Elevated serum tumor necrosis factor-alpha and endothelin 1 levels correlate with increased C-peptide concentration in android type obesity.
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Adult↗
Biomedical subjects
M Kovács
Publications and source records attributed to M Kovács.
Inhibition of GH release of rats by new potent antagonists of growth hormone-releasing hormone (GH-RH).
Biological activity of a new series of potent GH-RH antagonists containing formyl or phenylacetyl group at the N-terminus of the sequence [D-Arg2,Phe(4-Cl)6,Nle27]hGH-RH(1-29)NH2, as well as various substitutions in positions 8, 15, or 28, and in some cases Agm in position 29, was evaluated in vivo. All five antagonists, administered at a 27-fold molar excess to rats, suppressed the GH-releasing effect of exogenous GH-RH(1-29)-NH2 by 64-75%. The inhibitory effects lasted for more than 15 min. The most potent analogue, PhAc-[D-Arg2,Phe(4-Cl)6,Abu15,Nle27]hGH-RH(1-28)Agm (MZ-5-156), showed an in vivo potency 7-16 times higher than the early antagonist [Ac-Tyr1,D-Arg2]hGH-RH(1-29)-NH2, which was used as standard. MZ-5-156 was capable of decreasing serum GH levels after intravenous, intraperitoneal, or intramuscular administration. In vitro, in the superfused rat pituitary cell system, MZ-5-156 induced a prolonged inhibition of GH release after continuous long-term administration and showed a potency more than 100 times greater than the standard antagonist. These results show that N-terminal acylation with phenylacetic acid of the sequence [D-Arg2,Phe(4-Cl)6,Nle27]hGH-RH(1-29)-NH2, containing modifications in positions 8, 15, 28, or 29, results in antagonists with high and protracted potency both in vivo and in vitro. In view of high antagonistic activity and prolonged duration of action, some of these antagonists of GH-RH may find clinical application for the treatment of IGF-dependent cancers.
Animals↗
Drugs acting on calcium channels modulate the diuretic and micturition effects of dexmedetomidine in rats.
The purpose of this study was to assess the effects of calcium channel antagonist, verapamil, and agonist, Bay K 8644, on the alpha 2-adrenoceptor agonist, dexmedetomidine-induced (300 micrograms kg-1 subcutaneously) diuresis and overflow incontinence, in rats. Ultrasonography study revealed that verapamil (2.5 mg kg-1 subcutaneously) or Bay K 8644 (0.5 mg kg-1 intraperitoneally) coadministrations delayed dexmedetomidine-induced bladder filling and significantly prolonged the latency of urination (P < 0.05). Bay K 8644 decreased relative bladder volume and stopped continuous urination from dexmedetomidine, whereas verapamil had neither effect. However, none of the drugs eliminated the overflow incontinence. Dexmedetomidine alone increased the hourly and total (for 4 hours) urine volume. Bay K 8644 (0.5 or 1 mg kg-1) dose-dependently decreased the diuretic effect of dexmedetomidine (P < 0.01). Verapamil (0.5, 1 or 2.5 mg kg-1) dose-dependently decreased urine volume in the first hour (P < 0.01), and thereafter potentiated the diuretic effect of dexmedetomidine. Simultaneous determinations of mean arterial blood pressure (MAP) and urine output after dexmedetomidine and the highest dose of verapamil coadministration demonstrated a significant correlation between these variables (r = 0.537; P < 0.001). MAP of 100 mmHg or less was associated with a urine output significantly lower (P < 0.001) than that at higher pressures. Thus, hypotension during the first hour after dexmedetomidine-verapamil may explain the transient reduction in urination during this period. We conclude that modulation of calcium channel affects dexmedetomidine actions on both urine formation and micturition. Since both alpha 2-adrenoceptor agonists and calcium channel blockers have frequently been used for antihypertensive therapy and as adjuvant drugs during anesthesia, these interactions may have some practical importance.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Chronic administration of a new potent agonist of growth hormone- releasing hormone induces compensatory linear growth in growth hormone-deficient rats: mechanism of action.
