Experimental and clinical correlation in acute pancreatitis pathogenesis

Pathological aspects in 100 cases of operated A.P. different in severity are not strictly related to aetiological conditions. Clinical observations have suggested some components of pathogenesis: obstruction of bilio-pancreatic inflow in duodenum at the beginning of the attack, bilio-pancreatic reflux on cholangiograms, strong secretory digestive stimulation before attack. Some experimental animals models (dogs) which can mimic pathogenic mechanism (obstruction of pancreatic flow, common bilio-pancreatic duct, closed duodenal loop, acute cholecystitis) have revealed characteristic pathological changes depending on the initiating process. Our conclusion that severity of pathological changes in A.P. are determined by the initiating mechanisms which may differ in some aetiological condition or may be common for different ones.     

Haemorrhagic hydrops of the gallbladder

Primary carcinoma of the fallopian tube is uncommon; optimal primary treatment is still not well defined, and little information is available about the efficacy of cisplatin-based combination chemotherapy. Thirty-eight patients with fallopian tube carcinoma were treated with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and cisplatin (50 mg/m2) (CAP). Thirty-two patients received the combination chemotherapy as first-line treatment after cytoreductive surgery, whereas six subjects were treated for recurrent disease. The patients received a median of six cycles of therapy (range, four to nine). At the initiation of chemotherapy, 24 patients had measurable lesions. In this group of patients, 15 had a clinical complete response (CR), four had a partial response (PR), three had stable disease (SD), and two had progressive disease (PD) after chemotherapy. The overall clinical response rate (CR + PR) was 80%. Ten of the 14 CR patients who were submitted to second-look operation (SLO) were found free of disease, in pathologic complete response (pCR). Three pCR patients relapsed, and two of them died despite second-line treatment. Nine patients achieving PR, SD, and PD after first-line chemotherapy were further treated (five with chemotherapy, two with radiotherapy, two with progesteron), but none responded to second-line treatment and all died (median survival, 9 months). Fourteen patients without gross residual disease after cytoreductive surgery had no measurable lesions and were not evaluable for response. Seven of them had negative SLO and remain disease free. Three patients (two stage III and one stage II) who refused SLO relapsed 14, 16, and 26 months after completion of chemotherapy. The median survival for the entire group was 38 months, and the 5-year survival rate was 35%. The toxicity of the regimen was moderate. The CAP regimen appears to be active in primary fallopian tube carcinoma and yields response rates comparable to those reported for epithelial ovarian cancer.     

Diagnostic testing for endolymphatic hydrops

The development of a sensitive and specific diagnostic test for endolymphatic hydrops has eluded investigators for over 30 years. The absence of such a test has hampered basic and clinical research into Meniere's disease and related entities. Presently used tests are limited in their applicability because of their low sensitivity and specificity and a poor understanding of the underlying physiologic principles. Despite this, it is generally agreed that some of these studies have merit in selected situations. This article reviews the present state of diagnostic testing for endolymphatic hydrops. The use of nonspecific studies, such as basic audiometry and tests for recruitment, and "specific" studies, such as electrocochleography and dehydration testing, are critically reviewed.     

Laboratory experience with experimental endolymphatic hydrops

Experimental endolymphatic hydrops refers to the creation of hydrops in the experimental animal and represents a histologic correlate for Meniere's disease. Details of the surgical means to create this condition in guinea pigs are provided. Alterations in endolymph fluid composition and relative endolymph pressure occur with hydrops. Deterioration in auditory and vestibular function secondary to hydrops can develop.     

