Associations of progesterone receptor polymorphisms with age at menarche and menstrual cycle length.

BACKGROUND: Age at menarche and menstrual cycle characteristics are indicators of endocrine function and may be risk factors for diseases such as reproductive cancers. The progesterone receptor gene (PGR) has been identified as a candidate gene for age at menarche and menstrual function. METHODS: Women office workers ages 19-41 self-reported age at menarche and participated in a prospective study of menstrual function and fertility. First-morning urine was used as the DNA source. 444 women were genotyped for a functional variant in PGR, rs1042838 (Val660Leu), and 264 women were also genotyped for 29 other SNPs across the extended gene region. RESULTS: Genetic variation across PGR was associated with age at menarche using a global score statistic (p = 0.03 among non-Hispanic whites). Women carrying two copies of the Val660Leu variant experienced menarche 1 year later than women carrying one or no copies of the variant (13.6 ± 0.5 vs. 12.6 ± 0.1; p = 0.03). The Val660Leu variant was also associated with decreased odds of short menstrual cycles (17-24 days) (OR, 95% CI: 0.54 [0.36, 0.80]; p = 0.002). CONCLUSION: Genetic variation in PGR was associated with age at menarche and menstrual cycle length in this population. Further investigation of these associations in a replication dataset is warranted.

The clients' perspective--do military uniform and rank impact on the therapeutic relationship between military mental health clients and clinicians.

OBJECTIVE: To measure the perception of military mental health clients of the impact of wearing military uniform on the therapeutic relationship between client and clinician and to ascertain if uniform and rank is perceived as a barrier. METHOD: A brief questionnaire was distributed to Departments of Community Mental Health to be disseminated to their mental health clients to measure their responses. RESULTS: 282 responses from mental health clients were collected over a 30 day period regarding the impact that military uniform makes to the therapeutic relationship with the clinician. 63% (n = 178) regarded uniform as negatively influencing their relationship with the clinician, 37% (n = 104) responded that it did not. 39% (n = 111) believed rank to be a barrier, whereas 61% (n = 171) did not believe it affected the relationship. CONCLUSION: The majority of military mental health clients regard the wearing of uniform as negative to the therapeutic relationship and a significant minority have similar feelings about rank. Military mental health practitioners should consider the impact of these results on the therapeutic relationship with military patients.

Anorexia of aging in long term care: is dronabinol an effective appetite stimulant?--a pilot study.

INTRODUCTION: Anorexia and subsequent weight loss increase the risk of death in long term care (LTC) residents. In patients who fail to respond to nutritional intervention, orexigenic drugs are sometimes prescribed. There is limited data regarding the safety and efficacy of these drugs in older adults. OBJECTIVE: To examine the effect of a 12-week course of dronabinol on LTC residents with anorexia and significant weight loss. DESIGN, SETTING, PARTICIPANTS: Retrospective observational study on residents in five LTC facilities in a major metropolitan area. RESULTS: Twenty-eight subjects (22F, 6M) were involved in the study. Mean age 79.5 +/- 19.8 years (range 46-98 y). Mean body weight, serum albumin and serum prealbumin at baseline were 105.7 +/- 24.7 lbs, 3.39 +/- 0.47 g/dl and 22.15 +/- 7.92 mg/dl respectively. 15 subjects (53.5%) gained weight on dronabinol, of which 10 (67%) gained more than 5 lbs and 6(40%) gained more than 10 lbs. Five (33%) subjects gained less than 5 lbs. Residents who lost weight on dronabinol were younger than those who gained weight (70.9 +/- 5.62 y and 90.8 +/- 7.84 y respectively; p = 0.007) Overall, the mean weight gain on dronabinol was 3 +/- 8.01 lbs (p=0.2). Eleven subjects lost weight (mean loss 3 +/- 2.6 lbs). Of the subjects who lost weight 7 (64%) died compared with 4 (26%) in the subgroup who gained weight. CONCLUSIONS: Dronabinol therapy was well tolerated. Overall, there was a trend toward weight gain in LTC residents treated with 12 weeks of dronabinol. Failure to respond to dronabinol may indicate increased risk of death.

Do military uniform and rank impact on the therapeutic relationship between military mental health clients and clinicians?

OBJECTIVE: to measure the perceptions of military staff of the impact of wearing military uniform on the therapeutic relationship with mental health clients. METHOD: a brief questionnaire was distributed to all military clinicians in Departments of Community Mental Health to measure their attitudes. RESULTS: there was a 67.9% (n=70) response rate regarding the impact of uniform on the therapeutic relationship. 20% of responses were positive, 31% negative, 37% mixed and 12% gave no answer. CONCLUSION: there was no clear pre-existing literature on this issue. Overall, the wearing of uniform appeared to be perceived positively positive. There is a need to assess clients' points of view in future studies.

