprotein metabolism that could account for differences in risk of CVD as a function of treatment.
Influence of apolipoprotein E genotype on the response to caloric restriction in type 2 diabetic patients with hyperlipidaemia
Authors: Tamasawa N. , Murakami H. , Yamato K. , Matsui J. , Tanabe J. , Suda T.
Published: August 2003

Aims:  Hyperlipidaemia is a major predisposing factor to atherosclerosis in patients with type 2 diabetes. Apolipoprotein (apo) E polymorphism influences lipoprotein metabolism, and the present study was undertaken to explore the relation, in type 2 diabetics, between apo E genotype and the plasma lipid response to dietary therapy.

Methods:  The subjects were 104 patients with type 2 diabetes and hyperlipidaemia, and the difference, due to apo E genotype, in dietary response was followed for 4–6 weeks. The caloric intake was maintained in the range 20–25 kcal/kg, and the medications for diabetes were not changed during the follow‐up period.

Results:  Plasma total cholesterol (TC) and triglyceride (TG) levels were significantly lowered by the dietary treatment in patients with apo E genotypes of ε3/3, ε2/3 and ε3/4; however, the lipid levels in patients with ε2/4 did not respond to the diet.

Conclusions:  apo E genotype should be taken into consideration in the treatment of hyperlipidaemia in diabetic patients.
Alterations in semen parameters in men with epilepsy treated with valproate or carbamazepine monotherapy
Authors: Røste L. S. , Taubøll E. , Haugen T. B. , Bjørnenak T. , Sætre E. R. , Gjerstad L.
Published: August 2003

Men with epilepsy are known to have reduced fertility. Whether this is drug‐induced or a result of the epilepsy itself is still under debate. Few studies have been carried out on semen from men with epilepsy. The aim of the present study was first to investigate possible drug‐specific effects of long‐term treatment with either valproate or carbamazepine on semen quality and testicular size, and secondly to see whether the results in epilepsy patients differed from healthy fertile males. Men with epilepsy, 20–40 years old, having used either valproate (n = 16) or carbamazepine (n = 20) for >2 years, were included. The semen data of healthy fertile men without epilepsy in the same age group (n = 90) were used as controls. The semen was examined according to WHO (1999). No significant differences in semen quality were seen between men receiving either valproate or carbamazepine. However, semen from the valproate‐treated, as opposed to the carbamazepine‐treated, differed from controls with regard to tail abnormalities. Absolute testicular size was not significantly different between the two treatment groups. However, after correcting for changes in body mass index (BMI), the testicular size/BMI ratio was lower in the valproate‐treated patients. The valproate‐treated patients gained significantly more weight than the carbamazepine‐treated patients after start of current medication. No differences between the patient groups were found in terms of libido/potency or number of pregnancies fathered. When comparing all epilepsy patients with healthy fertile males, there was a significant reduction in the percentage of rapidly progressive motile sperms in the semen from epileptic patients. The semen from men with epilepsy also showed significant differences from the controls regarding neck and head abnormalities of the spermatozoa.
Evolving atherosclerosis at carotid and intracranial arteries in Japanese patients with ischemic heart disease: a 5‐year longitudinal study with MR angiography
Authors: Uehara T. , Tabuchi M. , Mori E. , Yamadori A.
Published: August 2003

