Non-invasive method for assessment of inflammation.

This article explores the potential of non-invasive measurement for elevated levels of erythrocyte aggregation in vivo, which have been correlated with a higher risk of inflammatory processes. The study proposes utilizing a dynamic light scattering approach to measure aggregability. The sensor modules, referred to as "mDLS," comprise VCSEL and two photodiodes. Two of these modules are placed on an inflatable transparent cuff, which is then fitted to the subject's finger root, with one sensor module positioned on each side. By temporarily halting blood flow for one minute using over-systolic inflation of the cuff, signals from both sensors are recorded. The study involved three distinct groups of subjects: a control group consisting of 65 individuals, a group of 29 hospitalized COVID-19 patients, and a group of 34 hospitalized patients with inflammatory diseases. Through experimental results, significant differences in signal kinetic behavior were observed between the control group and the two other groups. These differences were attributed to the rate of red blood cell (RBC) aggregation, which is closely associated with inflammation. Overall, the study emphasizes the potential of non-invasive diagnostic tools in evaluating inflammatory processes by analyzing RBC aggregation.

Impact of Fitness Status on the Optically Measured Hemodynamic Indexes.

The physiological characteristics of skin blood flow can be described in terms of the hemodynamic indices (HI). The HI is derived from the laser speckle characteristics, which are governed by the cutaneous blood flow. A miniaturized dynamic light-scattering sensor was used to measure the speckle pattern from the finger root. Three groups of subjects from 15 to 25 years of age were tested. The first group included subjects who are actively engaged in sport activities; the second group included subjects with low level of physical activity; and the third group included healthy controls with moderate physical activity. The HI parameters were measured prior to and after the performance of a determined physical load. As a marker of cardiovascular fitness (CVF), we used the postload decay rate of HI. We found that the hemodynamic response to the physical load provides a statistically significant correlation with the postload heart rate decay. It was also found that postocclusion increase of the arterial HI is more prominent in the group with higher physical activity. These results indicate that hemodynamic indices can be used as an additional marker for cardiovascular fitness level.

[SKF index as a new non-invasive parameter for the evaluation of the biological age for healthy and sick people].

We have conducted a study on a large group of healthy and sick subjects and have demonstrated that a new index of coagulativety (SKF), based on measurement of the laser speckle signal from the finger root, correlates with chronological age ranging from 1 to 85 years old. The kinds of non-invasive measurements were obtained during two measurement sessions: one with the application of over-systolic occlusion and another without application of the occlusion. The very significant correlation with age was noted both during the stasis stage and during the non-occluding stage. We observed a higher SKF index in sick subjects, correlating directly with severity of illness. We speculated that the observed phenomena are caused by temporarily fluctuations in local blood viscosity associated with interactions of the Red Blood Cells and endothelial cells.

Cardiac troponin T is not increased in patients with hypothyroidism.

Patients with hypothyroidism often have increased creatine kinase (CK) levels. It is possible that there is increased production of CK, but other mechanisms, such as an increased cell membrane permeability or decreased enzyme clearance were also proposed. Recently, troponins T and I have been extensively studied because of their cardiac specificity. Cardiac troponins are sensitive and specific markers of cardiac injury. The objective of the study was to measure cardiac troponin T (cTnT) levels in patients with hypothyroidism. Twenty-five patients with primary hypothyroidism were evaluated (thyroid-stimulating hormone (TSH) >30 mU/L and low FT(4)). In all patients thyrotropin (TSH), free thyroxine (FT(4)), CK, CK-MB and cTnT were measured.There were 3 men and 22 women with a mean age of 47.5 +/- 12.4 years. TSH levels ranged from 31 to 75 mIU/L and mean FT(4) levels were 4.5 +/- 1.9 pmol/L. CK was normal in 11 patients and increased in 14. CK levels ranged between 86 and 1221 U/L (normal levels <170 in women, <195 in men) with a mean of 322 U/L +/- 279. CK-MB was increased in 4 patients (16%) and normal in 21. All 25 patients had normal cTnT levels, < 0.01 ng/mL (normal levels 0-0.1 microg/L). Increase in CK and its MB fraction are common in patients with hypothyroidism but cTnT levels are not, even in patients with increased CK-MB. Therefore, cTnT is a reliable marker of cardiac injury even in the hypothyroid patient.

Clinical relevance of non-palpable thyroid nodules as assessed by ultrasound-guided fine needle aspiration biopsy.