Experience with non-immunologic hydrops fetalis]

We studied the postnatal development of the release of acetylcholine (ACh) and of presynaptic, release-inhibiting muscarinic autoreceptors in the cell body region of the septohippocampal cholinergic pathway. To this end, septal slices (350 microns thick) from rats of various postnatal ages (postnatal day 3 [P3] to P16) were preincubated with [3H]choline and stimulated twice (S1, S2: 360 pulses, 2 ms, 3 Hz, 60 mA) during superfusion with physiological buffer containing hemicholinium-3 (10 microM). In parallel, the activities of hemicholinium-sensitive high-affinity choline uptake (HACU, in synaptosomes) and of choline acetyltransferase (ChAT, in crude homogenates) were determined as markers for the development of cholinergic functions. In septal slices preincubated with [3H]choline, the electrically evoked overflow of 3H at S1 increased from 0.31% (P3) to 2.10% of tissue 3H (P16), the latter value being still lower than that of septal slices from adult rats (3.46% of tissue 3H). Already at P3, the evoked overflow of 3H was Ca(2+)-dependent and sensitive to tetrodotoxin, indicating an action potential-evoked exocytotic mechanism of ACh release early after birth. Presence of the muscarinic agonist oxotremorine (1 microM) significantly inhibited the evoked ACh release in septal slices beginning from P5: no significant effect was detectable at P3. The ACh esterase inhibitor physostigmine (1 microM) exhibited significant inhibitory effects from P13 onwards. The muscarinic antagonist atropine (1 microM) enhanced the evoked ACh release only in septal tissue from adult rats. The specific activities of HACU, or ChAT showed a 2- or 8-fold increase, respectively, from P3 to P16. In conclusion, presynaptic cholinergic functions seem to develop almost in parallel both in the cell body and the target area of the septohippocampal projection: also in the septal region nerve terminals on axon collaterals are endowed very early (at least at P3) with the apparatus for action potential-induced, exocytotic release of ACh. In contrast, the appearance of feedback inhibition via presynaptic muscarinic autoreceptors is delayed. Autoinhibition due to endogenously released ACh can be detected only later, most probably when endogenous ACh concentrations in the septal nuclei have reached a threshold value.     

Case report--a neonate with nonimmune hydrops fetalis

AIM: To investigate the waste of laboratory reagents which resulted from the process of ordering biochemistry profiles. METHODS: The frequency of measurement of 15 analytes was recorded during the six months before the introduction of a system of discretionary requesting and analysis of samples (high capacity multichannel discrete analyser), and also during the same six month period one year and two years after its introduction. RESULTS: The frequency of measurement of 10 of the 15 analytes decreased during the six month period one year after the change to discretionary testing. The remaining five analytes were measured up to 22% more frequently. There was an overall decrease in the measurement of biochemical tests by 31,359. This created an annual cost saving of 7124 pounds. In the second year five analytes still continued to be measured less frequently than originally but the remaining 10 analytes were measured more frequently. This resulted in an overall increase in the measurement of biochemical tests by 53,678 compared with the six month period before discretionary analysis. The pattern of requests was similar during both periods of discretionary requesting studied and as a result, a small annual cost saving of 1672 pounds was again made. CONCLUSION: Discretionary requesting and analysis of tests may eliminate the measurement of clinically unnecessary test which had previously resulted from the processes of ordering tests. These cost savings may be rapidly eroded by an increase in the laboratory workload.     

Experimental hepatitis E: pathogenesis in cynomolgus macaques (Macaca fascicularis)

