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Biomedical subjects

R Sinclair

Publications and source records attributed to R Sinclair.

At least 19 recordsLinked to original sources

Long-term clearance of patch-stage mycosis fungoides with the 308-nm laser.

In order to investigate the effectiveness of the 308-nm xenon chloride laser in the treatment of patch-stage mycosis fungoides that is refractory to topical steroids, we conducted a prospective, histologically controlled, open-label pilot study. Eight patients with stage 1A or 1B cutaneous T-cell lymphoma that was unresponsive to application of potent topical steroids received 20 treatments with the laser over 10 weeks and were then followed up for a minimum of 30 months. Three patients had a complete clinical and histological response and remained free of disease after 30 months A further three patients had complete clinical and histological clearance of disease, but experienced relapse within the 30 months follow-up period. One patient withdrew from the study and one had a partial response. Further research to establish the role of the 308-nm laser in the treatment of MF appears justified.

Adolescent↗

Follicular miniaturization in female pattern hair loss: clinicopathological correlations.

BACKGROUND: The pathology of female pattern hair loss (FPHL) is characterized by an increase in the proportion of vellus follicles, manifest as a low terminal/vellus ratio. This is conventionally thought to be due to a progressive miniaturization of terminal hair follicles. There is also a prolongation of the latent period of the hair cycle (kenogen) in both male pattern hair loss and FPHL and follicles in kenogen may be difficult to classify histologically. Therefore, a low terminal/vellus ratio could be due to a preferential increase in the number of terminal follicles in kenogen rather than to a true increase in the number of vellus follicles. OBJECTIVES: To establish whether there is an increase in the absolute number of vellus follicles during the progression of FPHL, indicating a process of follicular miniaturization. METHODS: We studied 42 women complaining of hair loss. The severity of the hair loss was graded clinically on a five-point scale from 1 (no obvious hair loss) to 5 (severe hair loss). Three 4-mm punch biopsies were taken from the frontal scalp of each patient, sectioned horizontally and stained with haematoxylin and eosin. Two levels were studied on each biopsy: through the mid-infundibular region and through the mid-isthmus. The following were counted: total follicles, terminal follicles, vellus follicles, anagen and telogen/catagen follicles. The results from the three biopsies from each subject were averaged and statistical evaluations performed on the mean values. RESULTS: There was a progressive decline in mean total follicle count with increasing grade of hair loss (grade 1, 317 cm(-2); grade 5, 243 cm(-2)) and a more pronounced reduction in terminal follicle counts (grade 1, 263 cm(-2); grade 5, 96 cm(-2)). The absolute number of vellus follicles increased from 33 cm(-2) (grade 1) to 71 cm(-2) (grade 4), declining to 51 cm(-2) at grade 5. The terminal/vellus ratio fell from 12.8 (grade 1) to 2.3 (grade 4) and remained at this level thereafter. The proportion of follicles in telogen increased from 13.7% (grade 1) to 31.4% (grade 5). CONCLUSIONS: Our results show that there is an increase in vellus follicle numbers with increasing severity of hair loss in women with FPHL, suggesting that terminal follicles do indeed miniaturize. It is possible that there is also an increase in the number of follicles in a latent stage of telogen but this was difficult to assess from our data. The fall in total follicle counts with stabilizing of the terminal/vellus ratio in severe hair loss suggests that miniaturization does not stop with a vellus follicle but progresses to follicular deletion.

Alopecia↗

Anti-inflammatory properties of local anesthetics and their present and potential clinical implications.

Development of new local anesthetic agents has been focused on the potency of their nerve-blocking effects, duration of action and safety and has resulted in a substantial number of agents in clinical use. It is well established and well documented that the nerve blocking effects of local anesthetics are secondary to their interaction with the Na+ channels thereby blocking nerve membrane excitability and the generation of action potentials. Accumulating data suggest however that local anesthetics also possess a wide range of anti-inflammatory actions through their effects on cells of the immune system, as well as on other cells, e.g. microorganisms, thrombocytes and erythrocytes. The potent anti-inflammatory properties of local anesthetics, superior in several aspects to traditional anti-inflammatory agents of the NSAID and steroid groups and with fewer side-effects, has prompted clinicians to introduce them in the treatment of various inflammation-related conditions and diseases. They have proved successful in the treatment of burn injuries, interstitial cystitis, ulcerative proctitis, arthritis and herpes simplex infections. The detailed mechanisms of action are not fully understood but seem to involve a reversible interaction with membrane proteins and lipids thus regulating cell metabolic activity, migration, exocytosis and phagocytosis.

Anesthetics, Local↗

The Mouse Genome Database (MGD): from genes to mice--a community resource for mouse biology.

