Heparin-induced thrombocytopenia: pathophysiology

We have used computer modeling of insulin 3-D structure and experimental data about action of site point mutation on insulin activity to design functionally important domain with signaling activity and synthesized peptide than might be sufficient for the binding to insulin receptor. The designed and synthesized peptide consist of ten residues and may be obtained in two forms: oxidized and reduced (with or without disulfide bond). The synthesized decapeptide peptide represents functionally important site for binding to the insulin receptor. Amino acid residues at position 1-8 correlate with B-chain of insulin at position (B19-B26). Residues at position 9.10 correlate with A-chain at position A-10-A21. This peptide was tested with cell culture L-929 (glucose uptake) in comparison with bioactive commercial peptide (R-G-FF) and insulin. It was shown that synthesized peptide exhibit biological activity at molar concentration 0.01-1 mkM. Our results successfully demonstrate the synthetic insulin fragment have insulin-like biological activity.     

Self-sustained pH oscillations in immobilized proteolytic enzyme systems

The efficacy of doramectin, a novel avermectin, was assessed against both naturally-acquired and experimentally-induced infections of gastrointestinal roundworms, lungworms, kidneyworms, lice and mites in studies conducted across North America and Europe. Twenty-two studies evaluated efficacy against fourth larval and adult stages of the following nematode species: Hyostrongylus rubidus, Ascaris suum, Strongyloides ransomi, Oesophagostomum dentatum, Oesophagostomum quadrispinulatum, Trichuris suis, Metastrongylus spp. and Stephanurus dentatus. Efficacy was evaluated against the louse Haematopinus suis in six studies and against the mite Sarcoptes scabiei in four studies. A common study design was employed for each study type. In all studies, animals were allotted at random to a doramectin-treated or a saline-treated group. The doramectin-treated group received the drug at 300 micrograms kg-1 by intramuscular injection while the saline-treated group received saline by the same route. In the nematode studies, worm burdens were determined for each animal at slaughter 14-16 days after treatment. Efficacy against each nematode species/stage was assessed on the basis of percentage reduction in geometric mean worm burden in doramectin-treated animals compared with saline-treated controls. In louse and mite studies, counts were made immediately before treatment and then at weekly intervals for four weeks. Efficacy was based on a comparison of the level of infestation on the day of treatment with that on the last day of test. Data from individual studies were combined to derive a single estimate of efficacy against each of the parasite species represented in the study program. Efficacy of doramectin was 98% or greater against all nematode species except T. suis for which the efficacy was 87% and 79% against adult and fourth larval stage, respectively. Efficacy was 100% against both Haematopinus suis and Sarcoptes scabiei.     

Impaired autoregulation in an experimental model of chronic cerebral hypoperfusion in rats

BACKGROUND AND PURPOSE: To verify the hypothesis that impaired autoregulation may contribute to cerebral swelling or hemorrhage after a sudden recovery of perfusion pressure, we studied the chronic effects of cerebral hypoperfusion on the autoregulatory responses of the pial arterioles in situ. METHODS: Eight to 12 weeks after a carotid-jugular fistula was created in rats, experiments were performed under alpha-chloralose and urethane anesthesia. Regional cerebral blood flow (rCBF) was determined by the hydrogen clearance method, and carotid pressure was measured. Using a closed cranial window, we determined the autoregulatory responses of the arterioles (30 to 50 microns) to both hypertension induced by norepinephrine and sudden fistula closure at various mean arterial pressures (MAPs). RESULTS: rCBF on the fistula side was reduced by 27%. Carotid pressure was significantly lower than normal but was immediately increased by fistula closure. The pial arterioles showed marked elongation and enlargement. During induced hypertension, the arterioles in the fistula group started to dilate at an MAP lower than that of the control group (130 versus 180 mm Hg, respectively). The arterioles constricted when the fistula was occluded at normal MAP. However, when the fistula was occluded at an MAP higher than 130 mm Hg, the vessels dilated. CONCLUSIONS: It was demonstrated that (1) chronic hypoperfusion induced impairment of the upper limit of autoregulation and (2) sudden fistula closure under hypertensive conditions caused vasodilation of the arterioles. These findings suggest that rapid restoration of perfusion pressure is possibly followed by a pressure breakthrough phenomenon in a chronically hypoperfused cerebrovasculature.     

