The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.     

Interaction of the atypical neuroleptic clozapine with 5-HT3 receptors in the cerebral cortex and superior cervical ganglion of the rat

Clozapine, an atypical neuroleptic drug devoid of extrapyramidal side effects, was a moderately potent, competitive inhibitor of the binding of [3H]quaternised ICS 205-930 to 5-HT3 receptor sites in rat cortical membranes, possessing a pKi value of 7.0. In contrast, several other antipsychotic agents, including fluphenazine, alpha-flupenthixol, haloperidol, spiperone and (-)-sulpiride were essentially inactive. Clozapine also antagonised the 2-methyl 5-HT-induced depolarisation of the rat isolated superior cervical ganglion, a response known to be mediated via 5-HT3 receptors. Clozapine (0.1-1 microM) induced parallel displacements to the right of the dose-response curve to 2-methyl 5-HT in this tissue, possessing a pKb value of 7.3. These data suggest that the atypical antipsychotic profile of clozapine may be related, at least, in part to its ability to interact with central 5-HT3 receptor sites.     

The use of bladder neck electric conductance (BNEC) in the investigation and management of sensory urge incontinence in the female.

Measurement of urethral electric conductance can be used to detect the movement of urine along the urethra by registering a change in conductivity reading. This technique has been employed in patients complaining of urge incontinence and has shown movements at the bladder neck when urgency is appreciated. Patients with sensory urgency have been successfully managed by learning to control the movements at the bladder neck during a conductivity recording.     

The mentored clinical casebook project at Harvard Medical School.

An excellent physician must be aware of the countless issues that affect each patient's health. Many medical education programs expose students to a broad spectrum of disparate knowledge and hope they will integrate all the pieces into a coherent whole. The authors describe an explicit approach to integration used at Harvard Medical School since 2003 that aims to enhance students' learning in medical school and throughout their medical careers: the Mentored Clinical Casebook Project (MCCP). The MCCP is constructed on the premise that such integration does not occur suddenly but, rather, is an unending process. A first-year student is assigned to one clinician and follows one patient for one year. The student is expected to spend as much time with the patient as possible, in both clinical and nonclinical settings, seek help from the clinician, and consult other experts and sources to develop a complete picture of the patient's life. The student must produce a casebook that includes, but is not limited to, the patient's history; basic science, clinical, socioeconomic, and cultural issues; and self-reflection. The MCCP is intended to allow students to develop a deeper and more diverse understanding of what comprises a patient's health care life, to discern the patient as a person and the person as a patient. This educational project has been popular with students since its inception, providing them with a personal framework from which to address the needs of future patients and introducing them to how much they will continue to learn from their patients.     

Sudden unexpected death in infancy associated with maltreatment: evidence from long term follow up of siblings.

AIMS: To identify any association between sudden unexpected death in infancy (SUDI) and maltreatment within local families. METHODS: Retrospective enquiry and subsequent follow up of all siblings and later births within the families. Full investigation of the circumstances of all unexpected deaths. Setting: Scarborough and Bridlington Health Districts and Trusts, North and East Yorkshire. SUBJECTS: All local families losing a baby from SUDI, 1982-96. Follow up to end of 2000. MAIN OUTCOME MEASURES: Court judgements and the objective decisions of legally constituted Social Services Case Conferences to place siblings on the Child Protection Register (CPR), or provide equivalent safeguards. RESULTS: Sixty nine families had 72 unexpected deaths; three families had two deaths, with two families raising maltreatment issues. Three families had other children subsequently put on the CPR, all identifiable as likely problems of maltreatment at the time of the single SUDI. In 64/69 families, no child protection issues were formally raised at the time of the SUDI; 41/64 of these families already had 63 children. Four families were lost to follow up after the SUDI; 52/60 of the remaining families have had 93 more children without objective evidence of maltreatment. CONCLUSIONS: The association of SUDI and maltreatment within families was at the lower end of previous estimates, 3-10%. Child protection intervention is rarely needed, but investigation and follow up for maltreatment is mandatory where apparent life threatening episodes are reported with a second baby, and after a recurrence of apparent SUDI.     

Thoracic outlet syndrome: a comprehensive evaluation

Using various modalities, 480 patients were evaluated for thoracic outlet compression syndrome. Of this group, 300 patients were eventually diagnosed as having thoracic outlet syndrome after extensive evaluation. Ninety of these patients underwent a total of 103 operative procedures for thoracic outlet decompression. Nerve conduction velocities and directional Doppler studies were the most useful adjuncts in making the diagnosis. Surgical therapy after proper selection yielded an 80.6 per cent long-term "good" operative result and an additional 6.9 per cent long-term "fair" operative result in follow-up to 12 years.     

Hamstring injuries in sprinting - the role of eccentric exercise

This paper assesses a specific connective tissue insufficiency induced hamstring injury occurring in the late swing/early stance phase of sprinting and jumping activities. A literature review related to hamstring injury demonstrates that eccentric muscle action is capable of producing very high forces within the series elastic component (SEC) of the hamstrings in this phase of sprinting. These high forces have been shown to be related to hamstring injury. The utilization of eccentric exercise training regimens can prevent this injury by strengthening the SEC, resulting in a musculotendinous structure theoretically capable of both generating and withstanding higher eccentric and concentric forces.A clinical approach utilizing an eccentric exercise regimen designed to strengthen the hamstrings in the late swing/early stance phase is outlined. A pilot study investigating the exercise indicates it is a valid method of preventing and rehabilitating the hamstring injury in terms of the positions at risk while sprinting, the angular velocities achieved, and the torques produced. J Orthop Sports Phys Ther 1989;10(9):343-349.