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Biomedical subjects

M Giacomini

Publications and source records attributed to M Giacomini.

At least 19 recordsLinked to original sources

A change of heart and a change of mind? Technology and the redefinition of death in 1968.

In 1968, an ad hoc committee of Harvard faculty publicly redefined death as "brain death". What interests and issues compelled the redefinition of death, and formed the "spirit" of this precedent-setting policy? This paper reports on an historical study of the files of the Harvard ad hoc committee, the proceedings of an international conference on ethical issues in organ transplantation, and a review of the medical literature and media in the decades preceding the redefinition of death. This analysis of the technological and professional forces involved in the redefinition of death in 1968 questions two common theses: that technological "progress", primarily in the areas of life support and electroencephalography, literally created brain-dead bodies and dictated their defining features (respectively), and that Harvard's definition of brain death by committee constituted a net loss of autonomy for medicine. In fact, medical researchers through the 1960s disputed and negotiated many features of the brain death syndrome, and transplantation interests-perhaps more kidney than heart-played a particularly influential role in tailoring the final criteria put forth by Harvard in 1968. It is also doubtful whether Harvard's definition of brain death by multidisciplinary committee undermined medical privilege and autonomy. The Harvard Ad Hoc Committee may not have succeeded in establishing definitive, indisputable brain death criteria and ensuring their consistent application to all clinical cases of brain death. However, it did gain significant ground for transplant and other medical interests by (1) establishing brain death as a technical "fact" and the definition of brain death as an exercise for medical theorists, (2) involving non-medical ethics and humanities experts in supporting the technical redefinition of death, and, (3) successfully involving transplant surgeons in the redefinition of death and attempting (albeit unsuccessfully) not to exclude them from the actual diagnosis of death in individual cases.

Brain Death

Clearance of mucus from endotracheal tubes during intratracheal pulmonary ventilation.

BACKGROUND: Intratracheal pulmonary ventilation (ITPV) is a form of tracheal gas insufflation in which all gas emerges in a cephalad direction from the tip of a reverse-thrust catheter positioned within an endotracheal tube. In vitro experiments have shown that this rapid gas flow, with 5 ml/h of normal saline added to the gas flow, continuously removes tracheal secretions from within the endotracheal tube. The authors evaluated its effectiveness to remove mucus in long-term studies in sheep. METHODS: Fourteen healthy sheep were tracheally intubated and ventilated for 3 days with ITPV or with volume-controlled ventilation. Measurements were made of the total amount of secretions within the endotracheal tubes (weight gain), the protein content within the endotracheal tubes, and the increase in resistance to constant air flow. The structure of the airways was examined grossly and histologically. Three additional sheep were ventilated for 24 h with ITPV, and Evans Blue dye was added to the saline to assess the distribution of the infused saline. RESULTS: There was significantly less mucus in endotracheal tubes of sheep ventilated with ITPV than with conventional ventilation, as shown by minimal weight gain (0.70 +/- 0.14 g vs. 2.44 +/- 0.81 g; P < 0.001), lower protein content (14.09 +/- 10.79 mg vs. 294.99 +/- 153.06 mg; P < 0.001), and lower resistance to constant air flow (6.15 +/- 0.54 cm H2O x 1(-1) x s(-1) vs. 15.34 +/- 5.28 cm H2O x 1(-1) x s(-1); P < 0.001). Results of gross and histological examinations of the tracheas of animals in both groups were similar, and the tracheas were well preserved. More than 95% of the instilled saline was recovered during ITPV. Only traces of Evans Blue dye were found near the tip of the endotracheal tubes. CONCLUSION: Intratracheal pulmonary ventilation makes it possible to keep the endotracheal tubes of sheep ventilated for 3 days free of mucus without suctioning.

Animals

Artificial neural network identification of heterotrophic marine bacteria based on their fatty-acid composition.

The traditional approach to biochemical identification of marine fresh isolates requires considerably long culture preparation times and large quantities of expensive materials and reagents, and the results are not reliable. On the other hand, taxonomy tests based on DNA composition, although sensitive and reliable, require long execution time and high costs. A method is presented for the classification of fatty-acid profiles, extracted from marine bacteria strains, at genus level based on supervised artificial neural networks. The proposed method allows the correct identification of all patterns belonging to the test set. Moreover, a quantitative measure of the importance of each fatty acid for bacterial classification is also achieved. This measure allows the determination of a cluster of fatty acids to be controlled with greater care. The results show that the proposed method is reproducible and rapid, so that it can be routinely used in the marine microbiology laboratory to identify fresh isolates.

