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Aims The Semmes-Weinstein monofilament is the most widely used test to diagnose the loss of protective sensation. The commonly used protocol of the International Consensus on the Diabetic Foot includes a ‘sham’ application that allows for false-positive answers. We sought to study the heretofore unexamined significance of false-positive answers. Methods Forty-five patients with diabetes and a history of pedal ulceration (Group I) and 81 patients with diabetes but no history of ulceration (Group II) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, 1st metatarsal and 5th metatarsal areas were used. At each location, the test was performed three times: 2 actual and 1 “sham” applications. Scores were graded from 0 to 3 based upon correct responses. Determination of loss of protective sensation was performed with and without calculating a false-positive answer as a minus 1 score. Results False-positive responses were found in a significant percentage of patients with and without history of ulceration. Introducing false-positive results as minus 1 into the test outcome significantly increased the number of patients diagnosed with loss of protective sensation in both groups. Conclusions False-positive answers can significantly affect Semmes-Weinstein monofilament test results and the diagnosis of LOPS. A model that accounts for false-positive answers is offered. Copyright © 2013 John Wiley & Sons, Ltd.

Background The possible effect of random intrasite placement on the outcome of the Semmes–Weinstein monofilament (SWF) test is not known. We sought to determine the significance of this variable in the diagnosis of loss of protective sensation (LOPS) in patients with diabetes. Methods Forty-five patients with diabetes with history of pedal ulceration (group 1), 81 patients with diabetes without history of ulceration (group 2) and 21 non-diabetic controls (group 3) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, first and fifth sub-metatarsal areas were divided into peripheral and interior zones resulting in a total of six zones. Results Mean total scores of monofilament test were significantly lower in peripheral zones as compared with interior zones of both feet in all three groups and affected the resulting percentage of loss of protective sensation. Conclusions Intrasite monofilament placement can significantly affect monofilament test results and the diagnosis of loss of protective sensation. A model that corrects the effect of random intrasite placement is needed. Copyright © 2013 John Wiley & Sons, Ltd.

The lesser digits are frequent sites of elevated plantar pressure and ulceration in the diabetic foot. We sought to determine whether debridement of callus and the wearing of a custom molded digital orthosis could significantly reduce digital plantar pressure. Fourteen patients with distal digital callus were studied. For each patient, the toe with the highest plantar pressure was selected. A computerized pressure mat was used to record the plantar pressure before and after debridement with and without a moldable silicone digital orthosis. Mean peak plantar digital pressures before treatment were 2.80+/-0.7 kg/cm2 for the entire group. The digital orthosis alone reduced plantar pressure to a mean of 1.95+/-0.65 kg/cm2 p < 0.05. Treatment by debridement similarly reduced pressure to 1.99+/-0.76 kg/cm2 p < 0.05. The most effective reduction of pressure for all patients, as well as the most statistically significant, occurred when both treatments were given, with mean peak plantar pressure falling to 1.28+/-0.61 kg/cm2 p < 0.01. Debridement and custom molded digital orthoses alleviate distal digital plantar pressure. Since elevated plantar pressure increases the risk of neuropathic ulceration, these treatments should be considered in the prophylactic care of appropriate patients.

Th1/Th2 cytokine imbalance has been demonstrated in Type 1 diabetes (T1DM) patients. We characterized the peak levels, secretory pattern and total cytokine production of the Th1 cytokines (IL-2 and IFN gamma) and Th2 cytokines (IL-4 and IL-10), by stimulated peripheral blood mononuclear cells of twenty six first-degree relatives of T1DM patients, and eleven matched controls. At enrollment, first degree relatives demonstrated a significant increase in peak and overall secretion of IL-2; P

Recent evidence suggests that autoimmune animal diabetes is associated with an imbalance between the Th1 and Th2 arms of the cellular immune system. However, limited data is available regarding the Th1/Th2 imbalance in human Insulin dependent diabetes mellitus (IDDM) patients. Therefore, we examined the peak levels, secretory pattern and total cytokine production (calculated as the area under the curve, AUC) of the Th1 cytokines, IL-2 and IFN-gamma, and Th2 cytokines, IL-4 and IL-10, from stimulated peripheral blood mononuclear cells, from 17 IDDM patients and 24 normal controls. In contrast to controls, diabetic patients were characterized by an early, uniformly low secretion of Th2 cytokines, followed by a late increased secretion of Th1 cytokines. This resulted in significant differences in secretory patterns of IFN-gammaIL-2, IL-4 and IL-10 between the two groups; P0.001, P0.005, P0.005 and P0.001, respectively. No correlation was found in the diabetic patients between any profiles of the cytokines and their various clinical parameters, including age, gender, disease duration, insulin requirements or glycated hemoglobin levels. In conclusion, our data provides the first comprehensive evidence for an independent and persistent impairment of both Th1 and Th2 cytokine secretory patterns in IDDM patients.