A prospective, randomized clinical study of adjunctive peripheral parenteral nutrition in adult subacute care patients.

BACKGROUND: A number of frail, older, undernourished patients cannot maintain adequate oral intake to meet protein-calorie needs after an illness, even when high-density nutritional supplements are added. Tolerance to enteral nutrition by gastric tube is poor in this group of patients. Peripheral parenteral nutrition is an effective method of administering nutritional support to patients with mild to moderate nutritional deficiencies who are unable to receive enteral nutrition or for whom enteral nutrition alone cannot meet energy needs. However, no data exists for the use of peripheral parenteral nutrition longer than two weeks and overall there are remarkably few studies on the efficacy of peripheral parenteral nutrition. METHODS: A Phase 4, single center, prospective, randomized, parallel group design clinical trial was conducted to evaluate long-term safety of peripheral parenteral nutrition in post-acute patients receiving inadequate enteral nutrition. Nutritional status was measured by the Mini-Nutritional Assessment and functional status by the Functional Inventory Measure. Subjects received a mean duration for peripheral parenteral nutrition of 15.8 +/- 6.7 days (range 8-23). RESULTS: The peripheral parenteral nutrition group demonstrated several trends towards improvement in prealbumin, CD4 cell count, and functional status compared to the untreated control group. Two patients in the peripheral parenteral nutrition group developed low-grade phlebitis; however, this did not result in discontinuing intravenous therapy. No other adverse events occurred. This study demonstrates that peripheral parenteral nutrition is feasible and safe in postacute care. CONCLUSIONS: We conclude that peripheral parenteral nutrition can be safely administered in post-acute settings with a low rate of complications.

Impaired cognitive function and mental performance in mild dehydration.

Dehydration is a reliable predictor of impaired cognitive status. Objective data, using tests of cortical function, support the deterioration of mental performance in mildly dehydrated younger adults. Dehydration frequently results in delirium as a manifestation of cognitive dysfunction. Although, the occurrence of delirium suggests transient acute global cerebral dysfunction, cognitive impairment may not be completely reversible. Animal studies have identified neuronal mitochondrial damage and glutamate hypertransmission in dehydrated rats. Additional studies have identified an increase in cerebral nicotinamide adenine dinucleotide phosphate-diaphorase activity (nitric oxide synthase, NOS) with dehydration. Available evidence also implicates NOS as a neurotransmitter in long-term potentiation, rendering this a critical enzyme in facilitating learning and memory. With ageing, a reduction of NOS activity has been identified in the cortex and striatum of rats. The reduction of NOs synthase activity that occurs with ageing may blunt the rise that occurs with dehydration, and possibly interfere with memory processing and cognitive function. Dehydration has been shown to be a reliable predictor of increasing frailty, deteriorating mental performance and poor quality of life. Intervention models directed toward improving outcomes in dehydration must incorporate strategies to enhance prompt recognition of cognitive dysfunction.

Atypical presentation of scabies among nursing home residents.

BACKGROUND: Scabies epidemics are not uncommon in nursing homes. Effective treatment is enhanced by prompt clinical diagnosis and early intervention. The clinical presentation of scabies may vary in older, immunocompromised or cognitively impaired persons. METHODS: We performed a retrospective study of all residents diagnosed with scabies in a multilevel long-term care geriatric facility. The duration of the outbreak was from May to September 2000. RESULTS: Fifteen residents contracted scabies during the outbreak. All affected residents had predominantly truncal lesions. Twelve residents had diffuse erythematous, papulosquamous lesions. Pruritus occurred in only 5 residents. Three residents with severe dementia and notably impaired functional status failed to respond to Permethrin cream (5%). All 3 residents responded to treatment with oral Ivermectin. CONCLUSION: Older nursing home residents with scabies may present with atypical skin lesions. Residents with cognitive impairment and restricted mobility may be treatment resistant. The diagnosis of scabies should be considered in any nursing home resident with an unexplained generalized rash. Residents with dementia and severe functional impairment that fail to respond to Permethrin cream (5%) may benefit from treatment with oral Ivermectin.

Pigmented uveal tumours in a transgenic mouse model.

