Search PubMed⌕ Search

Biomedical subjects

J Roy

Publications and source records attributed to J Roy.

At least 55 records · Page 3Linked to original sources
PubMed1999

Monte Carlo simulations of prostate implants to improve dosimetry and compare planning methods.

The objective of this study is to use Monte Carlo simulations to assess the sensitivity of implant planning methods to seed misplacement. A model of seed misplacement is first developed. It is based upon data gathered after a study on source migration performed on 30 patients treated with I-125 transperineal implants. It consists of applying elementary transformations to every needle in a loading plan to produce a distorted implant mimicking the effect of migration. After being validated, the model has been used to tune the inverse planning system in use at our institution. The new planning system is now used clinically and actual results are compared with those predicted by simulations. Simulations were also used to compare our planning method with others. The new planning system increased the average postimplant dose-volume histogram DVH(160) from 82% to 93%, which is the value predicted by the simulations. This improvement is due to an increased dose margin providing coverage even in the presence of migration. At the same time, the dose to the urethra remained at 267 Gy because of a special protection feature included in the planning system. Some other implant planning methods are not as robust [average DVH(160) ranging from 76% to 85%] and deliver a higher dose to the urethra (close to 400 Gy). To conclude, a simple model of source migration can provide realistic feedback about sensitivity to migration of planning methods. It allowed a significant clinical improvement at our institution. The improved inverse planning system provided better coverage with fewer seeds (but equal total activity) than a manual method. Hence, a properly tuned inverse planning system has the potential to deliver the less sensitive plans. The model also helped demonstrate that planning methods are not equally robust to migration and that they should not be evaluated solely by the plans they produce, but also by their clinical (or simulated) results.

Biophysical Phenomena↗
PubMed1999

Chronic treatment with finasteride daily does not affect spermatogenesis or semen production in young men.

PURPOSE: Finasteride, an oral type 2, 5alpha-reductase inhibitor, is used in 1 mg. daily doses for the treatment of male pattern hair loss. A dose of 5 mg. finasteride daily reduces ejaculate volume by approximately 25%, and reduces prostate volume by approximately 20% and serum prostate specific antigen (PSA) by approximately 50% in men with benign prostatic hyperplasia. To our knowledge no data exist on the effect of 1 mg. finasteride daily on ejaculate volume or other semen parameters, or on the prostate in young men. Therefore, we studied the potential effect and reversibility of effect of 1 mg. finasteride daily on spermatogenesis, semen production, the prostate and serum PSA in young men. MATERIALS AND METHODS: In this double-blind, placebo controlled multicenter study 181 men 19 to 41 years old were randomized to receive 1 mg. finasteride or placebo for 48 weeks followed by a 60-week off-drug period. Of the 181 men 79 were included in a subset for the collection and analysis of sequential semen samples. RESULTS: There were no significant effects of 1 mg. finasteride on sperm concentration, total sperm per ejaculate, sperm motility or morphology. Ejaculate volume in subjects on finasteride decreased 0.3 ml. (-11%) compared to a decrease of 0.2 ml. (-8%) for placebo, with a median between treatment group difference of -0.03 ml. (1%, 90% confidence interval -10.4 to 13.1, p = 0.915). There were significant but small decreases in prostate volume (-2.6%) and serum PSA (-0.2 ng./ml.) in the finasteride group, which reversed on discontinuation of the drug. CONCLUSIONS: Treatment with 1 mg. finasteride daily for 48 weeks did not affect spermatogenesis or semen production in young men. The effects of 1 mg. finasteride daily on prostate volume and serum PSA in young men without benign prostatic hyperplasia were small and reversible on discontinuation of the drug.

Adult↗
PubMed1999

Effect of time exposure to high altitude on zinc and copper concentrations in human plasma.

