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The Tribal Health Initiative model for healthcare delivery: a clinical and epidemiological approach.

BACKGROUND: Tribal populations generally have poor health outcomes, often because of a healthcare delivery system that does not cater to their needs. This study evaluates a current healthcare model for tribals, and explores it in combination with the health status of the target population, placing emphasis on the long term sustainability and cross-implementation of the model. METHODS: We examined the health system from the perspective of the base hospital, by concentrating on mortality patterns, inpatient incidence of selected infectious and non-infectious illnesses, and the preventive and curative health services administered by the hospital to the community. RESULTS: Gender susceptibility patterns revealed disparities in anaemia and tuberculosis besides fluctuations in gastrointestinal disorders, tuberculosis and typhoid. A combination of gender- and age-susceptibility patterns revealed specific age intervals for mental health-related disorders. Mortality patterns indicated an Increase in youth deaths and suicide, with an overall reduction in infant mortality. However, an increased tribal confidence in allopathic medicine was noted after implementation of the health system. CONCLUSION: The base tribal hospital is important in administering primary and secondary healthcare, health education, disease surveillance, community outreach and for continued confidence in allopathic medicine. Diet-based morbidities may be combated via organic farming and banning local alcohol production, while anaemia may be combated through continued iron, salt and folic acid supplementation to women. The formulation of mental health programmes and long term educational initiatives at the village level are critical to reducing suicide and infant mortality. Further epidemiological studies are required to gain a complete picture of health within the population, and successful implementation of the model elsewhere must factor in sociocultural disparities among tribes.

Adolescent↗

[Perilymphatic fistula].

Perilymphatic fistulae are the first cause of perceptive deafness that may be amenable to surgical treatment. After a complete study of the literature, we have made a retrospective analysis of 48 ear explorations in 37 children. These children presented with a variable degree of progressive or fluctuating perceptive deafness without any obvious etiology. Computed tomography, especially aimed at detecting an abnormality in the patency of the aqueduct of the cochlea, seems to be the most efficient criterion of selection to establish an indication for surgical exploration. The extent of the perilymphatic fistulae and their location, mainly at the level of the fissura ante fenestram, call to our mind the possibility of an arrest in the differentiation of the otic capsule, with a persistent anomalous patency of the aqueduct of the cochlea. The results of this study mainly demonstrate stabilizations of hearing, while spectacular improvements still are anecdotal. On the other hand, morbidity is very low and mainly results from insufficient surgery to fill in the fistula. Further studies are needed, especially to better understand the pathophysiology of the perilymphatic fistulae, and their results must certainly be appreciated in the longer term.

Adolescent↗

Interaction of monoclonal anti-peptide antibodies with lysozyme.

The interaction of monoclonal anti-peptide antibodies with the free peptide and its protein counterpart has been evaluated for hen egg white lysozyme and the peptide constituting residues 38 to 45. Fluorescence methodology has been developed for the measurement of association constants based on resonance energy transfer between the excited tryptophan of antibody and bound peptide ligand conjugated to a fluorescent probe. Five antibodies, four IgM and one IgG, have been assayed by ELISA, and have demonstrated binding to the adsorbed peptide alone, to the adsorbed lysozyme alone, or to both. Multivalent interaction with the adsorbed ligand is a key factor in the efficacy of binding. Measurement of binding constants in homogeneous solution, by equilibrium dialysis and energy transfer, demonstrated that lysozyme was bound to an IgG antipeptide antibody with an association constant (4 X 10(2) M-1) 200-fold less than that for the free peptide (8 X 10(4) M-1). It was also inferred for IgM that an association constant of the order of 10(2) M-1 was sufficient to effect selective interaction in a system providing multivalent interaction. The shared conformations between protein and peptide, implied by the specific reactivity of the anti-peptide antibody with the protein, points to structural fluctuations of the surface regions and residues of globular proteins.

Animals↗

Epidemiology of hearing impairment in childhood.

Consensus about the etiology and prevalence of childhood hearing loss (HL) is difficult to discern. Genuine effects, such as those attributable to environment, are obscured by inconsistencies in data collection and analysis techniques. Prevalence, for example, depends upon test type, hearing loss criteria and age at evaluation. An etiologic classification which clarifies the interaction between time of insult, causation and time of expression of hearing loss is proposed and used for selective review. Much sensorineural hearing loss (SNHL) is of unknown cause. Where the cause is known, genetic causes are common, and influenced by consanguinity. Infectious causes of HL reflect seasonal and epidemic fluctuation, as well as geographic and temporal variation. Non-infectious causes vary more closely with differences in the environment and level of health care. In the western world, the most common cause of conductive hearing loss (CHL) is serous otitis media. In many developing regions, middle ear disease abounds and often is of the dangerous cholesteatomatous type. Certain populations are intermediate, with acute suppurative and chronic otitis media being almost endemic, yet rarely cholesteatomatous.