Progression of atherosclerosis at extracranial carotid and intracranial arteries in patients with ischemic heart disease (IHD) is not well defined. We carried out a 5‐year longitudinal study with magnetic resonance angiography (MRA) of patients with IHD to assess the incidence of progression of atherosclerosis at extracranial carotid and intracranial arteries and to determine predictors of the progression. We previously performed carotid and intracranial MRA on 67 patients who had received selective coronary angiography for the clinical diagnosis of IHD. Of these 67 subjects, 41 patients gave informed consent to undergo MRA reexaminations to evaluate changes of extra‐ and intracranial arteries over a 5‐year period. The degree of stenosis was divided into five grades depending on the narrowness of the arteries, i.e. normal, mild, moderate, severe and occluded. The average of follow‐up period with MRA examination was 58.8 months. The progression of atherosclerosis, as defined as an increase of one grade of the stenosis rating, including both the exacerbation of pre‐existing stenosis and the appearance of new stenotic lesions, were found in five patients (12.2%) for the cervical carotid artery and in only one patient (2.4%) for the intracranial artery. A multiple logistic regression analysis revealed that baseline carotid artery stenosis (P = 0.008), age (P = 0.047), and coronary events during the follow‐up period (P = 0.048) were significant and independent predictors of progression of carotid atherosclerosis. In conclusion, our findings suggest that follow‐up evaluation of the carotid artery is indicated for patients with IHD in whom carotid artery stenosis was detected on an initial examination. Further study is needed with larger numbers of patients to confirm these findings.
Tremor of the mouth floor and anti‐glutamic acid decarboxylase autoantibodies
Authors: Vianello M. , Morello F. , Scaravilli T. , Tavolato B. , Giometto B.
Published: August 2003

Involuntary movements of the mouth can present as palatal tremor, which is frequently associated with hypertrophy of the inferior olivary nucleus and can be accompanied by contraction of other muscles of the head. We report the case of a 39‐year‐old man with autoimmune thyroiditis and diabetes who complained of involuntary rhythmic tremor involving the muscles of the floor of the mouth, which interfered with breathing and swallowing. Cerebrospinal fluid (CSF) examination showed the presence of oligoclonal bands and screening for anti‐neuronal antibodies revealed high titres of anti‐glutamic acid decarboxylase autoantibodies (GAD‐Ab). Tremor responded to treatment with benzodiazepines. The correlation between the tremor and antibody positivity is unclear although an alteration of the gabaergic system mediated by the antibodies may be hypothesised on the basis of an inflammatory CSF profile.
Iatrogenic Creutzfeldt–Jakob disease subsequent to dural graft: persisting risk after 1987
Authors: Boutoleau C. , Guillon B. , Martinez F. , Vercelletto M. , Faure A. , Fève J. R.
Published: August 2003

The first case of Creutzfeldt–Jakob disease (CJD) related to the use of a dura mater graft of cadaveric origin was identified in 1987 and this procedure is now considered as one of the main causes of iatrogenic CJD. Although the decontamination procedure for the preparation of graft material was modified, the product was withdrawn from the market in many countries a few years later and replaced by synthetic material. In this context, two patients treated in our institution developed CJD following a cadaveric dural graft performed after cerebral and lumbar trauma. Their clinical presentation, showing predominant cerebellar symptoms, late deterioration and myoclonic jerks, and a rapid disease course until death, was similar to that of previously reported cases involving the iatrogenic form. As the graft for one of the patients was performed in 1991 (several years after modification of the decontamination procedure), this fourth reported case suggests that the risk of iatrogenic CJD may have persisted in some patients treated after 1987, when grafts of cadaveric origin were totally abandoned.
Guillain–Barré syndrome with marked pleocytosis or a significant proportion of polymorphonuclear granulocytes in the cerebrospinal fluid: neuropathological investigation of five cases and review of differential diagnoses
Authors: Rauschka H. , Jellinger K. , Lassmann H. , Braier F. , Schmidbauer M.
Published: August 2003

In cases with otherwise clinically typical Guillain–Barré syndrome (GBS), pronounced cerebrospinal fluid (CSF) pleocytosis or the mere presence of CSF‐polymorphonuclear granulocytes should alert the physician to consider alternative diagnoses. Therefore, we retrospectively studied the neuropathology of central and peripheral nervous system in two cases with a CSF cell count of more than 50/μl and in three cases with a significant proportion of polymorphonuclear granulocytes in the CSF sediment. All cases fulfilled the required criteria for the diagnosis of GBS, the duration from onset to death ranged from 4 to 100 days. Neuropathological investigations included routine staining procedures and immunohistochemistry for antigens of glial and haematopoetic cells as well as for products of relevant neurotropic viruses. Demyelinating polyradiculitis was present in four cases, in one patient with a survival time of 4 days the type of damage to myelinated fibres was unclassifiable. In the central nervous system a consistent finding was diffuse activation of microglia, only one case showed mild meningeal and lower brainstem inflammation. Viral products were generally absent. In summary, the neuropathological findings confirm that marked CSF pleocytosis or the presence of polymorphonuclear granulocytes does not rule out the diagnosis of GBS.
Cognitive processing in completely paralyzed patients with amyotrophic lateral sclerosis
Authors: Kotchoubey B. , Lang S. , Winter S. , Birbaumer N.
Published: August 2003