BACKGROUND: Research has focused mainly on the relationship of zinc and copper contents and physical stresses like running, cycling, etc. It has also been reported that other forms of stresses change the concentration of these trace elements in humans. However,there are no reports on the effects of high altitude induced hypoxic stress on the plasma levels of these metals. Since hypoxia is one of the important stresses, we considered it appropriate to observe the changes in the levels of zinc and copper concentrations and in certain related zinc and copper enzymes and hormones in the plasma of human volunteers on acute induction to high altitude. From these findings, we intended to ascertain whether supplementation of these trace elements would be required for optimal health under such conditions. HYPOTHESIS: On acute induction to hypoxia, contents of these trace elements may change as the requirements of stressed organs and tissue may increase. Hence, further supplementation may be beneficial under hypoxic stress for better adaptability. METHOD: Volunteers were divided into two groups: with and without zinc and copper salt supplementation. Blood samples were collected at sea level and on induction to acute hypoxia on days 3 and 10. Trace mineral contents and their related enzyme (alkaline phosphatase) and hormone (ceruloplasmin) levels were determined in plasma samples. RESULTS: Plasma zinc contents were significantly reduced upon induction to high altitude in the non-supplemented group, but not in the zinc-supplemented group. Alkaline phosphatase activity increased significantly upon induction to the high altitude stress. The enzyme activity remained elevated up to day 10 of the stress. Plasma copper contents and ceruloplasmin activity did not change upon induction to high altitude. CONCLUSION: Under hypoxic stress, circulating levels of zinc and alkaline phosphatase in plasma changed appreciably as plasma zinc was transported into the organs and tissues. However, circulating levels of copper and ceruloplasmin in plasma did not change, indicating no extra supplementation of copper is required under hypoxic stress.

Acute Disease↗
PubMed1999

Control of smooth muscle cell proliferation--the role of the basement membrane.

In atherogenesis and in response to vessel injury, arterial smooth muscle cells (SMCs) are activated from a quiescent, differentiated state into an actively proliferating and synthetic phenotype which migrate into the intima where the cells participate in the formation of a fibrous plaque or intimal hyperplasia. The mechanisms involved in the control of SMC function are not clear and no preventive therapy against SMC activation is available. Interactions between SMCs and the extracellular matrix have been shown to influence SMC structure and function through integrin-mediated signaling processes. The SMC basement membrane is a specific form of extracellular matrix which seems to be crucial for the maintenance of SMC quiescence and the disruption of these interactions is part of cellular activation after atherogenic or traumatic stimuli. This concept of "negative growth control" may constitute a future target for the development of new strategies in the prevention of SMC activation in atherogenesis and restenosis formation.

Animals↗
PubMed1998

Glutamate potentiates the toxicity of mutant Cu/Zn-superoxide dismutase in motor neurons by postsynaptic calcium-dependent mechanisms.

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene are responsible for a subset of familial cases of amyotrophic lateral sclerosis. Using a primary culture model, we have demonstrated that normally nontoxic glutamatergic input, particularly via calcium-permeable AMPA/kainate receptors, is a major factor in the vulnerability of motor neurons to the toxicity of SOD-1 mutants. Wild-type and mutant (G41R, G93A, or N139K) human SOD-1 were expressed in motor neurons of dissociated cultures of murine spinal cord by intranuclear microinjection of plasmid expression vector. Both a general antagonist of AMPA/kainate receptors (CNQX) and a specific antagonist of calcium-permeable AMPA receptors (joro spider toxin) reduced formation of SOD-1 proteinaceous aggregates and prevented death of motor neurons expressing SOD-1 mutants. Partial protection was obtained by treatment with nifedipine, implicating Ca2+ entry through voltage-gated calcium channels as well as glutamate receptors in potentiating the toxicity of mutant SOD-1 in motor neurons. Dramatic neuroprotection was obtained by coexpressing the calcium-binding protein calbindin-D28k but not by increasing intracellular glutathione levels or treatment with the free radical spin trap agent, N-tert-butyl-alpha-phenylnitrone. Thus, generalized oxidative stress could have contributed in only a minor way to death of motor neurons expressing the mutant SOD-1. These studies demonstrated that the toxicity of these mutants is calcium-dependent and provide direct evidence that calcium entry during neurotransmission, coupled with deficiency of cytosolic calcium-binding proteins, is a major factor in the preferential vulnerability of motor neurons to disease.

2-Amino-5-phosphonovalerate↗
PubMed1998

Specific telomerase RNA residues distant from the template are essential for telomerase function.