It is known from autopsy data that thyroid nodules are far more common than can be detected by palpation alone. With the wide use of modern non-invasive imaging many non-palpable thyroid nodules are discovered but the proper approach to these nodules is still debatable. In a retrospective study, we reviewed the data from 186 US-guided FNA biopsies (US-FNAB) performed between May 1995 and March 1997 at the Sapir Medical Center, Israel, a iodine-sufficient urban area. Sixty-one of the 186 US-FNAB of the thyroid were performed in non-palpable nodules. The mean size of these nodules was 2.4 +/- 1.0 cm (mean +/- SD) ranging from 1.1-5.5 cm. Description of the nodule consistency was available in 53 cases; 42/53 were solid and 11/53 were solid-cystic. FNAB was diagnostic in 46 patients and non-diagnostic in 15. Forty-three of the diagnostic cytology reports were benign, one revealed papillary carcinoma, one had suspicious findings and the third was suspicious for a follicular neoplasm. The last two patients were referred to surgery and a follicular adenoma was found in both. Among the 61 non-palpable thyroid nodules, only one was papillary carcinoma, a prevalence of 1.6%. The other two patients referred to surgery had benign lesions. We found a low prevalence of malignancy in relatively large non-palpable thyroid nodules.

Appropriateness of nitrate use in a general medicine population.

BACKGROUND: Nitrates are one of the most commonly prescribed drug groups for cardiac disease, especially for angina pectoris and congestive heart failure. The chronic efficacy of nitrates is limited by the development of tolerance, which can be attenuated by use of sustained-release preparations or administration of regular-release preparations asymmetrically. OBJECTIVE: To determine whether patients receiving isosorbide 5-mononitrate (ISMN) use the drug in a pharmacologically appropriate manner and whether they had been instructed in the prophylactic use of sublingual nitrates prior to effort. METHODS: We administered a questionnaire regarding details of nitrate use to 229 patients with ischemic heart disease using oral ISMN, prescribed prior to their current admission. The study was conducted in a 600-bed university-affiliated hospital. RESULTS: We found that only 15% of patients receiving regular-release ISMN were taking the drug asymmetrically. In contrast, 82.6% of the patients receiving sustained-release ISMN were using the drug properly. Only 38.1% of the patients treated with regular-release ISMN were treated with the dose recommended in the literature. Furthermore, of the 190 patients who reported experiencing effort angina, only 17.9% had been instructed in the prophylactic use of nitrates prior to effort. CONCLUSIONS: The majority of patients (85%) using regular-release ISMN were taking the medication in an inappropriate fashion, while most patients taking sustained-release preparations were using them properly. More than half the patients treated with regular-release ISMN were treated with doses exceeding the recommended dose. In addition, most patients experiencing effort angina had not been instructed regarding the prophylactic use of nitrates. These findings suggest that both physicians and pharmacists must be reminded of the continuing need to properly counsel patients regarding appropriate drug use.

Autoimmune thyroid disease and antiphospholipid antibodies.

OBJECTIVE: Autoimmune thyroid disease (ATD) is associated with circulating autoantibodies reactive with epitopes on thyroid tissue and that are thought to be pathogenic in the development of these diseases. Antiphospholipid antibodies (APLA) are a family of immunoglobulins that recognize a variety of plasma proteins in association with anionic phospholipids. These antibodies may lead to a number of clinical syndromes including venous and arterial thromboses, thrombocytopaenia, and recurrent fetal loss. We have studied the prevalence of APLA in patients with ATD and have determined the prevalence of the APLA syndrome among APLA-positive patients. DESIGN: The study was a retrospective survey of patients with autoimmune thyroid disease attending the endocrinology clinic of a tertiary care academic hospital. PATIENTS AND MEASUREMENTS: One hundred and thirty patients with autoimmune thyroid disease from the endocrinology clinic at our hospital were studied. 84% had chronic thyroiditis and 16% had Graves' disease. Free T4 and thyroid stimulating hormone (TSH) levels, antimicrosomal and antithyroglobulin antibodies, and an antiphospholipid antibody test were performed on all subjects. RESULTS: 43% of patients with chronic thyroiditis and 43% of patients with Graves' disease were APLA positive, with an overall rate of 43% APLA positivity among patients with ATD. Of the 56 patients that were APLA positive, forty-eight (86%) had APLA of the IgG subtype, four (7%) had IgM antibodies, and nine (16%) had both IgG and IgM antibodies. None of the patients had clinical evidence of the APLA syndrome. CONCLUSIONS: We conclude that the prevalence of APLA in ATD is increased compared to healthy individuals but that this is likely to be an epiphenomenon. However, prolonged follow up is necessary in order to determine the true clinical significance of these antibodies in ATD patients.

Sweet's syndrome and subacute thyroiditis.

A 63 year old woman developed biopsy documented lesions of acute febrile neutrophilic dermatosis (Sweet's syndrome) one week after the onset of subacute thyroiditis. This is only the second reported case of such an association. The role of cytokines in the development of both subacute thyroiditis and Sweet's syndrome may be the link between these two conditions.

Effect of melatonin on sleep quality of COPD intensive care patients: a pilot study.

