Management of Latent Tuberculosis Infection in Saudi Arabia: Knowledge and Perceptions Among Healthcare Workers.

Background Tuberculosis (TB) continues to pose a serious threat to public health despite great efforts. For many years, management and screening for active TB cases have been the main focus of TB control programs. Latent TB is a stage where TB can be prevented and controlled. Therefore, designing a comprehensive TB control program that includes latent tuberculosis infection (LTBI) management diseases is needed to be implemented among the healthcare workers (HCWs) who have been found to be at a higher risk for active TB compared to the general population. The objective of the study The objective of the study is to assess the knowledge and perceptions of LTBI among HCWs. In addition to estimating the prevalence of LTBI among HCWs using closed-end questions in a self-administered questionnaire. Subjects and methods Through a cross-sectional study and non-random sampling technique, 324 (84%) healthcare workers who met the inclusion criteria completed and submitted the electronic questionnaire. Results Among all participants, the study reported a good knowledge about LTBI; however, a third of HCWs had poor knowledge about the difference between LTBI and active TB. Eighteen percent of participants were diagnosed with LTBI, and two-thirds accepted the treatment. Of all participants who started the treatment, 55% completed the treatment course. The compliance rate was high among young HCWs and physicians who had a short course of LTB treatment regimen.  Conclusion The study reported a low acceptance and completion rate of LTBI therapy among HCWs. Low knowledge about some clinical facts of LTBI, the long duration of treatment, and being the treatment optional in Saudi health institutes were all barriers to accepting and completing the treatment of LTBI. All of these factors need to be addressed to increase the compliance rate to LTBI treatment.

Antagonism of progesterone receptor suppresses carotid body responses to hypoxia and nicotine in rat pups.

We tested the hypothesis that antagonism of progesterone receptor (PR) in newborn rats alters carotid body and respiratory responses to hypoxia and nicotinic receptor agonists. Rats were treated with the PR antagonist mifepristone (daily oral gavage 40 µg/g/d) or vehicle between postnatal days 3 and 15. In 11-14-day-old rats, we used in vitro carotid body/carotid sinus nerve preparation and whole body plethysmography to assess the carotid body and ventilatory responses to hypoxia (65 mmHg in vitro, 10% O2 in vivo) and to nicotinic receptor agonists (as an excitatory modulator of carotid body activity-nicotine 100 µM for in vitro studies, and epibatidine 5 µg/kg, i.p., which mainly acts on peripheral nicotinic receptors, for in vivo studies). The carotid body responses to hypoxia and nicotine were drastically reduced by mifepristone. Compared with vehicle, mifepristone-treated rats had a reduced body weight. The ventilatory response to epibatidine was attenuated; however, the hypoxic ventilatory response was similar between vehicle and mifepristone-treated pups. Immunohistochemical staining revealed that mifepristone treatment did not change carotid body morphology. We conclude that PR activity is a critical factor ensuring proper carotid body function in newborn rats.

Sudden infant deaths in sitting devices.

BACKGROUND: As episodes of decreased oxygenation levels have been recorded in premature infants placed in car seats, it is believed that these infants are at risk of life-threatening events and death. No data on the prevalence of such infant deaths are available. The aim of our study was to determine the incidence of sudden deaths in infants occurring in sitting devices in a whole population and to determine whether premature infants account for a disproportionate number of these deaths. DESIGN: Retrospective population-based cohort study reviewing all cases of sudden unexpected death in infants between birth and 1 year of age that occurred in the province of Quebec between January 1991 and December 2000. RESULTS: Of the 508 deaths reviewed, 409 were unexplained and 99 were explained after investigation. Seventeen deaths occurred in a sitting device, of which 10 were unexplained. There was no excess of premature infants dying. However, there was an excess of infants of less than 1 month of age found to have died in a sitting position in the unexplained death group. In addition, three infants who died in a sitting position had an increased risk of upper airway obstruction. CONCLUSION: Although very few deaths occurred in car seats, our results suggest that caution should be used when placing younger infants in car seats and similar sitting devices, whether the infants have been born prematurely or not. We also recommend that more attention be given to infants at increased risk of upper airway obstruction.