AIMS/BACKGROUND: The authors have developed transgenic mouse strains at the Arizona Cancer Center using a tyrosinase promoter to target expression of the mutated T24 Ha-ras gene in melanin producing cells. Histopathology and electron microscopy (EM) were performed to characterise the intraocular tumours observed phenotypically. METHODS: Transgenic TPras mice (n = 8) and normal, age matched control mice (n = 6) were sacrificed at 3 weeks, 6 weeks, 7 weeks, 4 months, 5 months, 9 months, and 11 months. Six were processed in formalin for light microscopic examination and eight in a glutaraldehyde/formalin solution for electron microscopic examination. RESULTS: Six of the TPras mice were found to have bilateral pigmented melanocytic/RPE proliferations of the uveal tract. The cytological characteristics of the tumours included low nuclear to cytoplasmic ratios (N:C ratios), bland nuclei, and abundant intracytoplasmic melanin. By EM two populations of cells were identified, including spindle-shaped cells with round to oval melanin granules and cuboidal cells with apically located, cigar-shaped, melanin granules, and basement membrane formation. A 3 week and an 11 month old TPras mouse had a higher grade, bilateral, melanocytic proliferation of the uveal tract which, although not metastatic, was morphologically melanoma. Cytological features included increased N:C ratios, nuclear pleomorphism, and prominent nucleoli. The uveal tract was normal in both eyes in all of the control animals. CONCLUSION: Pigmented intraocular tumours developed in transgenic strains of mice that express a mutated Ha-ras gene in melanin producing cells. The morphology was most consistent with a melanoma in two of the mice and a benign melanocytic/RPE proliferation in the remaining mice.

Prevalence and causes of undernutrition in medical outpatients.

PURPOSE: To assess the prevalence, common causes, and frequency of recognition and treatment of undernutrition in older and younger medical outpatients using a cross-sectional survey design with 2-year follow-up of undernourished subjects. PATIENTS AND METHODS: Charts of 1017 adult patients attending a hospital outpatient department were reviewed for the presence of undernutrition, and 85 patients meeting inclusion criteria for undernutrition were evaluated and followed for 2 years. An initial evaluation focused on nutritional, cognitive, and affective status and on nutritional attitudes using two subscales of the EAT-26 eating disorder inventory. After 2 years, initial data plus outpatient records were evaluated by 2 independent reviewers to determine a primary cause of undernutrition and to assess the recognition and treatment of undernutrition by the primary physician. RESULTS: Undernutrition was identified in 46 (11%) and 44 (7%) of older and younger subjects respectively; odds ratio (OR) (95% [confidence interval (CI)]) for older versus younger=1.65 (1.06 to 2.51). The primary cause of undernutrition differed between age groups but was deemed treatable in nearly 90% of all subjects. Undernutrition was recognized in 19 (43%) older subjects and 5 (12%) younger subjects (OR=5.47 [1.87 to 16.0]), and appropriate intervention(s) were instituted in 6 (14%) and 2 (5%) of older and younger subjects, respectively (OR=3.08 [0.668 to 14.21]). Older subjects scored higher on the EAT-26 oral control subscale than did younger subjects (4.7 versus 2.5, P=0.004) but similarly on the EAT-26 dieting subscale (5.2 versus 6.3, P=0.332); these relationships did not change with control for potentially confounding variables. CONCLUSIONS: In this study, undernutrition was relatively common, usually amenable to treatment, but frequently undetected and undertreated in both older and younger medical outpatients. Older undernourished subjects exhibited higher oral control needs than younger persons, which may have implications for the pathophysiology and treatment of their malnutrition. Further improvement in detection and intervention is warranted in both younger and older age groups.

Fine-needle aspiration cytology of pleuropulmonary blastoma: case report and review of the literature.

This report describes the fine-needle aspiration (FNA) cytology of a case of pleuropulmonary blastoma in a 3-yr-9-mo-old male. Pleuropulmonary blastoma is considered by most authors to be distinct from pulmonary blastoma and is a rare malignant tumor of the intrathoracic cavity. FNA smears were cellular with numerous small ovoid to spindled cells with oval to elliptical nuclei exhibiting finely granular chromatin and inconspicuous nucleoli. The cytoplasm was scant and eosinophilic with indistinct borders. Focal chondroid material and blastema-like cells were noted. The differential diagnosis suggested by the cytologic findings included rhabdomysosarcoma, teratoma, neuroblastoma, malignant mesenchymoma, pleuropulmonary blastoma, and metastatic tumor. To our knowledge, this is the first report of the cytology of this tumor.

Left atrial myxomas--a case report.

A 49-year-old woman presented with symptoms of congestive cardiac failure. Cardiac auscultation revealed a crunching sound difficult to characterise in addition to a pansystolic murmur maximally audible in the 4th left intercostal space. The ausculatory findings varied from day to day but were unaffected by posture or exercise. A clinical impression of left atrial myxoma was confirmed by two dimensional echocardiography which revealed a well circumscribed mass almost completely filling the left atrium with a pedicle attached to the interatrial septum. The patient's cardiac failure improved with conservative management using frusemide and digoxin. The patient, however, refused cardiac surgery which is the definitive management of this disease.