The Mouse Genome Database (MGD) forms the core of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a model organism database resource for the laboratory mouse. MGD provides essential integration of experimental knowledge for the mouse system with information annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genotype (sequence) through phenotype information, including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships among genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent improvements in MGD discussed here include the enhancement of phenotype resources, the re-development of the International Mouse Strain Resource, IMSR, the update of mammalian orthology datasets and the electronic publication of classic books in mouse genetics.

Animals↗

Treatment of female pattern hair loss with oral antiandrogens.

BACKGROUND: It has not been conclusively established that female pattern hair loss (FPHL) is either due to androgens or responsive to oral antiandrogen therapy. OBJECTIVES: To evaluate the efficacy of oral antiandrogen therapy in the management of women with FPHL using standardized photographic techniques (Canfield Scientific), and to identify clinical and histological parameters predictive of clinical response. METHODS: For this single-centre, before-after, open intervention study, 80 women aged between 12 and 79 years, with FPHL and biopsy-confirmed hair follicle miniaturization [terminal/vellus (T/V) hair ratio < or = 4 : 1] were photographed at baseline and again after receiving a minimum of 12 months of oral antiandrogen therapy. Forty women received spironolactone 200 mg daily and 40 women received cyproterone acetate, either 50 mg daily or 100 mg for 10 days per month if premenopausal. Women using topical minoxidil were excluded. Standardized photographs of the midfrontal and vertex scalp were taken with the head positioned in a stereotactic device. Images were evaluated by a panel of three clinicians experienced in the assessment of FPHL, blinded to patient details and treatment and using a three-point scale. RESULTS: As there was no significant difference in the results or the trend between spironolactone and cyproterone acetate the results were combined. Thirty-five (44%) women had hair regrowth, 35 (44%) had no clear change in hair density before and after treatment, and 10 (12%) experienced continuing hair loss during the treatment period. Ordinal logistic regression analysis to identify predictors of response revealed no influence of patient age, menopause status, serum ferritin, serum hormone levels, clinical stage (Ludwig) or histological parameters such as T/V ratio or fibrosis. The only significant predictor was midscalp clinical grade, with higher-scale values associated with a greater response (P = 0.013). CONCLUSION: Eighty-eight percent of women receiving oral antiandrogens could expect to see no progression of their FPHL or improvement. High midscalp clinical grade was the only predictor of response identified. A placebo-controlled study is required to compare this outcome to the natural history of FPHL.

Adolescent↗

The lack of significant changes in scalp hair follicle density with advancing age.

BACKGROUND: Age-related reduction in hair is seen in the axillary and pubic regions as well as the scalp; however, it has not been investigated qualitatively on the scalp. Horizontally sectioned scalp biopsy is an ideal tool to investigate the impact of advancing age on scalp hair follicle density and morphology. OBJECTIVES: To examine the effect of age and follicle miniaturization on total hair count in 1666 horizontally sectioned mid-scalp biopsies from 928 women aged between 13 and 84 years with hair loss. METHODS SETTING: Specialist hair loss referral clinic in a teaching hospital. DESIGN: Analysis of data set. Methods: All scalp biopsies were 4 mm in diameter and taken from the crown. Miniaturization was assessed by calculating the ratio of terminal to vellus-like hairs (T/V) at the mid-isthmus level and considered significant if the ratio was < or = 4 : 1. Fibrosis was documented when present. Linear regression was used to examine the association between total hair count, age and miniaturization. RESULTS: The average number of hair follicles per biopsy was 39.6 (SD +/- 10.8). A highly significant negative association (P < 0.0001) was found between age and total follicle number, although the predictive value of age in total hair count was found to be small [root error mean square (R2) < 2%]. Controlling for T/V < or = 4 : 1, the association was weakened, but remained significant. The relationship unconfounded by T/V < or = 4 : 1 shows that for every additional year of ageing, 0.077 total hair follicles (0.22%) are lost per biopsy. CONCLUSIONS: Age and follicular miniaturization were found to be extremely weak predictors of total hair count in women with hair loss.

Adolescent↗

The Mouse Genome Database (MGD): integrating biology with the genome.

The Mouse Genome Database (MGD) is one component of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a community database resource for the laboratory mouse. MGD strives to provide a comprehensive knowledgebase about the mouse with experiments and data annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genetic, genotype (sequence) and phenotype information including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships between genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent developments in MGD discussed here include an extensive integration of the mouse sequence data and substantial revisions in the presentation, query and visualization of sequence data.

Animals↗

Women who present with female pattern hair loss tend to underestimate the severity of their hair loss.