The relationship between cardiac contraction and intramyocardialhemodynamics

Since coronary venous flow is squeezed out from the myocardial vascular bed by the extravascular compressive force of heart muscle, the coronary venous system provides a suitable model to investigate the relationship between cardiac contraction and intramyocardial hemodynamics. To investigate coronary venous flow velocity in more detail, we previously developed a laser Doppler velocimeter (LDV) with an optical fiber. Furthermore, we have recently developed a needle probe charge-coupled device (CCD) videomicroscope to visualize intramyocardial microvessels. In this article, we report I) blood flow velocity waveforms in the epicardial small veins of the left ventricle and 2) subendocardial venular diameter changes during a cardiac cycle     

Factors affecting young children's mental development and their significance in intervention

Factors affecting their developmental quotients (DQ) in 48 normal young children, who were involved in regular development assessments at child health care outpatient visits and whose parents received child-rearing guidance at Chaoyangmen Subdistrict of Dongcheng District, Beijing, and 43 controls aged 36 months were analyzed. Factors, such as their parents' receiving child-rearing guidance, paternal education, maternal education, paternal occupation, type of nursery schools, home environment quality score (HEQS) at 24 and 36 months of age, and mothers' knowledge of child-rearing were associated with children's DQ at their age of 36 months, with statistical significance at a level of 0.05 in univariate analysis. With multiple regression analysis, HEQS at the age of 36 months, family size at the age of 24 months, paternal education, children's sex, and mothers' age had influences on DQ at age of 36 months with statistical significance, and the degree of correlation of HEQS with DQ at 36 months was much higher than that of other factors, and it suggested that HEQS was an important link in child developmental intervention.     

School-based health care for urban minority junior high school students

OBJECTIVE: To describe the use of school-based health clinics by urban minority junior high school students. DESIGN: Review of demographic and utilization data collected by service providers during clinic visits. SETTINGS AND PARTICIPANTS: Health clinics in four junior high schools that enrolled predominantly Hispanic students who were residing in an economically disadvantaged, medically underserved New York (NY) school district. RESULTS: Of 5757 students who were enrolled in the schools, 5296 (92%) obtained parental consent to use the clinics, and 3723 (65%) used the clinics during the 1991-1992 academic year. Clinic users were 11 to 15 years old, 50% male and 50% female, 81% Hispanic and 14% black, and 29% sixth graders, 33% seventh graders, and 38% eighth graders. Clinic users made 16,340 clinic visits during the 1991-1992 academic year. Presenting complaints were mental health problems (32%), illness (14%), injury (12%), physical examination (5%), immunization (3%), follow-up (21%), and other (13%). Referral sources were clinic outreach (48%), self (44%), and school personnel (8%). Disposition of visits was on-site treatment (92%), referral to an affiliated hospital (5%), and referral elsewhere (3%). Compared with a nationwide group of high school-based clinics that served predominantly black adolescents, these clinics provided more mental health care (31% vs 21%), similar illness/injury care (32% vs 30%), and less preventive (10% vs 24%) and reproductive/contraceptive (7% vs 12%) care. CONCLUSIONS: Junior high school-based clinics can provide a wide range of primary and preventive health care services for large numbers of medically underserved youths. The provision of mental health services may fill a critical need among inner-city adolescents. Clinic outreach may be necessary to maximize utilization, especially among high-risk students.     