Analysis of GPT activity in mammalian cells with a chromosomally integrated shuttle vector containing altered gpt genes.

The molecular mechanisms of reversion in mammalian cells were studied utilizing the pZipGptNeo shuttle vector, with the bacterial gpt gene in the vector integrated into the chromosomal DNA of mouse cells. From mutant cell lines containing gpt genes with single base changes, revertants were selected for the reappearance of GPT activity. The copy number and expression of the gpt genes in such revertants were analyzed, and the GPT activity encoded by revertant genes in both mammalian cells and bacteria characterized. Revertants with wild-type amino acid sequence had, on average, the highest levels of GPT activity. Revertants with amino acid sequences different from the original mutants but not corresponding to wild-type had, on average, approximately half the level of GPT activity as wild-type revertants. Revertants that still contained the original mutation in the gpt gene had even lower levels of activity. These revertants were found to have amplified mutant gpt genes, which, when transferred into bacteria, were seen to encode for GPT polypeptides with partial enzymatic activity. A revertant in which the original mutation that destroyed the AUG translational start codon was retained but in which there was a secondary mutation upstream of the start codon also was characterized. The second mutation generated an in-frame CUG codon that apparently functioned as an alternative, upstream translational start codon.

A search for anomalies in the zeta, alpha, beta, and gamma globin gene arrangements in normal black, Italian, Turkish, and Spanish newborns.

Globin gene mapping analyses of DNA from numerous Black babies, and from newborns from Sardinia, Sicily, Turkey, and Spain have identified the following: A high incidence of alpha-thalassemia-2 heterozygotes among Black babies with less than 1% Hb Bart's at birth and a high incidence of alpha-thalassemia-2 among Sardinians, but not among Sicilian, Turkish, and Spanish babies. A relatively high incidence of zeta-thalassemia was present among Black babies only, while triplicated zeta was seen in four of the five populations. Two Black babies were each found to have a different theta 1 deletion; two Sardinian babies had a newly discovered approximately 2.5 kb deletion between zeta and psi zeta; four babies had the rare Bgl II polymorphism between psi zeta and psi alpha; and one Black baby lacked the Eco RI site 3' to zeta. Quantitation of the zeta chain by reversed phase high performance liquid chromatography showed that two-thirds of the babies with four alpha genes (alpha alpha/alpha alpha) had levels between 0.1 and 1.0%, while nearly 90% of the babies with -alpha/alpha alpha had similar levels (averaging 0.2% for alpha alpha/alpha alpha; 0.35% for -alpha/alpha alpha; 0.75% for -alpha/-alpha). Additional data indicated that the occurrence and level of zeta are related to the level of beta, i.e. the gestational age. The presence of a zeta triplication did not affect the level of zeta in cord blood. The extensive search for gamma-globin gene anomalies resulted in the discovery of a chromosome with five gamma genes. gamma-Thalassemia was rare in all populations, while the -G gamma-G gamma- gene arrangement was mainly observed among Black babies; this arrangement is primarily responsible for high G gamma levels in cord blood samples. The strong correlation between the presence or absence of a C----T mutation at position -158 (measured in Xmn I digests) and the level of G gamma was confirmed for adult blood samples. A search for possible anomalies in the -delta-beta- region through gene mapping with Eco RV gave negative results except for the discovery of a polymorphic site 5' to delta in one of the 371 Black babies tested.

Effects of vasoactive intestinal peptide on canine prostatic contraction and secretion.

Vasoactive intestinal peptide (VIP)-like immunoreactivity was found in intrinsic autonomic ganglion cells and nerve fibers located at the surface and within the canine prostate. In anesthetized dogs, porcine VIP (100-3,000 ng/kg iv) decreased arterial pressure and increased heart rate but did not result in the release of fluid from the prostate, indicating that VIP neither contracted glandular smooth muscle to expel fluid nor provoked secretion. Intravenous infusions of VIP at 10, 50, 100, and/or 200 ng X kg-1 X min-1 produced dose-related decreases in arterial pressure, increases in heart rate, and potentiation of the secretory response to the intravenous administration of pilocarpine and to electrical stimulation of the hypogastric nerves at 2 but not at 20 Hz. VIP at 1 microgram/ml neither contracted isolated strips of prostate nor modified their contraction by norepinephrine. It is unlikely that VIP mediates hypogastric nerve-induced prostatic contraction or secretion in the dog, but VIP may serve as a neuromodulator of nerve-induced secretion.