Children with acute lymphoblastic leukemia (ALL) who have completed 2.5 to 3 years of initial chemotherapy have an off-therapy relapse rate of approximately 20%. In an attempt to improve the survival of children with a late bone marrow (BM) relapse (ie, occurring greater than 6 months after cessation of primary therapy), the Pediatric Oncology Group designed a randomized study to compare the efficacy of doxorubicin/prednisone and cytarabine/teniposide in a multidrug retreatment chemotherapy program. Treatment consisted of remission reinduction with vincristine, prednisone, and doxorubicin, central nervous system prophylaxis with triple intrathecal chemotherapy, and continuation therapy (for 132 weeks) with alternating cycles of oral 6-mercaptopurine/methotrexate and intravenous vincristine/cyclophosphamide. Patients received intermittent courses of either prednisone/doxorubicin (regimen 1) or teniposide/cytarabine (regimen 2) during continuation therapy and a late intensification phase with either vincristine, prednisone, and doxorubicin (regimen 1) or teniposide and cytarabine (regimen 2). One hundred two of 105 evaluable patients (97%) achieved a second complete remission. Twenty-eight of 50 patients on regimen 1 have failed compared with 28 or 52 patients on regimen 2 (log-rank analysis, P = .68), indicating that this trial was inconclusive as to which treatment regimen was superior. The overall 4-year event-free survival for children with a late BM relapse was 37% +/- 6%. Age less than 10 years at initial diagnosis (P < or = .001), white blood cell count less than 5,000/microL at relapse (P = .036) and duration of first remission greater than 54 months (P = .039) were independently associated with a more favorable outcome. While the randomized trial was inconclusive, prolonged second complete remissions were secured in more than one-third of children with a late BM relapse of ALL. The prognostic factors identified may help select children with a late BM relapse who can be successfully retreated with chemotherapy alone.     

Experimental study of the pathogenesis of acute acalculous cholecystitis: role of autonomic denervation

This study was undertaken to elucidate the role of autonomic denervation in the pathogenesis of acute acalculous cholecystitis. In Experiment I, the gallbladder was denervated by performing either celiac neurotomy (sympathetic denervation) or truncal vagotomy (parasympathetic denervation), or both, in dogs. In Experiment II, 45-min ischemia and 90-min reperfusion of the gallbladder with or without autonomic denervation were performed by simultaneously occluding the middle hepatic artery and superior mesenteric vein. Celiac neurotomy, and truncal vagotomy, or both, did not cause cholecystitis. Sympathetic denervation, however, decreased the amount of mucin in the gallbladder mucosa and parasympathetic denervation caused reduction of the tissue blood flow, as well as the accumulation of lipid peroxide and xanthine oxidase in the gallbladder mucosa. These changes were most remarkable 1-2 weeks after denervation and were alleviated 4 weeks after denervation. Ischemia-reperfusion 2 weeks after denervation caused more severe cholecystitis than ischemia-reperfusion alone. The most severe inflammation developed in animals that received both celiac neurotomy and truncal vagotomy. These results suggest that autonomic denervation alone does not induce acute cholecystitis, but that it plays an important role in the progression of the inflammatory process in ischemia-reperfusion injury.     

A case of spontaneous resolution of nonimmune hydrops fetalis

Indoor average 222Rn concentrations have been measured in more than 400 houses in Istanbul city. The average radon concentrations in the houses were found to be between 10 Bq m-3 and 260 Bq m-3 and the mean value was 50 Bq m-3.     

Delayed endolymphatic hydrops: an analysis of 12 cases

Delayed Endolymphatic Hydrops (DEH) is a clinical entity which is characterized by an early phase with a profound sensorineural hearing loss in one ear. After a prolonged period of time (from 1 to 68 years) a late phase of the disease appears with different otologic symptoms. The ipsilateral type of endolymphatic hydrops appears in the deaf ear with consequent episodic vertigo. The contralateral type develops symptoms of endolymphatic hydrop in the previously normal ear, with the onset of fluctuating hearing loss and/or episodic vertigo. This paper is a review of 12 cases of DEH (7 ipsilateral and 5 contralateral, age ranging from 19 to 79 years). Diagnosis was established on the basis of clinical history and the results of audio-vestibular investigations, specifically designed to detect signs of endolymphatic hydrops (including the glycerol-test and neuroradiological imaging of the cerebello-pontine angle). In 8 patients the levels and frequency of anti-collagen I-II-IV-V, anti-laminin autoantibodies, complement, Ig and immuno-complexes were measured. Viral infections (measles, mumps, influenza) were thought to have caused the early phase in 6 cases. In the entire group of 12 patients the delay between the onset of the ear loss and vertigo averaged 12 years. In the group of the ipsilateral DEH, caloric tests showed in 5 cases a reduced or absent response of the deaf ear. About contralateral DEH, caloric tests showed bilateral reduced response in 2 cases, and, in 3 cases, a decreased response only in the previously normal ear. Regarding immunological study, an abnormal level of Ig and Complement was detected in 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Marked twin-twin transfusion in the absence of nonimmune hydrops

