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PubMed2001

Treatment of cancer pain with transdermal fentanyl.

Pain is a feature of many cancers, particularly in the advanced stages at which the palliative care approach to symptom control achieves the best outcomes. The holistic approach generally dictates that any treatment of the cancer per se has symptom control as the primary objective at this advanced stage. Pain, which invariably increases with disease progression, is treated with opioids and adjuvant analgesic drugs together with physical therapies. Orally administered opioid drugs are used preferentially because of cost and convenience, but other routes of administration (subcutaneous, rectal, spinal) are also possible. More recently, transdermal fentanyl has been evaluated in the treatment of moderate to severe cancer pain. The rate of fentanyl absorption is constant (after a lag period), and the dose is altered by increasing or decreasing the area of skin covered by the patch (size and/or number of patches). The dosing interval for these systems is generally 3 days. The extent of pain relief provided by transdermal fentanyl and sustained release morphine formulations is similar, with quality-of-life instruments showing no consistent preference for either formulation. Open studies have suggested a lower risk of constipation. Transdermal fentanyl is effective in the treatment of severe cancer pain, particularly when the oral route is unavailable.

Administration, Cutaneous↗
PubMed2004

Randomized comparison of loops for transurethral resection of the prostate: preliminary results.

PURPOSE: To evaluate the comparative efficacy and morbidity of standard transurethral resection of prostate (TURP) and transurethral vaporesection (TUVRP) using four types of loops. PATIENTS AND METHODS: In a one-to-one randomized study, 50 patients with lower urinary-tract symptoms suggestive of bladder outlet obstruction and benign prostatic enlargement underwent TURP. Clinical data were collected using digital rectal examination, transrectal ultrasonography for evaluation of prostate volume, IPSS and IIEF-5 questionnaires, and serum prostate specific antigen concentrations. Intraoperative blood loss and fluid absorption were evaluated by measuring serum hemoglobin and respiratory alcohol concentration. Patients were followed at 3 and 18 months with evaluation of clinical symptoms, flow rates, residual urine volumes, and complications. RESULTS: There were no significant differences in blood loss, intraoperative fluid absorption, procedure time, or weight of the resected tissue between standard TURP and TUVRP with the various loops. No significant complications (infections, urethral stricture, reintervention) were seen. CONCLUSIONS: In this comparison of the clinical outcome and morbidity of standard TURP versus different loops for TUVRP, there were no significant differences in any of the parameters evaluated.

Aged↗
PubMed1983

Plasma membranes, cell junctions and cuticle of the rectal chloride epithelia of the larval dragonfly Aeshna cyanea.

The cell membranes and cell junctions of the rectal chloride epithelia of the larval dragonfly Aeshna cyanea were examined in thin sections and by freeze-fracture. These epithelia function in active ion absorption and maintain a high concentration gradient between the haemolymph and the fresh-water environment. Freeze-fracturing reveals fine-structural differences in the intramembraneous particles of the luminal and contraluminal plasma membranes of these epithelia, reflecting the functional diversity of the two membranes, which are separated by the junctional complex. The particle frequency of the basolateral plasma membranes is reduced after transfer of the larvae into high concentrations of environmental salinity. The junctional complex is located in the apical region and composed of three types of cell junctions: the zonula adhaerens, seen in freeze-fracture as a nearly particle-free zone; the extended and highly convoluted pleated septate junction and randomly interspersed gap junctions of the inverted type. Gap junctions also occur between the basolateral plasma membranes. They provide short-cuts in the diffusion pathway for direct and rapid co-ordination of the interconnected cell processes. Colloidal and ionic lanthanum tracer solutions applied in vivo from the luminal side penetrate through the cuticle via epicuticular depressions, but invade only the apical portion of the junctional complex. This indicates that the pleated septate junction constitutes a structural control of the paracellular pathway across the chloride epithelia, which are devoid of tight junctions. The structure of the pleated septate junctions is interpreted as a device for the extension of the diffusion distance, which is inversely related to the net diffusion. A conservative estimate of the total length of the junction, and the number and extension of septa reveals that the paracellular route exceeds the transcellular route by a factor of 50.

Animals↗
PubMed1975

Bioavailability of acetaminophen suppositories.

Urinary excretion of acetaminophen after rectal administration of three suppository formatulations obtained from hospital and commercial sources was compared to that after oral administration of a tablet dosage form. The absorption of acetaminophen from the suppositories was extremely variable and showed relative bioavailabilities of 68.4 to 87.5% when compared to the oral absorption of the drug from the tablet. The rate of bioavailability differed markedly between products and, in one case, the suppository dose of acetaminophen was so slowly absorbed that the clinical effectiveness of the product is doubtful. The study points out the need for in vivo evaluation of hospital pharmacy manufactured products.