The most important application of pulmonary scintigraphy is in the evaluation of patients with possible pulmonary embolism. Classically, the perfusion defects of pulmonary embolism are wedge shaped, pleural based, and tend to affect both lungs randomly in a segmental or subsegmental distribution. The authors describe a patient with rare scintigraphic findings of complete unilateral absence of lung perfusion with normal lung ventilation caused by massive pulmonary embolism associated with activated protein C resistance. Correlative imaging with angiography and computed tomography (CT) is presented, and the differential diagnosis of this rare scintigraphic finding is discussed.

The Semmes-Weinstein monofilament is the most widely used test to diagnose the loss of protective sensation. The commonly used protocol of the International Consensus on the Diabetic Foot includes a 'sham' application that allows for false-positive answers. We sought to study the heretofore unexamined significance of false-positive answers.Forty-five patients with diabetes and a history of pedal ulceration (Group I) and 81 patients with diabetes but no history of ulceration (Group II) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, 1st metatarsal and 5th metatarsal areas were used. At each location, the test was performed three times: 2 actual and 1 "sham" applications. Scores were graded from 0 to 3 based upon correct responses. Determination of loss of protective sensation was performed with and without calculating a false-positive answer as a minus 1 score.False-positive responses were found in a significant percentage of patients with and without history of ulceration. Introducing false-positive results as minus 1 into the test outcome significantly increased the number of patients diagnosed with loss of protective sensation in both groups.False-positive answers can significantly affect Semmes-Weinstein monofilament test results and the diagnosis of LOPS. A model that accounts for false-positive answers is offered.

The possible effect of random intrasite placement on the outcome of the Semmes-Weinstein monofilament (SWF) test is not known. We sought to determine the significance of this variable in the diagnosis of loss of protective sensation (LOPS) in patients with diabetes.Forty-five patients with diabetes with history of pedal ulceration (group 1), 81 patients with diabetes without history of ulceration (group 2) and 21 non-diabetic controls (group 3) were studied. The three original sites of the International Consensus on the Diabetic Foot at the hallux, first and fifth sub-metatarsal areas were divided into peripheral and interior zones resulting in a total of six zones.Mean total scores of monofilament test were significantly lower in peripheral zones as compared with interior zones of both feet in all three groups and affected the resulting percentage of loss of protective sensation.Intrasite monofilament placement can significantly affect monofilament test results and the diagnosis of loss of protective sensation. A model that corrects the effect of random intrasite placement is needed.

1. Hypouricaemia is prevalent in diabetic patients. In most of the studies, the diabetic patients had some degree of diabetic nephropathy as evidenced by a decreased glomerular filtration rate and proteinuria. Therefore we studied renal uric acid handling in a group of type II diabetic patients with elevated glomerular filtration rates. 2. Eighteen type II diabetic patients with normal kidney functions and elevated glomerular filtration rate and a group of 18 healthy, age- and weight-matched control subjects, were studied. Serum fructosamine, creatinine and uric acid levels were determined. Twenty-four hour urine collections were obtained, and microalbumin, glucose, creatinine and uric acid, were measured. 3. The creatinine clearance was higher and the serum uric acid concentration was lower in the diabetic patients (P 4. It appears that the hypouricaemia and hyperuricosuria in diabetic patients are associated with an elevated glomerular filtration rate and a net tubular reabsorptive defect that may herald the development of diabetic nephropathy.

Intravenous insulin improves clinical outcome in patients hospitalized in intensive care units. Whether glucose control with multiple daily subcutaneous insulin injections (MDI) is beneficial in patients hospitalized in general medical wards is unknown. We tested the feasibility, safety and efficacy of glucose control with MDI in diabetic patients hospitalized in a general medicine ward.Eighty-eight adults with diabetes mellitus were studied in an internal medicine department. All patients were treated with subcutaneous pre-meal insulin analogue and Glargin insulin. A conservative and an intensified protocol was tested.Mean daily glucose levels decreased in the conservatively treated patients from 275+/-71 mg/dl at day 1 to 197.0+/-60 mg/dl at day 4 of hospitalization p=0.0001 and in the intensified protocol to 191+/-38 mg/dl already on day 1 remaining stable throughout the hospitalization. A mean daily glucose180 mg% was reached by day 2 in 48% of patients in the intensified and in 32% in the conservative groups. Only one serious event of hypoglycemia was noted in the intensified group.Intensive insulin treatment with MDI is feasible, safe and efficacious in general medicine wards.