Algorithms

Medical necessity in Canadian health policy: four meanings and ... a funeral?

Four meanings of medical necessity have emerged, evolved, and dominated past and current health policy debates about the appropriate level of service coverage under Canada's health insurance program. To explore the shift in definition, provincial government and national health care association position papers responding to federal legislative and policy reviews of Canada's health insurance program from 1957 to 1984 were examined, as were more current reports on medical necessity. Four meanings of medical necessity predominated: "what doctors and hospitals do"; "the maximum we can afford"; "what is scientifically justified"; and "what is consistently funded across all provinces." These meanings changed with time as different stakeholder associations and governments redefined the concept of medical necessity to achieve different policy objectives for health service coverage under Canada's health insurance program.

Attitude to Health

Intratracheal pulmonary ventilation and continuous positive airway pressure in a sheep model of severe acute respiratory failure.

STUDY OBJECTIVES: Previously we have shown that optimal pulmonary gas exchange can be sustained at normal airway pressures in a model of severe acute respiratory failure (ARF), using intratracheal pulmonary ventilation (ITPV), with weaning to room air. In an identical model of ARF, we have now explored whether ITPV, combined with continuous positive airway pressure (CPAP), can sustain adequate ventilation, with weaning to room air. DESIGN: Randomized study in sheep. SETTING: Animal research laboratory at the National Institutes of Health. INTERVENTIONS: ARF was induced in 12 sheep, using mechanical ventilation at peak inspiratory pressure of 50 cm H2O, but excluding 5 to 8% of lungs. Sheep were then randomized into two groups: the CPAP-ITPV group (n=6), in which ITPV was combined with a novel CPAP system; and a control group (n=6) in which the same CPAP circuit was used, but without ITPV. MEASUREMENTS AND RESULTS: All sheep in the CPAP-ITPV group were weaned to room air in 38.7+/-14 h. PaO2/fraction of inspired oxygen (FIO2) progressively increased from 108.8+/-43 to 355.7+/-93.1; PaCO2 remained within normal range; respiratory rate (RR) ranged from 18 to 120 breaths/min, and tidal volume (VT) was as low as 1.1 mL/kg. All sheep in the control group (CPAP alone) developed severe respiratory acidosis and hypoxemia after 4.8+/-4 h. PaO2/FIO2 decreased from 126.6+/-58.2 to 107.2+/-52.5 mm Hg, with a final PaCO2 of 166.8+/-73.3 mm Hg. CONCLUSIONS: All sheep treated with CPAP-ITPV maintained good gas exchange without hypercapnia at high RR and at low VT, with weaning to room air. All control animals treated with CPAP alone developed severe hypercapnia, respiratory acidosis, and severe hypoxemia, and were killed.

Acidosis, Respiratory

Regional cerebral blood flow (rCBF) in migraine during the interictal period: different rCBF patterns in patients with and without aura.

The aim of this study was to evaluate the rCBF (133Xe clearance method) in migrainous patients free from attack. Fifty patients suffering from migraine without aura (group M) and 20 suffering from migraine with aura (group MA) (age range 20-50 years) were submitted to 32 channel rCBF mapping during the interictal period. The rCBF data of patients were compared with those obtained from 60 healthy control subjects (group C) and 21 patients suffering from tension-type headache (group TH). The mean (average of all channels) rCBF values were: group M = 70.5 +/- 13.7 ml/100g/min; group MA = 56.6 +/- 11.4 ml/100g/min; group C = 62.3 +/- 8.3 ml/100g/min; group TH = 62.1 +/- 8.4 ml/100g/min (F = 11.93; p < 0.001). As expected, patients belonging to group TH had a normal rCBF. The mean rCBF of group M was significantly higher than that of groups C and TH, while in group MA it was significantly lower than in groups C and TH. Group M showed a diffuse hyperemia, while group MA showed rCBF values significantly lower than normal in posterior regions, according to aura. Our results suggest that: (a) the rCBF pattern in migrainous patients is different from that in both controls and TH patients, even during the interictal period; (b) patients suffering from migraine with and without aura are two distinct subpopulations with opposite rCBF deviations.

Adult

New ultrathin-walled endotracheal tube with a novel laryngeal seal design. Long-term evaluation in sheep.

