Kinetic study of smoking marijuana

Six subjects each smoked a 1% marijuana cigarette and 2 hr later smoked a second one. Plasma levels of delta-9-tetrahydrocannabinol were measured for 9 hr with a radioimmunoassay. Heart rate and self-reported "high" were measured for 2 hr after each cigarette. All three measures showed a rapid increase after the start of smoking with Cmax occurring before the end of smoking. There was a strong correlation between decrease in heart rate and plasma levels from 10 min after smoking until 120 min. All pharmacodynamic response measures returned to baseline values within approximately 2 hr.     

Failure of Nonoperative Management of Isolated Superior Mesenteric Artery Dissection

A case of isolated dissection of the superior mesenteric artery is presented here. This rare condition was confirmed angiographically in a 46-year-old man with persistent abdominal pain. He was treated initially with anticoagulation alone. One year later, he developed recurrent symptoms and had radiologic documentation of progression of the condition. Operative repair was performed and recovery was uneventful. This case demonstrates a failure of the nonoperative approach to this rare condition and suggests that disease progression may be inevitable. Early surgical correction may ease operative management.     

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration /= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.     

Increased placental apoptosis in intrauterine growth restriction

OBJECTIVES: Our purpose was to investigate a possible role for apoptosis in the pathophysiologic mechanisms of intrauterine growth restriction. STUDY DESIGN: Placental samples were obtained from 43 uncomplicated third-trimester pregnancies and from 26 pregnancies complicated by intrauterine growth restriction. The definition used to identify cases of intrauterine growth restriction depended on three criteria: clinical evidence of suboptimal growth, ultrasonographic evidence of deviation from an appropriate growth percentile, and individualized birth weight ratios <10th percentile. Light microscopy was used to quantify the incidence of apoptosis. Electron microscopy and TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick end labeling) staining were used to confirm the occurrence of apoptosis. RESULTS: Quantification of apoptosis (medians and interquartile ranges) resulted in the following values: normal third trimester (n = 43) 0.14% of cells (0.08% to 0.20%) and intrauterine growth restriction third trimester (n  = 26) 0.24% of cells (0.16% to 0.29%). The incidence of apoptosis was significantly higher in placentas from pregnancies with intrauterine growth restriction compared with normal third-trimester placentas (p < 0.01, Mann Whitney U test). CONCLUSIONS: These results suggest that apoptosis may play a role in the pathophysiologic mechanisms of intrauterine growth restriction.(Am J Obstet Gynecol 1997;177:401)     

Bisulfite-containing propofol: is it a cost-effective alternative to Diprivan for induction of anesthesia?

Propofol (Diprivan(TM); AstraZeneca, Wilmington, DE) is a commonly used drug for the induction of general anesthesia in the ambulatory setting. With the availability of a new bisulfite-containing generic formulation of propofol, questions have arisen regarding its cost effectiveness and safety compared with Diprivan(TM). Two hundred healthy outpatients were randomly assigned, according to a double-blinded protocol, to receive either Diprivan(TM) or bisulfite-containing propofol 1.5 mg/kg IV as part of a standardized induction sequence. Maintenance of anesthesia consisted of either desflurane (4%-8% end-tidal) or sevoflurane (1%-2% end-tidal) in combination with a remifentanil infusion (0.125 microg x kg(-1) x min(-1) IV). Patient assessments included pain on injection, induction time, hemodynamic and bispectral electroencephalographic changes during induction, emergence time, and incidence of postoperative nausea and vomiting. The two propofol groups were comparable demographically, and the induction times and bispectral index values during the induction were also similar. However, the bisulfite-containing formulation was associated with less severe pain on injection (5% vs 11%), with fewer patients recalling pain on injection after surgery (38% vs. 51%, P<0.05). None of the patients manifested allergic-type reactions after the induction of anesthesia. The acquisition cost (average wholesale price in US dollars) of a 20-mL ampoule of Diprivan(TM) was $15 compared with $13 for the bisulfite-containing propofol formulation. Therefore, we concluded that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM) for the induction of outpatient anesthesia. Implications: Bisulfite-containing propofol and Diprivan(TM) (AstraZeneca, Wilmington, DE) were similar with respect to their induction characteristics; however, the generic formulation was associated with a smaller incidence of injection pain. Assuming that the drug costs are similar, these data suggest that the bisulfite-containing formulation of propofol is a cost-effective alternative to Diprivan(TM).     

Ifosfamide, carboplatin, and etoposide with midcycle vincristine versus standard chemotherapy in patients with small-cell lung cancer and good performance status: clinical and quality-of-life results of the British Medical Research Council multicenter randomized LU21 trial.

