Experimental study on porous hydroxyapatite ceramics in repair of skull bone defect of rabbit

The experimental and clinical effectiveness of nasal salmon calcitonin (SCT) for treatment of osteoporosis in humans has been well established, but none is known yet about the pharmacokinetic property in relation to therapeutic efficacy, especially when used in a therapeutic dose range. This preclinical study was designed to evaluate such a property, first of all in rats, using a novel heterogeneous two-site enzyme immunoassay that has allowed us to evaluate the pharmacokinetic property of parenteral SCT in rats due to the high sensitivity (the detection limit = 2 pg of SCT/ml of plasma). It was found that as early as 10 min after the nasal dosing of 1.25, 5, or 20 U/rat, the SCT immunoactivity became detectable in plasma and thereafter it waned rapidly with time. Hypocalcemia developed in a dose-dependent manner, but with a delay of approximately 20 min from the peak of the immunoactivity and lasted hours. The pharmacokinetic parameters measured for the doses (1.25, 5, and 20 U/rat) were as follows; the AUCs (pg.hr/ml) = 20.8, 89.0, and 189, and the MRTs (min) = 52, 54, and 45, respectively. The results appear to suggest: (1) the unexpected quick transfer of nasal SCT into and from the circulation, (2) a delayed onset of hypocalcemia and possibly its anti-osteopenic action, both of which may last longer, (3) that keeping the plasma SCT above the in vitro anti-osteoclastic level (approximately 1 pM) only for a few hours per 2 days would be enough for inducing the distinct anti-osteopenic effect in rats, and (4) the feasibility of designing the clinical study as to the pharmacokinetics and pharmacodynamics of nasal SCT on humans.     

Seasonal variations in the composition of urine from normal subjects: a longitudinal study

The volume, pH and composition of 24-h urine samples, collected by 13 healthy male adults, were followed over a period of one year. Significant and systematic variations in urine pH, calcium, phosphate, oxalate, uric acid, potassium and magnesium were observed. A significant but non-sinusoidal variation in sodium excretion was found but there were no significant changes in urinary volume, creatinine or hydroxyproline. Many of the observed changes could be attributed to variations in the pattern of food consumption throughout the year but calcium, phosphate and oxalate were exceptions in that seasonal variations in these parameters appeared to be due to the effects of sunlight (or vitamin D) rather than to the diet.     

A quantitative assessment of the hardenability increase resulting from a superhardenability treatment

The superhardenability treatment, which consists of superheating steel melts to which fairly large aluminum additions have been made, has been studied in a wide range of low-alloy steels. By hardenability testing and dilatometry, it is shown that the treatment results in large and repeat-able hardenability increases due to a strong retardation of the ferrite/pearlite and bainite reactions. Superhardenability multiplying factors and equations which relate the ideal critical diameter of a superhardenable steel to its chemical content have been produced by using a combination of three hardenability tests. A mechanism for the superhardenability effect is proposed on the basis of the experimental finding that high austenitizing temperatures result in a loss of superhardenability.     

Morphological variations of the human gastric mucosa after omeprazole treatment: a scanning electron microscopic study

The effects of antiepileptic drugs on cognitive function in 48 healthy volunteers were assessed using event-related potentials (ERP) and the Attention Index included in the Wechsler Memory Scale, revised edition (WMS-R). The study was conducted over 1 week, using a double-blind design. Four drugs, carbamazepine (CBZ), phenytoin (PHT), valproate (VPA) and zonisamide (ZNS) were tested. Using an auditory oddball task, ERP measurements were made under two conditions with different tone intensities: Condition 1 used 70 db SPL; and Condition 2 used 30 db SPL. Results showed that CBZ prolonged target N1 and P3 latencies in Condition 1, and reduced frequent N1 amplitude in Condition 2, which suggests that CBZ may cause a change in sensory memory and prolong stimulus evaluation time. It is suggested that under a low stimulus intensity level, the sensory function itself was affected. Phenytoin was found to prolong target N1 latency in Condition 2, which also indicates a change in the sensory memory function. However, VPA did not significantly affect ERP components, except for the shortened frequent N1 latency, which could not be explained due to the limited information. It was found that ZNS augmented P3 amplitude in Condition 2, and reduced scores on the Attention Index. It is suggested that the augmentation of P3 amplitude was caused by the reduction of processing negativity as a result of the detrimental effect of ZNS on subjects' attention. However, the apparent difference between the ERP and behavioral indices suggests that caution should be exercised in assessing the results obtained only from ERP measurements.     