Adolescent↗

Mouse pancreatic beta-cells: tetraethylammonium blockage of the potassium permeability increase induced by depolarization.

1. Membrane potentials and input resistance were measured in beta-cells from mouse pancreatic islets of Langerhans in the presence or absence of D-glucose. 2. Tetraethylammonium (TEA) (a specific blocker of the K permeability increase induced by shifts in membrane potential from negative to positive values) was externally applied and its effects on potentials and input resistance evaluated. 3. In the absence of glucose, addition of TEA up to 20 mM to the perifusion medium did not affect the resting potential and the input resistance, the selectivity ratio PK/PNa (calculated from the constant field equation) remaining unchanged at about 30. 4. The characteristic response of the beta-cell membrane potential, in the presence of glucose, is a fluctuation between a silent phase at about -50 mV and an active phase at about -40 mV giving rise to a train of spikes. TEA abolishes this pattern and very much reduces the graded response of spike frequency normally seen with different concentrations of glucose. 5. Addition of glucose in the presence of up to 20 mM-TEA induces an increase in membrane resistance of about 4.10(7) omega. 6. TEA lowers the glucose level required to trigger the electrical activity from about 5.6 to about 4.6 mM. 7. TEA blocks the repolarization phase of action potentials induced by the addition of glucose or by depolarizing intracellular current injection. 8. In the presence of 11.1 mM-glucose and 20 mM-TEA the action potentials frequently crossed the zero line, the membrane potential reaching up to 25 mV during the peak of the spikes.

Action Potentials↗

The effects of monthly temperature fluctuations on mortality in the United States from 1921 to 1985.

The impact of short-term temperature fluctuations on mortality has been studied mainly on historical populations, thus providing a limited ability to generalize to contemporary conditions, which would be more useful in determining public health policies aimed at reducing mortality. Therefore, this study examined the effects of monthly temperature fluctuations on mortality in the United States from 1921 to 1985. Monthly data about mortality from the Vital Statistics and temperature from the National Oceanic and Atmospheric Administration and the US Department of Agriculture Weather Bureau were used. Six states were selected to be studied (Massachusetts, Michigan, Washington, Utah, North Carolina, and Mississippi). The analysis was carried out using distributed lag models. The analysis showed that warmer than usual temperatures in July and August, and unusually cold temperatures from January to June are linked to higher mortality. From September to December unusually low temperatures are associated with higher mortality in most states, while temperature has no significant effect on mortality in June and September. In January and February mortality is especially affected by unusually cold weather in the southern states of Mississippi and North Carolina. For example, a one degree drop in the mean temperature in 1921 is associated with a more than 3.5% increase in the February crude death rate in Mississippi and North Carolina and a less than 1% increase in the four other states examined. Finally, in the months from January to March the relationship between monthly fluctuations in the crude death rate and temperature declined over time and became relatively weak by 1985.

Humans↗

Genetic and environmental determinants of hypopus duration in the stored-product mite Lepidoglyphus destructor.

