Mortality in elderly patients with thermoregulatory failure

Fifty-four elderly patients with thermoregulatory failure were evaluated retrospectively. The most commonly associated cause was underlying sepsis, which occurred in 78% of cases. Underlying conditions that increased the incidence of hypothermia were hypoproteinemia (50%), cachexia (30%), and neuroleptic medications (21%), most commonly thioridazine. Digoxin toxicity was a common finding (20% of all cases). One third of the patients developed hypothermia in warm months and half of them developed it while in the hospital. Patients who presented with hypothermia from out of the hospital had lower temperatures, were more bradycardic and hemoconcentrated, and died more rapidly than the in-hospital group. This could be explained by lower outside temperature or delay in diagnosis and treatment of the underlying disease. The overall mortality rate was extremely high (74%) in both groups. The mortality rate was not affected by age, sex, or degree of hypothermia. We conclude that thermo-regulatory failure in the elderly can occur in warm as well as cold environments or climates. The development of hypothermia in elderly patients should be promptly treated as sepsis unless proven otherwise, in light of the poor prognosis of this condition.     

Varicella in a gorilla

Naturally occurring varicella was observed in a young gorilla in captivity. The isolate was demonstrated to be varicella-zoster virus by restriction enzyme analysis.     

Dissociation Between Changes in Intramyocardial Function and Left Ventricular Volumes in the Eight Weeks After First Anterior Myocardial Infarction

Objectives. We sought to examine the relation between regional changes in intramyocardial function and global left ventricular (LV) remodeling in the first 8 weeks after reperfused first anterior myocardial infarction (MI).

Background. Because of limitations in imaging methods used to date, this relation has not been thoroughly evaluated.

Methods. We studied 26 patients (21 men, 5 women; mean age 51 years) by magnetic resonance imaging (MRI) on day 5 ± 2 (mean ± SD) and week 8 ± 1 after their first anterior MI. All patients had single-vessel left anterior descending coronary artery disease and although they had received reperfusion therapy, all had regional LV dysfunction and an initial ejection fraction (EF) ≤50%. Short-axis magnetic resonance tagging was performed spanning the LV. Percent intramyocardial circumferential shortening (%S) on a topographic basis, LV mass index, LV end-diastolic volume index (LVEDVI), LV end-systolic volume index and LV ejection fraction (LVEF) were measured.

Results. Left ventricular mass index tended to decrease, whereas the LVEDVI increased from 82 ± 24 to 96 ± 27 ml/m² (p = 0.002). Left ventricular end-systolic volume index remained unchanged, whereas LVEF increased from 39 ± 12% to 45 ± 14% (p = 0.002). Apical %S improved from 9 ± 6% to 13 ± 5% (p < 0.0001), as it did in the midanterior (6 ± 6% to 10 ± 7%, p < 0.02) and midseptal regions (8 ± 7% to 12 ± 6%, p < 0.02). Early dysfunction in remote midinferior and basal lateral regions resolved by 8 weeks. By multivariate analysis, the only significant predictor of an increase in LVEDVI over the study period was peak creatine kinase (p = 0.04).

Conclusions. In the first 8 weeks after a large, reperfused anterior MI, %S improved in the apex, midanterior and midseptal regions and normalized in remote noninfarct-related regions, but LV end-diastolic volumes also increased. This increased LVEDVI correlated with infarct size by peak creatine kinase and was not related to changes in global and regional LV function.     

Consequences of misfilling contemporary vaporizers with desflurane

Desflurane is a volatile anaesthetic that combines low blood gas solubility (blood/gas partition coefficient =0.42 at 37° C), moderate potency (MAC = 6–7%), and high volatility (vapour pressure =681 mmHg at 20° C, boiling point = 23.5° C). The volatility and potency of desflurane prevent its safe use in vaporizers of traditional design. We present a mathematical model which demonstrates the potential for desflurane overdose if contemporary vaporizers are misfilled with desflurane. The most hazardous filling error occurs if an enflurane vaporizer is misfilled with desflurane. The calculated desflurane output of a misfilled enflurane vaporizer at a dial setting of 1% and a temperature of 22° C is 57.8%, or 9.6 MAC. For misfilled enflurane, isoflurane, and halothane vaporizers at dial settings equivalent to one MAC at 22° C, the calculated desflurane output is 14.0, 10.2, and 7.8 MAC, respectively. We conclude that the safe delivery of desflurane will require engineering safeguards, additional monitoring, and education of the anesthesia community.     

Radiologic search for embolized leaflets of prosthetic heart valves: A report of two cases

In a radiologic search for embolized leaflets of Edwards-Duromedics bileaflet valves in 2 patients, the embolized fragments were localized in the iliac vessels using computed tomography. Sonography was successful in one case and standard X-ray films of the abdomen were negative in both cases.In vitro investigations with Björk-Shiley and Edwards-Duromedics leaflets suggested that standard X-ray films of the abdomen and pelvis should be considered as the first investigational technique. If negative, computed tomography of the lower abdomen should be done.     