Developmental profile of cholinergic and purinergic traits and receptors in peripheral chemoreflex pathway in cats.

This study describes the developmental profile of specific aspects of cholinergic and purinergic neurotransmission in key organs of the peripheral chemoreflex: the carotid body (CB), petrosal ganglion (PG) and superior cervical ganglion (SCG). Using real time RT-PCR and Western blot analyses, we assessed both mRNA and protein expression levels for choline-acetyl-transferase (ChAT), nicotinic receptor (subunits alpha3, alpha4, alpha7, and beta2), ATP and purinergic receptors (P2X2 and P2X3). These analyses were performed on tissue from 1- and 15-day-old, 2-month-old, and adult cats. During development, ChAT protein expression level increased slightly in CB; however, this increase was more important in PG and SCG. In CB, mRNA level for alpha4 nicotinic receptor subunit decreased during development (90% higher in 1-day-old cats than in adults). In the PG, mRNA level for beta2 nicotinic receptor subunit increased during development (80% higher in adults than in 1-day-old cats). In SCG, mRNA for alpha7 nicotinic receptor levels increased (400% higher in adults vs. 1-day-old cats). Conversely, P2X2 receptor protein level was not altered during development in CB and decreased slightly in PG; a similar pattern was observed for the P2X3 receptor. Our findings suggest that in cats, age-related changes in cholinergic and purinergic systems (such as physiological expression of receptor function) are significant within the afferent chemoreceptor pathway and likely contribute to the temporal changes of O2-chemosensitivity during development.

Developmental pattern of M1 and M2 muscarinic gene expression and receptor levels in cat carotid body, petrosal and superior cervical ganglion.

Using real-time reverse transcriptase polymerase chain reaction, Northern blot, and Western blot analyses, we evaluated the developmental pattern of mRNA and protein expression level of muscarinic M1 and M2 receptors in the carotid body, petrosal ganglion and superior cervical ganglion of 1-day, 15-day, 2-month-old and adult cats. mRNA expression and protein levels of tyrosine hydroxylase, the rate limiting enzyme for dopamine synthesis, were also assessed. Carotid body M1 receptor mRNA, increased significantly by approximately 100% and 300% in 2-month and adult vs. 1- and 15-day-old cats, but protein level decreased gradually being approximately 50% lower compared with 1-day-old cats. In the petrosal ganglion, muscarinic M1 receptor mRNA level was higher in 15-day-old cats vs. 1-day-old, 2-month-old and adult cats and protein levels were about 30% lower than in 1- and 15-day-old cats. In the superior cervical ganglion, muscarinic M1 receptor mRNA was approximately 50% and 80% higher in 2-month-old and adult cats than 1- and 15-day-old, but no changes in the protein level except in 15-day-old cats which was approximately 40% higher than 1-day-old. There was no change of muscarinic M2 receptor mRNA or protein level in the carotid body or petrosal ganglion. However, in the superior cervical ganglion, the significant increase of mRNA of 30% and 50% in 2-month-olds and adults, respectively was not associated with an increase in receptor protein. Tyrosine hydroxylase mRNA and protein level decreased significantly with age in the carotid body and petrosal ganglion. In the superior cervical ganglion, the age dependent increase in tyrosine hydroxylase mRNA was not associated with any changes in the protein level. These results show that the expression of muscarinic M1 and M2 receptors are age and organ-dependent in cats. Consequently, these changes may modulate chemosensory activity during development since muscarinic M1 receptor is predominantly involved in postsynaptic chemosensory activity, while muscarinic M2 receptor modulates acetylcholine and dopamine release from chemosensitive cells.

Carotid sinus nerve chemosensory response to dopamine and acetylcholine in catecholamine depleted cats.

