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Biomedical subjects

V H Price

Publications and source records attributed to V H Price.

At least 19 recordsLinked to original sources

Anatomic, functional, and pathologic changes from internal ureteral stent placement.

The anatomic, hydrodynamic, functional, and pathologic changes associated with unilateral internal ureteral stenting were evaluated in 20 female canines. Selective glomerular filtration rates (GFR) were measured with technetium 99m diethylenetriamine pentaacetic acid (DTPA) renal scans (N = 14) prior to and several weeks after unilateral internal stent placement. Cystometry and cystography were done at weekly intervals to determine if reflux occurred and to measure the intravesical pressure to produce this reflux (N = 16). Ureteral lumenal capacities of mid 6-cm ureteral segments of stented and unstented ureters were compared. The mid-ureteral lumenal volumes were three times greater in the stented ureters (p < 0.002). There were no significant differences in the selective GFR before and after stenting. Low-pressure vesicoureteral reflux occurred at a mean intravesical pressure of 13.7 cm of water and was present in 84.6 percent (11/13) of the canines whose stents did not migrate or obstruct from encrustation. There were no significant alterations in serum chemistries or blood counts. Fluoroscopic imaging also showed ineffective ureteral peristalsis. This study confirms that internal ureteral stents cause vesicoureteral reflux and significant lumenal dilation without altering renal function.

Animals

Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration.

The therapeutic value of topical minoxidil in alopecia areata (AA) has been investigated in recent years, with variable results. Although the mechanism whereby minoxidil may stimulate hair regrowth in some cases of AA has not yet been elucidated, there have been reports of a decrease in the perifollicular infiltrates of mononuclear leukocytes (MNC)--particularly T lymphocytes--that characterize this condition, in patients "responding" to topical minoxidil. In a randomized and double-blind study, we have investigated the effect of 5% topical minoxidil versus placebo (vehicle alone) on the extent and composition of the perifollicular MNC infiltration in 20 patients having extensive AA (26-99% scalp hair loss). The proportions of hair follicles showing perifollicular infiltration by MNC and their main subsets were determined with histologic and immunohistochemical stainings of scalp biopsies obtained before treatment, after 12 weeks of randomized double-blind minoxidil versus placebo treatment, and after 12 additional weeks during which all patients received minoxidil. Six of the patients showed cosmetically acceptable hair regrowth (CAHR) at the end of the 24 weeks and this was associated with a significant decrease in the proportions of follicles infiltrated by total T and B lymphocytes, macrophages, and Langerhans cells at week 12, and by total T lymphocytes at week 24. However, no significant differences in the extent or composition of the perifollicular infiltrates were detected at week 12 between patients receiving minoxidil and placebo, or between the week-12 and week-24 biopsies of those patients who first received placebo and then minoxidil. These findings indicate that in AA the reduction in perifollicular T-cell infiltration associated with CAHR is not attributable to an effect of topical minoxidil.

Adolescent

Circadian rhythm of ornithine decarboxylase activity in small intestine of fasted rats.

The aim of this study was to determine whether the circadian changes in ornithine decarboxylase (ODC) activity of different segments of the small intestine were governed by factors other than food intake. First, the effects of fasting on mucosal ODC activity were examined. The results indicate that mucosal ODC activity in 24 hr and 48 hr fasted rats decreased significantly compared with ad libitum-fed rats. Second, the circadian rhythm of mucosal ODC activity was characterized by measuring mucosal ODC activity in fasted rats at four time points (09:00, 15:00, 21:00, and 03:00 hr; light period: 06:00-18:00 hr). The results from this study indicate that there is a detectable baseline ODC activity in different segments of fasting intestine. In duodenum, mucosal ODC activity was highest at 15:00 hr (light period), a time at which the rat was normally not eating. In jejunum and ileum, mucosal ODC activity increased between 21:00 and 03:00 hr (dark period). The observation that small intestine exhibits a distinct circadian rhythm of ODC activity in fasted rats suggests that not only food but also intrinsic factors can modulate physiologic oscillations in mucosal ODC activity.

