SUMMARY1. The circulatory and respiratory responses to severe arterial hypoxia were studied in normal rabbits, 'de-efferented' rabbits without functioning autonomic effectors, and atropinized animals before anaesthesia and during chloralose-urethane and sodium pentobarbitone anaesthesia. Net systemic autonomic activity and autonomic activity to the heart was assessed from a comparison of the responses of the various preparations.2. In the normal spontaneously breathing animal each anaesthetic had a similar mode of action, and modified qualitatively the circulatoryresponse present before anaesthesia. In the 'de-efferented' animal the circulatory response was determined by the local effects of hypoxia, and was altered only quantitatively during anaesthesia.3. In the normal unanaesthetized animal the reflex changes in autonomic activity during hypoxia consisted of a large increase in vagal efferent activity, a decrease in cardiac sympatho-adrenal activity, and an increase in total sympatho-adrenal constrictor activity. 4 In hypoxia during anaesthesia the vagal efferent activity no longer increased, but the change in sympatho-adrenal activity to heart and systemic circulation was the same as before anaesthesia in the spontaneously breathing animal. During anaesthesia with controlled ventilation systemic sympatho-adrenal activity increased further, and brady-

In order to determine the late results of reconstructive surgery for renovascular disease, a review was made of a series of 505 consecutive patients who underwent operation over a 20-year period. There were 257 males (50.9%) with an age range of 3-80 years. Renal artery bypass grafts were used in 75.4% (471/625) and thromboendarterectomy and/or patch angioplasty in 15.0% (94/625) of reconstructions. Associated vascular procedures were performed in 38.0% (186/489) of patients. Operative mortality (30-day) was 1.8% (9/489) overall, and 4.8% (9/186) with associated procedures but there was no operative mortality in 303 consecutive isolated renal artery reconstructions. The blood pressure was normal or improved in 65% of patients at a mean follow-up interval of 49.3 months, range 1-240 months. The best response rate was obtained in younger patients with isolated renal lesions. Linear regression analysis showed age at operation to be the most important determinant of blood pressure response (p < 0.003) with the presence or absence of diffuse atherosclerosis as another but less powerful determinant of responsiveness (p < 0.07). Crude 15-year survival was 70% (340/489). The overall five- and ten-year actuarial survival probabilities were 80 and 62% respectively. The most common causes of death were myocardial infarction, stroke, and cancer. Cox regression analysis for variables influencing survival indicated that age at operation (p < 0.001), sex (p < 0.01) and the presence or absence of fibromuscular disease (p < 0.002) were the major determinants of late survival with persistent severe hypertension exerting an important but lesser influence. The results of this study indicate that about two-thirds of patients will experience long-term relief of hypertension after operation and that the best long-term survival and blood pressure relief will be obtained in patients less than 50 years of age. Because hypertension in females is better tolerated, younger, male patients appear to have the most to gain from successful renovascular reconstruction.

Motivation Polymerase chain reaction (PCR) has been a revolutionary biomedical advancement. However, for PCR to be appropriately used, one must spend a significant amount of effort on PCR primer design. Carefully designed PCR primers not only increase sensitivity and specificity, but also decrease effort spent on experimental optimization. Computer software removes the human element by performing and automating the complex and rigorous calculations required in PCR primer design. Classification and review of the available software options and their capabilities should be a valuable resource for any PCR application. Results This paper focuses on currently available free PCR primer design software and their major functions (https://pcrprimerdesign.github.io/). The software are classified according to their PCR applications, such as Sanger sequencing, reverse transcription quantitative PCR, single nucleotide polymorphism detection, splicing variant detection, methylation detection, microsatellite detection, multiplex PCR and targeted next generation sequencing, and conserved/degenerate primers to clone orthologous genes from related species, new gene family members in the same species, or to detect a group of related pathogens. Each software is summarized to provide a technical review of their capabilities and utilities.

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Although blood spread of pulmonary malignancy presumably occurs through microembolization, frank embolization of tumor fragments is uncommon. The first reported case of bronchogenic carcinoma appearing as a peripheral arterial embolus is described. The patient, a 64-year-old female, had acute ischemia of the left leg secondary to tumor embolism to the left profunda femoris and popliteal arteries. Shortly after embolectomy, she suffered atelectasis of the whole left lung from an epitheloid carcinoma in the left main bronchus. Twenty-eight cases of frank tumor embolism to the arterial tree occurring during the course of a noncardiac malignancy have been reported. None, however, occurred as an initial event. Pulmonary metastasis in patients with advanced malignancy was the source of the arterial emboli in 45% (13/29) of reported cases, but bronchogenic carcinoma was the original cell type in 38% (11/29) of cases. In general, arterial tumor embolism is a complication of advanced malignancy usually originating from one of multiple pulmonary metastases. This first case report of tumor embolism to a lower extremity occurring as the initial event in the clinical course of a bronchogenic carcinoma serves to emphasize the protein manifestations of malignant disease.

In an attempt to improve the accuracy of central venous pressure (CVP) catheter tip location, 84 consecutive cardiac surgery patients in sinus rhythm were studied prospectively with respect to subclavian insertion of a CVP catheter using a guidewire technique. The presence of cardiac arrhythmia was used as an index of right atrial (RA) location of the guidewire tip, before threading the catheter over the guidewire. Correct catheter tip location (superior vena cava [SVC] or RA) was achieved in 100% of patients (N = 78) with premature atrial contractions (PACs) related to guidewire insertion. This fell to 50% (N = 4) if no arrhythmias were noted from the guidewire. Ventricular arrhythmias were noted in two of 84 patients (2.4%). Other problems related to the use of this technique are discussed.

From 1967 to 1979, 25 patients (pts) were operated on for fibromuscular disease (FMD) of the internal carotid artery (ICA). Eleven patients (44%) had transient weakness of an extremity, 4 had amaurosis fugax and 6 (24%) had an asymptomatic carotid bruit. Bilateral carotid arteriography showed significant stenotic lesions in 23 pts (92%) (bilateral in 10), arterial dissection in 1, and severe associated atherosclerosis with ICA endarterectomy and graduated internal dilatation (GID) (9 bilateral); 2 underwent GID with ICA endarterectomy and patch graft: 1 pt had tube graft replacement of the ICA. There was no operative mortality. One pt had a stroke during operation after tube graft replacement of the ICA. Of the 19 pts followed for 2 to 12 years (mean 7.3 years), 2 had late recurrence of mild symptoms. One pt required GID of the contralateral ICA recurrence of symptoms 4 years postoperatively. Graduated internal dilatation of fibromuscular disease of the internal carotid artery can produce long term relief of symptoms; recurrence is rare.

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