Life-saving Effect Research Articles

Efficacy of the Inflammatory Cell Infiltration Inhibitor IS-741 on Colitis Induced by Dextran Sulfate Sodium in the Rat

We examined the therapeutic effects of the inflammatory cell infiltration inhibitor IS-741 (N-(2-((ethylsulfonyl)amino)-5-(trifluoromethyl)-3-pyridinyl)-cyclohexanecarboxamide monosodium salt mono-hydrate) on a rat colitis model. As a result of its effects on leukocyte infiltration, IS-741 inhibits cell adhesion, alleviates symptoms and signs of pancreatitis and multiple organ failure and demonstrates a life-saving effect in a model of severe acute pancreatitis. A rat model was prepared by inducing colitis with 3% dextran sodium sulfate (DSS) and maintaining pathology with 1% DSS. Repeated oral administration of IS-741 at 1, 10 or 100 mg /kg per day was conducted for 2 weeks (during treatment with 1% DSS). IS-741 at each dose decreased the area of erosion in the large intestine, thickening of the wall of the large intestine and anemia caused by melena. Some effects of IS-741 were nearly equivalent to those of the control compound salazosulfapyridine. Furthermore, IS-741 markedly alleviated inflammatory cell infiltration into the intestinal wall. IS-741 improved lesions in a rat DSS model by inhibiting leukocyte infiltration, suggesting the possibility of clinical application of this drug for IBD.

Reversal of slow flow phenomenon during primary stenting by bail-out administration of abciximab.

BACKGROUND: Slow flow or no reflow phenomenon is increasingly being recognized as a serious problem during coronary angioplasty and stenting. This phenomenon is seen more often during angioplasty in highly thrombogenic milieux, especially in a setting of acute myocardial infarction. The treatment of this complication is often not satisfactory. In this study the authors assessed the efficacy of abciximab, a potent antiplatelet drug, in treating slow flow or no reflow phenomenon during primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI). METHODS: Twenty-one instances of persistent slow flow phenomenon were encountered in 131 consecutive patients subjected to primary PTCA for AMI (16%). It was more common in patients presenting with AMI complicated by cardiogenic shock (nine of 21, 43%). Of these 21 cases of slow flow, 10 patients were given injection abciximab during the procedure of primary PTCA as a bail-out measure after encountering the complication of slow flow or no reflow. A pre-discharge coronary angiography was carried out in all patients who survived. RESULTS: In seven of 10 patients in the abciximab group flow had improved to TIMI-3. In contrast, in the non-abciximab group TIMI flow improved in only four of 11 patients. Patients with persistent slow flow had significantly higher mortality at the first 30-day follow-up than patients with TIMI-3 flow (33% versus 1.8%, p<0.001). CONCLUSION: In this small nonrandomized study significant improvement in coronary flow was achieved by using intravenous abciximab after observing slow flow or no reflow phenomenon during primary PTCA. More frequent use of this drug in this milieu might help in preventing the development of this complication. Larger studies are warranted to confirm this life-saving beneficial effect of bail-out administration of abciximab during primary angioplasty.

Validating analytical judgments: the case of the airbag's lifesaving effectiveness

Abstract Based primarily on experimental testing and engineering judgment, early evaluations of airbags made variable predictions of their lifesaving benefits. The official estimates of the US government from 1977 to 1987 were that between 6000 and 9000 lives could be saved each year if all passenger cars were equipped with full-front airbags. Now, over a decade later, extensive real-world crash experience in the US has been analyzed to validate early predictions. Lifesaving estimates have been revised downward and the official US government position in 1997 was that, overall, approximately 3000 lives will be saved each year when the vehicle fleet is fully-equipped with frontal airbags. This article explores the reasons for poor validity of early lifesaving forecasts for airbags. We found that airbag effectiveness for unbelted adult occupants was overestimated, the number of adult motorists who would wear safety belts was underestimated, and that early analyses generally did not adequately address heterogeneity in the vehicle fleet or people. For each source of error, we discuss why technical specialists may have erred and what lessons can be gleaned from this case study in validation.

High blood levels of nitric oxide in rats subjected to prolonged respiratory arrest and their modulation during adrenocorticotropin-induced resuscitation.