Acetaminophen↗
PubMed2001

Recommendations for the clinical development of topical microbicides: an update.

Topical microbicides are products that are being developed to prevent HIV infection and other sexually transmitted diseases (STD) through topical application to the genital and rectal epithelial surfaces. This paper is an update of the clinical section of a general guidance for the development and evaluation of microbicidal products that was first published by the International Working Group on Microbicides (IWGM) in 1996. (The preclinical section of that document will be updated separately later.) All topical microbicides should be clinically evaluated in humans for safety and effectiveness. Safety studies are necessary to evaluate the potential for systemic absorption and toxicity as well as local toxic effects, such as irritation, ulceration, burning, and itching. Reported symptoms of burning and itching are relevant to future product use and acceptability. Irritation and ulceration of the vaginal, cervical, penile, or rectal epithelium have the potential to result in an increased transmission of HIV and other STD. Effectiveness studies to assess the prevention of HIV infection or STD, depending upon the product indication, are subsequently conducted. These trials need to be large enough to detect clinically meaningful levels of protection. For spermicidal microbicides, additional contraceptive effectiveness studies are also needed.

Administration, Topical↗
PubMed1991

Failure of cholinergic stimulation to induce a secretory response from the rectal mucosa in cystic fibrosis.

The secretory response to cholinergic stimulation was investigated in rectal biopsy specimens from children with cystic fibrosis and a control group using a modified Ussing chamber technique. Acetylcholine (10(-3) mol/l) increased the short circuit current in 12 control specimens by mean (SEM) 83.0 (16.4) microA/cm2, but samples from five children with cystic fibrosis failed to exhibit such a response (-1.4 (3.2) microA/cm2). Amiloride (10(-4) mol/l), which will inhibit electrogenic sodium absorption in viable tissues, caused similar reductions in the short circuit current of both control and cystic fibrosis tissues (control = -37.7 (7.7) microA/cm2; cystic fibrosis = -44.0 (9.3) microA/cm2). Thus, the failure of chloride secretion observed in the small intestine also exists in the rectal mucosa. This observation could be used both to aid diagnosis and to study the basic defect.

Acetylcholine↗
PubMed1988

Some major transport mechanisms of insect absorptive epithelia.

1. After hormonal stimulation, fluid reabsorption (JV) in locust hindgut from the KCl-rich, low-Na primary urine is driven primarily by an unusual mucosal electrogenic Cl- pump (JCl). 2. Cyclic-AMP increases JCl and also mucosal K+ and basolateral Cl- conductances, so that KCl absorption exceeds that of Na+ in rectum but not ileum. 3. Mucosal entry of Na+ occurs by exchange for NH4+ (H+), by cotransport with some neutral amino acids, and through putative channels. 4. However, transport of proline, the predominant organic substrate, is largely Na-independent and drives a sizable component of Jv in rectal but not ileal segments. 5. There is evidence for hormonal control of Na+ reabsorption in ileum but not rectum.

Absorption↗
PubMed1995

Metabolism of vasopressin, oxytocin, and their analogues in the human gastrointestinal tract.

The bioavailability from the gastrointestinal tract of peptides as large as nonapeptides is very low, which may be attributed to extensive lumenal and mucosal degradation. The aim of the present study was to investigate the stability of the neurohypophyseal hormones arginine-vasopressin (AVP), oxytocin (OT), and their synthetic analogues in human intestinal contents, small intestinal brush-border membranes, and gastric, rectal, and colonic plasma membranes. Peptides were incubated in gastrointestinal contents from healthy volunteers and in human intestinal mucosa homogenates. The extent of degradation was determined by reversed-phase high performance liquid chromatography (HPLC). AVP was rapidly degraded in the ileum fractions of the intestinal contents whereas 50% of the analogue 1-deamino-8-D-arginine vasopressin (dDAVP) remained intact after 35 min. The degradation was pH dependent, and a concentration-dependent inhibition was observed when aprotinin, a proteinase inhibitor, was preincubated with contents from the ileum. No degradation of AVP, dDAVP, or oxytocin analogues was observed in the mucosa homogenate from the stomach. The peptides were found to be rather slowly degraded by intestinal microvilli membranes and colonic and rectal plasma membranes. This degradation occurred essentially when reduced glutathione 10(-4) M was added to the incubations. In conclusion, the major enzymatic barrier to intestinal absorption of OT, VP, and their analogues is present in the intestinal juice and not in the mucosa, which, however, constitutes a major physical barrier to peptide transport.

