Immunolocalization of ClC-K chloride channel in strial marginal cells and vestibular dark cells

Secretion of K⁺ into endolymph depends on a particular constellation of ion transport proteins in the apical and basolateral membranes of strial marginal cells and vestibular dark cells. One fundamental component is the large chloride conductance of the basolateral membrane, which recycles chloride taken up by the Na⁺-K⁺-Cl⁻ cotransporter in the same membrane. Evidence has been reported recently that supports ClC-K, a channel subunit previously thought to be specific to the kidney, as being the molecular entity underlying this conductance. We have isolated protein from the gerbil kidney, stria vascularis and vestibular labyrinth and found by Western blot analysis a 60 kDa band, a 48 kDa band and 54 and 70 kDa bands, respectively, specifically labeled by ClC-K antibody. Subsequent immunohistochemical observations of the inner ear tissues with a confocal microscope on fluorescently labeled tissue sections showed the staining to be restricted to the basolateral region of strial marginal cells and vestibular dark cells. The cochlear staining was distinct from the distribution of the Kir4.1 (KCNJ10) K⁺ channel, known to be present only in strial intermediate cells. These findings support the contention that ClC-K is an important component of the basolateral Cl⁻ conductance that participates in K⁺ secretion by these epithelia.     

Digital toxicology education tools: education, training, case studies, and tutorials

This review presents a brief and non-comprehensive overview of a representative sampling of some of the broad array of toxicology-related learning, tutorial and information resources now becoming widely available to educators, health professionals, students and the general public in digital media and/or via the Internet. A broad variety of useful learning and reference resources in the general fields of toxicology and the environmental health sciences is provided to introduce the reader to the diverse types of information currently available. The sources and Internet links contained in this review will hopefully constitute a useful resource of basic toxicology information that should be readily accessible to most if not all readers.     

Pharmacological considerations during pregnancy

We present a brief overview of recent literature concerning some of the drugs used in pregnancy, labour and delivery. Obstetric anaesthesia continues to evolve through the reuse of old drugs such as magnesium sulphate or the manipulation of current drugs (e.g. propofol for emesis) in order to improve patient outcome. Pregnant women have traditionally been therapeutic orphans. The use of new agents such as levobupivacaine and ropivacaine in obstetric patients lags behind that of their non-pregnant counterparts. However, this gap is decreasing and these new drugs offer benefits to the parturient woman.     

Simultaneous in utero assessment of AV nodal and ventricular electrophysiologic parameters in the fetal sheep heart

Background Fetal tachyarrhythmias are usually of supraventricular origin. To investigate whether specific electrophysiologic properties of the fetal heart contribute to this preponderance by either favoring supraventricular tachycardias or by rendering ventricular tachycardias unlikely, we measured fetal electrophysiologic parameters in utero using transuterine fetal transesophageal electrocardiograms in fetal sheep. Since overdrive pacing may help to establish the mechanism of an arrhythmia and may be used to treat fetal tachycardias, different modes of transesophageal pacing in utero were also assessed. Methods and results Decapolar electrophysiology catheters were fetoscopically inserted into the esophagus of 9 fetal sheep (pregnancy duration 94 – 105 days, term = 145 days). Electrocardiograms were recorded simultaneously from all adjacent bipoles and from two pacing wires sutured onto the fetal shoulders. Pacing was attempted either via two adjacent electrodes of the intraesophageal catheter or via the most distal and most proximal electrode. Fetal cycle length, PQ, and QT intervals were close to (approx. 75 %), but fetal QRS duration was < 20 % of maternal values, thus shifting the relation between activation and repolarization towards longer excitation wave lengths. Fetal QT dispersion was small (≤ 10 ms). Atrial pacing was achieved in all fetuses using distant electrodes, and with lower thresholds when compared to closely spaced bipolar electrodes (p < 0.05). Conclusions (I) An altered relation between ventricular activation and repolarization and a low dispersion of ventricular repolarization may protect the fetal heart against ventricular reentrant tachycardias. (II) Relatively normal fetal AV nodal conduction delay already provides one of the prerequisites for supraventricular reentrant tachycardias involving the AV node at this stage of fetal development. (III) High-rate esophageal pacing of the fetal atria is best achieved using widely spaced bipolar pacing electrodes. Received: 26 July 2000, Returned for 1. revision: 16 August 2000, 1. Revision received: 28 November 2000, Returned for 2. revision: 18 December 2000, 2. Revision received: 23 January 2001, Accepted: 24 January 2001     