Animals

Effect of ischemia-reperfusion on lipid digestion and absorption in rat intestine.

The purpose of this study was to assess intestinal function after ischemia-reperfusion (I/R). In two groups of intestinal lymph fistula rats (experimental), the superior mesenteric artery (SMA) was isolated and occluded for 10 min. In the remaining two groups (controls), the SMA was isolated but not occluded. Twenty-four or forty-eight hours after I/R, a lipid test meal containing radioactive triolein was infused at 3 ml/h for 8 h. Radioactive lipid in lymph, lumen, intestinal wall, portal and systemic blood, epididymal fat pads, and liver was determined. Lymph radioactive lipid output was markedly depressed in the 24-h experimental rats compared with the other three groups, and this deficiency was restored 48 h after I/R. This reduction in lipid output in lymph appeared to be the result of an increased portal transport of the infused radioactive lipid rather than a deficiency of digestion or absorption of infused triolein. We have further validated the markedly increased portal transport of radioactive lipid after I/R by using Triton WR-1339, which blocks peripheral metabolism of hepatic very low-density lipoproteins (VLDL). When Triton WR-1339 was introduced in 24 experimental and control animals, the experimental rats accumulated significantly more radioactive lipid (12-14% of infused lipid) than the control animals (2-3% of infused lipid), indicating a marked increase in portal transport of radioactive lipid, which was taken up by the liver and then resecreted into circulation as VLDL. Thus intestinal lipid absorption is sensitive to the deleterious effects of ischemia followed by reperfusion, and therefore it may be used as a functional assessment of the small intestine after I/R-induced injuries.

Adipose Tissue

Ornithine decarboxylase is involved in repair of small intestine after ischemia-reperfusion in rats.

To assess whether ornithine decarboxylase (ODC) is involved in mucosal repair after ischemia-reperfusion (I/R), two approaches were used: 1) measurement of mucosal ODC activity at different intervals after I/R, and 2) inhibition of ODC activity with alpha-difluoromethylornithine (DFMO, an irreversible inhibitor). In the first series of experiments, rats were allowed to recover after superior mesenteric arterial occlusion (10 min) before harvesting the intestinal mucosa for measurement of ODC activity. ODC activity increased markedly 6 h after I/R, and greater than 72 h were required for enzyme activity to return to normal. DFMO treatment completely abolished the I/R-induced increase in ODC activity. In another series of experiments, rats with an intestinal lymph fistula were infused intraduodenally at 3 ml/h with vehicle or 2% DFMO in vehicle immediately after I/R. Lipid absorption was measured at 24 and 48 h after I/R. In the DFMO group, lymph radioactive lipid output at 24 h after I/R was significantly lower compared with time-matched sham-operated controls. Lymph lipid output in rats receiving the vehicle was restored to a normal level at 48 h after I/R. However, this restoration of normal lymphatic lipid transport at 48 h I/R was not observed in the DFMO group. These observations indicate that ODC activity plays an important role in the repair process that results in complete restoration of mucosal function 2 days after I/R.

Animals

Quantitative estimation of hair growth. I. androgenetic alopecia in women: effect of minoxidil.

Quantitative growth of hair over a 40-week period is reported for eight women with androgenetic alopecia. Using a random, double-blind protocol, the women were given either a 2% minoxidil solution or a placebo of vehicle only. Hair in a permanently marked site on the fronto-parietal scalp was pulled through a 1-cm-square clear plastic template, and the outline of the template was drawn on the scalp. The hair was carefully hand clipped and collected at five eight-week intervals (one untreated and four treated), using great care to collect only hairs within the marked area. Subsequent measurements included the total weight of hair grown in the marked area, the total number of hairs, and, on a randomized 50-hair subsample, the weight, lengths, and optical diameters. Calculated quantities included average weight per hair, average length, and average optical width. The average total hair weight of minoxidil-treated subjects increased over the 32-week test period by 42.5%, compared to 1.9% for the placebo-treated subjects (average p = 0.018). Changes for the average number count were 29.9% and -2.6%, respectively (average p = 0.022). These increases, observed using an unusually small number of subjects, clearly distinguished the treated subjects from the untreated. During the same test period, the averaged quantities of weight, diameter, and length from the 50-hair subsample showed insignificant change (p usually greater than 0.5). In addition to showing a larger percentage increase than did the total number, the total weight is not only easier to obtain, but less prone to error during sampling and measurement. Therefore, we recommend that total weight from a defined area be considered as the primary quantitative estimator for hair growth.