PURPOSE: Ifosfamide, carboplatin, etoposide, and vincristine, alone and in combination, are highly active against small-cell lung cancer (SCLC). This trial was designed to investigate whether survival could be improved by a regimen of all four drugs (ICE-V) compared with standard chemotherapy in patients with SCLC and good performance status, and to assess the patients' quality of life (QL). PATIENTS AND METHODS: Patients were randomly assigned to receive six cycles of either ICE-V at 4-week intervals without dose reduction or standard chemotherapy administered according to local practice. The recommended standard control regimens were cyclophosphamide, doxorubicin, and etoposide; and cisplatin and etoposide. RESULTS: A total of 402 patients were randomly assigned, and 350 (87%) patients have died. Overall survival was longer in the ICE-V group (hazard ratio, 0.74; 95% CI, 0.60 to 0.91; P = .0049), median survival was 15.6 months in the ICE-V group and 11.6 months in the control group, and 2-year survival rates were 20% and 11%, respectively. There was no evidence that the relative survival benefit for ICE-V was less in extensive-stage than in limited-stage patients. An increased rate of septicemia was reported in the ICE-V group (15% v 7% in the control group), but this did not result in an increase in reported treatment-related deaths (four patients [2%] in both groups). The findings on QL were broadly similar in both groups, with some benefit in favor of ICE-V. CONCLUSION: Compared with standard chemotherapy, the ICE-V regimen improves overall survival without QL penalties, despite an increased but manageable level of toxicity.     

Langerhans' cell histiocytosis in patients older than 21 years

In this retrospective review of 541 patients with Langerhans' cell histiocytosis, 211 (39%) patients were older than 21 years of age, whereas 330 (61%) were younger than 21 years of age. The adult patients had a mean age of 32 years (range, 21-69 years) with 159 (75%) men and 52 (25%) women, whereas the pediatric patients consisted of 176 (55%) boys and 144 (45%) girls. This male predominance in adults was statistically significant. Three adults had the Hand-Schuller-Christian variant, whereas the remaining adults (208) had eosinophilic granuloma. The rib accounted for 25% of the adult lesions and only 8% of the pediatric lesions. Spine involvement was less common in the adult group (3% versus 10%) and was predominantly thoracic. The adult patients had 40 (77%) diaphyseal lesions, 12 (23%) metaphyseal lesions, and no epiphyseal lesions. The pediatric patients had 75 (54%) diaphyseal, 59 (42%) metaphyseal, and five (4%) epiphyseal lesions. Radiographic evaluation revealed similar margin and matrix patterns in both groups, with a geographic lesion without sclerotic borders being the most common pattern. Langerhans' cell histiocytosis is considered a pediatric disease. However, this study showed a significant number (39%) of patients older than 21 years of age with this condition.     

Light microscopic observations on the formation of the layer of Hopewell-Smith in human teeth

Light microscopic examination of longitudinal ground sections of incompletely formed teeth revealed a layer on the external root surface of dentine which was continuous at the forming apex with the predentine. Dentinal tubules were observed transversing this layer, particularly in the cervical region. In more completely formed teeth, the layer was not clearly defined, though tubules were still present which reached the root surface.

Examination of tetracycline-labelled sections by light and fluorescent microscopy showed a band pattern which, taken with the previous evidence, led to the conclusion that an additional delayed calcification at the dentine root surface occurs after some calcified dentine has been laid down, but before any cement deposition. The situation of this calcification zone, external to the granular layer of Tomes, corresponded with the layer of Hopewell-Smith, and the evidence suggested that terminal portions of odontolast processes might be involved in its formation.     

Increased cerebrospinal fluid corticotropin-releasing factor concentrations during tryptophan depletion in healthy adults.

BACKGROUND: Brain serotonin neurotransmission and hypothalamic-pituitary-adrenal axis function are implicated in the pathophysiology of depression, and these systems interact in a reciprocal modulatory fashion. This study examined the effect of tryptophan depletion, which acutely reduces brain serotonin concentrations, on serial cerebrospinal fluid concentrations of corticotropin-releasing factor in healthy humans. METHODS: Five subjects completed a standard tryptophan depletion protocol, and four subjects participated in a comparison condition. Subjects underwent continuous sampling of cerebrospinal fluid via lumbar peristaltic pump. Concentrations of cerebrospinal fluid corticotropin-releasing factor were measured by radioimmunoassay. RESULTS: No mood changes were observed in either group. Tryptophan-depleted subjects exhibited significantly greater increases in corticotropin-releasing factor concentrations over time than subjects in the comparison condition. CONCLUSIONS: These findings highlight the potential importance of corticotropin-releasing factor and serotonin interactions and suggest that activation of corticotropin-releasing-factor-containing neurons could play a role in the emergence of mood symptoms following tryptophan depletion in vulnerable individuals.