Anaesthetized rats, endotracheally intubated and mechanically ventilated with room air, were subjected to a 5-min period of asphyxia by turning off the ventilator. The ventilator was then turned back on and, simultaneously, the animals were treated with either the adrenocorticotropin fragment 1-24 [ACTH-(1-24), 160 microg/kg in a volume of 1 ml/kg i.v.] or an equivalent volume of saline. Nitric oxide (NO)-haemoglobin formation was detected ex vivo in arterial blood by electron spin resonance spectrometry; arterial blood pressure, electrocardiogram (ECG) and electroencephalogram (EEG) were monitored for a 60-min observation period, or until prior death. During asphyxia, there was massive formation of NO (red cell concentrations 40-80 microM), associated with a dramatic fall in mean arterial pressure and pulse pressure, marked bradycardia and ECG signs of ischaemic damage, as well as an isoelectric EEG. Treatment with ACTH-(1-24) produced a prompt (within 15 min) and long-lasting drop in NO blood levels, associated with an almost immediate (within 1 min) restoration of cardiovascular function and with a more gradual recovery of EEG, which became normal after 3040 min; all parameters remained stable throughout the 60-min observation period. In saline-treated rats, on the other hand, there was a further increase in NO blood levels, as detected 3 min after treatment, and all died within 5-8 min. Moreover, pretreatment and treatment with S-methylisothiourea sulphate (SMT, 3 mg/kg i.v.), a relatively specific inhibitor of inducible NO synthase, inhibited NO formation, but did not affect the mortality rate (100% within 5-8 min). The present results provide the first evidence that prolonged asphyxia is associated with high blood concentrations of NO, and that the life-saving effect of melanocortin peptides in severe hypoxic conditions is associated with a complete normalization of NO blood levels. However, the lack of SMT protection in this experimental model seems to rule out the possibility that the ACTH-(1-24)-induced resuscitation is due to an effect on NO overproduction.

Emergency Bronchoscopy

A retrospective analysis was performed to study the efficacy and safety of bronchoscopy in emergency patients. Of the 577 emergency patients, 172 (29.8%) underwent a total of 191 emergency bronchoscopies for diagnostic and/or therapeutic purposes. The patients ranged in age from 4 days to 89 years (average, 39.8 years), and included 33 neonates and infants (< 2 years). Major indications for emergency bronchoscopy were atelectasis/airway mucus retention, adult respiratory distress syndrome or pulmonary edema, airway stenosis, pneumonia/empyema, airway bleeding, obstruction of the airway by a foreign body or aspiration, difficulty with intubation, and airway anomaly. Nineteen patients with life-threatening respiratory crises were saved as a direct result of the bronchoscopic procedures. In 72 of the 172 emergency patients (41.9%), bronchoscopy provided definitive diagnoses where other diagnostic modalities failed. Severe hypoxia and bradycardia during bronchoscopy were observed in two patients, but no deaths or serious complications were induced by bronchoscopic procedures. We conclude that bronchoscopy is indispensable for the management of emergency patients because of its life-saving and diagnostic effectiveness and is safe to perform even in high-risk situations.

Massive pulmonary hemorrhage in newborn infants successfully treated with high frequency oscillatory ventilation.

Massive pulmonary hemorrhage (MPH) in newborn infants is a catastrophic event with a fatal result. The aim of this study was to assess the efficacy of high frequency oscillatory ventilation (HFOV) as a rescue therapy for MPH in newborn infants. Eighteen newborn infants with MPH refractory to conventional mechanical ventilation were treated with HFOV. Changes in oxygenation were assessed using arterial-alveolar oxygen tension ratio (a/APO2) and oxygenation index (OI) during HFOV. The most common underlying disorder of MPH was preterm patent ductus arteriosus (PDA). Thirteen out of 18 (72%) newborn infants with MPH responded to HFOV and survived. Five out of 18 (28%) did not respond to HFOV and died. There were no differences between responders and nonresponders in gestational age, birth weight, pre-HFOV OI, and age of MPH onset. In responders, there was a rapid increase in a/APO2 from 0.18+/-0.04 to 0.40+/-0.08 at 30 minutes after HFOV. There was also significant decrease in OI from 14.9+/-4.7 to 8.1+/-1.5 at 1 hour after HFOV. We conclude that HFOV shows rapid and dramatic improvements and has ultimately life-saving effects in MPH of newborn infants.