Adolescent

Hormone replacement therapy acceptability to Nottingham post-menopausal women with a risk factor for osteoporosis.

In Nottingham we have assessed the acceptability of oral hormone replacement therapy (HRT) for an at risk group of post-menopausal women for osteoporosis. One hundred post-menopausal women between the ages of 50 and 70 years who had sustained a distal radial fracture were offered oral HRT. There was a 36% overall uptake of HRT with 9% of patients unable to take HRT because they had medical contraindications. The uptake in the 50-55 year age group was 54%. We conclude that in prospective studies of HRT for osteoporosis up to 50% of patients may not wish to take HRT and therefore study design should allow for this level of uptake.

Aged

Treatment of hirsutism with cimetidine.

We evaluated the efficacy of long-term cimetidine in treating hirsutism by monitoring four indices: subjective hair removal practice, grading of hair growth by the Lorenzo scale, photography, and hair weight measurement. Of 20 women with moderate to severe facial hirsutism treated with cimetidine, 300 mg four times daily, nine were followed for 48 weeks or longer. Of these nine subjects who completed 48-72 weeks of treatment, only two showed a decrease in hirsutism. None of the 11 subjects treated for less than 48 weeks had any decrease in hirsutism. We conclude that cimetidine, a weak antiandrogen, is not sufficiently effective to use in the treatment of hirsutism.

Adolescent

Loose anagen syndrome.

A distinctive new hair condition, the loose anagen syndrome, features anagen hairs that are loosely anchored and easily pulled from the scalp. The children studied had sparse hair that did not grow long and that pulled easily from the scalp. The majority of patients were blond girls, aged 2 to 5 years, but both sexes and those with dark hair can be affected. The hair was not fragile, and easily pulled hairs were misshapen anagen hairs without external root sheaths. Histologic examination of the hair showed abnormal premature keratinization of Huxley's and Henle's layers of the inner root sheath in some samples. Length and density of hair gradually increased with age, but anagen hairs remained loosely anchored in adulthood. This report describes findings in 22 children and five adults with the loose anagen syndrome.

Adult

HLA-DR expression by hair follicle keratinocytes in alopecia areata: evidence that it is secondary to the lymphoid infiltration.

There is evidence suggesting that alopecia areata (AA) may have an autoimmune pathogenesis, and it was recently reported that keratinocytes in the bulb of some hair follicles affected by this condition express class II HLA (HLA-DR) antigens, which are not present on the same cells in normal tissue. Since it has been proposed that an analogous ectopic HLA-DR expression by epithelial cells in other organs might be an early event leading to organ-specific autoimmunity, we have investigated the sequence in which perifollicular mononuclear cell (MNC) infiltration and ectopic HLA-DR expression on keratinocytes appear in recent-onset and long-standing cases of AA by immunostainings of affected and unaffected areas with monoclonal antibodies against leukocyte and HLA-DR antigens. In recent-onset AA lesions, ectopic HLA-DR expression on hair follicle keratinocytes was found only occasionally (in 3 out of 247 follicles examined) and was restricted to biopsies from the affected areas. This prevalence was significantly lower than the prevalence of hair follicles showing perifollicular MNC infiltrates in the same biopsies, and was also significantly lower than the prevalence of hair follicles showing ectopic HLA-DR expression on keratinocytes in the affected areas of longstanding cases. These findings suggest that in AA lesions the perifollicular MNC infiltration precedes the ectopic HLA-DR expression on hair follicle keratinocytes, and therefore argue against the notion of a primary role for that ectopic HLA-DR expression on epithelial cells in triggering the putative autoimmune response in AA.

Adolescent

Double-blind, placebo-controlled evaluation of topical minoxidil in extensive alopecia areata.

