Addiction potential of phentermine prescribed during long-term treatment of obesity.

OBJECTIVE: To investigate if phentermine treatment induces phentermine abuse, psychological dependence (addiction) or phentermine drug craving in overweight, obese and weight loss maintenance patients. To investigate whether amphetamine-like withdrawal occurs after abrupt cessation of long-term phentermine treatment. DESIGN: Clinical intervention trial with interruption of phentermine treatment in long-term patients. SUBJECTS: 269 obese, overweight or formerly obese subjects (age: 20-88 years, BMI: 21-74 kg m(-2)) treated with phentermine long-term (LTP, N=117), 1.1-21.1 years, or short-term (ATP, N=152), 4-22 days, with phentermine doses of 18.75-112.5 (LTP) and 15-93.75 (ATP) mg per day. MEASUREMENTS: Module K of the Mini International Neuropsychiatric Interview modified for phentermine (MINI-SUD), Severity of Dependence Scale (SDS), 45-item Cocaine Craving Questionnaire-NOW (CCQ-NOW) modified for phentermine (PCQ-NOW), and Amphetamine Withdrawal Questionnaire (AWQ) modified for phentermine (PWQ). RESULTS: MINI-SUD interviews were negative for phentermine abuse or psychological dependence in all LTP patients. SDS examination scores were low for all LTP and ATP patients, indicating they were not psychologically dependent upon phentermine. PCQ-NOW scores were low for all LTP and ATP patients, indicating neither short-term nor long-term phentermine treatment had induced phentermine craving. Other than an increase in hunger or eating, amphetamine-like withdrawal symptoms did not occur upon abrupt phentermine cessation as measured by sequential PWQ scores. CONCLUSIONS: Phentermine abuse or psychological dependence (addiction) does not occur in patients treated with phentermine for obesity. Phentermine treatment does not induce phentermine drug craving, a hallmark sign of addiction. Amphetamine-like withdrawal does not occur upon abrupt treatment cessation even at doses much higher than commonly recommended and after treatment durations of up to 21 years.

DNA degradation in the terminus region of resolvase mutants of Escherichia coli, and suppression of this degradation and the Dif phenotype by recD.

We recently proposed that guillotining of dimer chromosomes occurs at cell division in resolvase mutants of Escherichia coli. This was based on the abnormal pattern of cell division observed in 10-14% of the cells in microcolonies of xerC, xerD and dif mutants. A prediction of this guillotining is that DNA degradation should occur in the terminus region, in the vicinity of the dif locus. We have tested this by DNA-DNA hybridization and have observed that dif was absent in about 22% of the chromosomes in exponentially growing xerC mutants. A locus 206 kb from dif was not affected by this degradation. We have also observed that degradation did not occur in xerC recD mutants, and that the low efficiency of plating associated with the Dif phenotype was suppressed in this strain. A model is proposed in which rapid degradation of the terminus region does not occur in recD mutants following guillotining, and that this permits the initiation of repair of broken dimer chromosomes prior to completion of cell division.

Cell division, guillotining of dimer chromosomes and SOS induction in resolution mutants (dif, xerC and xerD) of Escherichia coli.

We have studied the growth and division of xerC, xerD and dif mutants of Escherichia coli, which are unable to resolve dimer chromosomes. These mutants express the Dif phenotype, which includes reduced viability, SOS induction and filamentation, and abnormal nucleoid morphology. Growth was studied in synchronous cultures and in microcolonies derived from single cells. SOS induction and filamentation commenced after an apparently normal cell division, which sheared unresolved dimer chromosomes. This has been called guillotining. Microcolony analysis demonstrated that cell division in the two daughter cells was inhibited after guillotining, and microcolonies formed that consisted of two filaments lying side by side. Growth of these filaments was severely reduced in hipA+ strains. We propose that guillotining at dif destroys the expression of the adjacent hipBA genes and, in the absence of continued formation of HipB, HipA inhibits growth. The length of the filaments was also affected by SfiA: sfiA dif hipA mutants initially formed filaments, but cell division at the ends of the filaments ultimately produced a number of DNA-negative cells. If SOS induction was blocked by lexA3 (Ind-), filaments did not form, and cell division was not inhibited. However, pedigree analysis of cells in microcolonies demonstrated that lethal sectoring occurred as a result of limited growth and division of dead cells produced by guillotining.

Experimental approaches towards interpreting dolphin-stimulated bioluminescence.