The aim of this study was to determine the role of endogenous dopamine (DA) and the combined effect of DA and acetylcholine (ACh) on the carotid sinus nerve chemosensory discharge (CSND). CSND was measured in vivo in 6 control cats and 6 cats pre-treated with reserpine and alpha-methyl-paratyrosine [catecholamine depleted group: CAD] during infusions of DA and DA+ACh. In normoxia, CSND was similar between CAD's and controls. DA induced CSND depression was transient in controls but sustained in CAD's. Addition of ACh increased CSND in both groups. In hypoxia (8% O(2) in N(2)), the dynamic CSND response was slowed by DA in CAD's but not controls. Addition of ACh increased this response in both groups. Neither DA nor DA+ACh altered the steady state hypoxic CSND in either group. It is concluded that endogenous DA is important in expressing the dynamic characteristics of both the response to exogenous DA and the response to hypoxia under constant DA infusion. The study also confirms the opposing effects of exogenous DA and ACh on the normoxic CSND.

Age-dependent effect of domperidone on dopamine release by the hypoxic carotid body in the rabbit.

The aim of this study was to identify the mechanisms that regulate dopamine release (DA(r)) by the hypoxic carotid body (CB) during development. CBs sampled from adult (n = 58) and 10-day-old (n = 53) rabbits were incubated for 1 h in a medium equilibrated with 8% O(2) in N(2) without or in the presence of the specific DA D(2) receptor antagonist domperidone, 0.01, 0.1 and 1 microM. DA and its major metabolite DOPAC were measured in the CB (DA(CB)) and in the medium (DA(r)) by HPLC+ED. In adults, each concentration of domperidone significantly decreased DA(CB) and increased DA(r), compared with control (p < 0.01). In contrast, in 10-day old, only the 1 microM domperidone concentration decreased DA(CB) and increased DA(r) compared with control (p < 0.001). The data show that domperidone increases CB DA(r) in response to hypoxia in a concentration- and age-dependent manner and suggest this response depends, in part, on the functional maturation of CB DA D(2) receptors.

Carbachol effect on carotid body dopamine in vitro release in response to hypoxia in adult and pup rabbit.

Dopamine (DA) release from the adult carotid body (CB) is dependent, in part, upon CB cholinergic receptor stimulation. The aim of the present study was to determine the role of cholinergic stimulation on DA release from rabbit pup CB with reference to adult's. CBs sampled from adult (n = 52) and 10-day-old (n = 49) rabbits were incubated in vitro for 1 h in a surviving medium bubbled with either 100 or 8% O2 in N2, without (control) or in the presence of the cholinergic agonist carbachol 1 microM. In adults, DA released (DAr) in the medium was significantly larger with 1 microM carbachol compared with control in either 100 or 8% O(2) (P < 0.01). In pups, carbachol 1 microM had no effect in 100% O2 but significantly increased DAr compared with control in 8% O2 (P < 0.01). The data suggest that cholinergic mechanisms regulating DAr are not fully expressed in pup rabbit CBs, in contrast with adults and thus, exhibit maturation-related functional differences.

Cholinergic dopamine release from the in vitro rabbit carotid body.

The aim of this study was to test whether cholinergic mechanisms regulate dopamine (DA) release from the carotid body (CB) and interact with DA D(2) autoreceptors. One hundred forty-two CBs from adult rabbits were infused in vitro in a surviving medium bubbled with O(2) (Bairam A, Marchal F, Cottet-Emard JM, Basson H, Pequignot JM, Hascoet JM, and Lahiri S. J Appl Physiol 80: 20-24, 1996). CB DA content and release were measured after 1 h of exposure to various treatments: control, cholinergic agonist (0.1-50 microM carbachol), full muscarinic antagonist (1 and 10 microM atropine), antagonists of M(1) and M(2) muscarinic receptors (1 and 10 microM pirenzepine and 10 microM AFDX-116, respectively), and the DA D(2) receptor antagonist domperidone (1 microM), alone and with carbachol (1 microM). Compared with control, the release of DA was significantly increased by carbachol (1-50 microM), AFDX-116, and domperidone and decreased by atropine (10 microM) and pirenzepine (10 microM). The effects of domperidone and carbachol were not significantly different but were clearly additive. It is concluded that, in the rabbit CB, M(1) and M(2) muscarinic receptor subtypes may be involved in the control of DA release, in addition to the DA D(2) autoreceptors.

