The distinction of bone and liver isoenzymes of alkaline phosphatase in serum using a monoclonal antibody

Out of 31 mouse monoclonal antibodies to human liver and bone ALP, one antibody coded BAP 1/9, showing a preference for binding the bone isoenzyme, and one antibody coded LAP 1/5, showing no preference, were selected to study binding of the serum forms of ALP. Using a plate capture assay format BAP 1/9 showed a 1.8-fold preference for binding purified bone versus liver ALP in the presence of 10% ALP-free serum compared with 2.1- to 2.25-fold preference in buffered salt solution. BAP 1/9 showed a preference for binding ALP from serum samples containing predominantly bone ALP compared to those containing predominantly liver ALP. Using predefined mixtures of serum forms of bone and liver ALP a linear relationship between ALP bound to BAP 1/9 and the fraction of bone ALP was obtained.     

Effects of "Below-Zero" Habituation on the Electrodermal Orienting Response to a Test Stimulus

Two experiments were designed to investigate the effect of below-zero habituation training on skin conductance response (SCR) amplitude to a change in auditory stimulus frequency. In both experiments, subjects were trained with a 1000 Hz tone until zero responding and then received 5, 10, or IS further training trials. In Experiment 1 (N=45), subjects then received 1 presentation of a test stimulus of 1400 Hz, while in Experiment 2 (N=45), the test stimulus was a tone of 670 Hz. On the basis of dual-process theory, it was hypothesized that response amplitude to the test stimulus would be inversely related to amount of below-zero training. However, the results of both experiments indicate that SCR amplitude was positively related to amount of below-zero training. These results suggest that in situations of extended habituation training, an expectancy or subjective probability of stimulus occurrence gradient is important in determining response amplitude to a test stimulus.     

Effects of Stimulus Intensity on Cardiovascular Activity

A between-groups design (N = 75) was employed to investigate the effects of stimulus intensity and repetition on cardiovascular activity. It was predicted that as intensity increased, the pattern of physiological activity would change, indicating a transition from the orienting to the defense reflex. Cardiovascular activity was represented by measures of heart rate, digital pulse amplitude, and cephalic blood content. Subjects received 12 presentations of a 1000 Hz tone of 45, 60, 75, 90, or 105 dB. Stimulus risetime was 30 msec and the duration 2 sec. Analyses of variance revealed reliable effects of intensity and repetition on all cardiovascular variables. However, neither these results nor additional multivariate analyses supported the differentiation of orienting and defense reflexes as suggested by Sokolov (1963) or Graham (1979). The importance of the startle reflex in the interpretation of these findings was discussed.     

Effect of replacement of extracellular sodium ions and of D-600 on the activation by adrenalin of adenylate cyclase in intact pigeon erythrocytes

The effect of replacement of extracellular Na⁺ by Li⁺, choline, K⁺ or sucrose on cyclic AMP formation in pigeon erythrocytes has been investigated. Replacement of extracellular Na⁺ by Li⁺, choline or sucrose but not by K⁺ inhibited the stimulation by adrenalin of cyclic AMP formation, but had no detectable effect on cyclic AMP content in the absence of adrenalin. This inhibition was observed in the presence or absence of extracellular Ca²⁺. The relative inhibition caused by Na⁺ removal decreased with increasing adrenalin concentration. It was concluded that extracellular Na⁺ or K⁺ ions were required for maximal activation of adenylate cyclase by low concentrations of adrenalin, and that this effect of monovalent cations may have been due to an effect on the affinity of the receptor for adrenalin.The verapamil derivative D-600 also inhibited the stimulation by adrenalin of cyclic AMP formation. This effect occurred in the absence of extracellular Ca²⁺ and hence seemed to be unrelated to the inhibition by D-600 of the slow Ca²⁺ channel in electrically excitable tissues.     

The action of pancreatic hormones on the cyclic AMP content of isolated chicken hepatocytes.

The hormonal control of cyclic AMP content was investigated in hepatocytes isolated by collagenase digestion from chicken liver. Glucagon (2.9 × 10⁻⁷M) increased cyclic AMP content within 1 min, and the concentration continued to increase for at least 30 min. More than 90% of the total cyclic AMP measured remained within the cells during this time. Significant stimulation of glycogenolysis was obtained with a glucagon concentration (2.9 × 10⁻¹¹M) which had no detectable effect on cyclic AMP content. Half-maximal increases in cyclic AMP content and glucose production were produced by glucagon concentrations of approximately 10⁻⁸ and 10⁻¹⁰M, respectively. Insulin (0.17–17 × 10⁻⁹M) and avian pancreatic polypeptide (0.24–240 × 10⁻⁹M) had no effect on cyclic AMP content either in the presence or absence of glucagon. Adrenaline increased cyclic AMP content, the minimum effective concentration being 5 × 10⁻⁸M. The cyclic AMP response to adrenaline reached a peak within 2.5 min, and the maximum increase was much less than that produced by glucagon.     