Cognitive functions have never been studied before in completely paralyzed patients, probably due to the lack of the appropriate method. In this study, three male patients in the last stage of amyotrophic lateral sclerosis (ALS) are examined. They were totally locked‐in, i.e., incapable of any voluntary response including eye movements. Given this complete lack of motor expression, the method of event‐related brain potentials (ERPs) was used. The ERP recording was carried out at the patients’ bedside. In one patient indications of preserved cognitive abilities including adequate language comprehension were obtained. The data of the second patient also demonstrate a high degree of intactness of complex cognitive functions, but some ERP phenomena were consistently abnormal, which may be interpreted as a consequence of disease‐related degenerative processes. In the third patient no electrocortical response which might indicate higher cortical processing was found. This first ERP study of totally paralyzed patients shows that some of them can possess high, perhaps even normal, information processing capacity after a long period of severe immobility and artificial ventilation.
Metabolic impairment of brain metabolism in patients with Lewy body dementia
Authors: Mirzaei S. , Rodrigues M. , Koehn H. , Knoll P. , Bruecke Th.
Published: August 2003

A reliable assessment of dementia is essential for a differentiated treatment. Recent studies have demonstrated a poor accuracy of clinical criteria for diagnosis of Lewy body dementia. Diffuse Lewy body disease (LBD) is the second most common cause of senile degenerative dementia and is characterized histologically by the occurrence of Lewy bodies in allocortical, neocortical and subcortical structures. Seven male patients (mean age 81 years) with clinically suspected diffuse LBD were investigated with 18F‐fluorodeoxyglucose (FDG)‐PET using a Siemens ECAT‐ART PET‐scanner. The 18F‐FDG‐PET showed a diffuse glucose hypometabolism in the entire cerebral cortex with relative sparing of the primary sensory‐motor cortex in all patients. This diffuse metabolic impairment in the entire cortex with relative sparing of central region seems to be a typical pattern for LBD, distinct from Alzheimer's disease.
Is there a link between the severity of sleep‐disordered breathing and atherosclerotic disease of the carotid arteries?
Authors: Kaynak D. , Göksan B. , Kaynak H. , Degirmenci N. , Daglıoglu S.
Published: August 2003

Epidemiological studies have shown a strong association between sleep‐disordered breathing (SDB) and cerebrovascular diseases. A total of 114 male patients, aged 40–65 years, referred to sleep laboratory for the evaluation of snoring and disturbed sleep were studied. Subjects were divided into three groups: habitual snoring, mild–moderate and severe obstructive sleep apnea syndrome (OSAS), respectively, determined by using three respiratory disturbance index (RDI) cut points (≤5, 5 < RDI < 30 and ≥30). Measurement of intima‐media thickness (IMT) and the presence of plaque were determined by ultrasonographic evaluation. Major vascular risk factors such as hypertension, diabetes, smoking, hyperlipidemia, and obesity were determined. The OSA groups had significantly higher IMT values compared with the habitual snoring group. Three groups were significantly different with regard to the presence of plaque. Age and body mass index were found to be significantly associated with IMT while age and RDI were found to be most probably predictive for plaque. There were no significant differences amongst the three groups with respect to age, prevalence of hypertension and diabetes, smoking, total cholesterol and total triglyceride levels. These findings suggested that SDB is a predisposing factor for the atherosclerotic process and precipitate plaque particularly when associated with higher RDI.
The burden of brain diseases in Europe
Authors: Olesen J. , Leonardi M.
Published: August 2003