The value of fine-needle aspiration biopsy in prostatic carcinoma,in comparison with core biopsy histology

Summary Patients in whom an abnormal rectal examination leads to the suspicion of prostatic carcinoma underwent both fine-needle aspiration biopsy for cytological evaluation and core biopsy for histological evaluation. The data from 826 paired observations, collected over a 7-year period are compared. The material available was inadequate for cytology in 94 cases (11.4%) and for histology in 18 cases (2.2%). Cytology results were classified as positive (Papanicolaou 4–5) or negative (1–3) for carcinoma, and histology results as indicative of malignancy or no proven malignancy. Initially the cytology results correlated with the histology results in 84.4%, with a sensitivity of 89.7% and a specificity of 81.5%. After revision of all discrepant slides these figures increased to 88.6%, 92.8% and 86.4%, respectively. Clinical or histological follow up of patients with discrepant results was conclusive in 36 patients, giving evidence of malignancy in 24 patients and of benign pathology in 12. In this discrepancy group, comparison of both cytological and histological results with these clinical data gave a sensitivity for cytology of 63% as against 37% for histology, and a specificity for cytology of 17%, as against 83% for histology. It is concluded that fine-needle aspiration biopsy cytology is a reliable, simple and sensitive technique that can be used to confirm a suspicion of prostatic carcinoma.     

Nephrotoxicity of 5-(N-phenylcarboxamido)-2-thiobarbituric acid in the Fischer 344 rat

Summary In the present investigation, administration of a single i.p. dose of the anticancer drug merbarone [5-(N-phenylcarboxamido)-2-thiobarbituric acid] produced an acute and reversible decrease in renal function in female but not male Fischer 344 rats. The renal lesion in female rats was biochemically characterized as a decrease inp-aminohippuric acid accumulation by renal slices along with polyuria, glucosuria, proteinuria, and enzymuria. These functional changes were accompanied by histopathologic changes of focal tubular necrosis that was confined to the deep cortex and outer stripe of the outer medulla. The changes in these parameters were dose-dependent and were observed at doses as low as 0.2×MELD¹⁰ (12 mg/kg). This low merbarone dose increased urinary glucose and protein excretion by 26- and 9-fold, respectively, in the initial 16-h urine collection in female rats. This increase was accompanied by a 2- to 15-fold increase in the excretion ofN-acetyl--d-glucosaminidase (NAG), -glutamyl transpeptidase (-GTP), and lactate dehydrogenase (LDH) activities. No significant changes in renal function were observed in male rats apart from mild enzymuria after a high dose of merbarone (36 mg/kg). The drug did not increase urea nitrogen levels in male or female rats, reflecting the focal nature of this tubular lesion. Merbarone produced small elevations in serum transaminase activities [i. e., glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] at doses that produced marked alterations in renal function in female rats, suggesting only mild hepatotoxicity. The present study establishes the kidney as a possible dose-limiting target organ for merbarone toxicity.     

Initial results of a phase I trial of continuous infusion SR 2508 (etanidazole): a radiation therapy oncology group study

To exploit both the oxygen-mimetic and "pre-incubation" or continuous exposure effects of the 2-nitroimidazole radiosensitizers, we are conducting a Phase I trial of continuous infusion SR 2508 for patients receiving brachytherapy. Following the administration of a loading dose of 2 g/m2, SR 2508 is administered by continuous infusion for 48 hr. Twenty-one patients have completed treatment. The initial total dose was 8 g/m2 with patients currently receiving 15 g/m2. No toxicity has been observed. At the higher doses the steady-state plasma concentrations have been between 50 and 70 micrograms/ml. It is not yet known whether or not hypoxic sensitizers will be of benefit clinically, and if so, when during a course of treatment is the optimal time to use them. Given the lack of toxicity and plasma concentrations achievable with continuous infusion, future studies will be conducted using SR 2508 during both the external beam and brachytherapy aspects of treatment.     

Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer

Human papilloma virus (HPV) type 16 infections of the genital tract are associated with the development of cervical cancer (CxCa) in women. HPV16-derived oncoproteins E6 and E7 are expressed constitutively in these lesions and might therefore be attractive candidates for T-cell-mediated adoptive immunotherapy. However, the low precursor frequency of HPV16E7-specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer. To overcome this problem, we have isolated T cell receptor (TCR) genes from four different HPV16E7-specific healthy donor and patient-derived human cytotoxic T lymphocyte (CTL) clones. We examined whether genetic engineering of peripheral blood-derived CD8+ T cells in order to express HPV16E711-20-specific TCRs is feasible for adoptive transfer purposes. Reporter cells (Jurkat/MA) carrying a transgenic TCR were shown to bind relevant but not irrelevant tetramers. Moreover, these TCR-transgenic Jurkat/MA cells showed reactivity towards relevant target cells, indicating proper functional activity of the TCRs isolated from already available T cell clones. We next introduced an HPV16E711-20-specific TCR into blood-derived, CD8+ recipient T cells. Transgenic CTL clones stained positive for tetramers presenting the relevant HPV16E711-20 epitope and biological activity of the TCR in transduced CTL was confirmed by lytic activity and by interferon (IFN)-gamma secretion upon antigen-specific stimulation. Importantly, we show recognition of the endogenously processed and HLA-A2 presented HPV16E711-20 CTL epitope by A9-TCR-transgenic T cells. Collectively, our data indicate that HPV16E7 TCR gene transfer is feasible as an alternative strategy to generate human HPV16E7-specific T cells for the treatment of patients suffering from cervical cancer and other HPV16-induced malignancies.