To assess the efficacy of a potent agonist analog of GH-releasing hormone (GH-RH), [Dat1,Gln8,Orn12,21,Abu15,Nle27,Asp28,A gm29]hGH-RH(1-29) (JI-38), we investigated the effects of its chronic administration on growth responses in monosodium glutamate (MSG)-lesioned and normal young rats. Body weight (BW), body length (BL), tibia length (TIL), and tail length (TAL) were monitored. Basal serum GH concentrations, GH responses to bolus injections of GH-RH, pituitary GH and serum IGF-I concentrations were measured by RIA. Pituitary GH-RH receptor concentration and binding affinity was also evaluated after the treatment. Neonatal treatment with MSG resulted, as expected, in blunted growth and a decrease in serum and pituitary GH concentration and serum IGF-I levels. A reduction in GH-RH receptor concentration, associated with increased binding affinity of the GH-RH receptor was also found. Chronic administration of GH-RH agonist JI-38 in doses of 2 micrograms at 12-hour intervals for 2 weeks markedly increased the GH responsiveness to GH-RH and stimulated growth, with MSG-treated animals achieving the growth rate of normal controls. Acceleration of growth was associated with stimulated GH synthesis and IGF-I secretion, although basal serum GH levels did not change. Pituitary GH-RH receptor concentration and binding affinity were not significantly modified by the treatment. Treatment of normal young growing rats with agonist JI-38 did not further increase the normal growth acceleration in these rats, but stimulated the GH synthesis and augmented the GH secretory responsiveness. The treatment of MSG-lesioned rats with GH-RH agonist was generally more effective in female than in male animals, and in some cases masked the sex differences in growth rate. Our findings provide the first evidence that the blunted growth rate of the MSG-lesioned rats is associated with a decreased pituitary GH-RH receptor concentration. Our work demonstrates that administration of GH-RH agonist JI-38 is able to restore the normal growth rate of the GH-deficient rats by stimulating GH synthesis and IGF-I secretion.
Animals↗
Synthesis of GnRH analogs having direct antitumor and low LH-releasing activity.
New chicken I GnRH agonists and antagonists have been synthesized and tested for their biological activities. The common feature of these analogs was that the molecules had a beta-L-aspartyl residue inserted in position 6. The agonist bound to the pituitary still had low endocrinological activity. On the other hand, it exhibited direct antitumor effect in in vitro assays. The endocrinological activity of the antagonist was low; however, it showed potent, direct antitumor activity. These observations might lead to the development of new GnRH analogs with selective antitumor effect.
Animals↗
Effects of continuous and repetitive administration of a potent analog of GH-RH(1-30)-NH2 on the GH release in rats treated with monosodium glutamate.
To assess the efficacy of a potent GH-releasing hormone (GH-RH) analog (D-Ala2,Nle27,Gaba30-GH-RH-(1-30)-amide) in the treatment of GH deficiency, we investigated the effects of chronic administration of this analog (A-495) on growth responses in monosodium glutamate (MSG)-lesioned rats. Basal serum GH concentrations, GH responses to bolus injections of GH-RH, as well as acceleration of body gain and linear growth were compared after long-term continuous and repetitive administration of A-495. The effects of continuous and repetitive administration of the analog on GH responses in vitro were also compared using the superfused pituitary cell system method. Treatment with MSG reduced the body weight and linear growth of the animals (-22% and -11%, respectively), the basal serum GH concentration (-66%), and the GH-RH-induced absolute GH responses (-61%) but did not alter the relative GH responses (to basal GH concentrations). Repetitive administration of 10 micrograms daily doses of A-495 at 24 h intervals for 2 weeks highly increased the GH responsiveness to GH-RH and induced catch-up growth, by which MSG-treated animals achieved the growth rate of normal controls. However, basal serum GH concentrations were only modestly enhanced. Continuous infusion of A-495 at the same daily dose resulted in slight increases in the GH-RH-induced GH rises, moderate acceleration of body gain, and no change in linear growth. Basal serum GH concentrations were not significantly influenced by this treatment. These results demonstrate that exogenous GH-RH pulses administered at lower frequency than the frequency of the physiological GH secretion are able to fully restore the normal growth rate of the GH deficient rats. The effectivity of the treatment is rather dependent on the magnitude of GH rises than the basal GH level. Although continuous administrations of the GH-RH is also have some effect on the body gain, repetitive administration is more effective at the same daily dose. Our results from in vitro experiments show that, in addition to the low magnitude of the GH-RH-stimulated GH rises, desensitization of the GH secretory response might also be accounted for the low effectivity of the continuously administered GH-RH. Present results demonstrate the therapeutic usefulness of our new GH-RH analog and are the first to evidence that GH-RH need not be administered as frequently as the appearance of the endogenous GH pulses to restore the normal growth of the GH deficient rats.