Intracavitary radiotherapy for refractory dysfunctional uterine bleeding. A case report

BACKGROUND: Pelvic irradiation was once a common treatment for dysfunctional uterine bleeding (DUB). Today the majority of women with DUB are successfully treated with hormonal therapy; patients unresponsive to hormonal therapy may require endometrial ablation or hysterectomy. We present a patient with severe, intractable DUB and contraindications to surgery who was treated with intracavitary radiotherapy. CASE: A 39-year-old, 150-cm-tall, 310-kg woman was referred for management of severe DUB refractory to medical management. The bleeding was successfully treated with intracavitary cesium. Hysterectomy was not recommended due to the operative risks posed by the patient's massive obesity. Because of technical difficulties during a previous dilation and curettage and the expense of long-term GnRH agonist therapy, the patient elected to undergo intracavitary radiotherapy. CONCLUSION: In selected patients, intracavitary radiotherapy can be used to treat DUB when conventional therapy fails or is contraindicated.     

A review of the relationship between parenteral nutrition and metabolic bone disease.

Metabolic bone disease (MBD) refers to the conditions that produce a diffuse decrease in bone density and strength because of an imbalance between bone resorption and bone formation. MBD can be a potential complication in patients receiving chronic parenteral nutrition (PN) therapy and the management of this condition presents a challenge for many clinicians. The etiology of PN-associated MBD is poorly understood, but traditional risk factors can include malnutrition, vitamin and mineral deficiencies, toxic contaminants in the PN solution, concomitant medications, and presence of certain disease states. Although additional studies are warranted to further elucidate the development and management of this condition, the following review discusses some of the important factors that may play a role in the genesis of PN-associated MBD and evaluates some potential strategies for the diagnosis and treatment of this complication.     

Safety of drugs commonly used to treat hypertension, dyslipidemia, and Type 2 diabetes (the metabolic syndrome): part 2

It is becoming increasingly acknowledged that people with Type 2 Diabetes represent what can be termed "an enriched population": a group that has the greatest risk of morbidity and mortality from cardiovascular diseases such as myocardial infarcts and strokes. Due to the tremendous toll, both human and financial, that these cardiovascular diseases result in, major efforts are being put forth to decrease their occurrence. It is clear that success in this endeavor is optimized by achieving target levels of glucose, blood pressure, and cholesterol. Analysis of the individual drugs used to treat these comorbidities of the cardiovascular dysmetabolic syndrome has brought an understanding that frequently monotherapy is ineffective, and a clear appraisal of the benefits of available pharmaceuticals can result in a successful decision about which agents to include in regimens of combination therapy. This success translates into ultimately reducing the untimely death and disability that is unfortunately all too common among the people with these illnesses. As diabetes continues to be increasing alarmingly among all segments of the population, there is an urgency for this need. The knowledge is present; only the application is not.     

Longitudinal prospective study of headache during pregnancy and postpartum

Chronic headache fluctuates in response to changes in hormonal levels. Headache generally improves with rising estrogen levels, and worsens with falling levels. Headache should, therefore, predictably improve with pregnancy and worsen postpartum. Several retrospective studies have confirmed this pattern. In this study, 49 pregnant women with chronic headache (18 with migraine, 16 with tension-type, and 15 with combined migraine and tension-type) were followed prospectively. Headache activity was recorded daily throughout pregnancy and for 3 months postpartum. Overall, there was a 30% improvement in headache between the second and third trimesters for the entire sample. This was not statistically significant. Headache improved significantly for 41% of the women, with a slightly greater tendency for headache to improve in women with migraine compared to those with tension-type or combined migraine and tension-type headaches. Headache activity was not influenced by history of menstrual migraine, history of headache change with prior pregnancies, parity, or breast-feeding. In general, women reporting headache at the end of their first trimester continued to report headache throughout pregnancy and postpartum.