The safety and efficacy of 3% topical minoxidil were evaluated in the treatment of extensive patchy alopecia areata, alopecia totalis, and alopecia universalis. Patients with extensive patchy alopecia areata had greater than 50% scalp hair loss. In this double-blind study, thirty subjects applied minoxidil or placebo to half of the afflicted scalp area twice daily, with overnight petrolatum occlusion, for 1 year. Both male and female subjects, ranging in age from 9 to 65 years, were enrolled, fifteen subjects to each treatment group. Minoxidil applications were generally well tolerated except for three instances of scalp itching and dermatitis, two of which necessitated discontinuing the medication. Hair growth was seen in seven of eleven evaluable subjects (63.6%) in the minoxidil group and in five of fourteen evaluable subjects (35.7%) in the placebo group. Excellent, cosmetically acceptable hair growth was seen in three of eleven minoxidil-treated subjects (27.3%) and in one of fourteen placebo-treated subjects (7.1%). Examination of vital signs and laboratory measurements revealed no evidence of systemic effects of minoxidil. Seven of the twelve subjects assayed in the minoxidil group had detectable minoxidil serum levels, ranging from 0.4 to 7.5 ng/ml.

Administration, Topical

Topical minoxidil (3%) in extensive alopecia areata, including long-term efficacy.

This study was conducted to further evaluate the safety and efficacy of 3% topical minoxidil in the treatment of extensive alopecia areata. Patients were assigned to one of two treatment regimens in a double-blind manner. One group applied 3% minoxidil to the scalp twice daily for 64 weeks; the other group applied placebo for the initial 12 weeks and then switched to 3% minoxidil for the remaining 52 weeks. Thirty male and female subjects, ages 7 to 63 years, with extensive alopecia areata affecting 25% to 100% of the scalp were enrolled, fifteen subjects to each treatment group. Twenty-four of the thirty subjects had greater than 75% scalp hair loss. At 12 weeks the group treated with 3% minoxidil had slightly more hair growth than the placebo group, but the difference was not statistically significant. At 64 weeks, thirteen of twenty subjects (65%) who began with less than full scalp involvement (25% to 99% scalp hair loss) had terminal hair growth that was incomplete or cosmetically acceptable; of these, nine (45%) were cosmetically acceptable, a response that is significant in patients with severe alopecia areata. No hair growth or only slight growth was seen in all nine patients with 100% scalp hair loss at baseline. Thus the extent of hair loss at baseline was correlated with response at 64 weeks. Twenty-one of the patients continued treatment for a second year. Of these, thirteen showed further growth, three had no further growth, and five who had cosmetically acceptable hair growth during the first year had some hair loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical

Topical minoxidil in extensive alopecia areata, including 3-year follow-up.

Perhaps the most intriguing aspect of topical minoxidil is the fact that this drug can promote hair growth in two unrelated conditions: alopecia areata (AA) and androgenetic alopecia. The two conditions have quite different underlying mechanisms. In AA, hair follicles respond to some signal or cell injury by entering a state of aborted cyclical activity; this state can reverse itself spontaneously, or it can be temporarily circumvented with nonspecific immunomodulating agents. In androgenetic alopecia, genetically marked hair follicles undergo progressive, androgen-mediated miniaturization; antiandrogens have been conventionally sought to intercept this process. It is not known how minoxidil promotes hair growth except that living follicles capable of stimulation and hypertrophy are required. It may be that minoxidil influences some fundamental signal to the follicular apparatus, irrespective of the pathophysiology involved. We have used topical minoxidil solution in 90 patients, aged 7-63 years, with extensive AA affecting 25-100% of the scalp. One study was double-blind, and placebo-controlled for an entire year. Minoxidil-treated patients responded better than placebo-treated patients. Both 3 and 5% topical minoxidil solutions have been used, and treatment with the 3% solution has continued for up to 3 years. The results of these studies will be discussed. While topical minoxidil is not very effective for those with 100% scalp hair loss, it is an effective, easy and safe treatment for those with AA affecting 25-99% of the scalp.

Administration, Cutaneous