Physostigmine has a life-saving effect in rats subjected to prolonged respiratory arrest

We have previously reported that centrally-acting cholinomimetic drugs have a prompt and sustained resuscitating effect in pre-terminal conditions of hemorrhagic shock in rats. Here we have studied the effect of physostigmine in another experimental condition of hypoxia in anesthetized rats, which were endotracheally intubated and subjected to prolonged (5 min) interruption of ventilation. This led to a dramatic fall in mean arterial pressure (MAP), pulse pressure (PP), heart rate (HR), pH, PO 2, SO 2 and base excess, while PCO 2 increased; the electroencephalogram (EEG) became isoelectric, and the electrocardiogram (ECG) showed marked bradycardia, P-wave inversion, partial atrio-ventricular block and S-T segment elevation; all saline-treated rats died of cardiac arrest within 7.01±0.85 min of ventilation being resumed. When ventilation resumption was associated with the simultaneous intravenous (i.v.) injection of physostigmine (70 μg/kg) there was an almost immediate and impressive increase in MAP, PP and HR, with normalization of ECG within 4 min and full recovery of EEG after 30–50 min. This was associated with a normalization of blood gases and pH. Fifteen days later 40% of treated animals were still alive and apparently in normal health, the mean survival time of the remaining 60% animals being 22.67±10.19 h. Pretreatment with atropine sulfate or hemicholinium-3 did not modify the response to physostigmine, which, however, was strongly antagonized by the intracerebroventricular injection of mecamylamine. These results suggest that centrally-acting cholinomimetic agents may have a resuscitating effect in pre-terminal conditions produced by prolonged asphyxia, probably through the direct activation of nicotinic receptors in the central nervous system.

Neue Airbag-assoziierte Verletzungsmuster nach Verkehrsunf�llen

Experimental studies have shown that in traffic accidents with frontal impact the new airbag system can significantly reduce the incidence of severe injuries and fatal outcome. The question of whether the airbag itself induces specific patterns of injury needs further investigation. Two cases of traffic accidents with airbag protection are presented here. The first case report clearly shows the life-saving and injury-reducing effect of the airbag system in a traffic accident with frontal impact at 100 km/h. In the second case only minor injuries of the face were diagnosed initially. Hemodynamic instability occurred after 3 h of hospitalization due to rupture of the azygos vein. Analysis of the presented cases shows that, besides the well-known benefits, there are certain injury patterns that seem to be related to the use of airbags. These have not been described before. It is concluded that patients who were involved in traffic accidents with airbag deployment have to be hospitalized and followed up carefully over time, even though they are initially stable, as potentially fatal sequelae of deceleration trauma can occur later. In our opinion it is not possible to estimate the severity of airbag-associated injuries with conventional methods.

Time to thrombolytic treatment: Factors affecting delay and their influence on outcome

One of the major limitations to realizing the full potential of the life-saving effects of thrombolytic therapy has been the failure to initiate treatment in the first 1 to 1.5 h after symptom onset. The barriers to early treatment include the following: 1). Most patients fail to react rapidly and appropriately to symptoms. 2) Few emergency medical/paramedic systems have established effective traige systems for patients with chest pain or have implemented prehospital electrocardiography to better manage patients with possible acute myocardial infarction. 3) Time to treatment after hospital arrival currently averages 1 to 1.5 h—two to three times longer than what should be necessary to initiate therapy in the patients with typical electrocardiographic and clinical findings and co-morbid risk factors. Trials evaluating the effects of prehospital-initiated therapy have all shown trends toward a reduction in mortality (1.8%) associated with early treatment; however, none has been large enough in and of itself to be conclusive. The goal in the corning years will be to decrease each of these components of delay by developing effective education programs for the lay public speeding and improving prehospital care by the routine use of electrocardiography and reducing hospital treatment times to ≤ 30 min in the “uncomplicated” patient.

