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Biomedical subjects

R E Link

Publications and source records attributed to R E Link.

16 recordsLinked to original sources
PubMed2001

Telesurgery. Remote monitoring and assistance during laparoscopy.

In comparison to open surgery, laparoscopy results in less postoperative pain, shorter hospitalization, more rapid return to the work force, a better cosmetic result, and a lower incidence of postoperative intra-abdominal adhesions. These advantages are indisputable when comparing large series for cholecystectomy and smaller series for pelvic lymph node dissection, nephrectomy, and bladder neck suspension in experienced hands. Urologists have an obligation to explore the application of these methods to urologic disease and to adjust the standard of care accordingly. Several barriers to the expansion of urologic laparoscopic surgery exist. The experience in extirpative and reconstructive urologic procedures is limited when compared with the data on cholecystectomy. These procedures are technically complex and demand advanced laparoscopic skills and familiarity with laparoscopic anatomy. The steep learning curve translates into long operative times and an unacceptably high rate of complications for inexperienced laparoscopic surgeons. Most practicing urologists have no formal training in advanced laparoscopy, and no formal credentialing guidelines exist. Telesurgical technology may provide one solution to this problem. Through telesurgical mentoring, less experienced surgeons with basic laparoscopic skills could receive training in advanced techniques from a world expert without the need for travel. These systems could also be used to proctor laparoscopic cases for credentialing purposes and to provide a more uniform standard of care. This review has outlined some of the exciting progress made in the field of telesurgery over the past 10 years and described some of the technical and legal obstacles that remain to be surmounted. During the 1990s, urologists were at the forefront of innovation in remote telepresence surgery. As the scope of minimally invasive urologic surgery expands during the first few decades of the twenty-first century, telesurgical mentoring should have an increasingly important role.

Education, Medical, Continuing↗
PubMed2001

Indications for pelvic lymphadenectomy in prostate cancer.

Clearly, pelvic lymphadenectomy can provide important staging information in the management of prostate cancer, but this benefit is counterbalanced by a modest increase in morbidity and the significant cost of the procedure. It is difficult to provide universal recommendations concerning the indications for pelvic lymphadenectomy. Part of the problem lies in the fact that urologists perform pelvic lymphadenectomy for several different reasons. Some surgeons perform pelvic lymphadenectomy to better counsel patients after radical prostatectomy about their risk for disease progression and for planning adjuvant radiotherapy or hormonal therapy. For these surgeons, preoperative clinical staging parameters do not exclude patients from pelvic lymphadenectomy, and frozen section analysis intraoperatively provides no useful information. Alternatively, the staging information from pelvic lymphadenectomy can be used to justify cancellation of the subsequent prostatectomy should regional spread of prostate cancer be identified, sparing the patient the morbidity of an unnecessary radical prostatectomy. With this approach, despite the false-negative rate of up to 30%, the expense of frozen section analysis seems justified. For this second group of surgeons, the problem becomes balancing the modest morbidity and cost of pelvic lymphadenectomy against the probability that nodal spread of prostate cancer will be missed if the procedure is omitted. The authors consider a greater than 4% risk for missing regional disease to be unacceptable in this setting. Following this assumption, Table 3 outlines parameters for clinical stage, Gleason score, and preoperative PSA within which pelvic lymphadenectomy is indicated. These recommendations are based on [table: see text] predictions from the Partin nomogram, which has been validated using a series of over 4000 patients. For the large number of patients with clinical T1c disease and a preoperative PSA less than 10 ng/mL, bilateral pelvic lymphadenectomy is indicated only if prostate biopsy identifies tumor of Gleason grade 4 or higher. For lower-grade tumors in this patient population, the risk for nodal metastasis was less than 5% in the Johns Hopkins and Mayo Clinic series of over 5800 patients with prostate cancer. For a large pool of patients, the several thousand dollar cost of pelvic lymphadenectomy and the risk for injury to the obturator nerves and vessels, the formation of lymphoceles, and chronic genital edema can be eliminated with low risk. A nomogram-based approach provides only a starting point for a decision analysis framework to determine whether the surgeon should perform lymphadenectomy at the time of radical prostatectomy because current nomograms predict only lymph node positivity. In a decision analysis framework, some patient and physician value is derived from a negative lymphadenectomy. Moreover, the morbidity associated with pelvic lymphadenectomy and the potential inconvenience associated with treating such morbidity also would be factored into the decision. Consequently, a decision analysis framework that takes into account prognostic value, costs, morbidity, and health state uses ultimately will provide the most informative method for determining when pelvic lymphadenectomy is indicated in patients with prostate cancer.