This paper reports a series of experiments over many years on hypopus duration and extends the preceding investigation (1987) on hypopus formation in Lepidoglyphus destructor (Schrank, 1781). The length of time required for hypopus physiogenesis (diapause development) is genetically programmed but influenced by environmental factors. This span of time is highly variable, and may extend from one week to more than a year. Spreading out the potential for hypopus completion over time is adaptive, since a pool of hypopodes with prolonged and staggered dormancies serves to spread the risk of emergence of tritonymphs over extended periods of time; it buffers the population against sudden drought to which all other stages of the life-cycle succumb. The additive structure and large variance of the genetic system underlying the length of time required for hypopus physiogenesis allows for the reconstitution of a broad spectrum of genotypes in every generation through the process of meiotic segregation and recombination during sexual reproduction. It favours stored variability, provides a 'fail-safe device' both for survival as well as development in irregularly fluctuating environments, and facilitates the adaptation of populations to local conditions. The trait for hypopus physiogenesis varies independently from that of hypopus formation, and is apparently free to adjust, without genetic constraints, towards an adaptive optimum. The response to selection is fast. Low environmental humidities and high temperatures accelerate physiogenesis of the hypopus. Completion of the hypopus stage and moulting to the tritonymph is triggered by high humidities at moderate temperatures. If environmental conditions preclude moulting, the hypopus following ending of physiogenesis enters a state of quiescence. In contrast the seasonal and largely predictably varying environments, in which essentially anticipatory and season-related token cues like photoperiod regulate the timing of so many arthropod life-cycles, L. destructor copes with sudden and fatal drought, as well as with unheralded and favourable humidities in its ephemeral habitats, mainly by excessive genetic polymorphism in hypopus duration and formation; some genotypes are always instantaneously fit to meet the respective environmental situation. The mite faces gradual food deterioration of its patchily distributed microhabitats by a short-term anticipatory and environmentally cued developmental switch mechanism, which lowers the threshold for hypopus induction. On top of genetic variability and phenotypic plasticity, any genotype X environment interaction provides for increasing flexibility above that from genetic polymorphism and environmental polyphenism alone. This extraordinary measure of adaptedness fits L. destructor for life in irregularly fluctuating environments.

Animals↗

Thymopentin treatment of selective IgA deficiency.

Thymic hormones have been shown to modulate immunoglobulin production in a number of experiments and it is generally agreed that this action is mediated by modulation of helper and/or suppressor T cell activities. The possibility of upregulating the immunoglobulins is of particular relevance in patients with hypogammaglobulinemias and this paper reports on the results of thymopentin treatment in 9 patients with selective IgA deficiency. Two out of 4 patients responded positively in an open-label trial; in one the serum IgA values remained stable up to 8 weeks after discontinuation of treatment whereas there was a rapid fall in the other. Both responders had consistently normal T4/T8 ratios during the treatment, whereas the nonresponders revealed high ratios with large fluctuations of the T4/T8 ratio. In a subsequent (still ongoing) double-blind trial in 5 patients (3 thymopentin, 2 placebo) no significant change of serum or secretory IgA levels has been observed. Taken together, the data suggest that the tested dose regimen of thymopentin (i.e. daily i.m. injections of 1 mg/kg for 2 weeks, then same dose 3 time weekly for 10 weeks) may only work in a subset of patients with selective IgA deficiency. In the present study we did not attempt to distinguish to which of the three known subgroups the 9 patients belonged, nor did we try alternative dose regimens of thymopentin.

Adjuvants, Immunologic↗

Permeation of both cations and anions through a single class of ATP-activated ion channels in developing chick skeletal muscle.

Micromolar concentrations of extracellular adenosine 5'-triphosphate (ATP) elicit a rapid excitatory response in developing chick skeletal muscle. Excitation is the result of a simultaneous increase in membrane permeability to sodium, potassium, and chloride ions. In the present study we quantify the selectivity of the ATP response, and provide evidence that a single class of ATP-activated ion channels conducts both cations and anions. Experiments were performed on myoballs using the whole-cell patch-clamp technique. We estimated permeability ratios by measuring the shift in reversal potential when one ion was substituted for another. We found that monovalent cations, divalent cations, and monovalent anions all permeate the membrane during the ATP response, and that there was only moderate selectivity between many of these ions. Calcium was the most permeant ion tested. To determine if ATP activates a single class of channels that conducts both cations and anions, or if ATP activates separate classes of cation and anion channels, we analyzed the fluctuations about the mean current induced by ATP. Ionic conditions were arranged so that the reversal potential for cations was +50 mV and the reversal potential for anions was -50 mV. Under these conditions, if ATP activates a single class of channels, ATP should not evoke an increase in noise at the reversal potential of the ATP current. However, if ATP activates separate classes of cation and anion channels, ATP should evoke a significant increase in noise at the reversal potential of the ATP current. At both +40 and -50 mV ATP elicited a clear increase in noise, but at the reversal potential of the ATP current (-5 mV), no increase in noise above background was seen. These results indicate that there is only a single class of excitatory ATP-activated channels, which do not select by charge. Based on analysis of the noise spectrum, the conductance of individual channels is estimated to be 0.2-0.4 pS.

Adenosine Triphosphate↗

Interval estimation of urban ozone level and selection of influential factors by employing automatic relevance determination model.

