Adenosine as a vasodilator in primary pulmonary hypertension

BACKGROUND. The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients. METHODS AND RESULTS. The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner. CONCLUSIONS. Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension.     

Questionnaire analysis of the swallowing‐related outcomes following total laryngectomy

Objective: To determine the effects of a total laryngectomy on the swallow and subsequent quality of life in head and neck cancer patients. Design: Cross‐sectional single centre cohort study. Setting: Head and Neck Oncology Unit, Tertiary Referral Unit. Patients: Sixty‐two patients who underwent total laryngectomy at our centre participated in the study. Methods: Subjects were stratified by age, sex, tumour stage, other procedures such as myotomy and nerve re‐implantation. Pharyngectomy, glossectomy, flap reconstruction, neck dissection and previous radio‐ and chemotherapy were also assessed to see if they affected swallow and subsequent quality of life. Main outcome was measured using the MD Anderson Dysphagia Inventory questionnaire. Results: Responses were received from 46 males and 16 females (response rate of 80.5%) with a mean age of 64.7 years (SD 9.4). Median follow‐up in patients was 90 months (range 1–276). The mean MD Anderson Dysphagia Inventory total score in our series of patients was 77.7 (SD 16.6). MD Anderson Dysphagia Inventory global score was 79.4 (SD 22.6), Emotional score was 77.7 (SD 17.8), Functional score 81.3 (SD 15.9) and Physical score was 74.1(SD 18). Statistically significant differences were seen between the emotional scores of glossectomised and non‐glossectomised patients (Mann Whitney, P = 0.04). No significant correlation was seen between the subscale scores and the remaining treatment variables such as age, gender, site, tumour stage, myotomy, nerve implantation, radiotherapy, reconstruction and major complications. Conclusion: This questionnaire study is the largest of its type to assess the swallow of patients who have undergone laryngectomy at a single centre. The overall result confirmed that most patients had a subjectively good swallow. Only glossectomy and the method of PE segment closure were shown to significantly affect swallowing outcomes following surgery. We recommend further work especially prospective studies pre and post surgery using this or similarly validated instruments to fully assess swallow in the laryngectomy population.     

Haemodynamic assessment of the femoropopliteal segment: comparison of pressure and Doppler methods using ROC curve analysis

Combined aorto-iliac and femoropopliteal vascular disease remains a problem in vascular surgery. Arteriography does not provide information on the relative contributions of the two lesions to the presenting symptoms. Aorto-iliac haemodynamics may reveal occult aorto-iliac disease but does not show whether combined proximal and distal reconstruction will be required to provide symptomatic relief. Haemodynamic assessment of both segments may help in this respect. A haemodynamic assessment of the femoropopliteal segment of 72 limbs in 38 patients is reported. The segmental pressure drop between a common femoral arterial cannula and a below-knee occlusion cuff is compared with a non-invasive Doppler method combining both transit time and damping factor. Comparison is made using receiver operating characteristic (ROC) curve analysis. The measurement of segmental pressure drop is more accurate than the Doppler method in detection of femoropopliteal stenoses of greater than 50 per cent of the luminal diameter (P less than 0.05).     

Use of steroids to suppress vascular response to radiation

A quantitative measure of the vascular permeability surface area product (PS) for albumin has been made using a double isotope technique. PS was significantly elevated in irradiated rat lung, heart, skin, and muscle, between 19 and 26 days following 18 or 25 Gray thorax irradiation. Administration of dexamethasone from 2 days before irradiation through the day of measurement suppressed the expected increase in PS in lung, heart, and muscle, but not in skin. Shorter periods of steroid administration were not as effective in suppressing this response to radiation exposure. Increased vascular permeability following radiation may be an essential element in the development of radiation fibrosis. We hypothesize that the ability to suppress this response could result in a long term reduction in the incidence of fibrosis.     

Technical Note: A comparison of a novel direct ophthalmoscope, the OptyseTM, to conventional direct ophthalmoscopes

Despite the current popularity of binocular indirect ophthalmoscopy, direct ophthalmoscopes are still commonly used by clinicians for fundus examination. They are considered to be expensive, however, and it has been suggested that this cost can prevent their use by healthcare professionals in developing countries. The Optyse Lens Free Ophthalmoscope is a novel direct ophthalmoscope, without a lens focus system, that allows for comparatively inexpensive manufacture and supply. We compared the clarity of view with the Optyse to that with standard direct ophthalmoscopes, over a sequential cohort of patients with a variety of refractive errors and ocular conditions. The grade of clarity of view with the Optyse Lens Free Ophthalmoscope was less than conventional ophthalmoscopes (Wilcoxon signed rank test, p < 0.0001). This grade of clarity of view was not associated with the ametropia of the ophthalmoscopic observation (Spearman r < or = 0.03, p > or = 0.28) but was with the presence of cataracts (chi2 test, p < 0.0001) with both the Optyse and the conventional ophthalmoscopes. Despite its limitations, the retinal view with Optyse was often within acceptable clinical limits suggesting that this relatively inexpensive ophthalmoscope may have a place when cost prohibits any other type of ophthalmoscope use.     

Effects of inorganic and triethyl lead and inorganic mercury on the voltage activated calcium channel of Aplysia neurons.

Using conventional two electrode voltage clamp techniques we have studied the effects of Pb2+, triethyl lead (TEL) and Hg2+ on voltage-activated calcium channels of Aplysia neurons and found that all three metals are potent inhibitors at micromolar concentrations. However, the time course of current reduction or block and its reversibility vary when comparing Pb2+ to TEL and Hg2+. With application of Pb2+ the calcium current decreases immediately and a steady state is reached within three to seven minutes, depending upon the concentration of Pb2+ (IC50 = 61 microM). The block was easily reversed upon wash out of Pb2+ with a time course similar to that of onset. Perfusion with either TEL (5 to 50 microM) or Hg2+ (5 to 200 microM) resulted only in a small reduction of current when the substances reached the cell membrane but with clear reduction within 2 min. The decrease continued at about the same speed for the total duration of the application. Upon washing there was no recovery of the response. At the onset of washing the rate of current decline stopped for several minutes, but then the current continued to decline at a slower rate in the absence of toxicant. Our data suggest that Pb2+ acts by a direct and reversible blockade of the calcium channel. In contrast TEL and Hg2+ act slowly and irreversibly to block calcium channels at concentrations which do not greatly affect membrane potential or resistance. In spite of the slow time course these substances are probably acting directly on the calcium channel.     

PCR-SSO typing for DR4-Dw subtypes: application to unrelated bone marrow transplant donor selection

Thirty-seven DR4-positive patient-unrelated bone marrow donor pairs previously DR/DQ restriction fragment length polymorphism (RFLP) typed and tested in mixed lymphocyte culture (MLC), have been DR4-Dw subtyped retrospectively using sequence specific oligonucleotide probes. We found that DR4-Dw subtyping substantially increased the accuracy of pre-MLC matching and could potentially accelerate donor searches by avoiding unnecessary MLC tests on Dw-mismatched donors.     

Pleomorphic adenoma arising in a salivary rest in childhood.

Two children with pleomorphic adenomas developing in heterotopic salivary tissue are presented. These are unusual lesions, rarely seen in adults and not previously described in the pediatric age group.