Frozen Sections↗
PubMed2001

Rebuilding the lower urinary tract after cystectomy: a roadmap for patient selection and counseling.

Numerous options exist for reconstructing the lower urinary tract after radical cystectomy. Deciding between continent and noncontinent urinary diversion can be challenging for both physician and patient. This process should be logical and should integrate factors including the patient's malignancy, comorbid disease, functional status, and personal preference. Thorough patient education and a delicate balance between risk and benefit are critical to the success of any strategy for urinary diversion. This review presents a basic algorithm for planning reconstructive options and counseling patients before cystectomy.

Counseling↗
PubMed2000

Laparoscopic radical prostatectomy.

Laparoscopic radical retropubic prostatectomy (LRRP) is a new technique for treating organ-confined prostate carcinoma. The procedure was first described and proven to be feasible in 1997. To date, the results from over 150 cases have been reported in the literature. LRRP appears to be an efficacious procedure and deserves careful consideration. However, open radical retropubic prostatectomy (RRP) is routinely performed with excellent results and minimal morbidity. Whether LRRP offers any compelling benefit over open RRP remains to be determined, and will require a systematic comparison of technical advantages, morbidity, and long-term functional outcomes.

Humans↗
PubMed1997

Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice.

1. The role of alpha2-adrenoceptor (AR) subtypes in the modulation of acute nociception, motor behaviour and body temperature, has been investigated by determining the activity of the alpha2AR selective agonist dexmedetomidine (Dex) in mice devoid of individual alpha2AR subtypes through either a point (alpha2A) or null (alpha2B/alpha2C) mutation ('knock-out'). 2. In a rodent model of acute thermal nociception, the mouse tail immersion test, Dex, in wild type (WT) control animals, produced a dose-dependent increase in the threshold for tail withdrawal from a 52 degrees C water bath with mean ED50 values of 99.9+/-14.5 (alpha2A), 94.6+/-17.8 (alpha2B) and 116.0/-17.1 (alpha2C) microg kg(-1), i.p. 3. In comparison to the WT controls, Dex (100-1000 microg kg(-1), i.p.), was completely ineffective as an antinociceptive agent in the tail immersion test in the alpha2A AR D79N mutant animals. Conversely, in the alpha2B AR and alpha2C AR knock-outs, Dex produced a dose-dependent antinociceptive effect that was not significantly different from that observed in WT controls, with ED50 values of 85.9+/-15.0 (P>0.05 vs WT control) and 226.0+/-62.7 (P>0.05 vs WT control) microg kg(-1) i.p., respectively. 4. Dex (10-300 microg kg(-1), i.p.) produced a dose-dependent reduction in spontaneous locomotor activity in the alpha2A, alpha2B and alpha2C AR WT control animals with ED50 values of 30.1+/-9.0, 23.5+/-7.1 and 32.3+/-4.6 microg kg(-1), i.p., respectively. Again, Dex (100-1000 microg kg(-1), i.p.) was ineffective at modulating motor behaviour in the alpha2A AR D79N mutants. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in spontaneous locomotor activity with ED50 values of 29.1+/-6.4 (P>0.05 vs WT control) and 57.5+/-11.3 (P>0.05 vs WT control) microg kg(-1), respectively. 5. Dex was also found to produce a dose-dependent reduction in body temperature in the alpha2A, alpha2B and alpha2C AR WT control mice with ED50 values of 60.6+/-11.0, 16.2+/-2.5 and 47.2+/-9.1 microg kg(-1), i.p., respectively. In the alpha2A AR D79N mutants, Dex had no effect on body temperature at a dose (100 microg kg(-1), i.p.) that produced a significant reduction (-6.2+/-0.5 degrees C; P<0.01 vs vehicle) in temperature in WT controls. However, higher doses of Dex (300 and 1000 microg kg(-1), i.p) produced a small, but statistically significant decrease in temperature corresponding to -1.7+/-0.4 degrees C and -2.4+/-0.3 degrees C (both P<0.01 vs vehicle), respectively. In the alpha2B AR and alpha2C AR knock-out mice, Dex produced a dose-dependent reduction in body temperature with ED50 values of 28.4+/-4.8 (P>0.05 vs WT control) and 54.1+/-8.0 (P>0.05 vs WT control) microg kg(-1), respectively. 6. In conclusion, the data are consistent with the alpha2A AR being the predominant subtype involved in the mediation of the antinociceptive, sedative and hypothermic actions of Dex. This profile would appear to indicate that an alpha2A AR subtype selective analgesic will have a narrow therapeutic window, particularly following systemic administration.