BACKGROUND: Female pattern hair loss (FPHL) is the preferred term for androgenetic alopecia in women. FPHL can be a source of considerable distress for affected women. Our hypothesis was that women with FPHL who seek treatment would rate their condition as more severe than would their treating doctors. OBJECTIVES: To identify discrepancies between the severity ratings of the women and their clinicians. METHODS: Participants were 30 women receiving treatment for biopsy-proven FPHL and 44 women on a waiting list to receive treatment for FPHL. Each woman completed a self-report photographic measure of severity of hair loss, specifically developed for the current study. RESULTS: Although no difference was found between the severity ratings of women receiving treatment and their clinicians, it was found that women in the waiting list group underestimated the severity of their hair loss compared with their clinicians' ratings. CONCLUSION: The results indicate that FPHL-affected women who seek treatment for FPHL do not overestimate the severity of the hair loss; in fact, they tend to underestimate. The present findings have implications for the treatment of FPHL.

Adult↗

Effect of alpha-trinositol on secretion induced by Escherichia coli ST-toxin in rat jejunum.

AIM: d-myo-inositol-1,2,6-trisphosphate (alpha-trinositol, PP56), is a synthetic isomer of the intracellular second messenger, d-myo-inositol-1,4,5-trisphospahate. The pharmacological actions of alpha-trinositol include potent anti-inflammatory properties and inhibition of the secretion induced by cholera toxin and obstructive ileus. In the present study, we investigated whether alpha-trinositol was able to influence the secretion induced by heat-stable ST-toxin from Escherichia coli in the rat jejunum. METHODS: A midline abdominal incision was performed in anaesthetized male Sprague-Dawley rats and a 6-7 cm long jejunal segment was isolated with intact vascular supply and placed in a chamber suspended from a force displacement transducer connected to a Grass(R) polygraph. Intestinal net fluid transport was continuously monitored gravimetrically. Crystalline ST-toxin (120 mouse units) was introduced into the intestinal lumen and left there for the rest of the experiment. When a stable secretion was observed, alpha-trinositol (60 mg kg-1 h-1) or saline were infused during 2 h, followed by a 2-h control period. RESULTS: alpha-Trinositol induced a significant (P < 0.001) inhibition of ST-toxin secretion within 30 min, lasting until 2 h after infusion had stopped. The agent also moderately increased (P < 0.05) net fluid absorption in normal jejunum. Mean arterial pressure (P < 0.001) and heart rate (P < 0.001) were reduced by alpha-trinositol. CONCLUSION: The inhibition by alpha-trinositol of ST-toxin induced intestinal secretion is primarily secondary to inhibition of secretory mechanisms and only to lesser extent due to increased absorption. The detailed mechanisms of action have not been clarified but may involve suppression of inflammation possibly by means of cellular signal transduction.

Animals↗

Update on cicatricial alopecia.

Cicatricial alopecia is an enigmatic group of hair disorders linked by the potential permanent loss of scalp hair follicles in involved areas. Progress in our understanding and treatment of these disorders has been stymied by the lack of clear diagnostic criteria for the current terms used to describe the various hair loss entities. Since all of these conditions evolve as the hair is destroyed or replaced, diagnosis is further made difficult by a lack of clinical and pathologic "snapshots" over the evolution of each disorder. Without some acceptance of general clinical and histological presentations in the early, mid and late stage of these disorders, one cannot begin to explore ways to make the diagnosis at a very early stage before significant follicular destraction has occurred (making the clinical diagnosis obvious) and when the damage is potentially repairable or progression preventable.

Alopecia↗

Androgenetic alopecia in men aged 40-69 years: prevalence and risk factors.

BACKGROUND: The epidemiology of androgenetic alopecia (AGA) is not fully understood. Although a strong genetic basis has long been identified, little is known of its non-genetic causes. OBJECTIVES: To estimate the prevalence of and to determine risk factors for AGA in men aged 40-69 years in Australia. METHODS: Men (n = 1390) were recruited at random from the electoral rolls to serve as controls in a population-based case-control study of prostate cancer. All were interviewed in person and direct observations of AGA were made. Men were grouped into the following categories; no AGA, frontal AGA, vertex AGA and full AGA (frontal and vertex AGA). Epidemiological data collected from these men were used for an analysis of risk factors for each AGA category using unconditional logistic regression with AGA category as the response variable adjusting for age, education and country of birth. RESULTS: The prevalence of vertex and full AGA increased with age from 31% (age 40-55 years) to 53% (age 65-69 years). Conversely, the proportion of men with only frontal AGA was very similar across all age groups (31-33%). No associations were found between pubertal growth spurt or acne, reports of adult body size at time of interview, urinary symptom score, marital status, or current smoking status or duration of smoking and the risk of any form of AGA. The consumption of alcohol was associated with a significant increase in risk of frontal and vertex AGA but not full AGA. Men with vertex AGA had fewer female sexual partners but average ejaculatory frequency did not differ between men in different AGA categories. Reported weight and lean body mass at reaching maturity at about 21 years of age were negatively associated with vertex balding (P for trend < 0.05) but not with frontal AGA or full AGA. CONCLUSIONS: Evidence for environmental influences on AGA remains very slight. Our study failed to confirm previously reported or hypothesized associations with smoking and benign prostatic hypertrophy. The associations that we found with alcohol consumption and with lean body mass at age 21 years would be worthy of further research if they were able to be replicated in other studies.