Time to thrombolytic treatment: Factors affecting delay and their influence on outcome

One of the major limitations to realizing the full potential of the life-saving effects of thrombolytic therapy has been the failure to initiate treatment in the first 1 to 1.5 h after symptom onset. The barriers to early treatment include the following: 1). Most patients fail to react rapidly and appropriately to symptoms. 2) Few emergency medical/paramedic systems have established effective traige systems for patients with chest pain or have implemented prehospital electrocardiography to better manage patients with possible acute myocardial infarction. 3) Time to treatment after hospital arrival currently averages 1 to 1.5 h—two to three times longer than what should be necessary to initiate therapy in the patients with typical electrocardiographic and clinical findings and co-morbid risk factors. Trials evaluating the effects of prehospital-initiated therapy have all shown trends toward a reduction in mortality (1.8%) associated with early treatment; however, none has been large enough in and of itself to be conclusive. The goal in the corning years will be to decrease each of these components of delay by developing effective education programs for the lay public speeding and improving prehospital care by the routine use of electrocardiography and reducing hospital treatment times to ≤ 30 min in the “uncomplicated” patient.

Life-saving effect of pyridoxalated hemoglobin-polyoxyethylene conjugate on carbon monoxide intoxication of rabbits.

We examined whether pyridoxalated hemoglobin-polyoxyethylene conjugate (PHP) could be life-relievable for carbon monoxide (CO) intoxication. Toxic gas (O2, 5.0%; CO2, 16.0%; CO, 1.8%; and N2, 77.2%) was inhaled by rabbits anesthetized with urethane and the following parameters were measured: blood pressure, arterial and venous Po2, Pco2, pH, and carboxyhemoglobin (COHb). When mean blood pressure reached 0 or 20 mm Hg as an index after inhalation of the toxic gas, the toxic gas was switched to air; intravenous infusion of physiological saline or PHP (1.2 g/20 ml/kg/30 min) was simultaneously initiated. In the experiment using 0 mm Hg blood pressure, PHP prolonged the survival time and exhibited significant temporary recovery of P02 and Pco2 in comparison with saline. In the experiment using the 20 mm Hg blood pressure, a significant difference in each parameter was observed between the saline and PHP groups. Two of 8 animals in the saline group died without any recovery of each parameter. All 6 animals in the PHP group survived and each parameter recovered. PHP accelerated recovery from high COHb concentrations, low arterial and venous Po2, reduction of arterial and venous Pco2, and elevations of pH and blood pressure. These results suggest that PHP treatment during the early stage of CO intoxication is life-saving and effective in facilitating the recovery of various functions.

The use of antihypertensive agents in prevention and treatment of diabetic nephropathy

Diabetic nephropathy is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h), a relentless decline in glomerular filtration rate, and elevated systemic blood pressure. The prevalence of an abnormally elevated albumin excretion rate (> 30 mg/24 h) is approximately 40% in patients with both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Diabetes has become the leading cause of end-stage renal failure in the United States and Japan and it is still the second leading cause in Europe. Identification of patients at high risk of developing diabetic nephropathy is possible by screening for microalbuminuria (30 to 300 mg/24 h). Randomized controlled trials in normotensive IDDM and NIDDM patients with persistent microalbuminuria indicate that angiotensin-converting enzyme (ACE) inhibitors diminish urinary albumin excretion rate and postpone or may even prevent progression to clinically overt diabetic nephropathy. These findings suggest that screening and intervention programs are likely to have life-saving effects and lead to considerable economic savings. High blood pressure is an early and frequent phenomenon that can accelerate the course of diabetic nephropathy. Besides ACE inhibitors, conventional antihypertensive treatment (mainly beta-blockers and diuretics) reportedly reduce albuminuria and diminish the loss of kidney function in IDDM patients with diabetic nephropathy. The same beneficial effect has been demonstrated using ACE inhibition combined with diuretics in hypertensive IDDM patients with overt nephropathy.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of full-time, specialized physician supervision on the success of a large, urban emergency medical services system