The burden [as defined by the World Health Organisation (WHO)] of brain diseases (neurological, neurosurgical and psychiatric diseases together) is very high and yet resources spent on these diseases are not necessarily commensurate with the extent of this burden. However, hard data on the burden of brain diseases in Europe have not previously been easily accessible. The Global Burden of Disease (GBD) 1990 study conducted jointly by the WHO, Harvard University and the World Bank provided new measures that are now becoming universally accepted and have been used also in a repeat study: The GBD 2000. The key parameter of the study is disability adjusted life years (DALY), which is the sum of years of life lost (YLL) caused by premature death and years of life lived with disability (YLD). In the present report, data from the GBD 2000 study and from the World Health Report 2001 on brain diseases is extracted for the territory of Europe. This territory corresponds roughly to the membership countries of the European Federation of Neurological Societies. The WHO's Report has a category called neuropsychiatric diseases, which comprises the majority but not all the brain diseases. In order to gather all brain diseases, stroke, meningitis, half of the burden of injuries and half of the burden of congenital abnormalities are added. Throughout Europe, 23% of the years of healthy life is lost and 50% of YLD are caused by brain diseases. Regarding the key summary measure of lost health, DALY, 35% are because of brain diseases. The fact that approximately one‐third of all burden of disease is caused by brain diseases should have an impact on resource allocation to teaching, reasearch, health care and prevention. Although other factors are also of importance, it seems reasonable that one‐third of the curriculum at medical school should deal with the brain and that one‐third of life science funding should go to basic and clinical neuroscience. In addition, resource allocation to prevention, diagnosis and treatment of brain diseases should be increased to approach, at least, one‐third of health care expenditure. With the present data on hand, neurologists, neurosurgeons, psychiatrists, patient organizations and basic neuroscientists have a better possibility to increase the focus on the brain.
Dog‐ears: a useful artifice in the closure of extensive wounds
Authors: De Giorgi V , Mannone F , Quercioli E , Giannotti V , Piccolo E , Carli P
Published: August 2003

Background Wounds too extensive to permit primary repair by suturing can be closed using a skin graft or skin flap and the choice of method depends on a series of factors. Practice and personal experience play a role, as well as the characteristics of the lesion and its site. Each case poses special problems, so it is not possible to establish firm rules.

Objective To present a surgical technique for the closure of a circular defect located on the dorsum of the foot, which resulted from the extirpation of a melanoma by surgery.

Methods In this case we used a mixed procedure consisting of skin flaps and a double full‐thickness skin graft. For this operation we used dog‐ears resulting from the circular exeresis performed for the extirpation of the tumour.

Results The reconstructive results were good and there were no postoperative complications.

Conclusions We consider this procedure particularly suitable for certain anatomical sites, such as the dorsum of the foot, where the skin is less elastic and thinner; and for patients who are not willing to accept skin removal from other sites or for flaps to be made with more invasive operations and more constructed scars.
Pustular acral erythema in a patient with acute graft‐versus‐host disease
Authors: Ruiz‐Genao DP , GF‐Villalta MJ , Peñas PF , Fraga J , García‐Díez A , Fernández‐Herrera J
Published: August 2003

Acral erythema is a well‐known side‐effect of chemotherapy treatment but it is not common in patients undergoing bone marrow transplant. We report a post‐transplant patient with clinical and histological acute graft‐versus‐host disease (GVHD) who concurrently developed acral erythema presenting as painful, well‐defined and self‐limiting palmar erythema with pustules. A skin biopsy from the palm showed abnormal keratinocyte maturation and eccrine squamous syringometaplasia. This case illustrates the difficulties in establishing the differential diagnosis of cutaneous eruptions in patients undergoing bone marrow transplant.
Overexpression of bcl‐2 in lymphocytes of psoriatic skin
Authors: Yildiz L , Bariş S , Senturk N , Kandemir B
Published: August 2003