The reverse transcriptase telomerase is a ribonucleoprotein complex that adds telomeric repeats to chromosome ends, using a sequence within its endogenous RNA component as a template. Although templating domains of telomerase RNA have been studied in detail, little is known about the roles of the remaining residues, particularly in yeast. We examined the functions of nontemplate telomerase residues in the telomerase RNA of budding yeast Kluyveromyces lactis. Although approximately half of the RNA residues were dispensable for function, four specific regions were essential for telomerase action in vivo. We analyzed the effects of mutating these regions on in vivo function, in vitro telomerase activity, and telomerase RNP assembly. Deletion of two regions resulted in synthesis of stable RNAs that appeared unable to assemble into a stable RNP. Mutating a region near the 5' end of the RNA allowed RNP assembly but abolished enzymatic activity. Mutations in another specific small region of the RNA led to an inactive telomerase RNP with an altered RNA conformation.

Deoxyribonucleases, Type II Site-Specific↗
PubMed1998

Role of the striatum, cerebellum and frontal lobes in the automatization of a repeated visuomotor sequence of movements.

Recently, Doyon et al. [20] demonstrated that lesions to both the striatum and to the cerebellum in humans produce a similar deficit in the learning of a repeated visuomotor sequence, which occurs late in the acquisition process. We now report the results of two experiments that were designed to examine whether this impairment was due to a lack of automatization of the repeating sequence of finger movements by using a dual-task paradigm and by testing for long-term retention of this skill. In Experiment 1, the performance of groups of patients with Parkinson's disease, or with damage to the cerebellum or to the frontal lobes, was compared to that of matched control subjects on the Repeated Sequence Test (primary task) and the Brooks' Matrices Test (secondary task). These two tests were administered concomitantly in both early and late learning phases of the visuomotor sequence. Overall, the groups did not differ in their ability to execute the primary task. By contrast, in accordance with the predictions, patients in Stages 2-3 of Parkinson's disease or with a cerebellar lesion failed to reveal the expected increase in performance on the secondary task seen with learning, suggesting that the latter groups of patients did not have access to the same level of residual cognitive resources to complete the matrices compared to controls. In Experiment 2, the same groups of patients and control subjects were retested again 10-18 months later. They were given four blocks of 100 trials each of the repeating sequence task, followed by a questionnaire and a self-generation task that measured their declarative knowledge of that sequence. The results revealed a long-term retention impairment only in patients who changed from Stage I to Stage II of the disease (suggesting further striatal degeneration) during the one-year interval, or who had a cerebellar lesion. By contrast, performance of the three clinical groups did not differ from controls on declarative memory tests. These findings suggest that both the striatum and the cerebellum participate to the automatization process during the late (slow) learning stage of a sequence of finger movements and that these structures also play a role in the neuronal mechanism subserving long-term retention of such a motor sequence behavior.

Adult↗
PubMed1998

Biologic variability of prostate-specific antigen and its usefulness as a marker for prostate cancer: effects of finasteride. Finasteride PSA Study Group.

OBJECTIVES: The effects of finasteride on prostate-specific antigen (PSA) variability and usefulness in prostate cancer detection were examined. METHODS: Percent change and crossover of PSA levels between the low (1.0 to 3.9 ng/mL) and high (4.0 to 10.0 ng/mL) ranges were evaluated in 72 men with benign prostatic hyperplasia (BPH) and 77 men with both BPH and prostate cancer (PCa) treated with finasteride or placebo for 6 months. Patients with PCa were studied as a model for evaluating the effects on PSA levels in patients with BPH and latent PCa. As recommended on the product label, PSA levels for finasteride-treated patients were doubled for interpretation. RESULTS: In patients with BPH, most placebo- and finasteride-treated patients with low PSA levels at baseline had subsequent PSA levels below 4.0 ng/mL throughout the study. Among patients with high baseline PSA levels, only 1 of 17 finasteride-treated patients, compared with 8 of 13 placebo-treated patients, crossed into the low range. In the BPH/PCa study, most placebo-treated patients maintained PSA levels in the same range (15 of 19 less than 4.0 ng/mL; 14 of 16 greater than 4.0 ng/mL). Almost one third of finasteride-treated patients with low PSA levels at baseline crossed into the high range (8 of 22), whereas most patients with high PSA levels at baseline were not masked with treatment, with PSA levels remaining high (12 of 15). CONCLUSIONS: PSA levels cross between the low and high PSA ranges in both finasteride- and placebo-treated patients with BPH and those with both BPH and PCa. Doubling the PSA levels in finasteride-treated patients allows appropriate interpretation of PSA values and does not mask the detection of PCa.

