Digital clubbing and lung cancer

We present three critically ill patients with severe renal failure who required haemofiltration or haemodiafiltration, with high-efficiency or high-flux membranes, while receiving an intravenous infusion of morphine. We show that despite the very high ultrafiltrability/diffusability of free morphine, only 1-3% of the total amount of infused morphine is removed in 24 h. This is in marked contrast to haemodialysis where, owing to much higher dialysate flow rate, a significant quantity of free morphine is removed.     

Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome

Women with polycystic ovary syndrome (PCOS) are characterized by defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis. We administered the insulin-sensitizing agent troglitazone to 13 obese women with PCOS and impaired glucose tolerance to determine whether attenuation of hyperinsulinemia ameliorates these defects. All subjects had oligomenorrhea, hirsutism, polycystic ovaries, and hyperandrogenemia. Before and after treatment with troglitazone (400 mg daily for 12 weeks), all had 1) a GnRH agonist (leuprolide) test, 2) a 75-g oral glucose tolerance test, 3) a frequently sampled iv glucose tolerance test to determine the insulin sensitivity index and the acute insulin response to glucose, 4) an oscillatory glucose infusion to assess the ability of the beta-cell to entrain to glucose as quantitated by the normalized spectral power for the insulin secretion rate, and 5) measures of fibrinolytic capacity [plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator]. There was no change in body mass index (39.9 +/- 1.4 vs. 40.2 +/- 1.4 kg/m2) or body fat distribution after treatment. Both the fasting (91 +/- 3 vs. 103 +/- 3 mg/dL; P < 0.001) and 2 h (146 +/- 8 vs. 171 +/- 6 mg/dL; P < 0.02) plasma glucose concentrations during the oral glucose tolerance test declined significantly. There was a concordant reduction in glycosylated hemoglobin to 5.7 +/- 0.1 from a pretreatment level of 6.1 +/- 0.1% (P < 0.03). Insulin sensitivity increased from 0.58 +/- 0.14 to 0.95 +/- 0.26 10(-5) min-1/pmol.L (P < 0.01) after treatment as did the disposition index (745 +/- 135 vs. 381 +/- 96; P < 0.05). The ability of the beta-cell to appropriately detect and respond to an oscillatory glucose infusion improved significantly after troglitazone treatment; the normalized spectral power for the insulin secretion rate increased to 5.9 +/- 1.1 from 4.3 +/- 0.8 (P < 0.05). Basal levels of total testosterone (109.3 +/- 15.2 vs. 79.4 +/- 9.8 ng/dL; P < 0.05) and free testosterone (33.3 +/- 4.0 vs. 21.2 +/- 2.6 pg/mL; P < 0.01) declined significantly after troglitazone treatment. Leuprolide-stimulated levels of 17-hydroxyprogesterone, androstenedione, and total testosterone were significantly lower posttreatment compared to pretreatment. The reduction in androgen levels occurred independently of any changes in gonadotropin levels. A decreased functional activity of PAI-1 in blood (from 12.7 +/- 2.8 to 6.3 +/- 1.4 AU/mL P < 0.05) was associated with a decreased concentration of PAI-1 protein (from 64.9 +/- 9.1 to 44.8 +/- 6.1 ng/mL; P < 0.05). No change in the functional activity of tissue plasminogen activator (from 5.3 +/- 0.4 to 5.1 +/- 0.5 IU/mL) was observed despite a decrease in its concentration (from 9.6 +/- 0.9 to 8.2 +/- 0.7 ng/mL; P < 0.05). The marked reduction in PAI-1 could be expected to improve the fibrinolytic response to thrombosis in these subjects. We conclude that administration of troglitazone to women with PCOS and impaired glucose tolerance ameliorates the metabolic and hormonal derangements characteristic of the syndrome. Troglitazone holds potential as a useful primary or adjunctive treatment for women with PCOS.     

Curvature-mediated interactions between membrane proteins

Membrane proteins can deform the lipid bilayer in which they are embedded. If the bilayer is treated as an elastic medium, then these deformations will generate elastic interactions between the proteins. The interaction between a single pair is repulsive. However, for three or more proteins, we show that there are nonpairwise forces whose magnitude is similar to the pairwise forces. When there are five or more proteins, we show that the nonpairwise forces permit the existence of stable protein aggregates, despite their pairwise repulsions.     

A novel MPTP primate model of Parkinson''s disease: neurochemical and clinical changes

In the present study, substance P receptor binding was localized in the dorsal column nuclei (DCN) of the rat, cat, monkey, and human. Bolton-Hunter-labeled [125I]substance P binding was most concentrated in the cell nests of the core region, but was present throughout the DCN of each species. The distribution of substance P receptors may reconcile apparent mismatches between the widespread responsiveness of DCN neurons to substance P and the restricted distribution of substance P containing afferents.     