Sleep deprivation is extremely common in the intensive care unit (ICU), and this lack of sleep is associated with low melatonin secretion. The objective of the current study was to explore the effect of exogenous melatonin administration on sleep quality in patients hospitalized in the pulmonary intensive care unit (ICU). We performed a double-blind, placebo-controlled study in the pulmonary ICU of a tertiary care hospital. Eight adult patients hospitalized in the pulmonary ICU with respiratory failure caused by exacerbation of chronic obstructive pulmonary disease (COPD) or with pneumonia were studied. Patients received either 3 mg of controlled-release melatonin or a placebo at 22:00, and sleep quality was evaluated by wrist actigraphy. Treatment with controlled-release melatonin dramatically improved both the duration and quality of sleep in this group of patients. Our results suggest that melatonin administration to patients in intensive care units may be indicated as a treatment for sleep induction and resynchronization of the "biologic clock." This treatment may also help in the prevention of the "ICU syndrome" and accelerate the healing process.

Patients in the intensive care unit suffer from severe lack of sleep associated with loss of normal melatonin secretion pattern.

BACKGROUND: Patients hospitalized in the intensive care unit (ICU) tend to become agitated and confused, and many even develop temporary psychoses (the ICU syndrome). We wondered whether the regulation of sleep and the secretion of melatonin is abnormal in ICU patients. Therefore, we studied the association of sleep-wake pattern in patients hospitalized in the ICU, their melatonin secretion rates, and profile compared with a control group of patients in general medical wards. METHODS: Sleep was assessed by actigraphy. Urine was collected every 3 hours for 24 hours. Melatonin secretion was assessed by measuring the melatonin metabolite 6-sulphatoxymelatonin by enzyme-linked immunosorbent assay. RESULTS: Actigraphy suggested that the ICU patients lacked normal sleep behavior for the entire study period, except for occasional short naps. Compared with controls, the nocturnal peak of melatonin secretion was absent, except in two patients in the nonventilated group, and showed a flat curve. CONCLUSIONS: Our results suggest that lack of sleep is indeed a severe problem in ICU patients and is accompanied by impairment of normal melatonin secretion. The possibility that melatonin administration may prove useful in improving sleep patterns in ICU patients deserves further study.

Internal jugular vein thrombosis in patients with ovarian hyperstimulation syndrome.

OBJECTIVE: To describe a case of bilateral internal jugular vein thrombosis complicating ovarian hyperstimulation syndrome (OHSS). DESIGN: Case report. SETTING: Internal medicine ward in a teaching hospital. PATIENT: A 28-year-old nulliparous woman undergoing IVF. INTERVENTION(S): Ultrasonographic Doppler of the neck veins was performed because of pain and swelling in the neck, and bilateral jugular vein thromboses were detected. Laboratory evaluation revealed activated protein C resistance caused by factor V Leiden mutation. Low-molecular-weight heparin (enoxaparin) was administered for the remainder of the pregnancy and for 6 weeks after delivery. MAIN OUTCOME MEASURE: Resolution of jugular venous thromboses documented by ultrasonographic Doppler and normal progression of pregnancy. RESULT(S): The patient delivered healthy twins at term. There were no complications arising from the jugular vein thromboses or the low-molecular-weight heparin treatment. CONCLUSION(S): Unusually located venous thrombosis should prompt an evaluation for a hypercoagulable state. The high prevalence (4%-7%) of factor V Leiden mutation in most Western populations and the mutation's potential contribution to thrombotic complications in OHSS suggest that screening for this abnormality in women undergoing IVF may be indicated.

Digoxinlike immunoreactive factor isolated from human pleural fluid is structurally similar to digoxin.

To further define the chemical structure of human endogenous digoxinlike immunoreactive factors (DLIF) we used human pleural effusions as a source of the substance. Digoxinlike immunoreactive factor activity was detected by radioimmunoassay in the pleural fluid of each of four patients; average concentration was 0.35 ng/mL. The chemical profile of DLIF was determined by initial extraction and concentration of DLIF by ion exchange chromatography followed by reverse phase-high-pressure liquid chromatography (RP-HPLC) separation and purification. Using high-pressure liquid chromatography cochromatography of DLIF, together with several radioactively marked glycosides, we observed a single peak of DLIF activity that was chromatographically identical to digoxin. The present study further supports the recent finding that DLIF is related structurally to the cardiac glycosides, and for the first time it has been proven that DLIF is present in pleural fluids.

Induction of apoptosis by chlorodeoxyadenosine and dexamethasone in B-chronic lymphocytic leukemia.