Adult↗
PubMed1998

Large cell lymphoma complicating persistent polyclonal B cell lymphocytosis.

Persistent polyclonal B cell lymphocytosis (PPBL) is a rare lymphoproliferative disorder of unclear natural history and its potential for B cell malignancy remains unknown. We describe the case of a 39-year-old female who presented with stage IV-B large cell lymphoma 19 years after an initial diagnosis of PPBL; her disease was rapidly fatal despite intensive chemotherapy and blood stem cell transplantation. Because we had recently identified multiple bcl-2/Ig gene rearrangements in blood mononuclear cells of patients with PPBL, we sought evidence of this oncogene in this particular patient: bcl-2/Ig gene rearrangements were found in blood mononuclear cells but not in lymphoma cells. Owing to the possible role of Epstein-Barr virus (EBV) in the pathogenesis of PPBL, we also hypothesized our patient might have an EBV-related lymphoproliferative disorder. Despite serologies consistent with past exposure to this virus, it was not found in lymphoma cells using a sensitive polymerase chain reaction technique. We conclude that non-Hodgkin's lymphoma may occur during the course of PPBL. However, longer follow-up in more patients will be needed in order to better clarity the risk of hematologic malignancy in patients with PPBL.

Adult↗
PubMed1998

Experimental and Monte Carlo dosimetry of the Henschke applicator for high dose-rate 192Ir remote afterloading.

We have performed extensive computational and experimental dosimetry of the Henschke applicator with respect to high dose-rate 192Ir brachytherapy using a GAMMAMED remote afterloader. Our goal was to generate clinically useful two- and three-dimensional look-up tables. Dose measurements of the Henschke applicator involved using TLD chips placed in a polystyrene phantom. Monte Carlo simulations were performed using the MCNP code. The computational models included the detailed geometry of 192Ir source, tandem tube, and shielded ovoid. The measured dose rates were corrected for the dependence of TLD sensitivity on the distance of measurement points from the source. Transit dose delivered during source extension to and retraction from a given dwell position was estimated by Monte Carlo simulations, and a correction was applied to the experimental values. For the applicator tandem, the ratio of dose rates obtained by MCNP to those measured by TLD chips ranges from 0.92 to 1.10 with an average of 0.98 and a standard deviation of 0.02. The measured and calculated dose rates at 1 cm on the transverse axis are 1.10 cGy U-1 h-1. For the shielded ovoid, the ratio ranges from 0.88 to 1.16 with an average of 1.00 and a standard deviation of 0.07. Causes of the discrepancy between the Monte Carlo and TLD results were identified. We found that the combined uncertainty of measured dose rates due to these causes is 5.6% for the applicator tandem and 8.4% for the shielded ovoid. Therefore, the results of the Monte Carlo simulation are considered to have been validated by the measurements within the uncertainty involved in the calculation and measurements.

Brachytherapy↗
PubMed1998

Demonstration and immunolocalization of ATP diphosphohydrolase in the pig digestive system.

Two isoforms of ATP diphosphohydrolase (ATPDase; EC 3.6.1.5) have been previously characterized, purified, and identified. This enzyme is an ectonucleotidase that catalyzes the sequential release of gamma- and beta-phosphate groups of triphospho- and diphosphonucleosides. One of its putative roles is to modulate the extracellular concentrations of purines in different physiological systems. The purpose of this study was to define, identify, and localize these two isoforms of ATPDase in the pig digestive system. ATPDase activity was measured in pig stomach, duodenum, pancreas, and parotid gland. Enzyme assays, electrophoretograms, and Western blots with a polyclonal antibody that recognizes both isoforms demonstrate the presence of ATPDase in these organs. Immunolocalization showed intense reactions with gastric glands (parietal and chief cells), intestine (columnar epithelial cells), parotid gland, and pancreas. Smooth muscle cells all along the digestive tract were also highly reactive. Considering the variety of purinoceptors associated with the digestive system, the ATPDase is strategically positioned to modulate purine-mediated actions such as electrolyte secretion, glandular secretion, smooth muscle contraction, and blood flow.

Animals↗
PubMed1998

All patients with persistent polyclonal B cell lymphocytosis present Bcl-2/Ig gene rearrangements.