Adrenergic alpha-Agonists↗
PubMed1997

Genetic alteration of alpha 2C-adrenoceptor expression in mice: influence on locomotor, hypothermic, and neurochemical effects of dexmedetomidine, a subtype-nonselective alpha 2-adrenoceptor agonist.

alpha 2-Adrenergic receptors (alpha 2-ARs) regulate many physiological functions and are targets for clinically important antihypertensive and anesthetic agents. Three human and mouse genes encoding alpha 2-AR subtypes (alpha 2A, alpha 2B, and alpha 2C) have been cloned. We investigated the involvement of the alpha 2C-AR in alpha 2-adrenergic pharmacology by applying molecular genetic techniques to alter the expression of alpha 2C-AR in mice. The effects of dexmedetomidine, a subtype-nonselective alpha 2-AR agonist, on monoamine turnover in brain and on locomotor activity were similar in mice with targeted inactivation of the alpha 2C-AR gene and in their controls, but the hypothermic effect of the alpha 2-AR agonist was significantly attenuated by the receptor gene inactivation. Correspondingly, another strain of transgenic mice with 3-fold overexpression of alpha 2C-AR in striatum and other brain regions expressing alpha 2C-AR showed normal reductions in brain monoamine metabolism and locomotor activity after dexmedetomidine, but their hypothermic response to the alpha 2C-AR agonists was significantly accentuated. The hypothermic effect of alpha 2-AR agonists thus seems to be mediated in part by alpha 2C-AR. Some small but statistically significant differences between the strains were also noted in brain dopamine metabolism. Lack of alpha 2C-AR expression was linked with reduced levels of homovanillic acid in brain, and mice with increased alpha 2C-AR expression had elevated concentrations of the dopamine metabolite compared with their controls.

Adrenergic alpha-Agonists↗
PubMed1996

Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c.

alpha2-Adrenergic receptors (alpha2ARs) are essential components of the neural circuitry regulating cardiovascular function. The role of specific alpha2AR subtypes (alpha2a, alpha2b, and alpha2c) was characterized with hemodynamic measurements obtained from strains of genetically engineered mice deficient in either alpha2b or alpha2c receptors. Stimulation of alpha2b receptors in vascular smooth muscle produced hypertension and counteracted the clinically beneficial hypotensive effect of stimulating alpha2a receptors in the central nervous system. There were no hemodynamic effects produced by disruption of the alpha2c subtype. These results provide evidence for the clinical efficacy of more subtype-selective alpha2AR drugs.