Bcl‐2 overexpression in lymphocytes play an important part in immunological and inflammatory diseases. In the present study, we investigated the bcl‐2 expression in dermal lymphocytes of psoriatic skin biopsy samples. From the archives of the Department of Pathology, Ondokuz Mayis University Medical School (Samsun, Turkey), tissue sections belonging to 28 psoriasis cases and 10 chronic non‐specific inflammatory skin disease cases were immunohistochemically stained by bcl‐2. Positive staining was semiquantitatively graded from 1+ to 4+. Of the 28 psoriasis cases 20 were found to express bcl‐2. Our data suggest that bcl‐2‐mediated inflammation plays a part in the pathogenesis and recurrent character of psoriasis.
Basal cell carcinoma showing connections with epidermal cysts
Authors: Tanaka M , Terui T , Sasai S , Tagami H
Published: August 2003

Basal cell carcinomas arising from epidermal cysts are rare. A 76‐year‐old Japanese man had had a blackish nodule on his right knee for 15 years, under which he later noticed the development of a subcutaneous nodule. On histological examination masses of tumour cells showed the feature of adenoid and solid patterns of basal cell carcinoma that were connected to the wall of epidermal cysts in many places as well as with the overlying epidermis.
Multiple agminated superficial arteriovenous haemangioma on the scalp
Authors: Grunwald MH , Cagnano E , Barki Y , Halevy S
Published: August 2003

We describe a patient with an unusual presentation of multiple arteriovenous haemangioma (AVH) grouped in one area of the scalp. The diagnosis was confirmed by histological, X‐ray and ultrasound studies. These lesion represent a rare, benign, acquired vascular hamartomatous formation that arises from the suprapapillary vascular plexus.
Reconstruction of Skin Defects After Radical Excision of Anorectal Giant Condyloma Acuminatum: 6 cases
Authors: Meštrović Tomislav , Čavčić Josip , Martinac Pero , Turčić Josip , Župančić Božidar , Marija Čavčić Ana , Jelinčić Željko
Published: August 2003

The authors report six cases of giant condyloma accuminatum and evaluate the use of mesh‐skin grafts in covering the skin defect after radical local excision of perianal giant condyloma acuminatum. Medical records of six patients suffering from the giant condylomata acuminata and treated surgically at the Department of Surgery, Clinical Hospital Center Zagreb, were examined. Use of mesh‐skin grafts in covering the skin defect after radical local excision of GCA was compared to other methods of treating the skin defect after radical excision of perianal lesions such as secondary wound healing. Four patients were treated by radical local excision and two patients were treated by abdominoperineal resection. There were partial graft failures (satisfactory result) in all patients and complete healing took about 3 to 4 weeks from time of grafting. A mesh‐skin graft was used to cover the skin defect. There were no recurrences, wound infections, wound bleeding, hypertrophic scars, or mesh‐like skin appearance of the recipient site. Therefore a good cosmetic and functional result was achieved. Use of mesh‐grafts in covering the wounds after radical excision of anorectal giant condylomata acuminata compares favorably to healing by secondary intention in terms of wound healing time, and gives good functional and cosmetic results.
Mineral oil granuloma of the penis
Authors: Hohaus K , Bley B , Köstler E , Schönlebe J , Wollina U
Published: August 2003

We report a 30‐year‐old‐patient with penile sclerosing lipogranuloma following injections of Vaseline. He was successfully treated by complete surgical removal of the subcutaneous material and excision of atrophic skin, followed by penoplasty. Temporary impairment of wound healing was overcome by application of topical carbon dioxide gas. A brief review on international literature is given.
The Phenotypic Consequences of CFTR Mutations
Authors: Rowntree Rebecca K. , Harris Ann
Published: August 2003

