Actions of cisplatin on the electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats

In this study we have employed the whole cell patch clamp technique to investigate the effects of an anti-cancer drug cisplatin on basic electrophysiological properties of cultured dorsal root ganglion neurones from neonatal rats. The results show that within the clinical concentration range, cisplatin (0.1 to 10 microM) caused a decrease in input conductance, and complex changes in resting membrane potential in these cultured sensory neurones. The dominant effects of cisplatin on input conductance may be due to inhibition of leak conductances. Transplatin (5 microM) was significantly less effective than cisplatin at reducing input conductance which suggests a degree of stereoselectivity. Cisplatin (1 to 5 microM) transiently increased excitability of the cultured neurones as reflected by a reduction in the threshold for activation of action potentials by 8 mV. The rise time, peak amplitude and duration of action potentials were not changed by acute application of 5 microM cisplatin. Long term treatment of neurones with cisplatin (5 microM), for up to 1 week reduced the viability of the cultures, and attenuated neurone excitability, although input conductance of the cells was significantly increased to 322 +/- 49 M omega (n = 9) compared with controls of 210 +/- 20 M omega (n = 30; P < 0.05). Acute and chronic treatment of cultured neurones with cisplatin therefore produced contrasting actions.     

Pathogenetic aspects of the L-arginine-NO metabolic pathway in arteriosclerosis and possible therapeutic aspects

A yearly pattern in the occurrence of uterine cervical cancer (UCC), obtained from cytological examinations reported as type V (cases concluding a malignant alteration), has been previously shown for data obtained in the Monterrey Metropolitan Area (state of Nuevo Leon, Mexico) for a span of 10 years (1978-1987), with a peak of relative incidence in the month of February being high stable for consecutive years. With the aim of extending and validating those results, we analyzed the monthly totals of positive detected cases of UCC in the states of Nuevo Leon, Chihuahua, Coahuila, and Tamaulipas (covering most of Northern Mexico) during the same period. To eliminate bias due to the seasonal variation in the number of screening smears, data were first expressed in relation to the number of cytological examinations done the same month. The least-squares fit of a 1-year cosine curve to the data of relative incidence in the four states reveals a statistically significant yearly pattern (p = .008), with a maximum of relative incidence in February almost double that during the rest of the year. Results indicate that the relative incidence of UCC is higher than the yearly average during the winter, with secondary peaks in May and October. In view of the nonsinusoidal waveform in the incidence of UCC, we undertook a multiple-component analysis, allowing several cosine functions to be simultaneously fitted to the data. Results indicate that the yearly pattern in the relative incidence of UCC can be represented by a model that includes two components with periods of 12 and 4 months (p = .004). The same model can be documented as statistically significant independently for each of the four states. These results, summarizing over 2200 positive cases of UCC detected in more than 1,100,000 screening smears, are in full agreement with those found previously for part of the state of Nuevo Leon and reveal a highly stable and predictable yearly pattern of variation in the relative incidence of UCC in Northern Mexico.     

Cardiovascular effects produced by R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin in the preoptic area of conscious rats

The effect of ancrod-induced defibrinogenation on thrombosis and bleeding time was determined in anesthetized rats. Functional plasma fibrinogen levels were reduced 42, 71, 94 and 93% by ancrod doses of 5, 10, 20 and 30 U/kg, respectively, while a 2.5 U/kg dose was without significant effect. Ancrod inhibited vena cava thrombosis induced by partial stasis of blood flow combined with mild vascular injury. Thrombus weight was decreased 85 and 93% by the 10 and 20 U/kg doses, but was unaffected at lower doses. In contrast, ancrod doses of up to 30 U/kg did not significantly decrease carotid artery thrombi formed in response to oxidative transmural vessel injury. Ancrod caused a dose-dependent increase in bleeding time measured by puncturing small mesenteric arteries with a hypodermic needle. The bleeding time increase was approximately 38% in response to the 2.5 and 5 U/kg doses, and 182% in response to the 10 U/kg dose. These studies demonstrate that ancrod-induced reductions in plasma fibrinogen more effectively inhibit venous compared to arterial thrombosis, although these activities require doses that also increase bleeding time in small arteries.     

Electrical pacing of the paralyzed human larynx

This study represents the first attempt to electrically pace the paralyzed human larynx. The goal was to determine if electrical stimulation of the posterior cricoarytenoid muscle could produce functional abduction of the vocal fold in pace with inspiration. An external apparatus was used to sense inspiration and reanimate the unilaterally paralyzed larynx of a thyroplasty patient. Stimuli were delivered through a needle electrode to locate and pace the abductor muscle. The magnitude of electrically induced abduction was comparable to spontaneous movement on the normal side. The abduction was appropriately timed with inspiration: this finding demonstrated that this simple pacing system could effectively modulate stimulation with patient respiration.     

Outcome of patients with haemorrhagic shock: an indicator of performance in a trauma centre

The survival rate of patients admitted to the Royal Prince Alfred Hospital (RPAH) from the central Sydney area with a major injury has improved since regionalization of trauma services in early 1992. This improvement has been attributed to education, better hospital care and changing trauma epidemiology. This study was conducted to assess whether the outcome of patients admitted with haemorrhagic shock had improved. This is proposed as a more subtle indicator of hospital performance than overall survival rates. A prospective before and after study was carried out comparing outcome in the 18 months preceding 1 January 1992 with that in the subsequent 18 months. Entry criteria to the study included all primary retrievals from the central Sydney area to RPAH with injury severity scores (ISS) > 15. Outcomes were compared generally and in those who were in a state of haemorrhagic shock (systolic blood pressure < or = 90 mmHg) on arrival at the emergency department. Three hundred and eight patients were entered into the study. Stratification showed similar numbers, demographic features and mechanisms of injury in the two groups. Forty patients were in a state of haemorrhagic shock on admission. The overall mortality was reduced from 31% to 11% (P < 0.001) over the two phases of the study. The mortality from blood loss in the 40 shocked patients fell from 10/25 in the first period to 2/15 (P = 0.07) in the latter. These improved survival rates were felt to reflect the value of the educational and organizational initiatives introduced following designation of the hospital as a trauma centre.