Adrenergic alpha-Agonists↗
PubMed1995

Targeted inactivation of the gene encoding the mouse alpha 2c-adrenoceptor homolog.

alpha 2-Adrenergic receptors (alpha 2-ARs) regulate a wide range of physiological functions and are targets for clinically important antihypertensive and anesthetic agents. Three genes encoding alpha 2-AR subtypes have been cloned in humans and mice, but the physiological significance of each subtype has not been completely characterized. The available agonist and antagonist compounds are not sufficiently subtype selective to allow the unambiguous dissection of these receptors in vivo. As an alternative approach, we have used gene targeting in embryonic stem cells to disrupt the Adra2c gene, which encodes the alpha 2c-AR subtype in mice. Adra2c-/Adra2c- animals do not express a functional alpha 2c-AR transcript, as detected by Northern blotting or reverse transcription-polymerase chain reaction analysis. In addition, these mice have markedly reduced [3H]rauwolscine binding in their caudate putamen and in other brain regions normally expressing Adra2c binding sites. Adra2c-/Adra2c- mice, however, are viable and fertile and appear grossly normal. Expression levels of Adra2a and Adra2b mRNA in brain and kidney are not altered by the Adra2c knockout. These data suggest that up-regulation of Adra2a or Adra2b does not compensate for the Adra2c deficiency and that the receptor encoded by Adra2c is not required for normal mouse development or for survival in a laboratory environment.

Animals↗
PubMed1993

Primary structure of the mouse beta 1-adrenergic receptor gene.

The mouse beta 1-adrenergic receptor was isolated from a genomic library and cloned into pBluescript SK-. Characterization of the clone revealed an open reading frame which encodes a predicted protein of 466 amino acids. The mouse beta 1 receptor is 92.7% identical to the human sequence, 98.5% identical to the rat sequence, and contains a consensus site for N-linked glycosylation at Asn-15 and a cAMP-dependent protein kinase phosphorylation site at Ser-301.

Amino Acid Sequence↗
PubMed1993

Linkage mapping of alpha-2 adrenergic receptor genes to mouse chromosomes 2 and 5.

alpha-2 adrenergic receptors can be subdivided into three related subtypes which are conserved in humans, rats, and mice. In the mouse, these receptors are encoded by three genes (Adra-2a, Adra-2b, Adra-2c). To gain insight into the evolution of this multigene family and to investigate whether these genes are candidates for previously identified mouse mutations, we have determined the map positions of the Adra-2b and Adra-2c genes. The Adra-2a gene has been previously mapped to mouse Chromosome (Chr) 19 (Oakey et al. Genomics 10, 338-344, 1991). Using segregation among recombinant inbred strains of a single-stranded conformational polymorphism specific for alleles of Adra-2b and Adra-2c, we present map positions for these genes on mouse Chrs 2 and 5, respectively. In the case of Adra-2b, these results have been confirmed by an analysis of somatic cell hybrids. In addition, we generate AKXD recombinant inbred strain distribution patterns for 11 previously defined SSLP microsatellite markers, further refining the haplotype maps for these chromosomes. Finally, several candidate mouse mutations that map close to Adra-2b and Adra-2c are discussed.

Animals↗
PubMed1992

Cloning and expression of the mouse homolog of the human alpha 2-C2 adrenergic receptor.

Three subtypes of alpha 2 adrenergic receptors have been identified in the human and rat. The subtype located on human chromosome 2 (alpha 2-C2) is unique in that it is expressed mainly in the peripheral tissues and lacks sites for N-linked glycosylation. We isolated the gene encoding the mouse homolog of the human alpha 2-C2 adrenergic receptor (M alpha 2-2H). The deduced amino acid sequence of the M alpha 2-2H shows 82% and 96% identity to the human alpha 2-C2 and the rat RNG alpha 2 adrenergic receptors, respectively. Southern blot analysis demonstrated that the M alpha 2-2H was encoded by a single copy gene and was distinct from the mouse homologs of the alpha 2-C4 and alpha 2-C10 adrenergic receptors. When expressed in COS-7 cells, the M alpha 2-2H exhibited a pharmacological profile similar to the human alpha 2-C2 and rat RNG alpha 2 receptors.

Adrenergic beta-Agonists↗
PubMed1990

Epithelial growth by rat vibrissae follicles in vitro requires mesenchymal contact via native extracellular matrix.