Flow-induced bioluminescence provides a unique opportunity for visualizing the flow field around a swimming dolphin. Unfortunately, previous descriptions of dolphin-stimulated bioluminescence have been largely anecdotal and often conflicting. Most references in the scientific literature report an absence of bioluminescence on the dolphin body, which has been invariably assumed to be indicative of laminar flow. However, hydrodynamicists have yet to find compelling evidence that the flow remains laminar over most of the body. The present study integrates laboratory, computational and field approaches to begin to assess the utility of using bioluminescence as a method for flow visualization by relating fundamental characteristics of the flow to the stimulation of naturally occurring luminescent plankton. Laboratory experiments using fully developed pipe flow revealed that the bioluminescent organisms identified in the field studies can be stimulated in both laminar and turbulent flow when shear stress values exceed approximately 0.1 N m-2. Computational studies of an idealized hydrodynamic representation of a dolphin (modeled as a 6:1 ellipsoid), gliding at a speed of 2 m s-1, predicted suprathreshold surface shear stress values everywhere on the model, regardless of whether the boundary layer flow was laminar or turbulent. Laboratory flow visualization of a sphere demonstrated that the intensity of bioluminescence decreased with increasing flow speed due to the thinning of the boundary layer, while flow separation caused a dramatic increase in intensity due to the significantly greater volume of stimulating flow in the wake. Intensified video recordings of dolphins gliding at speeds of approximately 2 m s-1 confirmed that brilliant displays of bioluminescence occurred on the body of the dolphin. The distribution and intensity of bioluminescence suggest that the flow remained attached over most of the body. A conspicuous lack of bioluminescence was often observed on the dolphin rostrum and melon and on the leading edge of the dorsal and pectoral fins, where the boundary layer is thought to be thinnest. To differentiate between effects related to the thickness of the stimulatory boundary layer and those due to the latency of the bioluminescence response and the upstream depletion of bioluminescence, laboratory and dolphin studies of forced separation and laminar-to-turbulent transition were conducted. The observed pattern of stimulated bioluminescence is consistent with the hypothesis that bioluminescent intensity is directly related to the thickness of the boundary layer.

Kinetic expression of endothelial adhesion molecules and relationship to leukocyte recruitment in two cutaneous models of inflammation.

BACKGROUND: Adhesive interactions between circulating leukocytes and endothelium is requisite for subsequent leukocyte extravasation at inflammatory sites. These adhesive events are mediated by a repertoire of proteins and carbohydrate moieties on both leukocyte and endothelial membranes. Understanding the kinetic expression of these adhesion molecules during an inflammatory cascade in vivo is important for the design and testing of rational therapeutic approaches directed at the blockade of adhesion molecule function in inflammatory disease. EXPERIMENTAL DESIGN: Two cutaneous inflammatory models were examined using healthy rhesus monkeys. Acute cutaneous injury was studied during a 72-hour period by intradermal injection of endotoxin (lipopolysaccharide) and subsequent biopsy. These tissues were then compared with those obtained from a cutaneous delayed-type hypersensitivity reaction (DHR), elicited by intradermal injections of mammalian tuberculin in sensitized animals and followed for up to 11 days. Expression of E-selectin, P-selectin, VCAM-1, and ICAM-1 was assessed using immunohistochemistry and compared with leukocyte localization and immunohistochemical expression of interleukin (IL) 1, IL-8 and tumor necrosis factor-alpha (TNF-alpha). Finally, relevant adhesion ligands on leukocytes were assessed using flow cytometry. RESULTS: The lipopolysaccharide model was characterized by early (0.5 hours) and sustained (up to 72 hours) expression of E-selectin on the superficial dermal vasculature, with maximal expression by 8 hours. The expression of VCAM-1 was either not detected or minimal. Neutrophil localization, as detected by elastase immunoreactivity, paralleled E-selectin expression with a 4- to 12-hour lag phase, being maximal by 24 hours. In contrast, DHR was characterized by the dual asynchronous expression of both E-selectin and VCAM-1. Localization of CD2+ lymphocytes, representing the predominant cell type recruited, kinetically followed the expression of E-selectin and VCAM-1, being maximal in number at approximately 48 hours after peak expression of both of these endothelial proteins. Neutrophil recruitment in lipopolysaccharide-induced injury was associated with immunohistochemical localization of TNF-alpha, IL-1, and IL-8, whereas only TNF-alpha was consistently detected in DHR. During DHR, blood lymphocyte expression of L-selectin, VLA-4 (CD49d; alpha chain), and lymphocyte function-associated antigen 1 (both CD11a (alpha chain) and CD18 (beta chain)) did not change. CONCLUSIONS: The results from this study demonstrate that cutaneous inflammatory infiltrates of varying cellular compositions are associated temporally and spatially with unique patterns of endothelial adhesion molecule and cytokine expression.

Hydrocephalus in Apert syndrome: a retrospective review.

A retrospective evaluation was carried out to define the incidence of hydrocephalus and associated factors in 44 patients with Apert syndrome treated at The Hospital for Sick Children in Toronto over a 22-year period. Forty-three of these patients underwent cranioorbital decompressive procedures within 1 year of birth. Fifteen of 25 (60%) patients who had either a computed tomography scan or pneumoencephalogram had ventriculomegaly, and 3 of the 25 (12%) had associated brain anomalies. Ten of the 44 (23%) patients had cerebrospinal fluid (CSF) shunts placed, 7 lumboperitoneal and 3 ventriculoperitoneal. Six of the shunts were placed early after cranioorbital procedures (CSF leaks in 5 cases and a subgaleal fluid collection in 1 case). The average IQ of 15 patients evaluated by the Wechsler Intelligence Scale was 72.5, indicative of significant intellectual impairment. There was no correlation between IQ and ventricular size. Although hydrocephalus characterized by progressive ventricular dilatation is uncommon in Apert syndrome, postoperative problems related to impaired CSF circulation are common and may indicate an underlying CSF absorptive deficit.