The bcl-2 gene belongs to a class of oncogenes involved in the inhibition of apoptosis. Most follicular lymphomas are associated with the t(14;18) translocation that juxtaposes the bcl-2 gene located on chromosome 18 to the immunoglobulin gene locus located on chromosome 14. Consequently, the bcl-2 gene is overly expressed and leads to an accumulation of mature clonal B cells. Prolonged survival of the B cell clone appears to be the early event in tumorigenesis, creating an increased risk of cumulative mutations. Interestingly, bcl-2/Ig gene rearrangements may be identified in nearly 50% of normal individuals but the outcome of normal individuals carrying high levels of t(14;18) is not well defined. Persistent polyclonal B cell lymphocytosis (PPBL) is a unique polyclonal lymphoproliferative disorder mostly restricted to women. We have recently demonstrated that PPBL is also associated with multiple bcl-2/Ig gene rearrangements. In this report, we have extended our analysis to additional patients and demonstrated that all patients presented multiple detectable t(14;18) translocated clones. In addition, Bcl-2 protein expression was increased. Our findings, along with the clinical features of PPBL, make this disorder an exceptional model for the study of B-cell homeostasis.

Adult↗
PubMed1997

Electronic portal imaging device detection of radioopaque markers for the evaluation of prostate position during megavoltage irradiation: a clinical study.

PURPOSE: This study was designed to assess daily prostatic apex motion relative to pelvic bone structures during megavoltage irradiation. METHODS AND MATERIALS: Radioopaque markers were implanted under ultrasound guidance near the prostatic apex of 11 patients with localized prostatic carcinoma. Patients were subsequently treated with a four field-box technique at a beam energy of 23 MV. During treatment, on-line images were obtained with an electronic portal imaging device (EPID). The marker was easily identified, even on unprocessed images, and the distance between the marker and a bony landmark was measured. Timelapse movies were also reviewed. After the completion of treatment, a transrectal ultrasound examination was performed in 8 of 11 patients, to verify the position of the marker. RESULTS: We acquired over 900 digital portal images and analyzed posterioanterior and right lateral views. The quality of portal images obtained with megavoltage irradiation was good. It was possible to evaluate pelvic bone structures even without image histogram equalization. Moreover, the radioopaque marker was easily visible on every online portal image. The review of timelapse movies showed important interfraction motion of the marker while bone structures remained stable. We measured the position of the marker for each fraction. Marker displacements up to 1.6 cm were measured between 2 consecutive days of treatment. Important marker motions were predominantly in the posteroanterior and cephalocaudal directions. In eight patients, we verified the position of the marker relative to the prostatic apex with ultrasound at the end of the treatments. The marker remained in the trapezoid zone. Intratreatment images reviewed in two cases showed no-change in marker position. Our results, obtained during the treatment courses, indicate similar or larger prostate motions than previously observed in studies that used intertreatment x-ray films and CT images. Marker implantation under transrectal ultrasound was well tolerated. CONCLUSIONS: Radioopaque marker and the use of electronic portal imaging give a direct evaluation of prostatic motion during radiation treatment. As suggested in previous studies the motions observed are predominantly in the posteroanterior and cephalocaudal directions. Therefore, prostate motion during treatment is important and must be considered especially when using conformal therapy.

Carcinoma↗
PubMed1997

Biologic variability of prostate-specific antigen and its usefulness as a marker for prostate cancer: effects of finasteride. The Finasteride PSA Study Group.

OBJECTIVES: The effects of finasteride on prostate-specific antigen (PSA) variability and usefulness in prostate cancer detection were examined. METHODS: Percent change and crossover of PSA levels between the low (1.0 to 3.9 ng/mL) and high (4.0 to 10.0 ng/mL) ranges were evaluated in 72 men with benign prostatic hyperplasia (BPH) and 77 men with both BPH and prostate cancer (PCa) treated with finasteride or placebo for 6 months. Patients with PCa were studied as a model for evaluating the effects on PSA levels in patients with BPH and latent PCa. As recommended on the product label, PSA levels for finasteride-treated patients were doubled for interpretation. RESULTS: In patients with BPH, most placebo- and finasteride-treated patients with low PSA levels at baseline had subsequent PSA levels below 4.0 ng/mL throughout the study. Among patients with high baseline PSA levels, only 1 of 17 finasteride-treated patients compared with 8 of 13 placebo-treated patients crossed into the low range. In the BPH/PCa study, most placebo-treated patients maintained PSA levels in the same range (15 of 19 less than 4.0 ng/mL; 14 of 16 greater than 4.0 ng/mL). Almost one third of finasteride-treated patients with low PSA levels at baseline crossed into the high range (8 of 22), whereas most patients with high PSA levels at baseline were not masked with treatment, with PSA levels remaining high (12 of 15). CONCLUSIONS: PSA levels cross between the low and high PSA ranges in both finasteride- and placebo-treated patients with BPH and those with both BPH and PCa. Doubling the PSA levels in finasteride-treated patients allows appropriate interpretation of PSA values and does not mask the detection of PCa.