The precise pathophysiology of development of nonimmune hydrops in either the recipient or donor twin associated with twin-twin transfusion syndrome is not entirely clear. At times the recipient twin may develop nonimmune hydrops, but at other times the donor twin, and infrequently both, may develop this ominous complication. We present an unusual cases of this syndrome in which discordant twins, despite neonatal hematocrit levels of 86 and 21% were both nonhydropic and discuss the possible underlying pathophysiology of this occurrence.     

Nonimmune fetal hydrops: diagnosis and obstetrical management

As the incidence of Rh-isoimmunization has been decreasing with the availability of Rh immune globulin, the proportion of cases of fetal hydrops from nonimmune causes has increased. Evaluation of the fetus with hydrops requires an integrated approach, beginning with targeted ultrasound evaluation and potentially including maternal and fetal blood testing and other invasive testing. Because the list of conditions that may cause hydrops is long and continues to grow, it is often difficult to make a precise diagnosis; however, through a systematic approach, one may frequently narrow the etiology to a category of disorders and determine whether any interventions are available that are likely to be helpful in improving the outlook for the fetus.     

Computer image analysis in the study of endolymphatic hydrops

A team of authors investigated antibody levels against spermatozoa and against the zona pellucida in sera and peritoneal fluids in infertile women where diagnostic laparoscopy was indicated. The immunological cause of infertility was diagnosed in some women with a normal laparoscopic finding on the inner genital, as well as in patients with endometriosis and in women with adhesions. A minimal antibody response to antigens of gametes was recorded in women with the diagnosis of uterus myomatosus, uterus hypoplasticus and polycystic ovary. The authors present detailed findings on antibodies in different groups of patients.     

Treatment of hemoglobin Bart''s hydrops with bone marrow transplantation

OBJECTIVE: It is currently proposed to perform tumour enucleation in mono-orchid patients presenting with a small germ cell tumour, in order to preserve physiological endocrine function. However, this conservative surgery must be accompanied by treatment of any carcinoma in situ lesions present in the remaining testicular parenchyma. MATERIAL AND METHODS: The presence of carcinoma in situ was investigated in 35 patients with germ cell tumour of the testis on samples obtained from the presumably healthy pulp of the orchidectomy specimen, adjacent to and away from the tumour. Samples away from the tumour were performed according to principle of surgical testicular biopsy. Histological examination also concerned the tissue situated in contact with the tumour. RESULTS: 25 patients (74.22%) presented intratubular germ cell dysplasia in the testicular parenchyma presumed to be healthy. These lesions were always concomitantly observed on samples performed adjacent to and away from the tumour. It was observed more frequently in seminomas, but was also observed in other histological forms. CONCLUSION: Because of the diffuse nature of carcinoma in situ in germ cell tumours of the testis, pulp samples adjacent to the tumour are sufficient to ensure the diagnosis during conservative surgery. Carcinoma in situ is currently treated by local radiotherapy.     

Changes in fetal karyotype in non-immune hydrops fetalis

BACKGROUND AND METHODS: Among the pregnant patients who underwent an amniocentesis at our department of prenatal diagnosis (Division of Gynecology and Obstetrics of the University "Federico II" in Naples) from 1989 to 1996, 16 patients were affected by non-immune hydrops faetalis associated with chromosomal diseases. RESULTS: The karyotype test revealed at an ultrasound exam of the fetus that 11 cases were affected by trisomy 21, 4 cases by Turner syndrome and one case by trisomy 18. This study took into consideration all the pathogenetic factors and the diagnostic problems of non-immune hydrops faetalis in fetus affected by associated chromosomal associated anomalies. CONCLUSIONS: Since the incidence of the chromosomal anomalies on fetus affected by non-immune hydrops foetal is was very high, there was the necessity to carry out a routine karyotype test if the ultrasonography revealed anomalies of the hydrops, during the first three months of pregnancy.     