Autoreceptor mechanism regulating carotid body dopamine release from adult and 10-day-old rabbits.

Dopamine (DA) release (r) from the carotid body (CB) is thought to be modulated by feedback inhibition mediated by DA D2 autoreceptors. We tested the hypothesis that CB DAr is autoregulated in a concentration and age dependent manner. Using an in vitro CB infusion model [Bairam, A., Marchal. F., Cottet-Emard, J.M., Basson, H., Pequignot, J.M., Hascoet, J.M., Lahiri, S., 1996b. Effects of hypoxia on carotid body dopamine content and release in developing rabbits. J. Appl. Physiol. 80, 20-24.], we evaluated under unstimulated conditions the effects of 0.001, 0.01, 0.1, 1.0 and 10.0 microM of the specific DA D2 receptor antagonist domperidone on CB DAr in adult rabbits. In 10-day-old rabbit pups, concentrations of 0.01, 0.1, 1.0 microM were studied. In adult CBs, domperidone increased DAr in a concentration-dependent manner. DAr (pmol/h) was significantly greater compared to control (without domperidone) starting at a domperidone concentration of 0.1 microM (P<0.01). In 10-day-old pup CBs, 1.0 microM domperidone was required to produce a significant increase of DAr (pmol/h) compared to control (P<0.005). However, control DAr (as % of total catecholamine) was about 40%; significantly higher than 24% observed in adult CBs (P<0.001). We conclude that in rabbit CB, DAr is controlled by an autoreceptor mechanism in a concentration-dependent manner and this mechanism is less developed in pups than in adults.

Expression of dopamine D1-receptor mRNA in the carotid body of adult rabbits, cats and rats.

Dopamine is a major neurotransmitter in the carotid body of several animal species and its functional role at the level of peripheral arterial chemoreflex pathway is attributed to the presence of the dopamine D2-receptors. We present evidence that the dopamine D1-receptor mRNA is also expressed in the carotid body of adult rabbits, cats and rats. A DNA fragment of 611 bp of this receptor was first isolated from rabbit. The nucleic acid sequence of this fragment was found to be 84.5% identical to that of rat. This specific 611 bp fragment was used as a probe to detect, either by Northern analysis or by the reverse transcription-polymerase chain reaction, the dopamine D1-receptor mRNA. The results revealed the presence of dopamine D1-receptor transcript in the carotid body as well as in the petrosal ganglion and the superior cervical ganglion from the three animal models studied here. The physiological significance of dopamine D1-receptor expression in the carotid body is discussed.

Expression of dopamine D2 receptor mRNA isoforms in the carotid body of rat, cat and rabbit.

Using the Reverse transcription-Polymerase chain reaction, we detected dopamine D2 receptor mRNA short and long isoforms in the adult carotid body of rats, cats, and rabbits. For these animals, the relative short/long ratios were 0.60, 0.65 and 0.57, respectively. Our results suggest that the variety of dopamine effects on carotid chemoreceptor activity, that has been related to species differences, may not be dependent on the expression levels of the dopamine D2 receptor mRNA isoforms in the studied species.

Effects of caffeine on carotid sinus nerve chemosensory discharge in kittens and cats.