Despite the universal proliferation of emergency medical services programs throughout the United States since 1970, only a few have ever documented a valid lifesaving effect, particularly in large, urban centers. The purpose of this study was to demonstrate the effect of specialized physician supervision on the effectiveness of an emergency medical services system. Prospective, cohort study. Large, urban municipality (population 2 million). Evaluation of victims of out-of-hospital sudden cardiac death cases, before (n = 152) and after (n = 200) the introduction of specialized physician supervision for the emergency medical services system. The hiring of a full-time, salaried emergency medical services system physician whose principal duties would be to provide intensive individualized training, direct operational supervision, and continuous system monitoring, including frequent on-scene oversight of emergency medical services personnel. Comparison of existing hospital discharge rates for out-of-hospital sudden cardiac death cases to those rates achieved 5 yrs after recruitment of the specialized emergency medical services system physician. A dramatic increase in hospital discharge rates was demonstrated for sudden death patients presenting with ventricular fibrillation, from zero at year 0 (0 of 152 patients survived), to 21% (42 of 200 patients) by year 5 (p < .001). This result was achieved despite the fact that all other related factors (budget, paramedic numbers, response times) significantly worsened during the comparison periods. The introduction of the new factor into the emergency medical services system (specialized physician supervision) was associated with significantly improved patient outcome. In view of current suboptimal outcome statistics found in most municipal emergency medical services programs across the United States, future goals of medical community leaders should be directed at efforts to properly train, certify, and establish appropriate positions for physicians who specialize in emergency medical services system supervision.

Near fatal pulmonary hypertension after surgical repair of congenital diaphragmatic hernia

The addition of 10-20 parts per million nitric oxide to the inspired gas was successful in controlling near fatal pulmonary hypertension after surgical repair of a congenital diaphragmatic hernia in a neonate. A preceding prostacyclin infusion was unable to prevent the failure of pulmonary perfusion. No side effect of nitric oxide therapy was observed, and ventilatory support could be substantially reduced as a result of the treatment. On the basis of the striking and lifesaving effects of nitric oxide therapy demonstrated in this child, we believe that nitric oxide treatment will prove to be a major contribution to the management of postoperative pulmonary hypertensive crises.

Determination of molar mass and molar mass distribution of blood plasma substitutes (plasma expanders)

Blood plasma substitutes, such as dextran and hydroxyethyl starch, cause an expansion of the liquid volume in blood vessels due to their high colloid-osmotic pressure and water-binding potential, and are therefore applied clinically as so-called plasma expanders for rapidly increasing the liquid volume. This potentially life-saving effect only applies while the plasma substitute is present in the bloodstream. For this reason knowledge of the retention time is of great importance. As the retention time is directly related to the molecular weight distribution of polydisperse hydrocolloids, an estimation of the parameters of this distribution is therefore of crucial significance in the quality control of plasma expanders. Besides absolute methods (e.g. GPC/LALLS), there is special interest in GPC as a relative method with calibration against narrow molecular weight standards. This is because of its wide distribution, the speed at which it can be carried out, and the low expenditure on apparatus. Furthermore, there are advantages if commonly accepted pharmacopoeial methods can be performed in a manner that allows the results to be compared easily. In order to implement the molecular weight determination method in Pharmacopoeia Nordica's (Ph.Nord, or Svensk Läkemedelsstandard “SLS”) dextran monograph, a suitable software for VAX computers was developed at the Max Planck Institut für Kohlenforschung in Mülheim/Ruhr.

TRANSMITTER INTERACTIONS IN THE CENTRAL CHOLINERGIC CONTROL OF BLOOD PRESSURE REGULATION

There are at least five mechanisms by which the central nervous system regulates neural and humoral systems that control the blood pressure (BP). Particular attention has been paid to central cholinergic-adrenergic interactions in the regulation of BP. Physostigmine and other anticholinesterases which penetrate the blood-brain barrier, both carbamates and organophosphates, produce an increase of BP. This effect can be abolished by atropine, but not by methylatropine. The available evidence indicates that physostigmine and other AChE inhibitors initially produce an activation of central muscarinic receptors, which subsequently leads to an increase of the peripheral adrenergic activity. The hypertensive response to physostigmine is possible only if a functionally competent ChE is present in the brain. This effect of physostigmine is regularly associated with a dose-related increase in the neural activity in the preganglionic fibers of the cervical sympathetic nerve. BP rise after physostigmine is significantly less in immunosympathectomized animals and almost completely abolished after chemical sympathectomy. Physostigmine significantly increased the plasma concentration of catecholamines. After electrocoagulation of the locus coeruleus, not only did a significant decrease occur in the basic level of noradrenaline in plasma, but there was also a strong depression of the noradrenaline plasma response to physostigmine and immobilization. Physostigmine increased lipolysis and glycogenolysis, whereas neostigmine did not produce any change. Several directly acting cholinergic agonists alter the functions of the cardiovascular system when injected directly into the cerebral ventricular system, or directly into various brain regions. The most probable sites of action of AChE inhibitors and directly acting cholinergic agonists are the locus coeruleus, the nucleus tractus solitarii and the rostral ventrolateral medulla (RVLM). The primary activation of the cholinergic synapse is believed to take place in RVLM. Met-enkephalin, Leu-enkephalin and beta-endorphin, when applied exogenously, depress or even abolish the hypertensive effect of physostigmine. The same type of response was obtained after application of substances which inhibit the enkephalin-degrading enzymes (bestatin, phosphoramidon). Thus, the exogenous or endogenous enkephalins activate the opioid receptors in the brain and at the same time produce a depression of the cholinergic-adrenergic interaction in the central nervous system, which is a prerequisite for the hypertensive response to physostigmine. The functional role of the central cholinergic mechanisms in BP control under physiological conditions has not been established with certainty. These mechanisms might have a more significant role under pathological or homeostatic disturbances. For example, physostigmine showed a life-saving effect in acute hypovolemic shock in rabbits.