Blood grouping with the Olympus PK7100 testing system.

The Olympus PK7100, an automated microtitre blood typing machine, identifies, aliquots, and dilutes samples, adds reagents, photometrically detects agglutination, and records reaction results, with a throughput of 240 samples/h. A total of 20,147 donors was tested in parallel with the Groupamatic 360. Of these, 207 could not be ABO typed after two runs. Three samples typed as B by the Olympus were found to be A2B. Seventy-seven could not be typed for D after two runs. Of these, 55 were Rh positive and 22 negative. The Olympus identified 37 of 48 Du positive samples as Rh positive, while it typed three as Rh negative, and eight as 'uncertain'. None of these samples was identified as Rh positive by the Groupmatic 360. The Olympus PK7100 is accurate, reliable, easy to operate, and capable of high throughput with minimal operator intervention.

Laboratory computers: tools for increased productivity.

Revolutionary changes in the computer industry brought about in part by the introduction of personal computers are now reaching into clinical laboratories everywhere. Although the true justification for any computer tool may be an intangible one such as improvement in service, such tools can typically be cost justified by increases in productivity alone. A broad spectrum of applications software useful in the medical laboratory is now available in any scale required to meet the needs of any size of laboratory. Perhaps one of the most dramatic changes in this field in the last several years has been the introduction of small-scale integrated laboratory systems that are true small-scale laboratory information systems. As a result, smaller laboratories can now acquire laboratory information systems appropriately scaled to their workload for a fraction of the cost of the large systems. These small laboratory information systems are typically more easily cost justified than larger ones. Achieving productivity gains using computer tools in the laboratory is a management-intensive process requiring careful analysis and thorough planning. Laboratory managers who eschew computer tools are now an anachronism; extinction of this species is imminent.

Malakoplakia of the female genital tract.

A rare case of malakoplakia of the uterine cervix and the pelvis occurring in an elderly woman who also had xanthogranulomatous pyelonephritis is described and compared with the 15 reported cases of malakoplakia of the female genital tract.

A community hospital laboratory computer system: an eight-year longitudinal study of economic impact.

An analysis of the intralaboratory economic effects of installation of a dedicated laboratory computer system in a 450-bed acute care general hospital laboratory is presented using data accumulated during an eight-year period. Data collection and analytic conventions used included: (1) an inflation factor derived from the CPI to adjust costs; (2) semilogarithmic plotting; (3) patient procedure counts tallied as the raw count for patient specimens according to the CAP Workload Recording Method; and (4) total workload (including patient standard and control items) recorded according to the CAP WRM. The authors conclude that computerization has produced: (1) a decrease in inflation adjusted labor costs per unit of work; (2) a decrease in inflation adjusted direct cost per unit of work; (3) A decline in the ratio of clerical to technical labor force; and (4) An increase in overall productivity of approximately 7%.

Angiosarcoma following therapeutic irradiation.

This paper reports a case of angiosarcoma of the terminal ileum in a 66-year-old female. This angiosarcoma developed 8 years after postoperative irradiation for ovarian carcinoma. This case appears to be the sixth case of angiosarcoma arising at the site of therapeutic irradiation thus far reported in the literature. The fact that the angiosarcomas in these cases developed in anatomic sites, which are unusual for angiosarcomas in general, suggests that there is a cause-and-effect relationship between irradiation and angiosarcoma. Apart from the direct carcinogenic effect of irradiation, prolonged stimulation for tissue repair resulting from tissue damage secondary to irradiation-induced vascular changes may also play an etiologic role in the development of angiosarcomas in these cases.

Radon in treatment of infiltrating carcinoma of urinary bladder.

Shown here are the results from the use of radon in the treatment of 146 patients with infiltrating carcinoma of the bladder. Ninety-four per cent of the tumors had invaded the muscle of the bladder; 54 per cent were Stage B2 or worse. Ninety per cent of the radon implantations were done cystoscopically. Twenty-one per cent of the patients survived five years or longer, free of recurrence. An additional 8 per cent were cured by follow-up treatment of recurrences. Complications and morbidity are minimal. Survival results compare favorably with more dangerous and debilitating methods of treatment.

Total retropubic prostatectomy for carcinoma of the prostate.

Results in 96 patients who had total retropubic prostatectomy were reviewed. The most common complications were impotence and difficulty with urinary control. The most serious were rectal injury and vesical neck contracture. Twenty-eight of 33 patients who were followed for five years after operation and eight of twelve who were followed for ten years were alive without evidence of recurrence of cancer. Evidence of recurrence was found only in patients in whom cancer had spread beyond the parenchyma of the prostate before operation. There were no operative deaths.