OBJECTIVE—To determine the effect of acute psychotic stress on glucose homeostasis in nondiabetic subjects. RESEARCH DESIGN AND METHODS—β-Cell function and insulin sensitivity were determined by the homeostasis model assessment in 39 nondiabetic patients with acute psychotic stress reaction admitted to a psychiatric ward. The clinical global impression (CGI) score was used to evaluate the level of psychological stress. Patients were assessed on admission, after 2 weeks, before discharge, and 6 months after discharge. RESULTS—The mean CGI score decreased significantly with time: 5.3 ± 0.8 and 1.6 ± 0.7 on admission and predischarge, respectively (P < 0.001). This was associated with a significant reciprocal increase of mean β-cell function from 96.8 ± 33.2 to 134.4 ± 60% at admission and postdischarge, respectively (P < 0.003), and a decrease of mean insulin sensitivity from 101.7 ± 36 to 77.1 ± 34.8% (P < 0.001). In contrast, mean glucose and HbA1c levels did not change significantly. Subgroup analysis demonstrated that patients with the highest stress score on admission (≥6) had significantly higher glucose (P = 0.01) and insulin levels (P = 0.04) than patients with lower score ( CONCLUSIONS—These data indicate that β-cell function and insulin sensitivity are inversely correlated with acute psychotic stress.

The aim of this study was to evaluate the prevalence of fibromyalgia (FM) in patients with diabetes mellitus (DM).The study included 100 consecutive unselected patients with DM attending our diabetes clinic. Patients were divided into two groups: 45 patients with type 1 diabetes and 55 patients with type 2 diabetes. A group of 50 healthy hospital staff members served as controls. The FM was diagnosed according to the 1990 American College of Rheumatology criteria. Counts of 18 tender points were performed by thumb palpation and assessed by dolorimeter. Routine biochemical tests and levels of HbA(1c) were recorded in each patient.The main outcome measure was the association of FM with DM. Fibromyalgia was diagnosed in 17 patients (17%) with DM and in only one (2%) healthy control ( P=0.008). No differences in patients were noted in the prevalence of FM between type 1 and type 2 diabetes (18.5% vs 15.5%, respectively). Patients with both FM and DM had significantly higher levels of HbA(1c) than DM patients without FM (9.2+/-1.1% vs 6.4+/-1.5%) ( P0.05). Similarly, the numbers of tender points, pain scores, and the prevalence of sleep disturbances, fatigue, and headaches were higher in this group of patients. A significant correlation was observed between the numbers of tender points and HbA(1c) levels in the DM patients with FM ( r=0.72, P=0.027).Fibromyalgia is a common finding in patients with types 1 and 2 diabetes, and its prevalence could be related to control of the disease. As with other diabetes complications, FM might be prevented by improved control of blood glucose levels.

Objectives—To determine the Th1/Th2balance in systemic lupus erythematosus (SLE) patients with inactive disease. Methods—A comprehensive analysis of peak secretion, overall cytokine production and secretory pattern of Th1and Th2cytokines from stimulated PBMC of 10 SLE patients with inactive disease and 10 age- and sex-matched controls. Results—No significant differences were found in the peak and total secretion of all cytokines, as well as in the Th1and Th2secretory patterns and proliferative response between the two groups. Conclusion—Th1and Th2balance in inactive SLE is normal.

We previously reported that a decreased TCR mediated activity of the GTP-GDP binding p21ras protooncogene is associated with prediabetes in non-obese diabetic (NOD) mice. Furthermore, prevention of autoimmune diabetes is associated with reversal of the p21ras signaling defect in NOD T cells. Based on these animal studies we determined the activation of p21ras in PBMC from patients with Insulin Dependent Diabetes Mellitus (IDDM), Non-Insulin Dependent Diabetes Mellitus (NIDDM) and normal healthy controls. Stimulation by PHA induced a decrease of 3.7 +/- 1.4% and an increase of 2.44 +/- 2.3%, p < 0.02 and 2.6 +/- 1.6%,p < 0.003 in the basal unstimulated p21ras activity in the IDDM, NIDDM and normal control groups, respectively. Expression of p21ras and its regulatory elements, the GTPase activating protein p120ras-GAP and the guanine nucleotide releasing factor (GNRF) hSOS, was comparable in the three groups. The in vitro proliferative response to PHA was comparable in the IDDM and control groups: stimulation index (SI) of 8.6 +/- 2.5 and 9.4 +/- 3.5 respectively, p < 0.44. No correlations were found in the IDDM patients between the degree of p21ras activation and the mitogen induced in vitro proliferative response or the various clinical parameters including age, gender, disease duration, daily insulin requirements and metabolic control. Taken together these data indicate that PBMC from IDDM patients are characterized by a persistent impairment in the activation of their p21ras. They also suggest that p21ras stimulated activity is a sensitive and independent parameter of PBMC activation in these patients.

