"I" becomes "L": modification of vertical mammaplasty

The problems of the vertical mammaplasty by Lejour (i.e., gathering the skin envelope in one vertical suture, frequent secondary healing problems, and later sagging of the inferior glandular part in the case of large and very large breasts) are well known. A simple modification of the Lejour technique, that is, adding a lateral inframammary scar to shorten the vertical scar length, is presented. The modified L technique was used in 45 patients (90 breasts) between October of 1999 and August of 2001. With an average follow-up of 13 months, the jugular notch-to-nipple distance was 21 cm, the vertical scar length was 8.4 cm, the lateral inframammary scar length was 11 cm, and the average resection weight was 625 g per breast (range, 200 g to 2080 g). Even among patients who had very large glandular bases and resection weights it was possible to achieve a breast base reduction, modeling the glandular corpus to a harmonic, well-projecting, and youthful shape. Slight wound-healing problems with spontaneous cicatrization within 2 weeks occurred in six patients. In two patients who exhibited gigantomastia up to 2080 g per breast, partial mamilla necrosis occurred on one side. Ninety-one percent of the patients reported being "very satisfied" with the outcome, and 9 percent reporting being "satisfied." The authors' modification of the vertical mammaplasty to an L-shaped scar technique enables the surgeon to apply the principles of the Lejour technique for higher resection weights and diminishes wound-healing problems, and it is still a scar-minimizing technique that results in a scar-free cleavage. It is easy to learn and an ideal standard technique for a teaching hospital.     

Nitration in neurodegeneration: deciphering the "Hows" "nYs"

Recent literature has ushered in a new awareness of the diverse post-translational events that can influence protein folding and function. Among these modifications, protein nitration is thought to play a critical role in the onset and progression of several neurodegenerative diseases. While previously considered a late-stage epiphenomenon, nitration of protein tyrosine residues appears to be an early event in the lesions of amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. The advent of highly specific biochemical and immunological detection methods reveals that nitration occurs in vivo with biological selectively and site specificity. In fact, nitration of only a single Tyr residue is often sufficient to induce profound changes in the activity of catalytic proteins and the three-dimensional conformation of structural proteins. Presumably, nitration modifies protein function by altering the hydrophobicity, hydrogen bonding, and electrostatic properties within the targeted protein. Most importantly, however, nitrative injury may represent a unifying mechanism that explains how genetic and environmental causes of neurological disease manifest a singular phenotype. In this review and synthesis, we first examine the pathways of protein nitration in biological systems and the factors that influence site-directed nitration. Subsequently, we turn our attention to the structural implications of site-specific nitration and how it affects the function of several neurodegeneration-related proteins. These proteins include Mn superoxide dismutase and neurofilament light subunit in amyotrophic lateral sclerosis, alpha-synuclein and tyrosine hydroxylase in Parkinson's disease, and tau in Alzheimer's disease.     

"Extracts from "Clinical evidence": Menopausal symptoms

DefinitionMenopause begins one year after the last menstrual period. Symptoms often begin in the perimenopausal years.Incidence/prevalenceIn the United Kingdom the mean age for the menopause is 50 years 9 months. The median onset of the perimenopause is between 45.5 and 47.5 years. One Scottish survey (of 6096 women aged 45 to 54 years) found that 84% had experienced at least one of the classic menopausal symptoms, with 45% finding one or more symptoms a problem.¹