BACKGROUND: A new endotracheal tube (ETT) was fabricated and tested in sheep. It had no tracheal cuff; airway seal was achieved at the level of the glottis through a no-pressure seal made of "gills"; the laryngeal portion was oval-shaped; and the wall thickness was reduced to 0.2 mm. METHODS: Sheep were tracheally intubated either with a standard tube or with the new tube, and their lungs were mechanically ventilated for 1 or 3 days. Air leak was recorded at different peak inspiratory pressures (PIPs). Liquid seepage into the trachea was assessed using an indicator dye. Tracheolaryngeal lesions were scored grossly and histologically. RESULTS: There was no air leak up to 40 cmH2O of PIP, in either group, in short- and long-term studies. Methylene blue leaked across the cuff in two sheep with standard ETTs. No dye leaked across the gills with the new ETTs. In the new ETT group, the trachea appeared better preserved, grossly and histologically, than in the standard ETT group at both 1 and 3 days (P < 0.05). At day 1, the larynx and vocal cords appeared grossly less injured in the new ETT group (P < 0.05), whereas there was no difference at day 3. Histology did not show significant difference on vocal cords, epiglottis, and larynx between the two groups at any time. CONCLUSIONS: The novel, no-pressure seal design of the new ETT is highly effective in preventing air leak and aspiration. It causes no significant tracheal injury.

Animals

An object programming based environment for protein secondary structure prediction.

The most frequently used methods for protein secondary structure prediction are empirical statistical methods and rule based methods. A consensus system based on object-oriented programming is presented, which integrates the two approaches with the aim of improving the prediction quality. This system uses an object-oriented knowledge representation based on the concepts of conformation, residue and protein, where the conformation class is the basis, the residue class derives from it and the protein class derives from the residue class. The system has been tested with satisfactory results on several proteins of the Brookhaven Protein Data Bank. Its results have been compared with the results of the most widely used prediction methods, and they show a higher prediction capability and greater stability. Moreover, the system itself provides an index of the reliability of its current prediction. This system can also be regarded as a basis structure for programs of this kind.

Amino Acid Sequence

Risk adjusting community rated health plan premiums: a survey of risk assessment literature and policy applications.

This paper surveys recent health care reform debates and empirical evidence regarding the potential role for risk adjusters in addressing the problem of competitive risk segmentation under capitated financing. We discuss features of health plan markets affecting risk selection, methodological considerations in measuring it, and alternative approaches to financial correction for risk differentials. The appropriate approach to assessing risk differences between health plans depends upon the nature of market risk selection allowed under a given reform scenario. Because per capita costs depend on a health plan's population risk, efficiency, and quality of service, risk adjustment will most strongly promote efficiency in environments with commensurately strong incentives for quality care.

Actuarial Analysis

Alterations of lung and chest wall mechanics in patients with acute lung injury: effects of positive end-expiratory pressure.

In 16 mechanically ventilated patients with acute lung injury (ALI) (eight patients with moderate ALI [moderate group], eight patients with severe ALI [adult respiratory distress syndrome, ARDS group]) and in eight normal anesthetized-paralyzed subjects (control group), we partitioned the total respiratory system mechanics into the lung (L) and chest wall (w) mechanics using the esophageal balloon technique together with the airway occlusion technique during constant flow inflation. We measured lung elastance (Est,L), chest wall elastance (Est,w), and total lung (Rmax, L) and chest wall (Rmax,w) resistance. Rmax,L includes airway (Rmin,L) and "additional" lung resistance (DR,L). DR,L represents the "additional" component due to the viscoelastic phenomena of the lung tissues and time-constant inequalities (pendelluft). Measurements were repeated at 0, 5, and 10 cm H2O of positive end-expiratory pressure (PEEP) in the control group and at 0, 5, 10, and 15 cm H2O PEEP in patients with ALI. The end-expiratory lung volume (EELV) was measured at each level of PEEP. Specific total lung (sRmax,L), airway (sRmin,L), and "additional" lung (sDR,L) resistances were obtained as Rmax,L x EELV, Rmin,L x EELV, and DR,L x EELV, respectively. At PEEP 0 cm H2O, we found that both Est,L (23.7 +/- 5.5 and 13.8 +/- 3.3 versus 9.3 +/- 1.7 cm H2O/L; p < 0.01) and Est,w (13.2 +/- 5.4 and 9.9 +/- 2.1 versus 5.6 +/- 2.3 cm H2O/L; p < 0.01) were markedly increased in patients with ARDS and moderate ALI compared with control subjects, with a significant (p < 0.01) effect of the severity of the disease on Est,L (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance

A qualitative process theory based model of the HIV-1 virus-cell interaction.