Cystic fibrosis is a common autosomal recessive disorder that primarily affects the epithelial cells in the intestine, respiratory system, pancreas, gall bladder and sweat glands. Over one thousand mutations have currently been identified in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that are associated with CF disease. There have been many studies on the correlation of the CFTR genotype and CF disease phenotype; however, this relationship is still not well understood. A connection between CFTR genotype and disease manifested in the pancreas has been well described, but pulmonary disease appears to be highly variable even between individuals with the same genotype. This review describes the current classification of CFTR mutation classes and resulting CF disease phenotypes. Complex disease alleles and modifier genes are discussed along with alternative disorders, such as disseminated bronchiectasis and pancreatitis, which are also thought to result from CFTR mutations.
Genetic Structure and Origin of Peopling in The Azores Islands (Portugal): The View from mtDNA
Authors: Santos C. , Lima M. , Montiel R. , Angles N. , Pires L. , Abade A. , Aluja Ma. P.
Published: August 2003

The Azores islands (Portugal), uninhabited when discovered by Portuguese navigators in the fifteenth century, are located in the Atlantic Ocean 1500 km from the European mainland. The archipelago is formed by nine islands of volcanic origin that define three geographical groups: Eastern (S. Miguel and Sta. Maria), Central (Terceira, Faial, Pico, Graciosa and S. Jorge) and Western (Flores and Corvo). To improve the genetic characterisation of the Azorean population, and to clarify some aspects related to the history of settlement, a study of mtDNA was conducted in the population of the archipelago. The HVRI region was sequenced and specific RFLPs were screened in 146 samples obtained from unrelated individuals with Azorean ancestry (50 from the Eastern group, 60 from the Central group, and 37 from the Western group). Samples were classified into haplogroups based on the information obtained from both sequencing and RFLP analysis.

All the analyses performed support the idea that, in the whole group of islands, the majority of mtDNA lineages originated from the Iberian Peninsula, mainly from Portugal (mainland). However contributions from other European populations, especially from Northern Europe, cannot be disregarded. The values obtained for the various diversity parameters in the Azores archipelago indicate that the Azorean population, as a whole, does not exhibit the typical characteristics of an isolated population. The analysis of genetic data by groups of islands showed that the Western group exhibited particular features. The distribution of haplogroups in the Western group is very atypical, being significantly different from what is observed in the Eastern and Central groups. Furthermore, the diversity values are, in general, lower than those observed in other populations used for comparison. African haplogroups were found in all the groups of islands. Therefore the presence of Moorish and African slaves on the islands, as reported in historical sources, is supported by the mtDNA genetic data, especially in the Eastern group. The presence of Jews in the Central group is also supported by the mtDNA data. Neither historical nor genetic data (phylogeography of mtDNA) supports the idea of a differential settlement history for the Western group; however, it is represented in the phylogenies as an isolated branch. The effect of genetic drift, induced by the reduced population size since peopling occurred, has led to a very atypical distribution of haplogroups/haplotypes in this group of islands.

We cannot ignore the influence of biodemographic and genetic processes, namely founder effect, genetic drift, migration, and even recent mutational events in the mtDNA lineages of the Azorean populations. Nevertheless, a great part of the variation in the Azorean mtDNA can be explained by the settlement history.
A Unified Approach to Modelling Linkage to Quantitative and Qualitative Traits
Authors: Houwing‐Duistermaat J. J. , Bijkerk C. , Hsu L. , Stijnen Th. , Slagboom E. P. , Van Duijn C. M.
Published: August 2003