Response-specific antiestrogen resistance in a newly characterized MCF-7 human breast cancer cell line resulting from long-term exposure to trans-hydroxytamoxifen

To understand better the antiestrogen-resistant phenotype that frequently develops in breast cancer patients receiving tamoxifen, we cultured MCF-7 breast cancer cells long-term (>1 yr) in the presence of the antiestrogen trans-hydroxytamoxifen (TOT) to generate a subline refractory to the growth-suppressive effects of TOT. This subline (designated MCF/TOT) showed growth stimulation, rather than inhibition, with TOT and diminished growth stimulation with estradiol (E2), yet remained as sensitive as the parental cells to growth suppression by another antiestrogen, ICI 164,384. Estrogen receptor (ER) levels were maintained at 40% of that in parent MCF-7 cells, but MCF/TOT cells failed to show an increase in progesterone receptor content in response to E2 or TOT treatment. In contrast, the MCF/TOT subline behaved like parental cells in terms of E2 and TOT regulation of ER and pS2 expression and transactivation of a transiently transfected estrogen-responsive gene construct. DNA sequencing of the hormone binding domain of the ER from both MCF-7 and MCF/TOT cells confirmed the presence of wild-type ER and exon 5 and exon 7 deletion splice variants, but showed no point mutations. Compared to the parental cells, the MCF/TOT subline showed reduced sensitivity to the growth-suppressive effects of retinoic acid and complete resistance to exogenous TGF-beta1. The altered growth responsiveness of MCF/TOT cells to TOT and TGF-beta1 was partly to fully reversible following TOT withdrawal for 16 weeks. Our findings underscore the fact that antiestrogen resistance is response-specific; that loss of growth suppression by TOT appears to be due to the acquisition of weak growth stimulation; and that resistance to TOT does not mean global resistance to other more pure antiestrogens such as ICI 164,384, implying that these antiestrogens must act by somewhat different mechanisms. The association of reduced retinoic acid responsiveness and insensitivity to exogenous TGF-beta with antiestrogen growth resistance in these cells supports the increasing evidence for interrelationships among cell regulatory pathways utilized by these three growth-suppressive agents in breast cancer cells. In addition, our findings indicate that one mechanism of antiestrogen resistance, as seen in MCF/TOT cells, may involve alterations in growth factor and other hormonal pathways that affect the ER response pathway.     

A longitudinal elasticity study of hair from the human head in forensic medicine

A rapid and sensitive method for assessing hair keratin stretch elasticity modulus has been developed. The technique is based on measuring the oscillation resonance frequency of hair fragments fixed at one end. The first results indicate a high sensitivity of the method and the possibility of its use in forensic medicine.     

Changes in medical students' perceptions of family practice resulting from a required clerkship

BACKGROUND: Career choice research has shown that exposing medical students to family medicine, through a special medical school emphasis or a required clerkship, correlates with an increased rate of selection of family practice. It has been hypothesized that actual exposure to family medicine mitigates the negative stereotypes held by many medical students. METHODS: This study used a qualitative strategy to examine how a family medicine clerkship altered medical students' perceptions and attitudes toward this specialty. A series of 12 focus groups were conducted with the students who had just completed a required family medicine junior core clerkship at our institution. RESULTS: Focus group findings confirmed the existence of negative stereotypes about family practice among medical students and provided additional information on their nature and origins. In addition, student comments indicated that a third-year family medicine clerkship experience dispelled this negative stereotyping and instilled in students a greater respect for and interest in family practice. CONCLUSION: Third-year clerkships can enhance students' perceptions of family practice by dispelling negative stereotypes and by providing medical students with a more accurate portrayal of the nature of this primary care specialty.     

A study of the degradation of phenoxyacid herbicides at different sites in a limestone aquifer

The biodegradation of three phenoxyalkanoic acid herbicides, viz. MCPA, dichlorprop and mecoprop, under aerobic and anaerobic conditions was investigated using microcosm techniques. The field studies were conducted in a limestone aquifer that had suffered contamination from leaking landfill sites in which phenoxyalkanoic acid herbicides (mostly mecoprop) had undergone disposal. The results from in situ field and laboratory microcosms indicated that under microbially active aerobic conditions the biotransformation of all three herbicides was rapid and that lag phases were short. Under fully aerobic conditions the concentration of each of the three herbicides was reduced from 2,000 micrograms/l to below the detection limit (approx. 10 micrograms/l) of the HPLC system, used for their analysis, within 14 days. However, under microbially active anaerobic conditions no degradation of the herbicides could be discerned over the 100-200 day duration of the experiments. This finding has significant implications for the disposal of phenoxyalkanoic acid herbicides particularly in situations where any resulting leachate may find its way into underlying water resources.     