Interventions

• Beneficial:OestrogensTibolone

• Likely to be beneficial:ProgestogensClonidine

• Unknown effectiveness:Phyto-oestrogensTestosteroneAntidepressants

PrognosisMenopause is a physiological event. Its timing may be genetically determined. Although endocrine changes are permanent, menopausal symptoms such as hot flushes, which are experienced by about 70% of women, usually resolve with time.² However, some symptoms, such as genital atrophy, may remain the same or worsen.AimsTo reduce or prevent menopausal symptoms, and to improve quality of life with minimum adverse effects.OutcomesFrequency and severity of vasomotor, urogenital, and psychological symptoms; quality of life.MethodsClinical Evidence search and appraisal December 1999. We included only randomised controlled trials (RCTs) and systematic reviews that met Clinical Evidence quality criteria.BenefitsVasomotor symptoms: We found no systematic review. We found over 40 RCTs comparing oestrogen versus placebo and various preparations and/or routes against each other. Most found that oestrogen reduced vasomotor symptoms (data from one RCT in 875 women: odds ratio 0.53, 95% confidence interval 0.31 to 0.93).³ Two RCTs found that transdermal oestrogen at a low dose of 25 μg daily reduced severity of vasomotor symptoms compared with placebo.^4,5 Urogenital system: We found one systematic review (search date 1995) and three subsequent RCTs. The review pooled data from six RCTs.⁶ It found that oestrogen improved urogenital symptoms regardless of the route of administration (no figures available). One subsequent RCT (n=136) found that low dose transdermal oestrogen (25 μg daily) combined with norethisterone acetate significantly reduced vaginal dryness and dyspareunia compared with placebo over six months.⁴ Two other RCTs (n=192) found that local administration of oestrogen using a silicone oestradiol releasing vaginal ring over 24-36 weeks improved vaginal oestrogenisation and pH compared with placebo.^7,8 One of these trials also found a significant reduction in incidence of urinary tract infection in treated women (P=0.008).⁷ Psychological symptoms: We found one systematic review (search date 1995, 14 RCTs, 12 cohort studies), which found that oestrogen reduced depressed mood among menopausal women.⁹ Duration of treatment ranged from one month to two years. Data pooling for oestrogen versus placebo (10 studies) found that oestrogen reduced depressive symptoms (no figures available). We found no RCTs of oestrogen treatment in women with clinically proved depression. We found one systematic review (search date 1996, 10 controlled trials, 9 observational studies) of the effects of oestrogen on cognitive function in postmenopausal women and women with Alzheimer''s disease.¹⁰ Studies were too weak to allow reliable conclusions. An additional crossover RCT (n=62) found a beneficial effect of oestrogen on sleep quality compared with placebo over seven months.¹¹ Quality of life: We found no systematic review. We found four RCTs (639 women, 3 RCTs placebo controlled, 3 versus progestogen), which found significant improvement in quality of life in women treated with oestrogen compared with baseline or placebo.^12–15 The largest RCT (242 women) found that oestrogen improved quality of life (P=0.0003) and wellbeing (P=0.003) compared with placebo over 12 weeks.¹²HarmsMany RCTs have found that oestrogen causes weight gain and breast tenderness in the short term. Although many women report an increase in weight when starting oestrogen, we found no evidence from RCTs that oestrogen causes significant weight gain in the long term. The most important long term adverse effects are increased risk of venous thromboembolic disease, endometrial cancer, and breast cancer.^16–18 The relation between oestrogen (as hormone replacement therapy) and breast cancer was reviewed in a reanalysis of 51 studies of more than 160 000 women.¹⁹ The review found that the risk of breast cancer increased by 2.3% (1.1% to 3.6%) each year in women using hormone replacement therapy. Five or more years after hormone replacement therapy was stopped, there was no significant excess of breast cancer.¹⁹CommentMany studies used selected populations such as women attending hospital clinics, who may be different in their behaviour, personality, and symptom profile to women of the same age seen in primary care or those who do not seek medical advice. Option: ProgestogensSummary We found good evidence from RCTs that progestogens reduce vasomotor symptoms. We found no good quality evidence on other outcomes, including quality of life.BenefitsWe found no systematic review. Vasomotor symptoms: We found five RCTs (257 women, all trials less than a year long), which found that women taking progestogens experienced a significant reduction in vasomotor symptoms compared with placebo.^20–24 The single RCT comparing oestrogen alone with progestogen (150 mg of depot medroxyprogesterone for 25 days a month) found that over three months, 18% of women taking oestrogens and 33% taking progestogen reported no vasomotor symptoms.²¹ One RCT (n=102) found that transdermal progesterone cream 20 mg daily improved vasomotor symptoms compared with placebo (P<0.001) but had no beneficial effect on bone density.²⁵ Urogenital system: We found no RCTs evaluating the effects of progestogens alone on urinary incontinence, the lower genital tract, or sex life. Psychological symptoms: We found no RCTs. Quality of life: One RCT of cyclical progestogen plus oestrogen for six months found no evidence of an effect on quality of life.²⁶ We found no studies of progestogen alone on quality of life.HarmsWe found two RCTs that evaluated harms of progestogens. The first compared continuous progestogen (norgestrel) and placebo in 321 women who had undergone hysterectomy and were already taking conjugated oestrogen. It found no difference in symptoms (including weight gain and bloating).