The truth, the whole truth, and nothing but the truth: Therapeutic privilege.

The term therapeutic privilege is unfamiliar in the medical field and often sparks questions and discomfort about its ethical implications. Therapeutic privilege refers to the act of withholding information by a clinician, with the underlying notion that the disclosure of this information would inflict harm or suffering upon the patient. This is a case of a 56-year-old woman who presented to our facility under critical conditions. She developed sepsis with acute respiratory failure, requiring intubation and mechanical ventilation. Prior to her admission, her husband had been admitted at our facility's intensive care unit. On the same day when our patient was extubated, her husband had died. The palliative care team was consulted to assist with disclosing this information to the patient in light of her emotional fragility, her anxiety, and concerns for her ability to receive such news given her own active illnesses.

Stereoelectronic and Resonance Effects on the Rate of Ring Opening of N-Cyclopropyl-Based Single Electron Transfer Probes.

N-Cyclopropyl-N-methylaniline (5) is a poor probe for single electron transfer (SET) because the corresponding radical cation undergoes cyclopropane ring opening with a rate constant of only 4.1 × 104 s-1, too slow to compete with other processes such as radical cation deprotonation. The sluggish rate of ring opening can be attributed to either (i) a resonance effect in which the spin and charge of the radical cation in the ring-closed form is delocalized into the phenyl ring, and/or (ii) the lowest energy conformation of the SET product (5•+) does not meet the stereoelectronic requirements for cyclopropane ring opening. To resolve this issue, a new series of N-cyclopropylanilines were designed to lock the cyclopropyl group into the required bisected conformation for ring opening. The results reveal that the rate constant for ring opening of radical cations derived from 1'-methyl-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-quinoline] (6) and 6'-chloro-1'-methyl-3',4'-dihydro-1'H-spiro[cyclopropane-1,2'-quinoline] (7) are 3.5 × 102 s-1 and 4.1 × 102 s-1, effectively ruling out the stereoelectronic argument. In contrast, the radical cation derived from 4-chloro-N-methyl-N-(2-phenylcyclopropyl)aniline (8) undergoes cyclopropane ring opening with a rate constant of 1.7 × 108 s-1, demonstrating that loss of the resonance energy associated with the ring-closed form of these N-cyclopropylanilines can be amply compensated by incorporation of a radical-stabilizing phenyl substituent on the cyclopropyl group. Product studies were performed, including a unique application of EC-ESI/MS (Electrochemistry/ElectroSpray Ionization Mass Spectrometry) in the presence of 18O2 and H218O to elucidate the mechanism of ring opening of 7•+ and trapping of the resulting distonic radical cation.

STAT1 deficiency in the heart protects against myocardial infarction by enhancing autophagy.

Previous studies have shown that the transcription factor signal transducer and activator of transcription 1 (STAT1) activation is increased in primary cardiac myocytes exposed to simulated ischaemia/reperfusion injury. This promotes apoptotic cell death by enhancing the expression of pro-apoptotic proteins. Autophagy has been demonstrated to play a cardioprotective role in the heart following myocardial infarction (MI). We therefore investigated the role of STAT1 in the intact heart subjected to MI and examined the contribution of autophagy in modulating the protective effect of STAT1 after MI injury. STAT1-deficient hearts had significantly smaller infarcts than wild-type hearts and this correlated with increased levels of autophagy shown by light chain 3 (LC3)-I/LC3-II conversion, and up-regulation of Atg12 and Beclin 1. Moreover, pre-treatment with the autophagy inhibitor 3-methyladenine reversed the cardioprotection observed in the STAT1-deficient hearts. These results reveal a new function of STAT1 in the control of autophagy and indicate a cross-talk between the cardioprotective versus the damaging effects of STAT1 in the intact heart exposed to MI injury.

The tert-butoxyl radical mediated hydrogen atom transfer reactions of the Parkinsonian proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and selected tertiary amines.

Previous studies have shown that the hydrogen atom transfer (HAT) reactions of tert-butoxyl radical from the Parkinsonian proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) occur with low selectivity at the allylic and non-allylic alpha-C-H positions. In this paper, we report a more comprehensive regiochemical study on the reactivity of the tert-butoxyl radical as well as on the associated primary kinetic deuterium isotope effects for the various hydrogen atom abstractions of MPTP. In addition, the results of a computational study to estimate the various C-H bond dissociation energies of MPTP are presented. The results of the present study show the allylic/non-allylic selectivity is approximately 73:21. The behavior of the tert-butoxyl radical mediated oxidation of MPTP contrasts with this reaction as catalyzed by monoamine oxidase B (MAO-B) that occurs selectively at the allylic alpha-carbon. These observations lead to the conclusion that the tert-butoxyl radical is not a good chemical model for the MAO-B-catalyzed bioactivation of MPTP.