Age Factors↗
"Auctoritas" psychiatric expert system shell.
We present a short description of a complex psychiatric computer expert system, including functions that help the physicians and the hospital staff in the administrative, diagnostic, therapeutic, statistical, and scientific work. There are separate data-storing, health insurance-supporting, or simple advisory programs, but we can not avail a system--in our country--that provides us with all these functions together. Hence the aim of our program is to produce a universal computer system that makes the patients' long distance follow-up possible. Our diagnostic expert system shell, which is appropriate for using the symptoms and criteria scheme of the internationally accepted diagnostic systems such as DSM and ICD, helps to archive homogeneous, up-to-date psychiatric nosology; this is essential for the correct diagnostic, statistical, and scientific work. Let us introduce our expert system. It consists of four parts: administration, diagnostic decision support system, activities concerning treatment, and statistics. The part called "Administration" contains all data about actual and emitted in-patients and out-patients, including their particulars and data necessary for health insurance (duration of treatment, diagnosis); here we find and edit medical documents. The most important part of the "Auctoritas" system is the "Diagnostic decision support system." In practice, expert systems use decision trees with yes-no logic, fuzzy logic, and pattern matching on the basis of the method of deduction; and backward chaining or forward chaining on the basis of the direction of deduction. Our system uses the methods of fuzzy logic and backward chaining. In other medical disciplines, good results are achieved by applying the pattern matching method; to make validity and verification researches, however, these systems are inappropriate. The diagnoses relying on the up-to-date psychiatric diagnostic systems--DSM-IV and ICD-X--are based on classical logic and can be correctly validated and verified. Hence we have chosen the fuzzy logic, which is the up-to-date extension of classical logic and influences the validity and verification researches, for the construction of our system. The diagnostic part is a shell that can be filled up optionally with knowledge bases of the DSM-IV, ICD-X, or other diagnostic systems and has the following structure. The diagnostic course is biphased as we can differ symptoms and criteria (duration of the illness, aethyological factors). We managed to extend the traditional applications using yes-no logic with three factors that make the system more sensitive and flexible. These are the scaling, sorting by importance of symptoms, and reliability-validity results. The "scaling" means that the physician scales the input symptoms by severity; this influences the statistical probability of the possible diagnoses. "Sorting by importance" is gauging certain symptoms by importance in a syndrome. Finally the third point, "reliability-validity results," means taking account of the latest validity values of a certain disorder of the used diagnostic system--according to the latest validity researches--and the diagnostical reliability of our expert system. The "Activity concerning treatment" is a practical part of our program that contents the examination and therapy scheduling and monitoring results. Under the point of "Statistics," we can prepare all data of the patients in various ways. In summary, the "Auctoritas" computer system is a global database managing the newly-developed advisory system; it is appropriate for managing a complete hospital network system for the continuing individual long-distance observation of patients. It collects all the necessary information of one patient in one file. The long-term benefit is that it can compile and process large amounts of information about the patients and help physicians come to scientific conclusions for research and publications.
Decision Making, Computer-Assisted↗
Mydriatic and antinociceptive effects of intrathecal dexmedetomidine in conscious rats.
A comparison was made of the dose-effect relationship of intrathecally applied dexmedetomidine as concerns its mydriatic and antinociceptive effects in rats. Pupil diameter was measured with a photographic method without anesthesia. Antinociception was measured by means of the tail-withdrawal test. The intrathecal (i.t.) administration of dexmedetomidine led to dose-dependent antinociception (P < 0.05) and mydriasis (P < 0.001). Both effects reached their maximum 10 min after drug application. The tail-withdrawal latency was prolonged by 9 micrograms dexmedetomidine. Mydriasis appeared on administration of a 1 microgram dose and its degree was proportional to the dexmedetomidine dosage up to 12 micrograms. A significant correlation was not found between pupil diameter and tail-withdrawal latency in the same rat after any dexmedetomidine dose. Based on the present experiments, we conclude that the mydriatic effect of i.t. dexmedetomidine appears at a lower dose than its antinociceptive effect. Our results suggest that the assessment of pupillary response is a sensitive method for estimation of the supraspinal effect of i.t. administered alpha 2-adrenoceptor agonists.