Middle ear overpressure treatment of endolymphatic hydrops in guinea pigs

Changes in sleep state and night-time body temperature were studied in 13 healthy young men. Temperature data showed serial dependence that was removed when considering three main segments of the thermogram: an initial rapid drop between 60 and 140 min after lights off, followed by a slower decrease to the thermal minimum and a final temperature increase until waking. The first segment was fitted by a two-term function, while the other two segments were fitted by linear regression. Temperature data obtained after fitting these models were stationary and used to calculate the fast Fourier transformation and the cross-correlation functions between the hypnogram and the thermogram of each subject. Attaining stationarity has unmasked short oscillations during sleep and some temperature series showed the presence of ultradian oscillations with a period of 90-100 min. Significant cross-correlations between sleep stages and body temperature were found, and the parameters of the two-term function fitted to the first temperature drop were related to the sign of the correlation and to that time series (sleep or temperature) which preceded the other during the night.     

Pathology of the endolymphatic duct and sac in inner-ear hydrops

The morphological substrate of Menière's disease is the endolymphatic hydrops. That can be idiopathic or secondary as a sequence of a labyrinthine disease of another cause. It is possible to coordinate function loss of the sensory end-organs and pathohistological findings, but not all failures are light-microscopically explainable. The reason for the hydrops is certainly a disturbance in the endolymph physiology. For the pathogenesis are important, besides the biochemistry of the inner ear-fluids, problems of the membranes and pathological changes on ductus and saccus endolymphaticus and perimacular areals and plana semilunata. The perilymphatic space, documentated on the example of the secondary hydrops, is certainly not only passively enrolled in the procedure. All observations bring the initiation and periodicity of attacks to another point of view. A complete solution has not been possible so far, especially in the case of the etiology in idiopathic hydrops.     

Sialidosis and galactosialidosis as the cause of non-immunologic hydrops fetalis

Two cases of non-immunological hydrops fetalis (NIHF) presenting with massive ascites are reported; in both patients an oligosaccharid-pattern in the urine typical for sialidosis resp. galactosialidosis was found. The cerebral sonography of both patients showed streaky echo enhancement in the region of the thalamostriatal vessels, which was interpreted as calcification of the vessels. The courses of the patients were characterised by recurrent infections, hepatosplenomegaly and myoclonus. Relevant literature reports on a large variability in the clinical appearance of oligosaccharidoses. The diagnosis of sialidosis is confirmed in cultured fibroblasts by the deficiency of alpha-N-acetylneuraminidase and, in case of galactosialidosis by the additional lack of beta-galactosidase. The precise diagnosis in NIHF is of increasing interest for prenatal diagnostic as well as for neonatological management.     

The efficacy of tympanic electrocochleography in the diagnosis of endolymphatic hydrops

Electrocochleography (ECoG), an objective electrophysiologic test, is useful in the clinical diagnosis of endolymphatic hydrops. The purpose of this study was further to define the role of ECoG in the diagnosis of this disease. A retrospective chart review of 100 patients undergoing tympanic ECoG was undertaken comparing symptoms, degree of hearing loss, duration of disease, and diagnosis with ECoG results. The apparent sensitivity and specificity of ECoG in the diagnosis of endolymphatic hydrops were determined to be 57% and 94%, respectively. Three of 30 positive ECoG results were falsely positive. Fluctuating hearing loss and the degree of hearing loss (< 40 dB) and duration of disease (< 48 months) were statistically significant in predicting positive ECoG results. We conclude that a positive ECoG result is helpful in objectively confirming the disease. However, a negative result does not rule out hydrops.