In this work, we focus on simulating the ground-level ozone (O3) time series and its daily maximum concentration in Hong Kong urban air by employing the multilayer perceptron (MLP) model combined with the automatic relevance determination (ARD) method (for simplicity, we name it as MLP-ARD model). Two air quality monitoring sites in Hong Kong, i.e., Tsuen Wan and Tung Chung, are selected for the numerical experiments. The MLP-ARD model based on Bayesian evidence framework can provide reliable interval estimation of real observation as well as offering efficient strategy to avoid over-fitting. The performance comparisons between MLP-ARD model and traditional artificial neural network (ANN) model based on maximum likelihood indicate that MLP-ARD model is more powerful to capture the wild fluctuation of O3 level especially during O3 episodes than the traditional model. Furthermore, it can assess and rank the input variables for the prediction according to their relative importance to the output variable, i.e., the daily maximum O3 concentration in this study. The preliminary experimental results indicate that nitric oxide (NO) and solar radiation are the most important input variables for O3 prediction at both selected sites. In addition, the previous daily maximum O3 level is also important for Tung Chung site. In this regard, MLP-ARD model is a feasible tool to interpret the real physical and chemical process of urban O3 variation.

Air Pollutants↗

A clinical and pharmacokinetic basis for the selection and use of slow release theophylline products.

In order to achieve the greatest chance for maximum benefit from theophylline in the management of chronic asthma, the serum concentration should be maintained in the therapeutic range of 10 to 20 micrograms/ml. Conventional rapid release formulations produce excessive fluctuations in serum concentrations that can result in variability in clinical response between doses. In contrast, slow release formulations have the potential to achieve relatively constant serum concentrations with 12-hour dosing intervals, thus providing around-the-clock stabilisation of the hyper-reactive airways that characterise chronic asthma. Furthermore, the decreased frequency of dosing with these formulations can improve patient compliance. However, significant differences in rate and extent of absorption exist between the available formulations. Single-dose bioavailability studies comparing a slow release product with an oral solution or plain uncoated tablet in a crossover design permit examination of the rate and extent of absorption. Comparison of a slow release product with an oral reference following multiple doses at steady-state permits examination of the extent but generally not rate of absorption. The mean fraction absorbed-time profile, calculated from a modification of the Wagner-Nelson equation, is a process-independent method of comparing rates of absorption of different products after single doses. A prospective study in 14 children with chronic asthma has demonstrated that this modified equation, when rearranged to iteratively solve for serum concentrations, can accurately predict steady-state serum concentrations for different dosing intervals in patient populations with different rates of elimination. When slow release products are compared in this manner at 8- or 12-hour dosing intervals for patients with slow elimination, clinically relevant differences between brands are not apparent. However, in patients with rapid elimination, i.e. children, cigarette smokers, and 25% of non-smoking adults, application of this method shows that only some formulations (i.e. 'Slo-Bid Gyrocaps' and 'Theo-Dur', which is also marketed under different brand names names such as 'Sustaire', 'Pulmi-Dur' and 'Theolin Retard') can maintain serum concentrations within the therapeutic range for an entire 12-hour dosing interval. More rapidly absorbed slow release products must be administered at 8-hour dosing intervals in patients with rapid elimination, despite promotional claims to the contrary. Current products promoted for once-a-day administration are clinically inadequate because of incomplete and erratic absorption, and/or excessive serum concentration fluctuations.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

Human consciousness and sleep/waking rhythms: a review and some neuropsychological considerations.

The relevance of sleep/waking rhythms to issues of human consciousness is reviewed from data in the literature and from personal studies. Consciousness is often considered to be markedly attenuated or absent in sleep. There is, however, much evidence for a rich subjective experience during sleep, much of which is not recalled later. This implies that William James' "stream of consciousness' persists continuously throughout sleep as well as wakefulness, but that problems of memory recall interfere with its being reported as such. Sleeping subjects show selective awareness of external stimuli, with significant stimuli generally leading to awakening and relatively nonsignificant stimuli, at least at times, being incorporated into the ongoing mental activity of REM or NREM sleep. Mentation throughout sleep is characterized by a high degree of autonomy and little willful control. Creative insight and problem solving of a very high order may occur in sleep and involve either dreaming or thought-like mentation. Parameters of waking consciousness show possibly sleep-related rhythmic fluctuations at both circadian (24 hr sleep/waking) and ultradian (90-120) min, NREM/REM sleep) rates. Moreover, waking consciousness is markedly influenced by the quality of temporal stability of preceding sleep. A substantial number of so-called "altered states of consciousness" is found to involve primarily or exclusively dysfunction of sleep/waking mechanisms. Cerebral lesions can produce selective impairment of aspects of sleep mentation. It is concluded that further analysis of subjective awareness in sleep or in partial sleep states is very relevant and indeed vital to a more comprehensive understanding of human consciousness.