For quantitative traits with a genetic component, random effects approaches are used to test for linkage at observed marker loci. We propose to use these approaches also for binary outcomes observed in sib pairs derived from a population‐based cohort study. In addition to a random effect modelling correlation due to polygenic effect, a random effect is included to model the correlation between siblings due to sharing alleles identical by descent (IBD) at the observed marker locus. A two‐step analysis is proposed. Firstly, score statistics are computed to test whether correlation is present in the data. Secondly, random effects models are fitted, yielding heritability estimates. To illustrate the methods, data on the contribution of the COL2A1 gene to various binary and quantitative outcomes including the presence of Heberden's nodes and bone mineral density (BMD) are analysed. For most of the traits studied, the score statistics were significant, indicating the presence of genetic effects. For BMD and for Heberden's nodes, the variance explained by the marker locus was 44% (P = 0.0008) and 15% (P = 0.38) respectively. We conclude that the score statistics can be used as a preliminary data analysis. In more sophisticated analysis, heritabilities can be estimated by fitting random effects models.
Genetic Variation at the Chromosome 16 Chemokine Gene Cluster: Development of a Strategy for Association Studies in Complex Disease
Authors: Fisher S. A. , Moody A. , Mirza M. M. , Cuthbert A. P. , Hampe J. , Macpherson A. , Sanderson J. , Forbes A. , Mansfield J. , Schreiber S. , Lewis C. M. , Mathew C. G.
Published: August 2003

The chemokine gene cluster [CCL22, CX3CL1, CCL17] (previously known as [SCYA22, SCYD1, SCYA17]) is a candidate locus for one of the susceptibility genes for inflammatory bowel disease that are located in the peri‐centromeric region of chromosome 16. Screening for sequence variation at this locus led to the detection of 14 single nucleotide polymorphisms (SNPs). An efficient experimental and computational approach was developed to estimate allele frequencies and pairwise linkage disequilibrium relationships between SNPs at this locus, and to test them for association with inflammatory bowel disease. The 12 common SNPs were assigned to 5 distinct linkage disequilibrium groups. Genotyping of one SNP from each linkage disequilibrium group in a large cohort of families with inflammatory bowel disease did not provide convincing evidence of association with either Crohn's disease or ulcerative colitis. We describe an efficient experimental design from SNP screening to association testing. This strategy can be used to test candidate genes for involvement in susceptibility to complex disease.
Statistical Analysis of Direct Identity‐by‐descent Mapping
Authors: Siegmund D. , Yakir B.
Published: August 2003

Genetic mismatch scanning has been suggested as a method for using affected pairs of ostensibly unrelated but putatively distantly related affecteds in isolated populations to map disease genes. We model the regions of identity‐by‐descent of these affected pairs as a continuous time two state process with unknown parameters that depend on the (unknown) relationships, and we estimate the unknown parameters from the observed data. Simulated data involving pairs of first to fourth cousins show that the procedure thus obtained has properties similar, albeit slightly inferior, to the case where the relationships of the affected pairs, hence the parameters governing the processes, are known.
Edge Effects on Liverworts and Lichens in Forest Patches in a Mosaic of Boreal Forest and Wetland
Authors: Moen Jon , Jonsson Bengt Gunnar
Published: August 2003

Abstract: In studies of edge effects, it is difficult to separate edge from size effects because size and edge are strongly correlated in most cases. In our study we separated these two effects by examining small forest patches of two different size classes ( <1 ha and 4–6 ha ), with patches chosen so that area and perimeter were not correlated within each class. We conducted our study in a mosaic of old‐growth Picea abies forest and wetland, consisting of forested moraine hills ( “islands” ) in a Sphagnum‐bog matrix. On each island, we demarcated a 0.1‐ha sample plot and measured site and forest characteristics. In each plot, we examined all fallen logs for the occurrence of epixylic hepatics ( liverworts ), and all standing trees for the occurrence of calicioid lichens. We examined correlations between species and area, shape, and distance to nearest edge. The effect of shape on forest‐interior conditions was analyzed with a core‐area model. Site and forest characteristics were similar between the island size groups. The majority of hepatics and lichens occurred more frequently on larger islands, and the cover of hepatics tended to be higher on larger islands. A rough estimation of depth‐of‐edge influence was made at 50 m, but the two species groups did not respond similarly to edge effects. The lichens showed several important correlations with island shape on small islands, suggesting that circular small islands may have a forest structure approaching interior conditions. Hepatics tended to respond to small islands as edge environments. We conclude that the response of species to edges is strongly species‐specific and context‐dependent. This points to the limitations of extrapolating results from studies on depth‐of‐edge influence to forest‐management situations.
Impact of Forest Fragmentation on Understory Plant Species Richness in Amazonia
Authors: Benítez‐Malvido Julieta , Martínez‐Ramos Miguel
Published: August 2003