Adult↗

Hair colouring, permanent styling and hair structure.

Hair is an important component of body image and has immense psychological importance for both men and women. Women, in particular, over the ages have modified their appearance through changing their hair colour or style. Hair can be straight, wavy or curly, blonde, black, brown or red. These natural variations are an important part of our identity that can be manipulated according to the dictates of fashion, culture or society. Different types of hair have varying affinity for the different colouring and waving methods. Damaged hair also has a different affinity for hair products than normal healthy hair. The hair shaft is remarkably strong and resistant to the extremes of nature. Hair cosmetics are widely available and manipulate the structural properties of hair. Whilst most procedures are safe, there is considerable potential for damage to the hair and hair problems of acute onset, including hair breakage, hair loss and loss of condition, are frequently blamed on the last product used on the hair. Hair problems are particularly prevalent among people who repeatedly alter the natural style of their hair.

Journal Article↗

There is no clear association between low serum ferritin and chronic diffuse telogen hair loss.

BACKGROUND: Low iron stores are considered a possible cause of chronic diffuse telogen hair loss in women. Estimation of serum ferritin is recommended as part of the initial assessment when women present with chronic diffuse telogen hair loss, and iron supplementation therapy is commonly recommended for those found to have low iron stores. OBJECTIVES: To evaluate the relationship between low serum ferritin (</=20 micro g L-1) and chronic diffuse telogen hair loss in women. METHODS: Between 1997 and 1999, 194 consecutive women who presented to a specialist hair clinic were assessed for diffuse telogen hair loss of greater than 6 months duration. All underwent biochemical investigations that included serum ferritin and had two 4-mm punch biopsies taken from the vertex of the scalp. One biopsy was sectioned horizontally and the other vertically. RESULTS: Twelve women were found to have a serum ferritin of 20 micro g L-1 or less (6.2%). Androgenetic alopecia was found on scalp biopsy in seven of these 12 women, while the other five women had normal histology. The five women with low iron stores and normal histology were treated with iron supplementation alone. This was continued until the serum ferritin was > 20 micro g L-1. Cessation or reversal of hair loss was not seen in any of these women. CONCLUSIONS: No direct relationship between low serum ferritin and hair loss can be established. The usefulness of serum ferritin in the routine investigation of women with chronic diffuse telogen hair loss is unclear, as is the role of iron supplementation therapy in the management of hair loss.

Adolescent↗

Telogen effluvium.

The term telogen effluvium, first coined by Kligman in 1961, refers to the loss of club (telogen) hair in disease states of the follicle. Kligman's hypothesis was that whatever the cause of hair loss, the follicle tends to behave in a similar way, namely the premature termination of anagen. "The follicle is precipitated into catagen and transforms into a resting stage that mimics telogen." Ipso facto the observation of telogen hair loss does not infer a cause. To establish the cause of the hair loss, one requires a history to identify known triggers, biochemical investigations to exclude endocrine, nutritional or autoimmune aetiologies and in many cases histology to identify the earliest stages of androgenetic alopecia. The duration of the hair loss at presentation helps predict those patients in whom further investigation will have the greatest yield. "It is unfortunate that baldness has been approached with an eye toward "regrowing" or "restoring hair", and thus with a tendency toward commercialism. Locked within the metamorphosing hair follicles in the balding scalp are all the secrets of growth and differentation. Searching for these secrets should transcend the eagerness to "regrow" hair on a bald scalp, an achievement which is of no great consequence. When we know these answers, we shall have the key, not to hair growth alone, but to all growth, which is, after all, the basis of all biological phenomena." William Montagna, 1959.

Acute Disease↗

Acute renal failure following ingestion of wild mushrooms.

We describe three cases of acute renal failure in young men who ingested wild mushrooms with the intent of producing hallucinations. Two cases remained dialysis dependent and, in these cases, renal biopsy revealed tubulointerstitial nephritis and fibrosis. Similar cases have been reported in other countries, but not in Australia. The most recognized mushroom nephrotoxin is orellanine, however the causative mushroom species and the actual toxin involved in these cases are unknown.

2,2'-Dipyridyl↗