Psychosocial impact of obstetric fistula in women presenting for surgical care in Tanzania

Introduction and hypothesis

World Health Organisation data suggest that two million women live with the physical and psychosocial effects of obstetric fistula. As part of an expanded fistula programme in Tanzania, Comprehensive Community Based Rehabilitation in Tanzania (CCBRT) introduced an evaluation strategy to include impact of surgery on psychosocial aspects of obstetric fistula. This is an initial report documenting morbidity on admission.

Methods

A questionnaire assessing the impact of obstetric fistula was developed taking into account literature in the field including sections on: patient contact information, transport costs and a set of statements regarding the effects of fistula. The effects were spread across five domains: the physical consequences of obstetric fistula, the effects of a difficult delivery and possible stillbirth, the experience of isolation, the inability to undertake daily living activities and feelings of depression. The questionnaire was administered in Kiswahili by Tanzanian counsellors shortly after admission of patients onto the fistula ward.

Results

A total of 100 fistula patients reported high rates of physical and psychosocial morbidity. Over half of the patients said they would not have been able to access treatment without the transport costs being covered.

Conclusions

Fistula patients are affected by extremely high rates of physical and psychosocial morbidity. Further work is required to confirm these findings, validate assessment tools and assess contributing factors in greater detail over time, such as the effect of stillbirth, as well as the impact of surgery.     

Intra‐articular tibiofemoral injection of a nonsteroidal anti‐inflammatory drug has no detrimental effects on joint mechanics in a rat model

Administration of intra‐articular medications, including corticosteroids and analgesics, is common clinical practice for knee pathology and dysfunction. Non‐steroidal anti‐inflammatory drugs (NSAIDs) are another category of medication commonly prescribed for their analgesic and anti‐inflammatory properties. Recent studies demonstrated the efficacy of injectable NSAIDs in the treatment of intra‐articular pathology and postoperative analgesia. However, little data exist regarding the safety of intra‐articular injection, despite the increase in its application. Therefore, we investigated the effects of intra‐articular NSAID injection on articular cartilage, the anterior cruciate ligament (ACL), and joint function in the rat. Sixty‐four Sprague‐Dawley rats were divided into either saline (SAL) or ketorolac (NSAID) tibiofemoral single injection treatment groups. Animals were euthanized at 2, 7, 28, and 84 days post‐injection for histological and mechanical analyses. Additionally, a subset of animals underwent longitudinal ambulatory evaluation to determine joint functional properties. We hypothesized that intra‐articular ketorolac injection would result in no detrimental mechanical, histological, or functional changes. No differences were reported between the NSAID and SAL groups in any of the parameters measured at any time point, demonstrating the potential safety of intra‐articular NSAID administration. Therefore, NSAID injection could be further considered for clinical application in humans. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1512–1519, 2014.     

Biceps Detachment Decreases Joint Damage in a Rotator Cuff Tear Rat Model

Background

Pathology in the long head of the biceps tendon often occurs in patients with rotator cuff tears. Arthroscopic tenotomy is the most common treatment. However, the role of the long head of the biceps at the shoulder and the consequences of surgical detachment on the remaining shoulder structures remain unknown.

Questions/purposes

We hypothesized that detachment of the long head of the biceps, in the presence of supraspinatus and infraspinatus tears, would decrease shoulder function and decrease mechanical and histologic properties of both the subscapularis tendon and the glenoid articular cartilage.

Methods

We detached the supraspinatus and infraspinatus or the supraspinatus, infraspinatus, and long head of the biceps after 4 weeks of overuse in a rat model. Animals were gradually returned to overuse activity after detachment. At 8 weeks, the subscapularis and glenoid cartilage biomechanical and histologic properties were evaluated and compared.

Results

The group with the supraspinatus, infraspinatus, and long head of the biceps detached had greater medial force and decreased change in propulsion, braking, and vertical force. This group also had an increased upper and lower subscapularis modulus but without any differences in glenoid cartilage modulus. Finally, this group had a significantly lower cell density in both the upper and lower subscapularis tendons, although cartilage histology was not different.

Conclusions

Detachment of the long head of the biceps tendon in the presence of a posterior-superior cuff tear resulted in improved shoulder function and less joint damage in this animal model.

Clinical Relevance

This study provides evidence in an animal model that supports the use of tenotomy for the management of long head of the biceps pathology in the presence of a two-tendon cuff tear. However, long-term clinical trials are required.