Arousal↗

TrkA immunoreactive astrocytes in dendritic fields of the hippocampal formation across estrous.

Neurotrophins are important modulators of structural synaptic plasticity. (Through trophic action (Jordan. J Neurobiol 40:434-445, 1999), astrocytes serve as permissive substrates to support axonal regrowth (Ridet et al. Trends Neurosci 20:570-571, 1997), and are involved in estrogen-induced synaptic structural plasticity (Garcia-Segura et al. Cell Mol Neurobiol 16:225-237, 1996). Previously, we reported that tyrosine kinase A receptor (TrkA) immunoreactivity was present both in presynaptic neuronal processes (axons and terminals) and in select astrocytes of the male rat hippocampal formation (Barker-Gibb et al. J Comp Neurol 430:182-199, 2001). We show that the number of TrkA-immunoreactive astrocytes in female rats fluctuates 16-fold across the estrous cycle in dendritic fields of the hippocampal formation, with the greatest number at estrus after the peak plasma estradiol concentration of proestrus. Few TrkA-labeled astrocytes were found in ovariectomized animals; after estrogen replacement, this number increased by 12-fold in the hippocampal formation, indicating estrogen-mediated induction. Dual-labeling studies showed that TrkA-labeled astrocytes were also immunoreactive for vimentin, a protein expressed by reactive astrocytes. Ultrastructural analysis of the dentate gyrus molecular layer demonstrated that TrkA immunoreactive astrocytes are positioned primarily next to dendrites and unmyelinated axons. Because nerve growth factor (NGF) has been reported to stimulate astrocytes to function as substrates for axon growth (Kawaja and Gage. Neuron 7:1019-1030, 1991), these findings are consistent with the theory that TrkA immunoreactive astrocytes serve a role in structural plasticity, axon guidance, and synaptic regeneration across the estrous cycle in the hippocampal formation.

Animals↗

Role of surgery in the treatment of motor complications.

When medications no longer provide patients with Parkinson's disease a reasonable quality of life due to the presence of levodopa-associated motor fluctuations and dyskinesias, surgical treatment is often pursued. Numerous studies have examined the antiparkinsonian efficacy of procedures currently available, but surprisingly few studies have evaluated their effect on motor response complications in a systematic, controlled manner, using appropriate instruments. Nonetheless, the combined evidence from uncontrolled case series and more recent randomized controlled trials reviewed here indicates that unilateral pallidotomy, bilateral pallidal deep brain stimulation, and bilateral subthalamic deep brain stimulation all substantially alleviate levodopa-induced dyskinesias and, to a lesser extent, motor fluctuations. Incorporation of standardized, validated instruments for the quantification of motor response complications in future surgical study protocols will not only allow more accurate comparison of different interventions but also will help physicians select the most appropriate procedure for their patients.

Antiparkinson Agents↗

Sustained-release (+)-PHNO [MK-458 (HPMC)] in the treatment of Parkinson's disease: evidence for tolerance to a selective D2-receptor agonist administered as a long-acting formulation.

4-Propyl-9-hydroxynaphthoxazine, or MK-458 (HPMC), a selective, nonergot D2 agonist administered orally twice a day in sustained-release form, was studied as adjunctive therapy with carbidopa-levodopa (Sinemet) in 12 Parkinson's disease patients with motor response fluctuations. The dosage of agonist was gradually increased over 12 weeks to a maximum tolerated level of up to 60 mg/day, and that of Sinemet was reduced concurrently. After 8 weeks, reduction of Sinemet averaged 45.1%, but over the next 4 weeks, despite a continued increase in dosage of the agonist, patients were unable to decrease their Sinemet further, and by 12 weeks mean reduction in Sinemet was only 32%. Only five patients completed the planned 24-week study, mostly due to progressive loss of efficacy. The MK-458 is capable of partially substituting for Sinemet in dosages employed in this study. Reduced sensitivity to the drug can appear over a relatively short time, perhaps as a result of down-regulation of postsynaptic dopamine receptors.

Activities of Daily Living↗

Selection and preliminary characterization of cycloleucine-resistant CHO cells affected in methionine metabolism.