Adrenergic alpha-Agonists↗
An ultrasonographic method for the evaluation of dexmedetomidine on micturition in intact rats.
We describe a simple, noninvasive, nontraumatic, and reproducible ultrasonographic method to determine the effect of the alpha 2-adrenoceptor agonist dexmedetomidine in anesthetic dose (300 micrograms/kg subcutaneously) on the micturition reflex in intact rats. The bladder volumes were estimated by an ellipsoid equation. To validate the reliability of the method, an in vitro model assessment also was performed. The mean difference between estimated and instilled volumes were 27.3 microL (-21.61, 76.23). The highly significant correlation (r = 0.98, p < .001) indicates that the ultrasonography with the equation is a reliable tool. After the dexmedetomidine administration to intact rats, urine dribbling occurred at 30 +/- 4.8 min. The volume threshold for urination was 2100 +/- 100 microL. Although dribbling of the urine was observed almost continuously, significant differences were not observed between bladder volumes obtained at any time (from 10 to 100 min). This study indicates that the alpha 2-adrenoceptor agonist dexmedetomidine inhibits the micturition reflex in intact rats. The method described, which is both noninvasive and nonpainful, may therefore be widely used to quantify in small animals pharmacological effects on the urinary bladder.
Animals↗
Effects of continuous and repetitive administration of a potent analog of GH-RH(1-30)NH2 on the GH release in rats.
We examined the desensitization and/or sensitization phenomenon in the pituitary GH responsiveness induced by continuous infusion and multiple pulses at different frequencies of a potent GH-RH analog [D-Ala2, Leu15, Nle27, GABA30-GH-RH(1-30)amide]. Further, we investigated the correlation between doses and GH responses, as well as between pulse frequency and GH responses in male rats in vivo and in vitro. Long-term, continuous administration was attained by osmotic minipumps releasing low and high doses of the analog for 14 days. The effects of repetitive administration of the GH-RH analog on the pituitary GH release was investigated by injecting 4-6 pulses of the analog at different doses and pulse frequencies. The in vitro experiments were performed in the superfused rat anterior pituitary cell system. Pituitary cells were challenged with continuous, repetitive and simultaneous continuous and repetitive perfusion of the analog. Continuous infusion with low doses of the GH-RH analog in vivo induced sensitization of the pituitary GH-secretory responsiveness and resulted in moderately increased GH releases (129% of the control) to additional bolus injections of the same analog, whereas continuous stimulation of the pituitary with high doses of the GH-RH analog evoked desensitization and resulted in blunted GH responses (29% of the control). Despite the desensitization of the pituitary GH-secretory responsiveness, high doses of the analog elevated the serum GH concentration to 310% and induced acceleration of body weight gain (160% of the control). Repetitive pulsatile administration of the GH-RH analog evoked both sensitization and desensitization of the pituitary GH-secretory responsiveness, depending on the dose and pulse frequency administered.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Diverse effects of a potent LH-RH antagonist on the LH and FSH release.
A potent LH-RH antagonist (Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10 LH-RH (Antag) was used to study the differential regulation of FSH and LH secretion by endogenous LH-RH in ovariectomized (OVX) and regularly cycling rats. The endogenous LH-RH was suppressed by single injections of Antag in OVX animals and by long-term treatment with Antag in normal and OVX rats. Serum and pituitary LH and FSH, as well as serum estradiol (E2) and progesterone (P) was determined by RIA during and/or after the treatment. The direct effect of the antagonistic analog on the ovarian P release was tested in vitro using the isolated luteal cell system. Single injections of the Antag in OVX animals caused prompt and marked suppression of the serum LH (-80%), while no decrease of the serum FSH. Long-term treatment with the same analog decreased the serum LH by 50% but did not modify the serum FSH. In normal rats, serum LH dropped to undetectable levels, while serum FSH did not change significantly. Long-term treatment with the antagonist also resulted in divergent alterations in the pituitary gonadotropin concentrations. In OVX animals, the pituitary LH content moderately elevated (+21%), however, the FSH did not change. In normal rats, ovarian cycles were interrupted, and no ovulation appeared during the treatment. The pituitary LH concentration increased by 46%, while the FSH decreased by 43%. Marked depression was found in the serum P (-60%) but no significant change in the serum E2 levels. Incubation of isolated luteal cells with the Antag did not influence the HCG-induced P secretion in vitro, demonstrating that the in vivo inhibitory effect of the antagonistic LH-RH analog on the P secretion asserts not directly on the ovarian LH-RH receptors, but through inhibition of the endogenous LH-RH. Our studies give evidence that the long-term treatment with LH-RH antagonist suppress the LH and P but not the FSH and E2 secretion, and provide new data suggesting the presence of a FSH-releasing factor in the CNS.
Amino Acid Sequence↗
New Gaba-containing analogues of human growth hormone-releasing hormone (1-30)-amide: I. Synthesis and in vitro biological activity.
Analogues of human growth hormone-releasing hormone (1-30)-amide have been developed. All analogues have been modified in position 27 with Nle and with Gaba in position 30. Additional D-amino-acids have been inserted in the GHRH(1-30)-NH2 sequence: A-1741: Nle27,Gaba30-GH-RH(1-30)-NH2 A-495: D-Ala2,Nle27,Gaba30-GH-RH(1-30)-NH2 A-515: D Ala2,Leu15,Nle27,Gaba30-GH-RH(1-30)-NH2 A-527: D-Ala2,D-Arg11,Leu15,Nle27,Gaba30-GH-RH(1-30)-NH2. Our analogues were synthesized by solid phase peptide synthesis and were tested is two different in vitro systems and in rat pituitary cell cultures. A-495 and A-1741 were found to be the most active in releasing GH, however they showed different activities in the two different test systems. A-495 exhibited higher potency in the superfusion system (1.63 fold potency of the GHRH (1-29)-amide), while A-1741 evoked higher GH release from cultured pituitary cells (1.5-2.5 times higher than the GH-RH(1-44)-amide). The other analogues (A-515 and A-527) were found to be equipotent to the standard molecule. We can conclude that Nle27 and Gaba30 substitutions appeared to be a good modification in in vitro test systems, and Gaba30 substitution served as a good spacer during the synthesis, since it made the coupling of the C-terminal amino acids easier and produced quantitative coupling. In addition to the advantageous properties in the synthesis these modifications with or without D-Ala at the N-terminus increased the in vitro biological activity to 1.5-2.5 fold of the GHRH molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
New Gaba-containing analogues of human growth hormone releasing hormone (1-30)-amide: II. Detailed in vivo biological examinations.
Analogues of human growth hormone-releasing hormone-(1-30)-amide [GH-RH(1-30)-amide] were tested for their ability to stimulate GH release in vivo by injecting the peptides intravenously (iv), subcutaneously (sc), and intramuscularly (im). The analogues involved derivatization with Nle27 and Gaba substituents at the C-terminus with or without D-amino acid(s) in the peptide chain. The potency of the analogues was compared to that of GH-RH(1-29)-amid testing their ability to release GH at 5, 15 and 30 min after the administration. In iv test the potency of the analogues was 1.2-2 times higher than that of the GH-RH(1-29)-amide, and no significant differences were detected between the potencies of the analogues with or without D-amino acid. In the sc test the analogue with D-Ala2, Nle27, and Gaba30 substitutions expressed 8.0-51.7 times higher potency than the GH-RH(1-29)-amide, however, the analogue with similar modifications but with L-Ala2 showed the same low potency (1.2-2.1) as in the iv test. Results from the im experiments were similar to those of SC test. The most potent analogues were those which had D-Ala2, Nle27, and Gaba30 substitutions with Gly15 or Leu15. Circular dichroism (CD) spectra of the analogues showed that Leu in position 15 increased the stability of the predominant alpha-helix conformation, which improved the absorption of the molecule.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
Antiovulatory doses of antagonists of LH-RH inhibit LH and progesterone but not FSH and estradiol release.
The differential regulation of immunoactive FSH and LH secretion by endogenous LH-RH was studied using LH-RH antagonists (Ac-D-Trp1,2, D-Cpa2, D-Lys6, D-Ala10LH-RH (MI-1544) and (Ac-D-Nal1, D-Phe(pCl2), D- Trp3, D-Cit6, D-Ala10LH-RH (SB-030) in ovariectomized (OVX) and regularly cycling rats. Single injections of 10 micrograms and 100 micrograms doses and long-term treatment with 10 micrograms doses of MI-1544 were used in OVX animals. Serum and pituitary LH and FSH, as well as serum estradiol and progesterone was determined by RIA during and/or after the treatment. Single injections of MI-1544 in OVX animals caused prompt (in 2 h) and long-lasting (for more than 24 h) suppression of the serum LH, while no or late decrease (after more than 6 h) of the serum FSH. Long-term treatment with the same analog decreased the serum LH (by 50%) and moderately increased the pituitary LH (by 21%) but did not change the serum and the pituitary FSH concentrations. In normal rats, long-term treatment with both of our analogs also resulted in divergent alterations in the LH and FSH concentrations. Serum LH dropped to undetectable levels,while serum FSH did not change significantly. Pituitary LH increased (by 31 to 41%), while FSH decreased (by 27 to 38%). Marked depression was found in the serum progesterone (by 64%) but no significant change in the serum estradiol levels, after the long-term treatment for 21 days. The ovarian cycles were interrupted, and no ovulation appeared during the treatment. Significant decrease was detectable in the weight of the ovaries (by 46%), whereas the weight of the uteri did not change or slightly elevated (by 22%), after the treatment with SB-030 or MI-1544, respectively.
Amino Acid Sequence↗
[Experience with surgical treatment of osteosarcoma].
The authors treated 79 patients with osteosarcoma by surgery and chemotherapy 1975 through 1991. The appearance, localization and differential diagnosis are discussed. Attention is called to the doctor's delay. The effective pre- and postoperative chemotherapy decreased the incidence of the lung metastases and increased the survival rate (71% 3 years overall survival and 41% 5 years survival) and made the limb-sparing surgery possible. The development of the reconstructive surgical technique and new designs of tumor endoprostheses enabled us to perform limb-sparing surgery in more than one third of the cases at the same survival chance. The limb-sparing means a decisive change in the quality of the rehabilitation of the osteosarcoma patients.
Adolescent↗
[Clinical and histological findings in HCV-caused hepatitis].
58 cases of acute HCV-hepatitis were studied from the debut of acute illness and were followed up over 1-12 years. A mean three week's delay of anti-HCV IgG (Ortho) positivity was observed after the first manifestation of hepatitis. 70.6% relapsed and a chronic hepatitis developed in 37.9%. Seven patients died in HCV-hepatitis. Clinical, chemical, morphological features of HCV-hepatitis different from other viral hepatitis are demonstrated. Persistence of morphological signs of lobular hepatitis after even several months of subacute and chronic outcome has been found characteristic in HCV-hepatitis. Difficulties in interpretation of liver morphology are discussed. Simultaneous evaluation of clinical picture, laboratory markers and morphology is necessary to select cases for therapeutic trials.
Acute Disease↗
[Delta virus infection in hemodialyzed kidney patients and patients with chronic liver diseases].
Sera of patients with chronic hepatitis and chronic haemodialysed uraemia were tested for both Hepatitis B virus and Hepatitis Delta virus markers from 1985. Hepatitis Delta virus seroconversion was found in 10 of 88 haemodialysed patients and anti-Delta-IgG sero-positivity in 11 of 108 chronic hepatitis patients. The clinical course of Delta superinfections in haemodialysed patients was as follows: 3 infections were symptomless, 7 patients had acute hepatitis, two of the latter group died because of fulminant hepatitis. Of the 11 HBsAg and anti-Delta-IgG positive chronic hepatitis patients 3 had primary hepatocellular cancer.
Carcinoma, Hepatocellular↗
[Hypereosinophilia syndrome of unknown origin].
The authors describe the case of a 19-year-old man with hypereosinophilic syndrome. At first the clinical picture suggested a localized eosinophilic gastrointestinal disease which rapidly progressed to the fatal disseminated form. The spectrum of hypereosinophilic syndrome is discussed and current thoughts on diagnosis, pathology and treatment presented.
Adult↗