²⁷ The second RCT (875 women) compared various oestrogen-progestogen combinations over three years.³ It found that additional progestogen increased breast discomfort (odds ratio 1.92, 1.16 to 3.09). Neither trial found evidence of an effect on cardiovascular events.CommentProgestogen is seldom given alone, which makes it hard to isolate its effects. When it was given without oestrogen, doses of progestogens were high, the lowest dose being 20 mg medroxyprogesterone acetate per day. Option: TiboloneSummary RCTs found that tibolone significantly improved vasomotor symptoms, libido, and vaginal lubrication.BenefitsWe found no systematic review. Vasomotor symptoms: We found three RCTs, two of tibolone versus continuous combined oestrogen/progestogen treatment over 48 and 52 weeks (672 women with menopausal symptoms)^28,29 and one versus placebo over 16 weeks (82 women with menopausal symptoms).³⁰ The first RCT found a slightly greater reduction in hot flushes with the combined regimen than with tibolone over 48 weeks (P=0.01). The second trial found a significant reduction in vasomotor symptoms from baseline in both groups (67/72 women on HRT and 58/68 women on tibolone, P<0.001) but no significant difference between groups. The third trial found tibolone reduced vasomotor symptoms by 39% compared with placebo (P=0.001). Urogenital system: We found two RCTs. The first RCT found no significant difference between tibolone and combined hormonal treatment in terms of subjective reports of vaginal lubrication; both interventions improved lubrication compared with baseline.²⁸ The second RCT (437 women) found that tibolone improved sexual satisfaction compared with oestradiol plus norethisterone (P<0.05).³¹ We found no RCTs examining effects on urinary incontinence. Psychological symptoms: We found no RCTs. Quality of life: We found no RCTs. Bone density: We found nine RCTs, which found that tibolone increased bone density over periods from 6 to 36 months compared with baseline or placebo.³²HarmsWe found no evidence on adverse effects from RCTs. One non-randomised controlled trial found that the main unwanted effect of tibolone was breakthrough bleeding, which occurred in about 10% of users.³³ We found no good evidence of androgenic adverse effects such as hair growth and greasiness of the skin. Two RCTs of short term use found a 33% reduction in plasma high density lipoproteins with tibolone,^34,35 although the long term effects on cardiovascular disease are unknown.CommentNone. Option: Phyto-oestrogensSummary Limited evidence from small RCTs suggests that soy flour, which contains phyto-oestrogens, may relieve vasomotor menopausal symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found three placebo controlled RCTs. Two evaluated soy supplements, which contain phyto-oestrogen, using double blind designs; the other, which was not blinded, evaluated isoflavone. The first RCT (58 postmenopausal women) compared soy flour versus wheat flour for 12 weeks and found that hot flushes were reduced significantly more in the group of women using soy flour (40% v 25% reduction).³⁶ The second RCT used a crossover design to evaluate six weeks'' administration of 34 mg soy protein daily. It found reduced severity but not frequency of vasomotor symptoms.³⁷ The third RCT (n=51) used a crossover design to compare isoflavone 40 mg daily with placebo. It found benefit from placebo compared with baseline, but not with isoflavone.³⁸ Urogenital system: We found no RCTs. Psychological symptoms: We found no RCTs. Beneficial effects of treatment on quality of life: We found no RCTs.HarmsWe found no evidence of significant adverse effects.CommentNone. Option: ClonidineSummary Two RCTs found that clonidine reduced vasomotor symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found two RCTs.^39,40 One crossover RCT (66 women) found that clonidine reduced the mean number of flushing attacks in the 14 days after crossover compared with placebo (56.8 v 64.3, P<0.05).³⁰ The second RCT (30 women) found that more women taking clonidine reported reduced flushes at 8 weeks (12/15 v 5/14, P<0.04).⁴⁰ Psychological symptoms: We found no RCTs. Quality of life: We found no RCTs.HarmsThe two RCTs found no significant difference in the incidence of unwanted effects between placebo and active treatment groups.^39,40CommentNone. Option: TestosteroneSummary We found evidence from RCTs that testosterone improves sexual enjoyment and libido. We found no studies evaluating effects on other commonly experienced menopausal symptoms.BenefitsWe found no systematic review. Vasomotor symptoms: We found no RCTs evaluating testosterone alone in women with menopausal symptoms. We found one RCT (93 postmenopausal women) comparing oestrogen alone and oestrogen plus methyltestosterone. This concluded that addition of a small dose of methyltestosterone reduced the dose of oestrogen needed to control menopausal symptoms.⁴¹ Urogenital system: We found two RCTs, one in 40 women and one crossover study in 53 women. Both found benefit from exogenous testosterone on self reported sexual enjoyment, desire, and arousal.^42,43 Psychological symptoms: We found no RCTs. Beneficial effects of therapy on quality of life: We found no RCTs.HarmsWe found no evidence from RCTs or other controlled studies on the incidence of androgenic adverse effects with testosterone.CommentNone. Option: AntidepressantsSummary We found insufficient evidence on the effects of antidepressants on menopausal symptoms.BenefitsWe found no systematic review or RCTs that specifically addressed the effects of antidepressants on menopausal symptoms or quality of life in menopausal women.HarmsWe found no evidence on adverse effects in postmenopausal women. Antidepressants as a group can cause many central nervous system adverse effects, including sedation and agitation, as well as urinary and vision problems, liver dysfunction, and cardiac dysrhythmias.⁴⁴CommentNone.     

