The clinical investigator最新文献

Peripheral nervous system complications are rare in patients with primary Sjögren's syndrome. We investigated a group of six women aged 43-64 years who complained of pain and sensory symptoms. Conventional neurophysiological tests reflecting large nerve fiber function revealed normal motor conduction in all patients, whereas sensory nerve action potentials were absent in two. On the other hand, quantitative thermometry and autonomic nerve function tests indicating small nerve fiber function were more sensitive in the assessment of nerve dysfunction; these showed abnormalities in all cases. Vibrametry showed dysfunctions in four patients. The latter methods possess great sensitivity in discovering sensory disturbances. Neurophysiological assessment of the sensory and autonomic nervous system demonstrating sensory neuropathy contributes to early diagnosis of primary Sjögren's syndrome.

The detection of DNA single-strand breaks (SSB) in human mononucleated white blood cells (MWBC) using a modified version of the nick translation assay is presented. This assay allows rapid and sensitive examination of SSB using only 5 ml heparinized blood for an eightfold determination. The assay was standardized by incubation of MBWC in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a known genotoxic agent. In vitro incubation of MWBC with MNNG induced a dose-dependent increase in DNA-SSB at doses between 5 and 500 microM MNNG. The detection limit for the assay was 5 microM MNNG. To assess the suitability of this assay to detect SSB in vivo a controlled study was performed in which volunteer smokers (n = 5), nonsmokers (n = 5) exposed to environmental tobacco smoke (ETS), and nonsmokers controls (n = 5) were compared. The study lasted 4 experimental days, 2 control and 2 exposure days. On control days (days 1 and 3) smokers and nonsmokers sat in an unventilated 45 m3 room for 8 h. On the exposure days (days 2 and 4) each of the five smokers smoked 24 cigarettes in 8 h, while the five nonsmokers were exposed to the ETS generated by the smoking volunteers. High exposure to tobacco smoke was confirmed by dosimetry of carboxyhemoglobin (CO-Hb), plasma nicotine and cotinine levels. Blood was drawn before and after each exposure on all 4 experimental days for determination of DNA-SSB in lymphocytes immediately after isolation of blood cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Histoplasma infections in Europe are rare, and acute disseminated histoplasmosis has only been observed in immunocompromised persons. We describe a case of acute disseminated histoplasmosis in a young, nonimmunocompromised European woman. The probable source of infection was Sri Lanka or the Maldives. At presentation she was severely ill with fever, lymphadenopathy, anemia, thrombocytopenia, hepatosplenomegaly, and polyserositis. Histologically, myelofibrosis and osteosclerosis were observed with extramedullary hematopoiesis. Histoplasma capsulatum yeasts were detected in bone marrow trephine biopsy by methenamine silver staining. Treatment with conventional and liposomal amphotericin B and subsequent itraconazole led to rapid and complete recovery.

This study investigated the effect of extracorporal lipid-lowering therapy by low-density lipoprotein (LDL) apheresis on coronary artery disease in a population characterized by early development and rapid progression of atherosclerosis. We treated 32 patients aged between 15 and 63 years with drug-refractory familial hypercholesterolemia, treated once a week by immuno-specific LDL apheresis for 3 years in a controlled prospective and non-randomized trial; 25 patients (14 females and 11 males) completed the study. Noninvasive data were obtained by physical examination, 12-lead ECG and exercise testing. Invasive cardiological data were obtained by cardiac catheterization according to a standardized protocol in four cardiological centers. Left ventricular ejection fraction was calculated using planimetry. Coronary stenoses were measured quantitatively in 23 defined coronary segments by a panel of four investigators with an electronic digital caliper. In addition, overall coronary atherosclerosis was visually qualified. Final decisions on a classification into one of three groups (regression, no change, progression) of coronary atherosclerosis were based on panel consensus. Six cardiac events occurred throughout the study: percutaneous transluminal coronary angioplasty in one patient, coronary bypass grafting in three and two deaths. Statistical analysis of exercise testing yielded no significant change for maximum power and work capacity during the study period. Hemodynamic data revealed no significant change; mean ejection fraction was calculated as 65.8 +/- 15.9% at study entry and 67.0 +/- 12.7% at completion. Quantitative measurement of 111 circumscribed coronary stenoses showed a mean stenosis degree of 45 +/- 26% at entry cineangio-film and 43 +/- 22% at final cineangio-film demonstrating no significant change.(ABSTRACT TRUNCATED AT 250 WORDS)