Objective To measure renal reabsorption of inorganic phosphorus and the calciotropic hormones in early Design Prospective, cross-sectional study. Setting Endocrine Institute at Assaf Harofeh and E. Wolfson Medical Centers; the Deparment of Obstetrics and Gynaecology, Sheba Medical Centre and Tel Aviv University. Population Three groups of healthy women were studied: pregnant women at the end of the first trimester (n= 20), pregnant women at the end of the third trimester (n= 22), and nonpregnant controls (n= 27). Methods and main outcome measures The renal tubular maximal phosphorus reabsorption per decilitre of glomerular filtrate (TmP/GFR) was measured in all women. Circulating levels of intact parathyroid hormone, calcitriol (1,25-dihydroxy vitamin D3) and insulin-like growth factor I were assayed in part of the women (8.11 of each group). Results TmP/GFR was elevated in the first trimester group (mean 0.263 mmol/L) compared with controls (95% CI 0.07–0.46, P= 0.003). Third trimester values did not differ fiom controls. Serum calcitriol in the first trimester group was higher (mean difference 17.68 pg/mL) compared with controls (95% CI 3.89–31.47, P= 0.006) and was higher still (mean difference 20.75 pg/mL) in the third trimester group (95% CI 1.01–40*49, P= 0.042). Serum parathyroid hormone in the first trimester group was lower than in controls or the third trimester group: mean differences were respectively. Parathyroid hormone levels correlated negatively to calcitriol levels in the combined control and first trimester groups (r= -0.54, P= 0.022) and negatively to TmP/GFR values in the combined three groups (r= -0.68, P= 0.042). First trimester levels of insulin-like growth factor I were lower than those in controls or in the third trimester: mean differences were 10.24 nmol/L (95% CI 2.05–1 8.43, P= 0.007) and 13.57 nmol/L (95% CI 4.23–22.91, P= 0.003), respectively. Conclusions The dominant change in mineral metabolism in pregnancy is a rise in calcitriol which most probably is responsible for the relative suppression of parathyroid hormone and thereby for the rise in TmP/GFR in early pregnancy. All the above support the transfer of minerals to the fetus without compromising maternal bone. The significance of circulating insulin-like growth factor I remains and late pregnancy. 4.40 pg/mL (95% CI -1.40 to 10.15, P= 0.078) and 8.18 pg/mL (95% CI 0.51–15.85, P= 0.019) unclear.

Zinc status was assessed in patients with type II diabetes mellitus and congestive heart failure (CHF). Three groups of patients were enrolled into the study: Group 1: 15 patients with type II diabetes mellitus and CHF; Group 2: 20 patients with isolated type II diabetes mellitus; and Group 3: nine patients with isolated CHF. Twenty-four-hour urine was measured for creatinine, protein, and zinc, and blood was drawn for creatinine, proteins, liver enzymes, hemoglobin A1c, and zinc. Insulin treatment and hemoglobin A1c were comparable in the diabetic patients of groups 1 and 2, but group 1 was also treated with captopril and diuretics like the CHF patients of group 3. Plasma zinc levels were statistically similar in all three groups, but urinary zinc excretion (mumol/24 h) and urinary zinc: creatinine (mumol/mmol) ratio were significantly higher in the type II diabetics and CHF group (27.2 +/- 1.5; 1.69 +/- 0.6, respectively) compared to the diabetic patients alone (19.4 +/- 0.76; 0.97 +/- 0.3, respectively) and the CHF patients (9.7 +/- 0.3; 0.62 +/- 0.3, respectively). and the CHF patients (9.7 +/- 0.3; 0.62 +/- 0.3, respectively). Patients with type II diabetes mellitus and CHF were treated with higher doses of captopril than the CHF patients (56.25 +/- 24 mg vs 18.8 +/- 11 mg P < 0.05). Thus, patients with type II diabetes mellitus and CHF excrete larger amounts of zinc, which may eventually lead to zinc deficiency.

The association of familial hypogonadism with progressive cerebellar ataxia is only rarely encountered. Both primary hypergonadotropic and secondary hypogonadotropic hypogonadism may appear with cerebellar ataxia. However, many of these patients suffer from a variety of neurological and/or somatic malformations. Females, which are relatively rarely affected, display primary amenorrhea. In this report, two sisters presented with secondary amenorrhea prior to the appearance of progressive cerebellar ataxia and were found to have hypogonadotropic hypogonadism. This unique family displays clinical evidence for the presence of a possible common mechanism responsible for progressive hypothalamic and cerebellar impairment of late onset.