Abstract: Forest fragmentation in the tropics severely affects large trees, but its effect on other life stages and plant life forms is poorly understood. In Central Amazonia, 9 to 19 years after fragmentation, we recorded species richness and net seedling recruitment rate in forest fragments of 1, 10, and 100 ha and in continuous forest. In 1991 all seedlings 5–100 cm tall within permanent 1‐m2 plots in fragments and continuous forest were counted and grouped into tree, liana, palm, and herb life‐form classes. In 1993 we manually removed all seedlings that were <1 m tall from the permanent plots. Six years and 5 months later ( 1999 ), all new seedlings recruited into the plots were counted, grouped into different life forms, and classified into distinct morphospecies. The species richness of recruited tree, liana, herb, and palm seedlings was lower in forest fragments than in continuous forest, with the 1‐ha fragment having the poorest species richness. The total number of recruited individuals was 40% less than that previously present for all life forms, except lianas. Liana recruitment was 7% to 500% higher than the original abundance in the forest fragments and continuous forest. In general, species similarity was higher among fragments than between fragments and continuous forest, with the 1‐ha fragment being less similar. Species rank/abundance curves showed that continuous forest species in all life forms tended to disappear in forest fragments, whereas common species in forest fragments were absent from continuous forest. Overall, our results suggest that the life‐form composition and structure of the regenerative plant pool in fragments were shifting toward a species‐poor seedling community. Losses of understory species diversity, but especially of tree seedlings, threaten the maintenance of rainforest biodiversity and compromise future forest regeneration.
Effects of Rock Climbing on the Land Snail Community of the Niagara Escarpment in Southern Ontario, Canada
Authors: McMillan Michele A. , Nekola Jeffrey C. , Larson Douglas W.
Published: August 2003

Abstract:The cliffs of the Niagara Escarpment provide habitat for extremely diverse communities of land snails that may be at risk as a result of recreational rock climbing. We examined the effects of rock climbing on the density, richness, diversity, and community composition of snails on the Niagara Escarpment in southern Ontario, Canada. We sampled from randomly selected climbed and unclimbed sections of cliffs on the plateau ( cliff edge ), cliff face, and talus ( cliff base ). Snail density, richness, and diversity were lower along climbing routes than in unclimbed areas, and community composition differed between climbed and unclimbed samples. These results suggest that rock climbing has significant negative effects on all aspects of the snail community on cliffs; therefore, we recommend the inclusion of gastropods in conservation plans for protected areas containing cliffs.
Role of Corridors in Plant Dispersal: an Example with the EndangeredRanunculus nodif lorus
Authors: Kirchner Florian , Ferdy Jean‐Baptiste , Andalo Christophe , Colas Bruno , Moret Jacques
Published: August 2003

Abstract:The proposition that the migration of organisms between habitat patches could be enhanced by corridors has been much discussed among conservation biologists. But the few experimental studies supporting the usefulness of corridors have all concerned animal species. We investigated the role of corridors in seed dispersal, studying population genetic and demographic structure in metapopulations of the rare, pond‐dwelling, autogamous plant speciesRanunculus nodiflorusL. in the Fontainebleau Forest ( France ). Differentiation on three polymorphic isozyme markers was strong among local populations ( ponds ) within metapopulations ( sites ) and moderate among metapopulations. Partial Mantel tests revealed that the connection of ponds through temporarily flooded natural corridors, facilitating seed migration, had a strong negative effect on genetic differentiation between local populations and that a pond was more likely to be colonized when connected by corridors to other occupied ponds. Thus, corridors are probably a key element of landscape structure for metapopulation dynamics inR. nodiflorus.From a conservation perspective, our results suggest that corridors could increase the chance of persistence of plant species living in fragmented habitats by promoting seed dispersal between habitat patches.