"Craziness" and "visions": experiences after a stroke.

For a stroke victim there may be at least three types of strange occurrences: incorrect saying, seeing, and thinking. To the patient only the third seems to be "crazy". After a stroke (left hemisphere), which mainly produced serious aphasia, I (the patient) felt crazy two or three times when someone said something I expected him to say. On the other hand, my initial aphasic "gibberish speech" and an occasional false vision did not seem crazy. In my case the vision is always a car or a child, seen on my extreme right, where I am otherwise blind from the stroke. I am always driving when it happens; in recent years this phenomenon occurs when I am tired or tense, or the light is poor. These rapid visions do not seem insane but merely physical problems in my eyes, much like ordinary people''s dreams.     

Lymphoma immunophenotyping: "borderline" lymphomas

Immunophenotyping of B-cell lymphoproliferative disorders is indispensable, especially in disorders with CD19(+) CD5(+) B lymphocytes, where we have to make the distinction between low grade neoplasia, such as chronic lymphocytic leukemia with CD23(+) malignant lymphocytes, and aggressive neoplasia such as mantle cell lymphoma with CD23(-) malignant lymphocytes. We found some cases of CD19(+) CD5(+) lymphoproliferative disorders that do not meet all criteria for diagnosis of chronic lymphocytic leukemia or mantle cell lymphoma. For instance, we found cases with a low or no expression of CD23, asociated with absence of expression of FMC7 and surface immunoglobulins. These cases could be classified as "borderline" CD19(+) CD5(+) B cell lymphoproliferative disorders, with an intermediate neoplasic grade.     

Orienting reflex: "targeting reaction" and "searchlight of attention"

The concept of orienting reflex based on the principle of vector coding of cognitive and executive processes is proposed. The orienting reflex to non-signal and signal stimuli is a set of orienting reactions: motor, autonomic, neuronal, and subjective emphasizing new and significant stimuli. Two basic mechanisms can be identified within the orienting reflex: a "targeting reaction" and a "searchlight of attention". In the visual system the first one consists in a foveation of a target stimulus. The foveation is performed with participation of premotor neurons excited by saccadic command neurons of the superior colliculi. The "searchlight of attention" is based on the resonance of gamma-oscillations in the reticular thalamus selectively enhancing responses of cortical neurons (involuntary attention). The novelty signal is generated in novelty neurons of the hippocampus, which are selectively tuned to a repeatedly presented standard stimulus. The selective tuning is caused by the depression of plastic synapses representing a "neuronal model" of the standard stimulus. A mismatch of the novel stimulus with the established neuronal model gives rise to a "novelty signal" enhancing the novel input. The novelty signal inhibits current conditioned reflexes (external inhibition) contributing to redirecting the behavior. By triggering the expression of early genes the novelty signal initiates the formation of the long-term memory connected with neoneurogenesis.     

Xeno-cannibalism: a survival "escamotage"

Several lines of evidence have demonstrated that self-cannibalism (macroautophagy) is a well regulated process of cell repair as well as of molecule and organelle recycling that allows the cells to survive. However, autophagic activity also represents a cell death pathway characterized by specific features that differentiate autophagy from other cell death processes. We found that cells that are able to exert intense autophagic activity were also able to engulf and digest entire cell siblings. This phenomenon represents a sort of xeno-cannibalism. We wonder whether these two phenomena, self and xeno-cannibalism, could be related the latter being an exacerbation of the first and providing a further survival option to the cells.     

"Epidemic" vs "epidemiological": linguistic aspects of epidemiological terminology

The meaning of the terms "epidemic" and "epidemiological" used in a medical discourse have been analyzed; differential signs have been found by the method of linguistic analysis, making it possible to avoid unjustified interchanges of these terms.