Apoptosis, programmed cell death, occurs in a variety of cellular systems and in response to many different stimuli. In the present study we examined the ability of dexamethasone (Dex) and chlorodeoxyadenosine (2-CdA) to induce apoptosis in lymphocytes of patients with B-chronic lymphocytic leukemia (B-CLL). Lymphocytes of 29 untreated patients and 9 healthy controls were isolated and incubated for 24 hours in the presence or absence of either Dex (2 microM) (n = 15) or 2-CdA (3 microM) (n = 14). Following incubation the cells were harvested and their DNA extracted and analysed for internucleosomal DNA cleavage by UV illumination after electrophoresis on agarose slab gel containing ethidium bromide. In the Dex group, 10 patients showed dexamethasone independent spontaneous apoptosis appearing 24 hours after the start of incubation. These were the only instances of dexamethasone-enhanced apoptosis. Five patients showed no spontaneous or dexamethasone induced apopto sis. Of the 2-CdA group, 5 showed spontaneous apoptosis enhanced by 2-CdA. No spontaneous apoptosis was observed in the cells from 9 other patients, however, 2-CdA induced apoptosis in 8 cases in this group. This study shows that monitoring of apoptosis in CLL may provide important information regarding susceptibility of the cells to drug induced apoptosis.

Serum enzyme activities following long-distance running: comparison between Ethiopian and white athletes.

Ethiopian runners are famous for their achievements in long-distance running. The recent immigration of Ethiopians to Israel provided an opportunity to compare some physiological variables between elite Ethiopian and white Israeli runners. Six Ethiopian and five white Israeli runners, aged 20 to 40 years, were studied before and after an 11 km race. Venous blood was sampled from each runner prior to the race, and 1 h, 48 h, and 5 days following the race. The activities of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) were measured, and levels of serum electrolytes, urea, creatinine, phosphorus, albumin, cholesterol, and alkaline phosphatase were also determined. CK activity rose 2.6-fold with a peak 5 days after the race. LDH and AST levels rose as well (1.4-1.3-fold, respectively). Significant elevations also occurred in serum phosphorus, uric acid, and creatinine concentrations 1 h after the race. In contrast to previous studies in which higher enzyme activities were reported in blacks, we did not detect any difference in serum enzyme values between black and white runners.

Identification and preliminary characterization of two human digitalis-like substances that are structurally related to digoxin and ouabain.

In order to characterize the structure of endogenous digitalis-like immunoreactive factor (DLIF), we utilized peritoneal dialysis fluid from patients with chronic renal failure as a source of endogenous digitalis-like immunoreactive factor (DLIF), and subjected it to one-step ion exchange chromatography, followed by one step reverse HPLC. Crude dialysis fluid contained 0.09 ng/ml of DLIF, and using Amberlite XAD-2 chromatography we extracted 110 ng of DLIF from 800 ml of dialysis fluid. By applying this partially purified DLIF to our HPLC system, we discerned three peaks of DLIF activity, with retention times of 34, 58 and 63 minutes. The first peak overlapped the elution profile of ouabain, and the third peak co-eluted precisely with digoxin. The second DLIF peak was not in proximity to any of the digitalis-like markers employed. Thus, our results indicate that DLIF isolated from peritoneal dialysis fluid exists in three distinct forms, one of which resembles ouabain, and one which is identical to digoxin.

Fatal methemoglobinemia caused by inadvertent contamination of a laxative solution with sodium nitrite.

We describe two cases of fatal methemoglobinemia resulting from ingestion of laxative solution inadvertently contaminated with sodium nitrite. Postmortem toxicological examination revealed methemoglobin levels in excess of 75% in both patients--a level that is uniformly fatal. The laxative solution was found to contain sodium nitrite instead of sodium sulphate at a concentration of 15 g/l. The pathophysiology of methemoglobinemia and a review of other reported cases of toxic methemoglobinemia are presented. Marked cyanosis in the face of intact cardiorespiratory function should alert the physician to the possibility of toxic methemoglobinemia.

Endogenous digoxin-like immunoreactive factor is elevated in advanced chronic respiratory failure.

Digoxin-like immunoreactive factor (DLIF) is an endogenous substance with natriuretic and diuretic activity. Elevated plasma levels of DLIF are found in various clinical states characterized by water and sodium retention. Chronic respiratory failure, particularly of an advanced stage, also is frequently associated with water and sodium retention. In order to determine whether elevated plasma levels of DLIF are present in chronic respiratory failure, we measured plasma DLIF levels in seven patients (four with COPD [two of whom had associated sleep apnea disturbance] and three with kyphoscoliosis) suffering from advanced chronic respiratory failure with severe hypoxemia and hypercapnia. We found that in these patients plasma levels of DLIF were significantly higher than in healthy control subjects. We conclude that patients with advanced chronic respiratory failure respond with increased levels of DLIF. This may represent an attempt at homeostasis of water and sodium metabolism which is frequently deranged in this clinical condition.