Adult↗
PubMed1997

Multiple bcl-2/Ig gene rearrangements in persistent polyclonal B-cell lymphocytosis.

Persistent polyclonal B-cell lymphocytosis is a benign lymphoproliferative disorder of unknown aetiology occurring exclusively in women, characterized by typical binucleated lymphocytes, polyclonal expansion of B cells and elevated serum IgM. Owing to the role of Bcl-2 oncogene in inhibition of apoptosis, we have investigated the presence of the bcl-2/Ig gene rearrangement. Bcl-2/Ig gene rearrangement was determined by polymerase chain reaction targeting the usual breakpoint regions of the t(14;18). Bcl-2/Ig gene rearrangement was identified in all six patients and, more importantly, multiple rearrangements were present in five patients. The frequency of the bcl-2/Ig gene rearrangement is estimated to be of one translocation in 1 x 10(2) to 1 x 10(3) peripheral blood mononuclear cells. We conclude that persistent polyclonal B-cell lymphocytosis is associated with bcl-2/Ig gene rearrangement. These findings are of clinical importance because these patients may be misdiagnosed as having a leukaemic expression of non-Hodgkin's lymphoma.

Adult↗
PubMed1997

Aggregation of mutant Cu/Zn superoxide dismutase proteins in a culture model of ALS.

Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene underlie some familial cases of amyotrophic lateral sclerosis (FALS), a neurodegenerative disorder characterized by loss of cortical, brainstem, and spinal motor neurons. To investigate the mechanisms responsible for the toxicity of mutant enzyme, SOD-1 cDNAs bearing mutations found in FALS patients (mSOD) were expressed in cultured spinal motor neurons, dorsal root ganglion (DRG) and hippocampal neurons. Many features of motor neuron disease seen in humans with FALS and in transgenic mouse models were reproduced, including preferential susceptibility of motor neurons to toxicity of mSOD. Abnormal cytoplasmic aggregation of mSOD protein was observed in mSOD-expressing motor neurons, but never in neurons expressing SODwt enzyme, and was followed by evidence of apoptotic cell death. Such aggregates were not observed in nonvulnerable neuronal populations expressing mSOD (DRG or hippocampal neurons). Aggregation of SOD-1 may contribute significantly to the death of motor neurons expressing mutations associated with FALS-1 and the mechanisms leading to aggregation may pertain to the specific vulnerability of motor neurons in this disease.

Amyotrophic Lateral Sclerosis↗
PubMed1997

Health status, treatment and drug use in rural Bangladesh: a case study of a village.

In Bangladesh, the government healthcare system remains a very minor source of health care for rural households. The availability of registered physicians is scare in rural areas, and the people, the majority of whom are underweight as indicated by body mass index measurement have to depend on pharmacy salespersons, quacks and herbal or spiritual healers. Unlike Australia, almost every pharmacy salesperson illegally recommends and sells prescription medicines. In addition, there are also unqualified village 'doctors' who do not own a pharmacy shop but provide written prescriptions. However, the treatments provided by these village 'doctors' remain open to question, with instances of maltreatment or inadequate treatment. The treatments are mostly symptomatic and polypharmacy is common, with antibiotics and vitamins prescribed widely. On the other hand, rural people sometimes do not buy all the drugs that are prescribed for them, partly because of financial constraint. In addition, self-medication is common. While family planning and immunisation are slowly becoming popular among rural families, general health knowledge is still poor. Public healthcare campaigns as well as proper training for the rural prescribers could be helpful in improving the present poor rural healthcare system.

Adolescent↗