Kaposi's sarcoma in renal transplant recipients

One hundred and seventeen of 270 (43%) recipients of organs obtained from donors with malignancies had evidence of transmitted cancers. In 9 instances these were removed from renal allografts immediately prior to transplantation. Including these cases there were 45 recipients of organs in which a neoplasm involved the allograft, 6 others in whom adjacent structures were invaded, and another 66 patients who had distant metastases. Precautions to prevent cancer transmission include meticulous preoperative screening of donors, careful examination of all organs at the time of harvesting, biopsy of any suspicious lesions, and routine donor autopsy, if possible.     

Cell cycle arrest, apoptosis and p53 expression in nickel(II) acetate-treated Chinese hamster ovary cells

This clinical report describes two patients presenting with progressive diaphyseal dysplasia (Camurati-Engelmann Disease) and cerebellar ataxia. The clinical and magnetic resonance imaging findings of the bony and cerebellar lesions are presented.     

Sintering of TCP-TiO2 biocomposites: influence of secondary phases

TCP-TiO2 ceramic biocomposites with various alpha-to-beta TCP ratios can be prepared by quenching the alpha phase. The presence of dopants (Ca, P, or Na) leads to the precipitation of secondary phases, which decreases the densification of titania. In the system TCP-TiO2, there is a eutectic with a composition of 63 wt% TCP-37 wt% TiO2 at a temperature of 1380 degrees C.     

Peptide mapping and amino acid sequencing of two catechol 1,2-dioxygenases (CD I1 and CD I2) from Acinetobacter lwoffii K24

The partial amino acid sequences of two catechol 1,2-dioxygenases (CD I1 and CD I2) from Acinetobacter lwoffii K24 have been determined by analysis of peptides after cleavages with endopeptidase Lys-C, endopeptidase Glu-C, trypsin, and chemicals (cyanogen bromide and BNPS-skatole). They include 248 amino acid sequences (4 fragments) of CD I1 and 211 amino acid sequences (5 fragments) of CD I2. Two enzymes have more than 50% sequence homology with type I catechol 1,2-dioxygenases and less than 30% sequence homology with type II catechol 1,2-dioxygenases. Two enzymes have similar hydropathy profiles in the N-terminal region, suggesting that they have similar secondary structures.     

Long-term clinical follow-up after directional coronary atherectomy

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.     

Risk factors and clinical outcomes between fungal and bacterial keratitis: a comparative study

OBJECTIVE: Thirty years ago, cardiopulmonary resuscitation (CPR) was primarily developed for otherwise healthy individuals who experienced sudden cardiac arrest. Today, CPR is widely viewed as an emergency procedure that can be attempted on any person who undergoes a cessation of cardiorespiratory function. Therefore, the appropriateness of CPR has been questioned as a matter of the outcome, the patient's preferences, and the cost. The objective of this article is to analyse ethical issues in prehospital resuscitation. ARGUMENTS: CPR is bound by moral considerations that surround the use of any medical treatment. According to Beauchamp and Childress, the hierarchy of justification in biomedical ethics consists of ethical theories, principles, rules, and particular judgements and actions. The decision to start CPR is based on the medical judgement that a person is suffering from circulatory arrest. The decision is justified by the moral rule that the victim of a cardiac arrest has the right to survive and to receive CPR. Moral rules are more specific to contexts and are based on ethical principles. The principle of beneficence means the provision of benefits for the promotion of welfare. Talking about beneficence in resuscitation means once again reporting stories of success, as many victims of pre- and in-hospital sudden death have been saved in the past. Nevertheless, resuscitative efforts still remain unsuccessful in the majority of cases, involving the principle of nonmaleficence. There is potential harm in CPR. Survivors may recover cardiac function, but sustain severe hypoxic brain damage, at worst surviving without awakening for months or years. In particular, post-traumatic CPR is associated with an extremely poor outcome, leading to the issue of futility. However, futility should be defined in a strict fashion, as there might be an individual chance of survival. The principle of respect for autonomy means the right of a patient to accept or reject medical treatment, which continues in emergency conditions and after the patient has lost consciousness. The time frame in CPR requires medical decision-making within seconds, and CPR is usually initiated without the patient's involvement. If the patient's wish's can be ascertained later on, life-sustaining therapies might be withdrawn at the time. Terminally ill but still competent patients should be encouraged to write a no-CPR document, which does not deny patients relief from severe symptoms, but might facilitate withholding resuscitative efforts at the scene. The principle of justice affects priorities in the allocation of health care resources. The decision made for a particular patient might delay or prevent emergency treatment in other patients who could receive greater benefit. CONCLUSIONS: The standard of care remains the prompt initiation of CPR. However, ethical principles such as beneficence, nonmaleficence, autonomy, and justice have to be applied in the unique setting of emergency medicine. Physicians have to consider the therapeutic efficacy of CPR, the potential risks, and the patient's preferences.