Resistance to cefoperazone-sulbactam in Klebsiella pneumoniae: evidence for enhanced resistance resulting from the coexistence of two different resistance mechanisms

We investigated the in vitro activity and the in vivo efficacy of the beta-lactam-beta-lactamase inhibitor combination cefoperazone-sulbactam against an isogenic series of Klebsiella pneumoniae strains. Both cefoperazone and cefoperazone-sulbactam were active in vitro against a susceptible clinical strain, and the combination was highly effective in the treatment of rat intra-abdominal abscesses. Loss of expression of a 39-kDa outer membrane protein resulted in at least a fourfold increase in the MICs of cefoperazone and cefoperazone-sulbactam but did not appreciably affect the in vivo efficacy of either regimen. Introduction of plasmid RP4, which encodes the TEM-2 beta-lactamase, into the susceptible strain resulted in the loss of in vitro activity and in vivo efficacy for cefoperazone. The in vitro activity of cefoperazone-sulbactam against this strain was diminished, but the antibiotic combination remained highly active in vivo. Introduction of RP4 into the strain lacking the 39-kDa outer membrane protein resulted in a fourfold increase in the in vitro MIC of cefoperazone-sulbactam in comparison with the beta-lactamase-producing susceptible strain and resulted in a loss of in vivo efficacy against infections caused by this strain. These results suggest that the combination of different resistance mechanisms, neither of which alone results in substantially diminished cefoperazone-sulbactam efficacy in vivo, can cause in vivo resistance to the beta-lactam-beta-lactamase inhibitor combination in K. pneumoniae.     

A study of replanted permanent teeth in different age groups

In the inpatient treatment of acute psychiatric episodes in children and adolescents, the psychiatrist must set up an initial treatment plan incorporating one or more psychotherapeutic modalities and adapt this plan to the patient's clinical course. This article summarises the clinical experience of a model unit at the University of Heidelberg, the result of a collaboration between the Department of General Psychiatry and the Department of Child and Adolescent Psychiatry at the Clinic of Psychiatry. A series of 116 adolescent admissions was reviewed for clinical diagnosis, the nature and frequency of psychotherapeutic modalities, and the role of family involvement in patient care. Differential and adaptative approaches to the selection of treatment modalities in the context of an acute care setting are emphasised.     

A missense mutation in hepatocyte nuclear factor-4 alpha, resulting in a reduced transactivation activity, in human late-onset non-insulin-dependent diabetes mellitus

OBJECTIVE: Results from several recent studies suggest that the levels of antigenic keratan sulfate (agKS) and hyaluronan (HA) in serum provide useful information about changes taking place in injured or diseased synovial joints. To improve our understanding of the significance of such changes, we investigated the points of entry of these molecules into the blood circulation and their subsequent clearance after experimentally induced injury to rabbit knee joint. METHODS: Chymopapain was injected into knee joints of 8 young adult rabbits to induce aggrecan degradation in articular cartilage within the injected joint. Levels of agKS and HA in serum from various blood vessels were measured before and 5 h after the injury. The statistical significance of injury related changes and differences among the different vessels were evaluated. RESULTS: After the injury, the level of agKS rose most significantly in the popliteal vein draining the injected knee joint and dropped rapidly by the time the blood reached the femoral vein. The level of agKS was similar, although lower, in other blood vessels but, in each case, it was significantly higher than before the injection. The level of HA showed a different pattern of changes after injection. While highest in the popliteal vein draining the injected knee, HA was markedly elevated in the cranial vena cava, close to the entry of lymph into the circulation, and was 50% lower in the hepatic than in the portal vein. CONCLUSION: (1) Measurement of agKS and HA in a blood vessel draining or close to an injured/diseased knee joint may provide more specific information about degradative changes taking place in that joint than measurement of levels of these markers in other blood vessels; (2) some HA molecules but no measurable amounts of agKS enter the blood circulation via the lymphatic system: and (3) HA but not agKS is very rapidly cleared from the blood by the liver.     