The life-saving effect of physostigmine in haemorrhagic shock

The intravenous injection of physostigmine (70 micrograms kg-1) produces a life-saving effect in acute haemorrhagic shock in non-anaesthetized rabbits. This effect is most probably due to a transfer of tissue fluids into circulation. The crucial beneficial effect of physostigmine might be a decrease of the capillary hydrostatic pressure due to changes in pre- to postcapillary resistance ratio. Both lines of defence comprise a normalization of blood pressure and normalization of blood volume, thus saving the life of the animal.

Risk reduction or risk compensation? The case of mandatory safety-belt use laws

The technological approach to risk regulation seeks to lessen the incidence of mortality and morbidity by modifying environmental conditions. Insofar as risk-taking behavior is purposive, social scientists have predicted that technological progress may be negated by various forms of “risk compensation.” The validity of this hypothesis is tested in the transportation sector with data from the U.S. on the effects of new mandatory safety-belt-use laws. A fixed-effects model of traffic fatality counts is estimated using pooled data from 50 states during the 1975–1987 period. Results suggest that such laws have reduced mortality among car occupants to a degree that is compatible with the predictions of technologists. However, there is weak evidence of increased mortality among some nonoccupants, a pattern predicted by risk-compensation theorists. The lifesaving effects of belt-use laws are largest in states that permit primary police enforcement and appear to be somewhat larger for front-seat occupants age 21 and under. Although offsetting behavior appears to be small relative to lifesaving effects, it may take several more years for any compensatory behavior to achieve a new equilibrium.

Norrbottnian Type of Gaucher Disease – Clinical, Biochemical and Molecular Biology Aspects: Successful Treatment with Bone Marrow Transplantation

The Norrbottnian type of Gaucher disease is a well defined nosological entity with a characteristic course and clinical manifestations. The disease is caused by a deficiency of the enzyme glucosylceramidase (cerebroside-beta-glucosidase). Studies of genomic DNA and cDNA encoding the enzyme show a single base substitution in exon 10 in the Norrbottnian patients. The enzymic lesion causes an accumulation of glucosylceramide and glucosylsphingosine in cells of the monocyte-macrophage system, particularly in spleen, liver and bone marrow. Early splenectomy results in severe symptoms from skeleton and CNS, owing to accelerated storage of glucosylceramide in these organs. Bone marrow transplantation had a life-saving effect and seems to be the method of choice for beneficial enzyme replacement therapy.

The Introduction of Smallpox Vaccine in 1803 and the Adoption of Immunization as a Government Function in Puerto Rico

HE yelling could be heard in the street, two floors down. Young soldiers rushed up the stairs, in order not to miss the action, while other witnesses nearby must have wondered why one physician had not yet thrown the other off the balcony. One hundred sixty thousand persons in Puerto Rico all know about this affair, it has been so public and scandalous.' A king's physician, the royal commissioner, was publicly insulting the city doctor, the man who had brought smallpox vaccination to the island! It had been the Spanish king's intention that the first arrival of vaccine to his American and Asian colonies would be due to a Royal Philanthropic Expedition, directed by the renowned physician and botanist Francisco Xavier de Balmis.2 Nevertheless, the widespread fame of the method, a desperate need for its life-saving effects, its availability in nearby non-Spanish locations, and the resourcefulness of colonists served to anticipate the expedition's task in the Caribbean.