Caffeine (C) decreases apneic episodes in premature infants and is thought to stimulate breathing mainly by a central mechanism. While the methylxanthines theophylline and aminophylline are known to alter the carotid chemoreceptor activity, there are little data on C. The aim of the study was to examine the effects of C on the carotid sinus nerve discharge (CSND) in developing animals. Nine kittens 17-21 days old and six adult cats that were anesthetized and artificially ventilated were studied. They received four consecutive doses of C, each of 10 mg/kg, administered at intervals of 20 min either as intravenous bolus injection (6 kittens, 3 cats) or continuous infusion (3 kittens, 3 cats). Bolus injections of C invariably induced a prompt but transient increase in the CSND from 4.1 +/- 0.6 to 8.1 +/- 1.0 (SE) impulses/s in kittens (P = 0.01) and form 3.9 +/- 0.1 to 7.9 to 1.0 impulses/s in cats (after the first injection). This response was associated with a significant decrease in arterial blood pressure. Continuous infusion of C did not induce any early change in either CSND or blood pressure in kittens or cats. Fifteen minutes after C injection or infusion was begun, CSND values in air, 8% O2-balance N2, or 100% O2 were not significantly different from control. Haloperidol administered at the end of the experiment in four cats and four kittens significantly increased CSND and did not suppress the early response to C injection. It is concluded that caffeine administered by bolus in the kitten induces a transient stimulation of the CSND that is associated with a decrease in the arterial blood pressure and is independent of the dopaminergic mechanisms in the carotid body. The lack of sustained effect implies the main mechanism to the ventilatory stimulation by C must be central.

Carotid body dopamine content and release by short-term hypoxia: effect of haloperidol and alpha methyl paratyrosine.

Dopamine (DA) is thought to modulate the transduction of the hypoxic stimulus by the glomus cell in the carotid body (CB). The hypothesis tested here is that presynaptic DA D2 receptors (D2's) located on the type 1 cell function as autoreceptors to control DA release and/or synthesis. The aim of the study was to compare the effects of blocking D2's with haloperidol and DA synthesis with alpha methyl paratyrosine (AMPT) on the in vitro carotid body DA response to hypoxia. 54 CB's sampled from adult rabbits were incubated for one hour in a surviving medium bubbled with either 100% O2 or 8% O2 Sixteen CB's served as control (100% O2: n = 8, 8% O2: n = 8), 18 (100% O2: n = 8, 8% O2: n = 10) were sampled from rabbits pretreated with AMPT and 20 (100% O2: n = 12, 8% O2: n = 8) were incubated with micromolar concentrations of haloperidol. At the end of exposure. DA contained in the carotid body (DACB) and released in the surviving medium (DAr) were measured by HPLC. In 100% O2 DACB was not different between either AMPT or haloperidol and control, but DAr was significantly higher in the haloperidol group compared with control (mean +/- SE: 26.6 +/- 7.4 versus 7.6 +/- 2.0 pmol/h, P < 0.02). In 8% O2, control DACB (576 +/- 133 pmol/CB) was significantly higher than AMPT or haloperidol (respectively 228 +/- 29.6 and 246 +/- 49.9 pmol/CB, P < 0.01) and control DAr (234 +/- 72.3 pmol/h) was also significantly higher than AMPT or haloperidol (respectively 28.8 +/- 5.2 and 40.6 +/- 11.4 pmol/h, P < 0.01). Finally, DAr was significantly larger in 8% O2 than in 100% O2 in control and AMPT groups (P < 0.01), but not in the haloperidol group. The increase in DAr by haloperidol in the resting CB is consistent with the blockade of D2's regulating DA release. The decreased DAr in 8% O2 after AMPT suggests that increased DA synthesis contributes to maintain DA secretion by the type I cell exposed to short term hypoxia. The lack of difference in DAr between 8% O2 and 100% O2 after haloperidol probably reflects non specific--i.e., D2 independent--effect of micromolar concentration of haloperidol on DA synthesis and/or sodium-calcium exchangers during hypoxia.

Expression of dopamine D2-receptor mRNA isoforms at the peripheral chemoreflex afferent pathway in developing rabbits.