An in vitro assay utilizing the rat vibrissa anagen follicle as a model for studying the epithelial-mesenchymal interactions (EMI) in hair growth is described. Through selective disruption of the epithelial-mesenchymal interface, we investigate whether the specialized extracellular matrix (ECM) of the dermal papilla and basement membrane zone (BMZ) serves a crucial function in hair follicle EMI. Epithelial bulbs incubated intact within their follicular sheaths incorporate thymidine primarily into cells of the hair matrix and outer root sheath, as shown by autoradiography. However, after removal of its mesenchymal associations (dermal papilla and extrabulbar connective tissue), the epithelial bulb showed no incorporation. Neither externally added collagen (type I or IV) nor the basement membrane components in Matrigel could substitute for the growth supporting influence of native surrounding stroma. Mechanical separation of the bulb from the dermal papilla in the basement membrane zone inhibited thymidine incorporation by the epithelium even though mesenchyme was still in close proximity. Enzymatic digestion of the dermal papilla ECM and the basal lamina by Dispase, a fibronectinase and type IV collagenase, also inhibited bulb growth without evidence of cytotoxicity. These experiments suggest that direct epithelial to mesenchymal contact is required for the support of follicular epithelial growth in vitro and that specific ECM components, possibly fibronectin and/or type IV collagen, rather than diffusable factors alone, play a crucial role in the mechanism of hair follicle EMI. The in vitro system described here provides an alternative to developmental EMI models and may serve as a valuable tool for studying EMI in the adult mammalian organism.

Animals↗
PubMed1990

Telogen skin contains an inhibitor of hair growth.

We have investigated whether C57B1-6 mouse skin with all its follicles in the telogen stage of the hair cycle contains a hair-growth inhibitory activity, as opposed to skin with anagen follicles. Crude aqueous extracts of whole telogen mouse skin (TE), anagen skin (AE) or vehicle alone (V) were injected intraperitoneally into mice in which anagen had previously been induced by plucking of telogen hair follicles. Injection of TE, but not AE or V, significantly retarded the development of anagen follicles, as measured by macroscopic and quantitative microscopic hair growth parameters (skin pigmentation and thickness, appearance of trichohyaline granules) and the incorporation of tritiated thymidine into mouse skin from animals previously treated with either TE or V (skin organ culture). This inhibitory activity seemed to be localized to the epidermis and was also present in rat epidermis. We suggest that this apparently non-species-specific inhibitor present in telogen skin may play a role in regulating the hair cycle in rodents.

Animals↗
PubMed1989

The induction of anagen hair growth in telogen mouse skin by cyclosporine A administration.

One clinical complication of immunosuppressive cyclosporine A (CsA) therapy is the stimulation of hair growth. Since few pharmacologic agents cause hypertrichosis, CsA appears particularly interesting for investigating the mechanisms which control normal hair formation. Previous investigators have shown that CsA affects the hair growth of the laboratory rat, several genetic variants of mice, as well as humans, and they have concluded that CsA influences keratinization predominantly. Using a well-defined in vivo assay which measures the induction of hair follicle growth, we report here that CsA induces resting (telogen) follicles to enter active growth (anagen) in normal laboratory mice (C57 B1-6), i.e., animals with a normal hair cycle. The experiments indicate that the rate of anagen induction is dependent on the dose, time course, and method of administration and that it may be mediated via a direct action of CsA on the skin and its appendages. These studies suggest that understanding the molecular mechanisms of CsA action on hair growth will help elucidate the mechanisms of normal anagen induction.

Administration, Topical↗
PubMedDate not supplied

The psoriatic epidermal lesion and anagen hair growth may share the same "switch-on" mechanism.

Based on striking parallels between the cell kinetics in the epidermal lesion of psoriasis and the proliferation of hair matrix keratinocytes during the anagen phase of the hair growth cycle, the hypothesis is proposed that both phenomena may share the same "switch-on" mechanism. Particular emphasis is placed on a comparison between the Koebner phenomenon in psoriasis and wounding-induced anagen hair growth. In discussing alternative theoretical models for the proposed common "switch-on" mechanism, some useful experimental tools are suggested. Research into the mechanisms which control epithelial proliferation in psoriasis and hair growth may provide new insights into other growth processes, such as embryonic organogenesis and neoplasia, in which similar epithelial-mesenchymal interactions play a pivotal role.

Animals↗