Cycloleucine is in vivo a potent inhibitor of S-adenosylmethionine (SAM) biosynthesis and subsequent methylation reactions in somatic mammalian cells. Cycloleucine-resistant (CLr) clones were isolated from CHO cells by single-step selection. Their phenotype was stable when they were grown in the absence of drug. These clones appeared randomly in cultures at the frequency of 5 x 10(-6)/cell/generation, as determined by a fluctuation test. EMS mutagenesis did not significantly increase this frequency. The cycloleucine-resistant phenotype was codominant in intraspecific hybrids. Cycloleucine-resistant clones showed increased SAM pools; on the contrary, methionine pools were not significantly affected in these clones when compared to the wild-type cells. This increased SAM production was correlated with an increase of methionine adenosyltransferase (MAT) SPECIFIC ACTIVITY IN RESISTANT CLONES UNDER VARIOUS GROWm. The mechanism of posttranscriptional control of MAT biosynthesis was not affected in the cycloleucine-resistant clones nor were the kinetic properties of the enzyme modified. The genetic or epigenetic origin of this resistance mechanism is discussed.

Amino Acids↗

Detection of immune complexes by their complement-dependent binding to bovine conglutinin: technical aspects of a solid-phase immunoenzyme microassay and its application to normal and pathological sera.

A micromethod for the solid-phase conglutinin binding assay (Con BA) for the detection of circulating immune complexes (CIC) is described, in which the use of microplates, glucose oxidase-coupled anti-human immunoglobulins and automatic OD recorder contributed to the speed and low cost of this reproducible and sensitive test. The Con BA values of a large population of healthy blood donors had a wide distribution which in our series of 189 appeared to be trimodal. The Con BA values clearly reflected the levels of the main Ig classes (M, G, and A). This was confirmed by follow up of 6 individuals with high initial Con BA values. For 4 of them, a parallel decrease in Con BA value and IgG concentration was observed. In the 2 others, the sustained high level of Con BA remained unexplained. Complement components and activity of these sera were within normal limits. Because of fluctuation in the aggregated human gamma-globulins (AHG) reference curve, expression of results was based upon the standard deviation of 6 normal sera. In view of the above results, these sera were selected from those with the lowest Con BA values. On the basis that Con BA and C1q BA may detect CIC differing in their ag/ab ratio, sera from rheumatoid arthritis and chronic active B hepatitis patients with or without conventional rheumatoid factors (RF) were analyzed by both Con BA and C1q BA. RF-containing sera, likely to contain CIC in antigen excess, contributed exclusively to the highest C1q BA and lowest Con BA values. In contrast C1q BA-Con BA+ sera were preferentially RF negative. It is proposed that the complexes thus detected may be of idiotype-anti-idiotype nature.

Antigen-Antibody Complex↗

Evaluation and management of premenstrual syndrome and premenstrual dysphoric disorder.

OBJECTIVE: To review premenstrual disorders, their varied symptoms, possible etiology, and treatment options. DATA SOURCES: Published articles identified through MEDLINE (1966-2001) using the search terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) and the additional terms treatment and etiology. Additional references were identified from the bibliographies of the retrieved articles. DATA SYNTHESIS: PMS refers to a group of menstrually related disorders that are estimated to affect up to 40% of women of childbearing age. The varied symptoms of PMS include mood swings, tension, anger, irritability, headache, bloating, and increased appetite with food cravings. PMS symptoms occur during the luteal phase of the menstrual cycle and remit with the onset of menstruation or shortly afterward. Approximately 5% of women with PMS suffer from PMDD, a more disabling and severe form of PMS in which mood symptoms predominate. Because no tests can confirm PMS or PMDD, the diagnosis should be made on the basis of a patient-completed daily symptom calendar and the exclusion of other medical disorders. The causes of PMS and PMDD are uncertain, but are likely associated with aberrant responses to normal hormonal fluctuations during the menstrual cycle. For most women, symptoms can be relieved or reduced through lifestyle interventions, such as dietary changes and exercise, and drug therapy with hormonal or psychotropic agents. For PMDD, selective serotonin reuptake inhibitors have recently emerged as first-line therapy. Certain dietary supplements, including calcium, also may be an option for some women. CONCLUSION: PMS and PMDD are complex but highly treatable disorders. Pharmacists can improve the recognition and management of these common conditions by providing patient education on premenstrual symptoms and counseling women on lifestyle interventions and pharmacotherapy to relieve their discomfort.

Female↗