The two isoforms of dopamine D2 receptor, D2 short (D2s) and D2 long, are generated by alternative splicing of premessenger RNA and differ in the length of their third cytoplasmic loop. Expression of these two isoforms has not yet been studied at the level of the peripheral arterial chemoreflex pathway. Using reverse transcriptase-polymerase chain reaction, we evaluated the relative abundance of dopamine D2 receptor mRNA by amplifying a common segment between both D2 receptor mRNA isoforms which reflects the total D2-receptor mRNA and the two isoforms in the carotid bodies, the petrosal ganglia, and the superior cervical ganglia of 1-, 10-, and 25-day-old and adult rabbits, GH4C1 cell line, which does not express D2 receptors, was used as negative control, whereas GH4C1 19 cell line, which expresses only the D2s mRNA and the striatum of each age, were used as positive controls. Both D2-receptor mRNA isoforms were found to be expressed in all organs studied of newborn and adult rabbits. The expression of total D2 receptor mRNA in 10- and 25-day-old and adult rabbits was found to be 3-, 5-, and 1.5-fold more, respectively, compared with 1-day-old rabbits for all organs studied. Our data suggest that the expression of D2-receptor mRNA is modulated with age at the level of the peripheral arterial chemoreflex pathway.

Effects of hypoxia on carotid body dopamine content and release in developing rabbits.

Hypoxia induces dopamine (DA) release from the carotid body (CB), but the role of DA during hypoxia in the postnatal maturation of carotid chemosensory discharge remains controversial. The aim of this study was to evaluate changes in CB content and release of DA evoked by hypoxia at different stages of development in the rabbit. Five groups of rabbits aged < or = 24 h (n = 9), 5 days (n = 27), 15 days (n = 18), 25 days (n = 16), and > or = 1 yr (n = 11) were studied. CBs were surgically removed and immediately incubated at 37 degrees C for 1 h in a surviving medium equilibrated with 100% O2 or 8% O2 in N2. The content of DA in the CB ([DA]CB) and the DA released in the surviving medium ([DA]r) were measured by high-performance liquid chromatography. [DA]CB was significantly larger in adults than in all pup groups in both 100% O2 [385.5 +/- 74.1 (SE) pmol/CB in adults and 43.6 +/- 6.0 pmol/CB in pups; P < 0.01] and hypoxia (518.1 +/- 99.9 pmol/CB in adults and 24.7 +/- 3.2 pmol/CB in pups; P < 0.01), presumably because of the larger CB mass. [DA]r was significantly larger in hypoxia than in 100% O2 only in 25-day-old rabbits (19.8 +/- 4.2 and 3.6 +/- 1.1 pmol/h, respectively; P < 0.01) and in adults (183.9 +/- 57.7 and 7.9 +/- 1.7 pmol/h, respectively; P < 0.01). The average ratio of [DA]r in hypoxia to [DA]r in 100% O2 ranged from 1.3 to 2.2 in the three younger age groups and was 5.5 and 23.3 in 25-day-old and adult rabbits, respectively. We conclude that the release of DA evoked by hypoxia is weak at birth and develops during the first weeks of life in rabbits.

Effects of haemorrhagic hypotension on carotid chemosensory discharge in the kitten.

Hypotension is known to affect the rate of carotid chemosensory activity in the adult cat, but the relationship between arterial blood pressure and carotid sinus nerve discharge has not been established in the kitten. The purpose of this study was to determine the response of carotid chemosensory afferents to hypotension induced in normoxia and in hyperoxia in eight kittens aged 1 to 25 days. Hypotension was obtained by a gradual decrease in blood volume. The activity of a few chemosensory fibres was recorded from one carotid sinus nerve. Baseline steady-state mean arterial blood pressure and carotid chemosensory activity were, respectively, 70.0 +/- 4.3 mmHg and 7.6 +/- 1.9 impulse/s (mean +/- SEM) in normoxia and 56.3 +/- 6.7 mmHg and 0.58 +/- 0.2 impulse/s in hyperoxia. Lowering arterial blood pressure below 37.5 +/- 3.5 mmHg in normoxia and 26.8 +/- 2.3 mmHg in hyperoxia was associated with a consistent increase in the rate of chemosensory discharge. Above this threshold, blood pressure variations had little effect on carotid chemoreceptor activity. These data are qualitatively similar to those of adult cats and provide evidence that, in newborn kittens, changes in arterial blood pressure will not influence carotid chemosensory discharge unless these changes are out of the physiological range.