Adult↗
PubMed1988

Biopharmaceutics, pharmacokinetics and pharmacology of psoralens.

The psoralen derivative 8-methoxypsoralen (8-MOP) and to a lesser extent some other psoralens, including 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP) have acquired a place in the treatment of psoriasis and other dermatoses. They are only active when combined with long-wave ultraviolet light: PUVA therapy (Psoralen plus UVA). Successful PUVA therapy depends on sufficiently high psoralen concentrations coinciding with the time of irradiation. The use of oral or rectal pharmaceutical formulations with 8-MOP dissolved in liquid is preferable to conventional tablets or capsules. Since no formulation of 5-MOP with fast and predictable absorption is available 8-MOP should be preferred in PUVA therapy. The effectiveness of oral TMP is doubtful, because of low serum concentrations, probably due to malabsorption.

Animals↗
PubMed1975

Mouse vaginal assay for topically effective chemotherapeutic agents.

A number of chemotherapeutic drugs have been subjected to intravaginal testing in mice to measure their local inhibitory activity on DNA, RNA, and protein synthesis in vaginal epithelium. The drugs have been tested at various concentrations and in different vehicles and evaluated by autoradiographic techniques. Systemic absorption of the drugs was monitored by simultaneous study of the gastrointestinal mucosa of the rectum. Methotrexate inhibited deoxyuridine incorporation into DNA in both vaginal and rectal epithelium. Several lipid-soluble analogues of methotrexate were found to have no effect on deoxyuridine incorporation. Nitrogen mustard and emetine have been shown to selectively inhibit DNA and protein synthesis, respectively, without systemic effects. This animal assay system may be useful for predicting the effectiveness of potential drugs for the topical treatment of psoriasis.

Administration, Topical↗
PubMed2002

[Transurethral resection of prostate perioperative hypotension]

OBJECTIVE: To identify the factors to transurethral resection of prostate (TURP) perioperative hypotension. METHODS: The study group included 130 patients undergoing TURP. The control group included 50 patients who had suprapubic prostatectomy. Absorption of irrigation fluid was measured by determining the serum gentamycin level. Blood loss of PURP patients was calculated as the product of the irrigation fluid volume and hemoglobin concentration (determined with a photometer) divided by the preopreative blood hemoglobin concentration. Body temperature was recorded using a rectal probe. Serum electrolytes were determined pre-and postop. RESULTS: The blood loss in study group (380.2+/-98.3)ml was significantly less than in the control group (460.1+/-52.5)ml, P<0.05. However, the incidence of hypotension was significantly higher than the control group 28%, 8%), P<0.01. Factors associated with TURP hypotension included volume of irrigation fluid absorption, blood loss, reduction in core temperature, decrease of serum sodium, operating time, prostate weight and volume and history of cardiovascular disease. After Logistic regression analysis, the most significant factors were excessive absorption of irrigation fluid and rapid central cooling. CONCLUSION: In our study TURP hypotension most closely correlated with volume of irrigation fluid absorbed and reduction in core temperature.

Journal Article↗
PubMed1971

Abnormalities in intestinal electrolyte transport in congenital chloridorrhoea.

An investigation of small intestinal electrolyte transport was performed in a subject with congenital chloridorrhoea using a constant perfusion technique. The results indicate that the diarrhoea was not due to an abnormally high rate of secretion of fluid into the duodenum, and transport of electrolytes and glucose was normal in the jejunum. In contrast there was a marked abnormality of electrolyte transport in the ileum, chloride, sodium, and water entering the lumen and bicarbonate being absorbed in the absence of any concentration gradients for these ions. This is clearly different from the finding in normal subjects of sodium chloride and water absorption and bicarbonate secretion. It is suggested that the likely prime mechanism for these abnormalities is a chloride/bicarbonate exchange acting in the direction of chloride secretion, that is, in the opposite direction to the normal anion exchange. The hydrogen ion gradient set up by this exchange could have induced a secondary reversal of the normal sodium/hydrogen exchange so that hydrogen was absorbed and sodium secreted. From an analysis of the stool electrolyte concentrations and the rectal electrical potential difference it is suggested that in the colon chloride was secreted and bicarbonate absorbed against electrochemical gradients. Here too a reversed chloride/bicarbonate exchange is possibly responsible for the composition of the faecal electrolytes. As evidenced by the low faecal sodium concentration and the normal rectal potential difference, sodium transport is probably normal in the colon.

Adolescent↗