Chemistry of the t-butoxyl radical: evidence that most hydrogen abstractions from carbon are entropy-controlled.

Absolute rate constants and Arrhenius parameters for hydrogen abstractions (from carbon) by the t-butoxyl radical ((t) BuO.) are reported for several hydrocarbons and tertiary amines in solution. Combined with data already in the literature, an analysis of all the available data reveals that most hydrogen abstractions (from carbon) by (t) BuO. are entropy controlled (i.e., TdeltaS > deltaH, in solution at room temperature). For substrates with C-H bond dissociation energies (BDEs) > 92 kcal/mol, the activation energy for hydrogen abstraction decreases with decreasing BDE in accord with the Evans-Polanyi equation, with alpha approximately 0.3. For substrates with C-H BDEs in the range from 79 to 92 kcal/mol, the activation energy does not vary significantly with C-H BDE. The implications of these results in the context of the use of (t) BuO. as a chemical model for reactive oxygen-centered radicals is discussed.

Intestinal obstruction at a provincial hospital in Kenya.

OBJECTIVE: To determine the presentation, aetiological pattern, management and outcome of intestinal obstruction at the Central Provincial General Hospital, Nyeri, Kenya. DESIGN: A descriptive retrospective study. SETTING: Surgical Department, Central Provincial General Hospital, Nyeri, Kenya. SUBJECTS: All patients who were admitted and operated on for intestinal obstruction in the surgical department of the above hospital between January 1992 and May 1999. RESULTS: A total of 139 patients were studied. There were 102 males and 37 females giving a male:female ratio of 2.8:1. The age range was two days to 85 years with the majority (43.2%) of the patients being in the age group 0-10 years. Vomiting and abdominal pain were the commonest symptoms while abdominal distension and abdominal tenderness were the leading signs. Abount seventy of the patients had any form of investigation with plain abdominal x-ray being the leading investigation. Sigmoid volvulus, external herniae, adhesions and bands and ileo-colic intussusception were the commonest causes of bowel obstruction. About a third (32.4%) of the patients were found to have gangrenous gut. Sixty three complications were recorded in 47 patients, with the leading complication being death (17.3%) followed by wound infection (14.4%). CONCLUSION: Five leading causes of intestinal obstruction in Nyeri, Kenya, are: sigmoid volvulus, external herniae, adhesions and bands, ileocolic intussusception and small bowel volvulus.

Head injuries at a Provincial General Hospital in Kenya.

OBJECTIVE: To review the pattern of head injuries, their management and the outcome. DESIGN: A retrospective and prospective descriptive study. SETTING: The Surgical Department, the Intensive Care Unit and the Mortuary at the Provincial General Hospital, Nyeri, Kenya. SUBJECTS: Three hundred and sixty one patients who were seen in the above units with any element of head injury from January 1995 to June 1996. RESULTS: Two hundred and fifty (69.3%) patients were admitted, treated and discharged. Eleven (3.0%) patients died in hospital while 100 (27.7%) were brought in dead. Head injuries accounted for 8.3% of the total admissions to the surgical wards. Road traffic accidents and assault were responsible for over 70% of the head injuries seen. Scalp wounds (52.6%) and fracture of the skull (47.9%) formed the commonest components of head injury. Skull X-rays films were the leading investigation done for head injury. A low Glascow coma scale was associated with a poor outcome. CONCLUSION: Head injuries are a significant cause of morbidity and mortality in our set-up, especially in the young.

Head injuries at a Provincial General Hospital in Kenya.

In this descriptive study, three hundred and sixty one patients with head injuries were studied over an eighteen month period. The age distribution showed two peaks at 0-5 years and 25-35 years. The commonest cause of head injuries was road traffic accidents (40.3%) followed by assault causing trauma to the head (30.5%). The overall mortality rate for patients with head injuries was 30.8% with an age distribution peak at 25-35 years. Associated injuries were found in 165 (45.7%) patients. Complications due to head injuries occurred in 43 (16.5%) patients.

War injuries of the chest.

One hundred and fifty battle casualties with injuries of the chest are reported; most of them resulted from shell fragments. More than 70 per cent were treated by closed drainage by a tube. Early thoracotomy was required in 7.3 per cent of cases, and 5 per cent required a late thoracotomy for complications. Selected cases of flail chest injuries were treated without operation. The mortality rate in our series was 3.3 per cent.