A comparative study of the action of different doses of prednisone and budesonide on the biochemical indices of bone metabolism in healthy volunteers

Our objective in this study was to determine effects, if any, of different doses of of prednisone and the inhalant steroid budesonide on the indices for bone formation (osteocalcin, PICP levels) and bone resorption (piridinoline, deoxypiridinoline, and hydroxyproline) in healthy volunteers (n = 78). In the two-week study, budesonide administered in daily doses of 0.8 and 1.2 mg failed to significantly decrease serum osteocalcin; even in excessively high doses of 2.4 and 3.2 mg/a day it was found out to be associated with but insignificant decrease of PICP level. Prednisone in both a 10 mg/a day and 40 mg/a day dose appeared to significantly decrease the above measures. We take it that budesonide has a lesser effect on collagen formation than it has on bone mineralization.     

Sampling from the recorded therapy interview: A comparative study of different segment lengths.

To assess the effect of variations in the length of segments sampled from individual psychotherapy recordings on ratings of patient Experiencing (EXP) (a dimension of Process), judges' ratings of 2-, 4-, 8-, and 16-minute segments drawn from 2 points (early and late) in therapy with psychotics, neurotics and normals are compared. The results indicate: interrater and rerate reliabilities are unaffected by segment length: the scale range covered does not vary as a function of segment length; the absolute level of Experiencing (EXP) ratings tends to be a positive function of segment length, but the relative ordering of individuals and the ability of the scale to reflect change in EXP is not related to variations in segment length. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A prospective study of bone loss in African-American and white women--a clinical research center study

Although bone loss occurs universally with age, the incidence of age-related osteoporotic fractures varies widely among ethnic groups. In the U.S., age-adjusted hip fracture incidence is 50% lower in African-American than in white women. Adult African-American women also have higher bone mass, but it is not known whether this difference is entirely due to higher peak bone mass or also results from slower rates of bone loss. Rates of bone loss were measured prospectively in 122 white and 121 African-American healthy, nonobese, pre- and postmenopausal women. Bone density was measured at 6-month intervals over a mean of 3-4 yr using single and dual photon absorptiometry of the forearm (cortical bone) and spine (trabecular bone). Similar rates of premenopausal bone loss were documented in both white and African-American women. However, in early menopause, bone loss was faster in the white women in the forearm (-2.4%/yr in whites vs. -1.2%/yr in African-Americans; P = 0.045), with a similar trend in the spine (-2.2%/yr in whites vs. -1.3/yr in African-Americans; P = 0.27). In women more than 5 yr postmenopause, the rates of bone loss did not differ by ethnic group. Our results indicate that the higher bone mass in African-American women is largely due to the attainment of a greater peak bone mass by early adulthood. However, slower rates of bone loss in the early postmenopausal period may also contribute to the higher bone density of older African-American women. Although bone loss occurs in both groups, there are ethnic differences in bone loss rates which indicate that data derived from white women cannot be simply extrapolated to nonwhite populations. Ethnic group-specific data on the determinants of bone homeostasis are needed.     

Effects of ketorolac on bone repair: A radiographic study in modeled demineralized bone matrix grafted rabbits

The treatment of instability of the multiply reoperated knee is a complex problem. The causes for failure are numerous and include repeated trauma, insufficient fixation and non-anatomic placement of the graft, inadequate replacement material, isolated anterior cruciate ligament (ACL) reconstruction in complex knee instability or the use of a ligament prosthesis. With every surgical procedure, however, the anatomical and technical conditions become worse. Problems like degenerative changes, joint stiffness and gait abnormalities occur and often become a more focal point than the instability itself. The purpose of this paper is to present the problems and the dilemma of instability of the multiply reoperated knee and the possible solutions. Between 1976 and 1996, a total of 1752 ACL reconstructions were carried out in Munich and Hannover. Of these, 228 (13%) were revision, mostly of failed ACL reconstructions performed elsewhere. Since 1989, we have chosen the severest cases from this group (more than three operations on the same knee) for this study. Seventeen patients were investigated who had undergone up to 25 operations. The mean number of operations was 7. All primary operations were performed in other hospitals. In 10 cases only the ACL reconstruction was performed as a final procedure, mostly in combination with other procedures like medial meniscus replacement, extra-articular stabilization or arthrolysis. In the other cases operations such as osteotomies, arthrodesis or amputation were necessary. The results present the main dilemma in instability of the multiply reoperated knee since they were not successful in all patients. Finally, 15 patients report still having instability, pain or swelling in isolation or in combination. Nine patients were satisfied with their subjective results. Even after the socalled definitive procedures, certain complications arose. The main goal in the treatment of instability of the multiply reoperated knee is to avoid a series of operations, hospitalization and history of illness. General revision surgery for the entire complaint is not the aim of the treatment. The specific problem of the patient should be extracted from the complex situation, and this should be solved with the most limited procedure possible only.