We present a qualitative model of the interaction between the HIV-1 virus and the human cell, based on qualitative process theory. This model takes into account a previous qualitative model of the cell growth. The model presented here can be regarded as a first step for setting up a comprehensive model of the HIV-1 virus-cell interaction in which the possible points where a drug can attack the virus are evident. The first simulation trials indicate that the presented model reproduces (even though in a simplified way) the features of the real behaviour that have been considered in the modelling phase. Although our simulation is limited in the knowledge it expresses, it still gives a stimulating opportunity for the evaluation of the criteria chosen as discriminant in the interaction between virus and cell.

Antiviral Agents

A qualitative model of the dynamics of blood glucose and its hormonal control.

A qualitative model of the short term glucose regulation system is presented. The model is based on the qualitative process theory, based on the concept of physical process defined by the property of causing changes in objects over time. The model has been successfully validated on inputs of several tests. It is intended to employ this model within a comprehensive system encompassing qualitative and quantitative aspects of modelling, building an environment useful for new treatment planning and for education.

Blood Glucose

Interpretation of gascromatographic data via artificial neural networks for the classification of marine bacteria.

We propose a new method for classification of marine bacteria. This method uses gaschromatograms, which contain information of fatty acid percentage contents of the fresh isolate. For the interpretation of these gaschromatograms we use a surpervisioned artificial neural network. We present a preliminary study on this matter, whose first results show good convergence and classification features.

Algorithms

A qualitative approach to cell growth modeling and simulation for cancer chemotherapy.

A qualitative model of cell growth, based on qualitative process theory, is presented. The model can be used to analyze the effects of the interaction of antiproliferative drugs on cells when the effects of each specific drug are known, mainly when designing multi-drug protocols for optimal cancer treatment.

Antineoplastic Combined Chemotherapy Protocols

Changes in the hypothalamo-corticotrope axis after bilateral adrenalectomy: evidence for a median eminence site of glucocorticoid action.

Bilateral adrenalectomy (ADX) leads to increased ACTH synthesis and secretion. It is thought that endogenous glucocorticoids exert a feedback mechanism at both pituitary and brain levels. The present study has been performed in order to determine the effect of ADX on the release of hypothalamic neuropeptides with corticotropin-releasing activity (CRA) and if there exists a median eminence site of glucocorticoid action to regulate hypothalamic-pituitary-adrenal (HPA) function. Adrenalectomized and sham-operated male rats were killed at different periods after surgery (2, 5, 7 and 14 days) and trunk blood was collected for ACTH and corticosterone (B) concentrations measurement. Brain (median eminence, ME; and medial basal hypothalamus, MBH) and pituitary (anterior lobe, AP; and neurointermediate lobe, NIL) tissues were dissected in order to evaluate either peptide content or in vitro hormone release. The results indicate that ADX blunted plasma B levels and increased AP ACTH content and secretion in a time-related fashion up to the 14th day. ADX significantly decreased both CRF and CRA contents in the ME at all periods studied; ME arginine-vasopressin (AVP) increased 7 and 14 days after ADX. MBH CRF decreased after ADX, but returned to sham value 2 weeks later; similarly, MBH AVP decreased at all periods after ADX. Removal of endogenous glucocorticoids did not vary neither oxytocin (OXY) content in the ME and MBH nor AVP and OXY contents in the NIL. In our superfusion experiments, we found that ADX increased basal AVP release and did not change spontaneous CRF secretion from ME terminals. Dexamethasone (Dxm, 10 nM) diminished AVP but not CRF output by ME tissues from adrenalectomized rats. A direct relationship was found between ME CRF and 28 mM KCl (hK+)-induced CRF release by MEs from adrenalectomized rats. ME fragments from adrenalectomized rats were hyperresponsive to kH+ stimulation of AVP release. Dxm (10 nM) decreased the hK(+)-evoked CRF and AVP release by MEs from adrenalectomized rats. ADX and dexamethasone treatment did not influence basal and hK(+)-elicited ME OXY release. Additionally, a rapid glucocorticoid inhibitory effect on ACTH secretion by isolated AP cells from both sham and adrenalectomized rats was found, and an in vitro corticotrope hyporesponse to 0.63 nM CRF and 9.25 nM AVP stimulation during several days after ADX.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy