Incomplete TFA deprotection of N-terminal trityl-asparagine residue in fmoc solid-phase peptide chemistry.

We demonstrate that TFA deprotection of trityl-protected N-terminal asparagine is incomplete under normal conditions, resulting in low yields or impure products. This phenomenon does not occur if the asparagine is internal, nor for trityl-protected N-terminal glutamine. Studies on the deprotection of H Asn(Trt)OH show that the incomplete deprotection is due to the extremely slow removal of a trityl group close to an amino group. The use of the new methyl-trityl protecting group overcomes this problem resulting in rapid and complete deprotection.


Canine ovulation timing.

The key endocrinologic event in the estrous cycle is the luteinizing hormone (LH) peak, which triggers ovulation and thus determines the fertile period. Although LH is impractical to measure directly, a coincidental rise in progesterone also occurs. The recent advent of in-house canine-specific progesterone assays allows accurate identification of the fertile period of the bitch.


An update of artificial insemination with fresh, chilled, and frozen semen.

Two major limitations have been identified in semen extender technology in the dog; the longevity of canine sperm cells is greatly decreased by cooling or freezing, and the anatomy of the canine cervix acts as a barrier to intrauterine deposition of semen via a vaginal insemination. Currently, the ability to predict ovulation time indirectly by measuring serum progesterone levels has increased the success rate using both chilled and frozen canine semen. The American Kennel Club now routinely registers litters produced with both of these methods, and will allow foreign semen from recognized kennel clubs to be imported for domestic use.


Semisynthesis of human growth hormone-releasing factors by alpha-amidating enzyme catalyzed oxidation of glycine-extended precursors.

Recombinant alpha-amidating enzyme was used in the semisynthesis (1-5 mg scale) of human growth hormone-releasing factor, GRF(1-44)-NH2, by in vitro enzymatic oxidation of the glycine-extended precursor, GRF(1-44)-Gly-OH, prepared by solid-phase synthesis. The equipotent analog, GRF(1-29)-NH2, and the superactive analog, [Ala15]-GRF(1-29)-NH2, were also prepared by this route and were fully characterized. Isolated yields of about 75% were obtained, and the products each possessed full potency in an in vitro rat pituitary bioassay and full receptor-binding affinity. Methods to monitor the amidation of polypeptide substrates and analyze the final products are described, including the use of capillary zone electrophoresis. A transient alpha-hydroxyglycine intermediate, [Ala15]-GRF(1-29)-Gly(alpha-OH)-OH, was isolated and characterized. Kinetic studies with this intermediate demonstrate that the rat alpha-amidating enzyme from recombinant mouse C127 cells possesses both the monooxygenase and lyase activities needed to catalyze both steps of the amidation process.


Potent agonists of growth hormone-releasing hormone. II.

Analogs of the 29-amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) or Lys-NH2 in position 29 have been synthesized by the solid-phase method, purified, and tested in vitro. Except for one peptide, all analogs contained desaminotyrosine (Dat) in position 1. All contained Nle27 in order to avoid oxidation of Met27. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27 and/or 28. Analogs [Dat1, Ala15, Nle27, Asn28]GH-RH(1-28)Agm (II, [Asn28]-Mz-2-51); [Dat1, Ala15, D-Lys21, Nle27, Asn28]GH-RH(1-28)Agm (III, MZ-3-125); and [Dat1, D-Asn8, Ala15, D-Lys21, Nl27, Asn28]GH-RH(1-28)Agm(IV, MZ-3-129) were 5.7, 2.8, and 3.9 times more potent in vitro, respectively, than GH-RH(1-29)NH2. However, if we compare the potencies of peptides II and III (analogs of the bovine sequence) with those of the analogs of human GH-RH (XII and XIII) [Dat1, Ala15, Nle27]GH-RH(1-28)Agm; [Dat1, Ala15, D-Lys21, Nle27]GH-RH(1-28)Agm, respectively, the GH-releasing potency was decreased by 50% and 33%, respectively, by the incorporation of Asn28. Our studies indicate that Lys-NH2 at the C-terminus of GH-RH(1-29) and/or beta-Ala, GABA (gamma-aminobutyric acid), and Phe in position 15 are disadvantageous, but potent GH-RH analogs can result from the combination of agmatine in position 29 with other substitutions.


Identification of a subunit contact site of the alpha-subunit of follitropin.

Using synthetic peptides, we previously identified portions of the lutropin alpha-subunit that are in contact with the beta-subunit. In order to elucidate structure/function differences of the glycoprotein hormones, a similar study was conducted for follitropin. Peptides corresponding to the follitropin alpha-subunit were synthesized using standard solid-phase procedures. Purified peptides were incubated in the presence of alpha- and beta-subunits of follitropin, and subunit recombination was monitored using gel permeation chromatography and reverse-phase high-pressure liquid chromatography. Peptide alpha 33-58, corresponding to a highly conserved portion of alpha-subunit, completely inhibited subunit recombination for 24 h, and allowed only partial (61%-71%) recombination after 48 h. Peptide alpha 51-65 or alpha 61-78 inhibited subunit recombination partially at 24 h, but almost full (greater than 80%) recombination was observed by 48 h. Peptides corresponding to the rest of the alpha-subunit, alpha 1-15, alpha 11-27, alpha 22-39, and alpha 73-92, did not inhibit recombination of the alpha- and beta-subunits. The data suggest that alpha-subunits have similar residues in contact with regions of the beta-subunits of both lutropin and follitropin, specifically involving residues from continuous regions of the alpha-subunit (residues 45-75). The data suggest that this region contains multiple sites of contact with the beta-subunit.


The use of reproductive hormones in canine reproduction.

Naturally produced and synthetically prepared reproductive hormones are frequently employed as pharmaceuticals in canine reproduction. Specific indications for the use of these preparations are few; too often hormonal therapies are used incorrectly and at times deleteriously. Appropriate uses of reproductive hormones are based on known physiological mechanisms in order to improve reproductive efficiency or to treat specific disorders.


The role of the veterinarian in genetic counseling.

When the veterinarian encounters a disorder with an unknown etiology, the following criteria can identify the potential contribution of the animals genome to the problem: 1. The disorder occurs with higher frequency in a group of related animals than in the general population. 2. A defect involves the same anatomic site in a group of related animals. 3. The disease has a consistent age of onset and clinical course. 4. The disease increases in frequency with inbreeding. 5. The disorder is consistently associated with a specific chromosomal anomaly. 6. The disorder can be traced to an abnormality in a single specific protein molecule. Veterinarians must access the information that knowledgeable breeders gather and channel that information constructively into diagnostic tests, test breedings, and data banks to work toward a common goal--discovery of the genetic basis of disease and development of appropriate breeding programs to minimize or eliminate debilitating genetic problems in dogs.


Synthetic vaccines and HIV-1 hypervariability: a "mixotope" approach.

The hypervariability of the gp120 envelope protein principal neutralizing domain, the V3 loop, represents a major problem in the design of vaccines against HIV-1. We have designed a mixed V3 loop peptide, termed "mixotope," obtained in a unique synthesis, and containing around 7.5 x 10(5) different sequences of 22 to 25 residues, organized around the conserved GPGR tetrapeptide. Free or coupled to a carrier protein, the "mixotope" induced in rabbits broadly specific antibodies, which recognized different individual V3 loop sequences, and the native gp120 protein. The "mixotope" approach may allow researchers to focus vaccine strategy against hypervariable functional epitopes of various pathogens.


Alkylation of tryptophan during deprotection of Tmob-protected carboxamide side chains.

Alkylation of tryptophan occurred during the synthesis of a 19-amino acid peptide of the following sequence: Tyr Ala Ala Gln Asn Arg Arg Gly Leu Asp Leu Leu Phe Trp Glu Gln Gly Gly Leu. Alkylation was found to occur during cleavage of the peptide from the solid support under acidic conditions in the presence of Tmob, which is used for protecting glutamine and asparagine. Presence of alkylated tryptophan was confirmed by mass spectrometry, HPLC and amino acid sequence analyses.


Mercury in a commercial preparation of rat amylin.

The biological activity of amylin is reported to vary widely depending on the source and purity of the material. Three commercial samples of rat amylin were compared for structural differences. The samples were nearly identical using most of the available analytical measures--amino acid analysis, HPLC retention, even Edman sequencing data. When the samples were compared by ion spray ionization mass spectrometry, the molecular mass of one sample was 200 daltons higher than anticipated. Careful analysis of the sample, including atomic emission spectrometry, revealed that a mercury atom was associated with the polypeptide. The mercury presumably resulted from a deprotection step in the synthesis, involving the removal of an acetamidomethyl group from cysteine.


Breeding kennel management.

Veterinarians and dog breeders should work together to establish protocols for health care and breeding management that are based on sound scientific principles as well as practical systems. These protocols should involve bitches, stud dogs, and puppies. Tantamount importance must be placed on record keeping so that problems may be identified and solved before they are irreversible.


The role of ultrasound in canine reproduction.

This article describes the role of ultrasound in the diagnosis of canine pregnancy. Advantages and disadvantages are discussed, and ultrasound is compared with traditional imaging methods.


Pregnancy diagnosis by biochemical assay.

If pregnancy diagnosis by biochemical assay is to become practical, new marker characterization will be required. Pregnancy marker development is reviewed in dogs and other species, as are molecular biology techniques that have the potential to reveal previously inaccessible targets in the dog.


Infertility in the male dog.

The diagnosis and characterization of infertility in the male dog depends largely on the initial history and semen evaluation and on following the course of infertility over time. The diagnostic testing described here is helpful for guiding therapy, but the prognosis in serious cases of infertility is usually poor. Cases of subfertility that are not progressive have a better prognosis with optimal breeding management. Finally, the clinician should remember that some insults to the testes are reversible with time so it is important not to administer therapy that will interfere with the dog's ability to recover. Client education is an important part of the management of male dog infertility because it is not uncommon for various drugs to be administered by the breeder, or at the breeder's request, without a sufficient diagnostic work-up. In addition, errors of breeding management may play a role in male dog infertility or limit the success of treatment.


4-Methyltrityl (Mtt): a new protecting group for the side chain protection of Asn and Gln in solid-phase peptide synthesis.

The trityl group was recently introduced for the protection of the side chain carboxamide function of asparagine and glutamine. The 4-methyltrityl (Mtt) group, a structural modification of trityl, is presented here and allows more rapid cleavage from the protected peptides. Procedures for the introduction of the group and comparative cleavage reactions are also presented.


Feeding to optimize canine reproductive efficiency.

The relationship between nutrition and reproduction is a topic of importance to veterinarians and breeders. Nutrient deficiencies, excesses, and imbalances all are capable of altering reproductive performance. Healthy adult dogs should be fed a diet high in digestibility, low in residue, and high in nutrient bioavailability. Rarely is nutritional intervention necessary during the first half of gestation. During the last half of gestation, switching to a growth/lactation diet and increasing intake by 1.2 to 1.4 x maintenance is indicated. Depending on breed and pup numbers, at peak lactation, feed intake may need to be increased by 2 to 4 x maintenance. The feeding goals of lactation are to minimize loss of bitch body condition score and optimize milk production and pup growth. After weaning, the female who is in poor body condition should remain on a diet rich in protein, fat, and trace nutrients until she is physically/nutritionally repleted.


The manufacturing process of recombinant factor VIII, recombinate.

In summary, this brief report documents the cell culture and rAHF purification systems used to produce rFVIII and has focused on the unique characteristics of the cell line, the production process, and purification system used. This review emphasizes the general philosophy used throughout the research and development of this innovative and complex therapeutic agent, in order to provide a safe and efficacious rAHF in the management of individuals with hemophilia A. This review provides a brief description of the in-process system and controls that have been incorporated to meet the high standards and safety objective.


[Options for continued development of medical care].

The German health care system is currently faced with challenges that stem from the changing demographic structure of the population as well as from the increasing implementation of costly technological advances in diagnosis and treatment in the presence of inadequate preventive and rehabilitative structures. Ever-rising expectations and demands on the part of German citizens and the increasing number of doctors are threatening to overburden the increasingly limited financial resources of the health care system. The pressure for allocatory measures has led to intense competition amongst the various specialties and sectors of the health care system. In this paper the author describes the current developments with regard to the evolution of the health care system in the near future. He predicts an increasing demand for long-term care facilities especially for the elderly, for more easily accessible rehabilitative services as well as a continuing increasing demand for high-tech services. The pressure of these qualitative as well as quantitative demands in the face of intersectoral competition and limited financial resources will necessarily lead to a restructuring of the professional as well as non-professional system with new forms of organization for in-patient as well as out-patient services that will address these issues.


[Health promotion and wellness programs in private corporate organizations. Problems of trans-national and trans-cultural transferability].

Health promotion and wellness programmes in corporate organisations are subjects of considerable interest to both the providers (companies) and the consumers (employees). Economic considerations constitute a significant factor in businesses' interest in adopting health promotion programmes and in the wellness communities attempts to sell such programming to business. Substantial elements of both the business and wellness communities believe that health promotion programmes are financially profitable in addition to, and as a result of, improving employee's health. A fact which has not yet attracted significant research activities is a comparative analysis of corporate health promotion and wellness programmes in different societies with different cultural backgrounds, corporate cultures and external environments. Especially the emerging of a "New Europe" after the full realisation of the Common Market (EC) after 1992 and the tremendous economic possibilities after substantial political changes in the political structure of the eastern part of Europe (on its way to capitalism) might make it worth to look into corporate wellness programs of European organisations and to discuss pros and cons after comparing them with the ones of their American counterparts. Most important facts in which US organisations differ from most European corporations are not only the internal corporate culture but also the external environment, such as direct government interventions and political pressure from the consumer interest groups (strong unions). In many European countries the government imposes a very tight regulatory and legal framework and dictates the way corporate organisations have to share the burden of health related costs and have to provide occupational, wellness or preventive programmes for their employees.(ABSTRACT TRUNCATED AT 250 WORDS)


[The tracer concept of quality assurance in the hospital--a critical evaluation].

The "tracer concept", on which the introduction of quality assurance measures in Germany according to section 137 GRG is based, are critically confronted with the general test philosophy. It is shown that this tracer methodology does not come up to expectations and should be abandoned. Development and introduction of indicators are recommended that would be more appropriate to attain the target of quality assurance: quality improvement.


[Organization of social medicine counseling according to section 275 Abs. 4 SGB V exemplified by the Mecklenburg-Vorpommern medical service].

In accordance with social legislation (statute-book of social law, SGB V, section 275, 4) compulsory sickness insurance is obliged to consult the Medical Advisory Service especially in case of general problems of medical supply and advice for patients, quality monitoring, negotiation strategies with all partners of the medical supply system, and for creating joint panels of physicians and sick insurance bodies, particularly examination committees. Exemplarily possibilities of management of these problems are described for the Medical Advisory Service of Mecklenburg-Vorpommern. This example may demonstrate in what way the Medical Advisory Service can bring its own sociomedical competence into play appropriate to regional needs as a service enterprise of the compulsory sickness insurance.


[Regional survey of the vaccination rate of 5th grade students exemplified by a rural district in Bavaria].

It was the purpose of this investigation to get a survey of the vaccination rate of eleven-to-twelve-year old pupils in a rural district of Bavaria. We could get the facts by checking the international certificates of vaccination during the medical examination of children in the fifth class of primary schools. The results show that the vaccination rate against polio and tetanus was sufficient, incomplete against diphtheria and insufficient against German measles, mumps and measles. Due to the good cooperation with the primary schools we could get the facts by studying thoroughly 75% of the pupil's certificates of vaccination. A regional survey is a good and inexpensive way of obtaining information on the vaccination rate and it is the last opportunity to achieve a systematic survey of the vaccination rate of children of a certain age. The sero-conversion rate cannot be judged by such a regional survey of the vaccination rate.


[The physician's role in relation to the guardianship law].

Legislation concerning guardianship and tutelage of the mentally and/or physically handicapped had so far been governed by the antiquated concept of mental diseases. The revised law (literally: "Care" law) took shape mainly on the lines of the development that followed the great "Psychiatry Inquiry Project" conducted in Germany a few years back. All decisions to be made on the grounds of the new law should always place the well-being of the mentally diseased and handicapped patients first. In this connection medical expertise is one of the most important decision aids for the judge who is called upon to decide on tutelage and guardianship. Hence, demands to be made on the quality of expertises are correspondingly high.


Metastatic mode and DNA ploidy in gastric carcinoma.

We studied the amounts of nuclear DNA in gastric cancer metastases histologically and cytochemically by flow cytometry, which was performed retrospectively on paraffin-embedded specimens from 95 patients. At surgery, all cases of aneuploid cancer were positive for lymph node metastases. Liver metastases were frequently seen in aneuploid cancer (63%, P < 0.01), while lung metastases were the most common in diploid cancer (50%, P < 0.05). The incidence of peritoneal metastasis was high in undifferentiated diploid cancer (72%, P < 0.01). Local lymph node recurrence after surgery was more common in aneuploid than in diploid cancer (P < 0.01). The incidence of bone and distant lymph node metastasis was found to be strongly dependent on tissue differentiation. The DNA ploidy pattern is thus considered to be closely linked to lymph node, liver, and lung metastases in gastric cancer.


Usefulness of preoperative low dose cisplatin treatment for advanced esophageal cancer.

In order to decrease the perioperative complications by preoperative cisplatin chemotherapy, the preoperative single administration of cisplatin (30 mg/m2) was performed weekly from one to six times in 36 consecutive patients with esophageal cancer classified as higher than Stage II. The survival curve of 17 patients in Stage III was significantly better (P < 0.05) than that of patients who had been treated without preoperative cisplatin treatment. In 3 of the 12 patients who had locally invasive cancer, either the main tumors or the metastatic lymph nodes, which had invaded the trachea or the left main bronchus, sufficiently receded, so that a curative esophagectomy became possible; 2 of them have survived over 33 months while 1 died of pneumonia 33 months after surgery. The number of perioperative complications was minimal, and thus, we consider that the postoperative use of cisplatin and fluorouracil is indicated in patients in whom a histological response is noted in the resected specimens.


Independent clinical and flow cytometric prognostic factors for the survival of patients with stage I gastric cancer.

Paraffin-embedded tumor samples from 151 patients with stage I gastric cancer were analyzed by DNA flow cytometry, and 80 patients received an infusion of bromodeoxyuridine (BrdU) to determine S-phase fraction. S-phase fractions of tumors were measured by the immunohistochemical method using anti-BrdU monoclonal antibody. Of the 151 patients, 81 (54%), and 70 (46%) showed diploid and aneuploid patterns. There was no significant association between DNA ploidy and wall invasion, histologic type, or lymphatic invasion. Aneuploid tumors were associated with positive-vessel invasion. When the DNA ploidy and clinicopathological parameters were simultaneously entered into the Cox regression model, DNA ploidy and wall invasion emerged as independent prognostic parameters. Aneuploid tumors had significantly higher values of BrdU labeling indices than diploid ones. These results indicate that the determination of DNA ploidy patterns may be an important prognostic factor in patients with stage I gastric cancer, and may be useful in deciding the therapeutic schedule of patients with gastric cancer.


The prognosis of patients with gastric cancer possessing sex hormone receptors.

Estrogen receptors (ER) and progesterone receptors (PgR) were immunohistologically investigated in 107 patients with gastric cancer who underwent curative resection. Both ER and PgR were detected only in the cancer cell nucleus. The ER positive rate was 27.7% for males and 31.0% for females, while the PgR positive rate was 9.2% for males and 11.9% for females. Clinicopathologically, the ER positive rate was slightly higher in young females and in cases of poorly differentiated gastric cancer. When cumulative survival rates were analyzed in relation to the presence or absence of receptors, the 10-year cumulative survival rate after surgery was significantly lower in the ER positive cases, being 15.7% cent, than in the ER negative cases, being 62.7%, and also significantly lower in the PgR positive cases, being 18.2%, than in the PgR negative cases, being 48.3%. The coexistence of ER and PgR in gastric cancer tissues suggests that the ER is physiologically active, or that ER positive gastric cancer is hormone-dependent. The poor prognosis of patients with receptor positive gastric cancer suggests that gastric cancer with these receptors is highly malignant.


Complete correction of the tetralogy of Fallot in adults using separated extracorporeal circulation to block intrathoracic collateral circulation and improve perfusion of the renal vasculature.

During the last 10 years, complete correction of the tetralogy of Fallot (TOF) has been performed on 28 adult patients using the "separated extracorporeal circulation" (separated ECC) technique developed by us. In addition to the usual ascending aortic and dual right arterial cannulations for ECC, the separated ECC also involved femoral arterial cannulation and the insertion of a catheter with two balloons via the other femoral artery. Flow via the ascending aorta and femoral artery were maintained separately during ECC. The urine output during separated ECC was significantly better than that during ordinary ECC (P < 0.01) and the operative field for intracardiac correction was clearer as a result of blocking the collateral circulation. Thus we believe separated ECC to be a superior method for total correction of TOF in adults, which may enhance the operative outcome.


An experience of cell sorting using samples isolated from paraffin-embedded tissue of neuroblastoma.

Flow cytometric DNA content analyses were performed on samples from 72 patients with neuroblastoma. Nuclear suspensions obtained from paraffin-embedded samples were prepared using the method described by Schutte et al. Determination of DNA ploidy was possible in 62 out of 72 patients. DNA diploidy was detected in 23 (37.1%) and DNA aneuploidy was found in 39 (62.9%) of these 62 patients. Cell sorting was performed on two peak areas of the DNA histogram of samples with aneuploidy. The sorted cells of the first peak area were composed of small round cells and were considered to be normal lymphocytes. The sorted cells of the second peak area were composed of relatively large cells with obvious nucleoli and were considered to be neuroblastoma cells. Thus, two cell components could be distinguished by cell sorting. It is concluded that cell sorting may be of benefit in giving detailed information about DNA histograms, even in samples obtained from paraffin-embedded tissue.


Microscopic and immunohistological studies on intimal hyperplasia of the arterially implanted autovein graft and its anastomosis in dogs.

The fate of intimal hyperplasia of arterially implanted autovein bypass grafts and their distal end-to-side anastomoses in dogs was studied microscopically and immunohistologically. The bypass grafting was done under conditions of abnormal blood flow and high peripheral resistance. Intimal hyperplasia of the graft first became evident 7 days after implantation and the thickness increased to about 500 microns 3 months or more after the implantation. The intimal hyperplasia was related to an active proliferation of smooth muscle cells which proved positive for alpha-smooth muscle actin staining. Moreover, it was more dominant at the toe and heel of the anastomosis and moderately apparent on the floor of the host artery. The constituent elements of the hyperplastic intima at the anastomosis were fibroblast-like cells and extracellular collagen fibers which were negative for alpha smooth muscle actin staining. This study revealed that the features of intimal hyperplasia at the distal anastomosis in autovein bypass grafting differed from those of the implanted autovein graft itself; the former being related to excessive proliferation of fibroblasts and collagen fibers while the latter displayed an active proliferation of smooth muscle cells.


Undifferentiated (embryonal) sarcoma of the liver: report of three cases.

Undifferentiated (embryonal) sarcoma is a rare malignant tumor of the liver. It typically presents in late childhood and its prognosis is poor. We experienced three cases of such a tumor during the period of 1976-1989; two of these patients are still alive without disease. Each case was independently treated with a combination of surgery and pre- and/or postoperative chemotherapy, which was found to be effective. In one surviving patient, cyclophosphamide and vincristine were found to be effective, while in the other a combination of cisplatin, Adriamycin (ADM), vincristine and cyclophosphamide was observed to induce a rapid reduction in the size of the recurrent tumor. Thus, an adequate combination of surgery and chemotherapy may improve the prognosis of this tumor.


Macronodular adrenal hyperplasia causing Cushing's syndrome: report of two cases and an overview.

Of the various entities producing adrenal hyperfunction, nodular adrenal hyperplasia is rarely described, however, recent reports have established it as a distinct cause of Cushing's syndrome. Although the etiology of this disease remains uncertain, two distinct forms are recognised, namely: macronodular hyperplasia and micronodular dysplasia. Establishing the diagnosis preoperatively is difficult but essential to ensure the correct treatment is performed. Two cases of macronodular hyperplasia are reported herein followed by a review of the available literature on this subject.


Stercoraceous perforation of the sigmoid colon: report of two cases.

Stercoraceous perforation of the sigmoid colon has rarely been reported in the literature. This lesion is assumed to be produced by the pressure from a hard scybalum resulting in a perforated ulcer with necrotic edges. Two cases of stercoraceous perforation of the sigmoid colon are presented in this paper. It is difficult to diagnose this lesion preoperatively, although ultrasonograms proved useful in showing the colon perforation. This lesion should always be suspected when a patient who has had chronic constipation presents with sudden severe abdominal pain. It is possible that this lesion is becoming more common as the mean age of the population increases and we stress the importance of immediate surgery and intensive care for improving the prognosis.


Portal vein thrombosis after splenectomy successfully treated by an enormous dosage of fibrinolytic agent in a short period: report of two cases.

Portal vein thrombosis (PVT) after splenectomy in a patient with portal hypertension occurs with unusually high frequency. Recently, two patients with PVT following splenectomy were treated by fibrinolytic therapy with an enormous dosage of urokinase (UK) in a short period. PVT was quickly dissolved without side effects and the patients are now doing well without any recurrence of PVT. Therefore, when there is no evidence of bowel infarction, fibrinolytic therapy with an enormous dosage of UK over a short period is deemed to be both effective and essential as a conservative therapy for PVT.


Intussusception of an appendiceal mucocele: report of a case.

A 66 year old Japanese female was admitted to our department for the examination and treatment of a mass in the cecum. She had experienced no symptoms or signs other than a positive test result for fecal occult blood. The mass in the cecum was confirmed by barium enema, colonofiberscopy and CT scanning. The presumptive diagnosis was a submucosal tumor of the cecum, however, a laparotomy subsequently revealed intussusception of an appendiceal mass. An ileocaecal resection with an ileocolic anastomosis was therefore performed and the mass was histologically diagnosed as a mucocele of the appendix. This patient is only the 24th case of intussusception of a mucocele of the appendix to be reported in Japan. A review of the available literature on this condition follows the case report.


Interferon alpha-2a shows antitumor activity in combination with 5-fluorouracil against human colon carcinoma xenografts: a study in reference to thymidylate synthetase activity inhibition.

To clarify the mode of antitumor activity shown by a combination of recombinant human interferon alpha-2a (IFN) and 5-fluorouracil (5-FU), experimental therapy was performed on human colon carcinoma (Co-4) xenografts serially transplanted into nude mice, using IFN and 5-FU, either alone or in combination. IFN alone showed dose-dependent antitumor activity and 5-FU also revealed a moderate antitumor effect. Although IFN, given as 600,000 units/mouse daily sc x 14, and 5-FU, given as 60 mg/kg q4d x 3 ip, showed additive antitumor activity against Co-4, the thymidylate synthetase (TS) inhibition rate was unchanged in the tumors treated with the IFN/5-FU combination in comparison with those treated with 5-FU alone. This suggests that the antitumor activity of IFN and 5-FU in combination does not involve augmentation of the TS inhibition by 5-FU.


Methods of resuscitation in low-Apgar-score newborn infants--a national survey.

The incidence, treatment and immediate course in infants with postnatal apnoea were studied. Information on all infants born in Sweden in 1985 with a low Apgar score (3 or less at 1 min or 6 or less at 5 min) was collected from the midwife and from the baby's chart. Of the 97,648 live births, 1633 (1.7%) had a low Apgar score. The risk increased with decreasing birthweight and with severe malformations. Before delivery, 19% of the low-Apgar-score infants were not expected to require resuscitation. Eighty percent of the ventilated infants were satisfactorily ventilated by bag and mask; the remainder were intubated. Of the ventilated infants, 78% developed spontaneous breathing within 10 min after birth and 89% within 20 min. Routine intubation or administration of buffer in cases of postnatal asphyxia had no influence on the time to onset of regular spontaneous breathing.


The effect of early and late cord-clamping on blood viscosity and other hemorheological parameters in full-term neonates.

This study was done to compare postnatal alterations in blood viscosity (capillary viscometer) and its determinants: hematocrit, plasma viscosity (capillary viscometer), red cell aggregation (Myrenne aggregometer) and red cell deformability (rheoscope) in the first five days of postnatal life in full-term neonates with early (< 10 s) and late (3 min) cord-clamping. The fetal blood volume of the placenta ("residual placental blood volume") decreased from 52 +/- 8 ml/kg of neonatal body weight after early cord-clamping to 15 +/- 4 ml/kg after later cord-clamping. Neonatal blood volume, calculated as the difference between an assumed total feto-placental blood volume of 115 ml/kg and the measured fetal blood volume of the placenta, was 50% higher in the late cord-clamped infants than in the early cord-clamped infants. Both groups showed similar viscosity, hematocrit and other rheological parameters in cord blood. In the infants with early cord-clamping, the hematocrit decreased from 0.48 +/- 0.04 l/l at birth to 0.43 +/- 0.6 l/l after 24 h (p < 0.05). Whole blood viscosity did not change significantly with age. After late cord-clamping, the hematocrit rose from 0.50 +/- 0.04% at birth to 0.63 +/- 0.05 l/l at 2 h of age (p < 0.005) and dropped to 0.59 +/- 0.5 l/l (p < 0.05) at 24 h. Blood viscosity increased by 40% (p < 0.001) within the first 2 h, but did not change significantly during the following five days. In both groups, plasma viscosity and red cell aggregation increased significantly (p < 0.05) on day 5 due to significant increases in total plasma protein and fibrinogen concentrations (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Randomized controlled trial of dexamethasone treatment in very-low-birth-weight infants with ventilator-dependent chronic lung disease.

This randomized controlled trial was designed to answer the question: does administration of dexamethasone to neonates with bronchopulmonary dysplasia decrease the need for assisted ventilation? Twenty-five infants with a birth weight < 1501 g, requiring mechanical ventilation and FiO2 of > or = 0.30 at 21-35 days of age, were randomized to treatment with iv dexamethasone or to sham injections for 12 days. The primary outcome criterion was extubation within seven days after study entry. Treatment (n = 12) and control (n = 13) groups were well matched at entry. Dexamethasone facilitated weaning from assisted ventilation (p = 0.0154). There was no increased incidence of infection. Dexamethasone treatment resulted in a significant increase in glucosuria (p = 0.0002) and in systolic blood pressure (p = 0.0034). There was a significant decrease in heart rate (p = 0.0001) and a significant weight loss (p = 0.0002) following dexamethasone treatment. Dexamethasone treatment facilitated weaning from assisted ventilation but several systemic effects were noted that deserve further evaluation before dexamethasone becomes routine treatment.


Total leukocyte and neutrophil count changes associated with antenatal betamethasone administration in premature infants.

The white blood cell counts of 84 premature infants were included in a retrospective study of 45 infants treated antenatally with betamethasone and 39 non-treated infants. A significant increase in neutrophil and immature neutrophil forms was found in the treated group when the drug was administered to the mother close to delivery. This effect lasted for three days. Afterwards, although the counts were not significantly high compared to the control group, their physiological decrease was delayed. This study indicates that the known stimulating effect of steroids on total leukocyte and neutrophil counts in adult humans and fetal lambs, also occurs in premature infants. This fact supports recent reports which propose the antenatal maternal administration of betamethasone as a cause of leukemoid reaction or leukocytosis after birth.


Insensible water loss from the skin during phototherapy in term and preterm infants.

The rate of evaporation from the skin was measured before and during phototherapy in 10 full-term and seven preterm infants (gestational age 29-33 weeks). The method for measurement of rate of evaporation was non-invasive and was based on determination of the water vapour pressure gradient close to the skin surface. All infants were studied naked in an incubator with an ambient relative humidity of 50% and with a controlled environment with respect to temperature and air velocity. In the term infants the mean rate of evaporation, measured from an interscapular skin area, was 3.1 g/m2h both before and after 30 min of phototherapy. In the preterm infants the corresponding value was 9.8 g/m2h before and 9.7 g/m2h after 120 min of phototherapy. Thus, in thermally stable infants, non-ionizing radiation from phototherapy equipment does not increase water loss from the skin.


Respiratory water loss and oxygen consumption in newborn infants during phototherapy.

Respiratory water loss was measured together with oxygen consumption (VO2) and carbon dioxide production (VCO2) in 11 full-term and eight preterm infants (mean gestational age 34 weeks, range 31-36 weeks) before and during 1 h of phototherapy. The method for determination of respiratory water loss, VO2 and VCO2 was based on an open flow-through system with a mass spectrometer for measurement of gas concentrations. All infants were studied naked in an incubator with an ambient relative humidity of 50% and with a controlled environment with respect to temperature and air velocity. The infants were calm during the measurements. Before phototherapy, in term infants respiratory water loss was 4.4 (SD 0.7) mg/kg min and VO2 5.9 (0.9) ml/kg min and in preterm infants respiratory water loss was 4.7 (0.8) mg/kg min and VO2 6.1 (0.8) ml/kg min. No significant difference was found between values obtained during or after 1 h of phototherapy and those obtained before.


Lipoproteins in preterm and small-for-gestational-age infants during the first week of life.

Plasma lipoprotein levels and composition have been determined in preterm and small-for-gestational-age (SGA) infants, and compared to full-term infants, during the first week of life. Significantly lower levels of HDL and higher levels of VLDL were found in both preterm and SGA infants in comparison to full-term healthy infants. These results suggest a low capacity to metabolize VLDL. Preterm infants showed a behaviour similar to full-term infants with regard to the changes in lipoprotein composition. Small-for-gestational-age infants showed a higher lipoprotein lipid content than preterm infants. A low ratio of cholesteryl ester to free cholesterol (CE/FC) was found in both preterm and SGA infants suggesting a reduced lecithin: cholesterol acyl transferase (LCAT) activity. In preterm infants we observed no changes in the CE/FC ratio during the first week of life, whereas in SGA infants this ratio increased after birth.


Essential fatty acids in human colostrum.

We analyzed the colostrum of 11 mothers, consuming a normal hospital diet, for total fat content and various fatty acids. Three of the mothers had given birth four weeks prematurely. Total fat content of the colostrum ranged from 2.16 to 3.65 g/100 ml. The major fatty acids were palmitic acid (16:0) and oleic acid (18:1) (24.3 and 39.7% (w/w), respectively). The dominating polyunsaturated fatty acid was linoleic acid (18:2n-6) (11.5% of the total fatty acids). Linolenic acid (18:3n-3) and docosahexaenoic acid (22:6n-3) accounted for 0.7 and 0.6%, respectively, of the sum of total fatty acids. The ratio of polyunsaturated to saturated fatty acids was 0.42, ranging from 0.28 to 0.5, and the ratio of n-6/n-3 fatty acids was 6:1. Linoleic acid and linolenic acid were positively correlated with each other (p < 0.02), whereas palmitic acid was negatively correlated with oleic acid (p < 0.05). We conclude that the average human colostrum contains the recommended level and balance of the essential fatty acids required by the newborn baby.


Transient colonization of the gut of newborn infants by orally administered bifidobacteria and lactobacilli.

We investigated if orally administered bifidobacteria and/or lactobacilli could be cultured from faeces of infants after antibiotic treatment, when these bacterial species are usually absent. Lyophilized Bifidobacterium longum, strain BB-536, B. breve, strain BB-576, or Lactobacillus acidophilus, strain LAC-343, were used. Doses of 3 x 10(9) cells of one strain, or a mixture of all three strains 3 x 10(9) cells each were fed three times daily at mealtimes to 11 infants aged 0-8 weeks. Treatment was started the first day after antibiotic treatment and was continued for 5 days. The bacterial species were isolated in 9 of 11, 7 of 10 and 2 of 9 specimens obtained on the last day of bifidobacteria or lactobacilli administration, 5 and 15 days thereafter, respectively. No side effects were noted.


Chlamydia trachomatis in neonatal respiratory distress of very preterm babies: biphasic clinical picture.

We observed 12 very preterm infants (10 males) with a peculiar respiratory syndrome characterized by early onset soon after birth and by a biphasic course. The severe first phase was characterized by a clinical pattern mimicking the idiopathic respiratory distress syndrome of prematurity. Gradually, respiratory symptoms decreased and assisted ventilation with oxygen therapy was reduced. In the second phase, a significant worsening of respiratory signs and the appearance of apneic spells were observed. Chest X-ray showed hypoexpansion of the lungs and the prevalence of a fine reticular pattern. Chlamydia trachomatis was identified in this second phase in conjunctival and pharyngeal swabs and/or on tracheal aspirates. Our data suggest that in the very preterm infants, chlamydial infection shows different clinical and laboratory features if compared with Chlamydia trachomatis pneumonia of infants born at term.


Transfer of specific IgG and IgG subclasses to herpes simplex virus across the blood-brain barrier and placenta in preterm and term newborns.

The kinetics of virus-specific IgG subclasses (IgG 1-4) among newborns and their mothers has not yet been determined. In this report, we examined anti-herpes simplex virus IgG activities (HSV-IgG) and its subclasses in CSF and serum of premature or term newborns without HSV infection and in the serum of their mothers using ELISA. We found that CSF/serum ratios of HSV-IgG and IgG subclasses (IgG 1-4) in newborns with a gestational age less than 38 weeks were higher than those of term newborns. These findings indicate that the blood-brain barrier against HSV-IgG and IgG subclasses is insufficient in newborns. Furthermore, we found that HSV-IgG subclasses, which were transferred across the placenta and later transferred across the blood-brain barrier had a tendency to be proportional to each of the maternal HSV-IgG subclasses.


Neurological adaptation of infants delivered by emergency or elective cesarean section.

The effects of intrapartal asphyxia on neonatal neurological condition have been studied in 17 full-term infants delivered by emergency cesarean section and in 30 full-term infants delivered by elective cesarean section used as controls. A neurological examination consisting of 31 items was performed on days 1, 2 and 5 after birth. A tonus score, an excitability score as well as the number of optimal responses were calculated. A follow-up examination was done at six months of age with a standardized neurological and developmental examination. The results showed that infants born after emergency cesarean section were significantly more hypotone the first two days after delivery than the infants in the elective cesarean section group. In regard to individual neurological items, significant differences were found between the emergency and elective cesarean section in reaction to sound, rooting, patellar, Moro and stepping reflexes with weaker reactions in the elective cesarean section group. Growth, psychomotor development and neurological status at six months did not differ significantly between the groups. Our findings indicate that full-term infants born after emergency cesarean section due to mild intrapartal asphyxia have a delayed neurological adaptation as expressed by poor muscular tonus during their first days of life compared with infants born after elective cesarean section.


Hyperbilirubinemia, hypocarbia and periventricular leukomalacia in preterm infants: relationship to cerebral palsy.

This study comprised 103 preterm infants with a gestational age less than 33 weeks who were born in Tampere University Hospital and who were followed up to two years of age. Sixty-four perinatal variables were compared to ultrasound findings in the neonatal period and neurologic handicap at the age of two years. Duration of hypocarbia (PCO2 < or = 30 mmHg) during the first 72 h and hyperbilirubinemia (the mean level of serum total bilirubin) at three days of age were independently and significantly related to periventricular leukomalacia, but not directly to cerebral palsy. The only perinatal variables related independently and significantly to cerebral palsy at two years of age were periventricular leukomalacia and ventriculomegaly. According to these results, periventricular leukomalacia was the main predictor of cerebral palsy in preterm infants. In addition to hypocarbia, hyperbilirubinemia may also be involved in the pathogenesis of extensive (severe cystic) periventricular leukomalacia.


Comparison between tape-recorded and amplitude-integrated EEG monitoring in sick newborn infants.

In 15 ill newborn infants a comparison between long-term multichannel and single-channel recordings of simultaneously tape-recorded (Medilog system) and amplitude-integrated EEG (Cerebral Function Monitor) was made. There was good agreement between the main type of background activity diagnosed with the tape-recorded and the amplitude-integrated EEG for all recordings. Two infants had repetitive subclinical and subtle seizure activity, lasting for several hours, which was detected by both techniques. Short, single seizures were diagnosed in the recordings of nine infants. When a single electrographic seizure appeared in an otherwise stable recording, it was identified by both the tape-recorded and the amplitude-integrated EEG. Very short (5-30 s) seizure patterns, which were diagnosed with the tape-recorded EEG, were not identified in the cerebral function monitor recordings. In the single-channel recordings of both the EEG and the cerebral function monitor there were, on some occasions, difficulties in distinguishing single seizures from interference due to external artefacts. In the multichannel recordings the diagnosis of seizure patterns was facilitated by comparison with the other channels. Both the Medilog EEG and the cerebral function monitor are feasible techniques for following cerebral electrical activity in sick neonates, although neither technique is specifically constructed for this purpose. For clinical use in the neonatal intensive care unit the advantage with the cerebral function monitor is the immediately available recording. The tape-recorded EEG offers possibilities of more channels and a higher reliability when diagnosing short subclinical seizures, however, only after offline analysis.


Sister chromatid exchanges in peripheral lymphocytes in newborns treated with phototherapy and vitamin E.

A study was undertaken to determine whether blue fluorescent light might affect the sister chromatid exchange (SCE) frequency of peripheral lymphocytes in icteric newborns undergoing continuous phototherapy treatment (72 h). Also, the potential preventive effect of vitamin E on SCE frequency was studied in a subgroup of 11 preterm and 9 fullterm newborns after daily administration of vitamin E (46.44 mumol/kg/d, im). The results revealed that only the preterm icteric newborns showed an increase in mean SCE frequency of peripheral lymphocytes after phototherapy (9%, p = 0.02), but in no case did the highest SCEs/cell ratio exceed the normal values. No correlation was found between the average SCE rate and birth weight, gestational age or bilirubin levels. Also, no difference in SCEs was observed between newborns treated or untreated with vitamin E.


Iron status in low-birth-weight infants, small and appropriate for gestational age. A follow-up study.

Iron nutrition was measured in 84 low-birth-weight infants. At birth, they were assigned to three groups: preterm infants appropriate for gestational age (n = 29); preterm infants small for gestational age (n = 17); and full-term infants small for gestational age (n = 38). A sub-sample of infants was supplemented with iron 3 mg/kg from two to four months of age. At birth, preterm appropriate-for-gestational-age infants had a lower hemoglobin concentration than full-term small-for-gestational-age infants (p < 0.01) and a higher serum ferritin than preterm small-for-gestational-age infants (p < 0.05). In the non-supplemented group, full-term small-for-gestational-age infants had significantly higher hemoglobin concentrations at four months of age. At this age, iron-supplemented preterm infants appropriate or small for gestational age had significantly higher hemoglobin levels than non-supplemented subjects, while iron supplementation did not have an effect on final hemoglobin concentration in full-term small-for-gestational-age infants. We conclude that preterm infants, irrespective of their adequacy for gestational age, show evidence of iron deficiency before four months of age. Full-term infants do not develop iron deficiency up to this age.


Relationship between neonatal behavior and subsequent temperament.

The validity of the neonatal behavioral assessment scale in predicting later infant temperament is of theoretical and clinical importance. The scale was administered to 47 full-term healthy neonates. Of these, 40 were followed and the infant characteristics questionnaire was given at four months of age. Significant correlations were revealed between the neonatal assessment items from the clusters of orientation and motor maturity and the temperament factors "fussy-difficult" and "unpredictable". Items from the cluster of autonomic stability correlated with the temperament factor "unadaptable." These correlations possibly indicate that perceived temperament does reflect intrinsic infant qualities.


Persistence of respiratory symptoms into the second year of life: predictive factors in infants born preterm.

Preterm infants frequently suffer from recurrent respiratory symptoms in the first year of life. Our aims were to assess if such respiratory morbidity persisted beyond the first year and to define the predictive factors. One hundred and seventeen infants (median gestational age 29 weeks) were followed prospectively for two years. Thirty-eight infants had symptoms only in the first year (group A) and in a further 20 infants, symptoms were present in both years (group B). Comparison of these two groups revealed no significant difference in birth weight or gestational age, but the duration of ventilation and increased inspired oxygen concentration were significantly longer in group B. Significantly more infants in group B had had an air leak in the neonatal period, and airways resistance at six months of age was also significantly higher in group B. We conclude that infants with severe neonatal respiratory distress are likely to have persisting respiratory morbidity and that respiratory function measurements at six months of age provide the most accurate predictor of chronic respiratory symptoms.


Gestational age correction for height in preterm children to seven years of age.

Correction for gestational age continues to make a difference to the height SD score (SDS) to the age of seven years in very preterm babies. The height SDS for children born at 28 weeks' gestation increased by 0.25 SDS when postconceptual age was used instead of real age. Extrapolating from these results, the effect of correction would be an increase of approximately 0.32 SDS for a seven-year-old of 24 weeks' gestation. Unsatisfactory growth may be masked by a steady or increasing real age SDS in a few children. The risks of stopping using postconceptual age at two or three years include both false confidence in genuine cases of growth retardation and misinterpretation of a decrease in height SDS as evidence of growth retardation. As the number of very preterm babies who survive increases so does the importance of these observations.


Hydrops fetalis associated with Ureaplasma urealyticum.

A hydroptic newborn was born at 32 weeks' gestation and at the age of 14 h died of post-asphyxial syndrome. Immunologic causes of hydrops fetalis were excluded, as were anomalies and chromosomal aberrations. Ureaplasma urealyticum was isolated in bronchial secretions, lung tissue and brain tissue of the newborn. Our findings suggest that U. urealyticum infection should be considered in the differential diagnosis of hydrops fetalis.


A case of familial nesidioblastosis: prenatal diagnosis of foetal hyperinsulinism.

Persistent neonatal hyperinsulinaemic hypoglycaemia due to nesidioblastosis is a rare condition probably transmitted by an autosomal recessive inheritance. Recurrent hypoglycaemic episodes become evident after birth and cause severe neurological damage without intensive treatment. The intrauterine detection of hypoglycaemia and hyperinsulinism in newborns subsequently diagnosed as affected by nesidioblastosis has not yet been reported. We describe a case of familial nesidioblastosis in which an intrauterine diagnosis could be suggested by high levels of insulin and C-peptide and low values of glucose in the amniotic fluid.


Neonatal Salmonella panama infection with meningitis.

Three full-term neonates contracted a hospital infection with Salmonella panama derived from the mother of one. Two had bacteraemia and meningitis; one developed a brain abscess and the other recurrent meningitis at two months. The third neonate had gastroenteritis only. Six months later they had developed normally and two were still excreting salmonellae in the stools.


Vitamin K prophylaxis and vitamin K deficiency bleeding (VKDB) in early infancy.

The efficacy of vitamin K prophylaxis (1 mg im or sc, or 1-2 mg orally both given as a single dose at birth) in the prevention of vitamin K deficiency bleeding in early infancy was estimated in Germany during a 15-month period between 1988 and 1989. Cases were identified by a survey of all paediatric hospitals and population denominators by a survey of all obstetric hospitals. Response rates were 85% and 68%, respectively. Thirteen cases of vitamin K deficiency bleeding in early infancy with confirmed prophylactic states were confirmed, seven of whom had intracranial haemorrhage. The estimated efficacy of single parenteral administration of vitamin K versus no prophylaxis was 96.7% (95% confidence interval: 74-99.6%) and for single oral administration versus no prophylaxis 80.4% (9.1-95.6%). Single parenteral vitamin K prophylaxis gave substantial protection against vitamin K deficiency bleeding in early infancy. Single oral prophylaxis appeared to be less effective, although the difference was not significant, as indicated by the wide overlap of the respective 95% confidence intervals.


Vitamin K status in cystic fibrosis.

Appearance of PIVKA-II (protein induced by vitamin K absence-II) in serum is a biochemical sign of insufficient vitamin K-dependent carboxylation of prothrombin. Plasma concentrations of PIVKA-II and vitamin K1 were determined in 24 children with cystic fibrosis. Eight were supplemented with vitamin K1. The purpose of the study was to determine the occurrence of vitamin K deficiency in cystic fibrosis and to evaluate the effect of vitamin K supplementation. PIVKA-II was detectable in only one unsupplemented child. In this patient, the concentration of vitamin K1 was below the limit of detection of 60 ng/l. Vitamin K1 levels in the other unsupplemented children were normal (mean 476 ng/l = 1 mmol/l). The supplemented patients showed extremely high levels of vitamin K1 (mean 22445 ng/l = 50 nmol/l). In conclusion, vitamin K deficiency occurs infrequently in cystic fibrosis. Checking the coagulation system is advised, but routine vitamin K supplementation is not recommended. If additional vitamin K is needed, the starting dose should not exceed 1 mg daily.


Neonatal polycythemia in appropriately grown infants of hypertensive mothers.

Neonatal polycythemia is a frequent finding after pregnancies complicated by diabetes and by maternal hypertension with intrauterine growth retardation (IUGR). It is still unclear if the association of polycythemia with hypertension is the result of IUGR or of hypertension per se. To establish the incidence of neonatal polycythemia in populations at risk, we analyzed the results of hematocrit values obtained from 1592 neonates born consecutively at the Hospital de Clinicas, Buenos Aires. Capillary hematocrit values were obtained by heel stick before 6 h of age. When the values were 65% or greater, new samples were obtained from an antecubital vein. The risk of polycythemia in appropriately grown infants of hypertensive mothers was 12.6-fold greater than the risk in the general population. These data show that maternal hypertension poses a significant risk for polycythemia, regardless of fetal growth. We suggest that, to prevent possible sequela, hematocrit is measured routinely in all infants of hypertensive mothers for prompt diagnosis and treatment.


Exogenous porcine surfactant (Curosurf) is inactivated by monoclonal antibody to the surfactant-associated hydrophobic protein SP-B.

A monoclonal antibody to the surfactant-associated hydrophobic protein SP-B was added at various concentrations to a standard preparation of porcine surfactant (Curosurf 10 mg/ml), and surface properties were evaluated with pulsating bubble. Retarded adsorption of surfactant was observed at antibody concentrations > or = 0.5 mg/ml and significantly increased values for minimum surface tension were observed at antibody concentrations > or = 1 mg/ml. In vivo effects of the antibody were tested in immature newborn rabbits ventilated with a standardized sequence of insufflation pressures. Animals receiving 0.1 ml surfactant (80 mg/ml) mixed with antibody at concentrations > or = 4 mg/ml had low tidal volumes, poor lung stability in pressure-volume recordings, poor alveolar expansion in histological sections and widespread epithelial necrosis in peripheral airways. Admixtures of IgG had no such effects. We conclude that this monoclonal antibody inactivates exogenous porcine surfactant, probably by preventing fast adsorption of surfactant lipids to the alveolar air-liquid interfaces.


Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus.

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.


Circulating levels of endothelin and atrial natriuretic factor during postnatal life.

We determined plasma endothelin-1-like immunoreactivity and atrial natriuretic factor concentrations in preterm and full-term newborn infants during the first month of life. Plasma endothelin-1-like immunoreactivity levels were far greater than those of maternal blood in the newborn infants. The highest plasma endothelin-1-like immunoreactivity levels were observed on the first day of life (8.7 +/- 3.7 pmol/l) and gradually decreased with age. There was no significant difference in plasma endothelin-1-like immunoreactivity levels between preterm and full-term infants. A good correlation was observed between plasma endothelin-1-like immunoreactivity levels and atrial natriuretic factor concentrations (p < 0.01). These results suggest that circulating endothelin may regulate the cardiovascular system in the newborn period.


Rapid decrease in tuberculin skin test reactivity at preschool age after newborn vaccination.

A study of tuberculin sensitivity was performed in 353 children aged 4-6 years, all vaccinated at birth with British BCG vaccine. Significant waning of tuberculin reactions with increasing age was found (p < 0.05). In the age group < 4.5 years, the mean tuberculin reaction was 6.6 mm, in the age group 4.5-5.5 years 5.2 mm and in the age group of > 5.5 years 3.5 mm. The number of children with positive reactions (> or = 5 mm) was 165 (40%) and those with strong reactions (> or = 10 mm) 49 (14%). None of the latter children had active tuberculosis during a follow-up period of 12 months. Eighty-three (24%) of the children had no reaction. The children who had been revaccinated with the MPR vaccine against measles, rubella and parotitis (n = 31) had significantly larger tuberculin reactions than the non-revaccinated children. Atopic dermatitis or infections during the preceding six months did not have any significant influence on reaction sizes. Our results demonstrate that the variation in size of tuberculin reactions after BCG vaccination at birth is large. We conclude that tuberculin sensitivity wanes rapidly by the age of 4.0-6.3 years.


Treatment of hypercholesterolemia in children and adolescents.

In patients with severe genetic hypercholesterolemia, therapeutic reduction of elevated serum total cholesterol and LDL cholesterol should begin in early childhood to lower the risks of cardiovascular disease later in life. We evaluated the effects of outpatient therapy with diet alone and with combined diet and drug therapy in children and adolescents with hypercholesterolemia of apparent dominant inheritance. Serum lipid values before and during dietary treatment were available in 35 patients (mean age at start of treatment 7.9 years, range 2.0-17.6 years) followed for an average duration of 17.5 months (range 4-70 months). A comparison between untreated state and combined therapy with diet and cholestyramine was possible in 14 patients (mean age 8.6 years, range 2.4-17.0 years) followed for 27.9 months (range 4-97 months). Dietary modification achieved by repeated counseling and training lowered serum total cholesterol by mean (+/- SE) 11.7 +/- 1.9% (p < 0.0001) and LDL cholesterol by 17.3 +/- 3.5% (p < 0.0001). However, five of 35 patients did not show an appreciable effect of therapy (cholesterol reduction < 5%), possibly because of non-compliance. Diet combined with cholestyramine in an average dose of 0.36 g/kg body weight/day reduced total cholesterol by 33.0 +/- 2.4% (p < 0.0001) and LDL cholesterol by 37.5 +/- 4.3% (p < 0.0001) and was effective in all patients. Both forms of treatment had no effect on serum triglycerides and HLD cholesterol. No serious side effects were noted, and percentile values for weight and height remained unchanged in all but three obese children.(ABSTRACT TRUNCATED AT 250 WORDS)


Growth and nutrition in 10 girls with Rett syndrome.

Cross-sectional and retrospective data on growth and anthropometric outcome, feeding problems and dietary intake are presented for 10 girls between three and 16 years of age with Rett syndrome. All girls had birth weight and length within the normal range for gestational age and development was considered normal until six to 24 months of age. The girls presented a fall off in linear growth during the first two years of life and at the time of study, all but one had height and/or weight for height below the 2.5th percentile of healthy children. The girls had good appetite but could not eat by themselves and oral-motor dysfunctions were common. The mean energy intake was 66.9% of the US recommendations according to age and 107.8% of the recommendations according to body weight. The intakes of thiamin, vitamin D, calcium and iron were considered low. None was anaemic. Different nutritional intervention strategies should be investigated to reduce and, if possible, prevent malnutrition and wasting in girls with Rett syndrome.


Does growth hormone treatment of patients with Turner's syndrome cause an abnormal body shape?

The effect of human growth hormone on the body shape of 51 patients with Turner's syndrome (aged 6-19 years) was evaluated. Biosynthetic growth hormone was given in a dose of 24 IU/m2 body surface/week for two years. Karyotype analysis on peripheral blood was performed. Patients older than 12 years also received 0.1 microgram ethinyl oestradiol/kg body weight/day orally. Body shape was characterized by studying pairs of measurements expressed as SD scores (z scores). As reference data, our own locally obtained data from normal children were used. After two years of growth hormone therapy, height, sitting height, bi-acromial and bi-iliac diameter increased from -3.7, -2.9, -1.7 and -1.2 to -1.3, -2.5, -0.6 and +0.5 z scores, respectively. The shape of the patients, expressed as height/bi-iliac diameter and also as sitting height/bi-iliac diameter became more abnormal. As no difference could be noted between the prepubertal and pubertal groups or between the XO and mosaic groups, it is suggested that growth hormone treatment causes a relatively wide pelvis in patients with Turner's syndrome.


Single daily doses of trimethoprim/sulphadiazine for three or 10 days in urinary tract infections.

We conducted a prospective randomized study to evaluate the efficacy of a single daily dose of 4 mg/kg of trimethoprim coupled with 17.5 mg/kg of sulphadiazine for three (group 1) or 10 days (group 2) in the treatment of uncomplicated urinary tract infections in children. Forty patients (nine boys and 31 girls) aged 2.5-18 years, presenting with a urinary tract infection were allocated to one of the two groups. Patients were seen three, 10, and > or = 38 days after the initiation of treatment. Control urine cultures were negative in all patients at days 3 and 10. Two patients in group 1 and one patient in group 2 suffered a relapse within a month. Single doses of trimethoprim/sulphadiazine for three or 10 days are effective in the treatment of uncomplicated urinary tract infections in children.


Acute renal failure in a neonate due to pelviureteric candidal bezoars successfully treated with long-term systemic fluconazole.

Systemic candidiasis with renal involvement is a rare but well-recognized complication during intensive care treatment in very-low-birth-weight infants. We report a term neonate who developed anuria associated with bilateral bezoar formation in the renal pelvis and candidemia. The treatment consisted of placement of a nephrostomy tube in the left kidney, short-term irrigation with amphotericin B and iv, and later, oral administration of fluconazole.


Intracardiac rhabdomyomas in neonates: report of three cases.

Three cases of intracardiac rhabdomyomas in neonates are presented. All were diagnosed by ultrasound, one prenatally and two directly after birth. Two of the patients were operated on during the neonatal period. The operations were carried out on the ultrasound findings alone. One patient was considered inoperable and died at three weeks of age. The two surviving patients have no cardiac symptoms and involution of the tumors has taken place. Two of the three patients have shown signs of tuberous sclerosis.


Anesthesia-induced rhabdomyolysis in infants with unsuspected Duchenne dystrophy.

Anesthesia-induced rhabdomyolysis in infancy may represent an unsuspected Duchenne dystrophy. In order to establish the diagnosis of this genetic disease more definitively, a dystrophin test is a requisite following the conventional creatine kinase test and light and electron microscopies of the muscle biopsy.


Noma neonatorum: an unusual case of noma involving a full-term neonate.

Noma neonatorum is a gangrenous process that occurs in the oral, nasal or anal area and occasionally the eyelids and scrotum of the newborn. The disease is caused by Pseudomonas aeruginosa and usually affects premature ill babies during the first few weeks of life. A full-term neonate with nasal and scrotal noma is uncommon and is therefore reported.


Shoshin beriberi in an infant of a thiamine-deficient mother.

The classical form of thiamine deficiency in children is comprised of peripheral neuropathy, encephalopathy and high-output cardiac failure, predominantly right-sided. "Shoshin beriberi" cardiac failure has a different presentation, with vasoconstriction, hypotension and severe metabolic acidosis. A three-month breast-fed infant developed these features (biochemical tests confirmed the diagnosis). His mother, although non-symptomatic, had biochemical evidence of thiamine deficiency.


Miliary tuberculosis with acute respiratory failure and histiocytic hemophagocytosis. Successful treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213.

A 14-year-old girl with high fever, dyspnea and bilateral miliary nodules on chest X-ray, developed a rapidly progressive respiratory failure associated with histiocytic hemophagocytosis. Histologic examination of bone marrow biopsy revealed tuberculous granulomas with caseating necrosis. We report a pediatric case in which treatment with extracorporeal lung support and epipodophyllotoxin VP 16-213 was successful.


Role of cereal-based oral rehydration therapy in persistent diarrhoea in children.

A total of 2000 children aged under five and 12,500 diarrhoea episodes were studied prospectively for assessing the efficacies of R-ORS and G-ORS and for comparing them with that of a comparison area using drugs for treatment. Efficacy was evaluated in terms of ORS use rate, consumption of ORS per episode, duration of diarrhoea and rate of recovery. The data were analysed to compare the rate of persistent diarrhoea in the three areas. Mean ORS consumption was 946 +/- 576 and 1236 +/- 766 ml per episode of watery diarrhoea in the R-ORS and G-ORS areas respectively. The mean durations of watery diarrhoea were 3.3 +/- 2.1, 5.4 +/- 3.5 and 8.8 +/- 5.5 days in the R-ORS, G-ORS and comparison area, respectively. The median durations for dysentery were 7, 9 and 12 days in the three areas respectively. The incidences of persistent diarrhoea following water diarrhoea were 0.4, 3 and 12% in the R-ORS, G-ORS and comparison area respectively, and, following dysenteric episodes, 8, 18 and 40%. The results of the study suggest that R-ORS can hasten recovery from both watery diarrhoea and dysenteries, thus reducing the incidence of persistent diarrhoea.


Is small bowel bacterial overgrowth of pathogenic significance in persistent diarrhea?

Bacterial overgrowth in the upper small intestine is postulated to cause persistent diarrhea. We compared the fecal and upper intestinal flora in 82 patients with persistent diarrhea aged < or = 36 months and weight-for-length < or = 90% of National Center for Health Statistics standards (NCHS) and 39 non-diarrheal children with age < or = 36 months, nutritionally matched with the patients and residing in the same environment. In the age groups < or = 12 months and > 12 months the duodenal fluid bacterial counts > or = 10(5)/ml were found with similar frequency in patients and controls for aerobic (p = 0.33; p = 0.1) and anaerobic (p = 1.0; p = 1.0) bacteria. However, the duodenal isolation rates of any aerobic bacteria (p < 0.05) without regard to counts and Enterobacteriaceae (p = 0.06) were higher in patients than in controls. Colonization with Enterobacteriaceae was directly correlated with increased stool weight over a 7-day observation period (p < 0.05; p < 0.01). One or more pathogens were isolated in the feces of 58% of the patients and 43.8% of the controls. Enteroadherent E. coli of the localized [EAEC-L] (p < 0.01) and aggregative [EAggEC] (p = 0.22) phenotypes were isolated more commonly from the feces of patients. The duodenal fluid detection rates for Klebsiella were significantly greater (p < 0.01) in patients, while Giardia lamblia was detected more commonly in the duodenal fluid of controls (p < 0.01). The presence of specific pathogens in the feces did not seem to be related to the extent of small bowel colonization.(ABSTRACT TRUNCATED AT 250 WORDS)


The role of the duodenal microflora as a determinant of persistent diarrhoea.

It has been suggested that proliferation of enterobacteriaceae and/or anaerobes in the duodenum of some children with acute diarrhoea determines whether the episode becomes persistent. A review of published studies and the comparison of cultures of duodenal aspirates from Peruvian children with acute and persistent diarrhoea and diarrhoea-free children did not support this hypothesis. Although many children had enterobacteriaceae and/or anaerobes cultured there was no correlation with clinical and nutritional outcome. Age, nutritional status, the environment and the aetiology of the episode were determinants of the duodenal microflora independent of diarrhoea. Culture of the duodenal aspirates did not increase the yield of enteropathogens which were isolated more frequently from stools than from the duodenum. Despite the presence of a single strain or serotype of enterobacteriaceae suggesting that these bacteria were colonizing the duodenum, we were unable to demonstrate any adherence mechanisms in the majority of them. Two of ten bacteria with no other evidence of virulence caused diarrhoea in the RITARD rabbit model.


Persistent diarrhea as a cause of childhood mortality in rural Bangladesh.

To determine the importance of persistent diarrhea in childhood mortality a multiple-step verbal autopsy method was used to study 1934 deaths in Matlab, Bangladesh. We found that most of the deaths from acute watery diarrhea occurred in infancy, whereas the peak of non-watery diarrhea deaths was in children over 12 months of age. Children suffering from persistent diarrhea and malnutrition were at highest risk of dying during their third year of life. Children with infectious diseases have a two to four times higher risk of dying if they are malnourished, and for diarrhea the risk is 17 times as high. Forty-nine percent of the diarrheal deaths were in children with malnutrition associated with persistent diarrhea. These results imply that fluid and dietary management are key aspects in the treatment of diarrhea, particularly for those episodes which persist. We conclude that attempts to reduce diarrhoeal deaths with vertical ORT programmes will not have major impact unless other interventions are directed to the persistent diarrhoea-malnutrition complex.


Clinical aspects of acute vs persistent diarrhea in Ho Chi Minh City, Vietnam.

A retrospective clinical study of acute and persistent diarrhea in children younger than three years of age was conducted for 12 months (October 1989 to September 1990) in a Pediatric Hospital in Ho Chi Minh City, South Vietnam. Most of the 3833 episodes of diarrhea identified were of short duration, with 77.7% lasting only 1-7 days. Only 5.3% of episodes lasted more than 14 days. Episodes of longer duration were associated with young age (0-5 months). Bloody stool was present in more than 40% of persistent episodes. Severe malnutrition was associated with persistent episodes that lasted 14-21 days (33%) or more than 22 days (59%). It is important that all patients with diarrhea have appropriate dietary management in addition to fluid therapy, and that future analysis examines etiologic factors to determine the optimal treatment of bloody diarrhea.


Persistent diarrhea in Vietnamese children: a preliminary report.

The clinical and laboratory features of persistent diarrhea were investigated in 83 children under three years of age who were treated in the Gastroenterology Division of the Institute for the Protection of Children's Health, Hanoi from August 1988 to August 1989. The number of cases of diarrhea was highest in the children aged 4-5 months. The mean age of the children studied was 6.6 +/- 3.4 months. The ratio of males to females was 2.6 and mean age of first episode of diarrhea was 4.3 +/- 3.4 months; persistent diarrhea was more common in children under six months of age than in older children. Persistent diarrhea occurred in the first diarrheal episode in 66.5% of cases. Recent nonenteric infections were found in 30% of the study group. Of the 83 children studied, 36% had stool specimens positive for enteric pathogens; 24% had enterotoxigenic Escherichia coli isolated, 8% had enteropathogenic E. coli, 5% rotavirus, 6% Candida, and 4% Giardia lamblia. The duration of diarrhea was longer in children who received antibiotics than in those who did not (p < 0.01).


Determinants of dietary intake during childhood diarrhea and implications for appropriate nutritional therapy.

Diarrheal diseases have a well recognized negative effect on children's growth, probably due in part to reduced dietary intake during illness. Previous studies have shown that the effects of diarrhea on dietary intake are greater among hospitalized children than among those observed in their homes. Breast milk intake does not change during diarrhea, however, so breast-fed children are less likely to reduce their total energy and nutrient intakes. Recent analyses of clinical studies found that acidosis and dehydration were most closely associated with reduced dietary intake of hospitalized patients. The implications of these and other studies for the dietary management of patients during and after diarrhea are discussed.


Lactose feeding during persistent diarrhoea.

Lactose intolerance is a recognized complication of some episodes of diarrhoea. Whereas it is of clinical importance in relatively few children with acute diarrhoea it seems to be a more common problem in children presenting with persistent diarrhoea, especially in malnourished children with severe diarrhoea. We describe a recent study which also demonstrated adverse clinical and nutritional consequences in the majority of children with mild but persistent diarrhoea consuming 6 g lactose/kg body weight/d. It is desirable to identify these children who need to reduce their lactose intake in order to limit unnecessary dietary changes which are expensive to implement and/or nutritionally disadvantageous. Admission clinical characteristics were analyzed for their ability to predict clinical outcome in a group of 33 children with persistent diarrhoea taking a lactose-containing diet. The results of tests of stool reducing substances and a lactose breath hydrogen test (LHBT) were analyzed in the same group whose clinical management had been independent of the test results. Eighty-nine percent of children who deteriorated had one of the following characteristics: age < 12 months, weight-for-height less than -2 SD below NCHS norms or fever > 37 degrees C. Children who unequivocally improved while continuing to take lactose could not be selected without the risk of including children who deteriorated. Neither tests of stool reducing substances nor the LBHT improved the predictive value of simple clinical parameters.(ABSTRACT TRUNCATED AT 250 WORDS)


Persistent diarrhoea: factors affecting absorption and clinical prognosis during management with a rice-based diet.

Twenty-six persistent diarrhoea patients aged 4 to 18 months were treated with a diet prepared with rice powder, soya oil, glucose, egg white and water. Absorption of macronutrients was estimated in a 72 h balance study and clinical response was examined during one week of dietary treatment. Nutrient absorption was compared with that of 25 healthy age-matched controls treated with the same diet. Twenty-one patients (81%) recovered from diarrhoea within seven days. Absorption of nutrients was significantly reduced among the persistent diarrhoea patients. More malnourished patients had a significantly reduced absorption of nutrients except carbohydrate and an increased severity and longer duration of diarrhoea. Total gut transit time had significant association with nutrient absorption in the persistent diarrhoea patients. The period of recovery negatively correlated with coefficient of absorption and positively with initial stool weight. Failure to recover was associated with severity of diarrhoea and systemic infection. The study indicates that nutrient absorption is significantly reduced in patients with persistent diarrhoea and nutritional status, and that initial purging rate and intestinal hurry are significantly related to the prognosis and nutrient absorption.


Nutritional management of persistent diarrhea: factors predicting clinical outcome.

In a prospective study we randomized 102 male children (age 6-36 months) with persistent diarrhea to receive a traditional rice-lentil (Khitchri) diet and yogurt (K-Y) or a soy formula (alone for seven days and then in combination with K-Y for seven days). Of 73 children satisfying the study criteria, 66 were successfully treated and there were 7 treatment failures. There was poor concordance between parental accounts of severity of diarrhea or vomiting and that observed after admission. Significant risk factors associated with treatment failure included younger age (p < 0.005) and vomiting at presentation (p < 0.02). The greatest number of risk factors associated with delayed recovery (> 10 days) were identified during an initial evaluation period (the first 8 h after admission). These included greater severity of watery diarrhoea (p < 0.01) and increased ORS intake (p < 0.02). Our data suggest that an initial evaluation period, including objective observations, may identify children with persistent diarrhea who are at greatest need of hospitalization.


Oral gentamicin is not effective treatment for persistent diarrhea.

We conducted a randomized, double-blind, placebo controlled clinical trial of oral gentamicin (10 milligrams/kilogram body weight/day for five days) in treatment of unselected cases of persistent diarrhea (duration 14-18 days at initiation of treatment) among 3-36-month-old children in a rural Guatemalan community. Following random assignment of each child to a treatment group, the appropriate dose of gentamicin or placebo was administered to the child three times daily by a study nurse; this nurse also identified the presence or absence of diarrhea on each day of treatment and for the next two days. Cure was defined as cessation of diarrhea during the five-day treatment period, sustained through at least the two days after completion of treatment. Among 92 evaluable cases who entered the clinical trial, there was essentially no difference in cure rate between gentamicin and placebo treatment groups (42% versus 43%). Enteroadherent strains of Escherichia coli were identified in 46% of children tested in this trial; no significant difference existed between treatment groups in frequency of isolation of this or any other enteropathogen. Among 40 children having successful duodenal cultures immediately prior to beginning treatment, > or = 10(4) aerobic organisms per milliliter of fluid were identified in 12 (30%); treatment groups did not differ substantially with respect to proportion of children identified with this level of duodenal microbial colonization. Failure of gentamicin treatment did not appear to be explained by emergence of resistance, although a small number of resistant enteropathogens were identified near the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidemiological and clinical characteristics of acute and persistent diarrhoea in rural Bangladeshi children.

A community-based longitudinal study of acute and persistent diarrhoea in 705 children less than five years old was carried out for a year in a rural area of Bangladesh. Diarrhoea morbidity data were collected from each study child every fourth day by home visit. Clinical features of diarrhoeal episodes and diarrhoeal management information were documented. The overall diarrhoeal incidence rate in the study children was 4.6 episodes per child per year. The incidence of persistent diarrhoea was 34/100 child-years. Persistent diarrhoea was positively associated with young age and more severe illness, characterized by the presence of clinical dehydration or blood in the stool in the first week. Use of ORT in the first week was positively associated and use of an antibiotic was negatively associated with the occurrence of persistent diarrhoea. Reduced breast-feeding and consumption of cow's milk at some time during the episode were also positively associated with persistence. This would suggest that appropriate fluid and dietary management for all episodes should be the goal. Children with more severe initial illness characterized by the presence of blood in the stool or clinical dehydration should have more careful follow-up to identify persistent episodes and adverse nutritional effects. Breastfeeding should be continued during acute diarrhoea, but the role of ORT, antibiotics and cow's milk deserves further investigation.


Epidemiology of persistent diarrhea among Guatemalan rural children.

A prospective, longitudinal two-year study to determine the epidemiology of persistent (> or = 14 days' duration) diarrhea in rural children of Guatemala was undertaken. Three-hundred and twenty-one children aged 0-35 months were kept under surveillance by twice-a-week home visits. The overall incidence of diarrhea was 0.147 per child-week; the incidence of persistent diarrhea was 0.014 per child-week. The peak of persistent diarrhea was observed in infants below six months of age, with a continuous decline thereafter. This trend in incidence of persistent diarrhea was associated with a higher proportion (16%) of illnesses persisting for more than 13 days in children younger than six months of age as compared to children 30-35 months old (4%). Males had more diarrhea (0.156 per child-week) than females (0.139 per child week). Among children above 18 months of age, the proportion of episodes that lasted for more than 13 days was lower in females than in males.


Epidemiology of persistent diarrhea and etiologic agents in Mirzapur, Bangladesh.

To determine the epidemiology and etiologic agents of persistent diarrhea we carried out an intensive diarrhea surveillance on children less than six years old in rural Bangladesh. From March 1987 to February 1989 we examined 363 children through diarrhea recall interviews and analyzed stool samples of all diarrhea cases for potential pathogens. Results showed that children had an average of two episodes per year and the incidence rate of diarrheal episodes defined as acute (< 14 d) and persistent (> or = 14 d) varied similarly with age. The peak incidence (episodes/child/year) of acute diarrhea (2.8) and persistent diarrhea (0.8) occurred in the 6-11 months age group. The data showed that an episode tended to be prolonged if the stool was loose/mucoid or bloody at onset. Aggregative adherent Escherichia coli was found significantly more often at onset in persistent than in acute episodes, whereas Shigella, Aeromonas, Giardia and toxigenic E. coli were isolated with less frequency in persistent than acute episodes. This suggests that other factors might be more important in the development of persistent diarrhea than specific pathogens.


Mortality associated with acute watery diarrhea, dysentery and persistent diarrhea in rural north India.

Mortality associated with diarrhea was investigated in a longitudinally followed cohort of children under six years of age in rural North India. During the follow-up, 1663 episodes of diarrhea and 23 diarrhea related deaths were recorded in 1467 children followed up for 20 months. The case fatality rate was 0.56% for acute watery diarrhea, 4.27% for dysentery and 11.94% for non-dysenteric persistent diarrhea. Most of the episodes lasted less than a week; 5.2% became persistent (duration > 14 days). The case fatality rate was similar in episodes of one and two weeks' duration (0.64% and 0.8%) and increased to 13.95% for persistent episodes. Of the total 86 persistent episodes, 22.1% were dysenteric; the case fatality rate for such dysenteric persistent episodes was 21.1% and for watery persistent diarrhea 11.4%. Diarrheal attack rates were similar among different nutritional groups, but diarrheal case fatality rates progressively increased with increasing severity of malnutrition, these were 24 times higher in children with severe malnutrition (7.48%) compared to those normally nourished (0.31%). With availability and use of oral rehydration therapy, dysentery and persistent diarrhea emerge as major causes of diarrhea related mortality, with underlying malnutrition as a key associated factor.


Etiologic agents in acute vs persistent diarrhea in children under three years of age in peri-urban Lima, Perú.

In a longitudinal study of acute and persistent diarrhea in 677 children less than three years old in a peri-urban community of Lima, Perú, during 27 months of surveillance, stools were cultured at the beginning of each diarrheal episode and on each subsequent week of illness. Analyzing stool cultures only from children who had not received antibiotic treatment in the 48 h prior to the culture, no association was found between any enteropathogen and persistent diarrhea. We did not find any increase in mixed infections in persistent diarrhea episodes as compared with acute diarrhea, controlling for age, season and anthropometric status. The isolation rate for any given enteropathogen was similar during the first, second, third or later week of illness, but when the presence of a specific enteropathogen was sought in sequential stools within a single episode, no evidence of persistent infection was found. This study shows that in developing countries with a high incidence of diarrheal diseases frequent re-infections with enteropathogens prevalent in the population are one reason for prolonged illnesses. Host factors that increase susceptibility to infection or decrease recovery from illness may also play a role. Further studies of these factors, such as micronutrient deficiencies, are needed to identify a public health intervention to control persistent diarrhea, a condition associated with mortality in many developing countries.


Persistent diarrhea in northeast Brazil: etiologies and interactions with malnutrition.

With the improved control of acute diarrheal illness mortality with oral rehydration therapy, persistent diarrhea is now emerging as a major cause of childhood mortality in tropical developing areas like the impoverished populations in Brazil's Northeast. "Graveyard surveillance" in the rural community of Guaiuba in northeastern Brazil revealed fully half of the 70% diarrhea mortality was due to persistent diarrheal illnesses. Furthermore, 11% of 14 or more diarrheal illnesses per child per year in an urban slum in Fortaleza persisted beyond 14 days, a definition that clearly identified the high risk children for heavy diarrhea burdens. Not only did heavy diarrhea burdens ablate the key "catch-up" growth seen in severely malnourished children and in children following previous diarrheal illnesses, but malnutrition significantly predisposed children to a greater incidence and duration of diarrhea as well as a greater incidence of persistent diarrhea. Etiologic studies of 37 children presenting with persistent diarrhea to Hospital das Clinicas in Fortaleza revealed that Cryptosporidium (in 13%) and enteroadherent E. coli (36% with aggregative, 29% with diffuse and 13% with localized adherence to HEp-2 cells) were the predominant potential pathogens found in the stool or upper small bowel. These findings suggest that persistent diarrhea is emerging as an important health problem in Brazil's Northeast, that it identifies a high risk child for heavy diarrhea burdens, that important interactions occur with malnutrition and that Cryptosporidium and enteroadherent E. coli warrant further study as potential etiologies of this major cause of morbidity and mortality.


Persistent diarrhea associated with AIDS.

Chronic diarrhea and wasting are very common manifestations of AIDS in adults in developing countries. Etiologic studies show that protozoa (including Cryptosporidium parvum, Isospora belli, and Enterocytozoon bieniusi) and Mycobacterium avium-intracellulara are the most frequently identified pathogens. Limited data in children suggest that common enteric pathogens are equally as likely in HIV+ and HIV- babies. Preliminary analysis of an ongoing longitudinal study of 469 babies born to mothers with known HIV serostatus in Kinshasa, Zaire, reveals progression of acute to persistent diarrhea is six times greater in HIV+ compared to HIV- babies, and 3.5 times greater in HIV- babies born of HIV+ mothers in comparison to HIV- babies with HIV- mothers. HIV+ babies were also at greater risk than HIV- babies to have recurrent episodes of diarrhea (RR = 2.3). Fifty percent of the deaths were due to acute or persistent diarrhea, and were strongly associated with HIV infection. Efforts to improve child survival in AIDS infected populations will need to address HIV infections in both mothers and infants.


Household behaviors in the management of diarrhea and their relevance for persistent diarrhea.

There has been a great deal of research in recent years on household behaviors related to diarrhea management. Most of the available data on household diarrhea management, however, pertains to acute diarrheal episodes. There is a dearth of knowledge concerning household and caretaker behaviors when the diarrhea is of longer duration. This paper briefly reviews some of what has been learned about household behaviors in the management of acute diarrhea and discusses its relevance for persistent diarrhea. Based upon what has been learned from anthropological studies of acute diarrhea and the little that is known about caretaker behavior during persistent diarrhea, a hypothetical model of the interactions among household behavior and characteristics of diarrheal episodes is presented. The model argues that maternal (or caretaker) concern increases with diarrheal duration, and that changes in behavior, both adaptive and maladaptive, are more likely to occur during an episode of persistent diarrhea, compared to acute. In some cases, these actions may directly influence the outcome of the episode. There is a need to better understand household case management behaviors through the continuum of diarrheal duration and the effect of these behavioral factors on episode outcome. This information is necessary in order to communicate effective messages to caretakers about what they should know and what they should do when persistent diarrhea occurs.


The child's disease (Doença de criança): popular paradigm of persistent diarrhea?

According to popular report, the folk illness, Doença de criança (The Child's Disease) is the leading cause of infant and childhood death in Northeast Brazil; most health professionals, however, are unaware it exists. Doença de criança is described based on ethnographic interviews with 50 traditional healers and 50 bereaved mothers whose children have died from the condition. Doença de criança is a sociocultural label developed by the popular medical system and applied to the end stages of severe childhood infectious diseases and malnutrition against a background of grinding poverty. Doença de criança is discussed as an analog to persistent diarrhea. Practical treatment and management implications of this relationship are presented. Doença de criança, most importantly, offers a new, holistic paradigm for the future study of persistent diarrhea.