The nifedipine gastrointestinal therapeutic system (GITS) is a recently developed controlled-release formulation for once-a-day dosing. We evaluated the influence of morning versus evening administration of the drug in a randomized double-blind cross-over study including 15 essential hypertensives. Five patients had to be excluded from blood pressure analysis because of noncompliance (three cases) or intolerable side effects (two cases). To assess the exact duration of the antihypertensive efficacy noninvasive automatic ambulatory blood pressure monitoring was performed. After a placebo period patients were given 30 mg nifedipine GITS either at 1000 or 2200 hours. Twenty-four-hours systolic and diastolic blood pressure profiles documented a sustained antihypertensive effect of both nifedipine regimens throughout the whole period without affecting the circadian rhythm. Statistical analysis revealed no significant difference between morning and evening administration. Two patients stopped their medication because of intolerable side effects (fatigue and muscle cramps, respectively). Two more cases suffered from mild reversible headache which provoked no discontinuation of the drug. In conclusion our results document a sustained antihypertensive efficacy of 30 mg nifedipine GITS in patients with moderate essential hypertension. Time of administration has no impact on day- and nighttime blood pressure control.

The purpose of this double-blind, placebo-controlled study was to determine and compare the clinical efficacy and tolerance of human leukocyte alpha-interferon (incorporated 2 x 10(6) IU/g) in hydrophilic cream to cure genital warts. Preselected Asian female patients (n = 150) aged 18-40 years (mean 22.5), with the clinical and biopsy-confirmed diagnosis of genital warts (mean 2.64), predominantly flat vaginal condylomas, were randomly allocated to 3 parallel groups. Each patient was given a coded tube containing 80 g placebo/active preparation with a graduated applicator. Patients were instructed to inject 6 g of the either alloted placebo/active cream deep into the vagina thrice a day for 3 consecutive days (group A) or 4 consecutive days (group B) per week, and if not cured the same treatment was extended to 3 more weeks (maximum 4 weeks active treatment). To assess the clinical efficacy patients were examined on a week-to-week basis. A total clearance of warts (biopsy-confirmed) was evaluated as a complete cure. Patients cured during the treatment were spared further treatment and were requested to visit us after 16 weeks for relapse control. As for the remaining patients, empty tubes were collected, and similarly coded replacement tubes were given for further treatment (in total 588 tubes were used). By the end of the treatment 57.2% lesions (227/397) were eliminated in all the groups: 48% patients in group A, 90% patients in group B, and 10% patients in placebo groups taken as completely cured.(ABSTRACT TRUNCATED AT 250 WORDS)

The Na+/H+ antiport is a membrane transport protein that extrudes intracellular protons in exchange for extracellular sodium. Some details of its physiological and pathophysiological role remain poorly defined. Experimental evidence suggests that the antiporter is involved in the regulation of cell volume. In the present study, we therefore investigated the activity of the lymphocyte Na+/H+ antiport in nine healthy volunteers following acute hypertonic (2.5%) saline infusion (4 mmol NaCl/kg over 120 min). Antiport activity was measured after acidifying the cells with Na+ propionate (5-40 mM) using the fluorescent dye bis-carboxyethyl carboxyfluorescein. Hypertonic saline induced significant increases in plasma osmolality (308.4 +/- 2.3 vs. 293.5 +/- 2.7 mOsm/kg; P < 0.01), serum Na+ (150.8 +/- 3.7 vs. 138.9 +/- 0.5 mmol/kg; P < 0.01), and Cl- concentrations (118.0 +/- 3.9 vs. 101.1 +/- 1.0 mmol/kg; P < 0.01). Extracellular hypertonicity was followed by a stimulated activity of the lymphocyte Na+/H+ antiport with an increase in the apparent Vmax values from 2.44 +/- 0.16 to 3.27 +/- 0.34 10(-3) s-1 (P < 0.01) and a slight rise in pK, from 6.81 +/- 0.03 to 6.87 +/- 0.03 (P < 0.05) after hypertonic saline. In addition to antiport activation, cytosolic alkalinization was observed with cytosolic pH values averaging 6.90 +/- 0.02 before and 6.99 +/- 0.02 (P < 0.01) after hypertonic saline. Our results show for the first time that acute extracellular hypertonicity in man due to hypertonic NaCl loading is associated with a stimulated lymphocyte Na+/H+ antiport activity and cytosolic alkalinization.

Total body water was measured by ethanol dilution and D2O stable isotope dilution in a group of 20 healthy volunteers (5 females and 15 males), predominantly 23- to 31-year-old students. Both indicator substances were given orally with an ethanol burden of 0.8 g/kg body weight and a D2O burden of 0.1 g/kg body weight after 12-h food and fluid restriction. This first direct comparison of total body water (TBW) from ethanol and D2O dilutions revealed the ethanol compartments to be smaller than those of D2O. The quotient of TBW (ethanol)/TBW (D2O) was 97.7%, which is the order of the quotient TBW (H2(18)O)/TBW (D2O) ( = 97%), well known from the literature and taken to represent relatively exactly the value of TBW overestimation (based on H/D exchange for acid protons) following D2O dilution [36]. Thus the value of TBW (ethanol) is almost identical to that of H2(18)O, which provides direct evidence that ethanol is distributed only in the body water.