The role of endoscopic third ventriculostomy in the management of shunt malfunction

OBJECTIVE: To evaluate the effectiveness of third ventriculostomy as an alternative to shunt revision in the management of shunt malfunction and infection in obstructive hydrocephalus. METHODS: All of the clinical notes of 30 patients treated with third ventriculostomy for malfunctioning or infected shunts between January 1, 1974, and December 31, 1996, were retrospectively reviewed. Third ventriculostomy was performed under fluoroscopic control in the first seven patients and endoscopically in the remainder. A successful outcome was achieved if further shunt revision surgery was avoided. The median follow-up duration was 8.7 years RESULTS: Twenty-three patients (76.7%) experienced successful outcomes, resulting in shunt independence. Of the seven failures, three were technical failures at the time of surgery and the remaining four were manifest within a median of 10 days, resulting in shunt revision. There have been no delayed failures. CONCLUSION: Third ventriculostomy is a valuable alternative to shunt revision in patients affected by obstructive hydrocephalus presenting with shunt malfunction or infection. It should be considered in all suitable cases as the first-line treatment for obstructive hydrocephalus of all causes. Because all failures were manifest within a short time, it is likely that these successes will be durable.     

Suprachiasmatic nucleus organization

OBJECTIVE: To assess the effect of a combined exercise and motivation program on the compliance and level of disability of patients with chronic and recurrent low back pain. DESIGN: A double-blind prospective randomized controlled trial. SETTING: Physical therapy outpatient department, tertiary care. PATIENTS: Ninety-three low back pain patients were randomly assigned to either a standard exercise program (n = 49) or a combined exercise and motivation program (n = 44). INTERVENTIONS: Patients were prescribed 10 physical therapy sessions and were advised to continue exercising after treatment termination. The motivation program consisted of five compliance-enhancing interventions. Follow-up assessments were performed at 3 1/2 weeks, 4 months, and 12 months. MAIN OUTCOME MEASURES: Disability (low back outcome score), pain intensity, physical impairment (modified Waddell score, fingertip-to-floor distance, abdominal muscle strength), working ability, motivation, and compliance. RESULTS: The patients in the motivation group were significantly more likely to attend their exercise therapy appointments (p = .0005). Four and 12 months after study entry there was a significant difference in favor of the motivation group with regard to the disability score (p = .004) and pain intensity (p < or = .026). At 4 months, there was a significant advantage for the motivation group in the fingertip-to-floor distance (p = .01) and in abdominal muscle strength (p = .018). No significant differences were found in motivation scores, self-reported compliance with long-term exercise, and modified Waddell score. In terms of working ability, there was a trend favoring the combined exercise and motivation program. CONCLUSION: The combined exercise and motivation program increased the rate of attendance at scheduled physical therapy sessions, ie, short-term compliance, and reduced disability and pain levels by the 12-month follow-up. However, there was no difference between the motivation and control groups with regard to long-term exercise compliance.     

Thrombocytopenia following liver transplantation is associated with platelet consumption and thrombin generation

PSA-based screening substantially increases the prostate cancer detection rate and the percentage of organ-confined tumors. It appears that there is some benefit from screening for prostate cancer because of the increased amount of potentially curable disease discovered and the fact that 96% of the pathologically staged tumors detected have histologic features associated with aggressive cancer. Additional evidence that nearly all tumors detected on the basis of initial PSA screening are apt to be clinically significant may be derived from the information that PSA-based screening decreases the incidence of incidental A1 grade III and A2 tumors but does not increase the detection of clinically insignificant A1 grade I and II tumors. At this time, PSA represents the most effective and valuable tool to detect early prostate cancer; therefore, PSA should be used to improve early diagnosis of prostate cancer. Some advances have been made with the introduction of age-specific reference ranges and the ability to measure free to total PSA ratios. The data presented support the clinical usefulness of age-specific reference ranges for serum PSA. Calculation of the free to total PSA ratio is valuable in deciding which screening volunteers require further evaluation, increases the specificity of PSA screening, and as demonstrated may be useful in deciding which patients with isolated PIN should undergo repeat biopsies. Based on these facts, PSA truly can be described as the most important and useful marker for adenocarcinoma of the prostate. Based on these encouraging results and the obligingness of the social insurances, we will be able to continue PSA screening for early detection of prostate cancer for all concerned Tyrolean men in the future.